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Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations (microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Abstract Observational studies have reported an association of obesity with periodontitis and tooth loss, yet findings remain inconsistent. We aim to investigate the genetic link underlying obesity-related traits (BMI [body mass index], WHR [waist-to-hip ratio], WHRadjBMI and childhood BMI), periodontitis and tooth loss. Leveraging summary statistics from large-scale genome-wide association studies, we comprehensively investigated the pair-wise genetic correlation using linkage disequilibrium score regression (LDSC) and SUPERGNOVA, identified shared loci using cross-phenotype association analysis (CPASSOC), and estimated causal association using Mendelian randomization. We identified a significant genetic correlation of obesity with tooth loss, but not with periodontitis. Partitioning the genome into LD-independent regions revealed 10 significantly shared local signals across six regions. Genome-wide cross-trait analysis uncovered 14 shared loci, four of which were colocalized: rs2064044 (PP4 = 0.94), rs6000329 (PP4 = 0.86), rs7134628 (PP4 = 0.86), and rs1286769 (PP4 = 0.90). Notably, rs1286769, identified via CPASSOC and validated through colocalization analysis, is located near RARβ, a gene associated with both BMI and denture use. Mendelian randomization revealed a nominally-significant causal association of obesity with periodontitis (P = 0.045) but a robust causal association with tooth loss represented by number of teeth (BMI: beta = $$\:-$$ 0.20, 95%CI = $$\:-$$ 0.26 to $$\:-$$ 0.14, P = 5.27 × 10–11; WHR: beta = $$\:-$$ 0.16, 95%CI = $$\:-$$ 0.24 to $$\:-$$ 0.08, P = 3.71 × 10–5). Results of CAUSE were consistent with main findings. From a genetic perspective, our work highlights an intrinsic link between obesity, periodontitis and tooth loss, which may add new lines of evidence and provide insights for clinical and public oral health applications.

Abstract Background The relationship between psoriasis and aging remains unclear. Biological age is considered as a tool for strong association with aging, but there is a lack of reports on the relationship between biological age and psoriasis. Therefore, this study aimed to explore the relationship between biological age and psoriasis. Methods Patients with psoriasis and non-psoriasis were recruited from National Health and Nutrition Examination Survey (NHANES) (12,973 cases), Medical Information Mart for Intensive Care (MIMIC-IV) (558 cases) and The First Clinical Medical College of Zhejiang Chinese Medical University (206 cases). Biological age was calculated using Klemera-Doubal method age (KDM-age) and phenotypic age (PhenoAge). Linear regression and logistic regression were used to explore the association between psoriasis and biological age advance. Cox regression was used to investigate the association between biological age advance and mortality. Finally, biological age advance was used to predict the death of psoriasis patients. Results In NHANES, linear regression showed that psoriasis led to a 0.54 advance in PhenoAge (Adjust Beta: 0.54, 95CI: 0.12–0.97, p = 0.018). The KDM-age advance due to psoriasis was not statistically significant (p = 0.754). Using data from China, we came to the new conclusion that for every unit rise in Psoriasis Area and Severity Index, PhenoAge advance rose by 0.12 (Beta: 0.12, 95CI: 0.01–0.22, p = 0.031). Using NHANES data, cox regression shows for every unit rise in PhenoAge advance patients had an 8% rise in mortality (Adjust hazard ratio: 1.08, 95CI: 1.04–1.12, p

In recent years, illegal passenger transport in freight trucks has become a critical concern for traffic safety and law enforcement. This study proposes an automated system for detecting illegal passenger transport using an improved CLIP-ILP (Illegal Passenger Detection) model. The proposed model incorporates multi-scale feature fusion, a cross-modal self-attention mechanism, and a more powerful text encoder to enhance detection performance. To evaluate the model, we constructed a comprehensive dataset consisting of tens of thousands of truck images, categorized into two types of trucks (four-wheeled and three-wheeled) and further classified into two subcategories: “illegal passenger transport” and “non-illegal passenger transport.” The model was trained using this dataset, with an emphasis on leveraging the CLIP framework’s ability to understand and integrate visual and textual data. Experimental results demonstrate that the proposed CLIP-ILP model achieves superior accuracy and robustness in detecting illegal passenger transport under various conditions. This research not only highlights the potential of deep learning technologies in enhancing traffic safety but also provides a novel and efficient approach for law enforcement agencies to monitor and address this growing issue effectively. You can access the code for our proposed method at https://github.com/wu-xuan-git/CLIP-ILP.

Abstract To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) and galactomannan (GM) testing in invasive pulmonary aspergillosis (IPA) and to compare mNGS with other diagnostic approaches (serum/bronchoalveolar lavage fluid (BALF)-GM and conventional microbiological tests (CMTs) including sputum smears and culture, BALF fungal culture, and bronchial brushing). In all, 237 patients were enrolled in this retrospective study, including 120 patients with IPA and 117 with non-IPA pulmonary infections treated at Henan Provincial People’s Hospital between June 2021 and February 2024. The diagnostic performance of mNGS was compared to conventional diagnostic methods including serum GM, BALF-GM, sputum smear microscopy, sputum culture, bronchial brushings, and BALF culture. The proportion of patients with underlying diseases was significantly higher in the IPA group than in the non-IPA group (P

Abstract In the field of gun launched missile extended range rocket, the propellant grain in the rocket needs to withstand significant launch loads during their firing phase, and also bear the high pressure caused by ignition, and the impact of launch overloads and ignition shocks on the structural integrity of propellants becomes very important. So this work investigated the dynamic initiation fracture toughness of the composite modified double-base (CMDB) propellant by both experiments and numerical simulations. The dynamic mechanical properties test of the cracked straight through flattened Brazilian disc (CSTFBD) specimens were conducted using a modified Split Hopkinson pressure bar (SHPB). By comparing the results of quasi static and dynamic numerical simulations, it was found that dynamic fracture initiation toughness can be determined by time-to-fracture using the quasi-static theory. The numerical simulation results combined with the ZWT constitutive model agree well with the experimental results, indicating that ZWT constitutive model is suitable for numerical simulation calculation of propellant structural integrity under dynamic load, and provides a theoretical basis for propellant structural integrity analysis under dynamic load. During the measurement of the mechanical response, the fracture surfaces of the dynamic test specimens were observed by electron microscopy scanning. Then the evolution of the microstructure synchronously was obtained. The scanning electron microscope (SEM) results revealed that fracture modes and breakage of the ammonium perchlorate (AP) particles in the surface layer played an important role in determining the failure mechanism, which revealed the failure mechanism of the propellant under dynamic load. The result of experimental measurement showed the influence of loading rate on the dynamic fracture initiation toughness of CMDB propellant.

Abstract As big data technologies continue to evolve, recommendation systems have found broad application in domains such as online retail and social networking platforms. However, centralized recommendation systems raise numerous data privacy concerns. Federated learning addresses these concerns by allowing model training on client devices and aggregating model parameters without sharing raw data. Nevertheless, federated learning faces critical challenges related to feature extraction efficiency and noise sensitivity, limiting its application in e-commerce recommendation systems where data heterogeneity and high-dimensional features are prevalent. To address these gaps, this paper introduces a novel multi-view federated learning framework, Fed-FR-MVD, designed to enhance feature extraction efficiency and improve recommendation accuracy in e-commerce applications. Fed-FR-MVD integrates a FR mechanism within a multi-view structure, incorporating both item and user perspectives to improve feature representation and robustness. This approach yields a 12%–18% increase in recommendation accuracy across various performance metrics compared to single-view and other multi-view methods. By addressing data heterogeneity and optimizing feature utilization through dynamic rescaling, Fed-FR-MVD effectively mitigates the impact of noisy data, with performance maintained across noise levels of 5%–15%. Experimental results demonstrate that Fed-FR-MVD fills a key research gap by providing a more resilient and efficient framework for federated recommendation systems in privacy-sensitive and data-diverse e-commerce environments.

Abstract The Lin Yimu’s tomb in Zhejiang Province, China, is a significant Qing Dynasty tabia structure that, despite relatively good preservation, has suffered damage from weathering, necessitating urgent restoration. In this study, we conducted a comprehensive scientific analysis of archaeological samples from the tabia of Lin Yimu’s tomb, employing a range of analytical techniques including X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM/EDX), Fourier transform infrared spectroscopy (FTIR), chemical methods, and measurements of hardness and strength. Analytical results revealed that the main phases of the sample are calcite, quartz, illite/mica, feldspar, with a minor presence of Tung oil. The proportion of calcium carbonate is approximately 27%, and the ratio of earth to sand is 1:2, suggesting a raw material formula mass ratio of lime-earth-sand of 3:4:8. The surface hardness of the sample is measured at 293 ± 15 HL, with a compressive strength of 5.5 ± 0.2 MPa. The sand used in the raw material has a medium particle size of 250 μm, while earth particles are predominantly around 17 μm. The sample exhibits a porosity of 27.5%, with pore sizes concentrated at 95 nm. These findings contribute significantly to our understanding of Qing dynasty tomb construction technologies and provide a solid scientific basis for the restoration of such historical sites.

Abstract Background Robot-assisted surgery (RAS) is being performed with increasing frequency in pediatric oncology. We report our experience with RAS for renal tumors in children and compare the outcomes between RAS and laparoscopic surgery (LAS). Methods A total of 23 patients with renal tumor who underwent minimally invasive surgery (MIS) between January 2020 and December 2023 were included in the study. The inclusion criteria enrolled in this study was unilateral tumors with maximum tumor diameter less than 10 cm. Patients who had enlarged lymph node, venous thrombosis, preoperative tumor rupture, bilateral renal tumor, or extrarenal extension on imaging were deemed contraindications and excluded. Patient demographics, operative details, postoperative outcomes and follow-up were recorded. Results Among these patients, 17 underwent RAS and 6 underwent LAS. In the RAS group, the median age was 64 months (range, 9–156) with a median weight of 19.48 kg (range, 8.4–46.5); the maximum tumor diameter at operation was 55.65 mm (range, 22–88); the operation time was 188.8 min (range, 120–210), the intraoperative blood loss was 20 ml (range, 5–50), and the length of postoperative hospital stay was 4 days (range 1–9). There was no significant difference in patients’ age, weight, location, tumor size, histological pattern and operation time between the two groups (P > 0.05). The RAS group had a significantly less intraoperative blood loss (P = 0.026) and less length of postoperative stay (P = 0.01) than the LAS group. Conclusion Our initial experience suggested that RAS in pediatric renal tumor was feasible and safe, and it reduced surgical trauma and accelerate postoperative recovery for the patients. Due to the limitations of sample size and study quality, the clinical importance of these findings still needs to be further verified.

PurposeThe persistent infection of high-risk HPV (HR-HPV) is intricately linked to the onset and progression of cervical cancer. This research endeavored to develop a high-throughput 2D PCR method for closed-tube genotyping of 11 HR-HPVs.MethodsBase-quenched probes were specifically designed for FAM, VIC, and CY5 channels. The 2D PCR system underwent optimization, with its detection performance assessed in terms of specificity and sensitivity. Plasmid mixtures was used to simulate multiple infections of HPV, providing preliminary insights into the detection efficacy and throughput of the 2D PCR technology. Ultimately, the detection capability of this method was assessed using clinical samples.ResultsThe sequenced tags, when paired with primers, could generate Tm differences exceeding 3°C. These were then integrated with a fluorescent channel and Tm to differentiate and identify target genes upon detection. The refined 2D PCR system was confirmed to be free from cross-reactions and exhibited high specificity, capable of detecting 12 target genes within a single tube. A total of 294 cervical exfoliated cell samples were tested using 2D PCR and flow fluorescence hybridization method. The overall concordance between the two detection methods was 96.17% (Kappa = 0.910).ConclusionThe 2D PCR method, which integrates asymmetric PCR amplification with melting curve analysis, has the capacity to detect 11 types of HR-HPVs across three channels. This closed-tube detection approach offers several benefits including high throughput, straightforward operation, and low detection cost. Consequently, it can be effectively utilized for early screening and prevention of cervical cancer.

Myasthenia gravis (MG) is an autoimmune disorder within the spectrum of neuromuscular rare diseases, characterized by fluctuating muscle weakness. This report presents a case of a middle-aged woman with a chronic onset of asymmetric upper limb weakness accompanied by difficulty in finger extension, without ptosis or fluctuation for 4 years. The patient was finally diagnosed with MG by a significant decrement of Compound Muscle Action Potential in repetitive nerve stimuli, positive anti-acetylcholine receptor antibodies as well as the presence of a mass located in the anterior mediastinum. With subsequent immunotherapies for one month, the patient exhibited marked enhancement in muscle strength, followed by an uneventful thymectomy. After two months, the patient’s symptoms were fully alleviated, as evidenced by the reduction in Quantitative MG Score from 9 to 4 points, Myasthenia Gravis Composite Score from 6 to 1 points, Myasthenia Gravis Activities of Daily Living Score from 4 to 1 points, and Myasthenia Gravis Quality of Life-15 score from 14 to 8 points respectively. This case highlights the importance of differentiating autoimmune disorders from hereditary neuromuscular diseases and initiating timely treatment.

Objective: Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) has an improving effect in cognitive function, but it is still not clear in what specific cognitive domains. We here combined a single session of TMS (HF-rTMS/iTBS) with electroencephalography (EEG) to clarify the effects of magnetic stimulation techniques on executive function, working memory, and visuospatial attention in healthy participants, and to investigate the underlying neurophysiological mechanisms. Methods: Fifty-one healthy participants were randomly assigned to three stimulation groups (HF-rTMS, iTBS, and sham groups). Classical psychological paradigms (task-switching, 2-back with visual Oddball) and event-related potentials (ERPs) were performed to compare the behavioral indices of each paradigm before and after the two stimulations, as well as the changes in the ERP components. Results: Analysis of behavioral indicators showed that reaction times in the 2-back paradigm were faster after HF-rTMS and iTBS than after sham stimulation. However, no statistically significant differences were observed in the behavioral changes in the task-switching and visual Oddball paradigms. ERP analysis showed that N2 amplitude in the frontal and central regions of the participants increased during the 2-back paradigm following HF-rTMS and iTBS; however, no statistically significant differences were observed between the ERP components of the task-switching and visual Oddball paradigms. Conclusion: Single sessions of HF-rTMS and iTBS on the L-DLPFC specifically enhanced working memory performance, with no significant effects on executive function and visuospatial attention. Both true stimulations elicited more negative N2 in the frontal and central channels during the 2-back paradigm, suggesting increased recruitment of cognitive resources from these brain areas. Although iTBS and HF-rTMS improved working memory behavior, iTBS’s shorter stimulation time suggests it may have greater potential for clinical applications in terms of time-benefit costs.

Background: Memantine, which is an FDA-proven drug for the treatment of dementia, exerts its function by blocking the function of NMDA (N-methyl-D-aspartate) receptor, a calcium-permeable ion channel that reduces cytotoxic calcium overload. Chondrocyte senescence is a crucial cellular event that contributes to articular cartilage degeneration during osteoarthritis (OA) development. To date, the effects of memantine and its downstream NMDA receptor on chondrocyte senescence and OA have been rarely reported. Methods: The protein levels of NMDA receptor and its agonistic ligand, glutamate, were compared between normal and OA chondrocytes. The quantity of intracellular calcium ions and the level of mitochondrial damage were evaluated using specific fluorescent probes and transmission electron microscopy (TEM), respectively. Chondrocyte senescence was evaluated by senescence-associated β-galactosidase (SA-β-Gal) staining and p16INK4a analysis. The function of NMDA receptor in chondrocyte senescence and OA was tested via agonists activation and gene knockdown experiments. The therapeutic effects of memantine on OA were examined both in vitro and in vivo. Additionally, to verify the findings from animal samples, a propensity score-matched cohort study was conducted using data from a United Kingdom primary care database (i.e., IQVIA Medical Research Database [IMRD]) to compare the risk of OA-related joint replacement involved in memantine initiators versus active comparators (i.e., acetylcholinesterase [AchE] initiators) in patients with dementia. Results: The protein expression of NMDA receptor and the secretion of glutamate were both significantly increased in OA chondrocytes. NMDA receptor activation was found to stimulate chondrocyte calcium overload, which further led to mitochondrial fragmentation and chondrocyte senescence. Blocking the NMDA receptor with memantine and N-methyl-D-aspartate receptor subunit 1(NR1, the gene encoding NMDA receptor) knockdown resulted in reduced calcium influx, mitochondrial fragmentation, as well as cellular senescence in OA chondrocytes. Intra-articular injection of memantine in OA mice also exhibited protective effects against cartilage degeneration. Moreover, in the 1:5 propensity score-matched cohort study consisting of 6218 patients (n = 1435 in the memantine cohort; n = 4783 in the AchE cohort), the memantine initiator was associated with a lower risk of OA-related joint replacement than AchE initiators (Hazard ratio = 0.56, 95 % confidence interval: 0.34 to 0.99). Conclusion: NMDA receptor plays an important role in inflammatory-induced cytotoxic calcium overload in chondrocytes, while memantine can effectively block the NMDA receptor to reduce chondrocyte senescence and retard the development of OA. The translational potential of this article: As a clinically licensed drug used for the treatment of dementia, memantine has shown promising therapeutic effects on OA. Mechanistically, it functions by blocking NMDA receptor from mediating chondrocyte senescence. The protective effects of memantine against OA were verified not only by in vivo and in vitro experiments but also via a propensity score-matched human cohort study. These findings presented robust evidence for repurposing memantine for the treatment of OA.

Abstract Background Sterigmatocystin (STE) is a mycotoxin widely found in contaminated food and foodstuffs, and excessive long-term exposure to STE is associated with several health issues, including infertility. However, there is little information available regarding the effects of STE toxin on the female reproductive system, particularly concerning oocyte maturation. Methods In the present study, we investigated the toxic effects of STE on mouse oocyte maturation. We also used Western blot, immunofluorescence, and image quantification analyses to assess the impact of STE exposure on the oocyte maturation progression, mitochondrial distribution, oxidative stress, DNA damages, oocyte ferroptosis and asymmetric division defects. Results Our results revealed that STE exposure disrupted mouse oocyte maturation progression. When we examined the cellular changes following 100 µM STE treatment, we found that STE adversely affected polar body extrusion and induced asymmetric division defects in oocytes. RNA-sequencing data showed that STE exposure affects the expression of several pathway-correlated genes during oocyte meiosis in mice, suggesting its toxicity to oocytes. Based on the RNA-seq data, we showed that STE exposure induced oxidative stress and caused DNA damage in oocytes. Besides, ferroptosis and α-tubulin acetylation were also found in STE-exposed oocytes. Moreover, we determined that STE exposure resulted in reduced RAF1 protein expression in mouse oocytes, and inhibition of RAF1 activity also causes defects in asymmetric division of mouse oocytes. Conclusions Collectively, our research provides novel insights into the molecular mechanisms whereby STE contributes to abnormal meiosis.

Summary: Global pandemic has emphasized the needs for advanced pathogen diagnosis in dealing with newly emerged infectious threats, including the Langya henipavirus (LayV). LayV, as an emerging zoonotic pathogen, has potential to cause pandemic, but lacks of rapid diagnostic tools, particularly at point-of-care level. Here, we leveraged the merits of CRISPR-Cas12a biosensing and established a highly sensitive LayV detection method. By integrating CRISPR-Cas12a with RPA, 10 copies/μL ultra-sensitive LayV RNA detection has been achieved at room temperature within 30 min. More importantly, this study developed a special horseradish peroxidase (HRP)-single-stranded DNA (ssDNA) reporter enabling CRISPR-Cas12a to detect LayV RNA without pre-amplification, achieving a sensitivity of 1,200 copies/μL detectable by the naked eye. These explorations can serve as accelerator for CRISPR-Cas biosensing toward rapid response for newly emerged biological threats, and also provide a method to realize simple, precise, and amplicon-free point-of-care pathogen screening for resource limited or underdevelopment regions.

ABSTRACT Neuroendocrine tumor (NET) is a deadly malignancy disease that can be found anywhere in the body. The lack of tumor‐specific treatment led to the worse prognosis of NET. Anaplastic lymphoma kinase‐tyrosine kinase inhibitors (ALK‐TKIs), such as alectinib and crizotinib, have been used in the treatment of NET patients with ALK rearrangement. However, the response to ensatinib in NET patients with rare ALK fusion has been rarely reported. Here, we report a 55‐year‐old Chinese female patient with NET (atypical carcinoid tumor) and a novel CEP44‐ALK rearrangement identified by next‐generation sequencing (NGS). NGS can provide more information on mutation landscape for rare neuroendocrine tumors to guide treatment and assist in clinical decisions by presenting molecular changes. The patient received ensartinib (225 mg/day) for 18 months until disease progression in June 2024 and achieved a radiographic partial response. Although patients with ALK fusions showed response to ensatinib in nonsmall cell lung cancer (NSCLC), this study first reports a metastatic NET case with a novel CEP44‐ALK rearrangement that responded favorably to ensartinib.

BackgroundPsoriatic arthritis (PSA) is an inflammatory joint disease associated with psoriasis (PSO) that can be easily missed. Existing PSA screening tools ignore objective serologic indicators. The aim of this study was to develop a disease screening model and the Psoriatic Arthritis Inflammation Index (PSAII) based on serologic data to enhance the efficiency of PSA screening.MethodA total of 719 PSO and PSA patients from the National Health and Nutrition Examination Survey (NHANES) (as training set and test set) and 135 PSO and PSA patients who were seen at The First Affiliated Hospital of Zhejiang Chinese Medical University (as external validation set) were selected, 31 indicators for these patients were collected as potential input features for the model. Least Absolute Shrinkage and Selection Operator (LASSO) was used to identify PSA-related features. Five models of logistic regression (LR), random forest, k-nearest neighbor, gradient augmentation and neural network were developed in the training set using quintuple cross validation. And we developed PSAII based on the results of LASSO regression and weights of logistic model parameters. All performance metrics are derived on the test set and the external validation set.ResultsFive variables were selected to build models, including age, lymphocyte percentage, neutrophil count, eosinophilic count, and C-reactive protein. In all established models, the LR model performed the best, with an Area Under Curve (AUC) of 0.87 (95% confidence interval (CI): 0.83-0.90) on the test set; on the external validation set the AUC was 0.82 (95%CI: 0.74-0.90). The PSAII formula was PSAII = percentage of lymphocytes × C-reactive protein/(neutrophil count × eosinophilic count × 10). The AUC of PSAII in the test is 0.93 (95%CI: 0.88-0.97), and the cutoff value is 18. The AUC of the external validation set is 0.81 (95%CI: 0.72-0.89).ConclusionsThis study developed and validated five models to assist screening for PSA by analyzing serum data from NHANES and Chinese populations. The LR model demonstrated the best performance. We created PSAII for PSA screening. However, the high false positive rate of PSAII makes it necessary to combine it with other PSA screening tools when applied.

Pseudomonas aeruginosa is one of the leading causes of nosocomial infections worldwide and has emerged as a serious public health threat, due in large part to its multiple virulence factors and remarkable resistance capabilities. Stk1, a eukaryotic-type Ser/Thr protein kinase, has been shown in our previous work to be involved in the regulation of several signalling pathways and biological processes. Here, we demonstrate that deletion of stk1 leads to alterations in several virulence- and resistance-related physiological functions, including reduced pyocyanin and pyoverdine production, attenuated twitching motility, and enhanced biofilm production, extracellular polysaccharide secretion, and antibiotic resistance. Moreover, we identified AlgR, an important transcriptional regulator, as a substrate for Stk1, with its phosphorylation at the Ser143 site catalysed by Stk1. Intriguingly, both the deletion of stk1 and the mutation of Ser143 of AlgR to Ala result in similar changes in the above-mentioned physiological functions. Furthermore, assays of algR expression in these strains suggest that changes in the phosphorylation state of AlgR, rather than its expression level, underlie changes in these physiological functions. These findings uncover Stk1-mediated phosphorylation of AlgR as an important mechanism for regulating virulence and resistance in P. aeruginosa.

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund’s adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

Study Region: China. Study Focus: Water resources are one of the indispensable and irreplaceable natural resources in the operation of social and economic sustainable development. When economic measures are used to manage water resources, the market mechanism can be used to fully optimize resource allocation and boost water use efficiency (WUE). While existing research have begun to explore the impact of water rights trading (WRT) on WUE, most remain theoretical, with empirical studies often neglecting time differences in WRT implementation across provinces, leading to unresolved endogeneity issues. To accurately assess the policy effects of WRT, our research constructs a multi-period DID mode that addresses these limitations. New Hydrological Insights for the Regions: This study reveals that WRT significantly improves WUE, with water use per unit of output decreasing by 574.724 units in agriculture, 366.136 units in industry, and 210.770 units overall, demonstrating robustness. The policy effects of WRT require time to materialize, showing both dynamic and spatial sustainability. Technological innovation (TEIN) and water factor mobility (FM) serve as intermediary variables through which WRT optimizes WUE, with TEIN exhibiting a masking effect on WUE improvement. These insights can contribute to improved water resource management globally by guiding the development of tailored water rights policies and strategies that incorporate market mechanisms, foster technological innovation, and improve overall WUE.

Summary: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood and adolescence. The availability of appropriate and well-characterized preclinical models for RMS is limited, posing a challenge for investigating the molecular mechanisms and evaluating new targeted compounds in preclinical settings. Here, we collected 51 RMS specimens (referred to as ZJUCH-RMS cohort) and established 9 patient-derived cells (PDCs) and validated the identity of these cells by the expression of RMS-specific markers. Whole-transcriptome analysis identified high-confidence mutations in ZJUCH-RMS cohort including RAS, TP53, ARID1A, MYOD1, and MYCN. Further studies showed that RMS PDCs retained the genetic alterations and the expression of RMS hallmark and dependency genes in matched primary tumors and acted as valuable tools to assess drug responses and pharmacogenomic interactions. Our study provides unique PDCs that are available for preclinical studies of RMS and further advances the feasibility of RMS PDCs as valuable tools for developing personalized treatments for patients.

T-2 toxin, a trichothecene mycotoxin, is an important environmental pollutant that poses a threat globally to the health of humans and animals. It has been found to induce nephrotoxicity; however, the precise molecular mechanism involved remains unclear. In this study, mice were administered at a single dose of 2 mg/kg body weight T-2 toxin intraperitoneally, and kidney function and ultrastructural observations were assessed after 1 d, 3 d, and 7 d. Histopathological findings revealed that exposure to T-2 toxin caused noticeable tubular degeneration, necrosis and epithelial cell shedding in mouse kidneys. Transmission electron microscopy indicated that exposure to T-2 toxin caused mitochondrial swelling and vacuolization. Transcriptomic data revealed significant differences in the expression of 1122, 58, and 391 genes in kidney tissues 1 d, 3 d, or 7 d after T-2 toxin exposure, respectively. Moreover, after 1 d, the downregulated differentially expressed genes (DEGs) were found to be involved in the cell cycle, p53 signaling, and cellular senescence pathways, while the upregulated DEGs were found to be associated with the ribosomal pathway. Temporal changes in gene expression patterns (i.e., after 3 d and 7 d) and disturbances in cellular metabolism during the recovery period (7 d) were detected in mouse kidneys after exposure to T-2 toxin. In conclusion, this study is the first to provide a comprehensive comparative transcriptomic analysis of T-2 toxin exposure-induced nephrotoxicity-related gene regulation at different time points and to investigate the mechanism underlying the nephrotoxicity of T-2 toxin at the mRNA expression level.

Cyanophages play a pivotal role in controlling cyanobacterial populations in aquatic environments. These dsDNA viruses harbor auxiliary metabolic genes (AMGs) that modulate the key metabolic processes of their cyanobacterial hosts, such as Photosynthesis, nutrient uptake for the optimization of viral replication. Recently, pan1~pan5 and pam1~pam5 cyanophages have been isolated from the fifth largest water resource in China; Lake Chaohu. Detailed genomic analysis of these phages revealed that these isolated cyanophages especially Pan1, Pam2 and Pam3 possess unique AMGs that significantly enhance the metabolic activities of their hosts, potentially leading to the suppression of bloom formation and stabilization of the ecological dynamics of Lake Chaohu. Our findings provide concrete evidence that cyanophages encoding AMGs could serve as effective biocontrol agents against harmful algal blooms, offering a targeted approach to manage these environmental threats. The integration of cyanophage-based management therapies with traditional methods could advance the efficiency and sustainability of controlling cyanobacterial outbreaks, paving the way for novel applications in water resource management. This review emphasizes the importance and critical need for further exploration of phage-host dynamics to fully harness the potential of cyanophages in ecosystem regulation.

Ground volume loss is an important parameter for settlement control and prediction in shield tunneling. This parameter is usually determined empirically, while its variation along the tunnel is not predictable. In this study, an analytical formula for ground volume loss is obtained based on physical derivation. The ground volume loss is divided into two components. Key operational parameters, i.e. face pressure, grouting pressure and grouting volume, are used to calculate the two components. The proposed formula is then validated against the field data collected from Changzhou Metro in thick silty clay layer. The validation shows that the new formula gives reasonable prediction of ground volume loss. Furthermore, the three model coefficients derived from physical calculation are very close to the regression coefficients based on statistical method. For EPB tunnels excavated in silty clay layer, the ground volume loss along a specific tunnel can be predicted by the new formula. The analysis also indicates that the surface settlement of EPB tunnel should be controlled by a balanced combination of varied operational parameters.

BackgroundThe burden of chronic kidney diseases (CKD) is continuously increasing in the globe. Environmental factors are one of the trigger factors for chronic kidney diseases of unknown etiology (CKDu). However, the current toxicological evidence on the renal effects induced by environmental high concentrations of multiple ions in drinking water and high temperature exposure is very limited. ObjectiveTo preliminary investigate the renal effects of exposure to drinking water with environmental high concentrations of fluoride, calcium, sodium, and bromide ions alone or in combination with high temperature in mice. MethodsA mouse drinking water exposure model was established using ICR male mouse (8 weeks old) with exposure to 3 mg·L−1 fluoride ions, 250 mg·L−1 calcium ions, 400 mg·L−1 sodium ions, and 1 mg·L−1 bromide ions (to mimic the high concentration of ions in the groundwater in the areas with a high prevalence rate of CKDu in Sri Lanka) and high temperature of 32 ℃. ICR male mice were randomly divided into a mixed fluoride-calcium-sodium-bromide ion and high temperature exposure group, exposure groups of each ion and high temperature alone, a fluoride-calcium-sodium ion exposure group, and a fluoride-calcium-sodium-bromide ion exposure group. In the control group, the animals were given normal purified water at room temperature of (23±2) ℃. After 12 consecutive weeks of exposure, body weights and liver (kidney) organ coefficients were determined. Assessment of renal histopathologic damage was performed by hematoxylin-eosin staining and pathology scoring. At the end of the 12-week exposure period, 24 h urine samples were collected for the measurements of creatinine (UCr), albumin (ALB), neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2-MG) levels. Cell apoptosis was assessed by TUNEL assay. ResultsThe mice in the mixed exposure group showed a significant decrease in body weight and marked increases in the scores of renal histopathological injuries and the urinary levels of β2-MG compared to those of the control mice (P0.05), but the renal histopathological injury scores were significantly increased (P0.05). Furthermore, the renal histopathological injury score showed no significant differences between the fluoride-calcium-sodium ion exposure group and the fluoride-calcium-sodium-bromide ion exposure group (P>0.05). The interaction between bromide ions and fluoride-calcium-sodium ions on renal tissue pathological damage was not statistically significant (P>0.05). Results from the TUNEL assay showed a significant increase in renal cell apoptosis in the fluoride-calcium-sodium ion exposure group (P

To investigate the impact of Jolkinolide B (JB) on renal cell carcinoma (RCC), we treated RCC cell lines with various concentrations of JB (0, 5, 25, 50 and 100 μM) for 24 hours and assessed cell viability using the cell counting kit-8 (CCK-8) analysis. Then, we examined JB’s effects on proliferation, migration, apoptosis, reactive oxygen species (ROS) accumulation, and endoplasmic reticulum (ER) stress through 5-ethynyl-2′-deoxyuridine (EdU) incorporation, transwell migration assays, flow cytometry, ROS level determination, and western blot assays. Furthermore, we investigated the potential mechanism using western blot. Our results showed that JB dose-dependently reduced cell viability in both 786-O and Caki1 cells. Additionally, JB at concentrations of 5, 25 and 50 μM decreased the number of EdU-positive and migrating cells in both cell lines. Additionally, these concentrations of JB increased apoptosis rates, relative protein expressions of cleaved caspase-3 and cleaved caspase-9, ROS levels, and relative protein expressions of C/EBP-homologous protein (CHOP) and activated transcription factor 4 (ATF4) in both 786-O and Caki1 cells. Mechanistically, treatment with all three concentrations of JB significantly downregulated phosphorylated p38 (p-p38)/p38, phosphorylated protein kinase B (p-AKT)/AKT and phosphorylated phosphatidylinositol-3-kinase (p-PI3K)/PI3K in a dose-dependent manner. In summary, JB inhibited proliferation and migration while promoting apoptosis, ROS accumulation, and ER stress in RCC cells, potentially through the inactivation of mitogen-activated protein kinase (MAPK) and AKT signaling pathways.

Abstract Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g−1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.

Abstract Currently, many real-time semantic segmentation networks aim for heightened accuracy, inevitably leading to increased computational complexity and reduced inference speed. Therefore, striking a balance between accuracy and speed has emerged as a crucial concern in this domain. To address these challenges, this study proposes a dual-branch fusion network with multiscale atrous pyramid pooling aggregate contextual features for real-time semantic segmentation (MAFNet). The first key component, the semantics guide spatial-details module (SGSDM) not only facilitates precise boundary extraction and fine-grained classification, but also provides semantic-based feature representation, thereby enhancing support for spatial analysis and decision boundaries. The second component, the multiscale atrous pyramid pooling module (MSAPPM), is designed by combining dilation convolution with feature pyramid pooling operations at various dilation rates. This design not only expands the receptive field, but also aggregates rich contextual information more effectively. To further improve the fusion of feature information generated by the dual-branch, a bilateral fusion module (BFM) is introduced. This module employs cross-fusion by calculating weights generated by the dual-branch to balance the weight relationship between the dual branches, thereby achieving effective feature information fusion. To validate the effectiveness of the proposed network, experiments are conducted on a single A100 GPU. MAFNet achieves a mean intersection over union (mIoU) of 77.4% at 70.9 FPS on the Cityscapes test dataset and 77.6% mIoU at 192.5 FPS on the CamVid test dataset. The experimental results conclusively demonstrated that MAFNet effectively strikes a balance between accuracy and speed.

The dual-cylinder parallel balance oil circuit is an important heavy-duty support mechanism. Driven by the automation and unmanned trend of equipment in various industries, the internal leakage analysis and corresponding fault diagnosis for this mechanism are increasingly being valued. To solve this problem, verified by numerous simulation analyses and theoretical deduction, the pressure signal in the rodless chamber during the pressure maintenance stage was used innovatively to construct the fault features of the internal leakage, which is common and low-cost to be obtained. Then, the wavelet packet decomposition was used to extract three energy features and two time-domain features. Finally, an internal leakage diagnosis was performed based on the five features extracted from the experimental data, and the accuracy and robustness of the proposed five features were verified, which indicated that the proposed fault features and diagnosis method are practical in engineering.

Psoriasis is a chronic, relapsing, inflammatory skin disease and has been increasing year by year. It is linked to other serious illnesses, such as psoriatic arthritis, cardiometabolic syndrome, and depression, resulting in a notable decrease in the quality of life for patients. Existing therapies merely alleviate symptoms, rather than providing a cure. An in-depth under-standing of the pathogenesis of psoriasis is helpful to discover new therapeutic targets and develop effective novel therapeutic agents, so it has important clinical significance. This article reviews the new progress in the study of pathogenesis and natural products of psoriasis in recent years. These natural products were summarized, mainly classified as terpenoids, polyphenols and alkaloids. However, the translation of experimental results to the clinic takes a long way to go.

IntroductionIn recent years, coxsackievirus (CV) A10 has been associated with increasing sporadic hand, foot, and mouth disease (HFMD) cases and outbreaks globally. In addition to mild symptoms such as pharyngitis and herpangina, CVA10-related complications or even fatality can occur. Currently, systematic phylogenetic studies of CVA10 are limited.MethodsIn this study, we first explored the epidemiological and genetic characteristics of CVA10 in Nanchang, an inland southeastern city of China, based on the HFMD surveillance network from 2015-2023.ResultsAmong 3429 enterovirus-positive cases, 110 (3.04%) were associated with CVA10, with a male-to-female ratio of 1.62. The median age of the CVA10 patients was 2.3 years (interquartile range, IQR 1.0-4.0), with 94.55% (104/110) of the patients aged less than 5 years. Phylogenetic analyses using the full-length VP1, 5’UTR, P1, P2, P3 sequences and near full-length genomes indicated that CVA10 strains (n = 57) isolated in Nanchang belonged to genogroup C; two strains identified in 2017 belonged to C1 subtypes clustered with strains from Vietnam, Madagascar, France and Spain; and the others belonged to C2 subtypes interdigitating with CVA10 isolates from mainland China, the United States and Australia. Through extensive analysis, we identified a rare F168Y mutation in epitope 4 of VP1 in a Madagascar strain of genogroup F and a Chinese strain of genogroup C. Based on Bayesian evolutionary analyses, the average nucleotide substitution rate for the VP1 gene of CV10 strains was 3.07×10–3 substitutions/site/year. The most recent common ancestor (tMRCA) of genogroup C was dated 1990.84, and the tMRCA of CVA10 strains from Nanchang was dated approximately 2003.16, similar to strains circulating in other regions of China, suggesting that the viruses were likely introduced and cryptically circulated in China before the establishment of the HFMD surveillance network. Recombination analysis indicated intertypic recombination of the Nanchang strain with the genogroup G strain in the 3D region.DiscussionGiven the shifting dominance of viral genotypes and frequent recombination events, the existing surveillance system needs to be regulated to enhance genomic surveillance efforts on a more diverse spectrum of genotypes in the future.

Objective This study ascertained current status and influencing factors of readiness for hospital discharge (RHD) of lung cancer (LC) patients with enhanced recovery after surgery (ERAS) concept-guided postoperative management. Methods This study prospectively and consecutively included 217 LC patients who underwent whole-course ERAS concept-guided postoperative management at the Department of Thoracic Surgery of Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University from November 2023 to April 2024. RHD, quality of discharge teaching (QDT), and social support (SS) were evaluated using RHDS, QDTS, and SSRS, followed by correlation analyses of RHD with the other 2 factors. The clinical baseline and pathological data were compared between the high and low RHD groups, and the characteristics showing statistical significance were assigned as independent variables for regression analysis with RHD as the dependent variable. Results RHD, QDT, and SS were above average among LC patients with ERAS concept-guided postoperative management, and RHD was positively correlated with both QDT and SS. Age, education level, self-care ability, number of admissions, and presence of drainage tubes were independent influence factors for RHD of LC patients with ERAS concept-guided postoperative management. Conclusion In LC patients with ERAS concept-guided postoperative management, RHD may be improved by increasing QDT and SS and intervened by factors such as age, education level, self-care ability, number of admissions, and presence of drainage tubes.

A range of fire experiments were conducted to explore fire characteristics and smoke dynamics in a 1/6-scale stairwell adjacent to a room at different external wind velocities. The results indicated that the flame volume during the initial stage and the time taken for combustion to enter the steady stage both decrease with the increasing wind velocity. There are two opposite effects of the external wind on the fire combustion in a burning room adjacent to a stairwell. The inhibition effect plays an important role at lower wind velocities, leading to a decrease in the mass loss rate (MLR) of the pool fire. Conversely, the promotion effect dominates at higher wind velocities, resulting in an increase in the MLR. Stack effect and external wind demonstrate a synergistic relationship during experiments, and a correlation of the airflow velocity, wind velocity and heat release rate (HRR) is established. There are intersections in temperature curves at different wind velocities due to the smaller temperature decay rate in the stairwell and the lower smoke temperature near the pool fire at a higher velocity. Furthermore, a prediction model is also proposed for the smoke temperature distribution inside the stairwell, taking into account the wind velocity and HRR.

In this work, we have designed and modeled an integrated plasmonic computing module, which operates at 200 GHz clock frequency for high-end streaming algorithm applications. Our work includes designing the individual optical components (modulator, logic gate, and photodetector) and high-speed electronic driver circuits and integrating the components considering their interactions. We have also holistically evaluated the system-level performance of the computing module, taking into account various factors such as power consumption, operational speed, physical footprint, and average temperature. Through rigorous numerical analyses, we have found that with the existing technology and available materials, the plasmonic computing module can best achieve a bit-error-ratio (BER) of $10^{-1}$ . The performance can be improved by using a high electrooptic coefficient material in the phase shifter and increasing the driver circuit’s swing to greater than 1 V.

Abstract Background Neuroepithelial transforming gene 1 (NET1) is a RhoA subfamily guanine nucleotide exchange factor that governs a wide array of biological processes. However, its roles in meiotic oocyte remain unclear. We herein demonstrated that the NET1-HACE1-RAC1 pathway mediates meiotic defects in the progression of oocyte maturation. Methods NET1 was reduced using a specific small interfering RNA in mouse oocytes. Spindle assembly, chromosomal alignment, the actin cap, and chromosomal spreads were visualized by immunostaining and analyzed under confocal microscopy. We also applied mass spectroscopy, and western blot analysis for this investigation. Results Our results revealed that NET1 was localized to the nucleus at the GV stage, and that after GVBD, NET1 was localized to the cytoplasm and predominantly distributed around the chromosomes, commensurate with meiotic progression. NET1 resided in the cytoplasm and significantly accumulated on the spindle at the MI and MII stages. Mouse oocytes depleted of Net1 exhibited aberrant first polar body extrusion and asymmetric division defects. We also determined that Net1 depletion resulted in reduced RAC1 protein expression in mouse oocytes, and that NET1 protected RAC1 from degradation by HACE1, and it was essential for actin dynamics and meiotic spindle formation. Importantly, exogenous RAC1 expression in Net1-depleted oocytes significantly rescued these defects. Conclusions Our results suggest that NET1 exhibits multiple roles in spindle stability and actin dynamics during mouse oocyte meiosis.

Considering the large-deformation and multi-propeller characteristics of very flexible aircraft, propeller effects are introduced and accessed in the wing static and dynamic aeroelastic analysis and different propeller distributions are utilized to obtain more aeroelastic benefits. The propeller–wing aeroelastic interactions are innovatively modeled in the paper. For propeller–wing aerodynamic interaction, propeller-induced velocities are considered and added in the nonplanar steady and unsteady vortex lattice methods. For propeller–wing structural interaction, the conversion of loads and displacements between attached propellers and the large-deformation wing is derived. Static aeroelastic cases indicate that thrust can reduce structural deformation and slipstream can cause considerable lift increment. Dynamic cases indicate that thrust can reduce the wing’s maximum response to gust and bring an improvement of 9.4% in the wing’s critical velocity, while slipstream can reduce the gust response amplitude. In addition, using smaller and more propellers is recommended instead of an individual larger propeller. Decreasing and increasing propeller speeds toward the wingtip is more beneficial for cruise status and gust alleviation, respectively.

The kiwifruit (Actinidia) is an important nutritional and economic fruit crop. However, the short edible window period of kiwifruit has seriously affected its market value. 1-Methylcyclopropene (1-MCP), as a novel ethylene inhibitor, is widely applied to delay fruit ripening and senescence. To our knowledge, there are limited studies on the effects of 1-MCP on fruit quality and metabolism of different kiwifruit varieties. Three kiwifruit cultivars (i.e., ‘Xuxiang’, ‘Huayou’, and ‘Hayward’) widely cultivated in China were chosen as our research objects. The variations of storage quality and metabolic characteristics of kiwifruits treated with various 1-MCP concentration (0 μL/L, 0.5 μL/L, and 1.0 μL/L) were systematically investigated. The results showed that 1-MCP treatment significantly improved the quality of kiwifruit during storage. Among them, for ‘Xuxiang’ and ‘Hayward’ varieties, 1.0 μL/L 1-MCP treatment could delay the decrease in fruit firmness, the increase in maturity index and cellulase activity, and inhibit the decrease in ascorbic acid (AsA) level. However, the 0.5 μL/L 1-MCP had a great influence on the chlorophyll content and maturity index of the ‘Huayou’ cultivar, and the preservation effect was satisfactory. In addition, gas chromatography–mass spectrometry (GC–MS) based metabolomics studies revealed that 1-MCP treatment affected carbohydrates metabolism, fatty acids metabolism, and amino acids metabolism in different kiwifruit varieties. Correlation analysis indicated that sugars metabolism has the closest relationship with postharvest physiological quality. This research indicated that the effectiveness of 1-MCP treatments was dependent on fruit variety and treatment concentration. Furthermore, these findings provide a theoretical foundation for extending the shelf life of different kiwifruit varieties.

The γ-aminobutyric acid (GABA) is a widely distributed neurotransmitter in living organisms, known for its inhibitory role in animals. GABA exerts calming effects on the mind, lowers blood pressure in animals, and enhances stress resistance during the growth and development of plants. Enhancing GABA content in plants has become a focal point of current research. In plants, GABA is synthesized through two metabolic pathways, the GABA shunt and the polyamine degradation pathway, with the GABA shunt being the primary route. Extensive studies have investigated the regulatory mechanisms governing GABA synthesis. At the genetic level, GABA production and degradation can be modulated by gene overexpression, signaling molecule-induced expression, transcription factor regulation, and RNA interference. Additionally, at the level of transporter proteins, increased activity of GABA transporters and proline transporters enhances the transport of glutamate and GABA. The activity of glutamate decarboxylase, a key enzyme in GABA synthesis, along with various external factors, also influences GABA synthesis. This paper summarizes the biological functions, metabolic pathways, and regulatory mechanisms of GABA, providing a theoretical foundation for further research on GABA in plants.

A multimode fiber-based sensor is proposed and demonstrated for the detection of lead traces in contaminated water. The sensing mechanism involves using a light sheet to excite a specific group of skew rays that optimizes light absorption. The sensing region features an inline microbubble structure that funnels the skew rays into a tight ring, thereby intensifying the evanescent field. The sensitivity is further refined by incorporating gold nanoparticles, which amplify the evanescent field strength through localized surface plasmon resonance. The gold nanoparticles are functionalized with oxalic acid to improve specificity for lead ion detection. Experiment results demonstrated the significantly enhanced absorption sensitivity of the proposed sensing method for large center offsets, achieving a detection limit of 0.1305 ng/mL (the World Health Organization safety limit is 10 ng/mL) for concentrations ranging from 0.1 to 10 ng/mL.

The snow-shaped distribution network is developed and upgraded from the traditional single-loop network and double-loop network structure. It is composed of three or four groups of single-loop networks in pairs that form a feeder cluster in the form of a ring network. Based on this topology, the coordinated optimization operation problem is studied. First, the game elements are analyzed, and then a cooperative game-based, coordinated optimization operation model is established by taking the minimum network loss and voltage deviation of the system as the utility function. Then, the alternating direction multiplier method (ADMM) is employed in Cplex solver to solve the established optimization model. Finally, a numerical case is given to verify the effectiveness of the proposed model and method. The results show that, by using the complementary difference relationship of source–charge characteristics between different regions in the snow-shaped distribution networks, the cooperative game model can realize the energy interconnection among different regions to improve the operation level.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)–PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING–PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING–PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Abstract Radar signal sorting is a vital component of electronic warfare reconnaissance, serving as the basis for identifying the source of radar signals. However, traditional radar signal sorting methods are increasingly inadequate and computationally complex in modern electromagnetic environments. To address this issue, this paper presents a novel machine-learning-based approach for radar signal sorting. Our method utilizes SemHybridNet, a Semantically Enhanced Hybrid CNN-Transformer Network, for the classification of semantic information in two-dimensional radar pulse images obtained by converting the original radar data. SemHybridNet incorporates two innovative modules: one for extracting period structure features, and the other for ensuring effective integration of local and global features. Notably, SemHybridNet adopts an end-to-end structure, eliminating the need for repetitive looping over the original sequence and reducing computational complexity. We evaluate the performance of our method through conducting comprehensive comparative experiments. The results demonstrate our method significantly outperforms the traditional methods, particularly in environments with high missing and noise pulse rates. Moreover, the ablation studies confirm the effectiveness of these two proposed modules in enhancing the performance of SemHybridNet. In conclusion, our method holds promise for enhancing electronic warfare reconnaissance capabilities and opens new avenues for future research in this field.

Large-depth and multiscale gradient microstructure in dual-phase Al0.6CoCrFeNi high entropy alloy (HEA) were fabricated by explosion hardening (EH) technique. The gradient microstructure evolution was investigated in detail. The microhardness distribution and tensile properties near EH affected surface were also determined. The formation and strengthening mechanisms of gradient microstructure after EH treatment were subsequently analyzed. Experimental results showed that the multiscale gradient microstructure in terms of grain size, phase morphology, dislocation structure, texture was induced in dual-phase (BCC + FCC) HEA by EH technique. The closer to EH affected surface, the finer grain size, higher dislocation density and stronger texture intensity. The deformation and break of spinodal decomposition and formation of new grain boundaries by dislocation structure contributed to grain refinement and transition of equiaxed grains to dendritic grains from lower area to EH affected surface. After EH treatment, the microhardness generally increased with a maximum increase of ∼67% within 5 mm from EH affected surface, the tensile yield stress increased from 320 MPa to maximum of 700 MPa. The strengthening mechanism is different at various depth positions: near EH affected surface, the main strengthening mechanism is high-density dislocations, stacking faults and grain refinement; in areas relatively far from EH affected surface, only dislocation structure contributed to the strengthening of mechanical properties.

Interfacial solar water evaporation is a reliable way to accelerate water evaporation and contaminant remediation. Embracing the recent advance in photothermal technology, a functional sponge was prepared by coating a sodium alginate (SA) impregnated sponge with a surface layer of reduced graphene oxide (rGO) to act as a photothermal conversion medium and then subsequently evaluated for its ability to enhance Pb extraction from contaminated soil driven by interfacial solar evaporation. The SA loaded sponge had a Pb adsorption capacity of 107.4 mg g−1. Coating the top surface of the SA sponge with rGO increased water evaporation performance to 1.81 kg m−2 h−1 in soil media under one sun illumination and with a wind velocity of 2 m s−1. Over 12 continuous days of indoor evaporation testing, the Pb extraction efficiency was increased by 22.0% under 1 sun illumination relative to that observed without illumination. Subsequently, Pb extraction was further improved by 48.9% under outdoor evaporation conditions compared to indoor conditions. Overall, this initial work shows the significant potential of interfacial solar evaporation technologies for Pb contaminated soil remediation, which should also be applicable to a variety of other environmental contaminants.

Abstract Recently, owing to the requirements of inference speed, most real-time semantic segmentation networks often have shallow network depth, which limits the receptive field size of the model, leading to the limited acquisition of semantic information and resulting in intraclass inconsistency and ultimately a decrease in segmentation accuracy. Additionally, the shallow network depth also restricts the feature extraction capability of the network, reducing its robustness and ability to adapt to complex scenes. To address these issues, a bilateral network with a rich semantic extractor (RSE) for real-time semantic segmentation (BRSeNet) is presented to perform real-time semantic segmentation. First, to solve the problem of insufficient semantic feature information extraction, an RSE is proposed, which includes a multiscale global semantic extraction module (MGSEM) and a semantic fusion module (SFM). The MGSEM can extract rich global semantics and expand the effective receptive field. Simultaneously, the SFM efficiently integrates multiscale local semantics with multiscale global semantics, resulting in more comprehensive semantic information for the network. Finally, based on the characteristics of detail and semantic branches, a bilateral reconstruction aggregation module is designed to reconstruct the contextual information of detail features, model the interdependencies on semantic feature channels, and enhance feature representation. Comprehensive experiments on the challenging Cityscapes and ADE20K datasets are conducted. The experimental results show that the proposed BRSeNet achieves mean intersection over union of 74.9% and 35.7% at inference speeds of 74 and 65 frames per second, respectively, and ensures a favorable balance between segmentation accuracy and inference speed.

Summary: p53 regulates multiple signaling pathways and maintains cell homeostasis under conditions of DNA damage and oxidative stress. Although USP7 has been shown to promote p53 stability via deubiquitination, the USP7-p53 activation mechanism has remained unclear. Here, we propose that DNA damage induces reactive oxygen species (ROS) production and activates ATM-CHK2, and CHK2 then phosphorylates USP7 at S168 and T231. USP7 phosphorylation is essential for its deubiquitination activity toward p53. USP7 also deubiquitinates CHK2 at K119 and K131, increasing CHK2 stability and creating a positive feedback loop between CHK2 and USP7. Compared to peri-tumor tissues, thyroid cancer and colon cancer tissues show higher CHK2 and phosphorylated USP7 (S168, T231) levels, and these levels are positively correlated. Collectively, our results uncover a phosphorylation-deubiquitination positive feedback loop involving the CHK2-USP7 axis that supports the stabilization of p53 and the maintenance of cell homeostasis.

The snow-shaped distribution network (SDN) is a cable distribution network composed of eight (or six) 10 kV feeders from four (or three) substations in a regular connection. Compared with the traditional 10 kV distribution network, SDN can support a wide range of load transfer among six or eight feeders. Aiming at the problem of load spatial-temporal unbalanced condition caused by the integration of distributed generators (DGs) and different load types in different feeders, this paper proposes a dynamic reconfiguration strategy for load balancing in SDN considering DGs and energy storage system (ESS). Firstly, the basic structure of SDN is analyzed and the power flow model for its dynamic reconfiguration is developed. Secondly, the dynamic reconfiguration optimization model for load balancing in SDN considering DGs and ESS is proposed to utilize the load transfer capability to mitigate the load unbalanced condition and reduce active power loss. Thirdly, the original non-convex model is converted into a mixed-integer second-order cone programming (MISOCP) model by applying the second-order cone relaxation and the big-M method, which is solved by CPLEX solver. Finally, the effectiveness of the proposed model and method are verified by an actual case in Tianjin and IEEE 33-node system. The analysis results show that the proposed method can significantly alleviate the load unbalanced spatial-temporal distribution and improve the economic efficiency by regulating the operation of SDN including ESS optimization and dynamic reconfiguration.

To prevent convulsions and falls of patients in the absence of medical staff, it is crucial to monitor their physical condition in hospital wards. However, several unresolved challenges in human joint recognition remain, such as object occlusion, human self-occlusion and complex backgrounds, resulting in difficulties in its practical application. In this paper, a multi-LiDAR system is proposed to obtain a multi-view human body point cloud. An improved V2V-Posenet model was introduced to detect the actual position of the human joint. In this system, each point cloud was spliced into a full point cloud and voxelized into the model. We also used a random voxel zero setting for data enhancement, constraining the relative length between human joints into a loss function and three-dimensional Gaussian filtering in a heat map for model learning. The improved model exhibited excellent performance in detecting human joints in hospital wards. The experimental results showed that the improved model achieved 91.6 % mean average precision, compared to 80.1 % for the original model and 77.4 % for the comparison algorithm A2J-Posenet. The speed of the improved model meets the requirements for real-time target detection.

Given its status as the largest water-using sector, it remains pivotal to enhance the water usage efficiency within the agricultural sector to safeguard water resources. The main goal of the Integrated Agricultural Water Pricing Reform (IAWPR) is to encourage water conservation and foster sustainable agricultural development. Nonetheless, achieving sustainable progress in agriculture necessitates a dual focus: not only on the sustainable exploitation of resources but also on upholding the welfare of the population. The impact of the policy on farmers' welfare is not straightforward and requires scientific verification. To this end, the study focuses on the new relationship between IAWPR and farmers' income, exploring its underlying mechanism to broaden the economic benefits of IAWPR. In addition, combining multi-phase Difference-in-Differences (DID) and biennial Malmquist-Luenberger (BML) productivity index overcomes the limitations of traditional measurement methods. The results indicate that the IAWPR has a significant positive impact on farmers, leading to a 31.9% increase in income, and the impact is even more pronounced in the non-farm sector. Furthermore, the IAWPR primarily operates through enhancing agricultural green total factor productivity (AGTFP), where technological change (TC) serves as the principal driving factor of improvements in agricultural efficiency.