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Abstract Background Water resources is an essential factor to ensure the sustainable development of the society, but along with the utilization and treatment of water resources, a large amount of carbon emissions will be generated. The study of carbon emissions in social water cycle system is of great significance in promoting the achievement of carbon peaking and carbon neutrality. This study calculated the carbon emissions generated in social water cycle system in nine provinces along the Yellow River, used the Tapio decoupling model to analyze the decoupling relationship between water and carbon emissions, and constructed the STIRPAT expanded model to analyze the main influencing factors of carbon emissions. Results (1) The total carbon emissions of the nine provinces showed an increasing trend over time, with a growth rate of 25.13%. (2) The carbon emission intensity of water use (1.60kg/m3) and drainage (1.45kg/m3) system is higher, the carbon emission intensity of water supply (0.30kg/m3) and water withdrawal (0.56kg/m3) system is lower. (3) The relationship between water resources utilization and carbon emissions along the Yellow River is generally in a state of negative decoupling and coupling. (4) Energy structure and population growth are the main factors affecting carbon emissions in social water cycle system, while water supply quantity and water use system are secondary factors. Conclusions Water use system is the main body of carbon emissions in social water cycle system, and as the water consumption increases, the carbon emissions will continue to increase. In order to reduce carbon emissions and mitigate climate change, carbon emission factors should be incorporated into water resources management.

The purpose of this study was to reduce the loss of spent laying hens during slaughtering by adjusting the parameters of scalding. The research object of this study was the spent laying hens with a rearing age of more than 400 days. The research meant to explore the effect of scalding methods on feather removing and muscle overheating. Three scalding parameters were set as follow: 65 ℃-3 min (high temperature scalding, HS), 60 ℃-4 min 20 s (medium temperature and slow scalding, MSS), and 58 ℃-4 min 20 s (low temperature and slow scalding, LSS). Broilers without scalding were set as the control group. The defeathering effect was characterized by measuring the feather retention force (FRF) and counting the number of feathers remaining after defeathering. The overheating degree of breast muscle was characterized by measuring meat color, depth of overheating area, DSC scanning and Raman spectrum scanning. The results showed that no significant difference in feather removal effects between HS treatments and LSS treatments, while the feather retention force and residual feather number of MSS treatment were significantly lower than those of the other two groups (P

Abstract Background Gibberella ear rot (GER) is one of the most devastating diseases in maize growing areas, which directly reduces grain yield and quality. However, the underlying defense response of maize to pathogens infection is largely unknown. Results To gain a comprehensive understanding of the defense response in GER resistance, two contrasting inbred lines ‘Nov-82’ and ‘H10’ were used to explore transcriptomic profiles and defense-related phytohormonal alterations during Fusarium graminearum infection. Transcriptomic analysis revealed 4,417 and 4,313 differentially expressed genes (DEGs) from the Nov-82 and H10, respectively, and 647 common DEGs between the two lines. More DEGs were obviously enriched in phenylpropanoid biosynthesis, secondary metabolites biosynthesis, metabolic process and defense-related pathways. In addition, the concentration of the defense-related phytohormones, jasmonates (JAs) and salicylates (SAs), was greatly induced after the pathogen infection. The level of JAs in H10 was more higher than in Nov-82, whereas an opposite pattern for the SA between the both lines. Integrated analysis of the DEGs and the phytohormones revealed five vital modules based on co-expression network analysis according to their correlation. A total of 12 hub genes encoding fatty acid desaturase, subtilisin-like protease, ethylene-responsive transcription factor, 1-aminocyclopropane-1-carboxylate oxidase, and sugar transport protein were captured from the key modules, indicating that these genes might play unique roles in response to pathogen infection, Conclusions Overall, our results indicate that large number DEGs related to plant disease resistance and different alteration of defensive phytohormones were activated during F. graminearum infection, providing new insight into the defense response against pathogen invasion, in addition to the identified hub genes that can be further investigated for enhancing maize GER resistance.

Abstract Background ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is thought to play a significant role both in tumor suppression and tumor initiation, which is highly dependent upon context. Previous studies have suggested that ARID1A deficiency may contribute to cancer development. The specific mechanisms of whether ARID1A loss affects tumorigenesis by RNA editing remain unclear. Results Our findings indicate that the deficiency of ARID1A leads to an increase in RNA editing levels and alterations in RNA editing categories mediated by adenosine deaminases acting on RNA 1 (ADAR1). ADAR1 edits the CDK13 gene at two previously unidentified sites, namely Q113R and K117R. Given the crucial role of CDK13 as a cyclin-dependent kinase, we further observed that ADAR1 deficiency results in changes in the cell cycle. Importantly, the sensitivity of ARID1A-deficient tumor cells to SR-4835, a CDK12/CDK13 inhibitor, suggests a promising therapeutic approach for individuals with ARID1A-mutant tumors. Knockdown of ADAR1 restored the sensitivity of ARID1A deficient cells to SR-4835 treatment. Conclusions ARID1A deficiency promotes RNA editing of CDK13 by regulating ADAR1.

Plate-based lattice structures are an emerging category of mechanical metamaterials with exceptional mechanical performance. In this work, plate-based SCFCC metamaterials of AlSi10Mg with various relative densities are fabricated by laser powder bed fusion (LPBF). Circular holes are strategically designed and placed at the center of each non-load-bearing face for residual powder removal. Quasi-static compression experiments and numerical simulations are performed to investigate their mechanical performance and deformation mechanisms. Results indicate that the elastic modulus of SCFCC metamaterials decreases by 3.5% with the presence of 0.9 mm diameter holes, while increasing the hole size shows negligible impact on the elastic modulus. The novel plate-based SCFCC structure exhibits superior mechanical properties and enhanced energy absorption capacity concerning conventional high-stiffness truss-based and shell-based counterparts. The improvement, at the relative density of 0.2, can be observed in terms of elastic modulus (around 50%), peak compressive strength (around 300%), energy absorption capacity (around 400% or 200%). When increasing the relative density from 0.2 to 0.5, plate-based SCFCC metamaterial still maintains superior mechanical performance while the gaps between SCFCC and its counterparts narrow down gradually owing to the loss of structural features. Moreover, mechanical characteristics and coefficients of three Gibson and Ashby analytical equations are determined. This work proposes a novel type of plate-based structure with both exceptional mechanical performance and good additive manufacturability, which opens a new avenue for the design of lightweight mechanical metamaterials.

Abstract Oil‐paper insulation material is an essential component for oil‐filled transformers, and polyimide (PI) insulation paper is a novel material in the field of electricity. The improvement of insulation class for insulation paper has gained significant attention in recent years. In this study, SiO2 nanoparticles were modified with a silane coupling agent (KH550), and the KH550‐SiO2 was added to the fibre membrane through in situ polymerisation. The chemical composition and microcosmic characteristics of the PI porous fibre membrane were characterised using FT‐IR and SEM FT‐IR and SEM. Consequently, the dielectric constant of the composite paper was reduced to 2.3 upon adding 3 wt% of KH550‐SiO2, and the dielectric strength reached its maximum value of 85 kV/mm. The results demonstrate that the insulation performance of the KH550‐SiO2/PI composite was significantly improved due to the incorporation of nano‐SiO2. This establishes an efficient approach for achieving excellent electrical and thermal properties in practical applications using the KH550‐SiO2/PI fibre membrane.

Knowledge graphs (KGs) serve as invaluable tools for organizing and representing structural information, enabling powerful data analysis and retrieval. In this paper, we propose a novel knowledge graph learning algorithm based on deep convolutional neural networks (KGLA-DCNN) to enhance the classification accuracy of KG nodes. Leveraging the hierarchical and relational nature of KGs, our algorithm utilizes deep convolutional neural networks to capture intricate patterns and dependencies within the graph. We evaluate the effectiveness of KGLA-DCNN on two benchmark datasets, Cora and Citeseer, renowned for their challenging node classification tasks. Through extensive experiments, we demonstrate that our proposed algorithm significantly improves classification accuracy compared to state-of-the-art methods, showcasing its capability to leverage the rich structural information inherent in KGs. The results highlight the potential of deep convolutional neural networks in enhancing the learning and representation capabilities of knowledge graphs, paving the way for more accurate and efficient knowledge discovery in diverse domains.

Abstract Harmonic magnetic gears (HMGs) have the advantage of lubrication‐free, high speed ratio and high torque density, which make it an attractive solution for safety critical applications. Due to eccentricity caused by machining and assembly, HMG suffers from dynamic eccentricity (DE) in operation, however, its effect on HMG performance is still unknown. Transmission characteristic of HMG under DE is studied. First, a magnetic equivalent circuit (MEC) model of HMG is proposed to build the magnetic coupling torque analytically, and the geometry of air gap is analysed parametrically to derive its equivalent reluctances. Flux density and coupling torque can be acquired by solving MEC equations. The accuracy of the MEC model is verified by finite element method. To study the transmission characteristic, an electromechanical coupling simulation framework for HMG is constructed, motion trajectories of rotors are investigated in case of DE, the output torque in locked‐rotor condition and speed response in continuous operation can be derived by simulation. It is found that torque ripples that have the same frequency with input rotor are induced by DE; the results are then verified in the experiment. This paper provides a theoretical guidance for the design and condition monitoring of HMG.

This study investigates the problem of finite-time output feedback stabilization in probability for a class of stochastic high-order nonlinear systems with unknown output function. By combining the homogeneous domination techniques, backstepping method and sign function, we obtain the output feedback controller that includes state controller and recursive reduced-order observer. Subsequently, we present an analytical method to deal with the unknown output function within the stochastic high-order nonlinear system such that the designed output feedback controller can make the closed-loop system globally finite-time stabilization in probability when the unknown output function belongs to the maximum open sector $\Omega $ . The numerical simulation results show that the proposed scheme is feasible.

ObjectiveThe purpose of this paper is to study the effects of cavitation models on the simulation of full-scale propeller cavitation. MethodsThe minimum rotational speed of the propeller required for cavitation is predicted by the Bernoulli equation, and the propeller's cavitation condition is observed by full-scale experiment. After determining the boundary layer mesh thickness and establishing the hydrodynamic model, meshes are generated. In the numerical simulation, the turbulence model is selected from either the standard \begin{document}$k - \varepsilon $\end{document} model or Realizable \begin{document}$k - \varepsilon $\end{document} model, and the cavitation model is selected from either the Schnerr−Sauer (S−S) model or the Zwart−Gerber−Belamri (ZGB) model. The maximum gas volume fraction on the surface of the propeller is tracked and recorded. In the meantime, the reliability of the numerical simulation is evaluated by observing the gas distribution on the surface of the propeller. And the simulation accuracy of the related models is compared. ResultsThe simulation results show that compared with the standard \begin{document}$k - \varepsilon $\end{document} turbulence model, the cavitation region obtained with the Realizable \begin{document}$k - \varepsilon $\end{document} model is significantly more consistent with the experimental results. By monitoring the maximum gas volume fraction on propeller's surface, it is found that the choice of turbulence model has little effect on the cavitation intensity, and the cavitation intensity obtained by S−S model is significantly higher than that obtained by the ZGB model. ConclusionsThis study shows that the turbulence model has a great influence on the area of the cavitation region, and cavitation models have a great influence on cavitation intensity. In terms of the simulation of propeller cavitation, the accuracy of the Realizable \begin{document}$k - \varepsilon $\end{document} model is higher than that of the standard \begin{document}$k - \varepsilon $\end{document} model.

There have been numerous theoretical and empirical transportation studies contesting the stability of commuting time over time. The constant commuting time hypothesis posits that people adjust trip durations, shift across modes, and sort through locations, so that their average commuting time remains within a constant budget. There is a discrepancy between studies applying aggregate analysis and those using disaggregate analysis, and differences in data collection may have contributed to the varying conclusions reported in the literature. This study conducts both aggregate and disaggregate analyses with two travel surveys of the Portland region. We employ descriptive analysis and t-tests to compare the aggregate commuting times of two years and use regression models to explore factors affecting the disaggregate commuting time at the individual trip level to examine whether the stability of the commuting time remains after substantial changes in the transportation and land use systems. Our study indicates that the average commuting time, along with the average commuting distance, increased slightly, as the mode share shifted away from driving during the examined period. The growth in shares of non-driving modes, which are slower than driving, coupled with an increased travel distance, contributed to the small increase in the average commuting time. Our analysis also indicates that the average travel speed improved for transit riders as well as drivers, contradicting earlier research that claims that public transit investment has worsened the congestion in Portland.

Nanoscale zero-valent iron (Fe) is a promising nanomaterial for remediating heavy metal-contaminated soils. Melatonin (MT) is essential to alleviate environmental stress in plants. However, the conjunction effects of Fe and MT (FeMT) on rice Cd, As accumulation and the mechanism of soil chemical and microbial factors interaction are unclear. Here, a pot experiment was conducted to evaluated the effects of the FeMT for rice Cd, As accumulation and underlying mechanisms. The findings showed that FeMT significantly reduced grains Cd by 92%–87% and As by over 90%, whereas improving grains Fe by over 213%. Soil available-Cd and iron plaques-Cd (extracted by dithionite-citrate-bicarbonate solution, DCB-Cd) significantly regulated roots Cd, thus affected Cd transport to grains. Soil pH significantly affected soil As and DCB-As, which further influenced roots As uptake and the transport to shoots and grains. The interactions between the soil bacterial community and soil Fe, available Fe, and DCB-Fe together affected root Fe absorption and transportation in rice. FeMT significantly influenced rhizosphere soil bacterial α- and β-diversity. Firmicutes as the dominant phylum exhibited a significant positive response to FeMT measure, and acted a key role in reducing soil Cd and As availability mainly by improving iron-manganese plaques. The increase of soil pH caused by FeMT was beneficial only for Actinobacteriota growth, which reduced Cd, As availability probably through complexation and adsorption. FeMT also showed greater potential in reducing human health and ecological risks by rice consumption and straw returning. These results showed the important role of both soil chemical and microbial factors in FeMT-mediated rice Cd, As reduction efficiency. This study opens a novel strategy for safe rice production and improvement of rice iron nutrition level in heavy-metals polluted soil, but also provides new insights into the intricate regulatory relationships among soil biochemistry, toxic elements, microorganism, and plants.

Abstract Major depressive disorder (MDD) is one of the most common and disabling mental disorders, and current strategies remain inadequate. Although mesenchymal stromal cells (MSCs) have shown beneficial effects in experimental models of depression, underlying mechanisms remain elusive. Here, using murine depression models, we demonstrated that MSCs could alleviate depressive and anxiety-like behaviors not due to a reduction in proinflammatory cytokines, but rather activation of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons. Mechanistically, peripheral delivery of MSCs activated pulmonary innervating vagal sensory neurons, which projected to the nucleus tractus solitarius, inducing the release of 5-HT in DRN. Furthermore, MSC-secreted brain-derived neurotrophic factor activated lung sensory neurons through tropomyosin receptor kinase B (TrkB), and inhalation of a TrkB agonist also achieved significant therapeutic effects in male mice. This study reveals a role of peripheral MSCs in regulating central nervous system function and demonstrates a potential “lung vagal-to-brain axis” strategy for MDD.

ObjectivesThis study aims to carry out systematic research on the hydrodynamic performance of a small unmanned catamaran. MethodsBased on STAR-CCM+ numerical simulation software, the hydrodynamic performance of a small unmanned catamaran in a hydrostatic state and self-propelled state under different Froude (Fr) numbers is numerically simulated. The unsteady RANSE model is selected and the Dynamic Fluid Body Interaction (DFBI) model and overset grid function are used to simulate the trim and heave of the catamaran. A body-force propeller is used to replace the propeller effect. The empirical formula of the friction resistance coefficient is used to verify the simulation results of the hydrostatic state. The self-propelled experimental results are then compared to the simulation results of the self-propelled state to verify the accuracy of the simulation results. ResultsWhen the propeller speed is 3 000 r/min, the difference in total resistance between the self-propelled and hydrostatic states of the small unmanned catamaran is 21.099%. Under different propeller rotation speeds, the relative errors of the thrust between the simulation and experimental results of the self-propelled catamaran is less than 10%. ConclusionsThe comparison between the simulation results and experimental results verifies the reliability of the simulation. The hydrodynamic performance of the self-propelled ship hull studied by the volume method is quite different from that under hydrostatic conditions. The numerical method can provide valuable references for further predicting the hydrodynamic performance of small unmanned catamarans.

Abstract Background There is no consensus on the optimal reconstruction technique after proximal gastrectomy. The purpose of this study was to retrospectively compare the surgical outcomes among esophagogastrostomy (EG) anastomosis, gastric tube (GT) reconstruction and double-tract (DT) reconstruction in patients who underwent laparoscopic proximal gastrectomy (LPG) to clarify the superior reconstruction method. Methods This study enrolled 164 patients who underwent LPG at the Northern Jiangsu People's Hospital in Jiangsu between January 2017 to January 2022 (EG: 51 patients; GT: 77 patients; DT: 36 patients). We compared the clinical and pathological characteristics, surgical features, postoperative complications, nutritional status, and quality of life (QOL) among the above three groups. Results Mean operative time was longer with the DT group than the remaining two groups (p = 0.001). With regard to postoperative complications, considerable differences in the postoperative reflux symptoms (p = 0.042) and reflux esophagitis (p = 0.040) among the three groups were found. For the nutritional status, total protein, hemoglobin and albumin reduction rates in the GT group were significantly higher than the other two groups at 12 months postoperatively. In the PGSAS-45, three assessment items were better in the DT group significantly compared with the esophageal reflux subscale (p = 0.047, Cohen’s d = 0.44), dissatisfaction at the meal (p = 0.009, Cohen’s d = 0.58), and dissatisfaction for daily life subscale (p = 0.012, Cohen’s d = 0.56). Conclusions DT after LPG is a valuable reconstruction technique with satisfactory surgical outcomes, especially regarding reduced reflux symptoms, improving the postoperative nutritional status and QOL.

Sn-doped Ga2O3 thin films and metal–semiconductor–metal (MSM) ultraviolet detectors were prepared using the co-sputtering method to enhance their photoelectric performance. The results revealed that Sn doping can effectively change the optical and electrical properties of thin films, greatly improving the photoelectric responsiveness of the devices. Through microstructure testing results, all of the thin film structures were determined to be monoclinic beta phase gallium oxide. At a DC power of 30 W, the thickness of the Sn-doped thin film was 430 nm, the surface roughness of the thin film was 4.94 nm, and the carrier concentration, resistivity, and mobility reached 9.72 × 1018 cm−3, 1.60 × 10−4 Ω·cm, and 45.05 cm3/Vs, respectively. The optical results show that Sn doping clearly decreases the transmission of thin films and that the bandgap can decrease to 3.91 eV. Under 30 W DC power, the photo dark current ratio of the detector can reach 101, time responses of tr = 31 s and tf = 22.83 s were obtained, and the spectral responsivity reached 19.25 A/W.

Abstract Objectives To investigate whether ferroptosis is involved in HCY-induced endothelial injury and the possible mechanism of HCY-induced ferroptosis. Methods EA. hy926 cells were cultured in vitro. Cells were intervened using HCY and Fer-1. The cells were divided into Control groups, HCY (4 mM), HCY (8 mM), HCY + Fer-1 (4 mM HCY + 0.5/2.5/5 µM Fer-1). CCK-8 assay was used to detect cell viability; Flow Cytometry was used to detect cellular Lip-ROS, TBA and Microplate assay was used to detect MDA&GSH, Western blot was used to detect the expression of ferroptosis-related proteins GPX4 and SLC7A11. Results HCY can inhibited the proliferation of EA. hy926 cells in a time- and concentration-dependent manner; Fer-1 inhibits HCY-induced ferroptosis in EA.hy926 cells in a concentration-dependent manner; Compared with the control group, the cell viability and GSH content in the HCY group was significantly decreased (p

Water resource health is one of the necessary conditions for society to achieve sustainable development. Due to the predominant focus of most studies on relatively short time spans, with limited attention to long time series and spatial trends, this study, using various regions of Henan Province as a case study, constructs a water resource security assessment framework based on the DPSIR model encompassing Drivers (D), Pressures (P), State (S), Impact (I), and Response (R) dimensions, with a selection of 19 evaluation indicators. Based on this evaluation index system, the CRITIC-TOPSIS evaluation method is formulated by integrating the CRITIC (Criteria Importance Through Intercriteria Correlation) and TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) models. This method is employed to assess the degree of water resource security in Henan Province from 2013 to 2022. And the Obstruction Degree Model is introduced to diagnose the water resource security levels in various regions of Henan Province. The assessment results indicate that over the past decade, the overall level of water resource security in various regions of Henan Province has shown an increasing trend. Irrigated area, per capita water resources, water consumption per unit of industrial value added, per acre water consumption for agricultural irrigation, the ratio of river length meeting water quality standards, groundwater supply proportion, and sewage treatment rate are identified as the primary obstacles influencing the water resource security levels in different regions of Henan Province. The research outcomes of this study can serve as theoretical foundations to enhance urban water resource security globally, ultimately facilitating sustainable development.

Deterministic polishing based on jet electrochemical machining (Jet-ECM) is a stress-free machining method for low-rigidity and ultra-precision workpieces. The nozzle is equivalent to a special tool in deterministic polishing, and the workpiece material is removed using the mechanism of electrochemical dissolution at the position where the nozzle passes. By precisely regulating the nozzle’s movement speed and dwell time, the quantity of material removed from the workpiece at a designated position can be finely adjusted. With this mechanism, the improvement of the workpiece shape accuracy can be achieved by planning the nozzle trajectory and nozzle movement speed. However, due to the positioning errors of the polishing device, the actual position of the nozzle may deviate from the theoretical position, resulting in errors in material removal amount, which affects the accuracy and stability of the polishing process. This study established a mathematical model to analyze the influence of nozzle positioning errors in deterministic polishing based on Jet-ECM. This model has been used to design a specific deterministic polishing device based on Jet-ECM. With the proposed deterministic polishing device, the surface shape of the workpiece is converged. The surface peak-to-valley (PV) value of the φ 50 mm workpiece (valid dimensions = 90% of the central region) indicated that the shape error of the surface was reduced from 2.67 μm to 1.24 μm in 34 min. The power spectral density (PSD) method was used to evaluate the height distribution and height characteristics of the workpiece surface. The results show that the low frequency spatial error is reduced significantly after processing. This study improves the accuracy of the stress-free deterministic polishing methods and further expands the use of deterministic polishing in industry.

Abstract Mesenchymal stromal cells (MSCs) have been considered a promising alternative for treatment of acute respiratory distress syndrome (ARDS). However, there is significant heterogeneity in their therapeutic efficacy, largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs. Here, we hypothesize that the cholinergic anti-inflammatory pathway (CAP), which is recognized as a neuroimmunological pathway, may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS. Using lipopolysaccharide (LPS) and bacterial lung inflammation models, we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) in lung tissue were significantly increased 6 hours after MSC infusion. When the vagus nerve was blocked or α7 nicotinic acetylcholine (ACh) receptor (α7nAChR)-knockout mice were used, the therapeutic effects of MSCs were significantly reduced, suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment. Our results further showed that MSC-derived prostaglandin E2 (PGE2) likely promoted ACh synthesis and release. Additionally, based on the efficacy of nAChR and α7nAChR agonists, we found that lobeline, the nicotinic cholinergic receptor excitation stimulant, may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study (ChiCTR2100047403). In summary, we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome, providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.

IntroductionThe exorbitant cost of accurately annotating the large-scale serial scanning electron microscope (SEM) images as the ground truth for training has always been a great challenge for brain map reconstruction by deep learning methods in neural connectome studies. The representation ability of the model is strongly correlated with the number of such high-quality labels. Recently, the masked autoencoder (MAE) has been shown to effectively pre-train Vision Transformers (ViT) to improve their representational capabilities.MethodsIn this paper, we investigated a self-pre-training paradigm for serial SEM images with MAE to implement downstream segmentation tasks. We randomly masked voxels in three-dimensional brain image patches and trained an autoencoder to reconstruct the neuronal structures.Results and discussionWe tested different pre-training and fine-tuning configurations on three different serial SEM datasets of mouse brains, including two public ones, SNEMI3D and MitoEM-R, and one acquired in our lab. A series of masking ratios were examined and the optimal ratio for pre-training efficiency was spotted for 3D segmentation. The MAE pre-training strategy significantly outperformed the supervised learning from scratch. Our work shows that the general framework of can be a unified approach for effective learning of the representation of heterogeneous neural structural features in serial SEM images to greatly facilitate brain connectome reconstruction.

The detection and real-time monitoring of temperature parameters are important, and indium oxide-based thin film thermocouples can be integrated on the surface of heaters because they operate normally under harsh conditions and provide accurate online temperature monitoring. The higher stability and appropriate optical and electrical properties of In2O3 make it very suitable as an electrode material for thermocouple sensors. This work demonstrates that copper doping can alter the optical and electrical properties of In2O3 films and regulate the output performance of thermocouples. Copper-doped In2O3 thin films were prepared using the magnetron co-sputtering method. The doping concentration of Cu was controlled using direct current (DC) power. An In2O3/Pt thermocouple sensor was prepared, and the optoelectronic and thermocouple properties were adjusted by changing the copper doping content. The thickness valve of the thin film sample was 300 nm. The results of the X-ray diffraction suggested that the structure of the doped In2O3 thin films was cubic. The results of the energy-dispersive X-ray analysis revealed that Cu was doped into the In2O3 thin films. All deposited films were n-type semiconductor materials according to Hall effect testing. The 4.09 at% Cu-doped thin films possessed the highest resistivity (30.2 × 10−3 Ω·cm), a larger carrier concentration (3.72 × 1020 cm−3), and the lowest carrier mobility (0.56 cm2V−1s−1). The optical band gap decreased from 3.76 to 2.71 eV with an increase in the doping concentration, and the transmittance of the film significantly reduced. When the DC power was increased, the variation range of Seebeck coefficient for the In2O3/Pt thermocouple was 152.1–170.5 μV/°C, and the range of thermal output value was 91.4–102.4 mV.

The five northwestern provinces face numerous challenges in sustainable development, particularly water scarcity, economic imbalances, and ecological degradation. This study aims to deeply assess the region’s water resource conditions, the current status of economic development, and the health of the ecosystem while exploring the relationships and coupling mechanisms among them. Using the obstacle model, the research analyzes the primary barriers affecting these three significant factors in the region. The study further reveals a continually improving trend of coordinated development within the water–economic–ecological system in the five northwestern provinces of China, indicating that water usage per ten thousand GDP is the primary obstacle. This research enriches our understanding of the development in China’s five northwestern provinces and provides a theoretical foundation for achieving sustainable development.

Abstract p53 is the most highly mutated tumor suppressor across multiple types of human cancers. The level and function of p53 are fine-tuned through multifaced mechanisms in which the protein–protein interaction between p53 and MDM2 is considered as a major circuit. Recent studies suggest therapeutic strategy attempts to restore p53 function by small molecule inhibitors targeting p53–MDM2 interaction can be a promising direction in treating cancers with wild-type or functional p53. Currently, clinical tests of the p53–MDM2 protein–protein interaction inhibitors (PPIs) are underway. However, it remains elusive about the biomarkers that may predict the therapeutic responses to those inhibitors. Here we report that RNA-binding protein LIN28B directly regulates p53 through binding to the 5′΄ untranslated region of p53 mRNA and blocks its translation by competing with a translation enhancer protein, ribosomal protein L26 (RPL26). This regulatory mechanism of LIN28B does not involve let-7 maturation or the canonical protein turnover pathway of p53. Furthermore, we show that inhibition of LIN28B unleashes the translational suppression of p53 through RPL26, and leads to enhanced sensitivities of cancer cells to inhibitors of p53–MDM2 interaction. Together, we demonstrate a competitive regulatory mechanism of p53 by LIN28B, which has important implications in developing biomarkers to the therapies aiming to reinstate p53 function.

Abstract Background Ocular adnexal B-cell lymphoma (OABL) is a rare subtype of non-Hodgkin lymphoma. The molecular characteristics of OABL remain poorly understood. We performed an integrated study to investigate the proteotranscriptome landscape and identify novel molecular characteristics and biomarkers of OABL. Methods Integrated quantitative proteome and transcriptome were performed on 40 OABL 12 idiopathic orbital inflammation, 6 reactive lymphoid hyperplasia, and 13 aesthetic orbital plastic surgery specimens. Complete clinicopathologic and prognostic data of the patients were recorded. Results We identified high global protein-mRNA concordance as a novel characteristic of OABL. High concordance was related to OABL recurrence. By integrated expression profile, motif enrichment and trend analysis, we found that alternative splicing is inflammation-independently dysregulated in OABL. After portraying the aberrant alternative splicing event landscape, we demonstrated the oncogenic role of ADAR, a core splicing regulator that regulates the splicing of Rho GTPase and cell cycle members. We found that ADAR regulates cell proliferation and Rho GTPase inhibitor sensitivity of lymphoma. We identified DNAJC9 as a potential biomarker for OABL in proteomic analyses. Immunohistochemistry and immunofluorescent staining showed the nuclear staining of DNAJC9 was significantly higher in extranodal marginal zone lymphomas compared with inflammation specimens. Conclusions These results provide an integrated gene expression profiling and demonstrate that high global protein-mRNA concordance is a prognosis-related molecular characteristic of OABL. We portray the alternative splicing events landscape of OABL, and reveal the oncogenic role of ADAR. We identified strong nuclear staining of DNAJC9 as a promising pathology diagnostic biomarker for extranodal marginal zone lymphomas.

Antimony (Sb) is a hazardous metal element that is potentially toxic and carcinogenic. Melatonin (MT) is an indole compound with antioxidant properties that plays an essential role in plant growth and alleviates heavy metal stresses. Nevertheless, little is known about the effects and mechanisms of exogenous MT action on rice under Sb stress. The aim of this experiment was to explore the mechanism of MT reducing Sb toxicity in rice via hydroponics. The results showed that Sb stress significantly inhibited the growth of rice, including biomass, root parameters, and root viability. Exogenous MT obviously alleviated the inhibition of Sb stress on seedling growth and increased biomass, root parameters, and root viability by 15–55%. MT significantly reduced the total Sb content in rice and the subcellular Sb contents in roots by nearly 20–40% and 12.3–54.2% under Sb stress, respectively. MT significantly decreased the contents of malondialdehyde (MDA, by nearly 50%), ROS (H2O2 and O2·−, by nearly 20–30%), and RNS (NO and ONOO−) in roots under Sb stress, thus reducing oxidative stress and cell membrane damage. Furthermore, MT reversed Sb-induced phytotoxicity by increasing the activities of antioxidant enzymes (SOD, POD, CAT, and APX) by nearly 15% to 50% and by regulating the AsA–GSH cycle. In conclusion, this study demonstrates the potential of MT to maintain redox homeostasis and reduce Sb toxicity in rice cells, decreasing the content of Sb in rice and thereby alleviating the inhibition of Sb on rice growth. The results provided a feasible strategy for mitigating Sb toxicity in rice.

Abstract Conjunctival melanoma (CM) is a rare and fatal ocular tumour with poor prognosis. There is an urgent need of effective therapeutic drugs against CM. Here, we reported the discovery of a novel potential therapeutic target for CM. Through phenotypic screening of our in-house library, fangchinoline was discovered to significantly inhibit the growth of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1. Further mechanistic experiments indicated that fangchinoline suppressed the homologous recombination (HR)-directed DNA repair by binding with far upstream element binding protein 2 (FUBP2) and downregulating the expression of HR factors BRCA1 and RAD51. In vitro and in vivo antitumour experiments revealed that fangchinoline increased the efficacy of cisplatin by blocking HR factors and reduced the drug dose and toxicity. In conclusion, our work provides a promising therapeutic strategy for the treatment of CM that is worthy of extensive preclinical investigation.

Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD), and intraperitoneal delivery of MSCs have become a more effective route for IBD treatment. However, the underlying mechanisms are still poorly understood. Here, we found that intraperitoneally delivered MSCs significantly alleviated experimental colitis. Depletion of peritoneal B cells, but not macrophages, clearly impaired the therapeutic effects of MSCs. Intraperitoneally delivered MSCs improved IBD likely by boosting the IL-10-producing B cells in the peritoneal cavity, and a single intraperitoneal injection of MSCs could significantly prevent disease severity in a recurrent mouse colitis model, with lower proinflammation cytokines and high level of IL-10. The gene expression profile revealed that thrombospondin-1 (THBS1) was dramatically upregulated in MSCs after coculture with peritoneal lavage fluid from colitis mice. Knockout of THBS1 expression in MSCs abolished their therapeutic effects in colitis and the induction of IL-10-producing B cells. Mechanistically, THBS1 modulates the activation of transforming growth factor-β (TGF-β), which combines with TGF-β receptors on B cells and contributes to IL-10 production. Blocking the interaction between THBS1 and latent TGF-β or inhibiting TGF-β receptors (TGF-βR) significantly reversed the THBS1-mediated induction of IL-10-producing B cells and the therapeutic effects on colitis. Collectively, our study revealed that intraperitoneally delivered MSCs secreted THBS1 to boost IL-10+Bregs and control the progression and recurrence of colitis, providing new insight for the prevention and treatment of IBD.

Bismaleimide (BMI) resin is an excellent performance resin, mainly due to its resistance to the effect of heat and its insulating properties. However, its lack of toughness as a cured product hampers its application in printed circuit boards (PCBs). Herein, a branched structure via Michael addition was introduced to a BMI system to reinforce its toughness. Compared with a pure BMI sample, the flexural strength of the modified BMI was enhanced, and its maximum value of 189 MPa increased by 216%. The flexural modulus of the cured sample reached 5.2 GPa. Using a scanning electron microscope, the fracture surfaces of BMI samples and a transition from brittle fracture to ductile fracture were observed. Furthermore, both the dielectric constant and the dielectric loss of the cured resin decreased. The breakdown field strength was raised to 37.8 kV/mm and the volume resistivity was improved to varying degrees. Consequently, the resulting modified BMI resin has the potential for wide application in high-frequency and low-dielectric resin substrates, and the modified BMI resin with a structure including three different diamines can meet the needs of various applications.

Grain-scale modelling and simulation is of vital importance during the full lifecycle of crystalline material miniature parts, whose mechanical responses depend on the actual material microstructure, part geometry and their correlation. Unfortunately, current studies fail to comprehensively consider indispensable microstructure information, and lack the consideration regarding part geometry. Therefore, this paper proposes and implements a geometry-considered 3D pseudorandom grain-scale modelling method, which takes into account the necessary actual microstructure information, part geometry and their mutual relations to generate accurate and efficient microstructure-dependent crystal plasticity finite element (M−CPFE) models. Firstly, the 3D actual grain-scale microstructure was acquired efficiently by combining 2D actual microstructures. Then the geometry-considered grain-scale microstructure was created pseudorandomly based on the actual 3D grain size, orientation and misorientation distributions. On this basis, the M−CPFE model was constructed accurately. The proposed method has been proved to have higher accuracy and robustness than the Voronoi random method on macroscopic response prediction, microstructure generation and microstructure evolution prediction. Furthermore, the applicability in micro-manufacturing and service has been demonstrated by micro sheet bending and micro impeller rotation simulations. There is a great potential for the full lifecycle tracking of crystalline material miniature parts with the help of the proposed method.

Niche theory is significant for understanding the function of community structure, interspecific relationships, and community dynamic succession. However, there are few studies on the soil animal niche in returning farmland to forest areas on the Loess Plateau, making it challenging to comprehend the utilization of soil animal resources, the stability of the local community, and the succession process in the areas. Therefore, this study collected soil animals in five typical vegetation types: Robinia pseudoacacia (R), Hippophae rhamnoides (H), Populus simonii (P), Pinus tabulaeformis (T), and Armeniaca sibirica x Hippophae rhamnoides (M), with abandoned grassland (G) used as a control group. Then, the number of soil animal taxa, individuals, diversity, and niche were sampled and examined in the study areas during the four seasons of spring, summer, autumn, and winter using the manual sorting method and the Tullgren method. The results revealed that 3872 soil animals from 3 Phyla, 8 Classes, 22 Orders, and 49 Families were captured in the study areas. The dominant groups of soil macrofauna were Diptera larvae, Julidae, and Formicidae, and the dominant groups of meso–micro soil fauna were Oribatida, Protospira, and Collembola juveniles. Soil animals have rich nutritional function groups, with the most saprophytic soil animal groups. The individual density and taxa number of soil animals in G were lower than other vegetation on the whole. H, M, and P had a higher Shannon–Winner index than the other vegetation. Seasonal changes had different effects on macro and meso–micro soil fauna. The diversity of soil macrofauna is higher in spring and summer, and that of meso–micro soil fauna is higher in autumn and winter. Oribatida, Diptera Larvae, and Formicidae had a large niche width in the main taxa of soil animals, with universal adaptability to the environment. Cicadellidae and Culicidae had narrow niche widths and were highly dependent on resources and the environment. There were 67 pairs of highly overlapped (Oik > 0.8) taxa of soil animals and 56 pairs of moderately overlapped (0.6 < Oik ≤ 0.8) taxa, accounting for 80.39% of the total number of taxa. Soil animals had high commonality in resource utilization, intense competition, and poor community stability. As a result, we can conclude that the soil animal community in the study areas was in the stage of succession.

Bismaleimide (BMI) resin has great potential in aerospace, electronic, and machinery fields due to its extraordinary thermal stability. Owing to BMI’s lower impact strength, various modified BMI resins have been prepared using CTBN, PEEK, fillers, and hyperbranched polymer to achieve higher impact strength. However, enhancement of toughness causes deterioration of other performance, such as Tg, thermal stability, and brittleness. In this work, BMI resin modified by hyperbranched polyimide (HBPI) was obtained. HBPI designed with flexible segments, unsaturated bonds, and a low degree of branching was synthesized. FT-IR and 13C-NMR were applied to confirm the successful fabrication of HBPI. The mechanical strength and dielectric properties of cured BMI resin containing various levels of HBPI were analyzed systematically. The impact and bending strength were improved significantly with increased HBPI content. When the content of HBPI is 40 wt.%, the impact strength and bending strength reach the maximum value of 32 kJ/mm and 88 MPa. In addition, the BMI cured with HBPI exhibits enhanced bending modulus to the value of 5.9 GPa. Furthermore, the dielectric strength of cured resin was improved to 28.3 kV/mm. The improved mechanical strength and enhanced dielectric properties are attributed to the increasing free volume induced by HBPI. These results indicate the promise of BMI resin modified by HBPI applied in insulating coatings and low dielectric laminates used in high frequency.

At present, the existing vegetable grafting machines are cutting and grafting operations for a single plant or row. They need to manually or automatically grab the seedlings, and their grafting efficiency is not significantly higher than that of manual grafting techniques. In this paper, grafted melon seedlings were the subject of the research. Based on the splice-grafting method, we designed a clamping and positioning device for full-tray seedlings and a mechanical device to realize full-tray grafting by locating the vegetable seedlings and completing the full-tray grafting process without damaging the seedlings. The results show that the cutting success rate for pumpkin rootstock and for melon scion reached 100% and 92%, respectively. The lengths of the long axis of the section of the rootstock and the scion were 6.2–7.7 mm, and the cutting angle was maintained at 30 degrees, thereby able to meet the requirements of the grafting method. The average grafting efficiency for the rootstock and scion were 2134 plants/h, and the average grafting success rate was 67%.

DC–DC converters are widely used. They are a typical class of strongly nonlinear time-varying systems that show rich nonlinear phenomena under certain working conditions. Therefore, an in-depth study of their nonlinear phenomena, characteristics, and generation mechanism is of great practical significance for gaining a deep understanding of this kind of switching converter, revealing the essence of these nonlinear phenomena and then optimizing the design of this kind of converter. Based on the fact that most of the inductance and capacitance are fractional-order, the nonlinear dynamic characteristics of the fractional-order (FO) DCM buck–boost converter are researched in this paper. The main research work and achievements of this paper include: (1) using the predictor–corrector method of fractional calculus, which is not limited by fractional order and can directly calculate the accurate values of the inductance current and capacitor voltage of the fractional converter; the predictor–corrector model of the FO converter is established. (2) The bifurcation diagrams are obtained based on this model, and the period-doubling bifurcation and chaotic behavior of the FO buck–boost converter are analyzed. (3) The phase diagrams are obtained and verified to the point that period-doubling bifurcation occurs; then, some conclusions are drawn. The results show that under certain operating and parameters conditions, the FO buck–boost converter will appear as a bifurcation and chaotic nonlinear phenomenon. Under the condition of the same circuit parameters, the stability parameter domains of the integer-order buck–boost converter and the FO buck–boost converter are different. Compared with the integer-order converter, the parameter stability region of the FO buck–boost converter is bigger. The FO buck–boost converter is more accurate at describing the nonlinear dynamic characteristics. Furthermore, the predictor–corrector method can also be applied to other FO power converters and provides theoretical guidance for converter parameter optimization and controller design.

miR-29a/b1 was reportedly involved in the regulation of the reproductive function in female mice, but the underlying molecular mechanisms are not clear. In this study, female mice lacking miR-29a/b1 showed a delay in vaginal opening, irregular estrous cycles, ovulation disorder and subfertility. The level of luteinizing hormone (LH) was significantly lower in plasma but higher in pituitary of mutant mice. However, egg development was normal in mutant mice and the ovulation disorder could be rescued by the superovulation treatment. These results suggested that the LH secretion was impaired in mutant mice. Further studies showed that deficiency of miR-29a/b1 in mice resulted in an abnormal expression of a number of proteins involved in vesicular transport and exocytosis in the pituitary, indicating the mutant mice had insufficient LH secretion. However, the detailed mechanism needs more research.

Cell-cell contact participates in the process of mesenchymal stromal cell (MSC)-mediated T cell modulation and thus contributes to MSC-based therapies for various inflammatory diseases, especially T cell-mediated diseases. However, the mechanisms underlying the adhesion interactions between MSCs and T cells are still poorly understood. In this study, we explored the interaction between MSCs and T cells and found that activated T cells could rapidly adhere to MSCs, leading to significant reduction of TNF-α and IFN-γ mRNA expression. Furthermore, TCR-proximal signaling in activated T cells was also dramatically suppressed in the MSC co-culture, resulting in weakened Ca2+ signaling. MSCs rapidly suppressed TCR signaling and its downstream signaling in a cell-cell contact-dependent manner, partially through the ICAM-1/CD43 adhesion interaction. Blockade of either ICAM-1 on MSCs or CD43 on T cells significantly reversed this rapid suppression of proinflammatory cytokine expression in T cells. Mechanistically, MSC-derived ICAM-1 likely disrupts CD43-mediated TCR microcluster formation to limit T cell activation. Taken together, our results reveal a fast mechanism of activated T cell inhibition by MSCs, which provides new clues to unravel the MSC-mediated immunoregulatory mechanism for aGVHD and other severe acute T cell-related diseases.

The prediction of marine elements has become increasingly important in the field of marine research. However, time series data in a complex environment vary significantly because they are composed of dynamic changes with multiple mechanisms, causes, and laws. For example, sea surface temperature (SST) can be influenced by ocean currents. Conventional models often focus on capturing the impact of historical data but ignore the spatio–temporal relationships in sea areas, and they cannot predict such widely varying data effectively. In this work, we propose a cyclic evolutionary network model (CENS), an error-driven network group, which is composed of multiple network node units. Different regions of data can be automatically matched to a suitable network node unit for prediction so that the model can cluster the data based on their characteristics and, therefore, be more practical. Experiments were performed on the Bohai Sea and the South China Sea. Firstly, we performed an ablation experiment to verify the effectiveness of the framework of the model. Secondly, we tested the model to predict sea surface temperature, and the results verified the accuracy of CENS. Lastly, there was a meaningful finding that the clustering results of the model in the South China Sea matched the actual characteristics of the continental shelf of the South China Sea, and the cluster had spatial continuity.

Uveal melanoma (UM) is the most common intraocular malignancy in adults. So far, no systemic therapy or standard treatment exists to reduce the risk of metastasis and improve overall survival of patients. With the increased knowledge regarding the molecular pathways that underlie the oncogenesis of UM, it is expected that novel therapeutic approaches will be available to conquer this disease. This review provides a summary of the current knowledge of, and progress made in understanding, the pathogenesis, genetic mutations, epigenetics, and immunology of UM. With the advent of the omics era, multi-dimensional big data are publicly available, providing an innovation platform to develop effective targeted and personalized therapeutics for UM patients. Indeed, recently, a great number of therapies have been reported specifically for UM caused by oncogenic mutations, as well as other etiologies. In this review, special attention is directed to advancements in targeted therapies. In particular, we discuss the possibilities of targeting: GNAQ/GNA11, PLCβ, and CYSLTR2 mutants; regulators of G-protein signaling; the secondary messenger adenosine diphosphate (ADP)-ribosylation factor 6 (ARF6); downstream pathways, such as those involving mitogen-activated protein kinase/MEK/extracellular signal-related kinase, protein kinase C (PKC), phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR), Trio/Rho/Rac/Yes-associated protein, and inactivated BAP1; and immune-checkpoint proteins cytotoxic T-lymphocyte antigen 4 and programmed cell-death protein 1/programmed cell-death ligand 1. Furthermore, we conducted a survey of completed and ongoing clinical trials applying targeted and immune therapies for UM. Although drug combination therapy based on the signaling pathways involved in UM has made great progress, targeted therapy is still an unmet medical need.

A comprehensive method is presented to investigate nonlinear dynamic responses of functionally graded rectangular plate with arbitrary boundary conditions under a moving mass, based on Rayleigh-Ritz solutions together with the penalty method (PM) and the Newmark with inverse Broyden quasi-Newton method. Different from the existing methods, all inertial effects associated with the moving mass, which affect the mass, damping, and stiffness matrices of system, are taken into account. The formulations are derived based on classical plate theory and von Kármán geometric nonlinearity, which considers large deformation without violating stress failure criteria. Material properties of FG plate vary continuously in the thickness direction according to the power law. The PM is employed to deal with the troublesome arbitrary constraints, which excludes an orthonormalization process for determining these admissible functions, and where only one set of admissible functions is used for arbitrary boundary conditions. The Newmark method together with the rank-one inverse Broyden quasi-Newton method is adopted to solve the nonlinear coupled differential equations of second order in time with more computational efficiency and avoiding numerical instability. Formulation and method of solution are validated by studying their convergence behavior and performing the comparison studies with existing results in the literature in the limit cases. In addition, influences of different material distribution, velocity of moving mass, different conventional, and unconventional boundary conditions on forced and free vibration responses are discussed.

In this paper, the vibration analysis of a partially constrained layer damping plate subjected to moving loads is investigated. In addition, the first four order damping loss factor of the system is optimized with the location of partially constrained layer damping as a design variable. The equations of motion of a partially constrained layer damping plate are derived through the Lagrange equation based on first order shear deformation theory (FSDT). Next, using an extended Rayleigh–Ritz solution together with the penalty method expresses the unknown displacement terms, and the differential quadrature method is proposed to obtain the dynamic response of the system in the time domain. A multi-population genetic algorithm (MPGA) is employed to deal with the optimization of the damping loss factor of a partially constrained layer damping plate. To ensure the accuracy of the method presented in this study, the numerical results are comprehensively verified by experiments and open literature. The optimization results show that the damping loss factor increases when the position of the patch is close to the constraint boundary, and the best strategy is to optimize the low order damping loss factor of the system under moving loads. It is believed that the research results are of interest to engineering science.

Wood veneer defect detection plays a vital role in the wood veneer production industry. Studies on wood veneer defect detection usually focused on detection accuracy for industrial applications but ignored algorithm execution speed; thus, their methods do not meet the required speed of online detection. In this paper, a new detection method is proposed that achieves high accuracy and a suitable speed for online production. Firstly, 2838 wood veneer images were collected using data collection equipment developed in the laboratory and labeled by experienced workers from a wood company. Then, an integrated model, glance multiple channel mask region convolution neural network (R-CNN), was constructed to detect wood veneer defects, which included a glance network and a multiple channel mask R-CNN. Neural network architect search technology was used to automatically construct the glance network with the lowest number of floating-point operations to pick out potential defect images out of numerous original wood veneer images. A genetic algorithm was used to merge the intermediate features extracted by the glance network. Multi-Channel Mask R-CNN was then used to classify and locate the defects. The experimental results show that the proposed method achieves a 98.70% overall classification accuracy and a 95.31% mean average precision, and only 2.5 s was needed to detect a batch of 50 standard images and 50 defective images. Compared with other wood veneer defect detection methods, the proposed method is more accurate and faster.

Several studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explore the possible pathogenetic role of SNAP-25 in schizophrenia. We showed that SNAP-25 conditional knockout (cKO) mice exhibited typical schizophrenia-like phenotype. A significantly elevated extracellular glutamate level was detected in the cerebral cortex of the mouse model. Compared with Ctrls, SNAP-25 was dramatically reduced by about 60% both in cytoplasm and in membrane fractions of cerebral cortex of cKOs, while the other two core members of SNARE complex: Syntaxin-1 (increased ~80%) and Vamp2 (increased ~96%) were significantly increased in cell membrane part. Riluzole, a glutamate release inhibitor, significantly attenuated the locomotor hyperactivity deficits in cKO mice. Our findings provide in vivo functional evidence showing a critical role of SNAP-25 dysfunction on synaptic transmission, which contributes to the developmental of schizophrenia. It is suggested that a SNAP-25 cKO mouse, a valuable model for schizophrenia, could address questions regarding presynaptic alterations that contribute to the etiopathophysiology of SZ and help to consummate the pre- and postsynaptic glutamatergic pathogenesis of the illness.