Jiangang Liu

Intrinsic disorder (ID) is highly abundant in eukaryotes, which reflect the greater need for disorder-associated signaling and transcriptional regulation in nucleated cells. Although several well-characterized examples of intrinsically disordered proteins in transcriptional regulation have been reported, no systematic analysis has been reported so far. To test for the general prevalence of intrinsic disorder in transcriptional regulation, we used the predictor of natural disorder regions (PONDR) to analyze the abundance of intrinsic disorder in three transcription factor datasets and two control sets. This analysis revealed that from 94.13 to 82.63% of transcription factors possess extended regions of intrinsic disorder, relative to 54.51 and 18.64% of the proteins in two control datasets, which indicates the significant prevalence of intrinsic disorder in transcription factors. This propensity of transcription factors to intrinsic disorder was confirmed by cumulative distribution function analysis and charge-hydropathy plots. The amino acid composition analysis showed that all three transcription factor datasets were substantially depleted in order-promoting residues and significantly enriched in disorder-promoting residues. Our analysis of the distribution of disorder within the transcription factor datasets revealed that (a) the AT-hooks and basic regions of transcription factor DNA-binding domains are highly disordered; (b) the degree of disorder in transcription factor activation regions is much higher than that in DNA-binding domains; (c) the degree of disorder is significantly higher in eukaryotic transcription factors than in prokaryotic transcription factors; and (d) the level of α-MoRF (molecular recognition feature) prediction is much higher in transcription factors. Overall, our data reflected the fact that eukaryotes with well-developed gene transcription machinery require transcription factor flexibility to be more efficient.

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.

Flexible electronic devices have attracted considerable attention in recent years. Textile fabrics have been widely used to fabricate flexible strain sensors owing to their high flexibility. However, the elasticity of ordinary textile fabrics is low, which limits their strain sensing range. In this article, we used a simple method to fabricate flexible strain sensing fabrics (FSSFs) through the coating of graphene oxide (GO) nanosheets on elastic nylon/polyurethane (nylon/PU) fabric, followed by reduction of GO with sodium borohydride. The reduced graphene oxide (RGO) nanosheets were adsorbed on the elastic fabrics to impart electrical conductivity to the fabrics. The coated fabrics were characterized with scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Raman scattering spectroscopy. The electromechanical performance and strain sensing properties of the FSSF were investigated. The fabricated strain sensor exhibited high sensitivity, a large workable strain range (0–30%), fast response and great stability. The mechanical property of fabrics did not change remarkably after the treatment with RGO. The surface resistance of the RGO/nylon/PU only increased from ∼112 KΩ/m2 to ∼154 KΩ/m2 after 8 washing cycles, exhibiting good washability. Furthermore, real-time monitoring of human motions, such as bending of finger and rotation of wrist, was achieved by the as-prepared FSSF. The RGO/nylon/PU fabrics as flexible strain sensors have potential applications in wearable electronic devices.

neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting.Postmenopausal women with stage I-IIIB HR+/HER2- breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response.Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes.Abemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2- early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation.

This review presents the recent developments in the research hotspots of advanced functional polymers; their concepts, design strategies, and applications are briefly discussed.

Abstract Distant metastasis (DM) is the main cause of treatment failure in locally advanced rectal cancer. Adjuvant chemotherapy is usually used for distant control. However, not all patients can benefit from adjuvant chemotherapy, and particularly, some patients may even get worse outcomes after the treatment. We develop and validate an MRI-based radiomic signature (RS) for prediction of DM within a multicenter dataset. The RS is proved to be an independent prognostic factor as it not only demonstrates good accuracy for discriminating patients into high and low risk of DM in all the four cohorts, but also outperforms clinical models. Within the stratified analysis, good chemotherapy efficacy is observed for patients with pN2 disease and low RS, whereas poor chemotherapy efficacy is detected in patients with pT1–2 or pN0 disease and high RS. The RS may help individualized treatment planning to select patients who may benefit from adjuvant chemotherapy for distant control.

Oncogenic B-RAF V600E mutation is found in 50% of melanomas and drives MEK/ERK pathway and cancer progression. Recently, a selective B-RAF inhibitor, vemurafenib (PLX4032), received clinical approval for treatment of melanoma with B-RAF V600E mutation. However, patients on vemurafenib eventually develop resistance to the drug and demonstrate tumor progression within an average of 7 months. Recent reports indicated that multiple complex and context-dependent mechanisms may confer resistance to B-RAF inhibition. In the study described herein, we generated B-RAF V600E melanoma cell lines of acquired-resistance to vemurafenib, and investigated the underlying mechanism(s) of resistance. Biochemical analysis revealed that MEK/ERK reactivation through Ras is the key resistance mechanism in these cells. Further analysis of total gene expression by microarray confirmed a significant increase of Ras and RTK gene signatures in the vemurafenib-resistant cells. Mechanistically, we found that the enhanced activation of fibroblast growth factor receptor 3 (FGFR3) is linked to Ras and MAPK activation, therefore conferring vemurafenib resistance. Pharmacological or genetic inhibition of the FGFR3/Ras axis restored the sensitivity of vemurafenib-resistant cells to vemurafenib. Additionally, activation of FGFR3 sufficiently reactivated Ras/MAPK signaling and conferred resistance to vemurafenib in the parental B-RAF V600E melanoma cells. Finally, we demonstrated that vemurafenib-resistant cells maintain their addiction to the MAPK pathway, and inhibition of MEK or pan-RAF activities is an effective therapeutic strategy to overcome acquired-resistance to vemurafenib. Together, we describe a novel FGFR3/Ras mediated mechanism for acquired-resistance to B-RAF inhibition. Our results have implications for the development of new therapeutic strategies to improve the outcome of patients with B-RAF V600E melanoma.

Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM). Ginsenoside Rg1, extracted from Radix Ginseng, exerts a [Formula: see text]-secretase inhibitor effect so as to decrease A[Formula: see text] aggregation. It can also inhibit the apoptosis of neuron cells. Tanshinone IIA, extracted from Radix Salviae miltiorrhizae, and baicalin, extracted from Radix Scutellariae[Formula: see text] can inhibit the oxidative stress injury in neuronal cells. Icariin, extracted from Epimedium brevicornum, can decrease A[Formula: see text] levels and the hyperphosphorylation of tau protein, and can also inhibit oxidative stress and apoptosis. Huperzine A, extracted from Huperzia serrata, exerts a cholinesterase inhibitor effect. Evodiamine, extracted from Fructus Evodiae, and curcumin, extracted from Rhizoma Curcumae Longae, exert anti-inflammatory actions. Curcumin can act on A[Formula: see text] and tau too. Due to the advantages of multi-target effects and fewer side effects, Chinese medicine is more appropriate for long-term use. In this present review, the pharmacological effects of commonly used active components derived from Chinese herbal medicines in the treatment of AD are discussed.

The morphological and structural features of the conjugated polymer films play an important role in the charge transport and the final performance of organic optoelectronics devices [such as organic thin-film transistor (OTFT) and organic photovoltaic cell (OPV), etc.] in terms of crystallinity, packing of polymer chains and connection between crystal domains. This review will discuss how the conjugated polymer solidify into, for instance, thin-film structures, and how to control the molecular arrangement of such functional polymer architectures by controlling the polymer chain rigidity, polymer solution aggregation, suitable processing procedures, etc. These basic elements in intrinsic properties and processing strategy described here would be helpful to understand the correlation between morphology and charge transport properties and guide the preparation of efficient functional conjugated polymer films correspondingly.

The correlated donor/acceptor (D/A) molecular orientation plays a crucial role in solution-processed all-polymer solar cells in term of photovoltaic performance. For the conjugated polymers PTB7-th and P(NDI2OD-T2), the preferential molecular orientation of neat PTB7-th films kept face-on regardless of the properties of processing solvents. However, an increasing content of face-on molecular orientation in the neat P(NDI2OD-T2) films could be found by changing processing solvents from chloronaphthalene (CN) and o-dichlorobenzene (oDCB) to chlorobenzene (CB). Besides, the neat P(NDI2OD-T2) films also exhibited a transformation of preferential molecular orientation from face-on to edge-on when extending film drying time by casting in the same solution. Consequently, a distribution diagram of molecular orientation for P(NDI2OD-T2) films was depicted and the same trend could be observed for the PTB7-th/P(NDI2OD-T2) blend films. By manufacture of photovoltaic devices with blend films, the relationship between the correlated D/A molecular orientation and device performance was established. The short-circuit current (Jsc) of devices processed by CN, oDCB, and CB enhanced gradually from 1.24 to 8.86 mA/cm(2) with the correlated D/A molecular orientation changing from face-on/edge-on to face-on/face-on, which could be attributed to facile exciton dissociation at D/A interface with the same molecular orientation. Therefore, the power conversion efficiency (PCE) of devices processed by CN, oDCB, and CB improved from 0.53% to 3.52% ultimately.

Here, the perovskite nucleation process was controlled, producing films with optimized morphology and crystal orientation <italic>via</italic> the application of selective solvent annealing.

A number of miRNAs have been found to be abnormally expressed or mutated in numerous cancers and thus, are considered to act as oncogenes or tumor suppressor genes. The aim of the present study was to investigate the effect of miR-181 on cisplatin-resistant non-small cell lung cancer (NSCLC). In patients with cisplatin-resistant NSCLC, miR-181 expression was found to be markedly decreased. In addition, in the cisplatin-resistant human lung adenocarcinoma cell line A549/DDP, miR-181 downregulation promoted cell growth and metastasis and inhibited cell apoptosis, whereas miR-181 overexpression exerted the opposite effects. Furthermore, miR-181 downregulation suppressed LC3 and ATG5 protein expression in A549/DDP cells through suppression of the PTEN/PI3K/AKT/mTOR pathway, whereas miR-181 overexpression recovered LC3 and ATG5 protein expression by promoting PTEN/PI3K/AKT/mTOR signaling. In turn, PTEN inhibitors reduced the anticancer effects of miR-181 overexpression on A549/DDP cell growth via the regulation of autophagy through the PI3K/AKT/mTOR pathway. Therefore, miR-181 may be a novel and important regulator of cisplatin-resistant NSCLC by serving a role in the regulation of apoptosis, as an established rate-limiting miRNA target.

This study demonstrates that the solubility properties of polymer donors are vitally important for layer-by-layer processed organic solar cells. Manipulating the solubility of an NTI-based polymer donor enables 17.59% efficiency for a PNTB6-Cl:N3 based device.

Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER+)/HER2- breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an "IFN-related palbociclib-resistance Signature" (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER+/HER2- tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.

Abstract The development of glioblastoma (GBM) is typically accompanied by marked changes in lipid metabolism. Oxylipins and their catalyzed enzymes lipoxygenases (LOXs) have been shown to participate in the development of cancers via multiple pathways, while the understanding of LOXs in GBM remains enigmatic. Thus, we aimed to explore the expression and functional roles of LOXs in the development of GBM. Here we showed that ALOXE3 was markedly down-regulated in human GBM. Knockdown of ALOXE3 in GBM cells fostered the orthotopic tumor growth and shortened lifespan in mice. ALOXE3 deficiency rendered GBM cells resistant to p53-SLC7A11 dependent ferroptosis, promoting GBM cell survival. Mechanistically, miR-18a directly targeted ALOXE3 and suppressed its expression and functions in GBM cells. Furthermore, ALOXE3 silencing promoted 12-hydroxyeicosatetraenoic acids (12-HETE) secretion from GBM cells, in turn, 12-HETE enhanced migration of GBM cells by activating G s -protein-coupled receptor (G s PCR)-PI3K-Akt pathway in an autocrine manner. Altogether, miR-18a/ALOXE3 axis exerts tumor promoting functions by regulating ferroptosis and migration of GBM cells. Targeting miR-18a/ALOXE3 axis may provide novel therapeutic approaches for GBM treatment.

Dementia has become one of the most important diseases threatening human health. Alzheimer's disease (AD) and vascular dementia (VaD) have the highest incidence rates among the types of dementia, but until now, therapeutic methods have been limited. Panax ginseng has been used in China for thousands of years to treat dementia, and modern medical studies have found that it contains multiple active components, such as ginsenosides, polysaccharides, amino acids, volatile oils and polyacetylenes, many of which have therapeutic effects in treating AD and VaD. Studies have found that ginsenosides have multitarget therapeutic effects in treating dementia, such as regulation of synaptic plasticity and the cholinergic system, inhibition of Aβ aggravation and tau hyperphosphorylation, anti-neuroinflammation, anti-oxidation effects and anti-apoptosis effects. Other active components of Panax ginseng, such as gintonin, oligosaccharides, polysaccharides and ginseng proteins, also have therapeutic effects on AD and VaD. The effectiveness of ginseng-containing Chinese medicine compounds has also been confirmed by clinical and basic investigations in treating AD and VaD. In this review, we summarized the potential therapeutic effects and related mechanisms of Panax ginseng in treating AD and VaD to provide some examples for further studies.

This study focuses on synthesizing a range of hydrolysis-modified poly(phthalazione ether nitrile) polymers with different quantities of carboxyl groups (HPPEN-COOH). These polymers are intended to enhance the bonding strength between carbon fibers (CFs) and poly(phthalazine ether sulfone ketone) (PPESK). The chemical structure of HPPEN-COOH was elucidated using FTIR spectroscopy, and the presence of HPPEN-COOH as a coating on the CFs surface was confirmed by XPS analysis. Compared with the UCF/PPESK composite, the interlaminar shear strength of the CF-5/PPESK composite increased by 39%. In the DMA test, the service temperature and storage modulus of the CF-5/PPESK composite were increased to 268°C and 112 GPa, respectively. Furthermore, the composite showed satisfactory performance in hydrothermal aging studies. This method is simple and easy to implement, has the potential for large-scale industrial production, and is an environmentally friendly method to improve the interface properties of the CF/PPESK composite.

We promoted order−disorder transformation of poly(3-hexylthiophene) (P3HT) in solution by ultrasonic oscillation which substantially improved crystallinity in its pure film. P3HT with low molecular weight (Mw) dispersed very well in p-xylene solvent and few aggregates generated in the solution. For P3HT with high Mw, the results suggested the coexistence of two phases: disordered coils in solution and ordered microcrystals in suspension. Upon ultrasonic oscillating, more ordered precursors generated in solution due to increased self-assembly from disordered to ordered configuration, which resulting from decreased extent of chains entanglement existing in high molecular system, and red shift at absorption maximum and growing intensity of the π−π* absorption at ca. 604 nm were observed in solution. The films prepared from the oscillated solution then showed increased degree of crystallinity, π−π interactions and homogeneously distributed nanofibrils, which should be attributed to the ordered precursors constructed in solution. Furthermore, the best crystallinity of the film was obtained at the oscillating time of 4 min, showing the equilibrium state between the increased content of crystalline molecules and the shortened crystalline length. This simple method paves the way for the decreasing chains entanglement during crystallizing process of conjugated polymer in solution, and it enriches the ways to improve crystalline order in thin films comprising crystallizable polymers.

Reliable profiling of the extracellular dopamine (DA) concentration in the central nervous system is essential for a deep understanding of its biological and pathological functions. However, quantitative determination of this neurotransmitter remains a challenge because of the extremely low concentration of DA in the cerebrospinal fluid (CSF) of patients. Herein, on the basis of the specific recognition of boronate toward diol and N-hydroxysuccinimide ester toward the amine group, a simple and highly sensitive strategy was presented for DA detection by using surface-enhanced Raman scattering (SERS) spectroscopy as a signal readout. This was realized by first immobilizing 3,3′-dithiodipropionic acid di(N-hydroxysuccinimide ester) on gold thin film surfaces to capture DA, followed by introducing 3-mercaptophenylboronic acid (3-MPBA)-functionalized silver nanoparticles to generate numerous plasmonic “hot spots” with the nanoparticle-on-mirror geometry. Such a dual-recognition mechanism not only avoids complicated bioelement-based manipulations but also efficiently decreases the background signal. With the direct use of the recognition probe 3-MPBA as a Raman reporter, the “signal-on” SERS method was employed to quantify the concentration of DA from 1 pM to 1 μM with a detection limit of 0.3 pM. Moreover, our dual-recognition-directed SERS assay exhibited a high resistance to cerebral interference and was successfully applied to monitoring of DA in CSF samples of patients.

Autophagy begins with the nucleation of phagophores, which then expand to give rise to the double-membrane autophagosomes. Autophagosomes ultimately fuse with lysosomes, where the cytosolic cargoes are degraded. Accumulation of autophagosomes is a hallmark of autophagy and neurodegenerative disorders including Alzheimer’s and Huntington’s disease. In recent years, the sources of autophagosome membrane have attracted a great deal of interests, even so, the membrane donors for autophagosomes are still under debate. In this review, we describe the probable sources of autophagosome membrane.

Abstract Anti-EGFR antibodies are effective in therapies for late-stage colorectal cancer (CRC); however, many tumours are unresponsive or develop resistance. We performed genomic analysis of intrinsic and acquired resistance to anti-EGFR therapy in prospectively collected tumour samples from 25 CRC patients receiving cetuximab (an EGFR inhibitor). Of 25 CRC patients, 13 displayed intrinsic resistance to cetuximab; 12 were intrinsically sensitive. We obtained six re-biopsy samples at acquired resistance from the intrinsically sensitive patients. NCOA4–RET and LMNA–NTRK1 fusions and NRG1 and GNAS amplifications were found in intrinsic-resistant patients. In cetuximab-sensitive patients, we found KRAS K117N and A146T mutations in addition to BRAF V600E, AKT1 E17K, PIK3CA E542K, and FGFR1 or ERBB2 amplifications. The comparison between baseline and acquired-resistant tumours revealed an extreme shift in variant allele frequency of somatic variants, suggesting that cetuximab exposure dramatically selected for rare resistant subclones that were initially undetectable. There was also an increase in epithelial-to-mesenchymal transition at acquired resistance, with a reduction in the immune infiltrate. Furthermore, characterization of an acquired-resistant, patient-derived cell line showed that PI3K/mTOR inhibition could rescue cetuximab resistance. Thus, we uncovered novel genomic alterations that elucidate the mechanisms of sensitivity and resistance to anti-EGFR therapy in metastatic CRC patients.

Reliable monitoring of metabolites in biofluids is critical for diagnosis, treatment, and long-term management of various diseases. Although widely used, existing enzymatic metabolite assays face challenges in clinical practice primarily due to the susceptibility of enzyme activity to external conditions and the low sensitivity of sensing strategies. Inspired by the micro/nanoscale confined catalytic environment in living cells, the coencapsulation of oxidoreductase and metal nanoparticles within the nanopores of macroporous silica foams to fabricate all-in-one bio-nanoreactors is reported herein for use in surface-enhanced Raman scattering (SERS)-based metabolic assays. The enhancement of catalytical activity and stability of enzyme against high temperatures, long-time storage or proteolytic agents are demonstrated. The nanoreactors recognize and catalyze oxidation of the metabolite, and provide ratiometric SERS response in the presence of the enzymatic by-product H2O2, enabling sensitive metabolite quantification in a "sample in and answer out" manner. The nanoreactor makes any oxidoreductase-responsible metabolite a candidate for quantitative SERS sensing, as shown for glucose and lactate. Glucose levels of patients with bacterial infection are accurately analyzed with only 20 µL of cerebrospinal fluids, indicating the potential application of the nanoreactor in vitro clinical testing.

Background Biliary tract cancers are aggressive, rare, gastrointestinal malignancies with a poor prognosis; approximately half of patients with these cancers survive for less than 1 year after diagnosis with advanced disease. We aimed to evaluate the efficacy and safety of ramucirumab or merestinib in addition to first-line cisplatin–gemcitabine in patients with locally advanced or metastatic biliary tract cancer. Methods We did a randomised, double-blind, phase 2 study at 81 hospitals across 18 countries. We enrolled patients with histologically or cytologically confirmed, non-resectable, recurrent, or metastatic biliary tract adenocarcinoma, who were treatment-naive, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0 or 1, estimated life expectancy of 3 months or more, and measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1. Eligible participants were randomly assigned (2:1:2:1) to receive either intravenous ramucirumab 8 mg/kg or placebo (on days 1 and 8 in 21-day cycles) or oral merestinib 80 mg or placebo (once daily) until disease progression, unacceptable toxicity, death, or patient or investigator request for discontinuation. All participants received intravenous cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 (on days 1 and 8 in 21-day cycles), for a maximum of eight cycles. Randomisation was done by an interactive web response system using a permuted block method (blocks of six) and was stratified by primary tumour site, geographical region, and presence of metastatic disease. Participants, investigators, and the study funder were masked to treatment assignment within the intravenous and oral groups. The primary endpoint was investigator-assessed progression-free survival (in the intention-to-treat population). The safety analysis was done in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT02711553, and long-term follow-up is ongoing. Findings Between May 25, 2016, and Aug 8, 2017, 450 patients were assessed for eligibility and 309 (69%) were enrolled and randomly assigned to ramucirumab (n=106), merestinib (n=102), or pooled placebo (n=101); 306 received at least one dose of study treatment. The median follow-up time for progression-free survival at data cutoff (Feb 16, 2018) was 10·9 months (IQR 8·1–14·1). Median progression-free survival was 6·5 months (80% CI 5·7–7·1) in the ramucirumab group, 7·0 months (6·2–7·1) in the merestinib group, and 6·6 months (5·6–6·8) in the pooled placebo group (ramucirumab vs placebo hazard ratio 1·12 [80% CI 0·90–1·40], two-sided stratified p=0·48; merestinib vs placebo 0·92 [0·73–1·15], two-sided stratified p=0·64). The most common grade 3 or worse adverse events were neutropenia (51 [49%] of 104 patients in the ramucirumab group; 48 [47%] of 102 in the merestinib group; and 33 [33%] of 100 in the pooled placebo group), thrombocytopenia (36 [35%]; 19 [19%]; and 17 [17%]), and anaemia (28 [27%]; 16 [16%]; and 19 [19%]). Serious adverse events occurred in 53 (51%) patients in the ramucirumab group, 56 (55%) in the merestinib group, and 48 (48%) in the pooled placebo group. Treatment-related deaths (deemed related by the investigator) occurred in one (1%) of 104 patients in the ramucirumab group (cardiac arrest) and two (2%) of 102 patients in the merestinib group (pulmonary embolism [n=1] and sepsis [n=1]). Interpretation Adding ramucirumab or merestinib to first-line cisplatin–gemcitabine was well tolerated, with no new safety signals, but neither improved progression-free survival in patients with molecularly unselected, locally advanced or metastatic biliary tract cancer. The role of these targeted inhibitors remains investigational, highlighting the need for further understanding of biliary tract malignancies and the contribution of molecular selection. Funding Eli Lilly and Company.

Polymer solar cells (PSCs) are promising for efficient solar energy conversion, but achieving high efficiency and device longevity within a bulk-heterojunction (BHJ) structure remains a challenge. Traditional small-molecule acceptors (SMAs) in the BHJ blend show thermodynamic instability affecting the morphology. In contrast, tethered SMAs exhibit higher glass transition temperatures, mitigating these concerns. Yet, they might not integrate well with polymer donors, causing pronounced phase separation and overpurification of mixed domains. Herein, a novel ternary device is introduced that uses DY-P2EH, a tethered dimeric SMA with conjugated side-chains as host acceptor, and BTP-ec9, a monomeric SMA as secondary acceptor, which respectively possess hypomiscibility and hypermiscibility with the polymer donor PM6. This unique combination affords a parallel-connected ternary BHJ blend, leading to a hierarchical and stable morphology. The ternary device achieves a remarkable fill factor of 80.61% and an impressive power conversion efficiency of 19.09%. Furthermore, the ternary device exhibits exceptional stability, retaining over 85% of its initial efficiency even after enduring 1100 h of thermal stress at 85 °C. These findings highlight the potential advantage of tethered SMAs in the design of ternary devices with a refined hierarchical structure for more efficient and durable solar energy conversion technologies.

In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab.Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive.This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available.The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort.Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).

The rapid development of computational pathology has brought new opportunities for prognosis prediction using histopathological images. However, the existing deep learning frameworks lack exploration of the relationship between images and other prognostic information, resulting in poor interpretability. Tumor mutation burden (TMB) is a promising biomarker for predicting the survival outcomes of cancer patients, but its measurement is costly. Its heterogeneity may be reflected in histopathological images. Here, we report a two-step framework for prognostic prediction using whole-slide images (WSIs). First, the framework adopts a deep residual network to encode the phenotype of WSIs and classifies patient-level TMB by the deep features after aggregation and dimensionality reduction. Then, the patients' prognosis is stratified by the TMB-related information obtained during the classification model development. Deep learning feature extraction and TMB classification model construction are performed on an in-house dataset of 295 Haematoxylin & Eosin stained WSIs of clear cell renal cell carcinoma (ccRCC). The development and evaluation of prognostic biomarkers are performed on The Cancer Genome Atlas-Kidney ccRCC (TCGA-KIRC) project with 304 WSIs. Our framework achieves good performance for TMB classification with an area under the receiver operating characteristic curve (AUC) of 0.813 on the validation set. Through survival analysis, our proposed prognostic biomarkers can achieve significant stratification of patients' overall survival (P 0.05) and outperform the original TMB signature in risk stratification of patients with advanced disease. The results indicate the feasibility of mining TMB-related information from WSI to achieve stepwise prognosis prediction.

The present study was the first to use the functional magnetic resonance imaging (fMRI) methodology to investigate the neural correlates of race categorization of own- and other-race faces. We found that Chinese participants categorized the race of Caucasian faces more accurately and faster than that of Chinese faces, replicating the robust effect of the other-race categorization advantage. Regions of interest (ROI) analyses revealed greater neural activations when participants were categorizing own-race faces than other-race faces in the bilateral ventral occipito-temporal cortex (VOT) such as the fusiform face areas (FFAs) and the occipital face areas (OFAs). Within the left FFA, there was also a significant negative correlation between the behavioral difference of own- and other-race face categorization accuracy and the activation difference between categorizing own- and other-race faces. Whole brain analyses showed that categorizing own-race faces induced greater activations in the right medial frontal cortex (MFC) and right inferior frontal gyrus (IFG) than categorizing other-race faces. Psychophysiological interaction (PPI) analyses revealed that the frontal cortical regions interacted more strongly with the posterior VOT during the categorization of own-race faces than that of other-race faces. Overall, our findings suggest that relative to the categorization of other-race faces, more cortical resources are engaged during the categorization of own-race faces with which we have a higher level of processing expertise. This increased involvement of cortical neural sources perhaps serves to provide more in-depth processing of own-race faces (such as individuation), which in turn paradoxically results in the behavioral other-race categorization advantage.

The present study focused on neural correlates underlying second-order deception. In first-order deception, the recipient of deception is unaware of the deceiver's deceptive intention. However, during second-order deception, the recipient is fully aware of the deceiver's deceptive intention and thus the deceiver needs to use both lies and truths to deceive the recipient. Using the functional near-infrared spectroscopy (fNIRS) methodology and a naturalistic interactive game, we found that second-order deception elicited significantly greater [oxy-Hb] changes in the prefrontal cortex (the right superior frontal gyrus (SFG), BA6) than the non-deceptive control condition. This finding suggests that second-order deception, like first-order deception, engages specifically the cortical regions associated with the planning of complex actions and goal processing. We also found that lying to deceive produced greater neural activities in the right middle frontal gyrus than truth-telling to deceive. This suggests that although both actions serve deceptive purposes, making a false statement contradicting the true state of affairs still requires more executive control and thus greater neural responses in the cortical regions associated with this function. In addition, we found that the successful deception produced greater neural activities in a broad area of the prefrontal frontal cortex than failure to deceive, indicating the involvement of the cortical reward system during second-order deception. Further, failure of truth-telling to deceive produced greater neural responses in the right SFG than failure of lying to deceive. The present findings taken together suggest that second-order deception engages both the cortical executive and reward systems.

Uniaxially aligned triisopropylsilylethynyl pentacene (TIPS-pentacene) crystals over a large area were fabricated using zone-casting technique. The array of TIPS-pentacene displayed a high orientation degree with a dichroic ratio (DR) of 0.80. The crystals were arranged with c axis perpendicular to the substrate and the long axis of the ribbon corresponded to the a axis of TIPS-pentacene. The properties of the solutions and the processing parameters were shown to influence the formation of the oriented TIPS-pentacene crystalline array. Solvent with a low boiling point (such as chloroform) favoured the orientation of the ribbon-like crystals. The concentration of the solution should be appropriate, ensuring the crystallization velocity of TIPS-pentacene matching with the receding of the meniscus. Besides, we proved that the casting speed should be large enough to induce a sufficient concentration gradient. The orientation mechanism of TIPS-pentacene was attributed to a synergy of the ordered nuclei and a match between the crystallization velocity and the casting speed. Field effect transistors (FETs) based on the oriented TIPS-pentacene crystalline array showed a mobility of 0.67 cm(2) V(-1) s(-1).

It was found that the H/J ratio of DTS(PTTh₂)₂ could be tuned from 0.30 to 1.40 by controlling the main solvent and additives, and the best PCE of 6.51% was achieved when the H/J ratio was 1.01.

Abstract The molecular orientation has a profound influence on the performance of organic solar cells. Both donor and acceptor adopt face‐on orientation guarantees efficient exciton dissociation and charge transport, which is a key to achieving high device performance. However, the molecules usually adopt edge‐on orientation in some blend systems, take small molecules based on an oligothiophene (DRCN5T): fused‐ring electron acceptor based on indacenodithieno[3,2‐b]‐thiophene core and thienyl side‐chains (ITIC‐Th) blend, for instance, the orientation of DRCN5T is edge‐on, which is detrimental to the photophysical process of the device. Herein, a solid additive strategy, that is, adding N2200 as a nucleus for DRCN5T, was proposed, which combined the nucleation process with molecular diffusivity, thus realizing the orientation transformation of DRCN5T from edge‐on to face‐on. Consequently, the device performance was significantly improved, and a clear relationship between molecular orientation and energy loss/biomolecular recombination was established. More importantly, this study revealed not only the thermodynamic factors, including the crystallinity of solid additive, the lattice matching degree, and miscibility between DRCN5T and solid additive but also the kinetic parameter, such as the diffusivity of DRCN5T are very important to efficiently regulate the molecular orientation. Overall, this study presents the in‐depth mechanism of orientation transformation via adding solid additives, which may provide a guideline for solid additive choices.

The chemical composition of Mentha haplocalyx volatile oils from different origins was studied by gas chromatography/mass spectrometry (GC/MS) and comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC × GC/TOFMS). A total of 67 compounds were identified by GC/MS and a total of 1956 compounds were identified by GC × GC/TOFMS from five Mentha haplocalyx samples in different origins. In the GC × GC/TOFMS chromatogram, the classification of group type could be clearly observed. The results of GC × GC/TOFMS showed that there were some significant differences in chemical composition of Mentha haplocalyx between Anhui and other geographically areas, especially the biologically active ingredient of Isopiperitone, Levomenthol and Isomenthone. They were more abundant from Anhui than that from other origins. Principal component analysis (PCA) of GC/MS and GC × GC/TOFMS data was performed. The results showed that the PCA model constructed with the data of GC × GC/TOFMS was better than that of GC/MS to identify the authenticity of Mentha haplocalyx medicinal materials. Using the particle-assisted solvent flotation method, the active compounds were enriched from Mentha haplocalyx samples, which could be further used for food additive or pharmacological activity research.

To identify and quantify biologically active components in rat serum after orally administrating the decoction of Bulpleurum falcatum L. and Fractus aurantii, one of traditional Chinese medicines (TCMs), high-performance liquid chromatography (HPLC)-tandem mass spectrometry method was developed and validated. The HPLC separation was carried out on a Waters Nova Pak C(18) column using acetonitrile and water as mobile phase after the sample of rat serum was cleaned up with solid-phase extraction. Atmospheric pressure chemical ionization in the negative ion mode and selected reaction monitoring (SRM) method was developed to determine the active components. Three flavonoids of hesperidin, neohesperidin and naringin were identified in the serum by comparing their retention times and three independent SRM precursor/product ion transitions with those of corresponding reference standards. The concentrations of naringin, hesperidin and neohesperidin in rat serum determined by SRM measurement were 16.3, 11.9 and 14.3 ng/ml, respectively, after orally administrating the decoction of B. falcatum L. and F. aurantii. This method was validated in terms of recovery, linearity, accuracy and precision (intra- and interday variation). The recoveries from spiked control samples were 93.0, 89.3 and 91.2% for hesperidin, neohesperidin and naringin, respectively. Linearity in rat serum was observed over the range of 2.0-50.0 ng/ml. Percent bias (accuracy) and precision were well within the acceptable range and the relative standard deviation (R.S.D.) of the measured rat serum samples was less than 10% (n=5).

The film morphology and nanostructure of the soluble fullerene, [6,6]-phenyl-C61 butyric acid methyl ester (PCBM), are crucial for its applications in organic thin film devices, such as organic solar cells and organic thin film transistors. In this work, the morphology, structural transformation, and crystallite orientation of PCBM film under thermal annealing as a function of annealing temperature, processing solvents, and solution concentrations are systematically investigated. Crystalline PCBM films with needle-like crystallites, axialitic aggregates, and faceted slices are formed in the annealing process. The axialites, made up of needle-like aggregates, are proposed to be partially developed spherulites frozen at the early growth stage formed through low-angle branching. The faceted slices are found to be PCBM single crystallites with hexagonal packing in the film plane. The film undergoes both amorphous-to-crystalline and crystalline-to-crystalline phase transformations as the annealing temperature is increased. The former transformation, corresponding to the self-organization of disordered PCBM molecules in the kinetically frozen films, occurs at a relative low temperature once the motion of these molecules is thermally activated, whereas the later one, corresponding to the transformation between two thermally stable crystalline phases, occurs when further increasing the annealing temperature. The PCBM crystallites composing these films are found to have an orientation preference normal to the film surface, which can be attributed to the confinement of film thickness for PCBM crystallite growth.

In this paper, mixed-solvent vapor-assisted imprinting annealing was proposed to improve the lateral phase separation, vertical distribution of fullerene component and the photon absorption in poly[N-9′-heptadecanyl-2,7-carbazole-alt-5,5-(4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)] (PCDTBT):[6,6]-phenyl-C71 butyric acid methyl ester (PC70BM) blend system. After the mixed-solvent vapor-assisted imprinting annealing (one is good for PCDTBT, that is, carbon disulfide (CS2) and the other is good for PC70BM, that is, tetrahydrofuran (THF)) for 20 min at the vapor pressure of P = 0.9 (25 °C), both the crystallinity of PCDTBT and the aggregation of PC70BM were promoted, resulting an interpenetrating network, as confirmed by spectroscopic ellipsometry (SE) and transmission electron microscope (TEM). Furthermore, the fullerene content on the top surface was enhanced due to the reduced energy difference between the top and bottom surface of the film as well, which was demonstrated by X-ray photoelectron spectroscopy (XPS). Besides the morphology transition, surface relief grating structures were also introduced to the film surface, resulting in an increased probability of photon absorption due to light diffraction. As a consequence, the final structure of active layer was effective in enhancing photon absorption, improving the carrier mobility, and reducing the carrier recombination, which lead to a power conversion efficiency (PCE) of 7.20% under AM1.5G illumination, almost 55% higher than PCE of reference device (PCE = 4.66%).

Abstract High-sensitivity C-reactive protein (hs-CRP) is independently associated with cardiovascular events in coronary artery disease (CAD) patients and reducing the hs-CRP level may further benefit this population. We conduct this parallel design, randomized-controlled trial to assess the effectiveness of adjunct sodium tanshinone IIA sulfate (STS) therapy on circulating inflammation markers in CAD patients. Unstable angina or non-ST-elevation myocardial infarction patients with increased hs-CRP level were randomly assigned to atorvastatin-based standard medical therapy or standard therapy plus STS injection (80 mg, once daily for 14 consecutive days). The primary outcome was hs-CRP level. After the 14-day treatment, the experimental group (n = 35) exhibited significantly lower levels of hs-CRP than the control group (n = 35) (1.72 vs 3.20 mg/L, p = 0.0191). Lower levels of interleukin-6, monocyte chemotactic protein-1 (MCP-1), and soluble CD40 ligand were also observed in the experimental group. Angina symptoms were also better controlled in the experimental group. At 30 days after treatment completion, MCP-1 levels remained lower in the experimental group than in the control group (313.88 vs 337.91 pg/mL, p = 0.0078). No serious adverse events occurred. Our study demonstrates that on the basis of standard medical therapy, STS further reduce elevated hs-CRP and other circulating inflammation markers in CAD patients. (Chictr.org number: ChiCTR-TRC-12002361).

Fibroblasts from patients with Type I bipolar disorder (BPD) and their unaffected siblings were obtained from an Old Order Amish pedigree with a high incidence of BPD and reprogrammed to induced pluripotent stem cells (iPSCs). Established iPSCs were subsequently differentiated into neuroprogenitors (NPs) and then to neurons. Transcriptomic microarray analysis was conducted on RNA samples from iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E) or 4 weeks (termed late neurons, L). Global RNA profiling indicated that BPD and control iPSCs differentiated into NPs and neurons at a similar rate, enabling studies of differentially expressed genes in neurons from controls and BPD cases. Significant disease-associated differences in gene expression were observed only in L neurons. Specifically, 328 genes were differentially expressed between BPD and control L neurons including GAD1, glutamate decarboxylase 1 (2.5 fold) and SCN4B, the voltage gated type IV sodium channel beta subunit (-14.6 fold). Quantitative RT-PCR confirmed the up-regulation of GAD1 in BPD compared to control L neurons. Gene Ontology, GeneGo and Ingenuity Pathway Analysis of differentially regulated genes in L neurons suggest that alterations in RNA biosynthesis and metabolism, protein trafficking as well as receptor signaling pathways may play an important role in the pathophysiology of BPD.

Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics-based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573-86. ©2016 AACR.

This paper assessed the evidence of Panax notoginseng preparations in patients suffering from UAP using meta-analysis and systematic review methods. Methods were according to the Cochrane Handbook and analysed using Revman 5.3. A search of PubMed, Cochrane Library, Embase, MEDLINE, Chinese national knowledge infrastructure (CNKI), Vip information database, Wanfang data and Chinese Biomedical Literature Database (SinoMed) was conducted to identify randomized controlled trials (RCTs) of P. notoginseng preparations on UAP regardless of blinding, sex and language. The outcomes include all-cause mortality, cardiac mortality, cardiovascular events, UAP symptoms, improvement of electrocardiogram and adverse events. Eighteen RCTs including 1828 patients were identified. The level of reporting is generally poor. Among 18 studies, 16 studies were prescribed P. notoginseng injections, and two studies were oral P. notoginseng preparations. Reduction of cardiovascular events (RR:0.35;95% CI:0.13 to 0.94), alleviation of angina pectoris symptoms (RR:1.23;95% CI 1.18 to 1.29), improvement of ECG (RR:1.22;95% CI 1.15 to 1.28) and reduced frequency of angina pectoris (MD:-1.48; 95% CI -2.49 to -0.48) were observed. Cardiac mortality and duration of angina pectoris were not statistically significant. Panax notoginseng is beneficial to UAP patients; the results of these reviews may have important implications to clinical work. Copyright © 2017 John Wiley & Sons, Ltd.

The rational design of the morphology of ternary all-polymer solar cells (all-PSCs) having broadened photon harvesting is crucial to achieve high device performance. However, multicomponent blends often illustrated an unfavorable morphology such as large-sized phase separation due to their complicated interaction. Herein, we proposed to solve these problems by employing two donors with good miscibility (J51 and PTB7-Th), which also have similar compatibility with the acceptor (N2200). The resultant ternary blend films of J51:PTB7-Th:N2200 feature a uniform phase separation morphology due to the reduced competitive effect of intermolecular interactions. As an additional polymer donor, PTB7-Th could not only enhance the absorption of the binary blend but also act as a crystallization regulator to boost the face-on orientation in ternary blends. Accordingly, the J51:PTB7-Th:N2200 ternary blends exhibited improved sunlight absorption and higher and well-balanced carrier mobility accompanied by enhanced carrier extraction. With the nonhalogenated cyclopentyl methyl ether as the processing solvent, the ternary all-PSCs showed outstanding power conversion efficiency (PCE) higher than 9% when varying the PTB7-Th weight ratio in donors from 20 to 50%. Due to the PTB7-Th content holding a 30% weight ratio in donors, the ternary all-PSCs demonstrated the optimal PCE of 9.60%, which perform better than those of binary all-PSCs (PCE = 7.58 or 5.63%).

Background: Alzheimer’s disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for &gt;2000 years and is now gaining attention as a potential treatment for AD and VaD. Methods: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. Results: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Aβ generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit γ-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Aβ deposition, and promote neural stem cell differentiation, thereby improving cognitive function. Conclusion: The “One-Molecule, One-Target” paradigm has suffered heavy setbacks, but a “multitarget- directed ligands” strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.

Naphthalenothiophene imide (NTI), bearing six-membered imide and a five-membered aromatic ring, was synthesized by a one-step Suzuki reaction in high yield. NTI is an electron-deficient monomer that could effectively lower the HOMO energy level of the polymer. Thus, the NTI-based polymer PNTB1 has a low-lying HOMO energy level (−5.42 eV) without introducing any F or Cl group into the polymer backbone. By mixing with a nonfullerene electron acceptor Y6, solar cell devices exhibit power conversion efficiency as high as 15.18%. Because of the high efficiency of the NTI-based polymer and avoidance of multi-step synthesis of introducing other electron-accepting groups into the polymer chain, the electron-deficient NTI is a promising building unit for high-performance polymer donors.

Biochemical recurrence (BCR) occurs in up to 27% of patients after radical prostatectomy (RP) and often compromises oncologic survival. To determine whether imaging signatures on clinical prostate magnetic resonance imaging (MRI) could noninvasively characterize biochemical recurrence and optimize treatment. We retrospectively enrolled 485 patients underwent RP from 2010 to 2017 in three institutions. Quantitative and interpretable features were extracted from T2 delineated tumors. Deep learning-based survival analysis was then applied to develop the deep-radiomic signature (DRS-BCR). The model’s performance was further evaluated, in comparison with conventional clinical models. The model achieved C-index of 0.802 in both primary and validating cohorts, outweighed the CAPRA-S score (0.677), NCCN model (0.586) and Gleason grade group systems (0.583). With application analysis, DRS-BCR model can significantly reduce false-positive predictions, so that nearly one-third of patients could benefit from the model by avoiding overtreatments. The deep learning-based survival analysis assisted quantitative image features from MRI performed well in prediction for BCR and has significant potential in optimizing systemic neoadjuvant or adjuvant therapies for prostate cancer patients.

Different local morphologies of poly(3-hexylthiophene) (P3HT, Mw = 87 000 and 30 000–40 000 g mol − 1) are grown on a patterned substrate, which is composed of octadecyltrichlorosilane (OTS area) stripes on a silicon wafer (SiOx area), via dip coating from the aged solutions. Bundles of P3HT (Mw = 87 000 g mol − 1) nanorods on the SiOx area and long nanofibrillar crystals on the OTS area are generated simultaneously from the one-day-aged 1 mg ml − 1 solution, while oriented P3HT (Mw = 30 000–40 000 g mol − 1) nanofibrillar crystals parallel to the long axis of the OTS pattern form on the OTS area from the seven-days-aged solution (1 mg ml − 1). Different dimensional sizes of the P3HT aggregate in the toluene solution upon aging and the flow of the solution from SiOx to the OTS area, on which the receding contact angle is larger than that on the SiOx area, determines the local structures of the P3HT film on the patterned substrate.

In this work, solvent chloronaphthalene (CN) and polymer acceptor an alternating copolymer of perylene diimide and carbazole (PCPDI) were utilized as co-additives to optimize the nanoscale phase-separated morphology and photovoltaic properties of bulk-heterojunction (BHJ) polymer solar cells based on the poly(3-hexyl thiophene) (P3HT)/N,N'-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI) system. The domain size of EP-PDI molecules together with that of P3HT distinctly decreased by adding a 0.75 vol% CN additive. The optimized lateral phase separation increased the donor-acceptor interfacial area and facilitated the exciton dissociation process, leading to 5-fold enhancement of short-circuit current (JSC). Furthermore, when PCPDI was employed as a co-additive, acceptor materials (including PCPDI and EP-PDI) were prone to aggregation towards the top surface of blend films, improving vertical phase separation of active layers. PCPDI incorporation, which improved the percolation pathways for electron carriers, suppressed the crystallinity of P3HT distinctly. Thus, much more balanced charge transport was achieved by PCPDI addition, which resulted in almost 1-fold enhancement of open-circuit voltage (VOC) by reducing nongeminate recombination. As a consequence, cooperative effects of CN and PCPDI additives improved the nanoscale phase-separated morphology in lateral and vertical directions simultaneously, achieving the enhancement in both VOC and JSC.

Control over both molecular order and long-range alignment order in films of the donor–acceptor copolymer of 3,6-bis(thiophen-2-yl)-N,N′-bis(2-octyl-1-dodecyl)-1,4-dioxo-pyrrolo[3,4-c]pyrrole and thieno[3,2-b]thiophene (PDBT-TT) was demonstrated via off-center spin-coating (OCSC) from its blend solution with polystyrene (PS). It was found that the dichroic ratio (DR) of OCSC blend films was dependent on both the physical process of spin-coating and the effect of PS chains. The highest DR of 2.75 was obtained via OCSC from the blend solution in oDCB at 1500 rpm. Meanwhile, both the intrachain and interchain molecular order were improved in blend films compared with neat ones, which were indicated by the red-shift of the max absorption, enhanced J-aggregation absorption, and smaller π–π stacking distance (from 3.77 to 3.70 Å). According to the results of the investigation into the macro anisotropy, micro morphology, solution rheology properties, and photophysics features of films, an overall mechanism of simultaneous control over molecular and long-range order of D–A copolymer films was proposed. On the one hand, a larger viscosity and the pseudoplastic nature of the solution tuned by choosing good solvents with high boiling points and adding PS resulted in a better chain disentanglement, better shear transfer, and a slower contact line receding velocity to induce an enhanced alignment of chains and thus fibrillar aggregates. Also, the critical contact line receding velocity for alignment dominated by the solvent evaporation rate accounted for the variation of DR with OCSC rates. A vertical phase separation accompanying the formation of aligned fibrils during OCSC was also confirmed due to the friction shear between air and solution surface. On the other hand, the negligible dependence of the blend OCSC film’s photophysical and morphological features on the solvent suggested the critical role of PS in determining the better intrachain conjugation in blend films, which was attributed to multiple reasons, like limited phase separation room, a coil-toward conformation promotion, and a high surface energy. Furthermore, the enhanced π-attraction and smaller steric hindrance induced by improved intrachain conjugation accounted for the smaller π–π stacking distance in the blend films than that in the neat ones.

Herein, balanced intermixed and pure crystalline phases in N,N′-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI)-based non-fullerene organic solar cells (OSCs) were achieved via selective solvent additives (SAs). Poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b′]dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] (PTB7) and 7,7′-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b′]dithiophene-2,6-diyl)bis(6-fluoro-4-(5′-hexyl-[2,2′-bithiophen]-5-yl)benzo[c][1,2,5]thiadiazole) (F-DTS) possessing different compatibilities with EP-PDI were selected as model systems to investigate the guideline of SAs selection for different non-fullerene-based systems. According to the solubility parameter difference (Δδ) between EP-PDI and SAs, five different SAs were divided into two types: (I) strong intermolecular interactions with EP-PDI molecules (with Δδ values less than 5 MPa1/2), (II) weak intermolecular interactions with EP-PDI molecules (with large Δδ values). For PTB7:EP-PDI system with large and obvious phase separation, the introduction of type (II) SAs provided extra interactions with EP-PDI molecules, thus effectively reducing EP-PDI aggregate domains and increasing intermixed fractions. The incorporation of type (II) SAs resulted in a greater yield of dissociated polarons, and the final device efficiency increased from 0.02% to 1.65%. On the contrary, for finely mixed F-DTS:EP-PDI systems, type (I) SAs were considerably more effective because of the fact that the required pure crystalline phases were readily induced by the unfavorable interactions. The charge transport pathways optimized by type (I) SAs improved device efficiency from 0.18% to 2.82%. Hence, by processing selective SAs, the fraction of intermixed and pure crystalline phases for PDI-based non-fullerene OSCs can be well regulated; therefore, the final performance for both systems can be significantly improved.

The orientation transition and self-epitaxial crystallization of all-conjugated diblock copolymers poly(p-phenylene)-block-(3-hexylthiophene) (PPP-b-P3HT) were systematically investigated by in situ temperature-resolved two-dimensional grazing incidence X-ray diffraction (2D GIXD) in step-by-step heating and cooling process. B39T18 was selected; the results of 2D GIXD showed that the PPP block crystal adopted a face-on orientation while the crystallization of P3HT block was hindered in as-casted films. Three different molecular orientations transition were obtained in self-epitaxial crystallization circles. First, P3HT crystallize with edge-on during the heating process and induced the PPP blocks crystallized with edge-on during the cooling process. Then, the as-casted film was heated in the melting temperature region of PPP blocks and isothermally crystallized. The partial melting of PPP blocks promoted the P3HT blocks crystallize in a face-on due to the steric limitation effect; PPP blocks crystallized ...

An organic donor–acceptor cocrystal with an ambipolar transporting property based on EP-PDI and H6TP was fabricated.

In this letter, we derive the distribution characteristics of first-order multipath ghosts in a nested multiple-input-multiple-output (MIMO) through-wall radar and evaluate the efficacy of the phase coherence factor (PCF) in ghost suppression. Different from a synthetic aperture radar, the first-order multipath echoes of a nested MIMO through-wall radar generate several ghosts. For example, for a nested MIMO array composed of a compact receiving subarray and M spatially dispersed transmitters, there are M ghosts at the same side of the wall as the array. The mth ghost is supposed to occur near the intersection of the line, connecting the target and the center of the receiving subarray, and the ellipse whose foci are the positions of the target and the mth transmitter. Under the assumption of phase uniform distribution clutter, the PCF can suppress the ghosts up to -20 lg(1 - √(M <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> - 1)/M <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ) dB, which is about 17.46 dB when M = 2.

Toll-like receptor-4 (TLR4) signaling has been implicated in innate immunity and acute inflammation following acute lung injury (ALI). As such, modulating inflammatory response through TLR4 represents an attractive therapeutic approach to treat ALI. Increasing evidence demonstrates that hyaluronan (HA) can modulate TLR4 activation and has shown early promise as a therapeutic agent in ALI. However, the mechanism associated with HA has not been fully elucidated. In the current study, we sought to determine the effects of HA on lipopolysaccharide (LPS)-induced inflammatory response and gain insights into the mechanism of action in mice with intratracheal instillation of LPS. Our results demonstrate that in contrast to mice challenged with LPS, pretreatment with HA significantly inhibited inflammatory cell recruitment, attenuated lung injury and suppressed the level of cytokine/chemokine in bronchial alveolar lavage fluid (BALF). Investigation of the mechanism responsible for inhibition of LPS activation showed HA treatment significantly inhibited the nuclear translocation of NF-κB p65 and protein expression of myeloid differentiation primary response protein (MyD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF) and p38 MAPK, JNK and ERK activation in lung tissue. Furthermore, we compared the protection effect of HA in TLR4-deficient mice with those of genetically matched wild type (WT) mice in an acute model of lung injury. However, in TLR4-deficient mice, HA pretreatment before LPS instillation fail to affect the LPS response. Therefore, our findings suggest that HA pretreatment attenuated LPS-induced ALI and the anti-inflammatory function of HA was partial dependent on TLR4, which shed new light on potential elements that regulate the lung injury response.

Control over polymeric bulk heterojunction (BHJ) morphology is one of the key factors in obtaining high-efficiency devices. The domain size influence on device performance is widely considered critical. In this paper, the fibril width of 3,6-bis-(thiophen-2-yl)-N,N′-bis(2-octyl-1-dodecyl)-1,4-dioxo-pyrrolo[3,4-c]pyrrole and thieno[3,2-b]thiophene (PDBT-TT):[6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) blend thin film was adjusted by different processing additives. By decreasing the solubility of PDBT-TT in different additives, the fibril width can be decreased from 65.7 nm to 14.8 nm. It is possible that the PDBT-TT seed-crystallite nuclei concentration is higher in the relatively low solubility solvents than that in the relatively high solubility solvents, thus leading to the formation of narrower fibrils. The PDBT-TT/PC71BM narrow fibrillar interpenetrating network structure was beneficial to exciton separation and charge transport processes. As a result, the solar cell with the narrowest fibril width has a higher short circuit current (Jsc) and fill factor (FF), thus achieving optimized device performance from less than 1% to 4.75%.

Journal of Polymer Science Part B: Polymer PhysicsVolume 54, Issue 18 p. 1811-1819 Full Paper Optimized domain size and enlarged D/A interface by tuning intermolecular interaction in all-polymer ternary solar cells Rui Zhang, Rui Zhang State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 China University of the Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 ChinaSearch for more papers by this authorHua Yang, Hua Yang Dongguan Institute of Neutron Science, No.1 Zhongziyuan Road, Dalang, Dongguan, 523803 ChinaSearch for more papers by this authorKe Zhou, Ke Zhou State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 China University of the Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 ChinaSearch for more papers by this authorJidong Zhang, Jidong Zhang State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaSearch for more papers by this authorJiangang Liu, Jiangang Liu State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaSearch for more papers by this authorXinhong Yu, Xinhong Yu State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaSearch for more papers by this authorRubo Xing, Rubo Xing State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaSearch for more papers by this authorYanchun Han, Corresponding Author Yanchun Han State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaCorrespondence to: Y. Han (E-mail: ychan@ciac.ac.cn)Search for more papers by this author Rui Zhang, Rui Zhang State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 China University of the Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 ChinaSearch for more papers by this authorHua Yang, Hua Yang Dongguan Institute of Neutron Science, No.1 Zhongziyuan Road, Dalang, Dongguan, 523803 ChinaSearch for more papers by this authorKe Zhou, Ke Zhou State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 China University of the Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 ChinaSearch for more papers by this authorJidong Zhang, Jidong Zhang State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaSearch for more papers by this authorJiangang Liu, Jiangang Liu State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaSearch for more papers by this authorXinhong Yu, Xinhong Yu State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaSearch for more papers by this authorRubo Xing, Rubo Xing State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaSearch for more papers by this authorYanchun Han, Corresponding Author Yanchun Han State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022 ChinaCorrespondence to: Y. Han (E-mail: ychan@ciac.ac.cn)Search for more papers by this author First published: 12 May 2016 https://doi.org/10.1002/polb.24083Citations: 25Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat ABSTRACT The selection of sensitizer and its existence in the blend films are important to the performance of all-polymer ternary solar cells. Herein, all-polymer ternary solar cell devices, which used poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b′] dithiophene-alt-3-fluorothieno[3,4-b]thiophene-2-carboxy-late] (PTB7-Th) as donor, poly[[N,N-bis(2-octyldodecyl)-napthalene-1,4,5,8-bis(dicarboximide)−2,6-diyl]-alt-5, 5′-(2,2′-bithiophene)] (N2200) as acceptor and poly[N−900-hepta-decanyl-2,7-carbazole-alt-5,5-(40,70-di-2-thienyl-20,10,30-benzothiadiazole) (PCDTBT) as sensitizer, are successfully demonstrated. The intermolecular interaction between donor PTB7-Th and sensitizer PCDTBT may lead to aggregation of PTB7-Th which decreases domain sizes and enlarges D/A effective interface area. In addition, the PCDTBT molecules also extend light absorption and cascaded energy levels of the ternary blend system. As a result, with 15% PCDTBT we get a power conversion efficiency of 5.11%, almost 20% higher than control device due to more favored exciton dissociation and higher charge transport efficiency. This study reveals a promising way to achieve high efficiency all-polymer solar cells using a low-band gap polymer PCDTBT. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 1811–1819 Citing Literature Volume54, Issue1815 September 2016Pages 1811-1819 RelatedInformation

Abstract Metastasis is the primary cause of cancer mortality. The primary tumors of colorectal cancer (CRC) often metastasize to the liver. In this study, we have collected 122 samples from 45 CRC patients. Among them, 32 patients have primary tumors, adjacent normal tissues, and matched liver metastases. Thirteen patients have primary tumors without distant metastasis and matched normal tissues. Characterization of these samples was conducted by whole-exome and RNA sequencing and SNP6.0 analysis. Our results revealed no significant difference in genetic alterations including common oncogenic mutations, whole genome mutations and copy number variations between primary and metastatic tumors. We then assembled gene co-expression networks and identified metastasis-correlated gene networks of immune-suppression, epithelial–mesenchymal transition (EMT) and angiogenesis as the key events and potentially synergistic drivers associated with CRC metastasis. Further independent cohort validation using published datasets has verified that these specific gene networks are up regulated throughout the tumor progression. The gene networks of EMT, angiogenesis, immune-suppression and T cell exhaustion are closely correlated with the poor patient outcome and intrinsic anti-PD-1 resistance. These results offer insights of combinational strategy for the treatment of metastatic CRC.

Abstract: Ginsenoside Re, an herbal ingredient from ginseng, has been demonstrated to protect the heart from various cardiovascular diseases. In this study, we investigated the protective effects and mechanisms of ginsenoside Re (Gin-Re) on cardiac function and left ventricular remodeling in a rat model of myocardial infarction (MI). After ligating the left anterior descending coronary artery, Wistar rats were treated with Gin-Re (135 mg/kg) by gavage everyday for 4 weeks. Serological detection showed that Gin-Re significantly inhibited myocardial injury and attenuated oxidative stress in MI rats. Echocardiographic observation showed that Gin-Re significantly improved cardiac function and prevented left ventricular dilatation induced by MI. Pathological observation found that Gin-Re significantly decreased interstitial fibrosis in the left ventricle of MI rats. Compared with the MI group, Gin-Re treatment promoted AMPKα phosphorylation, decreased TGF-β1 expression, and attenuated Smad2/3 activation. After Gin-Re treatment, the phosphorylation of FAK, PI3K p110α, and Akt was enhanced in MI rats, while PI3K p110β showed no difference compared with the MI group. These results indicate that Gin-Re may improve MI-induced cardiac dysfunction and mitigate ventricular remodeling through regulation of the AMPK/TGF-β1/Smad2/3 and FAK/PI3K p110α/Akt signaling pathways.

ShenmaYizhi decoction (SMYZD) is an effective prescription of traditional Chinese medicine used to treat vascular dementia (VD). Modern research methods have identified its active ingredients clearly as gastrodin, ferulic acid, ginsenosides, and β-sitosterol. Chronic cerebral hypoperfusion is a driving factor or risk factor for VD, which leads to the disturbance of mitochondrial structure and function.To observe whether SMYZD improves cognitive impairment by improving mitochondrial structure and function.Forty adult rats with vascular cognitive impairment (VCI) caused by the bilateral ligation of common carotid arteries were divided into four groups randomly, including the model group, donepezil group, and low-dose and high-dose SMYZD groups, with 10 rats in each group. Additionally, a sham group was established with 10 rats as the control group. The treatment groups were administered donepezil and two different dosages of SMYZD. The donepezil group was administered 0.45 mg/kg/d donepezil, and the SMYZ-L group was administered 2.97 g/kg/d SMYZ, which were equivalent to the clinical dosage. The SMYZ-H group was administered 11.88 g/kg/d SMYZ, which is 4 times higher than the clinically equivalent dosage. A sham-operated group was used as the control group and administered an equal volume of distilled water. The rats were treated by gavage for 8 consecutive weeks. Morris water maze (MWM) test was performed to evaluate the learning and memory ability. The mitochondria of brain tissue were extracted from brain for further test. Mitochondrial morphology and the signal path of AMPK/PPARα/PGC-1α/UCP2 in mitochondria were detected.With the SMYZD intervention, behavioral performance of rats and pathological changes of mitochondria of brain tissue were significantly improved. In the serum, SOD, GSH-Px, and GSH activities were increased, and the MDA content was decreased. Moreover, the AMPK, PPARα, PGC-1α, UCP2, and ATP5A mRNA and protein expression levels were also reversed by SMYZD.SMYZD may provide a potential therapeutic strategy via activating the AMPK/PPARα/PGC-1α/UCP2 signal pathway to improve mitochondrial structure and energy metabolism thereby alleviate vascular cognitive impairment.

Background Conventional parameters show limited and unreliable correlations with medulloblastoma prognosis. Aim To evaluate the factors influencing overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) in patients with medulloblastoma. Methods PubMed, EMBASE, the Cochrane Library, and Web of Science were searched for studies published up to May 2021. The associations between various clinical and treatment factors and survival parameters were assessed. Results Twenty-nine studies (8455 patients) were included. Desmoplastic medulloblastoma (HR=0.41, 95%CI: 0.31-0.56), M0 disease (HR=2.07, 95%CI: 1.48-2.89), WNT, SSH, group 4 (all P&amp;lt;0.05 vs. group 3), GTR vs. STR (HR=1.37, 95%CI: 1.04-1.08), radiotherapy (HR=0.45, 95%CI: 0.20-0.80), craniospinal irradiation (HR=0.49, 95%CI: 0.38-0.64), and high 5hmC levels (HR=2.90, 95%CI: 1.85-4.55) were associated with a better OS. WNT, SSH, group 4 (all P&amp;lt;0.05 vs. group 3), residual tumor ≤1.5 cm 2 (HR=2.08, 95%CI: 1.18-3.68), GTR vs. STR (HR=1.31, 95%CI: 1.03-1.68), craniospinal irradiation (HR=0.46, 95%CI: 0.37-0.57), high 5hmC levels (HR=3.10, 95%CI: 2.01-4.76), and &amp;lt;49 days between resection and radiotherapy (HR=2.54, 95%CI: 1.48-4.37) were associated with better PFS. Classic vs. desmoplastic medulloblastoma (HR=1.81, 95%CI: 1.04-3.16), SSH, WNT (both P&amp;lt;0.05 vs, non-SSH/non-WNT), GTR vs. STR (HR=2.01, 95%CI: 1.42-2.85), and radiotherapy (HR=0.31, 95%CI: 0.15-0.64) were associated with a better EFS. Conclusion Histology, molecular subgroup, GTR, and radiotherapy are significantly associated with survival parameters in patients with medulloblastoma. Nevertheless, high-quality prospective cohort studies are necessary to improve the conclusions.

Background Heart failure with preserved ejection fraction (HFpEF) is an increasing public health concern. Currently, data regarding the clinical application value of plasma Galectin-3 (Gal-3) in HFpEF are contradictory. Therefore, we performed the following meta-analysis to appraise the clinical implications of serum Gal-3 in HFpEF, including its capacity to predict new-onset disease, long-term unfavorable endpoints, and the degree of cardiac structural abnormality and left ventricular diastolic dysfunction (LVDD). Methods PubMed, Embase, Scopus, and Web of Science were retrieved exhaustively from their inception until November 30, 2021, to obtain studies assessing the correlation between plasma Gal-3 and the clinical features of HFpEF (new-onset HFpEF, adverse outcomes, and echocardiographic parameters related to abnormal cardiac structure and LVDD). Results A total of 24 papers containing 27 studies were ultimately included in the present research. The results of the meta-analysis revealed that high plasma Gal-3 levels are strongly associated with the following clinical characteristics of HFpEF: (i) the increased risk of new-onset HFpEF (HR: 1.11; 95% CI: 1.04-1.19; p = 0.910, I 2 = 0%; P = 0.002); (ii) the high risk of adverse outcomes of HFpEF patients [all-cause death (HR: 1.55; 95% CI: 1.27-1.87; p = 0.138, I 2 = 42%; P = 0.000) and the composite events [all-cause death and HF hospitalization (HR: 1.50; 95% CI: 1.30-1.74; p = 0.001, I 2 = 61%; P = 0.000) or cardiovascular (CV) death and HF hospitalization (HR: 1.71; 95% CI: 1.51-1.94; p = 0.036, I 2 = 58%; P = 0.000)]; (iii) echocardiographic indices [E/e ratio (r: 0.425, 95% CI: 0.184-0.617; p = 0.000, I 2 = 93%; P = 0.001) and DT (r: 0.502, 95% CI: 0.061-0.779; p = 0.001 I 2 = 91%; P = 0.027)]. Conclusions Plasma Gal-3 might be employed as an additional predictor for new-onset HFpEF, the adverse prognosis in HFpEF patients (all-cause death, the composite endpoints of all-cause death and HF hospitalization or CV death and HF hospitalization), and the severity of LVDD in HFpEF populations.

Support technology faces challenges in view of the large deformation of surrounding rock in three-soft coal roadways under high horizontal stress in Zijin Coal Mine, China. Geostress near the tested working face of the mine was measured and its distribution law was analyzed through theoretical analysis, numerical simulation analysis, and field measurement. The original supporting scheme of the three-soft coal roadway on the tested working face was analyzed to discover the deformation and failure mechanism of the surrounding rock of the original supporting roadway and the control measures. An optimized support scheme of H-G (hollow grouting) anchor cables, high strength bolts, W-shaped steel belts, metal meshes, and sprayed concretes was proposed for field applications. Based on the roadway in the tested 3201 working face at Zijin Coal Mine, the technical parameters for optimizing the combined support of the roadway were determined. The following results were be obtained through field measurement. The roadway was kept intact after excavation and the optimized support scheme was adopted in the three-soft coal roadway. No obvious deformation in appearance existed in the roof, floor, and roadway coal sides. Compared with the original support scheme, the stability of the roadways was improved visibly. The displacement of the roadway roof decreased from 100 to 30 mm, and that of the roadway coal walls decreased from more than 100 mm to less than 50 mm. This work verifies the effectiveness of a combined support scheme of H-G anchor cables, high strength bolts, W-shaped steel belts, metal meshes, and sprayed concretes to control deformations of surrounding rock in three-soft coal roadways. The new support scheme has good social and economic benefits and can be used as a reference for other roadway supports under similar conditions.

The objective of this study was to explore the application of radiomics combined with machine learning to establish different models to assist in the diagnosis of venous wall invasion in patients with renal cell carcinoma and venous tumor thrombus and to evaluate the diagnostic efficacy.We retrospectively reviewed the data of 169 patients in Peking University Third Hospital from March 2015 to January 21, who was diagnosed as renal mass with venous invasion. According to the intraoperative findings, 111 patients were classified to the venous wall invasion group and 58 cases in the non-invasion group. ITK-snap was used for tumor segmentation and PyRadiomics 3.0.1 package was used for feature extraction. A total of 1598 features could be extracted from each CT image. The patients were divided into training set and testing set by time. The elastic-net regression with 4-fold cross-validation was used as a dimension-reduction method. After feature selection, a support vector machines (SVM) model, a logistic regression (LR) model, and an extra trees (ET) model were established. Then the sensitivity, specificity, accuracy, and the area under the curve (AUC) were calculated to evaluate the diagnostic performance of each model on the testing set.Patients before September 2019 were divided into the training set, of which 88 patients were in the invasion group and 42 patients were in the non-invasion group. The others were in the testing set, of which 32 patients were in the invasion group and 16 patients were in the non-invasion group. A total of 34 radiomics features were obtained by the elastic-net regression. The SVM model had an AUC value of 0.641 (95% CI, 0.463-0.769), a sensitivity of 1.000, and a specificity of 0.062. The LR model had an AUC value of 0.769 (95% CI, 0.620-0.877), a sensitivity of 0.913, and a specificity of 0.312. The ET model had an AUC value of 0.853 (95% CI, 0.734-0.948), a sensitivity of 0.783, and a specificity of 0.812. Among the 3 models, the ET model had the best diagnostic effect, with a good balance of sensitivity and specificity. And the higher the tumor thrombus grade, the better the diagnostic efficacy of the ET model. In inferior vena cava tumor thrombus, the sensitivity, specificity, accuracy, and AUC of ET model can be improved to 0.889, 0.800, 0.857, 0.878 (95% CI, 0.745-1.000).Machine learning combined with radiomics method can effectively identify whether venous wall was invaded by tumor thrombus and has high diagnostic efficacy with an AUC of 0.853 (95% CI, 0.734-0.948).

OBJECTIVE To study the cytotoxicity of titanium dioxide nanoparticles (nano-TiO2)in neuroglia cells. METHODS ① In vitro, rat astrocytes were exposed to nano-TiO2 of 3 different diameters (10, 20 and 200 nm) at 5 different concentrations (6.25, 12.5, 25, 50 and 100 mg·L-1). Sulforhodamine B staining assay was carried out to evaluate the survival rate of nano-TiO2-treated cells for 72 h. ② In vivo, nano-TiO2 of these 3 different diameters at 0.1, 1.0 and 10.0 mg·kg-1 were intratracheally instilled into the bronchus of Wistar rats, respectively, 3 rats in each group. Seventy-two hours later, the content of nano-TiO2 and levels of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and IL-10 in brain tissue were measured with ICP-MS and radioimmunoassays. In addition, cellular morphology of rat neuralgia cells was observed by the light microscope and transmission electron microscope. RESULTS ① In vitro, the inhibiting effect of nano-TiO2 on the cell survival rate was significantly enhanced in a concentration-dependent manner and IC50of nano-TiO2 of the 3 diameters was 55.9, 66.0 and 3827.0 mg·L-1 at 72 h. There were also obvious changes in cellular configuration, such as sparse arrangement, increscent cell space, increased intracellular particles and decreasing cellular transparency. ② In vivo, when the rats were exposed to nano-TiO2 of 10 and 20 nm in diameter in 0.1 mg·kg-1or nano-TiO2 of 200 nm in diameter in 3 dosages, the contents of nano-TiO2, IL-1β,TNF-α and IL-10 in rat brain tissue did not show significant difference in the control and nano-TiO2-treated groups; when the rats were exposed to nano-TiO2 of 10 and 20 nm in diameter in 1.0 and 10.0 mg·kg-1, the contents of nano-TiO2 and the 3 cytokines in brain tissue increased compared with control group, especially nano-TiO2 in 10.0 mg·kg-1 group. Pathological observation indicated that the blood-brain-barrier was destroyed by nano-TiO2, which resulted in brain tissue necrosis and the entrance of nano-TiO2 into neuroglia cells to induce inflammation and cellular edema. CONCLUSION Nano-TiO2 is toxic to rat neuroglia cells. This toxicity may relate to the particle size and the mechanism may be associated with its induction of inflammation.

Executive function (EF) plays vital roles in our everyday adaptation to the ever-changing environment. However, limited existing studies have linked EF to the resting-state brain activity. The functional connectivity in the resting state between the sub-regions of the brain can reveal the intrinsic neural mechanisms involved in cognitive processing of EF without disturbance from external stimuli. The present study investigated the relations between the behavioral executive function (EF) scores and the resting-state functional network topological properties in the Prefrontal Cortex (PFC). We constructed complex brain functional networks in the PFC from 90 healthy young adults using functional near infrared spectroscopy (fNIRS). We calculated the correlations between the typical network topological properties (regional topological properties and global topological properties) and the scores of both the Total EF and components of EF measured by computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB). We found that the Total EF scores were positively correlated with regional properties in the right dorsal superior frontal gyrus (SFG), whereas the opposite pattern was found in the right triangular inferior frontal gyrus (IFG). Different EF components were related to different regional properties in various PFC areas, such as planning in the right middle frontal gyrus (MFG), working memory mainly in the right MFG and triangular IFG, short-term memory in the left dorsal SFG, and task switch in the right MFG. In contrast, there were no significant findings for global topological properties. Our findings suggested that the PFC plays an important role in individuals' behavioral performance in the executive function tasks. Further, the resting-state functional network can reveal the intrinsic neural mechanisms involved in behavioral EF abilities.

The present study examined how different brain regions interact with each other during spontaneous honest vs. dishonest communication. More specifically, we took a complex network approach based on the graph-theory to analyze neural response data when children are spontaneously engaged in honest or dishonest acts. Fifty-nine right-handed children between 7 and 12 years of age participated in the study. They lied or told the truth out of their own volition. We found that lying decreased both the global and local efficiencies of children's functional neural network. This finding, for the first time, suggests that lying disrupts the efficiency of children's cortical network functioning. Further, it suggests that the graph theory based network analysis is a viable approach to study the neural development of deception.

ABSTRACT The close π–π stacking and the high J‐aggregation during the formation of fibrillar morphology in films of the poly[[2,5‐ bis (2‐octyldodecyl)−2,3,5,6‐tetrahydro‐3,6‐dioxopyrrolo[3,4‐c]pyrrole‐1,4‐diyl]‐alt–[[2,2′‐(2,5‐thiophene) bis ‐thieno[3,2‐b]thiophen]‐5,5′‐diyl]] (PDPPTT‐T) are demonstrated via blending with polystyrene (PS). The hydrodynamic radius ( R h ) of PDPPTT‐T is decreased from 16.7 nm in the neat solution to 12.7 nm in the blend solution at the ratio of 1/20(PDPPTT‐T/PS). This phenomenon suggests that blending PS is beneficial for the disentanglement of PDPPTT‐T. The disentanglement of PDPPTT‐T facilitates the formation of fibrillar morphology. The growth of the fibrils occurs along the molecular backbones and the width of the fibrils is parallel to the π–π stacking direction. The disentanglement of PDPPTT‐T helps the molecules adjust conformation to improve J‐aggregation and decrease the π–π stacking distance. The maximum absorption is red‐shifted from 825 nm to 849 nm and the relative intensity of J‐aggregation (the 0‐0/0‐1 ratio) is increased from 1.19 to 1.60. The π–π stacking distance decreases from 3.57 to 3.52 Å. The charge‐carrier mobility will be improved in the fibrillar morphology with close π–π stacking and high J‐aggregation. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54 , 838–847

Human cardiovascular activities are important indicators of a variety of physiological and psychological activities in human neuroscience research. The present proof-of-concept study aimed to reveal the spatiotemporal patterns of cardiovascular activities from the dynamic changes in hemoglobin concentrations in the face. We first recorded the dynamics of facial transdermal blood flow using a digital video camera and the Electrocardiography (ECG) signals using an ECG system simultaneously. Then we decomposed the video imaging data extracted from different sub-regions of a face into independent components using group independent component analysis (group ICA). Finally, the ICA components that included cardiovascular activities were identified by correlating their magnitude spectrum to those obtained from the ECG. We found that cardiovascular activities were associated with five independent components reflecting different spatiotemporal dynamics of facial blood flow changes. The strongest strengths of these ICA components were observed in the bilateral forehead, the left chin, and the left cheek, respectively. Our findings suggest that the cardiovascular activities presented different dynamic properties within different facial sub-regions, respectively. More broadly, the present findings point to the potential of the transdermal optical imaging technology as a new neuroscience methodology to study human physiology and psychology, noninvasively and remotely in a contactless manner.

A sparse and uniform multiple-input-multiple-output array is generally utilized in through-wall radar to implement real-time imaging of moving targets. However, the array sparsity with the interelement spacing much bigger than half a wavelength gives rise to grating lobe interference smearing the images. In order to enhance the signal-to-interference ratio, this letter introduces the sign coherence factor (SCF) to weigh through-wall images to suppress the grating lobes. The SCF is first proposed in medical ultrasound imaging and directly reflects the coherence of sign bits of all the transmit-receive channels in each pixel. Since the SCF calculated only by the sign bits, it has the smallest amount of computations compared with two other weighing factors, namely, the coherence factor (CF) and the phase coherence factor (PCF), which have been applied to through-wall imaging already. Moreover, the SCF has comparable performance in suppressing grating lobes with the PCF, much better than the CF. These two advantages make the SCF the most suitable for real-time imaging of moving targets. The experimental results with a two-transmitting eight-receiving stepped-frequency continuous-wave through-wall radar verifies the excellent performance of the SCF.

Myocardial fibrosis is implicated as a leading risk factor for heart failure, arrhythmia, and sudden death after cardiac injury, as the excessive interstitial extracellular matrix impedes heart contraction and electrical conduction. Complicated mechanisms involving oxidative stress, pro-inflammatory cytokines, chemokine families, NLRP3 inflammasomes, growth factors, and non-coding RNAs participate in cardiac fibrogenesis and make it difficult to designate specific and effective therapies. Oriental herbs have been popular for thousands of years in the health care of Asian residents, due to their multi-targeted, multi-faceted approaches and their multi-functional effects in fighting difficult and complicated diseases, including cardiovascular disorders such as myocardial fibrosis. Curcumin, a natural polyphenol and yellow pigment obtained from the spice turmeric, was found to have strong anti-oxidant and anti-inflammatory properties. Increasing evidence has shown that curcumin can be used to prevent and treat myocardial fibrosis, when the myocardium suffers pathological pro-fibrotic changes in vivo and in vitro. The present review focuses on recent studies elucidating the mechanisms of curcumin in treating different pathologic conditions, including ischemia, hypoxia/reoxygenation, pressure or volume overload, and hyperglycemia or high-fat-induced cardiac fibrosis. Novel analogs such as C66, B2BrBC, Y20, and J17 have been designed to maximize the therapeutic potentials of curcumin. These optimized curcumin analogs with improved bioavailability and pharmacokinetic profiles need to be clinically verified before curcumin could be recommended for the treatment of myocardial fibrosis.

Abstract Macleaya cordata (Willd) R. Br. is a medicinal plant. The most important bioactive compounds of M. cordata are alkaloids that have many biological activities including antifungal, anti‐inflammatory, and antitumor. In this study, an ionic‐liquid‐modified high‐speed counter‐current chromatography method was established to obtain alkaloids from the fruits of M. cordata . The conditions of ionic‐liquid‐modified high‐speed counter‐current chromatography, including solvent systems, the content of ionic liquid (1‐butyl‐3‐methylimidazolium tetrafluoroborate [C 4 mim][BF 4 ]), and the posttreatment of the ionic liquid, were investigated. Five alkaloids protopine, allocryptopine, sanguinarine, 8‐O‐demethylchelerythrine, and chelerythrine were separated from the extract of the fruits using a high speed counter‐current chromatography with two‐phase solvent system composed of dichloromethane/methanol/0.3 mol/L hydrochloric acid aqueous solution/[C 4 mim][BF 4 ] (4:2:2:0.015, v/v). Their purities were 96.33, 95.56, 97.94, 96.22, and 97.90%, respectively. The results indicated that a small amount of ionic liquids as modifier of the two‐phase solvent system could shorten the separation time and improve the separation efficiency of the alkaloids from the fruits. The ionic‐liquid‐modified high‐speed counter‐current chromatography would provide a feasible way for highly effective separation of alkaloids from natural products.

The accurate phenotyping of the external quality attributes of potato tubers is important in potato breeding. Currently, the assessment of potato tuber shape, together with eye density and depth, are based on subjective naked eye visual evaluation. However, such a manual visual assessment makes it very difficult to reliably phenotype these and other important, more complicated, geometrical traits, such as shape uniformity. In this study, a 3D image analysis method has been developed for counting potato eyes and estimating eye depth based on an evaluation of the curvature of an acquired 3D point cloud. Six shape uniformity-related traits, together with their shape indices (SI), were measured for six potato varieties. These were collected from three field experiments designed initially to study the effects of variation in nitrogen (N), potassium (K) and compound fertilisers along with tuber mass, on all investigated external traits. We demonstrate that a 3D image analysis technique can estimate the number of potato eyes and their depth with a high degree of accuracy. In addition, three shape uniformity traits were identified as offering a better power discrimination between varieties. The preliminary experiment found potato tuber mass to significantly affect both the shape uniformity and eye count, while fertiliser treatments showed no effect on all traits except SI. However, further investigation with a larger sample size is required for confirmation.

Parkinson's disease is the second most common neurodegenerative disease. Researchers have shown that oxidative stress and apoptosis play an important role in the Parkinson's disease process. Isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is a natural flavonol compound and one of the main active ingredients of agricultural waste apple pomace. Increasing evidence indicates that this compound possesses anti-oxidation, anti-aging, and anti-inflammation properties. In this study, isoquercitrin was purified from apple pomace by high-speed countercurrent chromatography and its neuroprotective effect on Parkinson's disease was investigated in MPTP-induced acute mouse models. It was found that isoquercitrin ameliorated the animal behaviors against MPTP-induced neurotoxicity, mitigated the loss of dopamine neurons induced by MPTP, increased tyrosine hydroxylase and dopamine transporter expression, reduced the pro-apoptotic signaling molecule bax expression and inhibited MPTP-triggered oxidative stress. Our results demonstrated that isoquercitrin has protective effects on the MPTP subacute model mouse, which might be partially mediated through the actions of anti-oxidation and anti-apoptosis. Isoquercitrin might be a new promising protective drug for the improvement of Parkinson's disease.

The present study aimed to explore the difference in the brain function and structure between patients with major depressive disorder (MDD) and healthy controls (HCs) using two-center and multi-modal MRI data, which would be helpful to investigate the pathogenesis of MDD.The subjects were collected from two hospitals. One including 140 patients with MDD and 138 HCs was used as primary cohort. Another one including 29 patients with MDD and 52 HCs was used as validation cohort. Functional and structural magnetic resonance images (MRI) were acquired to extract four types of features: functional connectivity (FC), amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and gray matter volume (GMV). Then classifiers using different combinations among the four types of selected features were respectively built to discriminate patients from HCs. Different templates were applied and the results under different templates were compared.The classifier built with the combination of FC, ALFF, and GMV under the AAL template discriminated patients from HCs with the best performance (AUC=0.916, ACC=84.8%). The regions selected in all the different templates were mainly located in the default mode network, affective network, prefrontal cortex.First, the sample size of the validation cohort was limited. Second, diffusion tensor imaging data were not collected.The performance of classifier was improved by using multi-modal MRI imaging. Different templates would be suitable for different types of analysis. The regions selected in all the different templates are possibly the core regions to investigate the pathophysiology of MDD.

Glioblastoma stem cells (GSCs) and their interplay with tumor-associated macrophages (TAMs) are responsible for malignant growth and tumor recurrence of glioblastoma multiforme (GBM), but the underlying mechanisms are largely unknown.Cell viability, stemness, migration, and invasion were measured in GSCs after the knockdown of upstream stimulating factor 1 (USF1). Luciferase assay and chromatin immunoprecipitation qPCR were performed to determine the regulation of CD90 by USF1. Immunohistochemistry and immunofluorescent staining were used to examine the expression of USF1 and GSC markers, as well as the crosstalk between GSCs and TAMs. In addition, the interaction between GSCs and TAMs was confirmed using in vivo GBM models.We show that USF1 promotes malignant glioblastoma phenotypes and GSCs-TAMs physical interaction by inducing CD90 expression. USF1 predicts a poor prognosis for glioma patients and is upregulated in patient-derived GSCs and glioblastoma cell lines. USF1 overexpression increases the proliferation, invasion, and neurosphere formation of GSCs and glioblastoma cell lines, while USF1 knockdown exerts an opposite effect. Further mechanistic studies reveal that USF1 promotes GSC stemness by directly regulating CD90 expression. Importantly, CD90 of GSCs functions as an anchor for physical interaction with macrophages. Additionally, the USF1/CD90 signaling axis supports the GSCs and TAMs adhesion and immunosuppressive feature of TAMs, which in turn enhance the stemness of GSCs. Moreover, the overexpression of CD90 restores the stemness property in USF1 knockdown GSCs and its immunosuppressive microenvironment.Our findings indicate that the USF1/CD90 axis might be a potential therapeutic target for the treatment of glioblastoma.

In the field of organic solar cells (OSCs), shoulder side-chain engineering on Y-series non-fullerene acceptors (NFAs) has been the subject of great interest toward realizing high power conversion efficiencies (PCEs). Here, we report a procedure for post-attaching shoulder side chains on Y-series NFAs. Compared with the traditional procedure of pre-attaching side chains, this method has the advantages of using low-cost raw materials and of being more convenient for robustly attaching conjugated side chains. As a proof of concept, this method is successfully extended to the synthesis of oxygen (CY-O) and sulfur (CY-S) substituted alkylphenyl side chains. Interestingly, CY-O exhibits a higher crystallinity and suitable morphology and a better trade-off between charge separation rate and triplet generation processes. As a result, CY-O-based OSCs achieve a high PCE of 17.8% relative to that of CY-S (15.7%). Our results demonstrate that post-side-chain engineering is a convenient and low-cost method to construct high-performance NFAs.

This study is concerned with path planning in a structured greenhouse, in contrast to much of the previous research addressing applications in outdoor fields. The prototype mainly comprises an independently driven Mecanum wheel, a lidar measuring module, a single-chip microcomputer control board, and a laptop computer. Environmental information collection and mapping were completed on the basis of lidar and laptop computer connection. The path planning algorithm used in this paper expanded the 8-search-neighborhood of the traditional A* algorithm to a 48-search-neighborhood, increasing the search direction and improving the efficiency of path planning. The Floyd algorithm was integrated to smooth the planned path and reduced the turning points in the path. In this way, the problems of the traditional A* algorithm could be solved (i.e., slow the path planning speed and high numbers of redundant points). Tests showed that the turning points, planning path time, and distance of the improved algorithm were the lowest. Compared with the traditional 8-search-neighborhood A* algorithm, the turning point was reduced by 50%, the planning time was reduced by 13.53%, and the planning distance was reduced by 13.96%. Therefore, the improved method of the A* algorithm proposed in this paper improves the precision of the planning path and reduces the planning time, providing a theoretical basis for the navigation, inspection, and standardization construction of greenhouses in the future.

Numerous studies have used microarrays to identify gene signatures for predicting cancer patient clinical outcome and responses to chemotherapy. However, the potential impact of gene expression profiling in cancer diagnosis, prognosis and development of personalized treatment may not be fully exploited due to the lack of consensus gene signatures and poor understanding of the underlying molecular mechanisms. We developed a novel approach to derive gene signatures for breast cancer prognosis in the context of known biological pathways. Using unsupervised methods, cancer patients were separated into distinct groups based on gene expression patterns in one of the following pathways: apoptosis, cell cycle, angiogenesis, metastasis, p53, DNA repair, and several receptor-mediated signaling pathways including chemokines, EGF, FGF, HIF, MAP kinase, JAK and NF-κB. The survival probabilities were then compared between the patient groups to determine if differential gene expression in a specific pathway is correlated with differential survival. Our results revealed expression of cell cycle genes is strongly predictive of breast cancer outcomes. We further confirmed this observation by building a cell cycle gene signature model using supervised methods. Validated in multiple independent datasets, the cell cycle gene signature is a more accurate predictor for breast cancer clinical outcome than the previously identified Amsterdam 70-gene signature that has been developed into a FDA approved clinical test MammaPrint®. Taken together, the gene expression signature model we developed from well defined pathways is not only a consistently powerful prognosticator but also mechanistically linked to cancer biology. Our approach provides an alternative to the current methodology of identifying gene expression markers for cancer prognosis and drug responses using the whole genome gene expression data.

The aim of this study was to evaluate the anti-inflammatory profiling of the Chinese herbal formula Sini Tang (SNT) in myocardial infarction (MI) rats. SNT, a decoction consisting of four herbs: Aconitum carmichaelii , Cinnamomum cassia , Zingiber officinale , and Glycyrrhiza uralensis , was characterized as a remedy to treat syndromes corresponding to heart failure and MI in China. Potential biomarkers, which reflect the extent of myocardial necrosis and correlate with cardiac outcomes following MI, such as atrial natriuretic peptide (ANP), high sensitivity C-reactive protein (hs-CRP), and proinflammatory cytokines such as tumor necrosis factor- α , interleukin-6, and interleukin-1 β (TNF- α , IL-6, and IL-1 β ) were determined in plasma, serum, and in myocardial tissue of MI rats after treatment with SNT. Our data indicate that SNT decreased significantly the levels of hs-CRP, TNF- α , IL-6, and IL-1 β in MI rats. SNT decreased the expression of ANP levels in plasma and increased the vascular active marker nitric oxide, which limits vascular inflammation. In addition, SNT could decrease the expression of endothelin-1 levels in rat plasma post-MI. Our data suggest that the Chinese herbal formula SNT has the potential to improve cardiac function after MI. SNT may be a candidate for treating MI and its associated inflammatory responses.

A fibrillar morphology was obtained, compared to the featherless pristine films, via solvent annealing the films of a series of derivatives of poly(3-alkylthiophene)s (P3ATs): poly(3-dodecylthiophene) (P3DDT), poly(3,3'''-didodecyl-quaterthiophene) (PQT12), and poly(2,5-bis(3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene) (pBTTT12). Among the solvents used, including dichloromethane, chloroform, tetrahydrofuran, and carbon disulfide (CS2), CS2 was the best to induce fibril formation because its solubility parameter is closest to those of the P3AT derivatives. It was found that higher critical CS2 vapor pressures were needed to form crystal nuclei with increasing conjugation length and molecular weight of the P3AT derivatives; i.e., the critical vapor pressures for P3DDT 13.9k and PQT12 15.5k were 59.0% and 80.7%, respectively, and there were no nuclei of fibrils for pBTTT12 15.6k with the highest conjugation length, even at a CS2 vapor pressure of 98.3%. Meanwhile, at the highest vapor pressure, the fibril density decreased with increasing conjugation length and molecular weight of the P3AT derivatives. This is attributed to the rod-like conformation prevailing for polymers with larger conjugation length and higher molecular weight during solvent annealing, making the conformational transition toward coils more difficult and hindering diffusion of molecules. The results presented here are expected to be helpful for the design and processing of conjugated semiconductor polymers.

An organic photovoltaic (OPV) device based on a carbazole-derived copolymer poly[N-9′-heptadecanyl-2,7-carbazole-alt-5,5-(4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)] (PCDTBT) and N,N′-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI) was fabricated by incorporating alcohol-soluble phosphate group-containing perylene diimide derivative (PDIP) as a cathode interfacial layer. The final performance of PDI-based OPV device modified by PDIP layer enhanced due to both optimized interfacial contact and the formation of interfacial dipole. Firstly, the film roughness of active layer was reduced from 8.8 nm to less than 4.0 nm by the introduction of the relatively amorphous PDIP layer. Meanwhile, the surface of active layer became more hydrophilic with significantly decreasing the contact angle from 90° to 78°. Secondly, an interfacial dipole between active layer and metal electrode was formed as indicated by the surface potential measurement, which not only enhanced built-in potential but also improved charge transport and extraction. Thus, the final improved device performance of PDI-based OPV device with simultaneous enhancement of open-circuit voltage (VOC) and short-circuit current density (JSC) was achieved.

Conjugated polymer single crystals and nanowires show advantages for the study of intrinsic charge transport in conjugated polymers and achieve high device performance. However, preparation of conjugated polymer single crystals and nanowires, especially donor-acceptor (D-A) conjugated polymers, is challenging. In this review, the structural features of conjugated polymers are first described. Then, the mechanism of conjugated polymer crystallization in terms of thermodynamic equilibrium state, nucleation, and growth is discussed. Single crystals of poly(alkylthiophene)s (P3ATs) and nanowires of both P3ATs and D-A conjugated polymers are subsequently reviewed. Growth kinetics are a key issue in growing D-A-conjugated polymer crystals. Finally, the device performance based on conjugated polymer single crystals and nanowires is summarized.

Salvia miltiorrhiza Bge. (Danshen, DS) and Ligusticum chuanxiong Hort. (Chuanxiong, CX) have been widely used in traditional Chinese medicine to prevent and treat myocardial ischemia and renal insufficiency, and their extracts (Guanxinning injection, GXN) have been reported to exhibit antioxidant, anti-inflammatory, and anti-ischemia-reperfusion injury properties. It is well-established that ischemic postconditioning (IPOC) can protect against myocardial ischemia-reperfusion (I/R) injury in rats with chronic renal failure (CRF). However, little is known on whether GXN combined with IPOC may affect myocardial I/R injury in CRF rats. We sought to observe the effect of GXN combined with IPOC on myocardial I/R injury in CRF rats by quantifying changes in the expression of proteins related to mitochondrial dynamics.In a survey, 90 Wistar rats were randomly divided into 6 groups (15 rats per group): CRF group, I/R group, comorbid group (CRF + I/R), IPOC group, IPOC + GXN group and the sham group. Changes in blood myocardial injury markers, urea, and creatinine were analyzed. Heart tissues were harvested for histomorphometry and western blotting when rats were sacrificed. Myocardial infarction area was measured by Evans blue and Triphenyltetrazolium chloride solution staining. The expressions of mitochondrial fission relative proteins (DRP1 and FIS1) and mitochondrial fusion relative proteins (OPA1 and MFN1) were detected by western blotting.IPOC could significantly decrease myocardial injury markers and myocardial area of necrosis (AN)/area at risk (AAR) of the comorbid model rats. Further results showed that GXN combined with IPOC could significantly reduce CK-MB levels and myocardial AN/AAR in comorbid model rats compared with the IPOC group. Meanwhile, both IPOC and IPOC + GXN significantly reduced DRP1 levels and increased the MFN1 and OPA1 protein levels in the comorbid model rats. However, compared with the IPOC group, MFN1 and OPA1 protein levels increased significantly in the IPOC + GXN group.Extracts of DS and CX combined with IPOC exert a protective effect against myocardial I/R injury in rats with CRF, mediated by increased expression of mitochondrial fusion proteins (MFN1 and OPA1).

The full-length cDNA coding sequence is presented for the mouse laminin α4 chain. Comparison of the encoded amino acid sequence with human laminin α4 shows 88.3% identity. Northern blot analysis shows that mouse laminin α4 is strongly expressed in heart, lung and skeletal muscle, with only limited expression in brain, spleen, liver, kidney and testes.

This study compared Chinese participants' visual discrimination of Chinese faces with that of Chinese characters, which are highly similar to faces on a variety of dimensions. Both Chinese faces and characters activated the bilateral middle fusiform with high levels of correlations. These findings suggest that although the expertise systems for faces and written symbols are known to be anatomically differentiated at the later stages of processing to serve face processing or written-symbol-specific processing purposes, they may share similar neural structures in the ventral occipitotemporal cortex at the stages of visual processing.

In this study, we systematically investigated the morphological evolution of poly(3-hexylthiophene) (P3HT) and poly{2,7-(9,9-didodecyl-fluorene)-alt-5,5-[4′,7′-bis(2-thienyl)-2′,1′,3′-benzothiadiazole]} (PF12TBT) blend thin films cast from o-dichlorobenzene (oDCB) solution and its effect on photovoltaic performance. Blend ratio and film drying time both played a crucial role in determining polymer blend film morphologies, including phase-separated structure and domain size. An apparent morphological transformation from uniform morphology to droplet and bicontinuous structure could be observed with the P3HT/PF12TBT blend ratio ranging from 10/90 to 90/10. Uniform morphology resulted from one component becoming dominated, and thus no obvious phase separation could be observed. The formation of bicontinuous morphology via a spinodal decomposition mechanism which emerged at nearly equal blend ratio could be attributed to the similar and favorable solubility for both polymers in processing solvent, while the asymmetric composition led to the formation of droplet morphology via a spinodal decomposition mechanism. In addition, the increased domain size which resulted from coarsening of adjacent domains could be observed with the extending film drying time. Further expanding drying time, the thin films exhibited unsharp morphology with large domains which could be attributed to the mixing of polymer blend with the formation of vast P3HT crystallites and the aggregation of both donor and acceptor via molecular diffusion. On the basis of the varying morphologies, an approximate phase diagram of P3HT/PF12TBT blend was depicted. In order to demonstrate the effect of various morphologies on photovoltaic performance, devices based on films with three kinds of blend ratios (40/60, 50/50, and 60/40) while undergoing different drying time (20, 30, and 45 s) were prepared. As the drying time extended, a gradual decreased power conversion efficiency (PCE) could be observed for all blend ratio devices, which resulted from the dramatic morphological transformation from small domains to intermediate domains and then upsharp morphology with large domains ultimately.

Objective: The purpose of this study is to evaluate the potential diagnostic benefit of SPM-based semi-quantitative FDG-PET analysis in autoimmune encephalitis (AE) compared with visual analysis by experienced neuroradiologists using a larger sample size. Methods: This observational retrospective case series study was conducted from a tertiary epilepsy center between May 2014 and March 2017. Healthy individuals without any neurologic or psychiatric diseases were recruited as control. We determined brain FDG-PET abnormal glucose metabolism on medial temporal lobe and basal ganglia using semi-quantitative analysis and compared this method with visual analysis at the same time among patients with autoantibody positive AE. Results: Twenty-eight patients with clinically diagnosed AE and 53 healthy individuals without any neurologic or psychiatric diseases were recruited. On the medial temporal lobe and the basal ganglia, semi-quantitative analysis showed consistency with the visual assessment for whom they had abnormal metabolism by visual assessment. More importantly, 56% patients on medial temporal lobe and 73% patients on the basal ganglia respectively who were not identified by visual inspection can be detected by semi-quantitative analysis, demonstrating the greater sensitivity of semi-quantitative analysis compared with visual assessment. Significance: This study showed semi-quantitative brain FDG-PET analysis was better than visual analysis in view of observing the abnormal glucose metabolism of patients with autoantibody positive AE. Semi-quantitative FDG-PET analysis appears to be a helpful tool in early diagnosis of patients with AE.

Alzheimer's disease (AD) is the most common type of dementia worldwide. The deposition of amyloid β (Aβ) is one of the most important pathological changes in AD. Autophagy, which mediates degradation of toxic proteins and maintains normal neuronal function, is dysfunctional in AD; dysfunctional autophagy is believed to be a critical pathological feature of AD. Here, we evaluated the in vitro and in vivo effects of a traditional Chinese medicinal formula called Yizhiqingxin formula (YQF) on autophagy. We determined that treatment with a high dose of YQF improved spatial memory and decreased the hippocampal Aβ burden in APP/PS1 mice, an early onset AD model. Transmission electron microscopy and immunohistochemical data revealed that YQF enhanced autophagosome formation and also increased the levels of LC3II/LC3I and Beclin1. Further, we found that YQF treatment promoted autophagic activity by inhibiting the phosphorylation of the Mammalian target of rapamycin (mTOR) at the Ser2448 site. Moreover, the level of 4EBP1 increased after YQF intervention, indicating a suppression of mTOR signaling. YQF was also found to promote autophagosome degradation, as indicated by the decreased p62 levels and increased cathepsin D and V-ATPase levels. Taken together, YQF could improve spatial learning in APP/PS1 mice and ameliorate the accumulation of Aβ while promoting autophagy via mTOR pathway modulation.

To investigate alterations in neurocognitive, attention, paediatric sleep questionnaire (PSQ) scores and whole brain white matter (WM) integrity between children with mild and severe obstructive sleep apnoea (OSA) according to sex and whether these changes are associated with OSA severity. Fifty-seven children (36 males and 21 females) diagnosed with OSA were recruited for this study. Children of both sexes were divided into mild (male-MG, female-MG) and severe (male-SG, female-SG) groups according to OSA severity. Polysomnography (PSG), neurocognitive, attention and PSQ tests were compared between groups by one-way samples analysis of variance (ANOVA) F test. Diffusion tensor imaging (DTI) was scanned using a 3T GE MRI scanner and analysed by Tract-based Spatial Statistics (TBSS). Spearman correlation was calculated between DTI Eigenvalues and clinical characteristics. Compared to mild OSA patients, severe OSA patients presented greater severity of obstructive apnoea hypopnea index (OAHI), neurocognition, PSQ and attention tests in both male and female patients. Brain WM integrity in the male-SG, compared to the male-MG, demonstrated significantly reduced fractional anisotropy (FA) values in the right middle frontal gyrus and the right frontal sub-gyral regions and increased axial diffusivity (AD) values in the right inferior frontal gyrus, left parietal angular gyrus and sub-gyral regions, while no differences were found between the female-MG and female-SG. Alterations in male-SG brain regions were observably correlated with severity in male OSA patients. The integrity of WM, which regulates autonomic, cognitive, and attention functions, is impaired in male, but not female, children with severe OSA.

The volatile oil of Mentha haplocalyx is widely used in medicine, food, and cosmetics. However, a large amount of its residue after steam extraction of volatile oil is abandoned, resulting in a waste of resources. The method of aqueous two-phase flotation coupled with preparative high-performance liquid chromatography was established for the separation and purification of nonvolatile active compounds from Mentha haplocalyx for the first time. The parameters of the two-phase aqueous flotation were optimized. Under the optimal conditions including flotation solvent PEG 1000 aqueous solution (1:1, w/w), pH 5, (NH4 )2 SO4 concentration of 350 g/L in aqueous phase, N2 flow rate of 20 mL/min, and flotation time of 20 min, the flotation efficiency of linarin, hesperidin, and didymin was 82.24, 76.38, and 89.33%, respectively. The linarin and hesperidin with the high purities of 95.8 and 97.2%, respectively, were obtained by using preparative high performance liquid chromatography. The neuroprotective effect of linarin against H2 O2 -induced oxidative stress in rat hippocampal neurons was investigated. The experimental result indicated that linarin could alleviate H2 O2 -induced oxidative stress. The work indicated that the combination of aqueous two-phase flotation and preparative high performance liquid chromatography is a feasible and practical method for the purification of nonvolatile active substances from Mentha haplocalyx, which would provide a reference process for the comprehensive utilization of M. haplocalyx. Especially, linarin might be used as a good source of natural neuroprotectants.

Ling-Qui-Qi-Hua (LGQH) decoction, composed of Poria cocos (Schw.) Wolf, Cinnamomum cassia (L.) J. Presl, Paeonia veitchii Lynch, and Atractylodes macrocephala Koidz., is a compound formula derived from Ling-Gui-Zhu-Gan decoction recorded in the Treatise on Febrile and Miscellaneous. It has shown cardioprotective effects on patients or rats with heart failure with preserved ejection fraction (HFpEF). Nevertheless, the active ingredients of LGQH and its anti-fibrotic mechanism remain unknown.To determine the active ingredients in LGQH decoction and verify that LGQH decoction may inhibit left ventricular (LV) myocardial fibrosis in HFpEF rats by blocking the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway from the perspective of animal experiments.First, liquid chromatography-mass spectrometry (LC-MS) technology was used to identify active components in the LGQH decoction. Secondly, a rat model of the metabolic syndrome-associated HFpEF phenotype was established and subsequently received LGQH intervention. The mRNA and protein expression of targets in the TGF-β1/Smads pathway were detected by quantitative real-time polymerase chain reaction and western blot analysis. Finally, molecular docking was conducted to examine the interactions between the active ingredients in the LGQH decoction and key proteins of the TGF-β1/Smads pathways.According to LC-MS analysis, the LGQH decoction contained 13 active ingredients. In animal experiments, LGQH attenuated LV hypertrophy, enlargement, and diastolic function in HEpEF rats. Mechanically, LGQH not only down-regulated TGF-β1, Smad2, Smad3, Smad4, α-SMA, Coll I, and Coll III mRNA expressions and TGF-β1, Smad2, Smad3, P-Smad2/Smad3, Smad4, α-SMA, and Coll I protein expressions, but also up-regulated Smad7 mRNA and protein expressions, which ultimately led to myocardial fibrosis. Furthermore, molecular docking confirmed that 13 active ingredients in the LGQH decoction have excellent binding activities to the critical targets of the TGF-β1/Smads pathway.LGQH is a modified herbal formulation with multiple active ingredients. It might alleviate LV remodeling and diastolic dysfunction and inhibit LV myocardial fibrosis by blocking TGF-β1/Smads pathways in HFpEF rats.

Prostate cancer (PCa) is a pernicious tumor with high heterogeneity, which creates a conundrum for making a precise diagnosis and choosing an optimal treatment approach. Multiparametric magnetic resonance imaging (mp-MRI) with anatomical and functional sequences has evolved as a routine and significant paradigm for the detection and characterization of PCa. Moreover, using radiomics to extract quantitative data has emerged as a promising field due to the rapid growth of artificial intelligence (AI) and image data processing. Radiomics acquires novel imaging biomarkers by extracting imaging signatures and establishes models for precise evaluation. Radiomics models provide a reliable and noninvasive alternative to aid in precision medicine, demonstrating advantages over traditional models based on clinicopathological parameters. The purpose of this review is to provide an overview of related studies of radiomics in PCa, specifically around the development and validation of radiomics models using MRI-derived image features. The current landscape of the literature, focusing mainly on PCa detection, aggressiveness, and prognosis evaluation, is reviewed and summarized. Rather than studies that exclusively focus on image biomarker identification and method optimization, models with high potential for universal clinical implementation are identified. Furthermore, we delve deeper into the critical concerns that can be addressed by different models and the obstacles that may arise in a clinical scenario. This review will encourage researchers to design models based on actual clinical needs, as well as assist urologists in gaining a better understanding of the promising results yielded by radiomics.

Accurate differentiation between benign and malignant cystic renal masses (CRMs) is challenging in clinical practice. This study aimed to develop MRI-based machine learning models for differentiating between benign and malignant CRMs and compare the best-performing model with the Bosniak classification, version 2019 (BC, version 2019).Between 2009 and 2021, consecutive surgery-proven CRM patients with renal MRI were enrolled in this multicenter study. Models were constructed to differentiate between benign and malignant CRMs using logistic regression (LR), random forest (RF), and support vector machine (SVM) algorithms, respectively. Meanwhile, two radiologists classified CRMs into I-IV categories according to the BC, version 2019 in consensus in the test set. A subgroup analysis was conducted to investigate the performance of the best-performing model in complicated CRMs (II-IV lesions in the test set). The performances of models and BC, version 2019 were evaluated using the area under the receiver operating characteristic curve (AUC). Performance was statistically compared between the best-performing model and the BC, version 2019.278 and 48 patients were assigned to the training and test sets, respectively. In the test set, the AUC and accuracy of the LR model, the RF model, the SVM model, and the BC, version 2019 were 0.884 and 75.0%, 0.907 and 83.3%, 0.814 and 72.9%, and 0.893 and 81.2%, respectively. Neither the AUC nor the accuracy of the RF model that performed best were significantly different from the BC, version 2019 (P = 0.780, P = 0.065). The RF model achieved an AUC and accuracy of 0.880 and 81.0% in complicated CRMs.The MRI-based RF model can accurately differentiate between benign and malignant CRMs with comparable performance to the BC, version 2019, and has good performance in complicated CRMs, which may facilitate treatment decision-making and is less affected by interobserver disagreements.

EDITORIAL article Front. Plant Sci., 26 January 2024Sec. Sustainable and Intelligent Phytoprotection Volume 15 - 2024 | https://doi.org/10.3389/fpls.2024.1368694