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The ridgetail white shrimp (Exopalaemon carinicauda), belonging to the Palaemonidae family of crustaceans, is an economically important small-to-medium-sized shrimp in China that is naturally distributed on the coasts of the Yellow and Bohai Seas. Due to its rapid growth and high tolerance for environmental stress, the scale at which E. carinicauda is cultured has expanded in recent years. The reproductive performance of broodstock is crucial to the yield and quality of larvae, as the egg production of E. carinicauda is much lower than that of other economically important shrimps. Meanwhile, E. carinicauda seedling production mainly relies on wild shrimp or breeding parents, resulting in low fertility and poor seed quality, such that the cultivation of E. carinicauda is often hindered by a slow growth rate and poor disease resistance, seriously limiting the development of the E. carinicauda farming industry. Optimizing growth and reproductive traits is vital for the animal aquaculture industry, as these traits are crucial for developing high-quality seedlings and are directly related to yield. Cultivating new varieties with high fertility and fast growth rates can effectively improve the aquaculture of E. carinicauda. In this study, we estimated the genetic parameters of growth and reproduction traits in E. carinicauda. We constructed 40 full-sibling lines of E. carinicauda and 25 half-sibling lines by pairing one male with two females. Thirty shrimps were randomly selected from each line at 50 d and 80 d of age, and the body length, total abdominal length, and body weight were measured to calculate the genetic parameters. The number of eggs, body length, body weight, and incubation time of the first spawning were measured to ensure that the culture conditions for each line were consistent. The main baits used during incubation were folded brachyuran rotifers (Brachinonus plicatilis) and brine shrimp (Artemia sinica). The heritability, phenotypic correlations, and genetic correlations of body weight, body length, total abdominal length traits, time of first spawning, absolute egg count, egg count per unit of body length, and egg count per unit of body weight in E. carinicauda were estimated at the ages of 50 and 80 d using a general linear model. The results showed that the heritability estimate values for body length, total abdominal length, and body weight at 50 d were approximately 0.27–0.69, 0.31–0.44, and 0.20–0.65, respectively, and those for body length, total abdominal length, and body weight at 80 d were approximately 0.39–0.54, 0.31–0.47, and 0.33–0.71, respectively. The heritability estimate values for the number of eggs, the number of eggs per unit of body length, the number of eggs per unit of body weight, and the time of the first spawning were approximately 0.45–0.52, 0.30–0.49, 0.43–0.48, and 0.33–0.77, respectively. The heritability estimate values for all three growth-related traits and four reproduction traits almost reached the level of medium-high heritability. The heritability estimate values for growth and reproduction traits based on full siblings reached a highly significant level according to t-tests. Therefore, the unbiased estimates of narrow-sense heritability for growth and reproduction traits were those estimated by the full-sibling variance component. The phenotypic and genetic correlations for growth and reproduction traits were approximately 0–0.756 9 and –0.006 5–0.951 4, respectively. The genetic correlation coefficients of body weight with body length and egg count were 0.951 4 and 0.205 8, respectively. The phenotypic correlation coefficients of body weight with body length and egg count were 0.742 0 and 0.212 4, respectively. However, the genetic and phenotypic correlations between body length and egg count were poor. Therefore, we suggest that body length and egg count be set as two different targets in breeding programs. The results indicate that the heritability estimate values for body length, total abdominal length, and body weight at 50 and 80 d and for reproduction traits including egg count, egg count per unit length or weight, and time of first spawning almost reached the level of medium-high heritability. The growth and reproductive traits of E. carinicauda can be selected through individual or population-phenotypic selection. The above results provide important basic data to support the breeding of E. carinicauda and have considerable application value for future breeding programs.

Abstract Background Acute myocardial infarction (AMI) is the most serious manifestation of coronary artery disease. At present, existing treatments cannot change the risk factors for the occurrence of the disease, so patients are prone to fear of progression or recurrence, and studies have shown that excessive fear will cause patients to over-examine, mental abnormalities, suicide and other behaviors, increase unnecessary medical care costs and the social medical burden. Thus to investigate the current situation of progression fear in patients with Acute Myocardial Infarction (AMI) admitted to hospital in stable stage and analyze its influencing factors. Methods This is a cross-sectional study. In this study, 160 AMI patients admitted to the Department of Cardiology of a 3 A hospital in Changchun from November 2022 to April 2023 were selected as the research sample by a convenient sampling method. Patients completed the general information questionnaire, the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the Brief Illness Perception Questionnaire (BIPQ), the Medical Coping Modes Questionnaire (MCSQ), the Social Support Rating Scale (SSRS), and the Positive Psychological Questionnaire (PPQ) at the time of stable condition. Using SPSS 25.0 software for data analysis, statistical methods mainly include descriptive statistics, analysis of variance, Pearson correlation analysis and multiple linear regression analysis. Results A total of 160 subjects were included, among which the score of simplified fear of progression scale was (33.43 ± 7.09), and the incidence of disorder of fear of progression was 50.60%. The influencing factors included gender (Beta = 0.118, P

Abstract Background Trichoderma reesei is renowned for its cellulase-producing ability and is used for biofuel production from lignocellulose. In plants and fungi, cellulase production is induced by cellulose and suppressed by glucose; however, whether metformin can enhance cellulase production and mitochondrial function in T. reesei remains unclear. Metformin reduces blood glucose levels by inhibiting hepatic gluconeogenesis; therefore, it is worth investigating whether metformin transmission modulates cellulase biosynthesis in T. reesei. Results Metformin increased cellulase production and the transcription of cellulase-related genes. It also enhanced the concentrations of Ca2+ in the cytosol and mitochondria and regulated the transcription levels of cellulase-related genes by modulating calcium homeostasis in T. reesei QM6a. In addition, metformin was identified as an antioxidant that can enhance cellulase activity by reducing reactive oxygen species (ROS). Our results demonstrated that metformin influences the state of mitochondria by enhancing mitochondrial activity and membrane potential to promote cellulase production. Conclusion Collectively, these results indicate that metformin enhances cellulase production, scavenges ROS, and protects mitochondrial activity in T. reesei. Graphical Abstract

Abstract Neuroendocrine prostate cancer (NEPC) arises from prostate adenocarcinoma after endocrine treatment failure and implies lethality and limited therapeutic options. Deciphering the molecular mechanisms underlying transdifferentiation from adenocarcinoma to NEPC may provide valuable therapeutic strategies. We performed a pan-cancer differential mRNA abundance analysis and identified that Kinesin-like protein (KIF1A) was highly expressed in NEPC. KIF1A knockdown impaired neuroendocrine(NE) features, including NE marker gene expression, stemness, and epithelial–mesenchymal transition (EMT), whereas KIF1A overexpression promoted these processes. Targeting KIF1A inhibited the growth of NE differentiated prostate cancer (PCa) cells in vitro and in vivo. Mechanistically, KIF1A bound with O-linked N-acetylglucosamine transferase (OGT) and regulated its protein expression and activity. Nuclear accumulation of OGT induced by KIF1A overexpression promoted intranuclear O-GlcNAcylation of β-catenin and OCT4 in nucleus. More importantly, our data revealed that OGT was critical for KIF1A induced NE differentiation and aggressive tumor growth. An OGT inhibitor, OSMI-1, can significantly inhibited NE differentiated PCa cell proliferation in vitro and tumor growth in vivo. Our findings showed that KIF1A promotes NE differentiation to NEPC by regulating the OGT-mediated O-GlcNAcylation. Targeting O-GlcNAcylation may impede the development of NEPC for a group of PCa patients with elevated KIF1A expression.

Myxomycetes play crucial ecological roles, yet their species diversity, distribution, and taxonomic relationships remain poorly understood. In this study, we examined 104 specimens from 19 provinces in China. Through morphological analysis, we identified a group of species with reduced lime formation, a feature typically associated with the Physaraceae, but with key morphological similarities to the Diderma. A comprehensive phylogenetic analysis was conducted using three genes (nSSU, EF-1α, and COI), resulting in a dataset of 452 sequences from 116 species. Notably, we identified a distinct clade within Didymiaceae containing species with fewer lime knots, a trait traditionally linked to Physaraceae. This clade, designated as the new genus Neodiderma, was phylogenetically positioned as a sister group to Diderma, potentially representing a transitional group between Didymiaceae and Physaraceae, supported by both morphological and molecular evidence. Eleven new species — N. macrosporum, N. pseudobisporum, N. verrucocapillitium, N. rigidocapillitium, N. rufum, Physarum guangxiense, P. subviride, P. nigritum, P. biyangense, P. neoovoideum, and P. jilinense — were identified from China, and their phylogenetic positions were analysed. Additionally, N. spumarioides (formerly Diderma spumarioides) was recombined. The new and recombined species were formally described and illustrated, and a key to the sections and species of Neodiderma and Physarum was provided.

Background: Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. However, there is currently no effective treatment for SOP. The Zhuangyao Jianshen Wan (ZYJSW) pill is traditionally believed to possess kidney-nourishing and bone-strengthening effects, demonstrating efficacy in treating fractures. Despite this, its effectiveness and mechanism in SOP remain unclear. This study aims to investigate the therapeutic potential of ZYJSW in treating SOP in senescence accelerated mouse prone 6 (SAMP6, P6) mice, and elucidate the underlying mechanisms. Methods: Four-month-old SAMP6 mice were categorized into six groups: the model group (SAMP6), low, medium, and high-dose ZYJSW treatment groups, calcitriol treatment (positive control 1) group, and metformin treatment (positive control 2) group. Gastric administration was carried out for 15 weeks, and a normal control group comprising four-month-old Senescence-Accelerated Mouse Resistant 1 (SAMR1) mice. Changes in body weight, liver and kidney function, bone protective effects, and muscle quality were evaluated using various assays, including H&E staining, Goldner staining, bone tissue morphology analysis, Micro-CT imaging, and biomechanical testing. Qualitative analysis and quality control of ZYJSW were performed via LC-MS/MS analysis. To explore mechanisms, network pharmacology and proteomics were employed, and the identified proteins were validated by Western blotting. Results: Oral administration of ZYJSW to P6 mice exerted preventive efficacy against osteopenia, impaired bone microstructure, and poor bone and muscle quality. ZYJSW attenuated the imbalance in bone metabolism by promoting bone formation, as evidenced by the upregulation of key factors such as Runt-related transcription factor 2 (RUNX2), Bone Morphogenetic Protein (BMP2), Osteoprotegerin (OPG) and Osteocalcin (OCN), while simultaneously inhibiting bone resorption through the downregulation of TNF receptor associated factor 6 (TRAF6), Tartrate resistant acid phosphatase (TRAP), Receptor activator for nuclear factor-κB ligand (RANKL) and Cathepsin K (CTSK). Additionally, ZYJSW enhanced muscle structure and function by counteracting the elevation of Ubiquitin (Ub), Muscle RING-finger protein-1 (Murf-1), F-Box Protein 32 (FBOX32), and Myogenin (Myog). Network pharmacology predictions, proteomics analysis corroborated by published literature demonstrated the role of ZYJSW involving in safeguarding mitochondrial biogenesis. This was achieved by suppressing GCN5L1 expression, contributing to the heightened expression of TFAM, PGC-1α, and nuclear respiratory factor-1 (NRF-1) proteins. ZYJSW also positively modulated Wnt signaling pathways responsible for bone formation, due to regulating expressions of key components like β-catenin, GSK-3β, and LRP5. In addition, ZYJSW causes the downregulation of the PI3K/Akt pathway by inhibiting the phosphorylation of both PI3K and Akt. Conclusions: The study highlights the significance of ZYJSW in preserving the health of both bone and muscle in P6 mice, potentially through the regulation of the GCN5L1-mediated PI3K/Akt/Wnt signaling pathway. The translational potential of this article: Our research provides evidence and a mechanistic rationale for ZYJSW as a candidate for SOP treatment, offering insights for further exploration and strategy development.

BackgroundThe population with diabetes in China is increasing year by year. Current research has found that either air pollution or temperature has an impact on the occurrence and development of diabetes, but the interaction between the two is unclear yet. ObjectiveTo investigate the effects and the lag effects of air pollutants and temperature on the risk of hospital admission for type 2 diabetes in Hefei, Anhui Province from 2016 to 2019, as well as to verify potential interaction between air pollutants and temperature. MethodsThis study collected hospital admission data for patients with type 2 diabetes from a tertiary hospital in Hefei, Anhui Province, and the corresponding monitoring data on air pollutants and meteorological factors from 2016 to 2019. Firstly, a distributed lag non-linear model (DLNM) was used to explore the effects of air pollutants and temperature on the risk of hospital admission for type 2 diabetes. Subsequently, a bivariate response surface model was used to explore potential interaction between temperature and various pollutants on frequency of hospital admission due to diabetes. Temperature was further divided into lower, medium, and higher levels by percentiles during the study period, and the potential interaction between air pollutants and temperature strata were verified . ResultsAfter controlling long-term trend, seasonal trend, holiday effect, and day of the week effect, the results of single pollutant models showed that for every 10 μg·m−3 increase in fine particulate matter (PM2.5), inhalable particulate matter (PM10), and nitrogen dioxide (NO2), the relative risk (RR) values for hospital admission due to type 2 diabetes were 1.032 (95%CI: 1.021, 1.043), 1.018 (95%CI: 1.008, 1.026), and 1.037 (95%CI: 1.016, 1.058), respectively; for every 1 mg·m−3 increase in carbon monoxide (CO), the RR value for hospital admission due to type 2 diabetes was 1.319 (95%CI: 1.163, 1.495); the increases in sulfur dioxide (SO2), ozone (O3), and daily average temperature showed no statistically significant impact on hospital admission due to type 2 diabetes. The results of bivariate response surface models suggested that daily average temperature and various pollutant levels spontaneously affected the risk of hospital admission for type 2 diabetes, but the stratified analysis did not find significant differences in the effect of PM2.5 on the risk of hospital admission due to type 2 diabetes across different temperature strata. ConclusionIncreases in the concentrations of PM2.5, PM10, NO2, and CO elevate the risk of hospital admission for type 2 diabetes. This study could not confirm the interactions between daily average temperature and various pollutants.

In view of the current situation that mine impact risk evaluation mainly focuses on the design stage or prior to the implementation of anti-impact measures, and lacks the safety evaluation of mining face after the implementation of anti-impact measures, the types of rock burst are divided into five types: coal type, coal pillar type, roof type, fault type and comprehensive type, taking into account the occurrence location, failure form, load type and focal location; based on the idea of classification prevention and control, a classification weighted evaluation method is proposed, considering the impact of impact risk, roadway surrounding rock, monitoring and early warning system, anti-impact support system, anti-impact rock pressure prevention measures and anti-impact management ability on anti-impact safety; the calculation formula of safety factor of anti-impact is given. The safety level of anti-impact is divided into three levels: safety, basic safety and unsafe. Taking the 31119 working face of a mine as an example, the complete process and result of anti-impact safety evaluation are given. The safety evaluation of some typical mining face with impact risk is carried out by using the classification weighting evaluation method, and the reliability of the evaluation results is verified by combining with the actual impact occurrence.

Abstract Background Huntington’s disease (HD) is a hereditary neurological disorder caused by mutations in HTT, leading to neuronal degeneration. Traditionally, HD is associated with the misfolding and aggregation of mutant huntingtin due to an extended polyglutamine domain encoded by an expanded CAG tract. However, recent research has also highlighted the role of global transcriptional dysregulation in HD pathology. However, understanding the intricate relationship between mRNA expression and HD at the cellular level remains challenging. Our study aimed to elucidate the underlying mechanisms of HD pathology using single-cell sequencing data. Results We used single-cell RNA sequencing analysis to determine differential gene expression patterns between healthy and HD cells. HD cells were effectively modeled using a residual neural network (ResNet), which outperformed traditional and convolutional neural networks. Despite the efficacy of our approach, the F1 score for the test set was 96.53%. Using the SHapley Additive exPlanations (SHAP) algorithm, we identified genes influencing HD prediction and revealed their roles in HD pathobiology, such as in the regulation of cellular iron metabolism and mitochondrial function. SHAP analysis also revealed low-abundance genes that were overlooked by traditional differential expression analysis, emphasizing its effectiveness in identifying biologically relevant genes for distinguishing between healthy and HD cells. Overall, the integration of single-cell RNA sequencing data and deep learning models provides valuable insights into HD pathology. Conclusion We developed the model capable of analyzing HD at single-cell transcriptomic level.

Abstract Background Bronchiectasis, once considered an orphan disease, is receiving attention globally owing to its increasing prevalence, healthcare burden, and associated morbidity. However, the prevalence of bronchiectasis is unclear. This meta-analysis estimates the prevalence of bronchiectasis in adults, providing a valuable reference for future research. Methods PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to May 31, 2024 for studies reporting the prevalence of bronchiectasis. Study selection, data extraction, and overall analysis of risk of the retrieved studies were conducted independently by two authors. The tool for assessing the risk of bias in prevalence studies was used to evaluate overall risk. Stata software (version 15.1) was used to performed the meta-analysis. Subgroup and sensitivity analyses were conducted to identify the source of heterogeneity. Funnel plots combined with Egger’s test were used to detect publication bias. Results The pooled prevalence of bronchiectasis in adults from 15 studies covering 437,851,478 individuals was 680 per 100,000 (95% CI: 634–727 per 100,000). Subgroup analysis showed that the prevalence of bronchiectasis in the United States, Korea, and China was 478 per 100,000 (95% CI: 367–588 per 100,000), 886 per 100,000 (95% CI: 778–993 per 100,000), and 759 per 100,000 (95% CI: 35–2399 per 100,000), respectively; 467 per 100,000 (95% CI: 416–518 per 100,000) in males and 535 per 100,000 (95% CI: 477–592 per 100,000) in females; 3958 per 100,000 (95% CI: 117–12637 per 100,000), 4677 per 100,000 (95% CI: 427–8928 per 100,000), and 3630 per 100,000 (95% CI: 158–7103 per 100,000) among never-smokers, ever-smokers, and current smokers, respectively; 430 per 100,000 (95% CI: 411–450 per 100,000), 380 per 100,000 (95% CI: 374–386 per 100,000), and 351 per 100,000 (95% CI: 342–360 per 100,000) among individuals with body mass index

Abstract Fusarium verticillioides is an important pathogen of maize and causes serious yield losses and food safety issues worldwide. F. verticillioides produces highly toxic mycotoxin Fumonisin B1 (FB1) in infested commodities which makes these food and feeds unsafe for humans and animals. For pathogenic fungi to successfully penetrate its plant hosts, the pathogen secretes hydrolytic enzymes that can facilitate penetration into the plant cutin layer. However, there is limited information on how cutinases transcriptionally regulated to impact F. verticillioides pathogenicity. In this study, our aim is to functionally characterize cutinase transcription factors that regulate key cutinase activities that are directly associated with F. verticillioides pathogenicity and FB1 biosynthesis. Gene deletion of cutinase transcription factor FvCTF1α did not affect the growth and morphology of the fungal mycelia on CMII medium, whereas the conidiation, utilization of sodium acetate and sodium oleate, stress tolerance against cell wall interfering agent, and the cutinase and pectinase activities in the ΔFvctf1α mutant were negatively impacted. FvCtf1α regulates the expression of induced cutinase genes FvCUT1 and FvCUT4 by binding to their GC-rich promoters. In addition, FvCtf1α, containing a novel function in regulating FB1, interacts with the promoter of FvFUM1 and FvFUM6 to down-regulate the expression of FvFUM1 and FvFUM6, resulting in decreased production of FB1 in the ΔFvctf1α strain. ΔFvctf1α exhibited decreased pathogenicity in maize due to the down-regulation of pathogenicity-related genes as well as key downstream cutinase genes FvCUT3 and FvCUT4 in F. verticillioides. We also demonstrated that FvCtf1α regulated FvCUT3 and FvCUT4 differently; FvCUT4 via direct regulation while FvCUT3 via indirect regulation by interacting with FvFarB, a homologous protein of FvCtf1α. Moreover, RNA-seq analysis showed that FvCtf1α was associated with many pathways, such as fatty acid metabolism, carbon source utilization, cell wall integrity, oxidative stress, and fumonisin synthesis in F. verticillioides. Our study demonstrated that FvCtf1α was not only involved in the regulation of cutinases but also a broad spectrum of pathways that ultimately affect F. verticillioides virulence and mycotoxin biosynthesis.

Abstract Objective This study aimed to reveal the role and mechanism of MG-132 in delaying hyperlipidemia-induced senescence of vascular smooth muscle cells (VSMCs). Methods Immunohistochemistry and hematoxylin-eosin staining confirmed the therapeutic effect of MG-132 on arterial senescence in vivo and its possible mechanism. Subsequently, VSMCs were treated with sodium palmitate (PA), an activator (Recilisib) or an inhibitor (Pictilisib) to activate or inhibit PI3K, and CCK-8 and EdU staining, wound healing assays, Transwell cell migration assays, autophagy staining assays, reactive oxygen species assays, senescence-associated β-galactosidase staining, and Western blotting were performed to determine the molecular mechanism by which MG-132 inhibits VSMC senescence. Validation of the interaction between MG-132 and PI3K using molecular docking. Results Increased expression of p-PI3K, a key protein of the autophagy regulatory system, and decreased expression of the autophagy-associated proteins Beclin 1 and ULK1 were observed in the aortas of C57BL/6J mice fed a high-fat diet (HFD), and autophagy was inhibited in aortic smooth muscle. MG-132 inhibits atherosclerosis by activating autophagy in VSMCs to counteract PA-induced cell proliferation, migration, oxidative stress, and senescence, thereby inhibiting VSMC senescence in the aorta. This process is achieved through the PI3K/AKT/mTOR signaling pathway. Conclusion MG-132 activates autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby inhibiting palmitate-induced proliferation, migration, and oxidative stress in vascular smooth muscle cells and suppressing their senescence.

Abstract Background Computerized adaptive testing (CAT) is an effective way to reduce time, repetitious redundancy, and respond burden, and has been used to measure outcomes in many diseases. This study aimed to develop and validate a comprehensive disease-specific CAT for chronic obstructive pulmonary disease (COPD) patient-reported outcome measurement. Methods The discrimination and difficulty of the items from the modified patient-reported outcome scale for COPD (mCOPD-PRO) were analyzed using item response theory. Then the initial item, item selection method, ability estimation method, and stopping criteria were further set based on Concerto platform to form the CAT. Finally, the reliability and validity were validated. Results The item discrimination ranged from 1.05 to 2.71, and the item difficulty ranged from − 3.08 to 3.65. The measurement reliability of the CAT ranged from 0.910 to 0.922 using random method, while that ranged from 0.910 to 0.924 using maximum Fisher information (MFI) method. The content validity was good. The correlation coefficient between theta of the CAT and COPD assessment test and modified Medical Research Council dyspnea scale scores using random method was 0.628 and 0.540 (P

Abstract Behçet’s disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein–protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723–0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

With the development of intelligent and connected vehicles, the expansion of software necessitates an increased significance and frequency of automotive firmware upgrades. The abundance of potential attack vectors and valuable data renders these upgrades enticing targets for attackers. However, the prevailing security services used for automotive firmware upgrades are no longer sufficient to meet security requirements. Hence, this paper proposes a Secure Automotive Firmware Upgrade Approach (SAFUA), aimed at enhancing authentication and communication security during automotive firmware upgrades. To address the heterogeneous performance of in-vehicle nodes and diverse application contexts, this approach introduces multiple authentication modes tailored to various upgrade scenarios. Moreover, hierarchical authentication and secure communication strategies are designed to achieve a balance between security and efficiency requirements. Consolidating these methodologies, a standardized automotive firmware upgrade process is delineated. Formal and informal verification of the proposed approach is conducted to attest its security efficacy. Furthermore, a simulated vehicular environment is constructed to evaluate the temporal and spatial efficiency of the approach across diverse bus and device configurations. The results confirm the adaptability of the secure upgrade approach outlined herein to the automotive firmware upgrade landscape, offering robust security alongside enhanced upgrade efficiency.

Background Cell death modulates the biological behaviors of tumors. However, the comprehensive role of the multiple forms of cell death in lower-grade glioma (LGG) is unknown.Methods We collected the transcriptional data of LGG patients from public repositories to comprehensively examine six cell death patterns (autophagy, apoptosis, cuproptosis, necroptosis, ferroptosis, and pyroptosis) in LGG samples and systematically correlated these patterns with patient survival, underlying biological processes, and drug sensitivity using serial bioinformatics analysis, clinical sample validation and in vitro assays.Results We identified and independently validated three reproducible cell death-based clusters associated with distinct clinical outcomes and tumor microenvironment characteristics. The Tumor Immune Dysfunction and Exclusion algorithm was applied for predicting how these three clusters would respond to immune checkpoint blockade (ICB) therapy; we found potential resistance of cluster B to ICB therapy. We also performed drug screening to identify cluster-specific drugs. Furthermore, a scoring system, designated as the CDPM score, was developed to estimate the cell death patterns of patients with LGG; this system could predict both LGG patients’ prognosis and immunotherapy efficacy. By performing multiplex immunofluorescence staining, we validated the correlations of GNAL expression with the molecular and clinical features of LGG in an independent LGG cohort. Finally, in vitro assays showed that GNAL promoted apoptosis and inhibited the proliferation of LGG cells.Conclusion The new cell death-based subtype system indicates several features of LGG biology and reveals novel insights into the use of precision medicine for treating LGG. The CDPM score could be used to predict the immunotherapy response and prognosis of LGG patients; moreover, it could indicate a novel direction for improving LGG management.

IntroductionInspired by the obstacle avoidance mechanism of goose neck, a theoretical design method of bionic robotic arm was proposed to solve the contradiction between high flexibility and strong bearing capacity in narrow space.MethodsTaking the goose neck as the test object, a narrow space test environment with a width of 10 cm was built, and a 6 × 4 obstacle matrix was set up, to analyze the maximum value of joint angle, motion rate and trajectory in different target areas.ResultsThe test results showed that the goose neck movement has continuity and transmissibility. The overall posture of the goose neck was adjusted through the synergistic movement of the anterior, middle and posterior segments to move toward the target position. The regulating effect of the anterior segment was significantly stronger than that of the middle and posterior segments. Specifically, the anterior segment of goose neck exhibited mostly transverse movement, with significant horizontal regulation; the middle segment of the goose neck was coupled with longitudinal movement, with similar movement ability in all directions, the posterior segment of the goose neck has mostly longitudinal movement, with significant height regulation.ConclusionIn addition, the YOLOv7-pose recognition network was used to recognize goose neck motion pose, which provides a new method for animal behavior research.

Batracomorphus is the most diverse and widely distributed genus of Iassinae. Nevertheless, there has been no systematic analysis of the genome structure and phylogenetic relationships of the genus. To determine the characteristics of the mitogenomes of Batracomorphus species as well as the phylogenetic relationships between them, we sequenced and compared the mitogenomes of 11 representative Batracomorphus species. The results revealed that the mitogenomes of the 11 Batracomorphus species exhibited highly similar gene and nucleotide composition, and codon usage compared with other reported mitogenomes of Iassinae. Of these 11 species, we found that the mitogenomes of four species were rearranged in the region from trnI-trnQ-trnM to trnQ-trnI-trnM, whereas the remaining species presented a typical gene order. The topologies of six phylogenetic trees were in agreement. Eurymelinae consistently formed paraphyletic groups. Ledrinae and Evacanthinae formed sister taxa within the same clade. Similarly, Typhlocybinae and Mileewinae consistently clustered together. All phylogenetic trees supported the monophyly of Iassinae, indicating its evolutionary distinctiveness while also revealing its sister relationship with Coelidiinae. Notably, the nodes for all species of the genus Batracomorphus were well supported and these taxa clustered into a large branch that indicated monophyly. Within this large branch, four Batracomorphus species with a gene rearrangement (trnQ-trnI-trnM) exhibited distinctive clustering, which divided the large branch into three minor branches. These findings expand our understanding of the taxonomy, evolution, genetics, and systematics of the genus Batracomorphus and broader Iassinae groups.

ObjectivesTo explore the relationship between glymphatic dysfunction and cognitive impairment in unilateral temporal lobe epilepsy (TLE).MethodsThis study retrospectively included 38 patients with unilateral TLE and 26 age- and gender-matched healthy controls (HCs). The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and cognitive assessment were obtained for each participant. Neuropsychological test batteries included Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination, Arithmetic Test (AT), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Boston Naming Test, Block design, Phonological Fluency Test (PFT), and Semantic Verbal Fluency (SVF).ResultsCompared to HCs, TLE patients had lower scores of MoCA, AT, DSST, DST, Block design, PFT and SVF (all p

BackgroundInadequate levels of vitamin D (VitD) have been linked to increased rates of various health conditions and mortality. However, little is known about the relationship between mortality outcomes and 25-hydroxyvitamin D [25(OH)D] levels in individuals with rheumatoid arthritis (RA). This study aimed to examine this association using data from the National Health and Nutrition Examination Survey.MethodsA cohort of 2,290 individuals aged 20 to 85 years with RA was analyzed. Lower 25(OH)D levels were inversely associated with all-cause mortality, with a hazard ratio (HR) of 0.91 (0.87 to 0.96) per 10 nmol/L increase. Comparatively, the HR for the VitD insufficiency group was 0.64 (0.50 to 0.83), and for the VitD sufficiency group, it was 0.60 (0.44 to 0.80), both compared to the VitD deficiency group. Cause-specific analysis showed that higher 25(OH)D levels were associated with reduced mortality from heart disease (HR: 0.88, 0.82 to 0.95) and malignant neoplasms (HR: 0.86, 0.79 to 0.94). No significant correlation was found between 25(OH)D levels and cause-specific mortalities for other conditions.ResultsStratified by gender, the HR for males was 0.92 (0.85 to 0.99) and for females was 0.91 (0.86 to 0.98) per 10 nmol/L increase in 25(OH)D levels. Among individuals aged 20-59 years, no significant correlation was observed, while for those aged 60 years and older, the HR was 0.86 (0.82 to 0.90) per 10 nmol/L increase. Nonlinear analysis identified a sharp increase in HR below 59.95 nmol/L, while HR remained below 1 for 25(OH)D levels above 59.95 nmol/L.ConclusionThis study reveals a strong negative correlation between 25(OH)D levels and overall mortality in individuals with RA. Notably, this association is particularly significant for mortality related to heart disease and malignant neoplasms. Targeted VitD supplementation should be emphasized, especially in individuals aged 60 years and older with RA. The proposed minimum threshold for adequate 25(OH)D levels in the RA population is 60 nmol/L.

The regeneration of maxillofacial bone defects associated with diabetes mellitus remains challenging due to the occlusal loading and hyperglycemia microenvironment. Herein, we propose a material-structure-driven strategy through the additive manufacturing of degradable Zn–Mg–Cu gradient scaffolds. The in situ alloying of Mg and Cu endows Zn alloy with admirable compressive strength for mechanical support and uniform degradation mode for preventing localized rupture. The scaffolds manifest favorable antibacterial, angiogenic, and osteogenic modulation capacity in mimicked hyperglycemic microenvironment, and Mg and Cu promote osteogenic differentiation in the early and late stages, respectively. In addition, the scaffolds expedite diabetic maxillofacial bone ingrowth and regeneration by combining the metabolic regulation effect of divalent metal cations and the hyperboloid and suitable permeability of the gradient structure. RNA sequencing further reveals that RAC1 might be involved in bone formation by regulating the transport and uptake of glucose related to GLUT1 in osteoblasts, contributing to cell function recovery. Inspired by bone healing and structural cues, this study offers an essential understanding of the designation and underlying mechanisms of the material-structure-driven strategy for diabetic maxillofacial bone regeneration.

Throughout pregnancy, maternal thyroid-related hormones are transported to the fetus via the placenta to allow normal fetal growth and development and are particularly important in the first and second trimesters of pregnancy. During maternal-fetal transport, in addition to thyroid-related hormones, thyroid-stimulating hormone receptor antibodies and antithyroid drugs can enter the fetus and interfere with development of the fetal thyroid gland and endocrine function, potentially leading to hyperthyroidism or hypothyroidism in the fetus or newborn. Several basic studies have been performed to demonstrate the important role of thyroid-related hormones in fetal and neonatal bone development. Ultrasound can assess neonatal skeletal maturity and bone development safely, rapidly, and effectively. This review aims to communicate the latest knowledge about maternal and fetal thyroid function in both normal and pathological pregnancies and summarize the latest advances in the potential effects of abnormal maternal thyroid function on bone development in the fetus and neonate. Finally, it discusses recent advances in research on ultrasound in the assessment of fetal and neonatal bone development.

Abstract Background Autophagy is a conserved catabolic process in eukaryotes that contributes to cell survival in response to multiple stresses and is important for organism fitness. Extensive research has shown that autophagy plays a pivotal role in both viral infection and replication processes. Despite the increasing research dedicated to autophagy, investigations into shrimp autophagy are relatively scarce. Results Based on three different methods, a total of 20 members of the ATGs were identified from F. chinensis, all of which contained an autophagy domain. These genes were divided into 18 subfamilies based on their different C-terminal domains, and were found to be located on 16 chromosomes. Quantitative real-time PCR (qRT-PCR) results showed that ATG genes were extensively distributed in all the tested tissues, with the highest expression levels were detected in muscle and eyestalk. To clarify the comprehensive roles of ATG genes upon biotic and abiotic stresses, we examined their expression patterns. The expression levels of multiple ATGs showed an initial increase followed by a decrease, with the highest expression levels observed at 6 h and/or 24 h after WSSV injection. The expression levels of three genes (ATG1, ATG3, and ATG4B) gradually increased until 60 h after injection. Under low-salt conditions, 12 ATG genes were significantly induced, and their transcription abundance peaked at 96 h after treatment. Conclusions These results suggested that ATG genes may have significant roles in responding to various environmental stressors. Overall, this study provides a thorough characterization and expression analysis of ATG genes in F. chinensis, laying a strong foundation for further functional studies and promising potential in innate immunity.

Abstract The correlation between lower psoas mass and the prognosis of osteoporotic vertebral compression fractures (OVCF) is still unclear. This study aims to investigate the impact of lower psoas mass on the prognosis of patients undergoing percutaneous vertebroplasty (PVP). One hundred and sixty-three elderly patients who underwent single-segment PVP from January 2018 to December 2021 were included. The psoas to L4 vertebral index (PLVI) via MRI were measured to assess psoas mass. Patients were divided into high PLVI (> 0.79) and low PLVI (≤ 0.79) groups based on the median PLVI in the cohort. The basic information (age, gender, body mass index (BMI) and bone mineral density (BMD)), surgical intervention-related elements (duration of operation, latency to ambulation, period of hospital stay, and surgical site), postoperative clinical outcomes (Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, Japanese Orthopaedic Association (JOA) scores), and incidence of secondary fractures) were compared. Patients showed no statistically significant differences in terms of age, gender, surgical sute, BMI, BMD and preoperative VAS, ODI, JOA scores (P > 0.05) between the two groups. However, there were significant differences in terms of latency to ambulation, period of hospital stay (P

Abstract Background Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. Methods Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. Results RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. Conclusion In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.

This study presents the initial sequencing and characterization of the complete mitochondrial genome (mitogenome) of Hyalinocerus flavoscutatus, making the first comprehensive exploration of the mitogenome in the Hyalinocerus. Utilizing next-generation sequencing techniques, we identified a circular DNA molecule spanning 15,307 bp. The mitogenome comprises 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a primary non-coding region. Maximum likelihood phylogenetic evaluation, based on 13 protein-coding genes and two ribosomal RNA genes, robustly supports H. flavoscutatus as the basal group within Idiocerini. This research unveils valuable insights into the mitogenome of H. flavoscutatus and enhances our understanding of phylogenetic placement within the broader context of related tribes.

Abstract Exopalaemon carinicauda, a eurythermal and euryhaline shrimp, contributes one third of the total biomass production of polyculture ponds in eastern China and is considered as a potential ideal experimental animal for research on crustaceans. We conducted a high-quality chromosome-level genome assembly of E. carinicauda combining PacBio HiFi and Hi-C sequencing data. The total assembly size was 5.86 Gb, with a contig N50 of 235.52 kb and a scaffold N50 of 138.24 Mb. Approximately 95.29% of the assembled sequences were anchored onto 45 pseudochromosomes. BUSCO analysis revealed that 92.89% of 1,013 single-copy genes were highly conserved orthologs. A total of 44, 288 protein-coding genes were predicted, of which 70.53% were functionally annotated. Given its high heterozygosity (2.62%) and large proportion of repeat sequences (71.49%), it is one of the most complex genome assemblies. This chromosome-scale genome will be a valuable resource for future molecular breeding and functional genomics research on E. carinicauda.

Abstract Background Non-small-cell lung cancer (NSCLC) accounts for 80–85% of all lung cancer and is the leading cause of cancer-related deaths globally. Although various treatment strategies have been introduced, the 5-year survival rate of patients with NSCLC is only 20–30%. Thus, it remains necessary to study the pathogenesis of NSCLC and develop new therapeutic drugs. Notably, PYK2 has been implicated in the progression of many tumors, including NSCLC, but its detailed mechanism remains unclear. In this study, we aimed to elucidate the mechanisms through which PYK2 promotes NSCLC progression. Methods The mRNA and protein levels of various molecules were measured using qRT-PCR, western blot (WB), and immunohistochemistry (IHC), respectively. We established stable PYK2 knockdown and overexpression cell lines, and CCK-8, EdU, and clonogenic assays; wound healing, transwell migration, and Matrigel invasion assays; and flow cytometry were employed to assess the phenotypes of tumor cells. Protein interactions were evaluated with co-immunoprecipitation (co-IP), immunofluorescence (IF)-based colocalization, and nucleocytoplasmic separation assays. RNA sequencing was performed to explore the transcriptional regulation mediated by PYK2. Secreted VGF levels were examined using ELISA. Dual-luciferase reporter system was used to detect transcriptional regulation site. PF4618433 (PYK2 inhibitor) and Stattic (STAT3 inhibitor) were used for rescue experiments. A public database was mined to analyze the effect of these molecules on NSCLC prognosis. To investigate the role of PYK2 in vivo, mouse xenograft models of lung carcinoma were established and examined. Results The protein level of PYK2 was higher in human NSCLC tumors than in the adjacent normal tissue, and higher PYK2 expression was associated with poorer prognosis. PYK2 knockdown inhibited the proliferation and motility of tumor cells and caused G1-S arrest and cyclinD1 downregulation in A549 and H460 cells. Meanwhile, PYK2 overexpression had the opposite effect in H1299 cells. The siRNA-induced inhibition of integrins alpha V and beta 1 led to the downregulation of p-PYK2(Tyr402). Activated PYK2 could bind to STAT3 and enhance its phosphorylation at Tyr705, regulating the nuclear accumulation of p-STAT3(Tyr705). This further promoted the expression of VGF, as confirmed by RNA sequencing in a PYK2-overexpressing H1299 cell line and validated by rescue experiments. Two sites in promoter region of VGF gene were confirmed as binding sites of STAT3 by Dual-luciferase assay. Data from the TGCA database showed that VGF was related to the poor prognosis of NSCLC. IHC revealed higher p-PYK2(Tyr402) and VGF expression in lung tumors than in adjacent normal tissues. Moreover, both proteins showed higher levels in advanced TNM stages than earlier ones. A positive linear correlation existed between the IHC score of p-PYK2(Tyr402) and VGF. Knockdown of VGF inhibited tumor progression and reversed the tumor promoting effect of PYK2 overexpression in NSCLC cells. Finally, the mouse model exhibited enhanced tumor growth when PYK2 was overexpressed, while the inhibitors PF4618433 and Stattic could attenuate this effect. Conclusions The Integrin αVβ1-PYK2-STAT3-VGF axis promotes NSCLC development, and the PYK2 inhibitor PF4618433 and STAT3 inhibitor Stattic can reverse the pro-tumorigenic effect of high PYK2 expression in mouse models. Our findings provide insights into NSCLC progression and could guide potential therapeutic strategies against NSCLC with high PYK2 expression levels.

Lots of large reservoirs have been built in the southwest mountainous areas of China, and the slope of reservoir shore is prone to landslides under complex geological conditions such as rainfall, reservoir water periodic fluctuation and earthquake. If the highway bridge foundation is located in the range of bank slope deformation or instability, huge lateral load may be generated on the bridge pier, thus endangering the foundation structure and the overall safety of the bridge. Taking the slope of Xiaojiang Bridge in Baihetan Reservoir as an example, this study applied GeoStudio to analyse the stability of bridge foundation slope under the combined condition of reservoir water fluctuation, rainfall and earthquake. As to the unstable slope under the combined rainfall condition of reservoir water fluctuation, the numerical method of Tsunami Balls (TB) was used to simulate the landslide dynamic process and evaluate the dynamic impact load of the bridge pier. The results show that the slope stability coefficient decreases due to the reservoir water fluctuation, which is the main factor affecting the slope stability. After seismic load is applied, the slope stability coefficient decreases sharply, while rainfall has limited influence on the stability coefficient. The impact load of the sliding body on the bridge pier increases first and then decreases with time, and the maximum impact load is 13890 kN, which appears after the maximum velocity of the sliding body. It is concluded that the stability of the bridge foundation slope on the bank of reservoir is reduced dramatically under the influence of reservoir water fluctuation, and the failure of the bridge foundation structure may be caused by the instability impact process of TB simulated sliding body. This study provides technical information for the disaster prevention and reduction and safe operation of large reservoir slopes and highway bridges.

Abstract The therapeutic efficacy of adoptive T cell therapy is largely restricted by reduced viability and dysfunction of CD8+ T cells. Continuous antigen stimulation disrupts the expansion, effector function, and metabolic fitness of CD8+ T cells, leading to their differentiation into an exhausted state within the tumor microenvironment (TME). While the function of the cell cycle negative regulator p16 in senescent cells is well understood, its role in T cell exhaustion remains unclear. In this study, we demonstrated that TCR stimulation of CD8+ T cells rapidly upregulates p16 expression, with its levels positively correlating with TCR affinity. Chronic TCR stimulation further increased p16 expression, leading to CD8+ T cell apoptosis and exhaustion differentiation, without inducing DNA damage or cell senescence. Mechanistic investigations revealed that p16 downregulates mTOR, glycolysis, and oxidative phosphorylation (OXPHOS) associated gene expression, resulting in impaired mitochondrial fitness, reduced T cell viability, and diminished effector function. Furthermore, the deletion of p16 significantly enhances the persistence of CD8+ T cells within tumors and suppresses the terminal exhaustion of tumor-infiltrating T cells. Overall, our findings elucidate how increased p16 expression reshapes T cell intracellular metabolism, drives T cell apoptosis and exhaustion differentiation, and ultimately impairs T cell anti-tumor function.

Peas had high nutritional values and low allergenicity as a bulk pulse. However, whole pea milk was prone to flocculation instability, which limited its application in food. In this paper, peeling peas were used as raw material and treated with high pressure homogenization coupled biological double enzymatic hydrolysis (medium temperature α-amylase and cellulase), and the stability and nutritional characteristics of whole pea milk were revealed under the optimal process through centrifugation precipitation rate and Box-Behnken design. The results showed that the stability of whole pea milk prepared by simultaneous enzymatic hydrolysis of α-amylase and cellulase was better than the counterparts processed with traditional filtering, individual enzymatic hydrolysis, and step hydrolysis of double enzymes. The optimal parameters of simultaneous enzymatic hydrolysis was as follows: Medium temperature α-amylase:cellulase was 4.5:5.5 (enzyme activity ratio, U/g starch), with a total addition of 12 U/g and 65 minutes of enzymic hydrolysis. The centrifugal precipitation rate of whole pea milk processed under the optimal conditions was the lowest (27.70%), and no significant precipitation stratification during 60 days of storage without filtration and without stabilizer. Compared with the pea milk obtained by the traditional individual nutrients formulation, the whole pea milk prepared under the optimized simultaneous enzymatic hydrolysis showed significantly improved stability. The starch digestion extent showed a reduce of 12.74%, while the protein digestion extent was increased by 16.41%. The study provides the theoretical guidance for the development of concentrated plant based milk.

Abstract Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS). The least absolute shrinkage and selection operator were utilized to assess the predictive efficacy of NRGs. Kaplan–Meier plots visualized survival estimates. ROC curves assessed the prognostic value of NRG-based features. A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Twenty-seven NRGs were found to significantly impact patient OS. Six NRGs—CFTR, ENO1, PARVB, DDIT4, MPO, LDLR—were notable for their strong predictive ability regarding patient survival. The ROC values for 1-, 3-, and 5-year survival rates were 0.794, 0.781, and 0.911, respectively. In the training set (TCGA-LAML), patients in the high NRG risk group showed a poorer prognosis (p

Abstract. The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T cells. Upon antigen exposure, T cells undergo metabolic reprogramming, leading to the development of functional effectors or memory populations. However, within the tumor microenvironment (TME), metabolic stress impairs CD8+ T cell anti-tumor immunity, resulting in exhausted differentiation. Recent studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell immunotherapy. In this review, we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory conditions. Furthermore, we delved into the different metabolic switches that occur during T cell exhaustion, exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion, ultimately leading to a persistently exhausted state. Understanding the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.

Macrophage senescence, manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype, has long been considered harmful. Persistent senescence of macrophages may lead to maladaptation, immune dysfunction, and finally the development of age-related diseases, infections, autoimmune diseases, and malignancies. However, it is a ubiquitous, multi-factorial, and dynamic complex phenomenon that also plays roles in remodeled processes, including wound repair and embryogenesis. In this review, we summarize some general molecular changes and several specific biomarkers during macrophage senescence, which may bring new sight to recognize senescent macrophages in different conditions. Also, we take an in-depth look at the functional changes in senescent macrophages, including metabolism, autophagy, polarization, phagocytosis, antigen presentation, and infiltration or recruitment. Furthermore, some degenerations and diseases associated with senescent macrophages as well as the mechanisms or relevant genetic regulations of senescent macrophages are integrated, not only emphasizing the possibility of regulating macrophage senescence to benefit age-associated diseases but also has an implication on the finding of potential targets or drugs clinically.

Arsenic is a pollutant that can cross the placenta; however, research on the effects of arsenic exposure during pregnancy on the fertility of female offspring is limited. To address this gap, we developed a mouse model to investigate the relationship between arsenic exposure during pregnancy and fertility in female offspring. Our fertility assessment revealed that gestational exposure to 1 mg/kg arsenic or higher (10 mg/kg) resulted in reduction in litter size, ovarian volume, and multistage-follicle number in female offspring. By assessing the in vitro developmental capacity of oocytes and zygotes, we confirmed that the reduced fertility was due not to impaired oocyte quality but rather to a reduction in oocyte quantity. Arsenic exposure impedes synapsis formation in MPI and compromises homologous recombination-mediated repair of double-strand breaks, resulting in fewer crossovers. This disruption activates the pachytene-checkpoint, hindering the progression of the MPI and resulting in the elimination of defective oocytes through p-Chk2 activation. Our study reveals for the first time the detrimental effects of arsenic exposure during pregnancy on the fertility of female offspring, underscoring the urgent need to prevent such exposure to safeguard reproductive health.

Abstract Macropsini is a tribe of Eurymelinae in the family Cicadellidae that is widely distributed worldwide. Still, its taxonomic status has been unstable, and the classification of certain clades at the genus level has been controversial. The aim of this study is to address the patterns and processes that explain the structure and the evolution of the mitogenomes of Macropsini, while contributing to the resolution of systematic issues involving five of their genera. To this task, the mitogenomes of 26 species of the tribe were sequenced and characterized, and their phylogenetic relationships were reconstructed. The results revealed that the nucleotide composition of mitochondrial genes in these 26 species was significantly skewed toward A and T. Codons ending with T or A in relative synonymous codon usage were significantly more prevalent than those ending with C or G. The parity plot, neutrality plot, and correspondence analysis revealed that mutation and selective pressure affect codon usage patterns. In the phylogenetic relationships of the Macropsini, the monophyly of Pedionis and Macropsis was well‐supported. Meanwhile, Oncopsis revealed paraphyletic regarding Pediopsoides. In conclusion, this research not only contributes the valuable data to the understanding of the mitogenome of the Macropsini but also provides a reference for future investigations on codon usage patterns, potential adaptive evolution, and the phylogeny of the mitogenome within the subfamily Eurymelinae.

Prostate cancer (PC) is the third most common male cancer in the world, which occurs due to various mutations leading to the loss of chromatin structure. There are multiple treatments for this type of cancer, of which chemotherapy is one of the most important. Sometimes, a combination of different treatments, such as chemotherapy, radiotherapy, and surgery, are used to prevent tumor recurrence. Among other treatments, androgen deprivation therapy (ADT) can be mentioned, which has had promising results. One of the drawbacks of chemotherapy and ADT treatments is that they are not targeted to the tumor tissue. For this reason, their use can cause extensive side effects. Treatments based on nanomaterials, known as nanomedicine, have attracted much attention today. Nanoparticles (NPs) are one of the main branches of nanomedicine, and they can be made of different materials such as polymer, metal, and carbon, each of which has distinct characteristics. In addition to NPs, nanovesicles (NVs) also have therapeutic applications in PC. In treating PC, synthetic NVs (liposomes, micelles, and nanobubbles) or produced from cells (exosomes) can be used. In addition to the role that NPs and NVs have in treating PC, due to being targeted, they can be used to diagnose PC and check the treatment process. Knowing the characteristics of nanomedicine-based treatments can help design new treatments and improve researchers’ understanding of tumor biology and its rapid diagnosis. In this study, we will discuss conventional and nanomedicine-based treatments. The results of these studies show that the use of NPs and NVs in combination with conventional treatments has higher efficacy in tumor treatment than the individual use of each of them.

Gastritis is a disease caused by multifactorial etiology. Ginger a widely used natural spice, possesses various beneficial properties, including antioxidant, neuroprotective, antidiabetic, anti-inflammatory and immu-nomodulatory. More and more studies have shown that ginger has significant efficacy in treating gastritis. The aim of this study was to evaluate the effectiveness of ginger in the treatment of gastritis and its mechanism. The chemical composition of ginger was determined by UPLC-HRMS. The biological state and intestinal propulsion rate in mice were measured. Serum levels of gastrointestinal hormone were measured using ELISA. Histopathological examination was performed to evaluate gastric tissue damage. Additionally, stomach tissues of mice from different groups were selected for transcriptomic analysis. The differentially expressed genes(DEGs) were identified. PCR verification of DEGs was then performed to explore key targets. Our findings demonstrated that ginger reversed the rate of small intestinal charcoal end-propulsion, increased the levels of the gastrointestinal hormones and attenuated the histopathological damage of the stomach in a model of gastritis in mice. Transcriptomic analysis revealed DEGs predominantly expressed in primarily associated with signal fransduction, extracellour transduction, extracellular space, inflammatory response and the extracellular region. KEGG pathway analysis implicated the involvement of AGE-RAGE, MAPK signaling and potentially other pathways. In addition, real-time quantitative PCR validation of six selected DEGs showed that the genes (IL-6, STAT3, SOCS3, BDNF, TRPV4, and ICAM1) suggested their potential roles as key targets of ginger's therapeutic action in the treatment of gastritis. This study reveals potential mechanism of ginger in treating gastritis, which provides new ideas and techniques for the clinical application of ginger.

Abstract Background Airborne pollen is a crucial risk factor in allergic rhinitis (AR). The severity of AR symptoms can vary based on pollen type and concentration. This study aimed to estimate the association between exposure to different pollen types and AR risk. Methods We obtained data from patients admitted to the Beijing Tongren Hospital for AR, and data on pollen concentration, meteorological factors, and fine particulate matter (PM2.5) from 13 districts in Beijing from 2016 to 2019. We used a time‐stratified case‐crossover study design and calculated odds ratios (ORs) related to the risk of AR associated with a 10 grain/1000 mm2 increase in total pollen concentrations for specific pollen types. A stratified analysis was conducted to assess whether the associations were varied by age and sex. Results The OR of AR associated with a 10 grain/1000 mm2 increase in the 7‐day average pollen concentration was 1.014 (95% CI: 1.014, 1.015), 1.076 (95% CI: 1.070, 1.082), 1.024 (95% CI: 1.023, 1.025), 1.042 (95% CI: 1.039, 1.045), 1.142 (95% CI: 1.137, 1.147), 1.092 (95% CI: 1.088, 1.097), 1.046 (95% CI: 1.035, 1.058), and 1.026 (95% CI: 1.024, 1.028) for total pollen, Ulmus, Cupressaceae, Populus, Fraxinus, Pinus, Betula, and Artemisia, respectively. Both tree pollen (Ulmus, Cupressaceae, Populus, Fraxinus, Betula, and Pinus) and weed pollen (Artemisia, Chenopodium, and Humulus) were correlated with an increased risk of AR. These associations remained consistent across distinct subgroups defined by both age and sex. Conclusion Exposure to pollen from trees and weeds might be associated with an increased risk of AR. This research provides valuable scientific support for both clinical practitioners and patients with AR regarding the hazards of pollen exposure.

BackgroundStress hyperglycemia ratio (SHR) is a newly suggested measure of stress-induced hyperglycemia that combines both short-term and long-term glycemic conditions. The study aimed to explore the association between SHR and the incidence of adverse clinical events with heart failure (HF) through a meta-analysis.MethodsCohort studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and CNKI. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity.ResultsTen studies involving 15250 patients with HF were included. Pooled results showed that compared to patients with lower SHR at baseline, those with a higher SHR were associated with an increased risk of all-cause mortality during follow-up (risk ratio [RR]: 1.61, 95% confidence interval [CI]: 1.17 to 2.21, p = 0.003; I2 = 82%). Further meta-regression analysis suggests that different in the cutoff of SHR significantly modify the results (coefficient = 1.22, p = 0.02), and the subgroup analysis suggested a more remarkable association between SHR and all-cause mortality in studies with cutoff of SHR ≥ 1.05 than those with cutoff of SHR < 1.05 (RR: 2.29 versus 1.08, p for subgroup difference < 0.001). Subsequent meta-analyses also showed that a high SHR at baseline was related to the incidence of cardiovascular death (RR: 2.19, 95% CI: 1.55 to 3.09, p < 0.001; I2 = 0%), HF-rehospitalization (RR: 1.83, 95% CI: 1.44 to 2.33, p < 0.001; I2 = 0%), and major adverse cardiovascular events (RR: 1.54, 95% CI: 1.15 to 2.06, p = 0.004; I2 = 74%) during follow-up.ConclusionA high SHR at baseline is associated with a poor clinical prognosis of patients with HF.Systematic review registrationhttps://inplasy.com, identifier INPLASY202430080.

Introduction: Tripterygium species have been traditionally used in Chinese medicine for treating various conditions. The aim of the study was to construct a drug-modified renal infarction targeting liposome (rTor-LIP) containing Tripterygium in order to improve the therapeutic effect on renal injury.Methods: rTor-LIP was prepared using the extruder method containing Tripterygium solution. The preparation was characterized by transmission electron microscopy, Marvin laser particle size analyzer, and Western blotting. In vitro experiments were conducted to verify the biocompatibility of rTor-LIP, and in vivo experiments were conducted to verify the therapeutic effect of rTor- LIP on renal injury.Results and discussion: The surface of rTor-LIP was regular and oval. In vitro results showed that after co-incubation with rTor-LIP, endothelial cells did not show significant apoptosis, and there were no significant abnormalities in the mitochondrial metabolism. The in vivo results showed that the morphology of endothelial cells in the rTor-LIP group was uniform and the cytoplasmic striations were clear, but the local striations had disappeared. Thus, rTor-LIP nano-targeted liposomes can effectively target hypoxic kidney tissue, providing a new idea for the treatment of renal infarction.

Abstract The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients’ orthodontic treatment.

Many rehabilitation exoskeletons have been used in the field of stroke rehabilitation. Generating human-like motion is necessary for exoskeletons to help patients perform activities of daily living (ADL) while maintaining interaction quality and ergonomics. However, most of the current motion generation algorithms utilize inverse kinematics (IK) to solve the final configuration before generation, and do not consider the movement of shoulder girdle. Separately considering the shoulder girdle motion and arm motion, this paper proposes an algorithm integrated IK to generate human-like motion. The arm moves towards the target with a bell-shaped velocity in the absence of the final configuration, and the shoulder girdle maintain natural passive motion. Moreover, the generated motion can be mapped to the configuration space of exoskeletons. Compared with the experimental data collected using a motion capture system, the values of RMSE and HPDI of the generated wrist trajectory in the task space are within 0.2 and 0.17, respectively, while those of RMSE in the joint space are within 15 deg, which demonstrates the human-like nature of the generated motion.

With the construction of the UHV (Ultra High Voltage) AC/DC hybrid power grid and the large-scale access to renewable energy such as wind power, frequency dynamic fluctuation has become a prominent problem affecting the safe and stable operation of large power grids. The expansion of the scale of the power system makes it impossible to use traditional fine modeling to analyze the power system. In order to reduce the calculation scale and storage capacity of power system frequency dynamic simulation, it is necessary to make appropriate equivalent simplification of the external system, so the appropriate dynamic equivalent method is of great significance. This paper mainly studies the equivalent model suitable for frequency dynamic analysis of large power grids. Firstly, the typical models of generator set and load are simplified, and the parameters that have a great influence on frequency in the simplified model are obtained through characteristic analysis. Then, a dynamic aggregation method of generator governor and prime mover parameters and load parameters based on regulation performance weighting (the parameters of the generator or load are weighted and summed according to its regulation ability on the system) is proposed. This method is applied to the simulation example of the East China Power Grid. The simulation proves that the frequency of the East China Power Grid before and after equivalence can be consistent under four different faults, which verifies the effectiveness of the equivalent method proposed in this paper in the frequency dynamic analysis of large power grids.