Shuo Zhang

Upgrading Methane Sans Oxygen Direct routes to converting methane to higher hydrocarbons can allow natural gas to be used to provide chemical feedstocks. However, the reaction conditions needed to activate the strong C-H bond tend to overoxidize the products. Guo et al. (p. 616 ) report a high-temperature nonoxidative route that exposes methane to isolated iron sites on a silica catalyst. Methyl radicals were generated and coupled in the gas phase to form ethylene and aromatics along with hydrogen. The isolation of the active sites avoided surface reactions between the radicals that would deposit solid carbon.

Porcine reproductive and respiratory syndrome (PRRS) is a severe viral disease in pigs, causing great economic losses worldwide each year. The causative agent of the disease, PRRS virus (PRRSV), is a member of the family Arteriviridae. Here we report our investigation of the unparalleled large-scale outbreaks of an originally unknown, but so-called “high fever” disease in China in 2006 with the essence of PRRS, which spread to more than 10 provinces (autonomous cities or regions) and affected over 2,000,000 pigs with about 400,000 fatal cases. Different from the typical PRRS, numerous adult sows were also infected by the “high fever” disease. This atypical PRRS pandemic was initially identified as a hog cholera-like disease manifesting neurological symptoms (e.g., shivering), high fever (40–42°C), erythematous blanching rash, etc. Autopsies combined with immunological analyses clearly showed that multiple organs were infected by highly pathogenic PRRSVs with severe pathological changes observed. Whole-genome analysis of the isolated viruses revealed that these PRRSV isolates are grouped into Type II and are highly homologous to HB-1, a Chinese strain of PRRSV (96.5% nucleotide identity). More importantly, we observed a unique molecular hallmark in these viral isolates, namely a discontinuous deletion of 30 amino acids in nonstructural protein 2 (NSP2). Taken together, this is the first comprehensive report documenting the 2006 epidemic of atypical PRRS outbreak in China and identifying the 30 amino-acid deletion in NSP2, a novel determining factor for virulence which may be implicated in the high pathogenicity of PRRSV, and will stimulate further study by using the infectious cDNA clone technique.

MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression. Functionally, an individual miRNA is as important as a transcription factor because it is able to regulate the expression of its multiple target genes. Recently, miR-221 and miR-222 have been found to play a critical role in cancer cell proliferation. However, their roles in vascular smooth muscle cell (VSMC) biology are currently unknown. In the present study, the time course changes and cellular distribution of miR-221 and miR-222 expression were identified in rat carotid arteries after angioplasty, in which their expression was upregulated and localized in VSMCs in the injured vascular walls. In cultured VSMCs, miR-221 and miR-222 expression was increased by growth stimulators. Knockdown of miR-221 and miR-222 resulted in decreased VSMC proliferation in vitro. Using both gain-of-function and loss-of-function approaches, we found that p27(Kip1) and p57(Kip2) were 2 target genes that were involved in miR-221- and miR-222-mediated effect on VSMC growth. Finally, knockdown of miR-221 and miR-222 in rat carotid arteries suppressed VSMC proliferation in vivo and neointimal lesion formation after angioplasty. The results indicate that miR-221 and miR-222 are novel regulators for VSMC proliferation and neointimal hyperplasia. These findings may also represent promising therapeutic targets in proliferative vascular diseases.

Abstract The desire to visualize noninvasively physiological processes at high temporal resolution has been a driving force for the development of MRI since its inception in 1973. In this article, we describe a unique method for real‐time MRI that reduces image acquisition times to only 20 ms. Although approaching the ultimate limit of MRI technology, the method yields high image quality in terms of spatial resolution, signal‐to‐noise ratio and the absence of artifacts. As proposed previously, a fast low‐angle shot (FLASH) gradient‐echo MRI technique (which allows for rapid and continuous image acquisitions) is combined with a radial encoding scheme (which offers motion robustness and moderate tolerance to data undersampling) and, most importantly, an iterative image reconstruction by regularized nonlinear inversion (which exploits the advantages of parallel imaging with multiple receiver coils). In this article, the extension of regularization and filtering to the temporal domain exploits consistencies in successive data acquisitions and thereby enhances the degree of radial undersampling in a hitherto unexpected manner by one order of magnitude. The results obtained for turbulent flow, human speech production and human heart function demonstrate considerable potential for real‐time MRI studies of dynamic processes in a wide range of scientific and clinical settings. Copyright © 2010 John Wiley & Sons, Ltd.

Reactive oxygen species (ROS)-induced cardiac cell injury via expression changes of multiple genes plays a critical role in the pathogenesis of numerous heart diseases. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate about 30% of the genes in a cell via degradation or translational inhibition of their target mRNAs. Currently, the effects of ROS on miRNA expression and the roles of miRNAs in ROS-mediated injury on cardiac myocytes are uncertain. Using quantitative real-time RT-PCR (qRT-PCR), we demonstrated that microRNA-21 (miR-21) was upregulated in cardiac myocytes after treatment with hydrogen peroxide (H(2)O(2)). To determine the potential roles of miRNAs in H(2)O(2)-mediated gene regulation and cellular injury, miR-21 expression was downregulated by miR-21 inhibitor and upregulated by pre-miR-21. H(2)O(2)-induced cardiac cell death and apoptosis were increased by miR-21 inhibitor and was decreased by pre-miR-21. Programmed cell death 4 (PDCD4) that was regulated by miR-21 and was a direct target of miR-21 in cardiac myocytes. Pre-miR-21-mediated protective effect on cardiac myocyte injury was inhibited in H(2)O(2)-treated cardiac cells via adenovirus-mediated overexpression of PDCD4 without miR-21 binding site. Moreover, Activator protein 1 (AP-1) was a downstream signaling molecule of PDCD4 that was involved in miR-21-mediated effect on cardiac myocytes. The results suggest that miR-21 is sensitive to H(2)O(2) stimulation. miR-21 participates in H(2)O(2)-mediated gene regulation and functional modulation in cardiac myocytes. miR-21 might play an essential role in heart diseases related to ROS such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.

Developing highly efficient oxygen evolution reaction (OER) catalysts and understanding their activity are pivotal for electrochemical conversion technologies. Here, we report NiFe Prussian blue analogue (PBA) as a promising electrocatalyst for OER in alkaline conditions. This material has an impressively low overpotential of 258 mV that reaches a current density of 10 mA cm-2. Post-mortem characterization showed that the as-prepared catalyst is entirely transformed into amorphous nickel hydroxide after the electrochemical treatment, and Ni(OH)2 acts as the active species. Operando X-ray spectroscopic studies further found that this in situ generated Ni(OH)2 displays an unique feature that allows deprotonation under applied potential creating NiOOH2- x that contains Ni4+ ions. The deprotonation reaction is reversible and potential-dependent, i.e., the amount of Ni4+ increases with increasing applied potential. Theoretical calculations were used to show that the role of Ni4+ is to trigger oxidized oxygen ions as electrophilic centers with the subsequent activation of anion redox reactions for OER.

LRRK2 autophosphorylation on Ser 1292 may be a useful indicator of kinase activity, providing a readout for screening candidate LRRK2 inhibitors.

Runoff forecasting is an important approach for flood mitigation. Many machine learning models have been proposed for runoff forecasting in recent years. To reconstruct the time series of runoff data into a standard machine learning dataset, a sliding window method is usually used to pre-process the data, with the size of the window as a variable parameter which is commonly referred to as the time step. Conventional machine learning methods, such as artificial neural network models (ANN), require optimization of the time step because both too small and too large time steps reduce prediction accuracy. In this work two popular variants of Recurrent Neural Network (RNN) named Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) networks were employed to develop new data-driven flood forecasting models. GRU and LSTM models are in theory able to filter redundant information automatically, and therefore a large time step is expected to not reduce prediction accuracy. The three models (LSTM, GRU, and ANN) were applied to simulate runoff in the Yutan station control catchment, Fujian Province, Southeast China, using hourly discharge measurements of one runoff station and hourly rainfall of four rainfall stations from 2000 to 2014. Results show that the prediction accuracy of LSTM and GRU models increases with increasing time step, and eventually stabilizes. This allows selection of a relatively large time step in practical runoff prediction without first evaluating and optimizing the time step required by conventional machine learning models. We also show that LSTM and GRU models perform better than ANN models when the time step is optimized. GRU models have fewer parameters and less complicated structures compared to LSTM models, and our results show that GRU models perform equally well as LSTM models. GRU may be the preferred method in short term runoff predictions since it requires less time for model training.

The effects of a tea polyphenols (TP) dip treatment on quality changes of silver carp (Hypophthalmicthys molitrix) during iced storage were examined over a period of 35 days. TP (0.2%, w/v) solution was used for the dip treatment. The control and the treated fish samples were analysed periodically for microbiological (total viable count), chemical (pH, TVB-N, TBA, K-value), and sensory characteristics. The results indicated that the effect of the TP dip treatment on the fish samples was to enable the good quality characteristics to be retained for longer and to extend the shelf life during the iced storage.

High-efficiency and high-selectivity catalytic oxidation of alkanes under mild conditions is a major objective of current catalysis chemistry and chemical production. Despite extensive development efforts on new catalysts for cyclohexane oxidation, current commercial processes still suffer from low conversion, poor selectivity, and excessive production of waste. We demonstrate the design and synthesis of composites made from metal nanoparticles and carbon quantum dots (CQDs) for high-efficiency and high-selectivity photocatalyst systems for the green oxidation of cyclohexane. Remarkably, the present Au nanoparticles/CQDs composite photocatalyst yields 63.8% conversion efficiency and 99.9% selectivity for the green oxidation of cyclohexane to cyclohexanone, using H2O2 under visible light at room temperature. Given its diversity and versatility of structural and composition design, metal nanoparticles/CQDs composites may provide a powerful pathway for the development of high-performance catalysts and production processes for green chemical industry.

LRRK2 kinase inhibitors, under development for Parkinson’s disease, have an effect on type II pneumocytes in nonhuman primate lung, suggesting that pulmonary toxicity may be a critical safety liability.

<h3>Importance</h3> Hypertension is a leading cause of premature death in China, but limited evidence is available on the prevalence and management of hypertension and its effect on mortality from cardiovascular disease (CVD). <h3>Objectives</h3> To examine the prevalence, diagnosis, treatment, and control of hypertension and to assess the CVD mortality attributable to hypertension in China. <h3>Design, Setting and Participants</h3> This prospective cohort study (China Kadoorie Biobank Study) recruited 500 223 adults, aged 35 to 74 years, from the general population in China. Blood pressure (BP) measurements were recorded as part of the baseline survey from June 25, 2004, to August 5, 2009, and 7028 deaths due to CVD were recorded before January 1, 2014 (mean duration of follow-up: 7.2 years). Data were analyzed from June 9, 2014, to July 17, 2015. <h3>Exposures</h3> Prevalence and diagnosis of hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or receiving treatment for hypertension) and treatment and control rates overall and in various population subgroups. <h3>Main Outcomes and Measures</h3> Cox regression analysis yielded age- and sex-specific rate ratios for deaths due to CVD comparing participants with and without uncontrolled hypertension, which were used to estimate the number of CVD deaths attributable to hypertension. <h3>Results</h3> The cohort included 205 167 men (41.0%) and 295 056 women (59.0%) with a mean (SD) age of 52 (10) years for both sexes. Overall, 32.5% of participants had hypertension; the prevalence increased with age (from 12.6% at 35-39 years of age to 58.4% at 70-74 years of age) and varied substantially by region (range, 22.7%-40.7%). Of those with hypertension, 30.5% had received a diagnosis from a physician; of those with a diagnosis of hypertension, 46.4% were being treated; and of those treated, 29.6% had their hypertension controlled (ie, systolic BP &lt;140 mm Hg; diastolic BP &lt;90 mm Hg), resulting in an overall control rate of 4.2%. Even among patients with hypertension and prior CVD, only 13.0% had their hypertension controlled. Uncontrolled hypertension was associated with relative risks for CVD mortality of 4.1 (95% CI, 3.7-4.6), 2.6 (95% CI, 2.4-2.9) and 1.9 (95% CI, 1.8-2.0) at ages 35 to 59, 60 to 69, and 70 to 79 years, respectively, and accounted for about one-third of deaths due to CVD (approximately 750 000) at 35 to 79 years of age in 2010. <h3>Conclusions and Relevance</h3> About one-third of Chinese adults in this national cohort population had hypertension. The levels of diagnosis, treatment, and control were much lower than in Western populations, and were associated with significant excess mortality.

Abstract Atroposelective synthesis of axially chiral biaryls by palladium‐catalyzed C−H olefination, using tert ‐leucine as an inexpensive, catalytic, and transient chiral auxiliary, has been realized. This strategy provides a highly efficient and straightforward access to a broad range of enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (95 to &gt;99 % ee ). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (95 to &gt;99 % ee , s ‐factor up to 600).

A highly soft, stretchable, and sticky polydimethylsiloxane-based elastomer is achieved by adding small fractions of an amine-based polymer. The modified elastomer is tuned with a simple mixing step and shows good processability for microstructure fabrication. The modified elastomer shows excellent compatibility with an epidermal strain sensor on human skin. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Developing a scalable approach to construct efficient and multifunctional electrodes for the hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR) is an urgent need for overall water splitting and zinc-air batteries. In this work, a freestanding 3D heterostructure film is synthesized from a Ni-centered metal-organic framework (MOF)/graphene oxide. During the pyrolysis process, 1D carbon nanotubes formed from the MOF link with the 2D reduced graphene oxide sheets to stitch the 3D freestanding film. The results of the experiments and theoretical calculations show that the synergistic effect of the N-doped carbon shell and Ni nanoparticles leads to an optimized film with excellent electrocatalytic activity. Low overpotentials of 95 and 260 mV are merely needed for HER and OER, respectively, to reach a current density of 10 mA cm-2 . In addition, a high half-wave potential of 0.875 V is obtained for the ORR, which is comparable to that of Pt/RuO2 and ranks among the top of non-noble-metal catalysts. The use of an "all-in-one" film as the electrode leads to excellent performance of the homemade water electrolyzer and zinc-air battery, indicating the potential of the film for practical applications.

Various well-defined Ni−Pt(111) model catalysts are constructed at atomic-level precision under ultra-high-vacuum conditions and characterized by X-ray photoelectron spectroscopy and scanning tunneling microscopy. Subsequent studies of CO oxidation over the surfaces show that a sandwich surface (NiO1−x/Pt/Ni/Pt(111)) consisting of both surface Ni oxide nanoislands and subsurface Ni atoms at a Pt(111) surface presents the highest reactivity. A similar sandwich structure has been obtained in supported Pt−Ni nanoparticles via activation in H2 at an intermediate temperature and established by techniques including acid leaching, inductively coupled plasma, and X-ray adsorption near-edge structure. Among the supported Pt−Ni catalysts studied, the sandwich bimetallic catalysts demonstrate the highest activity to CO oxidation, where 100% CO conversion occurs near room temperature. Both surface science studies of model catalysts and catalytic reaction experiments on supported catalysts illustrate the synergetic effect of the surface and subsurface Ni species on the CO oxidation, in which the surface Ni oxide nanoislands activate O2, producing atomic O species, while the subsurface Ni atoms further enhance the elementary reaction of CO oxidation with O.

Fractional-order Hopfield neural networks are often used to model how interacting neurons process information. To show reliability of the processed information, it is needed to perform stability analysis of these systems. Here, we perform Mittag-Leffler stability analysis for them. For this, we extend the second method of Lyapunov in the fractional-order case and establish a useful inequality that can be effectively used to this analysis. Importantly, these general results can help construct Lyapunov functions used to Mittag-Leffler stability analysis of fractional-order Hopfield neural networks. As a result, a set of sufficient conditions is derived to guarantee this stability. In addition, the general results can be easily used to the establishment of stability conditions for achieving complete and quasi synchronization in the coupling case of these networks with constant or time-dependent external inputs. Finally, two numerical examples are presented to show the effectiveness of our theoretical results.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV) with an average fatality rate of 12%. The clinical factors for death in SFTS patients remain unclear.Clinical features and laboratory parameters were dynamically collected for 11 fatal and 48 non-fatal SFTS cases. Univariate logistic regression was used to evaluate the risk factors associated with death.Dynamic tracking of laboratory parameters revealed that during the initial fever stage, the viral load was comparable for the patients who survived as well as the ones that died. Then in the second stage when multi-organ dysfunction occurred, from 7-13 days after disease onset, the viral load decreased in survivors but it remained high in the patients that died. The key risk factors that contributed to patient death were elevated serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase fraction, as well as the appearance of CNS (central nervous system) symptoms, hemorrhagic manifestation, disseminated intravascular coagulation, and multi-organ failure. All clinical markers reverted to normal in the convalescent stage for SFTS patients who survived.We identified a period of 7-13 days after the onset of illness as the critical stage in SFTS progression. A sustained serum viral load may indicate that disease conditions will worsen and lead to death.

Removing the influence of occlusion on the depth estimation for light field images has always been a difficult problem, especially for highly noisy and aliased images captured by plenoptic cameras. In this paper, a spinning parallelogram operator (SPO) is integrated into a depth estimation framework to solve these problems. Utilizing the regions divided by the operator in an Epipolar Plane Image (EPI), the lines that indicate depth information are located by maximizing the distribution distances of the regions. Unlike traditional multi-view stereo matching methods, the distance measure is able to keep the correct depth information even if they are occluded or noisy. We further choose the relative reliable information among the rich structures in the light field to reduce the influences of occlusion and ambiguity. The discrete labeling problem is then solved by a filter-based algorithm to fast approximate the optimal solution. The major advantage of the proposed method is that it is insensitive to occlusion, noise, and aliasing, and has no requirement for depth range and angular resolution. It therefore can be used in various light field images, especially in plenoptic camera images. Experimental results demonstrate that the proposed method outperforms state-of-the-art depth estimation methods on light field images, including both real world images and synthetic images, especially near occlusion boundaries.

Severe fever with thrombocytopenia syndrome bunyavirus is a newly discovered bunyavirus with high pathogenicity to human. The transmission model has been largely uncharacterized. Investigation on a cluster of severe fever with thrombocytopenia syndrome cases provided evidence of person-to-person transmission through blood contact to the index patient with high serum virus load.

Slow kinetics of polysulfide conversion reactions lead to severe issues for lithium–sulfur (Li–S) batteries, for example, low rate capability, polysulfide migration, and low Coulombic efficiencies. These challenges hinder the practical applications of Li–S batteries. In this study, we proposed a rational strategy of tuning the d-band of catalysts to accelerate the conversion of polysulfides. Nitrogen vacancies were engineered in hexagonal Ni3N (space group P6322) to tune its d-band center, leading to the strong interaction between polysulfides and Ni3N. Because of the greater electron population in the lowest occupied molecular orbital of Li2S4, the terminal S–S bonds were weakened for breaking. Temperature-dependent experiments confirm that Ni3N0.85 demonstrates a much low activation energy, thereby accelerating the conversion of polysulfides. A Li–S cell using Ni3N0.85 can deliver a high initial discharge capacity of 1445.9 mAh g–1 (at 0.02 C) and low decay per cycle (0.039%). The Ni3N0.85 cell can also demonstrate an initial capacity of 1200.4 mAh g–1 for up to 100 cycles at a high loading of 5.2 mg cm–2. The high efficiency of rationally designed Ni3N0.85 demonstrates the effectiveness of the d-band tuning strategy to develop low-activation-energy catalysts and to promote the atomic understanding of polysulfide conversion in Li–S batteries.

Abstract Unravelling the intrinsic mechanism of electrocatalytic oxygen evolution reaction (OER) by use of heterogeneous catalysts is highly desirable to develop related energy conversion technologies. Albeit dynamic self‐reconstruction of the catalysts during OER is extensively observed, it is still highly challenging to operando probe the reconstruction and precisely identify the true catalytically active components. Here, a new class of OER precatalyst, cobalt oxychloride (Co 2 (OH) 3 Cl) with unique features that allow a gradual phase reconstruction during OER due to the etching of lattice anion is demonstrated. The reconstruction continuously boosts OER activities. The reconstruction‐derived component delivers remarkable performance in both alkaline and neutral electrolytes. Operando synchrotron radiation‐based X‐ray spectroscopic characterization together with density functional theory calculations discloses that the etching of lattice Cl − serves as the key to trigger the reconstruction and the boosted catalytic performance roots in the atomic‐level coordinatively unsaturated sites (CUS). This work establishes fundamental understanding on the OER mechanism associated with self‐reconstruction of heterogeneous catalysts.

Aberrant activation of Bruton’s tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds. Compound BGB-3111 (31a, Zanubrutinib) demonstrates (i) potent activity against BTK and excellent selectivity over other TEC, EGFR and Src family kinases, (ii) desirable ADME, excellent in vivo pharmacodynamic in mice and efficacy in OCI-LY10 xenograft models.

In this paper, the global stability analysis of fractional-order Hopfield neural networks with time delay is investigated. A stability theorem for linear fractional-order systems with time delay is presented. And, a comparison theorem for a class of fractional-order systems with time delay is shown. The existence and uniqueness of the equilibrium point for fractional-order Hopfield neural networks with time delay are proved. Furthermore, the global asymptotic stability conditions of fractional-order neural networks with time delay are obtained. Finally, a numerical example is given to illustrate the effectiveness of the theoretical results.

Alzheimer's disease (AD), a common neurodegenerative disease in the elderly and the most prevalent cause of dementia, is characterized by progressive cognitive impairment. The prevalence of AD continues to increase worldwide, becoming a great healthcare challenge of the twenty-first century. In the more than 110 years since AD was discovered, many related pathogenic mechanisms have been proposed, and the most recognized hypotheses are the amyloid and tau hypotheses. However, almost all clinical trials targeting these mechanisms have not identified any effective methods to treat AD. Scientists are gradually moving away from the simple assumption, as proposed in the original amyloid hypothesis, to new theories of pathogenesis, including gamma oscillations, prion transmission, cerebral vasoconstriction, growth hormone secretagogue receptor 1α (GHSR1α)-mediated mechanism, and infection. To place these findings in context, we first reviewed the neuropathology of AD and further discussed new insights in the pathogenesis of AD.

In fused deposition modeling (FDM) using polyether-ether-ketone (PEEK), the dimensions of extruded filaments are unstable and there is insufficiency dimensional agreement between the fabricated part and design model. The present study presents the effects of the extrusion speed and printing speed on the microstructure and dimensions of an extruded PEEK filament in 3D printing. The extrusion process characterization including extrusion force and extrusion resistance was measured for the understanding of the evolution of extrusion process with the increase in extrusion speed. The relationship between the extrusion speed and the diameter of the extruded filament was established by measuring the diameter of the extruded filament at different extrusion speeds in freeform extrusion. Furthermore, PEEK was stably printed in an experiment with increasing printing speed and it was revealed that the control algorithm that mathematically replaces the nozzle diameter with the diameter of the extruded filament is feasible and effective. During PEEK FDM, the melt pressure in the chamber directly affects the surface morphology and extrusion diameter of the extruded filament, and higher melt pressure is beneficial to reducing surface defects of the extruded filament. A fluctuating extrusion force is the main constraint on the stability of extrusion. The optimized control algorithm between the extrusion speed and the diameter of the extruded filament improve the stability of PEEK FDM and improves the dimensional accuracy and surface morphology of printed PEEK parts. Furthermore, this study could be applied to reveal the instability of extrusion and select a set of suitable printing parameters during FDM.

The discovery of an emerging viral disease, severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), has prompted the need to understand pathogenesis of SFTSV. We are unique in establishing an infectious model of SFTS in C57/BL6 mice, resulting in hallmark symptoms of thrombocytopenia and leukocytopenia. Viral RNA and histopathological changes were identified in the spleen, liver, and kidney. However, viral replication was only found in the spleen, which suggested the spleen to be the principle target organ of SFTSV. Moreover, the number of macrophages and platelets were largely increased in the spleen, and SFTSV colocalized with platelets in cytoplasm of macrophages in the red pulp of the spleen. In vitro cellular assays further revealed that SFTSV adhered to mouse platelets and facilitated the phagocytosis of platelets by mouse primary macrophages, which in combination with in vivo findings, suggests that SFTSV-induced thrombocytopenia is caused by clearance of circulating virus-bound platelets by splenic macrophages. Thus, this study has elucidated the pathogenic mechanisms of thrombocytopenia in a mouse model resembling human SFTS disease.

The blood-brain barrier (BBB) poses a major challenge for developing effective antibody therapies for neurological diseases. Using transcriptomic and proteomic profiling, we searched for proteins in mouse brain endothelial cells (BECs) that could potentially be exploited to transport antibodies across the BBB. Due to their limited protein abundance, neither antibodies against literature-identified targets nor BBB-enriched proteins identified by microarray facilitated significant antibody brain uptake. Using proteomic analysis of isolated mouse BECs, we identified multiple highly expressed proteins, including basigin, Glut1, and CD98hc. Antibodies to each of these targets were significantly enriched in the brain after administration in vivo. In particular, antibodies against CD98hc showed robust accumulation in brain after systemic dosing, and a significant pharmacodynamic response as measured by brain Aβ reduction. The discovery of CD98hc as a robust receptor-mediated transcytosis pathway for antibody delivery to the brain expands the current approaches available for enhancing brain uptake of therapeutic antibodies.

Starting from our previous finding of 14 known drugs as inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19, we have redesigned the weak hit perampanel to yield multiple noncovalent, nonpeptidic inhibitors with ca. 20 nM IC50 values in a kinetic assay. Free-energy perturbation (FEP) calculations for Mpro-ligand complexes provided valuable guidance on beneficial modifications that rapidly delivered the potent analogues. The design efforts were confirmed and augmented by determination of high-resolution X-ray crystal structures for five analogues bound to Mpro. Results of cell-based antiviral assays further demonstrated the potential of the compounds for treatment of COVID-19. In addition to the possible therapeutic significance, the work clearly demonstrates the power of computational chemistry for drug discovery, especially FEP-guided lead optimization.

Data centers have recently gained significant popularity as a cost-effective platform for hosting large-scale service applications. While large data centers enjoy economies of scale by amortizing initial capital investment over large number of machines, they also incur tremendous energy cost in terms of power distribution and cooling. An effective approach for saving energy in data centers is to adjust dynamically the data center capacity by turning off unused machines. However, this dynamic capacity provisioning problem is known to be challenging as it requires a careful understanding of the resource demand characteristics as well as considerations to various cost factors, including task scheduling delay, machine reconfiguration cost and electricity price fluctuation.

We report the discovery of 3.76 s pulsations from a new burst source near Sgr A* observed by the NuSTAR observatory. The strong signal from SGR J1745−29 presents a complex pulse profile modulated with pulsed fraction 27% ± 3% in the 3–10 keV band. Two observations spaced nine days apart yield a spin-down rate of =(6.5 ± 1.4) × 10−12. This implies a magnetic field B = 1.6 × 1014 G, spin-down power =5 × 1033 erg s−1, and characteristic age P/2 =9 × 103 yr for the rotating dipole model. However, the current may be erratic, especially during outburst. The flux and modulation remained steady during the observations and the 3–79 keV spectrum is well fitted by a combined blackbody plus power-law model with temperature kTBB = 0.96 ± 0.02 keV and photon index Γ = 1.5 ± 0.4. The neutral hydrogen column density (NH ∼ 1.4 × 1023 cm−2) measured by NuSTAR and Swift suggests that SGR J1745−29 is located at or near the Galactic center. The lack of an X-ray counterpart in the published Chandra survey catalog sets a quiescent 2–8 keV luminosity limit of Lx ≲ 1032 erg s−1. The bursting, timing, and spectral properties indicate a transient magnetar undergoing an outburst with 2–79 keV luminosity up to 3.5 × 1035 erg s−1 for a distance of 8 kpc. SGR J1745−29 joins a growing subclass of transient magnetars, indicating that many magnetars in quiescence remain undetected in the X-ray band or have been detected as high-B radio pulsars. The peculiar location of SGR J1745−29 has important implications for the formation and dynamics of neutron stars in the Galactic center region.

MOF-derived Co₉S₈nanoparticles embedded in carbon doped with N and S showed super stability and high rate performance for supercapacitors.

Reducing soluble U(VI) to insoluble U(IV) is an ideal strategy to collect/remove uranium in water. In this work, a new way is reported to achieve this reduction through a photocorrosion-related photocatalysis process of SnO2/CdCO3/CdS (SCC) under visible light irradiation. The mechanism is systematically studied and discussed through a variety of characterization methods, such as X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), Mott-Schottky test, etc. The matching of energy band ensures the separation of photoelectrons and holes, which results in the decrease of charges’ recombination rate and the enhancement of photoreduction activity. The reduction process can be efficiently performed in the ternary complex of SCC in that the photo-generated holes are consumed by oxidization of S2− to S0 on CdS in SCC. Furthermore, uranium extraction could be achieved by SCC without any protective gases or electronic sacrificial agent, which shows great advantages in applications of U(VI) collection/removal.

Due to the lower rotational barriers, the catalytic asymmetric construction of atropisomeric species featuring a five-membered ring remains a formidable challenge. Herein, we describe a Pd-catalyzed atroposelective C–H alkynylation to synthesize such atropisomers. A wide range of atropisomers displaying either a stereogenic C–N or C–C bond featuring one or even two five-membered rings were obtained (up to 98% yield and up to >99% ee). Various five-membered heteroarenes, including pyrroles, thiophenes, benzothiophenes, and benzofurans were compatible with this protocol. Notably, this strategy offers the catalytic asymmetric synthesis of axially chiral 3,3′-bisbenzothiophene with good ee (93% ee). Computational studies revealed the key structural elements that differentiate the rotational barriers of benzothiophene and benzofuran moieties.

Graphene quantum dots (GQDs) with uniform sizes of less than 5 nm are synthesized by a novel top-down strategy. Nitric acid as a strong oxidant can be used to cut graphene oxide via sonication and hydrothermal processes. Moreover, purified GQDs are obtained from removing oxygen-containing functional groups in a heat treatment process. Both nanoscale size and edge effect of GQDs improve their abundant active sites and restrain the restack of graphene nanosheets. Meanwhile, their electrochemical performance demonstrates the properties of the GQDs for practical application in energy storage. The GQD electrode material shows an ideal electric double-layer capacitance behavior such as a high specific capacitance of 296.7 F g-1, a satisfactory energy density of 41.2 W h kg-1 at 1 A g-1, a low internal resistance, a small relaxation time, and an excellent cycling stability. The results illustrate excellent electrochemical activity, high conductivity, and enhanced ion transport rate on the surface of electrolyte and electrode. The advantages of GQDs confirm their unique characteristics for potential applications in the field of electrode materials for supercapacitors.

In 2012, an unprecedented large-scale outbreak of disease in pigs in China caused great economic losses to the swine industry.Isolates from pseudorabies virus epidemics in swine herds were characterized.Evidence confirmed that the pathogenic pseudorabies virus was the etiologic agent of this epidemic.

<italic>Operando</italic> XAS combined with DFT calculations allows us to draw a phase diagram of the surface chemical state as a function of applied potential, showing hydroxyl filling process and potential-dependent deprotonation process.

Proton-coupled monocarboxylate transporters MCT1-4 catalyze the transmembrane movement of metabolically essential monocarboxylates and have been targeted for cancer treatment because of their enhanced expression in various tumors. Here, we report five cryo-EM structures, at resolutions of 3.0–3.3 Å, of human MCT1 bound to lactate or inhibitors in the presence of Basigin-2, a single transmembrane segment (TM)-containing chaperon. MCT1 exhibits similar outward-open conformations when complexed with lactate or the inhibitors BAY-8002 and AZD3965. In the presence of the inhibitor 7ACC2 or with the neutralization of the proton-coupling residue Asp309 by Asn, similar inward-open structures were captured. Complemented by structural-guided biochemical analyses, our studies reveal the substrate binding and transport mechanism of MCTs, elucidate the mode of action of three anti-cancer drug candidates, and identify the determinants for subtype-specific sensitivities to AZD3965 by MCT1 and MCT4. These findings lay out an important framework for structure-guided drug discovery targeting MCTs.

Fractional-order neural networks play a vital role in modeling the information processing of neuronal interactions. It is still an open and necessary topic for fractional-order neural networks to investigate their global stability. This paper proposes some simplified linear matrix inequality (LMI) stability conditions for fractional-order linear and nonlinear systems. Then, the global stability analysis of fractional-order neural networks employs the results from the obtained LMI conditions. In the LMI form, the obtained results include the existence and uniqueness of equilibrium point and its global stability, which simplify and extend some previous work on the stability analysis of the fractional-order neural networks. Moreover, a generalized projective synchronization method between such neural systems is given, along with its corresponding LMI condition. Finally, two numerical examples are provided to illustrate the effectiveness of the established LMI conditions.

Light field cameras are considered to have many potential applications since angular and spatial information is captured simultaneously. However, the limited spatial resolution has brought lots of difficulties in developing related applications and becomes the main bottleneck of light field cameras. In this paper, a learning-based method using residual convolutional networks is proposed to reconstruct light fields with higher spatial resolution. The view images in one light field are first grouped into different image stacks with consistent sub-pixel offsets and fed into different network branches to implicitly learn inherent corresponding relations. The residual information in different spatial directions is then calculated from each branch and further integrated to supplement high-frequency details for the view image. Finally, a flexible solution is proposed to super-resolve entire light field images with various angular resolutions. Experimental results on synthetic and real-world datasets demonstrate that the proposed method outperforms other state-of-the-art methods by a large margin in both visual and numerical evaluations. Furthermore, the proposed method shows good performances in preserving the inherent epipolar property in light field images.

Targeting immune cells or factors are effective for patients with solid tumors. Myeloid-derived suppressor cells (MDSCs) are known to have immunosuppressive functions, and the levels of MDSCs in patients with solid tumor are assumed to have prognostic values. This meta-analysis aimed at evaluating the relationship between MDSCs and the prognosis of patients with solid tumors. We searched articles in PUBMED and EMBASE comprehensively, updated to March 2016. Eight studies with 442 patients were included in the meta-analysis. We analyzed pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). The results showed that MDSCs were associated with poor OS (HR, 1.94; 95% confidence interval [CI], 1.42-2.66; P < 0.0001) in patients with solid tumors. PFS/RFS (HR, 1.85; 95% CI, 1.16-2.97; P = 0.01) also indicated the association between MDSCs and prognosis. The HRs and 95% CIs for OS in Asian and non-Asian patients were 2.53 (95% CI 1.61-3.42, p < 0.00001) and 1.67 (95% CI 1.14-2.46, p < 0.0001), respectively. We further analyzed the data according to tumor types. The combined HRs and 95% CIs for OS were 1.26 (95% CI 1.10-1.44, p = 0.0003) for gastrointestinal (GI) cancer, 2.59 (95% CI 1.69-3.98, p < 0.0001) for hepatocellular carcinoma (HCC) and 1.86 (95% CI 1.26-2.75, p = 0.002) for other tumor types. In conclusion, MDSCs had a fine prognostic value for OS and PFS/RFS in patients with solid tumors. MDSCs could be used as biomarkers to evaluate prognosis in clinical practice.

Neurodegenerative diseases are a group of chronic progressive disorders characterized by neuronal loss. Necroptosis, a recently discovered form of programmed cell death, is a cell death mechanism that has necrosis-like morphological characteristics. Necroptosis activation relies on the receptor-interacting protein (RIP) homology interaction motif (RHIM). A variety of RHIM-containing proteins transduce necroptotic signals from the cell trigger to the cell death mediators RIP3 and mixed lineage kinase domain-like protein (MLKL). RIP1 plays a particularly important and complex role in necroptotic cell death regulation ranging from cell death activation to inhibition, and these functions are often cell type and context dependent. Increasing evidence suggests that necroptosis plays an important role in the pathogenesis of neurodegenerative diseases. Moreover, small molecules such as necrostatin-1 are thought inhibit necroptotic signaling pathway. Understanding the precise mechanisms underlying necroptosis and its interactions with other cell death pathways in neurodegenerative diseases could provide significant therapeutic insights. The present review is aimed at summarizing the molecular mechanisms of necroptosis and highlighting the emerging evidence on necroptosis as a major driver of neuron cell death in neurodegenerative diseases.

Asphaltenes are the heaviest components in crude oil. It is generally believed that asphaltenes adsorbed at oil/water interface can form a protective layer to stabilize the water-in-oil or oil-in-water emulsions. In this work, the effects of asphaltene concentration and temperature on the dynamic interfacial tension (IFT) of oil (i.e., toluene)/water interface were systematically investigated using a pendent drop shape method. The adsorption process shows three stages as a function of adsorption time. In Regime I, the reduction kinetics of IFT is diffusion-controlled, during which asphaltenes are adsorbed to the oil/water interface spontaneously. The interfacial diffusion coefficient of asphaltenes to the oil/water interface was found to increase with increasing temperature and decreasing asphaltene concentration, which is much lower than the bulk diffusion coefficient predicated by the Stokes–Einstein equation. In Regime II, the steric hindrance arisen from the adsorbed asphaltenes at oil/water interface from Regime I tends to inhibit further adsorption of asphaltenes to the interface. In Regime III, continuous adsorption of asphaltenes to the sublayer of the interface and reconfiguration of adsorbed asphaltenes or asphaltene aggregates occur, contributing to the continuous but very slow reduction of dynamic interfacial tension. Our results provide useful insights into the adsorption kinetics and adsorption mechanism of asphaltenes at oil/water interfaces under different asphaltene concentration and temperature conditions, with implications to many related interfacial phenomena (e.g., emulsion stability) where asphaltenes are present in oil production.

Developing highly-active and stable catalyst is key to water electrolysis technology. Here, we report a hydroxide-mediated nickel-based catalyst working well at industrial-relevant high-current-densities based on a charge-engineering strategy.

Magnetic microrobots can be actuated in fuel-free conditions and are envisioned for biomedical applications related to targeted delivery and therapy in a minimally invasive manner. However, mass fabrication of microrobots with precise propulsion performance and excellent therapeutic efficacy is still challenging, especially in a predictable and controllable manner. Herein, we propose a facile technique for mass production of magnetic microrobots with multiple functions using Spirulina (Sp.) as biotemplate. Core–shell-structured Pd@Au nanoparticles (NPs) were synthesized in Sp. cells by electroless deposition, working as photothermal conversion agents. Subsequently, the Fe3O4 NPs were deposited onto the surface of the obtained (Pd@Au)@Sp. particles via a sol–gel process, enabling them to be magnetically actuated. Moreover, the anticancer drug doxorubicin (DOX) was loaded on the (Pd@Au)/Fe3O4@Sp. microrobots, which endows them with additional chemotherapeutic efficacy. The as-prepared biohybrid (Pd@Au)/Fe3O4@Sp.-DOX microrobots not only possess efficient propulsion performance with the highest speed of 526.2 μm/s under a rotating magnetic field but also have enhanced synergistic chemo-photothermal therapeutic efficacy. Furthermore, they can be structurally disassembled into individual particles under near-infrared (NIR) laser irradiation and exhibit pH- and NIR-triggered drug release. These intriguing properties enable the microrobots to be a very promising and efficient platform for drug loading, targeted delivery, and chemo-photothermal therapy.

Graphene oxide (GO)-based nanofiltration membranes, featuring well-ordered microscopic structure, well-defined 2D nanochannels and superior molecular sieving ability, have attracted sustained research interest in molecular and ionic separation. However, most of current GO laminar membrane have a poor water flux and high rejection of both dyes and salts, which is not suitable for the dye/salt mixture separation. Herein, we report a vacuum filtration strategy to fabricate GO/NH2-Fe3O4 nanofiltration membranes with high water flux and excellent separation performance for dye/salts mixture by introducing NH2-Fe3O4. The NH2-Fe3O4 is not only worked as the rigid spherical nanospacer to tune GO interlayer spacing but also as crosslinkers to improve the stability of GO membrane in water. FTIR, XRD, SEM, zeta potential and contact angle were applied to analyze the chemical composition and morphology of as-prepared membranes. The effect of intercalated NH2-Fe3O4 nanoparticles on overall performance of the GO/NH2-Fe3O4 membranes was systematically investigated. The resulted membrane with 8 wt% of NH2-Fe3O4 loading has high water flux of up to 78 Lm−2 h−1, which is 4.8 times higher than that of pure GO membrane. Moreover, such membrane also displays high congo red rejection (94%) and low NaCl rejection (~15%), rendering the membranes promising for dye/salt mixtures separation.

This article concerns a novel auxiliary-model-based expectation maximization (EM) estimation method for Hammerstein systems with data loss by extending the EM method to estimate models with multiple parameter vectors. The novel EM method relaxes the requirements on an autoregression model with one parameter vector, interactively maximizes the expectation over multiple parameter vectors in a more general model, and uses the output of an auxiliary model to substitute the missing outputs in the information vector in iteration processes. A numerical simulation is employed to demonstrate the effectiveness of the proposed novel EM method.

Abstract Single-atom catalysts (SACs) have attracted tremendous research interests in various energy-related fields because of their high activity, selectivity and 100% atom utilization. However, it is still a challenge to enhance the intrinsic and specific activity of SACs. Herein, we present an approach to fabricate a high surface distribution density of iridium (Ir) SAC on nickel-iron sulfide nanosheet arrays substrate (Ir 1 /NFS), which delivers a high water oxidation activity. The Ir 1 /NFS catalyst offers a low overpotential of ~170 mV at a current density of 10 mA cm −2 and a high turnover frequency of 9.85 s −1 at an overpotential of 300 mV in 1.0 M KOH solution. At the same time, the Ir 1 /NFS catalyst exhibits a high stability performance, reaching a lifespan up to 350 hours at a current density of 100 mA cm −2 . First-principles calculations reveal that the electronic structures of Ir atoms are significantly regulated by the sulfide substrate, endowing an energetically favorable reaction pathway. This work represents a promising strategy to fabricate high surface distribution density single-atom catalysts with high activity and durability for electrochemical water splitting.

Developing new energy vehicles has been a worldwide consensus, and developing new energy vehicles characterized by pure electric drive has been China’s national strategy. After more than 20 years of high-quality development of China’s electric vehicles (EVs), a technological R & D layout of “Three Verticals and Three Horizontals” has been created, and technological advantages have been accumulated. As a result, China’s new energy vehicle market has ranked first in the world since 2015. To systematically solve the key problems of battery electric vehicles (BEVs) such as “driving range anxiety, long battery charging time, and driving safety hazards”, China took the lead in putting forward a “system engineering-based technology system architecture for BEVs” and clarifying its connotation. This paper analyzes the research status and progress of the three core components of this architecture, namely, “BEV platform, charging/swapping station, and real-time operation monitoring platform”, and their key technological points. The three major demonstration projects of the 2008 Beijing Olympic Games, the 2022 Beijing Winter Olympics, and the intelligent and connected autonomous battery electric bus project are discussed to specify the applications of BEVs in China. The key research directions for upgrading BEV technologies remain to be further improving the vehicle-level all-climate environmental adaptability and all-day safety of BEVs, systematically solving the charging problem of BEVs and improving their application convenience, and safeguarding safety with early warning and implementing active/passive safety protection for the whole life cycle of power batteries on the basis of BEVs’ operation big data. BEVs have acquired new technological features such as intelligent and networked technology empowerment, extensive integration of control-by-wire systems, a platform of chassis hardware, and modularization of functional software.

With the development of information technology, Internet-of-Things (IoT) and low-altitude remote-sensing technology represented by Unmanned Aerial Vehicles (UAVs) are widely used in environmental monitoring fields. In agricultural modernization, IoT and UAV can monitor the incidence of crop diseases and pests from the ground micro and air macro perspectives, respectively. IoT technology can collect real-time weather parameters of the crop growth by means of numerous inexpensive sensor nodes. While depending on spectral camera technology, UAVs can capture the images of farmland, and these images can be utilize for analyzing the occurrence of pests and diseases of crops. In this work, we attempt to design an agriculture framework for providing profound insights into the specific relationship between the occurrence of pests/diseases and weather parameters. Firstly, considering that most farms are usually located in remote areas and far away from infrastructure, making it hard to deploy agricultural IoT devices due to limited energy supplement, a sun tracker device is designed to adjust the angle automatically between the solar panel and the sunlight for improving the energy-harvesting rate. Secondly, for resolving the problem of short flight time of UAV, a flight mode is introduced to ensure the maximum utilization of wind force and prolong the fight time. Thirdly, the images captured by UAV are transmitted to the cloud data center for analyzing the degree of damage of pests and diseases based on spectrum analysis technology. Finally, the agriculture framework is deployed in the Yangtze River Zone of China and the results demonstrate that wheat is susceptible to disease when the temperature is between 14 °C and 16 °C, and high rainfall decreases the spread of wheat powdery mildew.

Bituminous coal is used widely for a variety of applications despite causing a range of problems within processes. The complexity and heterogeneity of the molecular structure of coal is one of the reasons for problems during use. Investigation into the molecular structure of the bituminous coal is reported from using X-ray diffraction (XRD), Raman spectroscopy, and Fourier Transform infrared (FTIR) spectroscopy experiments on four coal samples from coal mines in Northern China. The average lateral sizes (La), stacking heights (Lc) and interlayer spacing (d002) of the coal samples’ crystallite structures derived from the XRD ranged from 25.78 to 27.93 Å, 17.27 to 25.88 Å and 3.40 to 3.52 Å, respectively; and the G-D1, ID1/IG and La of the samples ranged from 245.06 to 249.63 cm−1, 2.18 to 2.48 and 18.16 to 20.64 Å, respectively. The FTIR spectra reveals that coal samples incorporate oxygen-containing functional groups, aliphatic functional groups, aromatic functional groups and hydroxyl functional groups. Results show these four coal samples contained a low degree of ordered microcrystalline units with a low degree of aromatic conformation. The samples have the largest proportion of oxygenated functional groups, followed by aromatic structures, aliphatic structures and hydroxyl groups. Results from this study could inform the ongoing study of molecular structural characteristics of bituminous coal as well as help our understanding of properties such as wettability and pore structure.

Electrochemical CO2 reduction (CO2R) is a sustainable way of producing carbon-neutral fuels, yet the efficiency is limited by its sluggish kinetics and complex reaction pathways. Developing active, selective, and stable CO2R electrocatalysts is challenging and entails intelligent material structure design and tailoring. Here we show a graphdiyne/graphene (GDY/G) heterostructure as a 2D conductive scaffold to anchor monodispersed cobalt phthalocyanine (CoPc) and reduce CO2 with an appreciable activity, selectivity, and durability. Advanced characterizations, e.g., synchrotron-based X-ray absorption spectroscopy (XAS), and density functional theory (DFT) calculation disclose that the strong electronic coupling between GDY and CoPc, together with the high surface area, abundant reactive centers, and electron conductivity provided by graphene, synergistically contribute to this distinguished electrocatalytic performance. Electrochemical measurements revealed a high FECO of 96% at a partial current density of 12 mA cm–2 in a H-cell and an FECO of 97% at 100 mA cm–2 in a liquid flow cell, along with a durability over 24 h. The per-site turnover frequency of CoPc reaches 37 s–1 at −1.0 V vs RHE, outperforming most of the reported phthalocyanine- and porphyrin-based electrocatalysts. The usage of the GDY/G heterostructure as a scaffold can be further extended to other organometallic complexes beyond CoPc. Our findings lend credence to the prospect of the GDY/G hybrid contributing to the design of single-molecule dispersed CO2R catalysts for sustainable energy conversion.

For the purpose of achieving excellent electromagnetic wave absorption performance, composition control and microstructure design of absorbers are crucial. Ti3C2Tx, transition metal carbides with remarkable conductivity and mechanical properties, are considered as common substrates to construct high-performance absorbers. In order to improve the impedance matching and enrich electromagnetic wave attenuation mechanism of single Ti3C2Tx substrate, transition metal sulfides (MoS2, NiS) with outstanding dielectric properties are introduced to fabricate the novel system of NiS/MoS2/Ti3C2Tx. Notably, this system has a unique multilayer-scale structure that spherical NiS particles are decorated on the multilayered Ti3C2Tx substrate and two-dimensional (2D) MoS2 nanosheets stack on the surface like scales. Under the synergistic effects of intense dielectric loss and multiple reflection, NiS/MoS2/Ti3C2Tx hybrid shows the wide effective absorption bandwidth (EAB) of 5.04 GHz at 2.1 mm and the minimum reflection loss (RLmin) of −58.48 dB at 2.4 mm. This work provides an innovative idea for the research of novel MXene-based absorbers.

In this work, a highly efficient uranium extraction method from water by the piezo catalytic reduction-oxidation process is reported by utilizing a hollow cubic shaped Zn2SnO4/SnO2 as piezo catalyst. The electrons and holes in Zn2SnO4/SnO2 are separated efficiently under the irradiation of ultrasound. After that, some of the piezo electrons reduce the adsorbed U(VI) to UO2, the others react with soluble oxygen to form H2O2, and oxidize UO2 to generate (UO2)O2∙2H2O, which could be efficiently separated from the solution. U(VI) piezo catalytic extraction rate could reach ~ 90% under the irradiation of ultrasonic waves (40 kHz, 120 W) within 5 h and only decreased by ~ 3% after four cycles. The present work advances piezo catalysis as a new route for uranium extraction from water, which may be applied in the extraction or removal of U(VI) in the U-containing wastewaters, providing new opportunities for resource-saving and environmental enhancement.

Ammonia (NH3) is an ideal carbon-free power source in the future sustainable hydrogen economy for growing energy demand. The electrochemical nitrate reduction reaction (NO3-RR) is a promising approach for nitrate removal and NH3 production at ambient conditions, but efficient electrocatalysts are lacking. Here, we present a metal-organic framework (MOF)-derived cobalt-doped Fe@Fe2O3 (Co-Fe@Fe2O3) NO3-RR catalyst for electrochemical energy production. This catalyst has a nitrate removal capacity of 100.8 mg N gcat-1 h-1 and an ammonium selectivity of 99.0 ± 0.1%, which was the highest among all reported research. In addition, NH3 was produced at a rate of 1,505.9 μg h-1 cm-2, and the maximum faradaic efficiency was 85.2 ± 0.6%. Experimental and computational results reveal that the high performance of Co-Fe@Fe2O3 results from cobalt doping, which tunes the Fe d-band center, enabling the adsorption energies for intermediates to be modulated and suppressing hydrogen production. Thus, this study provides a strategy in the design of electrocatalysts in electrochemical nitrate reduction.

Although transitional metal dichalcogenides have been regarded as appealing electrodes for sodium/potassium-ion batteries (SIBs/PIBs) owing to their high theoretical capacity, it is a key challenge to realize dichalcogenide anodes with long-period cycling performance and high-rate capability because of their poor conductivity and large volumetric change. Herein, polypyrrole-encapsulated VSe2 nanoplates (VSe2@PPy) were prepared by the selenization of VOOH hollow nanospheres and subsequent in situ polymerization and coating by pyrrole. Benefiting from the inherent metallicity of VSe2, the improvement in the conductivity and the structural protection provided by the PPy layer, the VSe2@PPy nanoplates exhibited enhanced sodium/potassium-storage performances, delivering a superior rate capability with a capacity of 260.0 mA h g-1 at 10 A g-1 in SIBs and 148.6 mA h g-1 at 5 A g-1 in PIBs, as well as revealing an ultrastability in cycling of 324.6 mA h g-1 after 2800 cycles at 4 A g-1 in SIBs. Moreover, the insertion and conversion mechanisms of VSe2@PPy in SIBs with intermediates of Na0.6VSe2, NaVSe2, and VSe were elucidated by in situ/ex situ X-ray diffraction combined with ex situ transmission electron microscopy observation and in situ potentio-electrochemical impedance spectroscopy during the sodiation and desodiation processes. Density functional theory calculations show that the strong coupling between VSe2 and PPy not only causes it to have a stronger total density of states and a built-in electric field, leading to an increased electrical conductivity, but also effectively decreases the ion diffusion barrier.

Colorectal cancer (CRC) has a high mortality rate and poor prognosis. Despite chemotherapeutic agents such as cisplatin, which has achieved a better prognosis and survival rate against cancer, drug resistance leads to significant challenges. Accumulating evidence suggests that YTHDF1, the N6-methyladenosine (m6A) “reader,” is an important regulator in tumor progresses. Herein, we report that YTHDF1 was significantly upregulated in human colon tumors and cell lines. Overexpression of YTHDF1 decreased the cisplatin sensitivity of colon cancer cells. From the established cisplatin-resistant CRC cell line (LoVo CDDP R), we detected that YTHDF1 was significantly upregulated in cisplatin-resistant CRC cells. Intriguingly, RNA sequencing (RNA-seq) results revealed that glutamine metabolism enzymes were clearly upregulated in LoVo CDDP R cells. Glutamine uptake, that is, glutaminase (GLS) activity, was upregulated in LoVo CDDP R cells. Furthermore, bioinformatics analysis indicated that the 3′ UTR of GLS1 contained a putative binding motif of YTHDF1, and an interaction was further validated by a protein-RNA interaction assay (RNA immunoprecipitation [RIP]). Furthermore, we demonstrated that YTHDF1 promoted protein synthesis of GLS1. Inhibiting GLS1 effectively synergizes with cisplatin to induce colon cancer cell death. Finally, that YTHDF1 mediated cisplatin through the GLS1-glutamine metabolism axis was validated by an in vivo xenograft mouse model. In summary, our study reveals a new mechanism for YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers. Colorectal cancer (CRC) has a high mortality rate and poor prognosis. Despite chemotherapeutic agents such as cisplatin, which has achieved a better prognosis and survival rate against cancer, drug resistance leads to significant challenges. Accumulating evidence suggests that YTHDF1, the N6-methyladenosine (m6A) “reader,” is an important regulator in tumor progresses. Herein, we report that YTHDF1 was significantly upregulated in human colon tumors and cell lines. Overexpression of YTHDF1 decreased the cisplatin sensitivity of colon cancer cells. From the established cisplatin-resistant CRC cell line (LoVo CDDP R), we detected that YTHDF1 was significantly upregulated in cisplatin-resistant CRC cells. Intriguingly, RNA sequencing (RNA-seq) results revealed that glutamine metabolism enzymes were clearly upregulated in LoVo CDDP R cells. Glutamine uptake, that is, glutaminase (GLS) activity, was upregulated in LoVo CDDP R cells. Furthermore, bioinformatics analysis indicated that the 3′ UTR of GLS1 contained a putative binding motif of YTHDF1, and an interaction was further validated by a protein-RNA interaction assay (RNA immunoprecipitation [RIP]). Furthermore, we demonstrated that YTHDF1 promoted protein synthesis of GLS1. Inhibiting GLS1 effectively synergizes with cisplatin to induce colon cancer cell death. Finally, that YTHDF1 mediated cisplatin through the GLS1-glutamine metabolism axis was validated by an in vivo xenograft mouse model. In summary, our study reveals a new mechanism for YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers.

Antioxidant treatment strategy by scavenging reactive oxygen species (ROS) is a highly effective disease treatment option. Nanozymes with multiple antioxidant activities can cope with the diverse ROS environment. However, lack of design strategies and limitation of negative correlation for nanozymes with multiple antioxidant activities hindered their development. To overcome these difficulties, here we used ZnMn2 O4 as a model to explore the role of Mn valency at the octahedral site via a valence-engineered strategy, and found that its multiple antioxidant activities are positively correlated with the content of Mn4+ . Therefore, through this strategy, a self-cascading antioxidant nanozyme LiMn2 O4 was constructed, and its efficacy was verified at the cellular level and in an inflammatory bowel disease model. This work not only provides guidance for the design of multiple antioxidant nanozymes, but also broadens the biomedical application potential of multiple antioxidant nanozymes.

The clinical treatment of chronic wounds caused by different pathophysiological ulcers like diabetic ulcers still remains a bottleneck. Although numerous approaches have been designed and developed, their therapeutic effects cannot meet the medical needs due to the complicated pathological microenvironment and restricted regenerative capacity of hard-healing chronic wounds. In this study, novel bi-layered and multifunctional dressing patches constructed with one layer of electrospun methacrylated gelatin (MeGel)/poly (L-lactic acid) (PLLA) radially-oriented nanofiber mats (RNMs) and one layer of Salvia miltiorrhiza Bunge-Radix Puerariae herbal compound (SRHC)-loaded MeGel hydrogel were designed to promote the closure and healing of diabetic wounds. An innovative electrospinning method was firstly designed and implemented to generate MeGel/PLLA RNMs, which were demonstrated to be a more appropriate nanofiber pattern for effectively guiding migration and promoting proliferation of human dermal fibroblasts (HDFs) compared with the conventional electrospun MeGel/PLLA haphazardly-oriented nanofiber mats (HNMs) and MeGel/PLLA uniaxially-oriented nanofiber mats (UNMs). Importantly, the in vivo mice acute full-thickness defect models also confirmed that MeGel/PLLA RNMs could significantly promote the cell migration and accelerate the healing rate throughout providing the cell recruitment and regulation abilities in comparison with MeGel/PLLA HNMs and UNMs. The MeGel hydrogel precursors loaded with different concentrations of SRHC were employed to generate the hydrogel layers on the MeGel/PLLA RNMs, and therefore a series of bi-layered wound dressing patches with integrated multifunctional properties were fabricated. All the bi-layered wound dressing patches with or without SRHC showed excellent hemostatic performances. The bi-layered dressing patches containing SRHC exhibited great antibacterial property to both E. coli and S. aureus, and also high cell survival rate to HDFs. For the in vivo full-thickness diabetic wound healing test, the bi-layered dressing patches without SRHC exhibited a faster wound healing rate compared with the medical gauzes. Furthermore, the 10% SRHC loaded bi-layered dressing patches significantly accelerated the high-quality regeneration and healing of diabetic wounds by effectively reducing the inflammation, promoting the vascularization, and facilitating the regeneration of hair follicles. Specifically, the 10% SRHC loaded bi-layered dressing patches presented a high healing area of 97.4 ± 2.8% at day 18 after surgery. Our present study demonstrated that the SRHC contained bi-layered dressing patches show great potential for the treatment of hard-healing diabetic wounds.

Metal-organic framework-derived composites have been widely used in electromagnetic wave (EMW) absorption, but the traditional synthetic strategy greatly limits the structure and species of MOFs. This research provided a solvent-free method to synthesize Co-MOF and its derivatives. Using CoSnO3 as the precursor, the preparation of Co-MOF is achieved by bridging the cobalt (II) ion of CoSnO3 and the 2-methylimidazole skeleton. The CoSn/N-doped carbon (CoSn/NC) composites derived from CoSnO3-MOF (Co-MOF with CoSnO3 as Co source) retain the original morphology of CoSnO3. Besides, the polarization effect produced by the N-doped carbon layers also benefits the excellent EMW absorption performance of the CoSn/NC composites. It is reflected in the minimum reflection loss (RL) of -48.2 dB at 2.2 mm and the effective bandwidth (EBA) of 5.84 GHz. This work provides a new channel to the construction of Co-MOFs, which could be extended to other Co-based oxides and vastly expand the species of MOFs based on metallic Co.

For the simultaneous photocatalytic reduction of hexavalent chromium (Cr(VI)) and the degradation of rhodamine B (RhB), directional charge-transfer channels and efficient separation of photogenerated holes and electrons are important. Herein, a Z-scheme heterojunction photocatalyst, protonated g-C3N4/BiVO4 decorated with wood flour biochar (pCN/WFB/BiVO4), was prepared through a hydrothermal reaction and electrostatic self-assembly for Cr(VI) photoreduction and RhB photodegradation. The morphological features, crystalline structure, chemical composition, optical properties, specific surface area, and photoelectrochemical properties of the prepared samples were investigated. The pCN/WFB/BiVO4 photocatalyst exhibited superior removal performance when used to remove Cr(VI) and RhB separately or RhB-Cr(VI) system. The biochar bridge served as a charge-transfer channel between two semiconductors, and the electrons in protonated g-C3N4 (pCN) and BiVO4 achieved a charge balance. This led to the formation of a Z-scheme heterojunction, fast photogenerated charge separation, and a powerful redox ability. The pCN/WFB/BiVO4 photocatalyst provides new insight into the mechanisms responsible for boosting multicomponent photocatalytic reactions, while constituting a promising candidate for wastewater treatment.

Designing highly active and more durable oxygen electrocatalysts for regenerative metal-air batteries and water splitting is of practical significance. Herein, an advanced Co/N-C-800 catalyst composed of abundant Co-Nx structures and carbon defects derived from cobalt phthalocyanine is synthesized. Remarkably, this catalyst exhibits favorable catalytic performance toward the oxygen evolution reaction (OER) with a receivable overpotential of 274 mV in an alkaline medium achieving a current density of 10 mA cm-2 and a Tafel slope of 43.6 mV decade-1, outperforming the commercial RuO2 catalyst. It further displays a high half-wave potential (0.82 V) for the oxygen reduction reaction in 0.1 M KOH. Theoretical calculations reveal that the Co-Nx active sites along with the carbon defects can decrease the adsorption energy of intermediates (OH*, O*, and OOH*) and enhance the electron-transfer ability, thus boosting the OER process.

Autonomous underwater vehicles (AUVs) have broad applications owing to their small size, low weight, strong ability to operate autonomously, and ability to replace humans in dangerous operations. AUV motion control systems can ensure stable operation in complex ocean environments and have attracted significant research attention in marine science and technology. The main difficulties with AUV motion control include the large uncertainties of dynamic and hydrodynamic characteristics and time delay of the signal transmission channel. In this study, we propose a robust fractional-order proportional–integral–derivative (FOPID) controller design for an AUV yaw control system. First, a three-dimensional stability region analysis method is proposed to achieve fractional orders. Unlike other stability region analysis methods, the proposed method is supported by theory instead of observation. Then, the other parameters are optimized according to the robust design specifications with respect to the parameter uncertainties. Therefore, the controlled system can tolerate different parameter uncertainties and fulfill transient performance specifications while maintaining system stability. The simulation results illustrate the superior robustness and transient performance of the proposed control algorithm.

Efficient n = O bond activation is crucial for the catalytic reduction of nitrogen compounds, which is highly affected by the construction of active centers. In this study, n = O bond activation was achieved by a single-atom catalyst (SAC) with phosphorus anchored on a Co active center to form intermediate N -species for further hydrogenation and reduction. Unique phosphorus-doped discontinuous active sites exhibit better n = O activation performance than conventional N -cooperated single-atom sites, with a high Faradic efficiency of 92.0% and a maximum ammonia yield rate of 433.3 μg NH4·h −1 ·cm −2 . This approach of constructing environmental sites through heteroatom modification significantly improves atom efficiency and will guide the design of future functional SACs with wide-ranging applications.

In this work, the centrosymmetry of Bi 2 S 3 nanorods is broken due to the introduction of large quantities of S i defects in the crystal lattice, which then endows the Bi 2 S 3 nanorods with the ability to efficiently reduce Cr(VI) by piezocatalysis. Most importantly, the piezocatalytic reduction could be significantly boosted by applying an alternating magnetic field (AMF). The AMF coupled piezocatalysis is achieved by H 2 O 2 and·O 2 - . AMF is found to facilitate the separation of electrons and holes due to the magnetoresistance effect of Bi 2 S 3 nanorods, thus remarkably enhancing the piezocatalysis by largely increasing the generation of H 2 O 2 . This work paves a new way for inducing the piezoelectricity of centrosymmetric materials by introducing defects and improving their catalytic activity through AMF, which has a great application potential in energy and environment fields. • Bi 2 S 3 nanorods were endowed with piezocatalytic performance due to the symmetry breaking effect. • Cr(VI) is highly efficient reduced to Cr(III) of the piezocatalysis. • The piezocatalysis is greatly boosted by applying an alternating magnetic field. • H 2 O 2 and·O 2 - were found to be generated and reduce Cr(VI) while pieozcatalysis.

Currently, understanding the structure and function of the microbial community is the key step in artificially constructing microbial communities to control soil heavy metal pollution. Abundant/rare microbial communities play different roles in different levels of concentrations. However, the correlation between heavy metals and rare/abundant subgroups is poorly understood. In this study, we used a metagenomics approach to comprehensively investigate the evolutionary changes in microbial diversity, structure, and function under different heavy metal concentration stress in soils surrounding gold tailings. The results show that the main pollutants were Pb, As, and Zn. Indigenous microorganisms have different responses to heavy metal concentrations. Bacteria are the main components of indigenous microorganisms, mainly including Actinobacteria, Proteobacteria, Chloroflexi, and Acidobacteria. With the increase of heavy metal pollution, the relative abundance of Proteobacteria increased, and that of Actinobacteria decreased. Archaea was significantly inhibited by heavy metal stress and was more sensitive to heavy metal concentration. The response of fungi to heavy metal concentration was not obvious. The results of KEGG pathways showed that carbon fixation was inhibited with increasing heavy metal concentrations, while nitrogen metabolism was in contrast. Abundant subcommunity had a greater correlation mainly with metal resistance mechanisms, and rare subcommunity plays a key role for soil nutrient cycling such as N, S cycling in soils contaminated. Overall, this study provides a comprehensive analysis of the effects of heavy metal stress at different concentrations on microorganisms in farmland around gold tailings and reveals the relationship between heavy metals on KEGG pathways.

The alkyl linker-based self-assembled monolayer (SAM) has emerged as an efficient hole-selective contact (HSC) for inverted perovskite solar cells (PSCs). Despite being effective in hole-extraction and interfacial passivation, its hole-transporting capability is limited by the insulating alkyl linker, along with poor stability due to the isolated and nonconjugated electron-rich moiety. Here, we report a series of conjugated SAMs that exhibit excellent photo- and electrical stabilities. The conjugated molecular structure not only enhances charge transport but also stabilizes the electron-rich arylamines through electron/charge delocalization. Moreover, it enables convenient modulation of frontier orbital energy levels for interfacial band alignment. By scrutinization of the conjugation-linker and hole-transporting head, an optimal conjugated SAM (MPA-Ph-CA) in combination with the standard triple cation perovskite Cs0.05(FA0.92MA0.08)0.95Pb(I0.92Br0.08)3 achieved an efficient inverted PSC with a power conversion efficiency (PCE) of 22.53% (certified 22.12%). Moreover, the MPA-Ph-CA based devices showed excellent stability, retaining over 95% of their initial PCEs under one sun constant irradiation for 800 h. The synchronously enhanced efficiency and stability suggest that conjugated SAM-based HSCs are promising for further advancing inverted PSCs.

Inverted perovskite solar cells still suffer from significant non-radiative recombination losses at the perovskite surface and across the perovskite/C60 interface, limiting the future development of perovskite-based single- and multi-junction photovoltaics. Therefore, more effective inter- or transport layers are urgently required. To tackle these recombination losses, we introduce ortho-carborane as an interlayer material that has a spherical molecular structure and a three-dimensional aromaticity. Based on a variety of experimental techniques, we show that ortho-carborane decorated with phenylamino groups effectively passivates the perovskite surface and essentially eliminates the non-radiative recombination loss across the perovskite/C60 interface with high thermal stability. We further demonstrate the potential of carborane as an electron transport material, facilitating electron extraction while blocking holes from the interface. The resulting inverted perovskite solar cells deliver a power conversion efficiency of over 23% with a low non-radiative voltage loss of 110 mV, and retain >97% of the initial efficiency after 400 h of maximum power point tracking. Overall, the designed carborane based interlayer simultaneously enables passivation, electron-transport and hole-blocking and paves the way toward more efficient and stable perovskite solar cells.

In this article, a multi-underwater unmanned vehicle (UUV) maneuvering decision-making algorithm is proposed for a counter-game with a dynamic target scenario. The game is modeled with interval-valued intuitionistic fuzzy rules, and an optimal maneuvering strategy is realized using a fractional-order recurrent neural network (RNN). First, underwater environments with weak connectivity, underwater noise, and dynamic uncertainties are analyzed and incorporated into the interval-valued intuitionistic fuzzy set. Then, the maneuvering decision-making model and the expected return of the multi-UUV countermeasure are designed based on the interval-valued intuitionistic fuzzy rules. Subsequently, to optimize the counter-game maneuvering strategy, a fractional-order RNN is formulated based on the Karush-Kuhn-Tucker optimality conditions. In addition, the existence and uniqueness of the optimal maneuvering solutions as well as the stability of the equilibrium point are discussed. Finally, simulation and experimental results are compared to determine the effectiveness of the proposed algorithm. The influence of the fractional order on the convergence rate and optimization error of the proposed algorithm is also minutely examined.

The development of wearable multifunctional electromagnetic protective fabrics with multifunctional, low cost, and high efficiency remains a challenge. Here, inspired by the unique flower branch shape of "Thunberg's meadowsweet" in nature, a nanofibrous composite membrane with hierarchical structure was constructed. Integrating sophisticated 0D@2D@1D hierarchical structures with multiple heterointerfaces can fully unleash the multifunctional application potential of composite membrane. The targeted induction method was used to precisely regulate the formation site and morphology of the metal-organic framework precursor, and intelligently integrate multiple heterostructures to enhance dielectric polarization, which improves the impedance matching and loss mechanisms of the electromagnetic wave absorbing materials. Due to the synergistic enhancement of electrospinning-derived carbon nanofiber "stems", MOF-derived carbon nanosheet "petals" and transition metal selenide nano-particle "stamens", the CoxSey/NiSe@CNSs@CNFs (CNCC) composite membrane obtains a minimum reflection loss value (RLmin) of -68.40 dB at 2.6 mm and a maximum effective absorption bandwidth (EAB) of 8.88 GHz at a thin thickness of 2.0 mm with a filling amount of only 5 wt%. In addition, the multi-component and hierarchical heterostructure endow the fibrous membrane with excellent flexibility, water resistance, thermal management, and other multifunctional properties. This work provides unique perspectives for the precise design and rational application of multifunctional fabrics.

The hot electrons in carbon-based materials exhibit interesting ballistic transport behaviors for designing high-performance single-electron transistors. However, the cooling of such hot electrons back to the equilibrium state may be slowed down by the excessively populated optical phonons, thus limiting their ballistic transport. Therefore, a thorough understanding of the coupling between hot electrons and optical phonons is of critical importance. Here, by varying the thickness of a multilayer graphene film on a supporting substrate, we investigated the competition pathways of the energy relaxation of the photoinduced hot electrons through coupling with the optical, surface, and acoustic phonons. The difference in the τ2 values indicates that thickness plays an important role in the optical phonon population. For the multilayer graphene film thickness less than 3 nm, the super-collision model describes the hot electron cooling dynamics that is strongly affected by the surface phonons from the supporting substrate. As the multilayer graphene film thickness increases from 3 to 20 nm, the accumulation of the optical phonons induces a hot optical phonon effect, resulting in a bottleneck of cooling of the hot electrons. As the multilayer graphene film thickness further increases from 20 to 40 nm, a direct coupling between the hot electrons and acoustic phonons starts to dominate. The surface states of the interfaces at the inner layers of the multilayer graphene film contribute to this direct coupling as an additional cooling channel. The quantitative understanding of the energy relaxation pathways of the hot electrons offers insights into designing high-performance single-electron transistors.

This paper proposes a selective kernel convolution deep residual network based on the channel-spatial attention mechanism and feature fusion for mechanical fault diagnosis. First, adjacent channel attention modules are connected with the spatial attention mechanism module, then all channel features and spatial features are fused and a channel-spatial attention mechanism is constructed to form the feature enhancement module. Second, the feature enhancement module is embedded in a series model based on selective kernel convolution and deep residual network and combined with multi-layer feature fusion information. The model can more effectively extract fault features from the vibration signal, compared with traditional deep learning methods, and the fault recognition efficiency is improved. Finally, the proposed method was used to experimentally diagnose bearing and gear faults, and identification accuracies of 99.87% and 97.77%, respectively, were achieved. Compared with similar algorithms, the proposed method has higher fault identification ability, thereby demonstrating the advantages of the channel-spatial attention mechanism network. In addition, the accuracy and robustness of the model were verified.

Global microplastic (MP) pollution is a serious environmental problem that has been found in various ecosystems, especially marine ecosystems. In this study, the water (surface, middle and bottom water), sediment and fish (pelagic, demersal and benthic fish) in the artificial reef area and adjacent waters in Haizhou Bay were collected, and the mechanism of MP transmission among the three media was analyzed. The results showed that >96 % of the plastics in the region were MPs. The shape of MPs was mainly fibrous (water (73.3 %), sediment (56 %), fish (95.3 %)), color was mainly blue (water (49.3 %), sediment (47 %), fish (72.3 %)), and the material was mainly PET (water (39.6 %), sediment (33 %), fish (86.6 %)). We found that, except for the natural deposition of MPs, MPs could be ingested by pelagic fish and transmitted through vertical movement in the water, while there was an interaction between MPs in benthic fishes and the middle-bottom waters. In addition, as relevant variables, body length and body weight were more likely to explain the number of MPs ingested by fishes than were δ13C and δ15N. Therefore, based on the linear relationship between δ15N and body length, we concluded that there was a weak trophic magnification effect of MPs ingested by fish in this region. This study provides unique information for further exploring the factors influencing the spatial distribution of MPs and the transmission mechanism of MPs in fish.

The release of wastewaters containing relatively low levels of nitrate (NO 3 − ) results in sufficient contamination to induce harmful algal blooms and to elevate drinking water NO 3 − concentrations to potentially hazardous levels. In particular, the facile triggering of algal blooms by ultra-low concentrations of NO 3 − necessitates the development of efficient methods for NO 3 − destruction. However, promising electrochemical methods suffer from weak mass transport under low reactant concentrations, resulting in long treatment times (on the order of hours) for complete NO 3 − destruction. In this study, we present flow-through electrofiltration via an electrified membrane incorporating nonprecious metal single-atom catalysts for NO 3 − reduction activity enhancement and selectivity modification, achieving near-complete removal of ultra-low concentration NO 3 − (10 mg-N L −1 ) with a residence time of only a few seconds (10 s). By anchoring Cu single atoms supported on N-doped carbon in a carbon nanotube interwoven framework, we fabricate a free-standing carbonaceous membrane featuring high conductivity, permeability, and flexibility. The membrane achieves over 97% NO 3 − removal with high N 2 selectivity of 86% in a single-pass electrofiltration, which is a significant improvement over flow-by operation (30% NO 3 − removal with 7% N 2 selectivity). This high NO 3 − reduction performance is attributed to the greater adsorption and transport of nitric oxide under high molecular collision frequency coupled with a balanced supply of atomic hydrogen through H 2 dissociation during electrofiltration. Overall, our findings provide a paradigm of applying a flow-through electrified membrane incorporating single-atom catalysts to improve the rate and selectivity of NO 3 − reduction for efficient water purification.

Four piperazine-amide-bridged d10 metal-organic coordination polymers, namely, [Zn(L)0.5(1,3-BDC)∙H2O]∙H2O (1), [Cd(L)(1,3-BDC)] (2), [Zn(L)0.5(5-MIP) ∙H2O]·H2O (3), [Cd(L)(5-MIP)] (4) were synthesized by the L ligand [N, N'-bis[(3-pyridin)acrylophenone] piperazine (L)] and two carboxylic acids with Zn/Cd(II) chloride under hydrothermal conditions. The title complexes were characterized by IR spectroscopy, powder X-ray diffraction and single-crystal X-ray diffraction. Complex 1 is a 1D ladder-like structure. Complex 2 is a 3D NaCl type framework. Complexes 3 and 4 are 63 and 44 connected 2D structures. The different structural details of the title complexes directed by caroxylates and the central metals were compared. The complexes 1–4 can be used as excellent fluorescent sensors toward nitrophenol (NOP) and nitroaniline (NA) with a low limit of detection and a high quenching constant, and have good anti-interference and recyclable characteristics. The feasibility of actual sample detection was verified by tap water, river water and wastewater samples. Taking complex 3 as an example, the mechanism was also explored by fluorescence lifetime experiment and the UV-visible absorption spectroscopy. The 3-modified visual detection cloth and test paper were also prepared by solid phase deposition method.

In this study, accumulated fermentable sugars from biosaccharified corn straw were used to generate methane through anaerobic digestion (AD). The results showed that reducing sugars from biosaccharification expanded corn straw (BECS) treated with Clostridium thermocellum XF811 accumulated with yields of 94.9 mg/g. The BECS used for AD was converted into a high methane yield (7436 mL), which was 49.3 % higher than that of expanded corn straw (ECS). High-throughput microbial analysis suggested that Methanoculleus and Methanobacterium greatly contributed to the high methane yield. Industrial experiments demonstrated that the methane production from BECS by AD was 72,955 m3, which increased by 13.2 % compared to that from ECS. Biosaccharification pretreatment accelerated ECS destruction and accumulated sugars, thereby increasing methane yields. This study provides a strategy for producing clean energy from lignocellulose biomass.

Lead halide perovskites show great potential to be used in wearable optoelectronics. However, obstacles for real applications lie in their instability under light, moisture and temperature stress, noxious lead ions leakage and difficulties in fabricating uniform luminescent textiles at large scale and high production rates. Overcoming these obstacles, we report simple, high-throughput electrospinning of large-area (> 375 cm2) flexible perovskite luminescent textiles woven by ultra-stable polymer@perovskite@cyclodextrin@silane composite fibers. These textiles exhibit bright and narrow-band photoluminescence (a photoluminescence quantum yield of 49.7%, full-width at half-maximum <17 nm) and the time to reach 50% photoluminescence of 14,193 h under ambient conditions, showcasing good stability against water immersion (> 3300 h), ultraviolet irradiation, high temperatures (up to 250 °C) and pressure surge (up to 30 MPa). The waterproof PLTs withstood fierce water scouring without any detectable leaching of lead ions. These low-cost and scalable woven PLTs enable breakthrough application in marine rescue.

Silicon-based complementary metal oxide semiconductor (CMOS) devices have dominated the technological revolution in the past decades. With increasing demands in machine vision, autonomous driving, and artificial intelligence, silicon CMOS imagers, as the major optical information input devices, face great challenges in spectral sensing ranges. In this paper, we demonstrate the development of CMOS-compatible infrared colloidal quantum-dot (CQD) imagers in the broadband short-wave and mid-wave infrared ranges (SWIR and MWIR, 1.5–5 μm). A new device architecture of trapping-mode detectors is proposed, fabricated, and demonstrated with lowered darkcurrents and improved responsivity. The CMOS-compatible fabrication process is completed with two-step sequential spin-coating processes of intrinsic and doped HgTe CQDs on an 8 in. CMOS readout wafer with photoresponse non-uniformity (PRNU) down to 4%, dead pixel rate of 0%, external quantum efficiency up to 175%, and detectivity as high as 2 × 1011 Jones for extended SWIR at 300 K and 8 × 1010 Jones for MWIR at 80 K. Both SWIR images and MWIR thermal images are demonstrated with great potential for semiconductor inspection, chemical identification, and temperature monitoring.

In this study, the advantages of laser texturing and micro-arc oxidation were combined to prepare an antiwear coating with a graded structure to improve the antiwear properties of titanium alloys. The morphology, structure, and composition of the coating were characterized by 3D surface profiler, SEM, EDS, and XRD, respectively. The antiwear properties and wear reduction effect of the composite coating were analyzed by using friction coefficient, wear rate, and wear scars. The results indicated that the micro-arc oxide coating consisted mainly of anatase and rutile, and higher proportions of rutile were detected in the laser texture composite micro-arc oxide (LT/MAO) coatings. The main elements of the micro-arc oxidation coating were Si, Ti, and O. Laser texturing can significantly reduce wear rates and improve the antiwear properties of the micro-arc oxidation coating. Compared with the untextured micro-arc oxidation coating, the wear rate and average friction coefficient of the LT/MAO coating were reduced by 26 % and 28 %, which were 0.262 × 10−6 mm3·N−1·m−1 and 0.23, respectively. Meanwhile, the LT/MAO coating exhibits longer life under extended wear. In the later stages of wear, the coating debris from the inner edge of the microgroove floated to the upper surface forming secondary lubrication and extending the protective effect of the micro-arc oxidation coating on the substrate.

Weeds are mainly spread by weed seeds being mixed with agricultural and forestry crop seeds, grain, animal hair, and other plant products, and disturb the growing environment of target plants such as crops and wild native plants. The accurate and efficient classification of weed seeds is important for the effective management and control of weeds. However, classification remains mainly dependent on destructive sampling-based manual inspection, which has a high cost and rather low flux. We considered that this problem could be solved using a nondestructive intelligent image recognition method. First, on the basis of the establishment of the image acquisition system for weed seeds, images of single weed seeds were rapidly and completely segmented, and a total of 47 696 samples of 140 species of weed seeds and foreign materials remained. Then, six popular and novel deep Convolutional Neural Network (CNN) models are compared to identify the best method for intelligently identifying 140 species of weed seeds. Of these samples, 33 600 samples are randomly selected as the training dataset for model training, and the remaining 14 096 samples are used as the testing dataset for model testing. AlexNet and GoogLeNet emerged from the quantitative evaluation as the best methods. AlexNet has strong classification accuracy and efficiency (low time consumption), and GoogLeNet has the best classification accuracy. A suitable CNN model for weed seed classification could be selected according to specific identification accuracy requirements and time costs of applications. This research is beneficial for developing a detection system for weed seeds in various applications. The resolution of taxonomic issues and problems associated with the identification of these weed seeds may allow for more effective management and control.

Abstract Artificial perception technologies capable of sensing and feeling mechanical stimuli like human skins are critical enablers for electronic skins (E‐Skins) needed to achieve artificial intelligence. However, most of the reported electronic skin systems lack the capability to process and interpret the sensor data. Herein, a new design of artificial perceptual system integrating ZnO‐based synaptic devices with Pt/carbon nanofibers‐based strain sensors for stimuli detection and information processing is presented. Benefiting from the controllable ion migration after indium doping, the device can emulate various essential functions, such as short‐term/long‐term plasticity, paired‐pulse facilitation, excitatory post‐synaptic current, and synaptic plasticity depending on the number, frequency, amplitude, and width of the applied pulses. The Pt/carbon nanofibers‐based strain sensors can detect subtle human motion and convert mechanical stimuli into electrical signals, which are further processed by the ZnO devices. By attaching the integrated devices to finger joints, it is demonstrated that they can recognize handwriting and gestures with a high accuracy. This work offers new insights in designing artificial synapses and sensors to process and recognize information for neuromorphic computing and artificial intelligence applications.

Lignin is the most abundant aromatic polymer from the natural and renewable lignocellulosic biomass resource. Developing highly efficient catalysts for lignin depolymerization to produce valuable monophenols with high yield and selectivity remains a desirable but challenging target in this field. Here, we design a synergistic catalyst combining atomically dispersed Mo centers and Al Lewis acid sites on a MgO substrate (Mo1Al/MgO) for the depolymerization of Eucalyptus lignin via the β-aryl ether bond cleavage. A near-theoretical monophenol yield of 46% with an ultrahigh selectivity of 92% for coniferyl and sinapyl methyl ether, as well as good cycling durability, was achieved simultaneously by Mo1Al/MgO in an inert N2 atmosphere. First-principles calculations and control catalytic experiments confirmed the synergistic catalysis mechanism between Mo1-O5 single-atom centers and the neighboring Al Lewis acid sites with the participation of a methanol solvent. This study validates the feasibility of designing better-performing catalysts with synergistic multiactive sites for the efficient and selective disassembly of complex renewable biopolymers into highly value-added products with lower cost and greater security.

Solar steam generation (SSG) is a very promising desalination technology. However, new photothermal materials are still to be explored to further reduce the cost, and the device structure is still to be innovated to improve the structural integrality and evaporation performance. In this work, an all-in-one highly-efficient and self-floating jellyfish-like SSG (SFJ-SSG) is developed based on partially carbonized Enteromorpha (EA) aerogel (PCEAA). The carbonized top surface exhibits high solar absorption ability and excellent photothermal effect, while the uncarbonized EA retains the hydrophilicity and high-water transport capability due to the nature of tubular algal plant. Moreover, the heat produced by photothermal effect of the carbonized EA is confined at the top surface due to the thermal insulation of the uncarbonized layer, which is very beneficial for interfacial water evaporation. After optimizing the carbonization time and the height of the SFJ-SSG, a high evaporation rate of 1.87 kg m-2h−1 is obtained under 1.0 sun irradiation, which outcompetes most SSG based on carbonized biomass. The development of SFJ-SSG based on EA not only minimizes the cost of SSG, but also solves the EA pollution, ensuring the broad prospect in practical applications.

The size of silver nanoparticles (Ag NPs) and loading amount of Ag NPs onto their substrate/carrier are two key factors for their efficient applications. Herein, we present a facile method for in situ synthesizing ultrafine and highly loaded Ag NPs on the surface of tannin-coated catechol-formaldehyde resin (TA-CFR) nanospheres. TA-CFR nanospheres act as green and highly efficient reducing agents for converting silver ions (Ag+) into Ag NPs, and the size of resultant Ag NPs is only ∼ 7.5 nm, and the Ag NPs loading capacity of TA-CFR is as high as 61.5 wt%, both of which contribute to the very high specific surface area of Ag NPs. Consequently, the as-synthesized TA-CFR@Ag composites show high catalytic performance, and the catalytic rate for the reduction of 4-nitrophenol is almost 10 times higher than that of the control. Meanwhile, TA-CFR@Ag composites also possess high antibacterial activity, efficiently inhibiting the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, tannin coating (thickness: ∼ 15 nm) minimizes the aggregation of Ag NPs, and enhances the reusability and stability of resultant Ag NPs, because of their high surface charges (the zeta potential is up to -65.5 ± 1.9 mV) and strong coordination capability with Ag NPs. This work provides a new frontier to develop multifunctional nanomaterials focusing on the green catalyst synthesis and environmental-remedy applications.

Modern perception systems of autonomous vehicles are known to be sensitive to occlusions and lack the capability of long perceiving range. It has been one of the key bottlenecks that prevents Level 5 autonomy. Recent research has demonstrated that the Vehicle-to-Vehicle (V2V) cooperative perception system has great potential to revolutionize the autonomous driving industry. However, the lack of a real-world dataset hinders the progress of this field. To facilitate the development of cooperative perception, we present V2V4Real, the first large-scale real-world multi-modal dataset for V2V perception. The data is collected by two vehicles equipped with multi-modal sensors driving together through diverse scenarios. Our V2V4Real dataset covers a driving area of 410 km, comprising 20K LiDAR frames, 40K RGB frames, 240K annotated 3D bounding boxes for 5 classes, and HDMaps that cover all the driving routes. V2V4Real introduces three perception tasks, including cooperative 3D object detection, cooperative 3D object tracking, and Sim2Real domain adaptation for cooperative perception. We provide comprehensive benchmarks of recent cooperative perception algorithms on three tasks. The V2V4Real dataset can be found at research.seas.ucla.edu/mobility-lab/v2v4real/.

Existing self-supervised medical image segmentation usually encounters the domain shift problem (i.e., the input distribution of pre-training is different from that of fine-tuning) and/or the multimodality problem (i.e., it is based on single-modal data only and cannot utilize the fruitful multimodal information of medical images). To solve these problems, in this work, we propose multimodal contrastive domain sharing (Multi-ConDoS) generative adversarial networks to achieve effective multimodal contrastive self-supervised medical image segmentation. Compared to the existing self-supervised approaches, Multi-ConDoS has the following three advantages: (i) it utilizes multimodal medical images to learn more comprehensive object features via multimodal contrastive learning; (ii) domain translation is achieved by integrating the cyclic learning strategy of CycleGAN and the cross-domain translation loss of Pix2Pix; (iii) novel domain sharing layers are introduced to learn not only domain-specific but also domain-sharing information from the multimodal medical images. Extensive experiments on two publicly multimodal medical image segmentation datasets show that, with only 5% (resp., 10%) of labeled data, Multi-ConDoS not only greatly outperforms the state-of-the-art self-supervised and semi-supervised medical image segmentation baselines with the same ratio of labeled data, but also achieves similar (sometimes even better) performances as fully supervised segmentation methods with 50% (resp., 100%) of labeled data, which thus proves that our work can achieve superior segmentation performances with very low labeling workload. Furthermore, ablation studies prove that the above three improvements are all effective and essential for Multi-ConDoS to achieve this very superior performance.

Nitrite pollution poses a serious threat to human health and the environment. In this study, a reliable and selective electrochemical (EC) sensor was developed for the quantitative determination of nitrite by combining flower-like three-dimensional (3D) MoS2 microspheres with two-dimensional (2D) C3N4 nanosheets. Benefiting from the synergistic effects of MoS2 and C3N4, the 3D MoS2/2D C3N4 nanocomposite displayed numerous active sites, a 3D mesoporous structure, high conductivity and excellent catalytic activity. The 3D MoS2/2D C3N4-modified glassy carbon electrode (GCE) exhibited a superior electrocatalytic activity toward nitrite oxidation, with a wider linear detection range (0.1–1100 μM), a lower detection limit (LOD) (0.065 μM, S/N = 3), outstanding stability, remarkable reproducibility and strong selectivity. Furthermore, the nitrite EC sensor was successfully applied to detect actual food and environmental samples involving sausage, pickled vegetables, river water and tap water, thus demonstrating the potential of the prepared 3D MoS2/2D C3N4/GCE for food analysis and environmental monitoring.

It is a common spoof to use a photograph to fool face recognition algorithm. In light of differences in optical flow fields generated by movements of two-dimensional planes and three-dimensional objects, we proposed a new liveness detection method for face recognition. Under the assumption that the test region is a two-dimensional plane, we can obtain a reference field from the actual optical flow field data. Then the degree of differences between the two fields can be used to distinguish between a three-dimensional face and a two-dimensional photograph. Empirical study shows that the proposed approach is both feasible and effective.

Pathogenic mutations in the amyloid precursor protein (APP) gene have been described as causing early onset familial Alzheimer disease (AD). We recently identified a rare APP variant encoding an alanine-to-threonine substitution at residue 673 (A673T) that confers protection against development of AD (Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., Hoyte, K., Gustafson, A., Liu, Y., Lu, Y., Bhangale, T., Graham, R. R., Huttenlocher, J., Bjornsdottir, G., Andreassen, O. A., Jönsson, E. G., Palotie, A., Behrens, T. W., Magnusson, O. T., Kong, A., Thorsteinsdottir, U., Watts, R. J., and Stefansson, K. (2012) Nature 488, 96–99). The Ala-673 residue lies within the β-secretase recognition sequence and is part of the amyloid-β (Aβ) peptide cleavage product (position 2 of Aβ). We previously demonstrated that the A673T substitution makes APP a less favorable substrate for cleavage by BACE1. In follow-up studies, we confirm that A673T APP shows reduced cleavage by BACE1 in transfected mouse primary neurons and in isogenic human induced pluripotent stem cell-derived neurons. Using a biochemical approach, we show that the A673T substitution modulates the catalytic turnover rate (Vmax) of APP by the BACE1 enzyme, without affecting the affinity (Km) of the APP substrate for BACE1. We also show a reduced level of Aβ(1–42) aggregation with A2T Aβ peptides, an observation not conserved in Aβ(1–40) peptides. When combined in a ratio of 1:9 Aβ(1–42)/Aβ(1–40) to mimic physiologically relevant mixtures, A2T retains a trend toward slowed aggregation kinetics. Microglial uptake of the mutant Aβ(1–42) peptides correlated with their aggregation level. Cytotoxicity of the mutant Aβ peptides was not dramatically altered. Taken together, our findings demonstrate that A673T, a protective allele of APP, reproducibly reduces amyloidogenic processing of APP and also mildly decreases Aβ aggregation. These effects could together have an additive or even synergistic impact on the risk of developing AD. Pathogenic mutations in the amyloid precursor protein (APP) gene have been described as causing early onset familial Alzheimer disease (AD). We recently identified a rare APP variant encoding an alanine-to-threonine substitution at residue 673 (A673T) that confers protection against development of AD (Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., Hoyte, K., Gustafson, A., Liu, Y., Lu, Y., Bhangale, T., Graham, R. R., Huttenlocher, J., Bjornsdottir, G., Andreassen, O. A., Jönsson, E. G., Palotie, A., Behrens, T. W., Magnusson, O. T., Kong, A., Thorsteinsdottir, U., Watts, R. J., and Stefansson, K. (2012) Nature 488, 96–99). The Ala-673 residue lies within the β-secretase recognition sequence and is part of the amyloid-β (Aβ) peptide cleavage product (position 2 of Aβ). We previously demonstrated that the A673T substitution makes APP a less favorable substrate for cleavage by BACE1. In follow-up studies, we confirm that A673T APP shows reduced cleavage by BACE1 in transfected mouse primary neurons and in isogenic human induced pluripotent stem cell-derived neurons. Using a biochemical approach, we show that the A673T substitution modulates the catalytic turnover rate (Vmax) of APP by the BACE1 enzyme, without affecting the affinity (Km) of the APP substrate for BACE1. We also show a reduced level of Aβ(1–42) aggregation with A2T Aβ peptides, an observation not conserved in Aβ(1–40) peptides. When combined in a ratio of 1:9 Aβ(1–42)/Aβ(1–40) to mimic physiologically relevant mixtures, A2T retains a trend toward slowed aggregation kinetics. Microglial uptake of the mutant Aβ(1–42) peptides correlated with their aggregation level. Cytotoxicity of the mutant Aβ peptides was not dramatically altered. Taken together, our findings demonstrate that A673T, a protective allele of APP, reproducibly reduces amyloidogenic processing of APP and also mildly decreases Aβ aggregation. These effects could together have an additive or even synergistic impact on the risk of developing AD.

NMDA receptors (NMDARs) are a major class of ionotropic glutamate receptors that can undergo activity-dependent changes in surface expression. Clathrin-mediated endocytosis is a mechanism by which the surface expression of NR2B-containing NMDA receptors is regulated. The C terminus of the NMDA receptor subunit NR2B contains the internalization motif YEKL, which is the binding site for the clathrin adaptor AP-2. The tyrosine (Y1472) within the YEKL motif is phosphorylated by the Src family of kinases and this phosphorylation inhibits the binding of AP-2 and promotes surface expression of NMDA receptors. Cdk5 is a serine/threonine kinase that has been implicated in synaptic plasticity, learning, and memory. Here we demonstrate that inhibition of Cdk5 results in increased phosphorylation of Y1472 NR2B at synapses and decreased binding of NR2B to beta2-adaptin, a subunit of AP-2, thus blocking the activity-dependent endocytosis of NMDA receptors. Furthermore, we show that inhibition of Cdk5 increases the binding of Src to postsynaptic density-95 (PSD-95), and that expression of PSD-95 facilitates the phosphorylation of Y1472 NR2B by Src. Together, these results suggest a model in which inhibition of Cdk5 increases the binding of Src to PSD-95 and the phosphorylation of Y1472 NR2B by Src, which results in decreased binding of NR2B to AP-2, and NR2B/NMDAR endocytosis. This study provides a novel molecular mechanism for the regulation of the surface expression of NR2B-containing NMDA receptors and gives insight into the Cdk5-dependent regulation of synaptic plasticity.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently identified to be caused by a novel bunyavirus (SFTSV). The clinical diagnosis is urgently needed to differentiate the disease from other infections. To develop a sensitive quantitative real-time RT-PCR assay for rapid detection of SFTSV viral RNA and evaluate potential use for clinical diagnosis of SFTS. Primers and probes were designed to target the L, M, and S segments of SFTSV, and standard curves were established based on serial dilutions of in vitro transcribed viral RNA or viral RNA extracts. The serum samples collected from 70 laboratory confirmed SFTS patients, 114 non-SFTS patients, and 400 healthy donors were analyzed. Based on three optimized primer–probe sets to detect L, M, S genes of SFTSV, the quantitative real-time RT-PCR assay could discriminate SFTSV infection from other vector-borne viral diseases in human with potential detection limit of 10 viral RNA copies/μl or 10 TCID50/ml virus load. Strong linear correlations (r2 > 0.99) between the Ct values and viral RNA standards over a liner range were obtained. The assay specificity was determined by sequence alignment and experimentally tested on various related viruses. Evaluation of the study method with clinical serum samples showed 98.6% clinical diagnostic sensitivity and over 99% specificity. The quantitative real-time RT-PCR assay established in this study can be used as a reliable method for early diagnosis of SFTSV infection.

Pyrazinamide (PZA) is a frontline anti-tuberculosis drug that plays a crucial role in the treatment of both drug susceptible and multidrug-resistant tuberculosis (MDR-TB). Resistance to PZA is most commonly associated with mutations in the pncA gene encoding nicotinamidase/pyrazinamidase which converts the prodrug PZA to the active form pyrazinoic acid (POA). RpsA (ribosomal protein S1) involved in trans-translation was recently shown to be a target of PZA and mutations in RpsA are found in some PZA-resistant TB strains. However, some other PZA-resistant strains lack mutations in either pncA or rpsA. To identify potential new mechanisms of PZA resistance, we isolated 174 in vitro mutants of M. tuberculosis H37Rv resistant to PZA to search for resistant isolates that do not have pncA or rpsA mutations. DNA sequencing revealed that 169 of the 174 (97.1%) PZA-resistant mutants had pncA mutations but 5 mutants lacked pncA or rpsA mutations. Whole genome sequencing analyses revealed that the 5 PZA-resistant mutants had different mutations all occurring in the same gene panD encoding aspartate decarboxylase, which is involved in synthesis of β-alanine that is a precursor for pantothenate and co-enzyme A biosynthesis. panD mutations were identified in naturally PZA-resistant Mycobacterium canetti strain and a PZA-resistant MDR-TB clinical isolate. Future studies are needed to address the role of panD mutations in PZA resistance and confirm PanD as a new target of PZA.

According to the latest revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (now known as the Alzheimer's Association) (NINCDS-ADRDA) diagnostic criteria for Alzheimer's disease dementia, the confidence in diagnosing mild cognitive impairment (MCI) due to Alzheimer's disease dementia is raised with the application of imaging biomarkers. These tests, added to core clinical criteria, might increase the sensitivity or specificity of a testing strategy. However, the accuracy of biomarkers in the diagnosis of Alzheimer's disease dementia and other dementias has not yet been systematically evaluated. A formal systematic evaluation of the sensitivity, specificity, and other properties of positron emission tomography (PET) imaging with the (11)C-labelled Pittsburgh Compound-B ((11)C-PIB) ligand was performed.To determine the diagnostic accuracy of the (11)C- PIB-PET scan for detecting participants with MCI at baseline who will clinically convert to Alzheimer's disease dementia or other forms of dementia over a period of time.The most recent search for this review was performed on 12 January 2013. We searched MEDLINE (OvidSP), EMBASE (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science and Conference Proceedings (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We also requested a search of the Cochrane Register of Diagnostic Test Accuracy Studies (managed by the Cochrane Renal Group).No language or date restrictions were applied to the electronic searches and methodological filters were not used so as to maximise sensitivity.We selected studies that had prospectively defined cohorts with any accepted definition of MCI with baseline (11)C-PIB-PET scan. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis for example NINCDS-ADRDA or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria.We screened all titles generated by electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. The identified full papers were assessed for eligibility and data were extracted to create two by two tables. Two independent assessors performed quality assessment using the QUADAS 2 tool. We used the hierarchical summary receiver operating characteristic (ROC) model to produce a summary ROC curve.Conversion from MCI to Alzheimer's disease dementia was evaluated in nine studies. The quality of the evidence was limited. Of the 274 participants included in the meta-analysis, 112 developed Alzheimer's dementia. Based on the nine included studies, the median proportion converting was 34%. The studies varied markedly in how the PIB scans were done and interpreted.The sensitivities were between 83% and 100% while the specificities were between 46% and 88%. Because of the variation in thresholds and measures of (11)C-PIB amyloid retention, we did not calculate summary sensitivity and specificity. Although subject to considerable uncertainty, to illustrate the potential strengths and weaknesses of (11)C-PIB-PET scans we estimated from the fitted summary ROC curve that the sensitivity was 96% (95% confidence interval (CI) 87 to 99) at the included study median specificity of 58%. This equated to a positive likelihood ratio of 2.3 and a negative likelihood ratio of 0.07. Assuming a typical conversion rate of MCI to Alzheimer's dementia of 34%, for every 100 PIB scans one person with a negative scan would progress and 28 with a positive scan would not actually progress to Alzheimer's dementia.There were limited data for formal investigation of heterogeneity. We performed two sensitivity analyses to assess the influence of type of reference standard and the use of a pre-specified threshold. There was no effect on our findings.Although the good sensitivity achieved in some included studies is promising for the value of (11)C-PIB-PET, given the heterogeneity in the conduct and interpretation of the test and the lack of defined thresholds for determination of test positivity, we cannot recommend its routine use in clinical practice.(11)C-PIB-PET biomarker is a high cost investigation, therefore it is important to clearly demonstrate its accuracy and standardise the process of the (11)C-PIB diagnostic modality prior to it being widely used.

To develop technical advances for real-time magnetic resonance imaging (MRI) that allow for improved image quality and high frame rates.The approach is based on a combination of fast low-angle shot (FLASH) MRI sequences with radial data sampling and view sharing of successive acquisitions. Gridding reconstructions provide images free from streaking or motion artifacts and with a flexible trade-off between spatial and temporal resolution. Immediate image reconstruction and online display is accomplished with the use of an unmodified 3 T MRI system. For receive coils with a large number of elements this process is supported by a user-selectable channel compression that is based on a principal component analysis and performed during initial preparation scans.In preliminary applications to healthy volunteers, real-time radial FLASH MRI visualized continuous movements of the temporomandibular joint during voluntary opening and closing of the mouth at high spatial resolution (0.75 mm in-plane) and monitored cardiac functions at high temporal resolution (20 images per second) during free breathing and without synchronization to the electrocardiogram.Real-time radial FLASH MRI emerges as a simple and versatile tool for a large range of clinical applications.

There is a high demand for potent, selective, and brain-penetrant small molecule inhibitors of leucine-rich repeat kinase 2 (LRRK2) to test whether inhibition of LRRK2 kinase activity is a potentially viable treatment option for Parkinson’s disease patients. Herein we disclose the use of property and structure-based drug design for the optimization of highly ligand efficient aminopyrimidine lead compounds. High throughput in vivo rodent cassette pharmacokinetic studies enabled rapid validation of in vitro–in vivo correlations. Guided by this data, optimal design parameters were established. Effective incorporation of these guidelines into our molecular design process resulted in the discovery of small molecule inhibitors such as GNE-7915 (18) and 19, which possess an ideal balance of LRRK2 cellular potency, broad kinase selectivity, metabolic stability, and brain penetration across multiple species. Advancement of GNE-7915 into rodent and higher species toxicity studies enabled risk assessment for early development.