Yin Chen

In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy.We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area.Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group.In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

Mucus hypersecretion and persistent airway inflammation are common features of various airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. One key question is: does the associated airway inflammation in these diseases affect mucus production? If so, what is the underlying mechanism? It appears that increased mucus secretion results from increased mucin gene expression and is also frequently accompanied by an increased number of mucous cells (goblet cell hyperplasia/metaplasia) in the airway epithelium. Many studies on mucin gene expression have been directed toward Th2 cytokines such as interleukin (IL)-4, IL-9, and IL-13 because of their known pathophysiological role in allergic airway diseases such as asthma. However, the effect of these cytokines has not been definitely linked to their direct interaction with airway epithelial cells. In our study, we treated highly differentiated cultures of primary human tracheobronchial epithelial (TBE) cells with a panel of cytokines (interleukin-1α, 1औ, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, and tumor necrosis factor α). We found that IL-6 and IL-17 could stimulate the mucin genes, <i>MUC5B</i> and<i>MUC5AC</i>. The Th2 cytokines IL-4, IL-9, and IL-13 did not stimulate <i>MUC5AC</i> or <i>MUC5B</i> in our experiments. A similar stimulation of <i>MUC5B/Muc5b</i> expression by IL-6 and IL-17 was demonstrated in primary monkey and mouse TBE cells. Further investigation of <i>MUC5B</i> expression demonstrated that IL-17's effect is at least partly mediated through IL-6 by a JAK2-dependent autocrine/paracrine loop. Finally, evidence is presented to show that both IL-6 and IL-17 mediate <i>MUC5B</i>expression through the ERK signaling pathway.

Background Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. Methods We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556. Findings Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0–3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81–3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0–3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20–7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31–7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. Interpretation There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. Funding Jiangsu Provincial Special Program of Medical Science.

Abstract Using microarray gene expression analysis, we first observed a profound elevation of human β-defensin-2 (hBD-2) message in IL-17-treated primary human airway epithelial cells. Further comparison of this stimulation with a panel of cytokines (IL-1α, 1β, 2–13, and 15–18; IFN-γ; GM-CSF; and TNF-α) demonstrated that IL-17 was the most potent cytokine to induce hBD-2 message (&amp;gt;75-fold). IL-17-induced stimulation of hBD-2 was time and dose dependent, and this stimulation also occurred at the protein level. Further studies demonstrated that hBD-2 stimulation was attenuated by IL-17R-specific Ab, but not by IL-1R antagonist or the neutralizing anti-IL-6 Ab. This suggests an IL-17R-mediated signaling pathway rather than an IL-17-induced IL-1αβ and/or IL-6 autocrine/paracrine loop. hBD-2 stimulation was sensitive to the inhibition of the JAK pathway, and to the inhibitors that affect NF-κB translocation and the DNA-binding activity of its p65 NF-κB subunit. Transient transfection of airway epithelial cells with an hBD-2 promoter-luciferase reporter gene expression construct demonstrated that IL-17 stimulated promoter-reporter gene activity, suggesting a transcriptional mechanism for hBD-2 induction. These results support an IL-17R-mediated signaling pathway involving JAK and NF-κB in the transcriptional stimulation of hBD-2 gene expression in airway epithelium. Because IL-17 has been identified in a number of airway diseases, especially diseases related to microbial infection, these findings provide a new insight into how IL-17 may play an important link between innate and adaptive immunity, thereby combating infection locally within the airway epithelium.

There are remarkable disparities among patients of different races with prostate cancer; however, the mechanism underlying this difference remains unclear. Here, we present a comprehensive landscape of the transcriptome profiles of 14 primary prostate cancers and their paired normal counterparts from the Chinese population using RNA-seq, revealing tremendous diversity across prostate cancer transcriptomes with respect to gene fusions, long noncoding RNAs (long ncRNA), alternative splicing and somatic mutations. Three of the 14 tumors (21.4%) harbored a TMPRSS2-ERG fusion, and the low prevalence of this fusion in Chinese patients was further confirmed in an additional tumor set (10/54=18.5%). Notably, two novel gene fusions, CTAGE5-KHDRBS3 (20/54=37%) and USP9Y-TTTY15 (19/54=35.2%), occurred frequently in our patient cohort. Further systematic transcriptional profiling identified numerous long ncRNAs that were differentially expressed in the tumors. An analysis of the correlation between expression of long ncRNA and genes suggested that long ncRNAs may have functions beyond transcriptional regulation. This study yielded new insights into the pathogenesis of prostate cancer in the Chinese population.

Osteoporosis is a progressive skeletal disease characterized by decreased bone mass and degraded bone microstructure, which leads to increased bone fragility and risks of bone fracture. Osteoporosis is generally age related and has become a major disease of the world. Uncovering the molecular mechanisms underlying osteoporosis and developing effective prevention and therapy methods has great significance for human health. Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into osteoblasts, adipocytes, or chondrocytes, and have become the favorite source of cell-based therapy. Evidence shows that during osteoporosis, a shift of the cell differentiation of MSCs to adipocytes rather than osteoblasts partly contributes to osteoporosis. Thus, uncovering the molecular mechanisms of the osteoblast or adipocyte differentiation of MSCs will provide more understanding of MSCs and perhaps new methods of osteoporosis treatment. The MSCs have been applied to both preclinical and clinical studies in osteoporosis treatment. Here, we review the recent advances in understanding the molecular mechanisms regulating osteoblast differentiation and adipocyte differentiation of MSCs and highlight the therapeutic application studies of MSCs in osteoporosis treatment. This will provide researchers with new insights into the development and treatment of osteoporosis.

The major challenge for accurate fingerprint-based indoor localization is the design of robust and discriminative wireless signatures. Even though WiFi RSSI signatures are widely available indoors, they vary significantly over time and are susceptible to human presence, multipath, and fading due to the high operating frequency. To overcome these limitations, we propose to use FM broadcast radio signals for robust indoor fingerprinting. Because of the lower frequency, FM signals are less susceptible to human presence, multipath and fading, they exhibit exceptional indoor penetration, and according to our experimental study they vary less over time when compared to WiFi signals. In this work, we demonstrate through a detailed experimental study in 3 different buildings across the US, that FM radio signal RSSI values can be used to achieve room-level indoor localization with similar or better accuracy to the one achieved by WiFi signals. Furthermore, we propose to use additional signal quality indicators at the physical layer (i.e., SNR, multipath etc.) to augment the wireless signature, and show that localization accuracy can be further improved by more than 5%. More importantly, we experimentally demonstrate that the localization errors of FM andWiFi signals are independent. When FM and WiFi signals are combined to generate wireless fingerprints, the localization accuracy increases as much as 83% (when accounting for wireless signal temporal variations) compared to when WiFi RSSI only is used as a signature.

<h3>Importance</h3> Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. <h3>Objective</h3> To evaluate the association between EVT and clinical outcomes of patients with acute BAO. <h3>Design, Setting, and Participants</h3> This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. <h3>Main Outcomes and Measures</h3> The primary outcome was the improvement in modified Rankin Scale scores (range, 0 to 6 points, with higher scores indicating greater disability) at 90 days across the 2 groups assessed as a common odds ratio using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as modified Rankin Scale scores of 3 or less (indicating an ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality. <h3>Results</h3> A total of 1254 patients were assessed, and 829 patients (of whom 612 were men [73.8%]; median [interquartile] age, 65 [57-74] years) were recruited into the study. Of these, 647 were treated with standard medical treatment plus EVT and 182 with standard medical treatment alone. Ninety-day functional outcomes were substantially improved by EVT (adjusted common odds ratio, 3.08 [95% CI, 2.09-4.55];<i>P</i> &lt; .001). Moreover, EVT was associated with a significantly higher rate of 90-day modified Rankin Scale scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75];<i>P</i> &lt; .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40];<i>P</i> &lt; .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.

Although chemotherapy, targeted therapy and endocrine therapy decrease rate of disease recurrence in most breast cancer patients, many patients exhibit acquired resistance. Hyperactivation of the PI3K/AKT/mTOR pathway is associated with drug resistance and cancer progression. Currently, a number of drugs targeting PI3K/AKT/mTOR are being investigated in clinical trials by combining them with standard therapies to overcome acquired resistance in breast cancer. In this review, we summarize the critical role of the PI3K/AKT/mTOR pathway in drug resistance, the development of PI3K/AKT/mTOR inhibitors, and strategies to overcome acquired resistance to standard therapies in breast cancer.

Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men.To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa.The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors.The genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses.We demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated.There are shared and salient genetic characteristics of PCa in Chinese and Caucasian men. Novel genetic alterations in PCDH9 and PLXNA1 were associated with disease progression.We reported the first large-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment.

The evolution of insect resistance to pesticides poses a continuing threat to agriculture and human health. While much is known about the proximate molecular and biochemical mechanisms that confer resistance, far less is known about the regulation of the specific genes/gene families involved, particularly by trans-acting factors such as signal-regulated transcription factors. Here we resolve in fine detail the trans-regulation of CYP6CM1, a cytochrome P450 that confers resistance to neonicotinoid insecticides in the whitefly Bemisia tabaci, by the mitogen-activated protein kinase (MAPK)-directed activation of the transcription factor cAMP-response element binding protein (CREB). Reporter gene assays were used to identify the putative promoter of CYP6CM1, but no consistent polymorphisms were observed in the promoter of a resistant strain of B. tabaci (imidacloprid-resistant, IMR), which overexpresses this gene, compared to a susceptible strain (imidacloprid-susceptible, IMS). Investigation of potential trans-acting factors using in vitro and in vivo assays demonstrated that the bZIP transcription factor CREB directly regulates CYP6CM1 expression by binding to a cAMP-response element (CRE)-like site in the promoter of this gene. CREB is overexpressed in the IMR strain, and inhibitor, luciferase, and RNA interference assays revealed that a signaling pathway of MAPKs mediates the activation of CREB, and thus the increased expression of CYP6CM1, by phosphorylation-mediated signal transduction. Collectively, these results provide mechanistic insights into the regulation of xenobiotic responses in insects and implicate both the MAPK-signaling pathway and a transcription factor in the development of pesticide resistance.

The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment.We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for &gt;10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target &lt;120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres.Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups.Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion.The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.

Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine.We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 1011 viral particles per mL; 0·1 mL; low dose group), or a high dose (1·0 × 1011 viral particles per mL; 0·2 mL; high dose group) aerosolised Ad5-nCoV, or a homologous intramuscular vaccination with CoronaVac (0·5 mL). Only laboratory staff were masked to group assignment. The primary endpoint for safety was the incidence of adverse reactions within 14 days after the booster dose. The primary endpoint for immunogenicity was the geometric mean titres (GMTs) of serum neutralising antibodies (NAbs) against live SARS-CoV-2 virus 14 days after the booster dose. This study was registered with ClinicalTrials.gov, NCT05043259.Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p<0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p<0·0001).We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination.National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program.

Capillary imbibition, such as plant roots taking up water, reservoir rocks absorbing brine and a tissue paper wiping stains, is pervasive occurred in nature, engineering and industrial fields, as well as in our daily life. This phenomenon is earliest modeled through the process that wetting liquid is spontaneously propelled by capillary pressure into regular geometry models. Recent studies have attracted more attention on capillary-driven flow models within more complex geometries of the channel, since a detailed understanding of capillary imbibition dynamics within irregular geometry models necessitates the fundamentals to fluid transport mechanisms in porous media with complex pore topologies. Herein, the fundamentals and concepts of different capillary imbibition models in terms of geometries over the past 100 years are reviewed critically, such as circular and non-circular capillaries, open and closed capillaries with triangular/rectangular cross-sections, and heterogeneous geometries with axial variations. The applications of these models with appropriate conditions are discussed in depth accordingly, with a particular emphasize on the capillary flow pattern as a consequence of capillary geometry. In addition, a universal model is proposed based on the dynamic wetting condition and equivalent cylindrical geometry to describe the capillary imbibition process in terms of various solid topologies. Finally, future research is suggested to focus on analyzing the dynamics during corner flow, the snap-off of wetting fluid, the capillary rise of non-Newtonian fluids and applying accurate physical simulation methods on capillary-driven flow processes. Generally, this review provides a comprehensive understanding of the capillary-driven flow models inside various capillary geometries and affords an overview of potential advanced developments to enhance the current understanding of fluid transport mechanisms in porous media.

Chronic low-grade inflammation in adipose tissue (AT) is a hallmark of obesity and contributes to various metabolic disorders, such as type 2 diabetes and cardiovascular diseases. Inflammation in ATs is characterized by macrophage infiltration and the activation of inflammatory pathways mediated by NF-κB, JNK, and NLRP3 inflammasomes. Adipokines, hepatokines and myokines - proteins secreted from AT, the liver and skeletal muscle play regulatory roles in AT inflammation via endocrine, paracrine, and autocrine pathways. For example, obesity is associated with elevated levels of pro-inflammatory adipokines (e.g., leptin, resistin, chemerin, progranulin, RBP4, WISP1, FABP4, PAI-1, Follistatin-like1, MCP-1, SPARC, SPARCL1, and SAA) and reduced levels of anti-inflammatory adipokines such as adiponectin, omentin, ZAG, SFRP5, CTRP3, vaspin, and IL-10. Moreover, some hepatokines (Fetuin A, DPP4, FGF21, GDF15, and MANF) and myokines (irisin, IL-6, and DEL-1) also play pro- or anti-inflammatory roles in AT inflammation. This review aims to provide an updated understanding of these organokines and their role in AT inflammation and related metabolic abnormalities. It serves to highlight the molecular mechanisms underlying the effects of these organokines and their clinical significance. Insights into the roles and mechanisms of these organokines could provide novel and potential therapeutic targets for obesity-induced inflammation.

Flexible conductive hydrogels with self-healing ability have attracted great attention in the fields of wearable devices and healthcare monitoring due to their recoverability and sustainability. Herein, the application of inorganic antimony sulfide (Sb2S3) as photothermal agent is extended to the field of self-healing hydrogel for the first time. A near-infrared (NIR) light-induced rapid self-healing double-network conductive hydrogel (SPOH gel) via on-demand irradiation was fabricated by incorporating dopamine (DA)-modified polypyrrole (PPy) coated Sb2S3 nanorod (Sb2S3 @PPy-DA) into the polymer matrix of polyvinyl alcohol (PVA)/poly(N-(2-hydroxyethyl)acrylamide) (pHEAA) in a water-glycerol dispersion medium. The SPOH gel with adhesive and anti-freezing properties exhibited robust tensile strength (1.25 MPa), large elongation (620%), high interfacial toughness (251 J/m2), and outstanding sensitivity (GF = 4.97). The incorporation of Sb2S3 @PPy-DA for SPOH gel endowed high conductivity (2.26 S/m) and promoted rapid self-healing process under NIR light irradiation (within 90 s). Moreover, SPOH gel could be widely applied to various applications, including monitoring various human motions as strain sensor, detecting electrocardiogram signals as biopotential electrodes, and harvesting energy as self-powered device. The multifunctional SPOH gel with the integrated attractive capabilities of rapid self-reparability and real-time physiological signal detection, providing a promising route to develop wearable smart devices in motion monitoring, healthcare management, and energy harvesting applications.

The accurate prediction of power load is helpful to make reasonable power generation plans and scientific dispatching schemes and achieve the goal of energy saving and emission reduction. There are many factors influencing the power load, and there may be a nonlinear relationship between the power load and these influencing factors. A new fractional multivariate grey Bernoulli model, referred to as MFGBM (q, r, N), is developed in this article for the short-term prediction of power load. The fractional differential equation and fractional accumulation generation are integrated into MFGBM (q, r, N). Second, this paper improves the grey wolf algorithm to better optimize many parameters in the model. The algorithm is improved by using a chaotic Tent map to optimize the initial population composition, adding inertia weights to change the position vector of the grey wolf, and introducing a nonlinear function and Lévy flight to enhance local exploitation and global exploration ability. Finally, this paper selects the daytime and nighttime power loads in Australia and takes the electricity price, humidity, and temperature as the influencing factors to validate the prediction capability of MFGBM (q, r, N). Our findings indicate that MFGBM (q, r, N) is highly applicable to short-term power system prediction.

Coronavirus disease 2019 (COVID-19) is an emerging human-to-human infectious disease that broke out in early December 2019 and threatens global public health, causing widespread concern. This respiratory disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The development of rapid and reliable techniques for COVID-19 diagnosis is a significant step to prevent further infections. Combinations of genome sequencing, nucleic acid molecular testing, clustered regularly interspaced short palindromic repeats editing technology, antigen/antibody detection, and computed tomography imaging have been implemented to identify and screen COVID-19 infections. Moreover, other new diagnosis methods such as dried blood spots and biosensors are being developed and are summarized here. This manuscript reviews currently available methods for SARS-CoV-2 detection with the aim of helping researchers develop timely and effective technologies to detect this emerging virus and its variants.

Lithium-ion batteries (LIBs) are frequently employed in electric vehicles for their high energy density and lengthy cycle life. However, efficient battery thermal management system (BTMS) is critical for ensuring the reliability, safety, and service life, as temperature greatly impacts their performance. The potential risks of battery fire and explosion under excessive temperatures necessitate the development of effective emergency management and technologies to maintain safe operation. Phase change material (PCM) which offers distinct advantages, including reasonable cost, low energy consumption, and excellent temperature uniformity, making it an attractive candidate for thermal management, has emerged as a promising solution for BTMS. This comprehensive review aims to shed light on PCM-based BTMS, and it is found that carbon-based additives are better than metal-based additives concerning density and stability, and the addition of polymers and nanomaterials can improve the structural stability and mechanical properties. However, the flammability of PCM exacerbates the fire risk and hazard of battery thermal runaway (TR), and this review also has a particular emphasis on enhancing PCM's flame retardant properties and exploring its applications in BTMS. Flame-retardant PCM can ensure the safety of LIB utilization process and has a promising application in suppressing TR. Moreover, there exists a prominent challenge of the comprehensive need for optimization of heat dissipation optimization and improvement of TR propagation suppression ability of PCM-based BTMS. Finally, the challenges and outlooks focus on the future PCM-based BTMS are disclosed, in the hope of bring new insights to building a synergistic BTMS.

Based on the concept of direct contact liquid cooling, a compact oil-immersed battery thermal management system is designed in this work. In the experiment, methyl silicone oil, white oil, and transformer oil are used as coolants to study the cooling effect and the heat transfer characteristics of the system. It is found that three oils show good cooling effects and temperature uniformity in general at three discharge rates. The maximum average temperatures of the battery module immersed in silicon oil, white oil, and transformer oil reach 53 °C, 47.3 °C, and 45.6 °C, respectively, under the maximum discharge condition (2 C). It decreases by about 25 %, 33 %, and 35 % compared with the maximum temperature of the battery module under natural convection cooling (70.5 °C). In addition, the theoretical analysis verifies that the battery heat production and the ratio of heat absorbed by three oils to the total heat production increases with the discharge rate. At the end of 2 C discharge, the ratio of heat absorbed by silicone oil, white oil, and transformer oil to the total heat production reaches 38.9 %, 46.3 %, and 49.5 %, respectively. Theoretical calculations show that all three oils can effectively absorb the heat generated by the battery, and especially transformer oil can achieve an excellent cooling effect. The results further confirm the effectiveness of the oil-immersed battery thermal management system, which provides additional new insights for the future development of battery thermal management systems based on immersion cooling.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide (TGP) and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP (5.1×10 3 Da) was composed of mannose, glucosamine, rhamnose, glucuronic acid, galactosamine, glucose, galactose, xylose, and fucose.It could significantly alleviate weight loss, reduce fasting blood glucose levels, reverse dyslipidemia, reduce liver damage from oxidative stress, and improve insulin sensitivity.RT-PCR and western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum, Akkermansia, and Bifidobacterium, restored the microbiota abundance in the intestinal tracts of mice with T2DM, and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.

Partially reduced metabolites of molecular oxygen, superoxide (O2-) and hydrogen peroxide (H2O2), are detected in respiratory tract lining fluid, and it is assumed that these are key components of innate immunity. Whether these reactive oxygen species (ROS) are produced specifically by the respiratory epithelium in response to infection, or are a non-specific by-product of oxidant-producing inflammatory cells is not well characterized. Increasing evidence supports the hypothesis that the dual function NAD(P)H oxidases/peroxidases, Duox1 and Duox2, are important sources of regulated H2O2 production in respiratory tract epithelium. However, no studies to date have characterized the regulation of Duox gene expression. Accordingly, we examined Duox1 and Duox2 mRNA expression by real-time PCR in primary respiratory tract epithelial cultures after treatment with multiple cytokines. Herein, we determined that Duox1 expression was increased several-fold by treatment with the Th2 cytokines IL-4 and IL-13, whereas Duox2 expression was highly induced following treatment with the Th1 cytokine IFN-gamma. Duox2 expression was also elevated by polyinosine-polycytidylic acid (poly(I:C)) and rhinovirus infection. Diphenyleneiodonium (DPI)-inhibitable apical H2O2 production was similarly increased by the addition of Th1 or Th2 cytokines. These results demonstrate for the first time the regulation of Duox expression by immunomodulatory Th1 and Th2 cytokines, and suggest a mechanism by which ROS production can be regulated in the respiratory tract as part of the host defense response.

Gel-forming mucins are major contributors to the viscoelastic properties of mucus secretion. Currently, four gel-forming mucin genes have been identified: MUC2, MUC5AC, MUC5B, and MUC6. All these genes have five major cysteine-rich domains (four von Willebrand factor [vWF] C or D domains and one Cystine-knot [CT] domain) as their distinctive features, in contrast to other non-gel-forming type of mucins. The CT domain is believed to be involved in the initial mucin dimer formation and have very succinct relationship between different gel-forming mucins across different species. Because of gene duplication and evolutional modification, it is very likely that other gel-forming mucin genes exist. To search for new gel-forming mucin candidate genes, a "Hidden Markov Model"(HMM) was built from the common features of the CT domains of those gel-forming mucins. By using this model to screen all protein databases as well as the six-frame translated expression sequence tag and translated human genomic databases, we identified a locus located at the peri-centromere region of human chromosome 12 and the corresponding homologous region of mouse chromosome 15. We cloned the 3' end of this gene and its mouse homolog. We found one vWF C domain, one CT domain, and various mucin-like threonine/serine-rich repeats. Phylogenetic analysis indicated the close relationship between this gene and the submaxillary mucin from porcine and bovine. A polydispersed signal was observed on the Northern blot, which indicates very large mRNA size. Further analysis of the upstream genomic sequences generated from human and mouse genome projects revealed three additional vWF D domains and many mucin-like threonine/serine-rich repeats. The expression of this gene is restricted to the mucous cells of various glandular tissues, including sublingual gland, submandibular gland, and submucosal gland of the trachea. Based on the chronological convention, we have given the name MUC19 to the human ortholog and Muc19 to the mouse.

CCL20, like human beta-defensin (hBD)-2, is a potent chemoattractant for CCR6-positive immature dendritic cells and T cells in addition to recently found antimicrobial activities. We previously demonstrated that IL-17 is the most potent cytokine to induce an apical secretion and expression of hBD-2 by human airway epithelial cells, and the induction is JAK/NF-kappaB-dependent. Similar to hBD-2, IL-17 also induced CCL20 expression, but the nature of the induction has not been elucidated. Compared with a panel of cytokines (IL-1alpha, 1beta, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 18, IFN-gamma, GM-CSF, and TNF-alpha), IL-17 was as potent as IL-1alpha, 1beta, and TNF-alpha, with a time- and dose-dependent phenomenon in stimulating CCL20 expression in both well-differentiated primary human and mouse airway epithelial cell culture systems. The stimulation was largely dependent on the treatment of polarized epithelial cultures from the basolateral side with IL-17, achieving an estimated 4- to 10-fold stimulation at both message and protein levels. More than 90% of induced CCL20 secretion was toward the basolateral compartment (23.02 +/- 1.11 ng/chamber/day/basolateral vs 1.82 +/- 0.82 ng/chamber/day/apical). Actinomycin D experiments revealed that enhanced expression did not occur at mRNA stability. Inhibitor studies showed that enhanced expression was insensitive to inhibitors of JAK/STAT, p38, JNK, and PI3K signaling pathways, but sensitive to inhibitors of MEK1/2 and NF-kappaB activation, suggesting a MEK/NF-kappaB-based mechanism. These results suggest that IL-17 can coordinately up-regulate both hBD-2 and CCL20 expressions in airways through differentially JAK-dependent and -independent activations of NF-kappaB-based transcriptional mechanisms, respectively.

A novel natural rubber/silica (NR/SiO2) nanocomposite is developed by combining self-assembly and latex-compounding techniques. The results show that the SiO2 nanoparticles are homogenously distributed throughout NR matrix as nano-clusters with an average size ranged from 60 to 150 nm when the SiO2 loading is less than 6.5 wt%. At low SiO2 contents (⩽4.0 wt%), the NR latex (NRL) and SiO2 particles are assembled as a core-shell structure by employing poly (diallyldimethylammonium chloride) (PDDA) as an inter-medium, and only primary aggregations of SiO2 are observed. When more SiO2 is loaded, secondary aggregations of SiO2 nanoparticles are gradually generated, and the size of SiO2 cluster dramatically increases. The thermal/thermooxidative resistance and mechanical properties of NR/SiO2 nanocomposites are compared to the NR host. The nanocomposites, particularly when the SiO2 nanoparticles are uniformly dispersed, possess significantly enhanced thermal resistance and mechanical properties, which are strongly depended on the morphology of nanocomposites. The NR/SiO2 has great potential to manufacture medical protective products with high performances.

Prostate cancer risk-associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk-associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10(-14)) and 19q13.4 (rs103294, P = 5.34 × 10(-16)) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10(-4)). These findings may advance the understanding of genetic susceptibility to prostate cancer.

Non-fouling surfaces that resist non-specific adsorption of proteins, bacteria, and higher organisms are of particular interest in diverse applications ranging from marine coatings to diagnostic devices and biomedical implants. Poly(ethylene glycol) (PEG) is the most frequently used polymer to impart surfaces with such non-fouling properties. Nevertheless, limitations in PEG stability have stimulated research on alternative polymers that are potentially more stable than PEG. Among them, we previously investigated poly(2-methyl-2-oxazoline) (PMOXA), a peptidomimetic polymer, and found that PMOXA shows excellent anti-fouling properties. Here, we compare the stability of films self-assembled from graft copolymers exposing a dense brush layer of PEG and PMOXA side chains, respectively, in physiological and oxidative media. Before media exposure both film types prevented the adsorption of full serum proteins to below the detection limit of optical waveguide in situ measurements. Before and after media exposure for up to 2 weeks, the total film thickness, chemical composition, and total adsorbed mass of the films were quantified using variable angle spectroscopic ellipsometry (VASE), X-ray photoelectron spectroscopy (XPS), and optical waveguide lightmode spectroscopy (OWLS), respectively. We found (i) that PMOXA graft copolymer films were significantly more stable than PEG graft copolymer films and kept their protein-repellent properties under all investigated conditions and (ii) that film degradation was due to side chain degradation rather than due to copolymer desorption.

Warm ischemic injury is one of the most important factors affecting renal function in partial nephrectomy (PN). The technique of segmental renal artery clamping emerges as an alternative to conventional renal artery clamping for renal hilar control. To evaluate the feasibility and efficiency of laparoscopic PN (LPN) with segmental renal artery clamping in comparison with the conventional technique. A total of 75 patients underwent LPN from June 2007 to November 2009. All patients had T1a or T1b tumor in one kidney and a normal contralateral kidney. Thirty-seven patients underwent surgeries with main renal artery clamping, and 38 underwent surgeries with segmental artery clamping. All procedures were performed by the same laparoscopic surgeon. Blood loss, operation time, warm ischemia (WI) time, and complications affected renal function before and after operation were recorded. All LPNs were completed without conversion to open surgery or nephrectomy. The novel technique slightly increased WI time (p < 0.001) and intraoperative blood loss (p = 0.006), while it provided better postoperative affected renal function (p < 0.001) compared with the conventional technique. The total complication rate was 12%. Among the 38 cases where segmental renal artery clamping was performed, 7 had to convert to the conventional method. Tumor size and location influenced the number of clamped segmental arteries. Long-term postoperative renal function is still awaited. LPN with segmental artery clamping is safe and feasible in clinical practice. It minimizes the intraoperative WI injury and improves early postoperative affected renal function compared with main renal artery clamping.

Mucociliary clearance is a critical innate defense system responsible for clearing up invading pathogens including bacteria and virus. Although the right amount of mucus is good, excessive mucus causes airway obstruction and tends to precipitate disease symptoms. Rhinovirus (RV) is a common cold virus that causes asthma and chronic obstructive pulmonary disease exacerbation. Mucus overproduction has been linked to the pathogenesis of RV-induced diseases and disease exacerbations. However, the molecular mechanism is not clear. In this study, using one of the major airway mucin-MUC5AC as marker, we found that both major and minor groups of RV induced mucin production in primary human epithelial cells and cell line. RV1A (a minor group of RV) could induce mucous cell metaplasia in vivo. Viral replication was needed for RV-induced mucin expression, and this induction was also dependent on TLR3, suggesting the involvement of double-stranded (ds) RNA signaling. Indeed, dsRNA alone could also induce mucin expression. TLR3-mediated mucin induction was negatively regulated by MyD88, and only partially dependent on TRIF, which suggests a departure from well-documented TLR3 signaling paradigm that mediates inflammatory and other innate defense gene inductions. In addition, TLR3 signaling activated epidermal growth factor receptor (EGFR) through inductions of the expression of EGFR ligands (transforming growth factor-alpha and amphiregulin), which in turn activated EGFR-ERK signaling and mucin expression through an autocrine/paracrine loop. This novel coupling of antiviral defense machinery (i.e., TLR3) and major epithelial proliferation/repair pathway (i.e., EGFR) might play an important role in viral-induced airway remodeling and airway disease exacerbation.

The incidence of prostate cancer (PCa) within Asian population used to be much lower than in the Western population; however, in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly. This collaborative report summarized the latest epidemiology information, risk factors, and racial differences in PCa diagnosis, current status and new trends in surgery management and novel agents for castration-resistant prostate cancer. We believe such information would be helpful in clinical decision making for urologists and oncologists, health-care ministries and medical researchers.

Benzothiazole (BTH) and its derivatives 2-(methylthio)bezothiazole (MTBT), 2-benzothiazolsulfonate (BTSA), and 2-hydroxybenzothiazole (OHBT) are refractory pollutants ubiquitously existing in urban runoff at relatively high concentrations. Here, we report their oxidation by CuFe2O4-activated peroxomonosulfate (PMS/CuFe2O4), focusing on kinetics and transformation intermediates. These benzothiazoles can be efficiently degraded by this oxidation process, which is confirmed to generate mainly sulfate radicals (with negligible hydroxyl-radical formation) under slightly acidic to neutral pH conditions. The molar exposure ratio of sulfate radical to residual PMS (i.e., Rct) for this process is a constant that is related to the reaction condition and can be easily determined. The reaction rate constants of these benzothiazoles toward sulfate radical are (3.3 ± 0.3) × 109, (1.4 ± 0.3) × 109, (1.5 ± 0.1) × 109, and (4.7 ± 0.5) × 109 M–1 s–1, respectively (pH 7 and 20 °C). On the basis of Rct and these rate constants, their degradation in the presence of organic matter can be well-predicted. A number of transformation products were detected and tentatively identified using triple-quadruple/linear ion trap MS/MS and high-resolution MS. It appears that sulfate radicals attack BTH, MTBT, and BTSA on their benzo ring via electron transfer, generating multiple hydroxylated intermediates that are reactive toward common oxidants. For OHBT oxidation, the thiazole ring is preferentially broken down. Due to competitions of the transformation intermediates, a minimum PMS/pollutant molar ratio of 10–20 is required for effective degradation. The flexible PMS/CuFe2O4 could be a useful process to remove the benzothiazoles from low dissolved organic carbon waters like urban runoff or polluted groundwater.

A homogeneous exopolysaccharide, designated As1-1, was obtained from the culture medium of the mangrove endophytic fungus Aspergillus sp. Y16 and purified by anion-exchange and gel-permeation chromatography. Results of chemical and spectroscopic analyses, including one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopy showed that As1-1 was mainly composed of mannose with small amounts of galactose, and that its molecular weight was about 15 kDa. The backbone of As1-1 mainly consists of (1 → 2)-linked α-d-mannopyranose units, substituted at C-6 by the (1 → 6)-linked α-d-mannopyranose, (1→)-linked β-d-galactofuranose and (1→)-linked β-d-mannopyranose units. As1-1 possessed good in vitro antioxidant activity as evaluated by scavenging assays involving 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide radicals. The investigation demonstrated that As1-1 is an exopolysaccharide different from those of other marine microorganisms, and could be a potential antioxidant and food supplement.

Multifunctional theranostics have offered some interesting new opportunities for cancer therapy and diagnosis in the last decade. Herein, magnetic mesoporous silica nanoparticles (M-MSNs) were designed and synthesized, then the photosensitizer chlorin e6 (Ce6) and antitumor drug doxorubicin (Dox) were adsorbed onto the M-MSNs. Biocompatible alginate/chitosan polyelectrolyte multilayers (PEM) were assembled on the M-MSNs to achieve a pH-responsive drug delivery system and adsorb P-gp shRNA for reversing the multidrug resistance. The obtained M-MSN(Dox/Ce6)/PEM/P-gp shRNA nanocomposites were characterized using TEM, SEM, X-ray diffraction, BET, FTIR and electrophoresis. The nanocomposites with average diameter of 280 nm exhibited a pH-responsive drug release profile, and more singlet oxygen generation in cancer cells after laser illumination. CCK-8 assay and calcein-AM/PI co-staining showed that the multifunctional nanocomplexes significantly increased cell apoptosis in vitro. With tumor-bearing Balb/c mice employed as the animal model, combined photodynamic therapy and chemotherapy was carried out, also achieving synergistic anti-tumor effects in vivo. The cores of bifunctional Fe3O4-Au nanoparticles in the multifunctional nanocomposites enabled dual-modal MR and CT imaging, which illustrated strong tumor uptake of these nanocomposites after intravenous injection into tumor-bearing mice. This work highlights the great potential of magnetic mesoporous silica nanocomposites as a multifunctional delivery platform, which is promising for imaging-guided cancer combination therapy with high efficacy.

Human sperm cryopreservation in assisted reproductive technology is the only proven method that enables infertile men to father their own children. However, freezing and thawing reduces spermatozoon motility, viability, and fertilizing ability. An association between dysfunctional spermatozoa due to cryoinjury and protein changes has not been established. We investigated through proteomic analysis the differential protein characteristics between freeze‐thawed and fresh sperm samples obtained from nine normozoospermic donors. Twenty‐seven proteins differed in abundance between the two groups, and results were verified for four proteins via Western blot and immunofluorescent staining. These proteins are putatively involved in sperm motility, viability, acrosomal integrity, ATP and isocitrate content, mitochondrial membrane potential, capacitation, acrosome reaction, and intracellular calcium concentration. These marked differences suggest that dysfunctional spermatozoon after cryopreservation may be due to protein degradation and protein phosphorylation.

A sulfated polysaccharide FEP from marine green alga Enteromorpha clathrata was extracted with hot water and further purified by ion-exchange and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that FEP was a high arabinose-containing sulfated polysaccharide with sulfate ester of 31.0%, and its average molecular weight was about 511 kDa. The backbone of FEP was mainly composed of (1 → 4)-linked β-l-arabinopyranose residues with partially sulfate groups at the C-3 position. In vitro anticoagulant assay indicated that FEP effectively prolonged the activated partial thromboplastin time and thrombin time. The investigation demonstrated that FEP was a novel sulfated polysaccharide with different chemical characteristics from other sulfated polysaccharides from marine algae, and could be a potential source of anticoagulant.

PIWI-interacting RNAs (piRNAs) are a newly identified class of small non-coding RNAs that can play important roles in germline development and carcinogenesis. In this study, piRNA microarrays were used to investigate global piRNA expression in three bladder cancer tissues and their adjacent normal tissues. Using the 3' untranslated region (UTR) sequence complementarily method, we predicted the target gene of piRNA. Our results showed that the expression levels of 106 piRNAs were up-regulated and 91 were down-regulated in bladder cancer tissues, among which the fold-change of down-regulated piRNA DQ594040 associated with bladder cancer (piRABC) was the highest piRNA. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm piRABC expression in paired bladder cancer tissues and their adjacent normal tissues (n = 25). Over-expression of piRABC can inhibit bladder cancer cell proliferation, colony formation, and promote cell apoptosis (all P < 0.05). Luciferase reporter gene assays indicated that piRABC could increase the luciferase activity of TNFSF4. Western blotting analyses and ELISA assays also confirmed that the expression of TNFSF4 protein was up-regulated in control subjects compared with bladder cancer subjects. In conclusion, piRABC plays a crucial role in the development of bladder cancer.

Minimizing warm ischemic (WI) injury is one technical focus of partial nephrectomy (PN). Inducing regional ischemia in the tumor area by clamping segmental renal arteries has become an alternative method to decrease WI injury. To study the technical feasibility of precise segmental artery clamping under the guidance of dual-source computed tomography (DSCT) angiography during laparoscopic partial nephrectomy (LPN) and to analyze the factors affecting surgical outcomes. Retrospective analysis of 125 patients with unilateral kidney tumor treated from December 2009 to November 2011 with a mean follow-up of 18 mo. All patients received retroperitoneal LPN with the feeding segmental arteries precisely clamped. Most of the target branches were dissected close to the hilar parenchyma. The tumor was excised after precise clamping and renorrhaphy was performed. Univariable and multivariable logistic regression analyses were performed for categorical variables, and continuous variables were analyzed by linear regression. The target branches were isolated and clamped successfully in all patients without clamping the main renal artery. Median estimated blood loss (EBL) was 200 ml, and nine patients received blood transfusion. The accuracy of feeding artery orientation by DSCT angiography reached 93.6%. Tumor size, location, and growth pattern independently influenced the number of clamped branches. The number of clamped branches was significantly associated with postoperative renal function and EBL. Limitations of this study include its retrospective nature and that data are from a single-surgeon series. The precise segmental artery clamping technique under the guidance of DSCT angiography is feasible and efficient to excise the tumor and to protect the normal parenchyma. The number of clamped branches is associated with tumor characteristics and can predict EBL and loss of renal function.

The development of a facile and versatile strategy to endow surfaces with synergistically anti-inflammatory, antimicrobial, and anticoagulant functions is of particular significance for blood-contacting biomaterials and medical devices. In this work, we report a simple and environmentally friendly “one-pot” method inspired by byssal cuticle chemistry, namely, [Fe(dopa)3] coordination chemistry for assembly of copper ions (Cu2+) and plant polyphenol (tannic acid)/catecholamine (dopamine or norepinephrine) to form metal–phenolic/catecholamine network-based coatings. This one-pot method enabled us to easily develop a multifunctional surface based on the combination of the characteristic functions of metal ions and plant polyphenol or catecholamine. The residual phenolic hydroxyl groups on the coatings imparted the modified surface with excellent antioxidant and anti-inflammatory functions. The robust chelation of copper ions to the metal–phenolic/catecholamine networks provided not only durable antibacterial property but also glutathione peroxidase like catalytic capability to continuously and controllably produce antithrombotic nitric oxide by catalyzing endogenous S-nitrothiol. The biological functions of such coatings could be well regulated by adjusting the ratios of the feed concentration of Cu2+ ions to plant polyphenol or catecholamine. We envision that our simple, multifunctional, and bioinspired coating strategy can hold great application promise for bioengineering blood-contacting devices.

Abstract Ubiquitously distributed in different plant species, plant lectins are highly diverse carbohydrate‐binding proteins of non‐immune origin. They have interesting pharmacological activities and currently are of great interest to thousands of people working on biomedical research in cancer‐related problems. It has been widely accepted that plant lectins affect both apoptosis and autophagy by modulating representative signalling pathways involved in Bcl‐2 family, caspase family, p53, PI 3K/Akt, ERK , BNIP 3, Ras‐Raf and ATG families, in cancer. Plant lectins may have a role as potential new anti‐tumour agents in cancer drug discovery. Thus, here we summarize these findings on pathway‐ involved plant lectins, to provide a comprehensive perspective for further elucidating their potential role as novel anti‐cancer drugs, with respect to both apoptosis and autophagy in cancer pathogenesis, and future therapy.

The Yunmengshan metamorphic core complex (YMMCC) is situated in the northern part of the eastern North China Craton (NCC). The main structures in the YMMCC area include the arcuate Sihetang shear zone (SHTSZ) and the NE-striking Shuiyu shear zone (SYSZ). We present structural and geochronological evidence to show that the SHTSZ was a top-to-the-SSW thrusting zone formed between 140 and 137 Ma. The SYSZ is an extensional, top-to-the-SE shear zone developed between 131 and 114 Ma, in association with intense magmatism and the development of the Huairou rifted basin in the hanging wall. Ductile shearing on the SYSZ was followed by isostatic rebound from 114 Ma to the end of the Early Cretaceous and then was replaced by brittle normal faulting. The normal displacement on the SYSZ and subsequent isostatic rebound led to the formation of the YMMCC. The mechanism of formation is consistent with a rolling-hinge model of detachment faulting and core complex formation. The structural evolution of the Yunmengshan area, in common with the whole eastern NCC, thus records a rapid switch from a NNE–SSW shortening regime to a NW–SE extension one in the earliest Cretaceous. The intense NW–SE extension of the Early Cretaceous, as recorded by the YMMCC, was associated with peak lithospheric thinning in the eastern NCC. We attribute the shortening to the final closure of the Mongol–Okhotsk Ocean between the Siberian Craton and the North China–South Mongol block, and the extension to the back-arc deformation related to the subduction of the Izanagi Plate in the Pacific Ocean. We suggest that the Yunmengshan area illustrates how back-arc compression can be driven by the overriding plate motion, while connection of the overriding plate to a larger continent favors subduction-related back-arc extension.

Summary Background Some patients with a phenotypic appearance of eosinophilic oesophagitis (EoE) respond histologically to PPI , and are described as having PPI ‐responsive oesophageal eosinophilia ( PPI ‐ REE ). It is unclear if PPI ‐ REE is a GERD ‐related phenomenon, a subtype of EoE, or a completely unique entity. Aim To compare demographic, clinical and histological features of EoE and PPI ‐ REE . Methods Two databases were reviewed from the Walter Reed and Swiss EoE databases. Patients were stratified into two groups, EoE and PPI ‐ REE , based on recent EoE consensus guidelines. Response to PPI was defined as achieving less than 15 eos/hpf and a 50% decrease from baseline following at least a 6‐week course of treatment. Results One hundred and three patients were identified (63 EoE and 40 PPI ‐ REE ; mean age 40.2 years, 75% male and 89% Caucasian). The two cohorts had similar dysphagia (97% vs. 100%, P = 0.520), food impaction (43% vs. 35%, P = 0.536), and heartburn (33% vs. 32%, P = 1.000) and a similar duration of symptoms (6.0 years vs. 5.8 years, P = 0.850). Endoscopic features were also similar between EoE and PPI ‐ REE ; rings (68% vs. 68%, P = 1.000), furrows (70% vs. 70%, P = 1.000), plaques (19% vs. 10%, P = 0.272), strictures (49% vs. 30%, P = 0.066). EoE and PPI ‐ REE were similar in the number of proximal (39 eos/hpf vs. 38 eos/hpf, P = 0.919) and distal eosinophils (50 vs. 43 eos/hpf, P = 0.285). Conclusions EoE and PPI ‐responsive oesophageal eosinophilia are similar in clinical, histological and endoscopic features and therefore are indistinguishable without a PPI trial. Further studies are needed to determine why a subset of patients with oesophageal eosinophilia respond to PPI .

Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.

MicroRNAs (miRNAs), abundant and highly stable in the plasma, have been widely reported. This greatly pursued us to investigate whether plasma miRNAs could be considered as powerful biomarkers for diagnosing bladder cancer (BC). We performed a plasma miRNAs profile with the TaqMan Low Density Array, and a two-phase validation to detect the candidate miRNAs expression by quantitative PCR. The receiver operating characteristic curve (ROC) and the area under curve (AUC) were used to evaluate diagnostic accuracy. A total of eight plasma miRNAs abnormally expressed between BC patients and healthy controls in microarray analysis (i.e., elevated miRNAs for miR-505, miR-363 and miR-663b, and decreased for miR-99a, miR-194, miR-100, miR-497 and miR-1 in BC plasma). In further independent cohorts, miR-497 and miR-663b with significantly differential expression were confirmed. Moreover, the AUC, sensitivity and specificity were raised to 0.711 (95% CI = 0.641-0.780), 69.7% and 69.6%, respectively, when miR-497 and miR-663b were integrated. This is the first study systematically exploring the existence of specific plasma miRNAs as early diagnostic biomarkers for BC in Chinese population; and these findings supported that plasma miR-497 and miR-663b could be promising novel circulating biomarkers in clinical detection of BC.

Perovskite solar cells are very promising for practical applications owing to their rapidly rising power conversion efficiency and low cost of solution-based processing. 2,2′,7,7′-Tetrakis(N,N-di-p-methoxyphenylamine) 9,9′-spirobifluorene (Spiro-OMeTAD) is most widely used as a hole-transporting material (HTM) in perovskite solar cells. However, the tedious synthesis and high cost of Spiro-OMeTAD inhibit its commercial-scale application in the photovoltaic industry. In this article, we report a carbazole-based compound (R01) as a new HTM in efficient perovskite solar cells. R01 is synthesized via a facile route consisting of only two steps from inexpensive commercially available materials. Furthermore, R01 exhibits higher hole mobility and conductivity than the state-of-the-art Spiro-OMeTAD. Perovskite solar cells fabricated with R01 produce a power conversion efficiency of 12.03%, comparable to that obtained in devices using Spiro-OMeTAD in this study. Our findings underscore R01 as a highly promising HTM with high performance, and its facile synthesis and low cost may facilitate the large-scale applications of perovskite solar cells.

Abstract Increasing evidence suggests that neuro-immune and neuro-glial interactions are critically involved in chronic pain sensitization. It is well studied how immune/glial mediators sensitize pain, but how sensory neurons control neuroinflammation remains unclear. We employed Myd88 conditional knockout (CKO) mice, in which Myd88 was deleted in sodium channel subunit Na v 1.8-expressing primary sensory neurons, to examine the unique role of neuronal MyD88 in regulating acute and chronic pain and possible underlying mechanisms. We found that baseline pain and the formalin induced acute inflammatory pain were intact in CKO mice. However, the late phase inflammatory pain following complete Freund’s adjuvant injection and the late phase neuropathic pain following chronic constriction injury (CCI), were reduced in CKO mice. CCI induced up-regulation of MyD88 and chemokine C-C motif ligand 2 expression in DRG neurons and macrophage infiltration into DRGs and microglia activation in spinal dorsal horns in wild-type mice, but all these changes were compromised in CKO mice. Finally, the pain hypersensitivity induced by intraplantar IL-1β was reduced in CKO mice. Our findings suggest that MyD88 in primary sensory neurons plays an active role in regulating IL-1β signaling and neuroinflammation in the peripheral and the central nervous systems and contributes to the maintenance of persistent pain.

Emerging evidence has shown that miRNA-mediated gene expression modulation contributes to chronic pain, but its functional regulatory mechanism remains unknown. Here, we found that complete Freund's adjuvant (CFA)-induced chronic inflammation pain significantly reduced miRNA-219 (miR-219) expression in mice spinal neurons. Furthermore, the expression of spinal CaMKIIγ, an experimentally validated target of miR-219, was increased in CFA mice. Overexpression of spinal miR-219 prevented and reversed thermal hyperalgesia and mechanical allodynia and spinal neuronal sensitization induced by CFA. Concurrently, increased expression of spinal CaMKIIγ was reversed by miR-219 overexpression. Downregulation of spinal miR-219 in naive mice induced pain-responsive behaviors and increased p-NMDAR1 expression, which could be inhibited by knockdown of CaMKIIγ. Bisulfite sequencing showed that CFA induced the hypermethylation of CpG islands in the miR-219 promoter. Treatment with demethylation agent 5'-aza-2'-deoxycytidine markedly attenuated pain behavior and spinal neuronal sensitization, which was accompanied with the increase of spinal miR-219 and decrease of CaMKIIγ expression. Together, we conclude that methylation-mediated epigenetic modification of spinal miR-219 expression regulates chronic inflammatory pain by targeting CaMKIIγ.

Cancer cells exhibit the ability to metabolise glucose to lactate even under aerobic conditions for energy. This phenomenon is known as the Warburg effect and can be a potential target to kill cancer cells. Several studies have shown evidence for interplay between microRNAs and key metabolic enzyme effecters, which can facilitate the Warburg effect in cancer cells. In the present study, a microRNA sponge forcibly expressed using a lentiviral vector was utilised to knock down miR-21 expression in vitro. qPCR and Western blot assays were performed to evaluate the expression of a regulatory factor related to aerobic glycolysis and the signalling pathway it regulates. In bladder cancer specimens, expression levels of glycolysis-related genes [glucose transporter (GLUT)1, GLUT3, lactic dehydrogenase (LDH)A, LDHB, hexokinase (HK)1, HK2, pyruvate kinase type M (PKM) and hypoxia-inducible factor 1-alpha (HIF-1α)] were higher in tumour tissues than in adjacent tissues, suggesting the role of glycolysis in bladder cancer. miR-21 inhibition in bladder cancer cell lines resulted in reduction in tumour aerobic glycolysis. Decrease in glucose uptake and lactate production was observed upon expression of the miR-21 sponge, which promoted phosphatase and tensin homologue (PTEN) expression, decreased phosphorylated AKT and deactivated mTOR. Furthermore, messenger RNA (mRNA) and protein expression levels of glycolysis-related genes were also lower in miR-21 sponge cells compared to miR-21 control cells. Our findings suggest that miR-21 acts as a molecular switch to regulate aerobic glycolysis in bladder cancer cells via the PTEN/phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Blocking miR-21 function can be an effective diagnostic and therapeutic approach either by itself or in combination with existing methods to treat bladder cancer.

Background and Purpose— Lipoxin A4 (LXA4) has been reported to reduce inflammation in several neurological injury models. We studied the effects of LXA4 on neuroinflammation after subarachnoid hemorrhage (SAH) in a rat model. Methods— Two hundred and thirty-eight Sprague–Dawley male rats, weight 280–320 g, were used. Exogenous LXA4 (0.3 and 1.0 nmol) were injected intracerebroventricularly at 1.5 hours after SAH. Neurological scores, brain water content, and blood–brain barrier were evaluated at 24 hours after SAH; Morris water maze and T-maze tests were examined at 21 days after SAH. The expression of endogenous LXA4 and its receptor formyl peptide receptor 2 (FPR2), as well as p38, interleukin-1β, and interleukin-6 were studied either by ELISA or by Western blots. Neutrophil infiltration was observed by myeloperoxidase staining. FPR2 siRNA was used to knock down LXA4 receptor. Results— The expression of endogenous LXA4 decreased, and the expression of FPR2 increased after SAH. Exogenous LXA4 decreased brain water content, reduced Evans blue extravasation, and improved neurological functions and improved the learning and memory ability after SAH. LXA4 reduced neutrophil infiltration and phosphorylation of p38, interleukin-1β, and interleukin-6. These effects of LXA4 were abolished by FPR2 siRNA. Conclusions— Exogenous LXA4 inhibited inflammation by activating FPR2 and inhibiting p38 after SAH. LXA4 may serve as an alternative treatment to relieve early brain injury after SAH.

Deeper mechanistic understanding of non-small cell lung cancer (NSCLC), a leading cause of total cancer-related deaths, may facilitate the establishment of more effective therapeutic strategies. In this study, pituitary tumor transforming gene (PTTG1) expression was associated with lymph node and distant metastasis in patients with NSCLC and was correlated with patient survival. Reduction of PTTG1 by small interfering RNA (siRNA) inhibits the migration and invasion of NSCLC cells by mediating matrix metalloproteinases expression. To the best of our knowledge, this study is the first to report that PTTG1 promotes epidermal growth factor (EGF) induced the phosphorylation of LIN-11, Isl1 and MEC-3 protein domain kinase and cofilin, a critical step in cofilin recycling and actin polymerization. Additionally, EGF-induced Akt phosphorylation was suppressed through knockdown of PTTG1. Interestingly, miR-186 can modulate PTTG1 protein expression. As observed from the animal experiment in this study, knockdown of PTTG1 through siRNA and overexpression of miR-186 inhibited invasive activity of NSCLC cells toward the SCID mice lung. In summary, our in vitro and in vivo results indicate that PTTG1 modulated by miR-186 has an important function in NSCLC invasion/metastasis. This study identified both PTTG1 and miR-186 as potential anti-invasion targets for therapeutic intervention in NSCLC.

<h2>Summary</h2> Nutrients are not only organic compounds fueling bioenergetics and biosynthesis, but also key chemical signals controlling growth and metabolism. Nutrients enormously impact the production of reactive oxygen species (ROS), which play essential roles in normal physiology and diseases. How nutrient signaling is integrated with redox regulation is an interesting, but not fully understood, question. Herein, we report that superoxide dismutase 1 (SOD1) is a conserved component of the mechanistic target of rapamycin complex 1 (mTORC1) nutrient signaling. mTORC1 regulates SOD1 activity through reversible phosphorylation at S39 in yeast and T40 in humans in response to nutrients, which moderates ROS level and prevents oxidative DNA damage. We further show that SOD1 activation enhances cancer cell survival and tumor formation in the ischemic tumor microenvironment and protects against the chemotherapeutic agent cisplatin. Collectively, these findings identify a conserved mechanism by which eukaryotes dynamically regulate redox homeostasis in response to changing nutrient conditions.

As a technique for precisely manipulating fluid at the micrometer scale, the field of microfluidics has experienced an explosive growth over the past two decades, particularly owing to the advances in device design and fabrication. With the inherent advantages associated with its scale of operation, and its flexibility in being incorporated with other microscale techniques for manipulation and detection, microfluidics has become a major enabling technology, which has introduced new paradigms in various fields involving biological cells. A microfluidic device is able to realize functions that are not easily imaginable in conventional biological analysis, such as highly parallel, sophisticated high-throughput analysis, single-cell analysis in a well-defined manner, and tissue engineering with the capability of manipulation at the single-cell level. Major advancements in microfluidic device fabrication and the growing trend of implementing microfluidics in cell studies are presented, with a focus on biological research and clinical diagnostics.

Accumulating evidence indicates that the lncRNAs play a critical role in cancer progression and metastasis. In this study, we found that MALAT1 upregulation was associated with larger tumor size and lymph-node metastasis, and also correlated with shorter overall survival of lung adenocarcinoma patients. Furthermore, MALAT1 promotes EMT and metastasis of lung adenocarcinoma cells in vitro and in vivo. In particular, MALAT1 upregulated the expression of miR-204 target gene SLUG through competitively 'spongeing' miR-204. In summary we unveil a branch of the MALAT1/miR-204/SLUG pathway that regulates the progression of lung adenocarcinoma.

Kidney injury molecule-1(KIM-1) is a type I membrane protein, comprising an extracellular portion and a cytoplasmic portion, which is expressed at very low levels in the normal kidney. The extracellular portion can cleave and rapidly enter tubule lumens after kidney injury, and can then be detected in the urine. It has been confirmed that the urine KIM-1 level is closely related to tissue KIM-1 level and correlated with kidney tissue damage. Not only is KIM-1 proven to be an early biomarker of acute kidney injury but it also has a potential role in predicting long-term renal outcome. This review summarizes the relationships between KIM-1 and kidney injury, especially in chronic kidney disease.

Bismuth-containing nanoparticles (BNPs) are potential enhancers for tumor radiotherapy. Improving the bioavailability and developing synergistic therapeutic regimens benefit the drug transformation of BNPs. In the present study, we prepare a mesoporous silica-coated bismuth nanorod (BMSNR) camouflaged by a platelet membrane (PM). This biomimetic material is termed BMSNR@PM. The PM camouflage enhances the immune escape of the BMSNRs by lowering endocytosis by macrophages in the reticuloendothelial system. Additionally, the PM camouflage strengthens the material tumor-targeting capacity and leads to better radiotherapeutic efficacy compared with bare BMSNRs. Owing to the photothermal effect, BMSNR@PMs alters the cell cycle of 4T1 cancer cells post-treatment with 808 nm near-infrared irradiation (NIR). The proportions of S phase and G2/M phase cells decrease and increase, respectively, which explains the synergistic effect of NIR on BMSNR@PM-based radiotherapy. BMSNR@PMs efficiently eradicates cancer cells by the combined action of photothermal therapy (PTT) and radiotherapy in vivo and markedly improves the survival of 4T1-tumor-bearing mice. The synergistic therapeutic effect is superior to the outcomes of PTT and radiotherapy performed alone. Our study demonstrates a versatile bismuth-containing nanoplatform with tumor-targeting, immune escape, and radiosensitizing functionalities using an autologous cell membrane biomimetic concept that may promote the development of radiotherapy enhancers.

Hybrid energy storage system (HESS) consisting of battery and supercapacitor (SC) is an effective approach to alleviate voltage stability problems brought by the fluctuation of renewable resources in a dc microgrid. This paper proposes a novel distributed control scheme for multiple HESSs based on a leaderless consensus protocol to realize the power splitting between batteries and SCs and thus regulate the dc bus voltage. Without assigning leaders among the batteries and SCs, each SC or battery has equal priority in participating in voltage or state of charge (SOC) regulation using only neighboring information exchange instead of global communication. This distributed approach makes the system robust against any physical failure or communication fault only if the remaining communication network is connected. Consensus for the state variable associated with the battery SOC, the SC terminal voltage, and the dc average bus voltage are all achieved in this scheme, and thus the voltage quality and the energy storage lifetime can be improved. In addition, the small-signal stability of a four-HESS system is investigated, and the impact of the control parameters on the system is analyzed. Simulations and experimental studies are conducted to demonstrate the effectiveness of the proposed control scheme in an islanded dc microgrid.

More than 50% of patients with colorectal cancer (CRC) are initially diagnosed with locally advanced CRC (LACRC), and half of those patients develop recurrence or metastasis after resection. Here, we investigated whether the novel index HALP, which is a combination of preoperative hemoglobin, albumin, lymphocyte and platelet levels, correlates with survival in LACRC patients. A total of 820 patients with LACRC from two independent hospitals were included in our study. The correlations between HALP and overall and cancer-specific survival were calculated using training and validation sets. Lower HALP values correlated with an increased risk of death and cancer-related death in both sets. Moreover, the risk score based on HALP allowed stratification of patients into distinct prognostic groups with greater accuracy than previously proposed indexes. These results suggest that HALP may be useful as a clinical prognostic factor for patients with LACRC.

Forkhead box class O family member proteins (FoxOs) are evolutionarily conserved transcription factors for their highly conserved DNA-binding domain. In mammalian species, all the four FoxO members, FoxO1, FoxO3, FoxO4, and FoxO6, are expressed in different organs. In bone, the first three members are extensively expressed and more studied. Bone development, remodeling, and homeostasis are all regulated by multiple cell lineages, including osteoprogenitor cells, chondrocytes, osteoblasts, osteocytes, osteoclast progenitors, osteoclasts, and the intercellular signaling among these bone cells. The disordered FoxOs function in these bone cells contribute to osteoarthritis, osteoporosis, or other bone diseases. Here, we review the current literature of FoxOs for their roles in bone cells, focusing on helping researchers to develop new therapeutic approaches and prevent or treat the related bone diseases.

This paper aims to crack the individual EV charging scheduling problem considering the dynamic user behaviors and the electricity price. The uncertainty of the EV charging demand is described by several factors, including the driver’s experience, the charging preference and the charging locations for realistic scenarios. An aggregate anxiety concept is introduced to characterize both the driver’s anxiety on the EV’s range and uncertain events. A mathematical model is also provided to describe the anxiety quantitatively. The problem is formulated as a Markov Decision Process (MDP) with an unknown state transition function. The objective is to find the optimal sequential charging decisions that can balance the charging cost and driver’s anxiety. A model-free deep reinforcement learning (DRL) based approach is developed to learn the optimal charging control strategy by interacting with the dynamic environment. The continuous soft actor-critic (SAC) framework is applied to design the learning method, which contains a supervised learning (SL) stage and a reinforcement learning (RL) stage. Finally, simulation studies verify the effectiveness of the proposed approach under dynamic user behaviors at different charging locations.

SARS-CoV-2 infection begins with the association of its spike 1 (S1) protein with host angiotensin-converting enzyme-2 (ACE2). Targeting the interaction between S1 and ACE2 is a practical strategy against SARS-CoV-2 infection. Herein, we show encouraging results indicating that human cathelicidin LL37 can simultaneously block viral S1 and cloak ACE2. LL37 binds to the receptor-binding domain (RBD) of S1 with high affinity (11.2 nM) and decreases subsequent recruitment of ACE2. Owing to the RBD blockade, LL37 inhibits SARS-CoV-2 S pseudovirion infection, with a half-maximal inhibitory concentration of 4.74 μg/mL. Interestingly, LL37 also binds to ACE2 with an affinity of 25.5 nM and cloaks the ligand-binding domain (LBD), thereby decreasing S1 adherence and protecting cells against pseudovirion infection in vitro. Intranasal administration of LL37 to C57 mice infected with adenovirus expressing human ACE2 either before or after pseudovirion invasion decreased lung infection. The study identified a versatile antimicrobial peptide in humans as an inhibitor of SARS-CoV-2 attachment using dual mechanisms, thus providing a potential candidate for coronavirus disease 2019 (COVID-19) prevention and treatment.

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; Asprosin, a novel peptide that has recently discovered as an important regulatory adipokine, is relevant to obesity in animals and adult humans. Little is known about its roles in children. The aim of the current study was to determine the potential role of asprosin and explore its relationship to various obesity-related markers in children with obesity. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A cross-sectional study was conducted among 119 Chinese children, including 79 children with obesity and 40 lean controls. Anthropometric parameters, clinical data, and circulating tumor necrosis factor-α (TNF-α), adiponectin, leptin, and asprosin levels were measured. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Serum asprosin concentrations were significantly elevated in children with obesity compared with lean controls. Children with insulin resistance (IR) had higher asprosin levels than non-IR group. Asprosin was positively correlated with waist-to-hip ratio (WHR), diastolic blood pressure, homoeostasis model of IR (HOMA-IR), leptin-to-adiponectin ratio, TNF-α independent of their body mass index, SDs score, and age. In multivariable linear regression analysis, WHR and HOMA-IR were associated with the circulating level of asprosin. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Circulating asprosins are increased in children with obesity and associated with IR. It may be proposed as a novel marker to predict advanced disease.

Limited regeneration capacity of cartilage can be addressed by tissue engineering approaches including localized delivery of bioactive agents using biomaterials. Although chitosan hydrogels have been considered as appropriate candidates for these purposes, however, their poor mechanical properties limit their real applications. Here, we develop in situ forming chitosan hydrogels with enhanced shear modulus by chemical modification of chitosan using N-(β-maleimidopropyloxy) succinimide ester (BMPS). Moreover, we utilize β-Glycerophosphate (β-GP) in the hydrogels for achieving thermosensitivity. We investigate the effects of BMPS, β-GP and chitosan concentration on rheological and swelling properties of the hydrogels. Accordingly, we generate significant statistical models by response surface method to predict these properties. These models provide us beneficial tools to tune the hydrogel properties depending on the cartilage defect location and properties. Finally, we incorporate a recently discovered small biomolecule, kartogenin (KGN), for promoting chondrogenesis of stem cells into the optimized hydrogel. The hydrogel's shear modulus is 78 ± 5 kPa which covers a wide range of human articular cartilage shear modulus (50-250 kPa). It can be injected to the defects non-invasively at room temperature which gels at 37 °C within minutes. Additionally, it provides a sustained KGN release for ∼40 days that may eliminate the need of multiple injections. In vitro chondrogenic results confirm enhanced chondrogenic differentiation of human adipose mesenchymal stem cells (hAMSCs) treated with KGN-loaded hydrogel, compared to pure KGN. Based on the enhanced hydrogel shear modulus, injectability, gelation behavior, long-term drug release and in vitro results, this thermosensitive hydrogel looks promising for cartilage tissue engineering.

The ongoing COVID-19 pandemic worldwide necessitates the development of therapeutics against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 and mediates viral entry into host cells. Herein, membrane nanoparticles (NPs) prepared from ACE2-rich cells were discovered to have potent capacity to block SARS-CoV-2 infection. The membranes of human embryonic kidney-239T cells highly expressing ACE2 were applied to prepare NPs using an extrusion method. The nanomaterials, termed ACE2-NPs, contained 265.1 ng mg-1 ACE2 on the surface and acted as baits to trap S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to HK-2 human renal tubular epithelial cells. Aside from affecting receptor recongnition, S1 translocated to the cytoplasm and induced apoptosis by reducing optic atrophy 1 expression and increasing cytochrome c release, which was also inhibited by ACE2-NPs. Further investigations revealed that ACE2-NPs efficiently suppressed SARS-CoV-2 S pseudovirions entry into host cells and blocked viral infection in vitro and in vivo. This study characterizes easy-to-produce memrbane nanoantagonists of SARS-CoV-2 that enrich the existing antiviral arsenal and provide possibilities for COVID-19 treatment.

Rationale:The dysfunctional gut-kidney axis forms a vicious circle, which eventually becomes a catalyst for the progression of chronic kidney disease (CKD) and occurrence of related complications.However, the pathogenic factors of CKD-associated intestinal dysfunction and its mechanism remain elusive.Methods: We first identified the protein-bound uremic toxin indoxyl sulfate (IS) as a possible contributor to intestinal barrier injury.Transepithelial electrical resistance, permeability assay and transmission electron microscopy were carried out to evaluate the damaging effect of IS on intestinal barrier in intestinal epithelial cells, IS-injected mice and CKD mice.In vitro and in vivo experiments were performed to investigate the role of IS in intestinal barrier injury and the underlying mechanism.Finally, CKD mice treated with AST-120 (an oral adsorbent for IS) and gene knockout mice were used to verify the mechanism and to explore possible interventions for IS-induced intestinal barrier injury.Results: Transepithelial electrical resistance and the expressions of tight junction-related genes were significantly suppressed by IS in intestinal epithelial cells.In vitro experiments demonstrated that IS inhibited the expression of dynamin-related protein 1 (DRP1) and mitophagic flux, whereas DRP1 overexpression attenuated IS-induced mitophagic inhibition and intestinal epithelial cell damage.Furthermore, IS suppressed DRP1 by upregulating the expression of interferon regulatory factor 1 (IRF1), and IRF1 could directly bind to the promoter region of DRP1.Additionally, the decreased expression of DRP1 and autophagosome-encapsulated mitochondria were observed in the intestinal tissues of CKD patients.Administration of AST-120 or genetic knockout of IRF1 attenuated IS-induced DRP1 reduction, mitophagic impairment and intestinal barrier injury in mice.Conclusions: These findings suggest that reducing IS accumulation or targeting the IRF1-DRP1 axis may be a promising therapeutic strategy for alleviating CKD-associated intestinal dysfunction.

Distinguishing the respective roles of climate change and anthropogenic activities can provide crucial information for sustainable management of the environment. Here, using the residual trend method (RESTREND), which measures the residue of the actual and potential trends of vegetation, we quantified the relative contributions of human activities (e.g., ecological restoration, overgrazing, and urbanization) and climate change (the warmer and wetter trend) to vegetation dynamics in China during 1988-2018 based on multiple vegetation indices, including the vegetation optical depth (Ku-VOD, C-VOD), normalized difference vegetation index (NDVI), and gross primary productivity (GPP). The results showed that the VOD, NDVI, and GPP exhibited overall increasing trends during 1988-2018. Human activities contributed >70% to the increases in NDVI and GPP in China, whereas a counterbalanced contribution of human activities and climate change was identified for the VOD dynamics (51% vs. 49%). Regions with high contributions from human activities to NDVI, GPP, and VOD were located in northeastern, southern, central, and northwestern China. In northern China, the positive impacts of human activities on NDVI (78%) and BEPS-GPP (83%) were greater than those of climate change. In contrast, human activities contributed 96% to the decrease in Ku-VOD over the same period. Before 2000, climate change promoted increases in GPP and NDVI in most regions of southern China. The increasing rates of GPP and NDVI accelerated after 2000 due to afforestation. However, human activities like overgrazing and urbanization have led to decreases in Ku-VOD in northern and southwestern China, and in C-VOD in northeastern, eastern, central, southwestern, and southern China. In all, the relative roles of climate and human factors varied in different regions when NDVI, GPP, or VOD were individually considered. Our results highlighted that the regional-scale vegetation conditions should be taken into full account to achieve sustainable management of ecosystems.

The ongoing depletion of shallow resources has led to the mining of progressively deeper deposits, where high-temperature thermal stresses pose heat hazards and threaten worker safety. Mitigating geothermal hazards is therefore an essential component of mining operations in deep mines. In this paper, a novel synergetic mining approach is proposed that controls heat hazards at low cost and simultaneously exploits mineral and geothermal energy. Injection and production channels are designed below the ventilation tunnel to synchronously cool the tunnel surrounding rock and exploit mine geothermal energy. A fully coupled numerical model is established that simultaneously simulates heat and mass transfer in a large-scale ventilation network and geological reservoir. The cooling effect on the tunnel and heat recovery capacity of geothermal exploitation are investigated to assess the feasibility of the proposed scheme. Three case studies are presented to identify the impact of the water injection and production channel layout on the heat and mass transfer characteristics in the rock layer. The temperature of the tunnel surrounding rock is cooled over a few years via low-temperature water injection into the mine and heat production in the deep rock layer; this rapidly reduces the air temperature inside the tunnel. The total heat production rate initially rapidly increases and then gradually decreases. In the ninth year, the maximum heat production rate of the production channel reached 6.01 × 103 kW. The cooling effect on the roadway and heat production performance are optimal when the water injection channel is arranged under the air intake side of the main ventilation roadway of the mine and the heat production channel is arranged in the deep rock under the return air side of the roadway. After 4 years of water injection, the temperature at the end of the tunnel in Case 1 rapidly decreased to 30.9 °C; this temperature is 6.6 °C and 3.4 °C lower than those in Cases 2 and 3, respectively. Longer injection channel lengths can significantly reduce the injection pressure requirement in the injection channel. Shorter distances between the injection channel and tunnel are associated with faster reductions of the tunnel temperature. This technique significantly improves the thermal comfort inside the tunnel and produces considerable geothermal energy; a single heat production channel can produce 1.68 × 1015 J over a period of 10 years.

Rationale: Acute kidney injury (AKI) is a common critical illness in the clinic and currently lacks effective treatment options. Ischemia reperfusion injury (IRI) is a major pathogenic factor for AKI. Due to the deficiency of selenium (Se) in AKI patients, we intended to treat IRI-induced AKI using a Se rebalancing strategy in the present study. Methods: Sodium selenate, ascorbic acid, and bovine serum albumin (BSA) were employed to prepare nanomaterials termed Se@BSA nanoparticles (NPs) using a simple method. Experiments with human renal tubular epithelial HK-2 cells exposed to hypoxia/reoxygenation (H/R) and IRI-AKI mice were used to evaluate the therapeutic efficiency of Se@BSA NPs. Transcriptome sequencing, further molecular biology experiments, and pathologic analysis were performed to investigate the underlying mechanisms. Results: Se@BSA NPs accumulated in mouse kidneys and could be endocytosed by renal tubular epithelial cells after intravenous administration. In vitro studies showed that Se@BSA NP treatment markedly increased the levels of glutathione peroxidase (GPx)-1 and suppressed NLRP3 inflammasome activation in H/R cells, which resulted in reductions in the proteolytic cleavage of pro-Caspase-1 into active Caspase-1 and the maturation of inflammatory factors. Mouse experiments confirmed these findings and demonstrated an inspiring mitigative effect of Se@BSA NPs on IRI-induced AKI. Owing to modulation of the GPx-1/NLRP3/Caspase-1 pathway, Se@BSA NPs dramatically inhibited fibrosis formation after AKI. Conclusion: This study provides an effective therapeutic option by applying easy-to-produce Se-containing nanomaterials to remedy Se imbalance and impede inflammatory responses in the kidney, which is a promising candidate for AKI treatment.

Prior studies have investigated the clinical and imaging factors for hemorrhagic transformation (HT), especially symptomatic intracranial hemorrhage (sICH); however, whether alteplase increases the risk of HT after endovascular thrombectomy (EVT) is unknown. This study aimed to assess clinical and imaging features associated with HT, sICH, and parenchymal hematoma (PH) in patients with acute ischemic stroke after EVT, with and without intravenous alteplase in DIRECT-MT (Direct Intraarterial Thrombectomy to Revascularize Acute Ischemic Stroke Patients with Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: a Multicenter Randomized Clinical Trial).The DIRECT-MT trial is a randomized trial of EVT alone versus intravenous thrombolysis combined with EVT. HT, sICH, and PH was evaluated on follow-up computed tomography. Multivariable ordinal logistic regression analysis was used to test the association of stepwise selected determinants with HT, sICH, and PH.In total, 633 patients were analyzed; 261 (41.2%) had HT; 34 (5.4%) had sICH; and 85 (13.4%) had PH. The median age was 69, and 56.7% were men. The median National Institutes of Health Stroke Scale score was 18, and 320 patients were in combination-therapy group. Symptomatic intracranial hemorrhage was associated with higher baseline National Institutes of Health Stroke Scale score (adjusted odds ratio [OR], 1.06 [95% CI, 1.10-1.12]) and higher glucose level at hospital arrival (adjusted OR, 1.14 [95% CI, 1.00-1.29]). No association was found between alteplase treatment and HT, sICH, or PH. The independent predictor of sICH was higher baseline National Institutes of Health Stroke Scale score (adjusted OR, 1.09 [95% CI, 1.01-1.18]) in EVT alone group, and history of anticoagulant drugs (adjusted OR, 3.75 [95% CI, 1.07-13.06]), higher glucose level at hospital arrival (adjusted OR, 1.19 [95% CI, 1.03-1.38]), >3 passes of device (adjusted OR, 4.42 [95% CI, 1.36-14.32]) in combination-therapy group.In DIRECT-MT, independent predictors of sICH were baseline National Institutes of Health Stroke Scale score and glucose level at hospital arrival. Alteplase treatment did not increase the risk of HT, sICH, or PH after EVT. The independent predictor of sICH was different in EVT alone group and combination-therapy group.URL: https://www.gov; Unique identifier: NCT03469206.

Biochar has been globally recognized as a novel and eco-friendly soil ameliorant to mitigate hazardous effects of salinization on soil health, and mediate carbon and nitrogen (N) nutrient cycling in agricultural ecosystems. However, knowledge pertaining to the regulatory mechanism of biochar application on nitrification in the salt-affected soil is limited. In this study, field plot experiment for three consecutive years and an aerobic incubation experiment with three biochar application rates (7.5, 15, and 30 ton ha−1) and N fertilizer (225 kg N ha−1 yr−1) were conducted. We investigated the effect of combined application of biochar and N fertilizer on soil chemical and microbial properties, nitrification kinetic parameters, and the abundance of ammonia monooxygenase (subunit A, amoA) gene of ammonia-oxidizing bacteria (AOB) and archaea (AOA). Our results showed that biochar addition increased soil pH, cation exchange capacity, available potassium, and microbial biomass carbon, and decreased the numbers of amoA-AOB gene in the salt-affected soil applied with N fertilizer. The nitrification process and fitted kinetic parameters were negatively responsive to the combined application of biochar and N fertilizer, which reduced the nitrification potential and potential nitrification rate, and prolonged the duration of nitrification. The nitrification rate and abundance of amoA-AOB and amoA-AOA genes decreased under biochar and N fertilizer addition, and biochar played the predominant role in the inhibiting effect, which aggravated with the increase of biochar rate. The AOB dominated the autotrophic nitrification with the nitrification rate having higher positive correlation with abundance of amoA-AOB gene than with that of amoA-AOA gene. The abundance of both amoA-AOB and amoA-AOA genes showed significantly negative correlation with nitrate nitrogen (NO3−-N) concentration. In conclusion, biochar and N fertilizer addition inhibited the autotrophic nitrification rate mainly by greatly reducing the abundance of amoA-AOB gene, which was adaptive to the changing soil microhabitat traits induced by biochar application and N fertilization.

Variety of ion-doped apatite coatings, especially strontium substituted hydroxyapatite (SrHA), have attracted eventful attention for medical metal surface modifications due to their excellent cytocompatibility and organizational affinity. However, they are still not commercially used in clinics because of their inappropriate biomechanical properties, and lack of osteoinductivity and antibacterial capabilities. Here, silver (Ag) doped SrHA (SrAgHA)/graphene oxide (GO) composite coatings were fabricated on titanium (Ti) substrate via electrodeposition (ED) and this combination has been reported for the first time. Morphological observations revealed that GO facilitated HA pricker-like crystals to grow in longitudinal directions, changing into a bone-like microneedles structure. SrAgHA/GO showed good mechanical properties to ensure mechanical strength required for the bone repair coating. The roughness of samples decreased from 120 ± 19 μm for the SrAgHA/GO coated Ti to 527 ± 66 μm for HA coated Ti. Although the introduction of GO makes the composite coating have a significant decreased roughness, it has no effect on the hydrophilicity of the composite coating, which is almost superpotropic. Ion release evaluation demonstrated that the presence of GO slowed the release rate of Sr and Ag, which was beneficial to reduce the cytotoxicity accompanying high concentration of Ag release. Simultaneously, GO increased the surface hydrophilicity and mechanical strength of the SrAgHA/GO. In addition, the corrosion rates of investigated coatings increased in the following order: SrAgHA/GO < SrHA/GO < SrAgHA < HA < Ti. SrAgHA/GO coatings demonstrated an effective antibacterial effect against common bacteria in clinical. The co-doping of Sr and GO in SrAgHA/GO coatings can effectively mitigate the cytotoxicity of Ag and promote the cytocompatibility of HA. The SrAgHA/GO coating did not exhibit any cytotoxicity, which can greatly promote adhesion, extension, proliferation and early differentiation of osteoblasts. Therefore, high cytocompatibility, excellent antimicrobial activity, and good mechanical properties of the SrAgHA/GO-coated Ti samples combined with its exceptional corrosion resistance performance displayed the beautiful prospect of the SrAgHA/GO-coated Ti for applications in hard tissue implant. • The SrAgHA/GO coating was fabricated by ED on titanium substrate. • The SrAgHA/GO composite coating has good mechanical properties. • The SrAgHA/GO coating has moderate roughness and hydrophilicity. • The coating had a good antimicrobial effect for E. coli and S. aureus . • The SrAgHA/GO coating exhibited excellent osteoinductivity.

Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF).We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study limitations include the absence of vaccine effectiveness in a real-world setting and current lack of immune persistence data.Heterologous boosting with ZF2001 following primary vaccination with Convidecia is more immunogenic than a single dose of Convidecia and is not associated with safety concerns. These results support flexibility in cooperating viral vectored and recombinant protein vaccines.Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine; ClinicalTrial.gov NCT04833101.

Macrophages are heterogeneous and play critical roles in development and disease, but their diversity, function, and specification remain inadequately understood during human development. We generated a single-cell RNA sequencing map of the dynamics of human macrophage specification from PCW 4–26 across 19 tissues. We identified a microglia-like population and a proangiogenic population in 15 macrophage subtypes. Microglia-like cells, molecularly and morphologically similar to microglia in the CNS, are present in the fetal epidermis, testicle, and heart. They are the major immune population in the early epidermis, exhibit a polarized distribution along the dorsal-lateral-ventral axis, and interact with neural crest cells, modulating their differentiation along the melanocyte lineage. Through spatial and differentiation trajectory analysis, we also showed that proangiogenic macrophages are perivascular across fetal organs and likely yolk-sac-derived as microglia. Our study provides a comprehensive map of the heterogeneity and developmental dynamics of human macrophages and unravels their diverse functions during development.

High cobalt (Co) levels in tumors are associated with good clinical prognosis. An anticancer regimen that increases intratumoral Co through targeted nanomaterial delivery is proposed in this study. Bovine serum albumin and cobalt dichloride are applied to prepare cobaltous oxide nanodots using a facile biomineralization strategy. After iRGD peptide conjugation, the nanodots are loaded into dendritic mesoporous silica nanoparticles, generating a biocompatible product iCoDMSN. This nanocomposite accumulates in tumors after intravenous injection by deep tissue penetration and can be used for photoacoustic imaging. Proteomics research and molecular biology experiments reveal that iCoDMSN is a potent ferroptosis inducer in cancer cells. Mechanistically, iCoDMSNs upregulate heme oxygenase 1 (HMOX1), which increases transferrin receptors and reduces solute carrier family 40 member 1 (SLC40A1), resulting in Fe2+ accumulation and ferroptosis initiation. Furthermore, upregulated nuclear factor erythroid 2-related factor 2 (NRF2), arising from the reduction in Kelch-like ECH-associated protein 1 (KEAP1) expression, is responsible for HMOX1 enhancement after iCoDMSN treatment. Owing to intensified ferroptosis, iCoDMSN acts as an efficient radiotherapy enhancer to eliminate cancer cells in vitro and in vivo. This study demonstrates a versatile Co-based nanomaterial that primes ferroptosis by expanding the labile iron pool in cancer cells, providing a promising tumor radiotherapy sensitizer.

<h2>Summary</h2><h3>Background</h3> Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster. <h3>Methods</h3> This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 10¹¹ viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 10¹¹ viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group <i>vs</i> homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing. <h3>Findings</h3> Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% <i>vs</i> 9% and 14%, respectively; p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7–837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0–672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 [48·0–71·4]; p<0·0001). <h3>Interpretation</h3> A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac. <h3>Funding</h3> National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan.

We propose a label-free biosensor based on a porous silicon resonant microcavity and localized surface plasmon resonance. The biosensor detects SARS-CoV-2 antigen based on engineered trimeric angiotensin converting enzyme-2 binding protein, which is conserved across different variants. Robotic arms run the detection process including sample loading, incubation, sensor surface rinsing, and optical measurements using a portable spectrometer. Both the biosensor and the optical measurement system are readily scalable to accommodate testing a wide range of sample numbers. The limit of detection is 100 TCID50/ml. The detection time is 5 min, and the throughput of one single robotic site is up to 384 specimens in 30 min. The measurement interface requires little training, has standard operation, and therefore is suitable for widespread use in rapid and onsite COVID-19 screening or surveillance.

The prominent role of drylands in the global ecosystem calls for a deeper understanding of the responses of dryland vegetation to ongoing environmental drivers in the context of global climate change. Here, we first investigated the spatial and temporal trends of global dryland vegetation based on multiple satellite- and model-based indices, including the normalized difference vegetation index (NDVI), leaf area index (LAI), vegetation optical depth (VOD), and gross primary productivity (GPP) during 1988–2018. Then, the impacts of a set of environmental drivers (i.e. mean annual precipitation (MAP), mean annual temperature (MAT), soil moisture (SM), and vapor pressure deficit (VPD)) on vegetation dynamics were quantified using partial correlation analysis and structural equation model. All four indices increased strongly before 2000 but slowed afterward. The variation in dryland vegetation was more related to SM anomaly in comparison with other environmental drivers. The variation induced by SM was amplified by high VOD in some continents. Furthermore, MAT contributed similarly as SM to vegetation dynamics in North America. The four vegetation indices exhibited divergent responses to environmental drivers due to their characteristics. At the continental scale, NDVI was only relevant to variation in VPD in North America. In contrast to NDVI, LAI, and VOD, GPP was more closely associated with the variation in SM and VPD. Roughly half of the GPP variation was attributable to the combination of SM and MAT in North America and Australia, whereas they have low predictive power (∼30%) in Eurasia, Africa, and South America. SM was closely linked to the vegetation changes in grasslands and shrublands; however, this impact varied among the continents. Our results advance the current understanding of dryland vegetation dynamics and shed new light on improving dryland carbon flux simulation by fully considering the role of soil moisture.

Thermal environment prediction has become increasingly significant in recent years with its promise of wide application in underground structures. The current work presents a numerical method for the feasible and effective analysis of the airflow and surrounding rock temperatures in ultralong mine ventilation roadways to understand their dynamic heat transfer. To reduce the modeling effort and computation time with satisfactory accuracy, the ventilation roadway is approximated as a one-dimensional (1D) line element. Still, the surrounding rock of the roadway remains three-dimensional (3D). An equivalent heat transfer coefficient calculates the dynamic heat transfer in the radial direction of the roadway. A case analysis of the Sanhejian coal mine ventilation roadways in China is performed, and a comparison between the simulated results and field measurements indicates that the predicted airflow temperature shows good agreement. The change in the underground thermal environment concerning ventilation time is systematically investigated in detail. The surrounding rock of the roadway adjusts the underground thermal environment through heat absorption or heat release, and the temperature distribution of the surrounding rock presents a "V" shape in winter and a "W" shape in summer. The self-compression of air contributes to a remarkable heat source for the increase in airflow temperature in the air intake shaft. A roadway with a low initial temperature of the surrounding rock after long-term ventilation can effectively cool the high-temperature airflow underground in early summer. The reduction in ventilation volume will increase the cooling degree of airflow by the surrounding rock in long-term ventilation roadways in summer. Still, the airflow will be heated more significantly in short-term ventilation roadways. In addition, the increase in the average annual ambient temperature will result in a linear rise in underground airflow temperature.

Bemisia tabaci has developed high resistance to many insecticides and causes substantial agricultural and economic losses annually. The insecticide resistance of whitefly has been widely reported in previous studies; however, the underlying mechanism remains little known. In this study, we cloned two P450 genes: CYP6DW3 and CYP6DW5v1; these genes were markedly overexpressed in imidacloprid-resistant whitefly populations compared with susceptible populations, and knockdown of these genes decreased the imidacloprid resistance of whitefly. Moreover, heterologous expression of whitefly P450 genes in SF9 cells and metabolic studies showed that the CYP6DW3 protein could metabolize 14.11% imidacloprid and produced imidacloprid-urea in vitro. Collectively, the expression levels of CYP6DW3 and CYP6DW5v1 are positively correlated with imidacloprid resistance in B. tabaci. Our study further reveals that cytochrome P450 enzymes affect the physiological activities related to resistance in insects, which helps scholars more deeply understand the resistance mechanism, and contributes to the development of integrated pest management framework.

Angiotensin-converting enzyme inhibitors are widely used for treatment of hypertension and related diseases. Here, six karnamicins E1-E6 (1-6), which bear fully substituted hydroxypyridine and thiazole moieties are characterized from the rare actinobacterium Lechevalieria rhizosphaerae NEAU-A2. Through a combination of isotopic labeling, genome mining, and enzymatic characterization studies, the programmed assembly of the fully substituted hydroxypyridine moiety in karnamicin is proposed to be due to sequential operation of a hybrid polyketide synthase-nonribosomal peptide synthetase, two regioselective pyridine ring flavoprotein hydroxylases, and a methyltransferase. Based on AlphaFold protein structures predictions, molecular docking, and site-directed mutagenesis, we find that two pyridine hydroxylases deploy active site residues distinct from other flavoprotein monooxygenases to direct the chemo- and regioselective hydroxylation of the pyridine nucleus. Pleasingly, karnamicins show significant angiotensin-converting enzyme inhibitory activity with IC50 values ranging from 0.24 to 5.81 μM, suggesting their potential use for the treatment of hypertension and related diseases.

Sulfur dioxide (SO2) has been widely applied as an important additive in various foods and drugs due to its antioxidant, antiseptic and bleaching properties. SO2 in living organisms plays a key biological role as an antioxidant in a variety of life activities. However, abnormal levels of SO2 in both food and living organisms could cause harm and even serious illness, such as diseases related to the respiratory and cardiovascular systems and cancers. Therefore, it is of great practical significance to accurately determine the level of SO2 in food and organisms. In this work, we synthesized a novel near-infrared ratiometric fluorescent probe (NTO) using xanthene and benzopyran as the matrix for the detection of SO2. NTO demonstrates a rapid response (within 8 s), high selectivity, excellent sensitivity (LOD = 3.64 μM) and a long emission wavelength (800 nm), which could be applied to SO2 monitoring in a complex environment. NTO showed a high recovery (90%-110%) of SO2 in food samples such as beer and rock sugar. The results of HeLa cell experiments indicate that NTO has excellent fluorescence labeling ability for SO2 in endoexogenous-sulfide metabolism. In addition, we applied it to mice with acetaminophen (APAP)-induced acute liver injury and observed changes in SO2 during liver injury. Based on these results, we believe that this will provide a convenient visual tool for the detection of the SO2 content in food safety and biomedicine.

In the application of lithium-ion battery (LIB) modules, the pivotal factor in ensuring battery safety performance lies in enhancing thermal management effectiveness and adeptly curbing the thermal runaway propagation (TRP). This paper synthesizes the innovative type of high thermal conductivity composite phase change material (CPCM) and flame retardant phase change material (RPCM) with the inclusion of intumescent flame retardant (IFR). The structural and thermal attributes of these phase change materials (PCMs) are meticulously examined. The findings reveal that the RPCM, fortified with 10% SiC and 10% IFR, attains a peak thermal conductivity of 4.022 W/(m·K) and latent heat of 112.9 J/g. Diverse PCMs are then employed to scrutinize the thermal management of single cell and the mitigation of TRP in battery modules. The outcomes of charging and discharging cycles demonstrate that PCM cooling effectively curbs maximum temperature elevation. The most efficient PCMs reduce the maximum temperature by around 7.8 ℃ and 7.4 ℃. The impact of RPCMs and aerogel on curtailing TRP unveils that their amalgamation notably diminishes the risk of TRP and prolongs the propagation time. This research contributes a novel approach by exploring advanced PCMs potential to tackle heat dissipation optimization and TRP suppression for LIB modules simultaneously, and these findings proffer valuable information into enhancing battery operational safety.

Direct contact liquid cooling has demonstrated superior cooling capacity and heat exchange efficiency in battery thermal management when compared to alternative methods. This article presents the design of a battery thermal management system (BTMS) utilizing dynamic circulating transformer oil as an immersion cooling medium. This oil-immersed BTMS is examined for its cooling performance across different flow rates, ranging from 30 to 600 ml/min, with an analysis of heat transfer characteristics during dynamic cycles. The findings reveal that transformer oil can significantly reduce the temperature of the battery module under circulating flow conditions. Even at the lowest flow rate of 30 ml/min, the maximum temperature of the battery module remains below 45 °C. However, beyond a flow rate of 200 ml/min, specifically in the range of 300–600 ml/min, the temperature drop in the battery module becomes less noticeable. Theoretical analysis indicates that at 200 ml/min (Re = 44.1), the dynamic circulation cooling system achieves its best cooling efficiency. These results underscore the effectiveness of the oil-immersed BTMS as an efficient thermal management solution for cylindrical battery modules, supported by both experimental and theoretical perspectives.

This study aimed to investigate global, regional, and national trends in osteoarthritis disability-adjusted life years (DALYs) from 1990 to 2019, identify the burden of osteoarthritis in different age groups, and assess age, period, and cohort effects on osteoarthritis DALYs. A comprehensive analysis of the Global Burden of Disease Study 2019 data, covering 204 countries and territories. We conducted a comprehensive analysis using data from the Global Burden of Disease Study 2019, encompassing 204 countries and territories. Age-standardized DALY rates were calculated, and the age-period-cohort model was employed to examine the age, period, and cohort effects on osteoarthritis DALYs. The annual percentage change (APC) and average annual percentage change (AAPC) were estimated to evaluate trends in DALYs. Globally, osteoarthritis DALYs increased by 114.48 % between 1990 and 2019, with an age-standardized DALY rate growth of 3.3 %. The largest relative growth in DALYs occurred in Middle and Low-middle Socio-Demographic Index (SDI) regions. DALYs increased significantly in almost all age-specific groups, particularly among 45–74 years old age groups. Age, period, and cohort effects analysis revealed a general increase in osteoarthritis DALYs risk over time, with some variations by SDI quintiles and sex. The steepest increase in DALYs occurred in the 30–34 years age group, and the trend attenuated with increasing age. Males showed significantly slower DALYs growth than females in age groups with non-overlapping 95 % confidence intervals. Age effects were consistently higher in females, especially in high-SDI countries. Period and cohort effects generally demonstrated a climbing risk of osteoarthritis DALYs across different SDI quintiles, with more pronounced increases in lower-SDI regions. Our findings highlight the substantial and increasing burden of osteoarthritis at global, regional, and national levels from 1990 to 2019, with significant variations by age, period, and cohort. These results underscore the importance of developing targeted public health strategies and interventions to address the growing impact of osteoarthritis, particularly in lower-SDI regions and among older populations.

The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy.To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset.Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313).Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone.The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT.In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes.In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.

It remains challenging to remove nitrogen oxides (NOx), benzene (C6H6), and toluene (C7H8) simultaneously under conditions of low oxygen and high SO2 concentration. Herein, CuCe, MnCe, and CoCe doped WTiO2 catalysts were designed. The prepared CuCe-WTiO2 catalyst consistently maintained more than 85% NO, 92% C6H6, and 91% C7H8 removal in 260–420 °C under 3.33% O2 and 1000 ppm SO2. The adequate charge flow between the catalyst surface and the gas molecules was enhanced, promoting SO2 tolerance of CuCe-WTiO2. More NH3, NH4+, and -NH2 were adsorbed with acid sites on the CuCe-WTiO2 surface. The high concentration of adsorption centers and superior redox properties effectively improved the co-catalytic efficiency. The primary intermediates in the reduction processes via the Langmuir-Hinshelwood and Eley-Rideal mechanisms were NO2, bridged nitrite (NO2–), and monodentate nitrite (NO2–). The generation of reactive chemisorbed oxygen (Oα) becomes more accessible with the transfer of electrons from Ce4+ to adsorbed O2. C6H6 and C7H8 are progressively oxidized by Oα and eventually completely mineralized to CO2 and H2O. This study is anticipated to offer a new option for co-catalytic removal of NO, C6H6, and C7H8.

Electrocatalytic conversion of CO2 into high-value products provides a promising means to solve the problem of the greenhouse effect and energy storage but is limited by its sluggish kinetics and poor selectivity. In this work, we report cucurbit[6]uril (CB[6]) modified gold nanoparticles (Au-CB[6] NPs) with different sizes (40 nm, 60 nm, and 80 nm) using a facile in situ method and investigate their electrocatalytic performance for CO2 reduction reaction (CO2RR). The 60 nm Au-CB[6] NPs exhibits exceptional selectivity for CO with the highest Faraday efficiency (FECO) reaching 97.6% at 0.6 V vs. reversible hydrogen electrode (RHE) and excellent stability with FECO over 95% for 10 h. The partial current density of CO formed by 60 nm Au-CB[6] NPs is 8.1 mA/cm2, which is 18-fold that of 60 nm gold nanoparticles (Au NPs). Additionally, when the size increases from 40 nm to 80 nm, the CO selectivity of Au-CB[6] NPs remains around 97%, but that of Au NPs decreases from 81% to 61%. The ligand dominated catalytic performance of Au-CB[6] NPs can be attributed to the excess CB[6] coating on catalyst's surface, which creates a CO2 enriched and hydrophobic environment. The CB[6] modification on Au NPs not only improves the catalytic activity, but it also suppresses the size effect for selectivity in electrocatalytic CO2RR, which proposes a universal strategy for other nanostructures to simplify preparation and separation process and still maintain decent catalytic performance.

Surgical resection is widely recognized as one of the most effective treatments for cancer. However, it requires precise and convenient visualization of tumor boundaries to assist surgeons. Persistent luminescence nanoparticles...

Rhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations.Because the epithelial cell layer is the primary target of RV infection, we hypothesize that RV-induced airway disease is associated with the perturbation of airway epithelial gene expression.In this study, well differentiated primary human airway epithelial cells were infected with either RV16 (major group) or RV1B (minor group).Transcriptional gene profiles from RV-infected and mock-infected control cells were analyzed by Affymetrix Genechip, and changes of the gene expression were confirmed by real-time RT-PCR analysis.At 24 h after infection, 48 genes induced by both viruses were identified.Most of these genes are related to the IFN pathway, and have been documented to have antiviral functions.Indeed, a significant stimulation of IFN-␤ secretion was detected after RV16 infection.Neutralizing antibody specific to IFN-␤ and a specific inhibitor of the Janus kinase pathway both significantly blocked the induction of RV-inducible genes.Further studies demonstrated that 2-aminopurine, a specific inhibitor double-stranded RNA-dependent protein kinase, could block both IFN-␤ production and RV-induced gene expression.Thus, IFN-␤dependent pathway is a part of the double-stranded RNA-initiated pathway that is responsible for RV-induced gene expression.Consistent with its indispensable role in the induction of antiviral genes, deactivation of this signaling pathway significantly enhanced viral production.Because increase of viral yield is associated with the severity of RV-induced airway illness, the discovery of an epithelial antiviral signaling pathway in this study will contribute to our understanding of the pathogenesis of RV-induced colds and asthma exacerbations.

The feasibility of applying chitosan, as prepared from the crab chitin, was assessed in this study for the coagulation of colloidal particles. A series of batch flocculation tests with chitosan under different conditions was also conducted. The results indicate that chitosan is a potent coagulant for bentonite suspension. The relationship between the optimum chitosan dosage and the turbidity of the bentonite suspension is presented as a linear correlation. The evidence infers that an adequate range of the coagulant dosage is the primary consideration in determining the removal efficiency for the turbidity of the source water. It also indicates that the coagulation behavior for kaolinite by chitosan is different from that of bentonite, i.e., chitosan fails to form a good aggregate with kaolinite. Turbid water containing particles which show behavior similar to kaolinite apparently need to have some bentonite particles added as coagulant aid, thereby improving the aggregation of the colloid particles with chitosan. Moreover, the effect of pH on the coagulation efficiency of chitosan is insignificant. The evidence infers that charge neutralization is not a major mechanism controlling the formation of floc for chitosan coagulation.

Two water-soluble extracellular polysaccharides, ETW1 and ETW2, were isolated from the marine bacterium Edwardsiella tarda by ion-exchange and size-exclusion chromatography, and their structures were investigated. ETW1 and ETW2 are mannans, with molecular weights of about 29 and 70kDa, respectively. The main chain of the polysaccharides consists of (1-->3)-linked mannose residues, and branched mannose linkages were also detected. The branch points are located at the C-2 and C-6 positions of the (1-->3)-linked mannose residues. The side chains are composed of (1-->2)-linked mannose residues and (1-->)-linked mannose residues. Antioxidant properties of the two extracellular polysaccharides were evaluated with hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals scavenging activities and lipid peroxidation inhibition in vitro, and results showed that ETW1 and ETW2 had good antioxidant and hydroxyl and DPPH radicals scavenging activities. ETW1 exhibited higher antioxidant activity than ETW2, and could be a potential source of antioxidant and used as possible food supplement or ingredient in the pharmaceutical industry.

The present investigation was carried out to evaluate the safety of the lipid-soluble ethanol extracts from rhizome of Salvia przewalskii Maxim (SPM) by determining its potential toxicity after acute and subacute administration in rodents.For the acute study, SPM extract was administered to mice in single doses given by gavage, intramuscular and intraperitoneal route. General behavior adverse effects and mortality were determined for up to 14 days. In the subacute study, the extract was administered orally at doses of 0, 50 and 250 mg/kg daily for 30 days to rats. Body weight, heart rate, blood pressure, biochemical and hematological parameters were determined at the end of 0, 15 and 30 days of daily administration.In acute study, SPM extract caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the extract were 1723, 288 and 500 mg/kg, when given by gavage, intramuscular and intraperitoneal routes, respectively, and the lowest-observed adverse effect levels (LOAEL) were 1981, 840 and 781 mg/kg. Mortality increased with increasing doses, with LD(50) of 2547.8, 901.3 and 780.8 mg/kg for the oral, intramuscular and intraperitonal administration. In subacute study, daily oral administration of SPM extract for up to 30 days did not result in death or significant changes in the body weight, heart rate and blood pressure, hematological and mainly biological parameters. In biological analysis, some significant changes occurred, including total protein and albumin, glucose and triglycerides, indicating that SPM extract has lipid-modulating activity.SPM extract was found to be low or non-toxic when acute toxicities and subacute toxicities in rodents. In view of the doses of the components consumed in traditional medicine, there is a wide margin of safety for the therapeutic use.

An extracellular polysaccharide AVP was isolated from the fermented broth of coral-associated fungus Aspergillus versicolor LCJ-5-4. AVP was a mannoglucan with molecular weight of about 7 kDa, and the molar ratio of glucose and mannose was 1.7:1.0. On the basis of detailed one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic analyses, the backbone of AVP was characterized to be composed of (1 → 6)-linked α-d-glucopyranose and (1 → 2)-linked α-d-mannopyranose units. The mannopyranose residues in the backbone were substituted mainly at C-6 by the side chain of (1 → 2)-linked α-d-mannopyranose trisaccharides units. The antioxidant activity of AVP was evaluated with the scavenging abilities on 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals in vitro, and the results indicated that AVP had good antioxidant activity, especially scavenging ability on superoxide radicals. AVP was a novel extracellular polysaccharide with different structural characteristics from other extracellular polysaccharides and could be a potential source of antioxidant.

Imidacloprid (IC) is a systemic insecticide related to the tobacco toxin nicotine. IC is a toxic substance frequently used into combat insects, rodents and plants pests and other creatures that can pose problems for agriculture. We, therefore, planned this study to assess risk factors, biochemical and histological alterations associated with hepatotoxicity and nephrotoxicity. Forty-eight adult male albino mice were divided into four groups of 12 animals each. All the animals were given standard synthetic pellet diet. One group served as control, and the other three were served as experimental groups. Decrease in the body weight of the high dose group was observed at 15 mg/kg/day, and no mortality occurred during the treatment period. High dose of imidacloprid caused a significant elevation of serum clinical chemistry parameters, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate kinase (SGPT), alkaline phosphatase (ALP) and total bilirubin (TBIL). Histology of liver and kidney indicates hepatotoxicity and nephrotoxicity at a high dose of imidacloprid. Based on the morphological, biochemical and histopathological analysis, it is evident that imidacloprid induced toxicological effects at 15 mg/kg/day to mice. The results of the present study demonstrate that IC had significant effects on body weight, liver functions and kidney (p < 0.05) at a dose of 15 mg/kg body weight. IC treatment 5 and 10 mg/kg/day may be considered as no observed adverse effect level (NOAEL) for mice. It was concluded that IC can cause hepatotoxicity and nephrotoxicity at a dose much lower than the LD50 (131 mg/kg body weight) in mice.

The green alga Monostroma latissimum was boiled in hot water to obtain an anticoagulant-active polysaccharide. The crude polysaccharide was further purified on ion-exchange and size-exclusion chromatography to generate a polysaccharide PML of uniform size and charge. PML was a high rhamnose-containing sulfated polysaccharide with an average molecular weight of about 513 kDa. On the basis of detailed one- and two-dimensional nuclear magnetic resonance (1D, 2D NMR) spectroscopic analyses, the chain of the polysaccharide was characterized to consist of (1 → 3)-linked α-l-rhamnopyranose, (1 → 2)-linked α-l-rhamnopyranose and (1 → 2,3)-linked α-l-rhamnopyranose residues in a molar ratio of 4:1:1, and the sulfate groups were substituted at C-2 of the (1 → 3)-linked α-l-rhamnopyranose and C-3 of the (1 → 2)-linked α-l-rhamnopyranose residues. PML had a high anticoagulant activity as evaluated by assays of the activated partial thromboplastin time and thrombin time. The investigation demonstrated that PML appeared to be a sulfated rhamnan with different structural characteristics from other sulfated polysaccharides from Monostromaceae species, and could be a potential source of anticoagulant.

The major challenge for accurate fingerprint-based indoor localization is the design of robust and discriminative wireless signatures. Even though WiFi received signal strength indicator (RSSI) signatures are widely available indoors, they vary significantly over time and are susceptible to human presence, multipath, and fading due to the high operating frequency. To overcome these limitations, we propose to use FM broadcast radio signals for robust indoor fingerprinting. Because of the lower frequency, FM signals are less susceptible to human presence, multipath, and fading, they exhibit exceptional indoor penetration, and according to our experimental study they vary less over time when compared to WiFi signals. In this paper, we demonstrate through a detailed experimental study in three different buildings across the US, that FM radio signal RSSI values can be used to achieve room-level indoor localization with similar or better accuracy to the one achieved by WiFi signals. Furthermore, we propose to use additional signal quality indicators at the physical layer (i.e., SNR, multipath, etc.) to augment the wireless signature, and show that localization accuracy can be further improved by more than 5 percent. More importantly, we experimentally demonstrate that the localization errors of FM and WiFi signals are independent. When FM and WiFi signals are combined to generate wireless fingerprints, the localization accuracy increases as much as 83 percent (when accounting for wireless signal temporal variations) compared to when WiFi RSSI only is used as a signature.

High surface area activated carbon fibers (ACF) have been prepared from bamboo by steam activation after liquefaction and curing. The influences of activation temperature on the microstructure, surface area and porosity were investigated. The results showed that ACF from bamboo at 850 °C have the maximum iodine and methylene blue adsorption values. Aside from the graphitic carbon, phenolic and carbonyl groups were the predominant functions on the surface of activated carbon fiber from bamboo. The prepared ACF from bamboo were found to be mainly type I of isotherm, but the mesoporosity presented an increasing trend after 700 °C. The surface area and micropore volume of samples, which were determined by application of the Brunauer-Emmett-Teller (BET) and t-plot methods, were as high as 2024 m²/g and 0.569 cm³/g, respectively. It was also found that the higher activation temperature produced the more ordered microcrystalline structure of ACF from bamboo.

Radical nephrectomy with inferior vena cava (IVC) thrombectomy is the preferred treatment for renal cell carcinoma (RCC) with IVC thrombus. However, IVC thrombectomy using a laparoscopic approach has not been reported for high-level thrombi.To describe the surgical technique for laparoscopic IVC thrombectomy in patients with different thrombus levels and to assess its safety and feasibility.Retrospective review of medical records for 11 patients with right-side RCC, including six patients with level II IVC thrombus and five patients with level IV thrombus.Laparoscopic thrombectomy for level II thrombus was performed after clamping the infrarenal IVC, left renal vein, and infrahepatic IVC. Laparoscopic thrombectomy and thoracoscope-assisted open atriotomy for level IV thrombus were performed after establishing cardiopulmonary bypass and clamping the infrarenal IVC, left renal vein, and hepatoduodenal ligament.The intraoperative variables, postoperative complications, and surgical outcomes were assessed.The median operative time was 210min. The median IVC clamping time for patients with level II and level IV thrombus was 16.5 and 31min, respectively. The median estimated blood loss was 510ml, and no major intraoperative or postoperative complications occurred. One patient with level IV thrombus died of brain metastasis 6 mo after the operation, and the remaining ten patients had no local recurrence or distant metastasis during a median follow-up period of 31 mo.Laparoscopic IVC thrombectomy for level II thrombus and well-selected level IV thrombus may be a safe and technically feasible alternative to open surgery.We studied the treatment of patients with an inferior vena cava thrombus at different levels using a laparoscopic approach. This technique was safe and feasible in well-selected patients.

miRNAs play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. Because altered expression and function of miRNAs has been observed in bladder cancer, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single-nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA-disease associations in a two-stage model, consisting of 1,019 bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets, as well as the combined set [OR = 0.80, 95% confidence interval (CI) = 0.71-0.90, P = 2.92 × 10(-4)]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and TRAF6 in bladder cancer cells. Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer, suggesting it may represent a biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings.

Abstract BACKGROUND A rare mutation G84E in HOXB13 was recently identified to be associated with prostate cancer (PCa) in Caucasians. The goal of this study is to test association between HOXB13 genetic variants and PCa risk in Chinese men. METHODS All study subjects were part of the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). In the first stage, we screened for mutations by sequencing the HOXB13 coding region in 96 unrelated PCa patients. In stage 2, G84E and novel mutations found in stage 1 were genotyped in 671 PCa patients and 1,536 controls. In stage 3, mutation status in 751 additional PCa patients was imputed via haplotype. RESULTS The G84E mutation was not detected in this study. However, a novel mutation, G135E, was identified among 96 patients in stage 1. It was also observed twice in 575 additional PCa patients but not in 1,536 control subjects of stage 2. The frequency of G135E was significantly different between cases and controls, with a P ‐value of 0.027, based on Fisher's exact test. Haplotype estimation showed that G135E mutation carriers shared a unique haplotype that was not observed in other subjects. In stage 3, two more PCa patients were predicted to carry the G135E mutation. CONCLUSIONS We identified a novel rare mutation in the HOXB13 gene, G135E, which appears to be a founder mutation. This mutation is associated with increased PCa risk in Chinese men. Consistent with a previous report, our findings provide further evidence that rare mutations in HOXB13 contribute to PCa risk. Prostate 73: 169–175, 2013. © 2012 Wiley Periodicals, Inc.