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Bo Li,1,2 Xiao-Yong Zhang,1 Jian-Zhong Yang,1 Yu-Jie Zhang,1 Wen-Xin Li,1 Chun-Hai Fan,1 Qing Huang1 1Laboratory of Physical Biology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 2Department of Human Anatomy, College of Basic Medical Sciences, Jilin University, Changchun, People’s Republic of China Abstract: In this study, we assessed the in vivo behavior and toxicology of nanoscale graphene oxide (NGO) in mice after intravenous injection. The influence of a polyethylene glycol (PEG) coating on the distribution and toxicity of the NGO was also investigated. The results show that NGO is mainly retained in the liver, lung, and spleen. Retention in the lung is partially due to NGO aggregation. The PEG coating reduces the retention of NGO in the liver, lung, and spleen and promotes the clearance of NGO from these organs, but NGO and NGO-PEG are still present after 3 months. The PEG coating effectively reduces the early weight loss caused by NGO and alleviates NGO-induced acute tissue injuries, which can include damage to the liver, lung, and kidney, and chronic hepatic and lung fibrosis. Keywords: graphene oxide, biodistribution, toxicity, polyethylene glycol

Wei-Hsiu Hsu,1–3 Chi-lung Chen,2 Liang Tseng Kuo,2 Chun-Hao Fan,1 Mel S Lee,2 Robert Wen-Wei Hsu2 1Sports Medicine Center, Chang Gung Memorial Hospital at Chia Yi, Chia Yi, Taiwan; 2Division of Sports Medicine, Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Chia Yi, Chia Yi, Taiwan; 3Department of Medicine, Chang Gung University, Tao Yuan, Taiwan Background: Health-related fitness has been reported to be associated with improved quality of life (QoL) in the elderly. Health-related fitness is comprised of several dimensions that could be enhanced by specific training regimens. It has remained unclear how various dimensions of health-related fitness interact with QoL in postmenopausal women.Objective: The purpose of the current study was to investigate the relationship between the dimensions of health-related fitness and QoL in elderly women.Methods: A cohort of 408 postmenopausal women in a rural area of Taiwan was prospectively collected. Dimensions of health-related fitness, consisting of muscular strength, balance, cardiorespiratory endurance, flexibility, muscle endurance, and agility, were assessed. QoL was determined using the Short Form Health Survey (SF-36). Differences between age groups (stratified by decades) were calculated using a one-way analysis of variance (ANOVA) and multiple comparisons using a Scheffé test. A Spearman’s correlation analysis was performed to examine differences between QoL and each dimension of fitness. Multiple linear regression with forced-entry procedure was performed to evaluate the effects of health-related fitness. A P-value of

Abstract Background The role of the RING finger protein superfamily in carcinogenesis has been widely studied, but one member of this family, RNF19A, has not yet been thoroughly explored in bladder cancer (BCa). Methods The expression levels of RNF19A in BCa samples and cell lines were analysed through data mining of public resources and further experiments. BCa cells in which RNF19A was stably overexpressed or knocked down were generated through lentivirus infection. The effects of RNF19A on cell proliferation, migration, and invasion were explored by performing a series of in vitro experiments, including CCK-8, colony formation, wound healing, and Transwell invasion assays. Using bioinformatics methods and multiple experiments, including western blot, qRT‒PCR, immunoprecipitation, cycloheximide, ubiquitination, and rescue assays, the mechanism underlying the effect of RNF19A on the progression of BCa was investigated. Results Here, we found that RNF19A expression was reduced in BCa samples and cell lines and that lower RNF19A expression predicted shorter overall survival of BCa patients. Functionally, forced expression of RNF19A suppressed BCa cell proliferation, migration, and invasion by inactivating the AKT/mTOR signalling pathway, whereas silencing RNF19A had the opposite effects. Mechanistically, RNF19A could directly interact with ILK and promote its ubiquitination and degradation. Rescue experiments revealed that forced ILK expression partially rescued the decreased phosphorylation of AKT, mTOR, and S6K1 caused by RNF19A overexpression and that the increased levels of the p-AKT, p-mTOR, and p-S6K1 proteins induced by RNF19A knockdown were eliminated after silencing ILK. Similarly, the effects of RNF19A overexpression or knockdown on the phenotypes of cell proliferation, migration, and invasion could also be restored by forced or decreased ILK expression. Conclusions RNF19A suppressed the proliferation, migration, and invasion abilities of BCa cells by regulating ILK ubiquitination and inactivating the AKT/mTOR signalling pathway. RNF19A might be a potential prognostic biomarker and promising therapeutic target for BCa.

Abstract Milk, as a dietary supplement, is crucial for maintaining health and potentially preventing disease throughout life. Both traditional Chinese medicine and modern nutritional science have revealed that milk from different mammals can benefit humans, exhibiting distinct medicinal functions. It can be inferred that milk contains not only multiple nutrients but also an abundance of bioactive components that have health benefits for milk consumers. However, limited studies have focused on the differences in bioactive metabolites in milk derived from various ruminants and their distinct medical functions. Here, we present a comprehensive review of the diversity of microbial metabolites and their associated health benefits, which are primarily shaped by the rumen‐mammary gland axis. Our findings reveal the pivotal role played by microbial metabolites in facilitating the microbiome's influence on human physiology. Finally, we conclude that ruminant milk may offer a path to harness these metabolites’ therapeutic benefits. To increase these metabolites in milk, there is need to design dietary supplements for dairy ruminants, which could enhance milk's medicinal value and aroma, revolutionizing ruminant husbandry.

Abstract Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts’ experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.

Abstract Background Monitoring hand hygiene compliance (HHC) of healthcare providers (HCPs) in healthcare facilities is critical for hand hygiene (HH) promotion. However, less is known about the cost and effectiveness of different HHC monitoring tools. In this study, we aimed to compare various health economic indicators corresponding to electronic system-based monitoring (ESM) and manual paper-based monitoring (MPM) for HHC to provide evidence-based advice for HHC monitoring measures targeted selecting. Methods A before and after study in 40 clinical departments with 4,524 healthcare providers was conducted from December 2022 to January 2023 (MPM implementation phase) and March 2023 to May 2023 (ESM implementation phase). The cost-effectiveness, cost-efficiency, the extent of the Hawthorne effect, and indirect cost-benefit of the two monitoring methods were compared. Results The total cost spent on ESM for the 40 departments (17,702.92 CNY) was 4,123.76 CNY lower than that of MPM (21,826.68 CNY). The HHC of MPM (80.16%) was higher than that of ESM (69.82%) (p

Abstract Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²⁺) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²⁺ concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²⁺ influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.

Abstract The interplay between crystals and epithelial cells forms the cornerstone of kidney stone development, communication between epithelial cells and macrophages emerging as a pivotal role in this process. We conducted next-generation sequencing on the secreted exosomes of TCMK-1 cells treated with calcium oxalate monohydrate (OX_EXO) or controls (NC_EXO), and on the macrophage cell line RAW264.7 stimulated with OX_EXO or NC_EXO, followed by validation of differentially expressed target proteins and miRNAs through Western blot and PCR. UPSET plots were employed to identify genes co-targeted by exosomal miRNAs. Various bioinformatic analyses were employed to predict potential mechanisms of the dysregulated genes. We integrated sequencing data from the GEO database, and validated findings using clinical patient urine and kidney tissues. We identified 665 differentially expressed exosomal miRNAs between OX_EXO and NC_EXO. Among the top 10 down-regulated miRNAs, the most targeted genes were AAK1 and NUFIP2, whereas PLCB1 was significantly targeted among the top 10 up-regulated miRNAs. In clinical specimens, we confirmed the differential expressions of five homologous miRNAs, as well as CNOT3, CNCNA1C, APEX1, and TMEM199. In conclusion, treatment of TCMK-1 cells with calcium oxalate significantly alerted the expression profile of exosomal miRNAs, subsequently influencing gene expression in macrophages, thereby modulating the processes of kidney stone formation.

To help with the critical nurse staffing shortages in hospitals worldwide, robotic assistants are designed to handle frequently required tasks in the digital operating room (DOR), such as the guidance of the laparoscopic camera. To enable fluent collaboration between robots and clinicians, an intuitive and efficient communication interface is needed to allow for interaction using natural language. However, the demanding requirements of the surgical domain make it challenging to develop suitable solutions. A variety of different vocabulary or phrases may be used for expressing the same command. At the same time, surgical workflows may be highly dynamic - especially in emergency situations - and thus the system must be able to grasp the user’s intent both quickly and with high accuracy. This is especially true as only some clinicians may be authorized to request certain tasks, depending on their rank or field of expertise. To solve these challenges, our proposed communication system uses the fine-tuned deep learning model to recognize the speaker information, and the robot assistant takes action only when it detects the commands from the responsible clinician. Also, our proposed conversational functions enable the finetuned large language models to understand the current natural language command given previous command history. In this work, we present a communication system to recognize the speaking person and understand the intent of conversational commands quickly and accurately.

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639–0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882–0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60–80%, >40–60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51–0.97) to 0.48 (95% CI, 0.36–0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

This study investigates the advantages of combining Spark Plasma Sintering (SPS) with Laser Cladding (LC) technology in the production of AlCoCrFeNi high-entropy alloy (HEA). By comprehensively applying SPS and LC composite processing techniques, we achieve rapid preparation of high-performance AlCoCrFeNi HEA. SPS technology enables rapid sintering under high-temperature conditions, while LC technology allows precise control of microstructure generation on the workpiece surface. Experimental results show that AlCoCrFeNi HEA prepared by single SPS technology exhibits a body-centered cubic (BCC) solid solution structure, while AlCoCrFeNi HEA processed with a combination of SPS and LC techniques demonstrates a complex microstructure consisting of equiaxed BCC phase, uniformly distributed granular face-centered cubic (FCC) solid solution, and α-Al2O3 ceramic phase. Composite processing also eliminates voids and pores caused by single SPS processing, resulting in AlCoCrFeNi HEA with low porosity. Furthermore, the maximum hardness of AlCoCrFeNi HEA produced by composite processing technology is approximately 644.1HV, significantly higher than that of AlCoCrFeNi HEA processed solely by SPS (approximately 328.7HV). Wear test results show that AlCoCrFeNi HEA processed by composite machining exhibits significant advantages in wear resistance, with the width and depth of wear tracks significantly reduced compared to AlCoCrFeNi HEA processed solely by SPS technology, with a 33.17% higher wear rate. In conclusion, composite processing using SPS combined with LC technology enables rapid preparation of AlCoCrFeNi HEA with low porosity, high hardness, and high wear resistance.

[Objective] The engineering disturbances have triggered soil erosion events in subalpine meadows, intensify regional soil erosion and vegetation destruction. The relationship between physical and chemical properties and disintegration characteristics of subalpine meadow soils in central Yunnan was studied to provide reference for soil and water conservation and control and vegetation protection in sub-alpine meadow ecosystems. [Methods] By X-ray diffraction, electron microscopy scanning, and static water disintegration experiments were conducted to determine the physico-chemical properties, mineral composition, microscopic structure, and disintegration characteristics of subalpine meadow soils in central Yunnan. The correlation between soil disintegration and physico-chemical properties was analyzed to explore the reason of soil disintegration in sub-alpine meadows of central Yunnan. [Results] (1) The subalpine meadow soils in central Yunnan exhibited a high susceptibility to disintegration when encountering water. The resistance to disintegration of different parent materials in the same soil layer were as follows sandstone>limestone≈basalt. The characteristics of different soil layers in the same parent material were as follows leaching horizon>deposition layer>parent material layer. (2) Correlation analysis showed that the average soil disintegration rate was significantly negative correlated with organic matter (r=-0.84) and total nitrogen (r=-0.83), positively correlated with clay content (r=0.88), and positively correlated with montmorillonite (r=0.68) and hematite (r=0.77). (3) The main factors affecting the disintegration of subalpine meadow soils in central Yunnan were biological processes and swelling of hydrophilic clay minerals such as montmorillonite and illite. [Conclusion] The resistance to disintegration of subalpine meadow soils in central Yunnan was ranked as follows: Sandstone>limestone≈basalt for different parent materials, and leaching horizon>deposition layer>parent material layer for different soil layers. The subalpine meadow soil in central Yunnan was easy to disintegrate when exposed to water, the main factors affecting the disintegration of subalpine meadow soils in central Yunnan were biological processes and swelling of hydrophilic clay minerals such as montmorillonite and illite.

In this work, a novel graphite-based electrochemical filter was developed for the efficient and environmentally friendly treatment of uranium tailings leachate. The filter utilizes graphite particles as filler and carbon felt as a conductor, powered by a DC power supply and driven by a peristaltic pump. In a non-circulating continuous operation filter experiment, uranium tailings leachate was tested for uranium removal efficiency under different operating parameters such as voltage and residence time, using both synthetic wastewater and actual uranium mine wastewater. This study is based on the fundamental principles of metal electrochemical reduction. The efficacy of this device for the continuous flow treatment of uranium tailings leachate was systematically investigated. The mechanism of uranium tailings leachate treatment by the electrochemical filter was elucidated through electrochemical analysis and product characterization. The results highlight that voltage and hydraulic retention time are critical factors influencing the efficiency of electrochemical filter treatment. Specifically, 4.0 V and 10 hours were identified as the optimized voltage and suitable hydraulic residence time, respectively, for the treatment of uranium tailings leachate using the electrochemical filter, resulting in a uranium removal rate exceeding 97%. In actual uranium tailings leachate applications, the maximum extraction rate can reach 5275 μmol/(m3∙h), confirming the feasibility of electrochemical filter in removing uranium from actual uranium tailings leachate and its good selectivity in complex water quality applications, the device can be quickly applied to uranium tailings leachate collection facilities and achieve in-situ uranium extraction. The voltage increase can significantly enhance the uranium extraction performance and can be portablely deployed in uranium mine water. In-situ uranium processing and recovery is achieved in processing and collection facilities. Characterization techniques such as field emission scanning electron microscope-energy spectrum analyzer(FESEM-EDS) and X-ray photoelectron spectrometer(XPS) were employed to analyze the reaction products on the graphite particles, revealing that uranium was evenly distributed on the surface of graphite particles and exhibits a stable crystal structure, the main mechanism responsible for uranium removal was adsorption-reduction, with uranium recovery products deposited on the electrode surface in the form of a mixture of U(Ⅳ) and U(Ⅵ). A cost estimation shows that the operational cost of extracting uranium from uranium tailings leachate using this device falls within the range of 176.6 ￥/kgU to 587.5 ￥/kgU. This cost is significantly lower than that of conventional land-based uranium resource development, making it economically viable. This research provides both theoretical and technical support for the efficient and environmentally friendly treatment of uranium tailings leachate.

Abstract Aluminum (Al) is usually added to solid propellants to improve the combustion performance, however the condensed combustion products (CCPs) especially the large agglomerates generated from aluminum combustion can reduce the specific impulse of the engine, and result in two-phase loss, residue accumulation and throat liner ablation. Al and ammonium perchlorate (AP), as important components of NEPE propellants, can affect the formation process of the CCPs of aluminized NEPE propellants. To clarify the effect of Al and AP particle sizes on the properties of the CCPs of aluminized NEPE propellants, a constant-pressure quench vessel was adopted to collect the combustion products of four different formulations of NEPE propellants. It was found that the condensed combustion products are mainly divided into aluminum agglomerates and oxide particles, the diameter of the aluminum agglomerates of these four different formulations of NEPE propellants at 7 MPa was smaller than that in 3 MPa, and the shells of the aluminum agglomerates were smoother and the spherical shape was more perfect. X-ray diffraction analysis of the CCPs of the four NEPE propellants under 3 MPa revealed the presence of both Al and Al2O3. With the increase of the particle size of Al and AP, the oxidation degree of aluminum particles decreases. The particle size of the CCPs of the four different formulations of NEPE propellants under 1 and 3 MPa was analyzed by using a laser particle size analyzer, it is found that the increase of AP particle size is helpful to reduce the size of condensate combustion products. Based on the classical pocket theory, establishing a new agglomeration size prediction model, which can be used to predict the agglomeration size on the burning surface. Compared with the empirical model, the new agglomeration size prediction model is in good agreement with the experimental results.

In this paper, we established a $ T1 $ criterion for the boundedness of Laguerre-Calderón-Zygmund operators on BMO$ _{L_{\alpha}}(0, \infty) $ associated with Laguerre operators $ L_\alpha(\alpha > -\frac{1}{2}) $. As applications, we proved the boundedness on BMO$ _{L_{\alpha}}(0, \infty) $ of variation operators for semigroups related to the Laguerre operator $ L_\alpha $.

Abstract Background and purpose To investigate the feasibility of synthesizing computed tomography (CT) images from magnetic resonance (MR) images in multi-center datasets using generative adversarial networks (GANs) for rectal cancer MR-only radiotherapy. Materials and methods Conventional T2-weighted MR and CT images were acquired from 90 rectal cancer patients at Peking University People’s Hospital and 19 patients in public datasets. This study proposed a new model combining contrastive learning loss and consistency regularization loss to enhance the generalization of model for multi-center pelvic MRI-to-CT synthesis. The CT-to-sCT image similarity was evaluated by computing the mean absolute error (MAE), peak signal-to-noise ratio (SNRpeak), structural similarity index (SSIM) and Generalization Performance (GP). The dosimetric accuracy of synthetic CT was verified against CT-based dose distributions for the photon plan. Relative dose differences in the planning target volume and organs at risk were computed. Results Our model presented excellent generalization with a GP of 0.911 on unseen datasets and outperformed the plain CycleGAN, where MAE decreased from 47.129 to 42.344, SNRpeak improved from 25.167 to 26.979, SSIM increased from 0.978 to 0.992. The dosimetric analysis demonstrated that most of the relative differences in dose and volume histogram (DVH) indicators between synthetic CT and real CT were less than 1%. Conclusion The proposed model can generate accurate synthetic CT in multi-center datasets from T2w-MR images. Most dosimetric differences were within clinically acceptable criteria for photon radiotherapy, demonstrating the feasibility of an MRI-only workflow for patients with rectal cancer.

To establish a rapid detection method for norovirus GII.2 genotype, this study employed reverse transcription recombinase polymerase amplification (RT-RPA) combined with CRISPR/Cas12a and lateral flow strip (RT-RPA-Cas12a-LFS). Here, the genome of norovirus GII.2 genotype was compared to identify highly conserved sequences, facilitating the design of RT-RPA primers and crRNA specific to the conserved regions of norovirus GII.2. Subsequently, the reaction parameters of RT-RPA were optimized and evaluated using agar-gel electrophoresis and LFS. The results indicate that the conserved sequences of norovirus GII.2 were successfully amplified through RT-RPA at 37°C for 25 minutes. Additionally, CRISPR/Cas12a-mediated cleavage detection was achieved through LFS at 37°C within 10 minutes using the amplification products as templates. Including the isothermal amplification reaction time, the total time is 35 minutes. The established RT-RPA-Cas12a-LFS method demonstrated specific detection of norovirus GII.2, yielding negative results for other viral genomes, and exhibited an excellent detection limit of 10 copies/μl. The RT-RPA-Cas12a-LFS method was further compared with qRT-PCR by analyzing 60 food-contaminated samples. The positive conformity rate was 100%, the negative conformity rate was 95.45%, and the overall conformity rate reached 98.33%. This detection method for norovirus GII.2 genotype is cost-effective, highly sensitive, specific, and easy to operate, offering a promising technical solution for field-based detection of the norovirus GII.2 genotype.

Background Breast cancer (BC) is one of most frequent female malignancies that poses multiple challenges in treatment and prevention. This study aimed to explore the role of miRNAs and their target genes during the BC progression. Methods Based on the BC data (113 normal and 1,118 tumor samples) from the TCGA-BRCA dataset, a single-sample gene set enrichment analysis (ssGSEA) was applied to calculate the cancer migration scores, and weighted gene co-expression network analysis (WGCNA) were performed using the WGCNA R package, with a focus on the set of genes associated with cancer migration. Key modules and hub genes related to cell migration and signaling pathways were identified. Survival analysis of hub genes was conducted using the survminer R package, and prediction of regulatory miRNAs were performed to analyze their impact on BC prognosis. In addition, the BC cell lines MCF-7 and MDA-MB-231 were used to further explore the effect of hsa-miR-1972 mimics on the gene expression and angiogenic factor regulation. Results The study classified important modules (MEblue, MEmagenta, MEpink, and MEfloralwhite) associated with cell migration and identified three hub genes, namely, MRPL20, COL4A1 and VWF. Survival analysis showed that certain hub genes with a low expression were related to a poor prognosis, whereas low-expressed COL4A1 and VWF were related to better survival outcomes. We also found that hsa-miR-1972 mimics significantly downregulated critical genes involved in BC metastasis and angiogenesis and effectively inhibited the proliferation of BC cell lines, showing a strong therapeutic potential. Manipulation of VWF expression in cells overexpressing hsa-miR-1972 had significant effects on the malignant markers and angiogenic factors, suggesting a novel therapeutic direction for BC treatment. Conclusion Our study highlighted the complex interplay of genetic factors in BC progression as well as the therapeutic potential of targeting specific miRNAs and their related hub genes. These findings provided novel insights into the pathogenesis of BC and suggested new direction for the therapeutic development for the cancer.

ObjectiveSmartphone addiction is on the rise globally. This study aimed to compare the rehabilitative effects of transcranial direct current stimulation (tDCS) and exergames on smartphone addiction among college students. Additionally, we discussed the central mechanisms through changes in electroencephalography (EEG) to provide clinical insights.MethodsThirty-six participants were randomly assigned to three groups: control group, tDCS group (bilateral dorsolateral prefrontal cortex stimulation), and exergame group. The intervention lasted for 4 weeks with twice-weekly sessions. Outcome measures included the Smartphone Addiction Scale - Chinese Version (SAS-C), Iowa Gambling Task (IGT) net scores, and event-related potential (ERP) data collected during the IGT, focusing on P300 and feedback-related negativity (FRN) amplitudes.ResultsAll groups showed significant reductions in SAS-C scores post-intervention. Behaviorally, post-intervention scores improved, indicating significant effects of different interventions on participants’ strategy choices. P300 amplitudes increased significantly at outcome electrode sites for all groups, with the most notable increase in tDCS group FC2 and CP1. FRN amplitudes decreased significantly post-intervention in the control and tDCS groups, with significant differences between the two groups.ConclusionAll three interventions appeared to have alleviating effect on smartphone addiction. After 4 weeks, participants showed improved executive control and decision-making abilities. Specifically, significant effects were observed in the tDCS group, with increased P300 amplitudes in the frontal, parietal, and central regions, as well as FRN amplitudes in the central and frontal regions. This suggested that tDCS enhanced psychological resources and improved inhibition control capabilities.

The centralization of household waste disposal represents a significant stride toward achieving ecological viability in rural China. This initiative can substantially alleviate the grassroots government's burden of managing rural household waste. The proliferation and utilization of smartphones, a powerful tool that can expedite and reduce the cost of imparting environmental protection knowledge to producers, is a beacon of hope in the fight against waste. This article, utilizing Probit modeling and micro-survey data from 2126 agricultural households in China, examines the effect of smartphone usage on farmers' participation in centralized household waste disposal. The findings indicate that smartphone usage significantly enhances farmers' engagement in centralized domestic waste disposal, motivating them to participate actively. Notably, this finding persists even after robustness tests. Further heterogeneity analyses indicate that older and low-income populations exhibit a more pronounced level of engagement in centralized household waste disposal. This paper presents these findings and underscores the importance of the proposed policies to enhance farmers' consciousness regarding the environmental implications of smartphone usage. These policies are not just suggestions but urgent and necessary steps towards a more technologically advanced and efficient waste management system, and their implementation is crucial for the future of waste management.

ABSTRACT Background Renal ischaemia‒reperfusion injury (IRI) is the primary cause of acute kidney injury (AKI). To date, effective therapies for delaying renal IRI and postponing patient survival remain absent. Ankyrin repeat domain 1 (ANKRD1) has been implicated in some pathophysiologic processes, but its role in renal IRI has not been explored. Methods The mouse model of IRI‐AKI and in vitro model were utilised to investigate the role of ANKRD1. Immunoprecipitation‐mass spectrometry was performed to identify potential ANKRD1‐interacting proteins. Protein‒protein interactions and protein ubiquitination were examined using immunoprecipitation and proximity ligation assay and immunoblotting, respectively. Cell viability, damage and lipid peroxidation were evaluated using biochemical and cellular techniques. Results First, we unveiled that ANKRD1 were significantly elevated in renal IRI models. Global knockdown of ANKRD1 in all cell types of mouse kidney by recombinant adeno‐associated virus (rAAV9)‐mitigated ischaemia/reperfusion‐induced renal damage and failure. Silencing ANKRD1 enhanced cell viability and alleviated cell damage in human renal proximal tubule cells exposed to hypoxia reoxygenation or hydrogen peroxide, while ANKRD1 overexpression had the opposite effect. Second, we discovered that ANKRD1's detrimental function during renal IRI involves promoting lipid peroxidation and ferroptosis by directly binding to and decreasing levels of acyl‐coenzyme A synthetase long‐chain family member 3 (ACSL3), a key protein in lipid metabolism. Furthermore, attenuating ACSL3 in vivo through pharmaceutical approach and in vitro via RNA interference mitigated the anti‐ferroptotic effect of ANKRD1 knockdown. Finally, we showed ANKRD1 facilitated post‐translational degradation of ACSL3 by modulating E3 ligase tripartite motif containing 25 (TRIM25) to catalyse K63‐linked ubiquitination of ACSL3, thereby amplifying lipid peroxidation and ferroptosis, exacerbating renal injury. Conclusions Our study revealed a previously unknown function of ANKRD1 in renal IRI. By driving ACSL3 ubiquitination and degradation, ANKRD1 aggravates ferroptosis and ultimately exacerbates IRI‐AKI, underlining ANKRD1's potential as a therapeutic target for kidney IRI. Key Points/Highlights Ankyrin repeat domain 1 (ANKRD1) is rapidly activated in renal ischaemia‒reperfusion injury (IRI) models in vivo and in vitro. ANKRD1 knockdown mitigates kidney damage and preserves renal function. Ferroptosis contributes to the deteriorating function of ANKRD1 in renal IRI. ANKRD1 promotes acyl‐coenzyme A synthetase long‐chain family member 3 (ACSL3) degradation via the ubiquitin‒proteasome pathway. The E3 ligase tripartite motif containing 25 (TRIM25) is responsible for ANKRD1‐mediated ubiquitination of ACSL3.

Background: Peony pollen (PP) has long been used as a functional food and herbal medicine. However, the potential protective effect and mechanisms of PP on benign prostatic hyperplasia (BPH) are still unclear. This study aims to explore the therapeutic effect and potential mechanisms of PP on BPH. Methods: The rat model of BPH was induced by subcutaneous injection of testosterone propionate (TP). Meanwhile, the model rats were treated with PP, and physiological and biochemical indexes, the steroid 5 alpha reductase 2 (SRD5A2), proliferating cell nuclear antigen (PCNA) and androgen receptor (AR) expressions, gut microbiota and short-chain fatty acids (SCFAs) were measured. Results: The results showed that the wet weight of prostate tissue and the thickness of epithelium decreased treated with PP significantly. In addition, the PP also adjusted the androgen levels, down-regulated the SRD5A2, PCNA and AR expressions, inhibited the expression of inflammatory factors including interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and reduced oxidative damage in BPH rats. It is worth noting that PP can obviously regulate the gut microbiota disorder of BPH rats, increase the abundance of beneficial bacteria (e.g., Romboutsia), reduce the abundance of pathogenic bacteria (e.g., norank_f_Oscillospiraceae), and stimulate the increase of SCFAs content. Conclusions: These data showed that PP can resist abnormal proliferation of the prostate by down regulation of SRD5A2, PCNA and AR expressions, attenuating oxidation stress and inflammatory damages and directly regulate the gut microbiota, especially the Firmicutes, and increased the level of SCFAs to ameliorate BPH. Therefore, PP might be an excellent natural plant for the development of BPH-related drugs or dietary supplements.

[ Objective ] VQ proteins are plant-specific proteins with the conserved VQ motifs ( Fxxh- VQxhTG ), which play an important role in plant growth and development as well as in response to abiotic stresses. The role of the VQ gene family in litchi ( Litchi chinensis ) had not been systematically studied. We identified the LcVQ gene family members as well as their expression patterns in different tissues of ly- chee and their responses to abiotic stresses. This laid a foundation for studying its stress-resistant mecha- nism. [ Methods ] The sequences of LcVQ genes were obtained from the L . chinensis genome using bioin- formatics methods , and their physicochemical properties , subcellular localizations , gene structures , and conserved motifs were analyzed ; a phylogenetic tree was constructed using MEGA 6.0 to analyze the phy- logenetic relationships of the VQ proteins in L . chinensis , Arabidopsis , and Oryza sativa ; the responses to various abiotic stresses were verified by the quantitative real-time PCR ( qRT-PCR ) . [ Results ] A total of 18 LcVQ genes were identified from L . chinensis genome , named as LcVQ1 - 18 , which were clustered into 9 subgroups. They were widely distributed on 11 of 15 chromosomes of lychee. The amino acid num- bers of LcVQ proteins were ranged from 111 to 427 , and molecular weights from 12.48 kD to 45.49 kD. Subcellular localizations showed that except for LcVQ15 and LcVQ17 were localized at the cytoplasm , all other LcVQ proteins were localized at the nucleus. The LcVQ promoters contained a large number of growth and development , plant hormone , and stress-responsiveness related response elements. The LcVQ genes expression was varied at different tissues , which was divided into universal expression and specific expression. Under the treatment of low temperature , high temperature , drought , and salt stress , we found that 4 , 3 , 3 , and 4 LcVQ genes were significantly up-regulated at 3 hours of treatment , respective- ly , indicating that these genes could respond to the abiotic stresses. [ Conclusion ] There are 18 VQ mem- bers in the L . chinensis genome with typical VQ binding domains and participate in different stress re- sponses.

This study aims to propose a radiomics model to identify male patients suffering from renal pelvis urothelial carcinoma (RPUC) with preoperative lymph node (LN) metastasis. In a study involving 133 male RPUC patients, 94 were assigned to a training group and 39 to a testing group. Their arterial-phase computed tomography (CT) images were analyzed to extract radiomics features, which were then refined through data reduction and feature selection. Using the least absolute shrinkage and selection operator (LASSO), a radiomics signature was created, which was then incorporated into a Logistic regression classifier in the training group to predict pathologic lymph node metastases. A comprehensive radiomics model was developed using multivariate logistic regression, integrating clinical risk factors. The model’s efficacy was evaluated in both sets using discrimination, calibration and decision curve analyses in both the training and testing sets. The constructed signature, composed of eight promising imaging-derived features, showed strong discrimination ability in both sets (training: area under the curve (AUC) 0.836 and testing: AUC, 0.817). When combined with CT-reported tumor status, the radiomics model demonstrated excellent calibration and discrimination, achieving an AUC of 0.849 in the training set and 0.851 in the testing set. The radiomics model, incorporating both the radiomics signature and the CT-reported tumor status, could help in the preoperative individualized prediction of LN metastasis in male patients with RPUC.

Abstract Background Tripartite motif-containing 26 (TRIM26), a member of the TRIM protein family, exerts dual function in several types of cancer. Nevertheless, the precise role of TRIM26 in clear cell renal cell carcinoma (ccRCC) has not been investigated. Methods The expression of TRIM26 in ccRCC tissues and cell lines were examined through the use of public resources and experimental validation. The impacts of TRIM26 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process were determined via CCK-8, colony formation, EdU incorporation, wound healing, Transwell invasion, Western blot, and Immunofluorescence assays. RNA-seq followed by bioinformatic analyses were used to identify the downstream pathway of TRIM26. The interaction between TRIM26 and ETK was assessed by co-immunoprecipitation, qRT-PCR, Western blot, cycloheximide (CHX) chase, and in vivo ubiquitination assays. Results We have shown that TRIM26 exhibits a downregulation in both ccRCC tissues and cell lines. Furthermore, this decreased expression of TRIM26 is closely linked to unfavorable overall survival and diseases-free survival outcomes among ccRCC patients. Gain- and loss-of-function experiments demonstrated that increasing the expression of TRIM26 suppressed the proliferation, migration, invasion, and EMT process of ccRCC cells. Conversely, reducing the expression of TRIM26 had the opposite effects. RNA sequencing, coupled with bioinformatic analysis, revealed a significant enrichment of the mTOR signaling pathway in the control group compared to the group with TRIM26 overexpression. This finding was then confirmed by a western blot assay. Subsequent examination revealed that TRMI26 had a direct interaction with ETK, a non-receptor tyrosine kinase. This interaction facilitated the ubiquitination and degradation of ETK, resulting in the deactivation of the AKT/mTOR signaling pathway in ccRCC. ETK overexpression counteracted the inhibitory effects of TRIM26 overexpression on cell proliferation, migration, and invasion. Conclusion Our results have shown a novel mechanism by which TRIM26 hinders the advancement of ccRCC by binding to and destabilizing ETK, thus leading to the deactivation of AKT/mTOR signaling. TRIM26 shows promise as both a therapeutic target and prognostic biomarker for ccRCC patients.

Introduction. The emergence of new scientific and clinical evidence on the use of retrograde intrarenal surgery (RIRS) for the management of kidney stones has prompted periodic systematisation, analysis, and evaluation of outcomes to standardise its application and determine future directions for research and development.Objective. To present the Russian adaptation of a guideline on retrograde intrarenal surgery from the International Urolithiasis Alliance guideline series to provide a theoretical basis for urologists performing RIRS.Materials & Methods. A systematic review was conducted on the RIRS-associated publications available in the PubMed database to prepare a set of recommendations during the period from 1 January 1964 until 1 October 2021. The recommendations were evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system, which classifies, evaluates, develops, and examines recommendations. The modified Oxford Centre for Evidence-Based Medicine's (OCEBM) system for categorising the level of evidence and relevant comments have been applied to assess the strength of the conclusions.Results. The research team conducted a comprehensive analysis of 36 published clinical guidelines on the following topics: 1. Indications and Contraindications 2. Preoperative Imaging 3. Preoperative Ureteral Stenting 4. Preoperative Medications 5. Perioperative Use of Antibiotics 6. Use of Antithrombotic Therapy 7. Anesthesia Issues 8. Intraoperative Positioning 9. Equipment 10. Complications.Conclusion. A series of recommendations for RIRS, offered here should help provide safe and effective performance of RIRS.

Abstract Objective Autophagy‐related 5 (ATG5) facilitates the pathologic process of acute ischemic stroke (AIS) via multiple ways. This study aimed to identify the association of serum ATG5 with clinical outcomes in AIS patients. Methods Serum ATG5 from 280 AIS patients were detected at admission, Day (D)1, D3, D7, D30, and D90 after admission by enzyme‐linked immunosorbent assay. The median (interquartile range) follow‐up was 21.1 (5.9–43.9) months. Another 50 healthy controls (HCs) were also enrolled for serum ATG5 determination. Results ATG5 was elevated (p 2 and mRS ≤2 at D90, respectively. ATG5 at admission, D1, D3, D30, and D90 was elevated in AIS patients with mRS >2 versus those with mRS ≤2 (all p

Objective(s): Bevacizumab is a commonly used anticancer drug in clinical practice, but it often leads to adverse reactions such as vascular endothelial damage, hypertension, arterial and venous thrombosis, and bleeding. This study investigated the protective effects of metformin against bevacizumab-induced vascular injury in a mouse model and examined the possible involvement of GDF15/PI3K/AKT/FOXO/PPARγ signaling in the effects.Materials and Methods: C57 male mice were purchased. To investigate metformin, the mice were assigned to the saline, bevacizumab (15 mg every 3 days), metformin (1200 mg/day), and bevacizumab+metformin groups. To investigate GDF15, the mice were assigned to the siNC+bevacizumab, siNC+bevacizumab+metformin, siGDF15+bevacizumab, and siGDF15+bevacizumab+metformin groups. Histological staining was used to evaluate vascular injury. Flow cytometry was used to evaluate apoptosis. ELISA was used to measure plasma endothelial injury markers and proinflammatory cytokines. qRT-PCR and western blot were used to determine the expression of GDF15 and PI3K/AKT/FOXO/PPARγ in aortic tissues.Results: Metformin alleviated bevacizumab-induced abdominal aortic injury, endothelial cell apoptosis, and systemic inflammation in mice (all P

Abstract Background Bladder cancer (BC) is the most common urinary tract malignancy. Aurora kinase B (AURKB), a component of the chromosomal passenger protein complex, affects chromosomal segregation during cell division. Mitotic arrest-deficient 2-like protein 2 (MAD2L2) interacts with various proteins and contributes to genomic integrity. Both AURKB and MAD2L2 are overexpressed in various human cancers and have synergistic oncogenic effects; therefore, they are regarded as emerging therapeutic targets for cancer. However, the relationship between these factors and the mechanisms underlying their oncogenic activity in BC remains largely unknown. The present study aimed to explore the interactions between AURKB and MAD2L2 and how they affect BC progression via the DNA damage response (DDR) pathway. Methods Bioinformatics was used to analyze the expression, prognostic value, and pro-tumoral function of AURKB in patients with BC. CCK-8 assay, colony-forming assay, flow cytometry, SA-β-gal staining, wound healing assay, and transwell chamber experiments were performed to test the viability, cell cycle progression, senescence, and migration and invasion abilities of BC cells in vitro. A nude mouse xenograft assay was performed to test the tumorigenesis ability of BC cells in vivo. The expression and interaction of proteins and the occurrence of the senescence-associated secretory phenotype were detected using western blot analysis, co-immunoprecipitation assay, and RT-qPCR. Results AURKB was highly expressed and associated with prognosis in patients with BC. AURKB expression was positively correlated with MAD2L2 expression. We confirmed that AURKB interacts with, and modulates the expression of, MAD2L2 in BC cells. AURKB knockdown suppressed the proliferation, migration, and invasion abilities of, and cell cycle progression in, BC cells, inducing senescence in these cells. The effects of AURKB knockdown were rescued by MAD2L2 overexpression in vitro and in vivo. The effects of MAD2L2 knockdown were similar to those of AURKB knockdown. Furthermore, p53 ablation rescued the MAD2L2 knockdown-induced suppression of BC cell proliferation and cell cycle arrest and senescence in BC cells. Conclusions AURKB activates MAD2L2 expression to downregulate the p53 DDR pathway, thereby promoting BC progression. Thus, AURKB may serve as a potential molecular marker and a novel anticancer therapeutic target for BC.

Abstract Growing skull fracture (GSF) is an uncommon form of head trauma among young children. In prior research, the majority of GSFs were typically classified based on pathophysiological mechanisms or the duration following injury. However, considering the varying severity of initial trauma and the disparities in the time elapsed between injury and hospital admission among patients, our objective was to devise a clinically useful classification system for GSFs among children, grounded in both clinical presentations and imaging findings, in order to guide clinical diagnosis and treatment decisions. The clinical and imaging data of 23 patients less than 12 years who underwent GSF were retrospectively collected and classified into four types. The clinical and imaging characteristics of the different types were reviewed in detail and statistically analyzed. In all 23 patients, 5 in type I, 7 in type II, 8 in type III, and 3 in type IV. 21/23 (91.3%) were younger than 3 years. Age ≤ 3 years and subscalp fluctuating mass were common in type I–III (P = 0.026, P = 0.005). Fracture width ≥ 4 mm was more common in type II–IV (P = 0.003), while neurological dysfunction mostly occurred in type III and IV (P

TNFRSF11B contributes to tumorigenesis in many malignancies. Nevertheless, its function and underlying tumorigenic mechanism in bladder cancer (BC) has been rare.The clinical significance and relevant signaling pathway of TNFRSF11B in BC were assessed using bioinformatic analysis. The determination of TNFRSF11B expression was conducted in bladder tissues and BC cells. BC cells were subjected to functional experiments to evaluate their ability to proliferate, migrate, and invade. Cell apoptosis experiments were conducted. The protein levels of markers associated with epithelial-mesenchymal transition (EMT) and molecules linked to the PI3K/AKT pathway were assessed. To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized. TNFRSF11B exhibited significant upregulation in both BC tissues and various cell lines. Inhibited TNFRSF11B expression impeded the growth, movement, infiltration of BC cells. Conversely, the ultimate outcome varied when TNFRSF11B was overexpressed. In vivo assay further confirmed the above results. Furthermore, TNFRSF11B promoted malignant traits by controlling the PI3K/AKT pathway. In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.

The severity of the dengue epidemic is on the rise, with its geographic range had expanded to southern Europe by 2024. In this August, the WHO updated the pathogens that could spark the next pandemic, dengue virus was on the list. Vaccines and drugs serve as powerful tools for both preventing dengue infections and treating patients. Animal models play a pivotal role in vaccine development and drug screening. Available potential susceptible animals, including non-human primates, rodents, pigs, and tree shrews, have been extensively explored to establish animal models of dengue disease. Despite significant advancements, there are still notable limitations. Different animal models exhibit distinct constraining factors such as viraemia, host susceptibility, immune function of the host, clinical symptoms, ADE (antibody-dependent enhancement) phenomena, cytokine storm response to various serotypes and strain variations. Furthermore, despite extensive research on the dengue virus receptor in recent years, genetically modified animal models immunocompetent harbouring dengue virus susceptibility receptors have not yet been available. This work reviewed the research progress of dengue virus receptors and dengue animal models, suggesting that the development of genetically modified murine models expressing dengue virus functional receptors may hold a promise for future dengue disease research, especially for its vaccine development.

Echocardiography is a key tool for the diagnosis of cardiac diseases, and accurate left ventricular (LV) segmentation in echocardiographic videos is crucial for the assessment of cardiac function. However, since semantic segmentation of video needs to take into account the temporal correlation between frames, this makes the task very challenging. This article introduces an innovative method that incorporates a modified mixed attention mechanism into the SegFormer architecture, enabling it to effectively grasp the temporal correlation present in video data. The proposed method processes each time series by encoding the image input into the encoder to obtain the current time feature map. This map, along with the historical time feature map, is then fed into a time-sensitive mixed attention mechanism type of convolution block attention module (TCBAM). Its output can serve as the historical time feature map for the subsequent sequence, and a combination of the current time feature map and historical time feature map for the current sequence. The processed feature map is then input into the Multilayer Perceptron (MLP) and subsequent networks to generate the final segmented image. Through extensive experiments conducted on two different datasets: Hamad Medical Corporation, Tampere University, and Qatar University (HMC-QU), Cardiac Acquisitions for Multi-structure Ultrasound Segmentation (CAMUS) and Sunnybrook Cardiac Data (SCD), achieving a Dice coefficient of 97.92 % on the SCD dataset and an F1 score of 0.9263 on the CAMUS dataset, outperforming all other models. This research provides a promising solution to the temporal modeling challenge in video semantic segmentation tasks using transformer-based models and points out a promising direction for future research in this field.

Background: SARS-CoV-2, first identified in Wuhan, China, in December 2019, has been gradually spreading worldwide since 2020. The relationship between SARS-CoV-2 infection and psychotic disorders has received much attention, and several studies have described the direct/indirect mechanisms of its effects on the brain, but no mechanism has been found to explain recurrent episodes of COVID-19-related psychotic symptoms. Case: We report the case of an 18-year-old female patient with no family or personal psychotic disorder history with multiple hospital admissions with symptoms such as disorganized speech and behavior, hyperactivity, restlessness, and impulsive aggression during the COVID-19 recovery period. Relevant tests revealed longitudinal changes such as persistent IL-6 and IL-10 elevation, abnormal discharges on EEG, and brain and hippocampal MRI abnormal signals. The patient was treated with antipsychotics, MECT, combination therapy of hormones and antivirals, then discharged after multiple treatment rounds. Conclusion: The case presented here outlines the possibility that the COVID-19 recovery period may be a critical period for acute psychotic episodes and that the patient's recurrent psychotic symptoms may be associated with neuro-immuno-endocrine dysfunction mediated by sustained cytokine synthesis, further causing structural and functional brain damage. Routine psychiatric evaluation and related screening should be performed at all stages of the illness to better identify, prevent, and effectively intervene in psychiatric disorders following COVID-19. Because many outcomes require long-term assessment, a clearer understanding of the impact of the COVID-19 epidemic on mental health is likely to emerge in the future.

Abstract Conductive polymer hydrogels have greatly improved the compatibility of electronic devices with biological tissues for human–machine interfacing. Hydrogels that possess low Young's modulus, low interfacial impedance, and high tensile properties facilitate high‐quality signal transmission across dynamic biointerfaces. Direct incorporation of elastomers with conductive polymers may result in undesirable mechanical and/or electrical performance. Here, a covalent cross‐linking network and an entanglement‐driven network with conductive poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) have been combined. The triple‐network conductive hydrogel shows high stretchability (with fracture strain up to 900%), low impedance (down to 91.2 Ω·cm2), and reversible adhesion. Importantly, ultra‐low modulus (down to 6.3 kPa) and strain‐insensitive electrical/electrochemical performance were achieved, which provides a guarantee for low current stimulation. The material design will contribute to the progression of soft and conformal bioelectronic devices, and pave the way to future implantable electronics.

Drought stress impairs crop growth and development. BEL1-like family transcription factors may be involved in plant response to drought stress, but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress. Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton (Gossypium hirsutum) response and defense to drought stress. Expression of GhBLH5-A05 in cotton was induced by drought stress. Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance, whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress. GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes. GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03. Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05. We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.

Increasing distributed generators (DGs) and flexible loads (FLs) enable distribution systems to provide both active and reactive power reserves (P-Q reserves) in supporting the frequency and voltage regulations of transmission systems. However, such requirements at the interface between the transmission system operator (TSO) and distribution system operator (DSO) affect the distribution system operation security, considering the uncertainties of DGs and FLs. To exploit the reserve potential of distribution systems, this paper investigates the voltage-dependent P-Q reserve capacity (V-PQRC) of such types of distribution systems. V-PQRC reflects the feasible space of P-Q reserves that the DSO can provide to the TSO taking the voltage deviation limit at TSO-DSO interface into consideration, while ensuring the distribution system operation security under uncertainties of DGs and FLs. An evaluation method for V-PQRC at the TSO-DSO interface is proposed. To improve the robust performance of the evaluation method, the DG uncertainty is captured by a generalized ambiguity set and the FL uncertainty is addressed by designing a constrained sliding mode controller (CSMC). Three objectives are considered in the evaluation, i.e., P reserve capacity, Q reserve capacity, and the voltage deviation limit at the TSO-DSO interface. Then, a multi-objective optimization model integrating the generalized robust chance-constrained optimization and CSMC (GRCC-CSMC) is established for V-PQRC evaluation to obtain the Pareto optimal reserve schemes. Finally, a non-approximated selecting (NAS) method is proposed to build up a simplified V-PQRC linear model, which can be convenient to apply in the transmission-distribution system coordination. Simulation results reveal that the V-PQRC evaluation method can achieve a good performance of accuracy and robustness against uncertainties.

Abstract Intervertebral disc degeneration is a natural process during aging and a leading cause of lower back pain. Here, we generate a comprehensive atlas of nucleus pulposus cells using single-cell RNA-seq analysis of human nucleus pulposus tissues (three males and four females, age 41.14 ± 18.01 years). We identify fibrotic late-stage nucleus pulposus cells characterized by upregulation of serglycin expression which facilitate the local inflammatory response by promoting the infiltration of inflammatory cytokines and macrophages. Finally, we discover that daphnetin, a potential serglycin ligand, substantially mitigates the local inflammatory response by downregulating serglycin expression in an in vivo mouse model, thus alleviating intervertebral disc degeneration. Taken together, we identify late-stage nucleus pulposus cells and confirm the potential mechanism by which serglycin regulates intervertebral disc degeneration. Our findings indicate that serglycin is a latent biomarker of intervertebral disc degeneration and may contribute to development of diagnostic and therapeutic strategies.

Abstract Epigenetic regulation is reported to play a significant role in the pathogenesis of various kidney diseases, including renal cell carcinoma, acute kidney injury, renal fibrosis, diabetic nephropathy, and lupus nephritis. However, the role of epigenetic regulation in calcium oxalate (CaOx) crystal deposition-induced kidney injury remains unclear. Our study demonstrated that the upregulation of enhancer of zeste homolog 2 (EZH2)-mediated ferroptosis facilitates CaOx-induced kidney injury. CaOx crystal deposition promoted ferroptosis in vivo and in vitro. Usage of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, mitigated CaOx-induced kidney damage. Single-nucleus RNA-sequencing, RNA-sequencing, immunohistochemical and western blotting analyses revealed that EZH2 was upregulated in kidney stone patients, kidney stone mice, and oxalate-stimulated HK-2 cells. Experiments involving in vivo EZH2 knockout, in vitro EZH2 knockdown, and in vivo GSK-126 (an EZH2 inhibitor) treatment confirmed the protective effects of EZH2 inhibition on kidney injury and ferroptosis. Mechanistically, the results of RNA-sequencing and chromatin immunoprecipitation assays demonstrated that EZH2 regulates ferroptosis by suppressing solute carrier family 7, member 11 (SLC7A11) expression through trimethylation of histone H3 lysine 27 (H3K27me3) modification. Additionally, SOX4 regulated ferroptosis by directly modulating EZH2 expression. Thus, this study demonstrated that SOX4 facilitates ferroptosis in CaOx-induced kidney injury through EZH2/H3K27me3-mediated suppression of SLC7A11. Graphical Abstract

Abstract Prostate cancer (PCa) is one of the most common malignant tumors affecting the male genitourinary system. However, there is currently a lack of effective treatments for patients with advanced prostate cancer, which significantly impacts men’s overall health. Exonuclease 1 (EXO1), a protein with mismatch repair and recombination functions, has been found to play a vital role in various diseases. In our study, we discovered that EXO1 acts as a novel biomarker of PCa, which promotes prostate cancer progression by regulating lipid metabolism reprogramming in prostate cancer cells. Mechanistically, EXO1 promotes the expression of SREBP1 by inhibiting the P53 signaling pathway. In summary, our findings suggest that EXO1 regulated intracellular lipid reprogramming through the P53/SREBP1 axis, thus promoting PCa progression. The result could potentially lead to new insights and therapeutic targets for diagnosing and treating PCa.

Abstract Textile-based wearable electronics have attracted intensive research interest due to their excellent flexibility and breathability inherent in the unique three-dimensional porous structures. However, one of the challenges lies in achieving highly conductive patterns with high precision and robustness without sacrificing the wearing comfort. Herein, we developed a universal and robust in-textile photolithography strategy for precise and uniform metal patterning on porous textile architectures. The as-fabricated metal patterns realized a high precision of sub-100 µm with desirable mechanical stability, washability, and permeability. Moreover, such controllable coating permeated inside the textile scaffold contributes to the significant performance enhancement of miniaturized devices and electronics integration through both sides of the textiles. As a proof-of-concept, a fully integrated in-textiles system for multiplexed sweat sensing was demonstrated. The proposed method opens up new possibilities for constructing multifunctional textile-based flexible electronics with reliable performance and wearing comfort.

Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the contents of 25 metal elements in base liquor of different ages for Maotai-flavor Baijiu from three companies. A discriminant model was constructed using chemometrics to identify key differential metal elements. The results showed that the contents of metal elements in base liquor were positively correlated with age for each brand. Principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least squares discriminant analysis (PLS-DA) could effectively distinguish among six age groups; among them, PLS-DA had the best degree of discrimination, and the results of the PLS-DA model were consistent with those of the PCA model. Five key differential metal elements, namely Al, Ca, K, Na and Fe, were determined in the base liquor stored for 0–10 years by PLS-DA and one-way analysis of variance (ANOVA). The differential metal elements were found to play a positive role in the storage of base liquor through gas chromatography triple quadrupole mass spectrometry (GC-TQ-MS) detection. The discriminant model could discriminate base liquor of different ages from other companies. In summary, ICP-MS combined with chemometric analysis can effectively classify and identify base liquor of different ages for Maotai-flavor Baijiu, and determine the changes of metal element contents in base liquor for Maotai-flavor Baijiu during storage more accurately and efficiently.

Job-shop scheduling problem (JSP) is a mathematical optimization problem widely used in industries like manufacturing, and flexible JSP (FJSP) is also a common variant. Since they are NP-hard, it is intractable to find the optimal solution for all cases within reasonable times. Thus, it becomes important to develop efficient heuristics to solve JSP/FJSP. A kind of method of solving scheduling problems is construction heuristics, which constructs scheduling solutions via heuristics. Recently, many methods for construction heuristics leverage deep reinforcement learning (DRL) with graph neural networks (GNN). In this paper, we propose a new approach, named residual scheduling, to solving JSP/FJSP. In this new approach, we remove irrelevant machines and jobs such as those finished, such that the states include the remaining (or relevant) machines and jobs only. Our experiments show that our approach reaches state-of-the-art (SOTA) among all known construction heuristics on most well-known open JSP and FJSP benchmarks. In addition, we also observe that even though our model is trained for scheduling problems of smaller sizes, our method still performs well for scheduling problems of large sizes in terms of makespan. Interestingly in our experiments, our approach even reaches zero makespan gap for 49 among 60 JSP instances whose job numbers are more than 100 on 15 machines.

Abstract Holographic 3D display is highly desirable for numerous applications ranging from medical treatments to military affairs. However, it is challenging to simultaneously achieve large viewing angle and high-fidelity color reconstruction due to the intractable constraints of existing technology. Here, we conceptually propose and experimentally demonstrate a simple and feasible pathway of using a well-designed color liquid crystal grating to overcome the inevitable chromatic aberration and enlarge the holographic viewing angle, thus enabling large-viewing-angle and color holographic 3D display. The use of color liquid crystal grating allows performing secondary diffraction modulation on red, green and blue reproduced images simultaneously and extending the viewing angle in the holographic 3D display system. In principle, a chromatic aberration-free hologram generation mechanism in combination with the color liquid crystal grating is proposed to pave the way for on such a superior holographic 3D display. The proposed system shows a color viewing angle of ~50.12°, which is about 7 times that of the traditional system with a single spatial light modulator. This work presents a paradigm for achieving desirable holographic 3D display, and is expected to provide a new way for the wide application of holographic display.

Well group layout is one of the key steps of groundwater recovery with pump and treat technology. In order to improve the remediation efficiency of pump and treat technology, a pollution field was taken as the research area, and a nonlinear-dynamic-multi-objective simulation-optimization model was established. The minimum capital cost, maximum pollutant removal rate and shortest remediation time were taken as the optimization objectives, and different extraction flows under single, double and three-well modes were set. The weighted optimization method is used to compare the well group layout scheme. The results show that: Overall, the single-well mode has poor remediation efficiency, when focusing on capital cost, the double-well pumping scheme is better overall, when focusing on the standard time, the mitsui-well pumping scheme is better overall; the single-well mode with constant flow is better than the multi-well modes, if the pumping flow is reduced appropriately in the late stage of the multi-well modes, the total amount of water pumped can be reduced and the capital cost can be saved, the dynamic management of well groups can improve the remediation efficiency. This study provides a reference for the application of weighted optimization method combined with numerical simulation method in well group layout optimization of pump and treat technology, and verifies the flexibility and practicability of weighted optimization method in well group optimization application.

Fertilizers that release nutrients slowly can provide crops with consistent nutrients, while soils with good water-holding capacity can alleviate the impact of droughts on crops. Sodium alginate/carboxymethyl starch sodium/polydopamine/urea (SCPU) is a new kind of slow-release fertilizer with water absorption property. In this study, the Box–Behnken response surface methodology (RSM) was used to reveal the effects of concentrations of sodium alginate, carboxymethyl starch sodium, urea, calcium chloride and dopamine on the encapsulation efficiency and water absorption of SCPU. The results show that the optimum preparation conditions to obtain the highest level of encapsulation efficiency (89.27%) and water absorption (167.05%) are 2.2% sodium alginate, 5% carboxymethyl starch sodium, 30% urea, 1.9% calcium chloride and 0.52% dopamine.

Background/Objectives: Damage to renal tubular cells (RTCs) represents a critical pathological manifestation in calcium oxalate (CaOx) stone disease, but the underlying mechanism remains elusive. Energy metabolism reprogramming is a vital influencer of RTC survival, and SMYD2 is a histone methylation transferase that has been extensively implicated in various metabolic disorders. Hence, this research aimed to identify whether SMYD2 induces the reprogramming of energy metabolism in RTCs exposed to CaOx nephrolithiasis. Methods: Kidney samples were obtained from patients who underwent laparoscopic nephrectomy for non-functioning kidneys caused by nephrolithiasis. The glyoxylate-induced CaOx stone mice model was established and treated with AZ505. The SMYD2-knockout HK-2 cell line was constructed. Histological changes were evaluated by HE, VK, Tunel, Masson stainings. The molecular mechanism was explored through co-immunoprecipitation and western blotting. Results: The results found that SMYD2 upregulation led to energy reprogramming to glycolysis in human kidney tissue samples and in mice with CaOx nephrolithiasis. We also identified the substantial involvement of glycolysis in the induction of apoptosis, inflammation, and epithelial–mesenchymal transition (EMT) in HK-2 cells caused by calcium oxalate monohydrate (COM). In vivo and in vitro results demonstrated that SMYD2 inhibition reduces glycolysis, kidney injury, and fibrosis. Mechanistically, SMYD2 was found to promote metabolic reprogramming of RTCs toward glycolysis by activating the AKT/mTOR pathway via methylated PTEN, which mediates CaOx-induced renal injury and fibrosis. Conclusions: Our findings reveal an epigenetic regulatory role of SMYD2 in metabolic reprogramming in CaOx nephrolithiasis and associated kidney injury, suggesting that targeting SMYD2 and glycolysis may represent a potential therapeutic strategy for CaOx-induced kidney injury and fibrosis.

N6-methyladenosine (m6A) is the most common modification in eukaryotic RNAs. Growing research indicates that m6A methylation is crucial for a multitude of biological processes. However, research on the m6A modifications in the regulation of porcine muscle growth is lacking. In this study, we identified differentially expressed genes in the neonatal period of muscle development between Large White (LW) and NingXiang (NX) pigs and further reported m6A methylation patterns via MeRIP-seq. We found that m6A modification regulates muscle cell development, myofibrils, cell cycle, and phosphatase regulator activity during the neonatal phase of muscle development. Interestingly, differentially expressed genes in LW and NX pigs were mainly enriched in pathways involved in protein synthesis. Furthermore, we performed a conjoint analysis of MeRIP-seq and RNA-seq data and identified 27 differentially expressed and m6A-modified genes. Notably, a typical muscle-specific envelope transmembrane protein, WFS1, was differentially regulated by m6A modifications in LW and NX pigs. We further revealed that the m6A modification accelerated the degradation of WFS1 in a YTHDF2-dependent manner. Noteworthy, we identified a single nucleotide polymorphism (C21551T) within the last exon of WFS1 that resulted in variable m6A methylation, contributing to the differing WFS1 expression levels observed in LW and NX pigs. Our study conducted a comprehensive analysis of the m6A modification on NX and LW pigs during the neonatal period of muscle development, and elucidated the mechanism by which m6A regulates the differential expression of WFS1 in the two breeds.