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The use of generative artificial intelligence (Gen-AI) to assist college students in their studies has become a trend. However, there is no academic consensus on whether Gen-AI can enhance the academic achievement of college students. Using a meta-analytic approach, this study aims to investigate the effectiveness of Gen-AI in improving the academic achievement of college students and to explore the effects of different moderating variables. A total of 28 articles (65 independent studies, 1909 participants) met the inclusion criteria for this study. The results showed that Gen-AI significantly improved college students' academic achievement with a medium effect size (Hedges's g = 0.533, 95% CI [0.408,0.659], p < 0.05). There were within-group differences in the three moderator variables, activity categories, sample size, and generated content, when the generated content was text (g = 0.554, p < 0.05), and sample size of 21-40 (g = 0.776, p < 0.05), the use of independent learning styles (g = 0.600, p < 0.05) had the most significant improvement in college student's academic achievement. The intervention duration, the discipline types, and the assessment tools also had a moderate positive impact on college students' academic achievement, but there were no significant within-group differences in any of the moderating variables. This study provides a theoretical basis and empirical evidence for the scientific application of Gen-AI and the development of educational technology policy.

This research aims to investigate information asymmetry in e-commerce supply chain channels and the impact of the fair preference model on the behavior and returns of channel members. Therefore, by contrasting it with the model in the completely rational case, this research establishes a more realistic principal-agent model and incorporates the fair preference model into the e-commerce supply chain channel. According to the model's analysis, the effort level of the retailer at each stage is positively correlated with the e-commerce efficiency coefficient, and the incentive coefficient of manufacturers is positively correlated with the e-commerce efficiency coefficient in the case where all rationality is assumed. Manufacturing companies' anticipated profits are positively correlated with the e-commerce efficiency coefficient. According to the fair preference model, retailers will put forth more effort to sell products when their fixed income from manufacturers is higher and their optimal effort level is positively correlated with that income. When e-commerce's efficiency coefficient is higher than 1, the retailer's revenue and effort exceeded those of traditional channels. Manufacturers and retailers both experience Pareto improvements in their earnings after the fair preference model is introduced.

Although microsurgical vasoepididymostomy (MVE) is an effective treatment for epididymal obstructive azoospermia, some patients may experience delayed patency or suboptimal semen parameters after patency. However, research into patency time, semen quality postpatency, and associated influencing factors remains limited. This study aimed to address these issues by evaluating 181 patients who underwent at least one-sided MVE employing asingle-armed longitudinal intussusception vasoepididymostomy technique, with a follow-up period of over 12 months for 150 patients. The overall patency rate was 75.3%, with 86.0% of patients achieving patency within 6 months following MVE. Unexpectedly, factors such as age, history of epididymitis, duration of surgery, side of anastomosis, sperm motility in epididymal fluid, and the site of anastomosis showed no correlation with patency time. Nonetheless, our univariate and multivariate linear regression analysis indicated that only the site of anastomosis was positively correlated with and could independently predict postoperative total motile sperm count. Therefore, the site of anastomosis might serve as a predictor for optimal postoperative semen quality following the MVE procedure.

Abstract Background Schizophrenia is associated with a high mortality rate due to the high risk of suicide. However, there is still a lack of evidence on the gender-specific risk factors for suicide among people with schizophrenia. In this study, we aimed to measure the sociodemographic and clinical correlates of suicide deaths in different genders among people with schizophrenia. Methods Data on patients with schizophrenia from 2013 to 2021 in Guangzhou, China were obtained from the National Information System for Psychosis (NISP), involving a total of 33,080 patients. Cox regression and Fine-Gray models were used to explore the sociodemographic and clinical risk factors for suicide mortality in different genders. Results The overall age-standardized mortality rates due to suicide were 133.89 (95% CI: 124.31-143.47) per 100,000 person-years for females and 163.25 (95% CI: 152.92-173.59) per 100,000 person-years for males. To be specific, lack of medical insurance, history of non-treatment, and history of suicidal behavior was associated with a higher risk for suicide mortality for females, while an age of 35–54, being hospitalized once, and the age of onset being > 28 years were linked to lower risk for suicide mortality for males. For both genders, a lower risk for suicide mortality was observed in patients at an older age (≥ 55 years) and with a history of hospitalization more than once, and a higher suicide mortality risk was found in married patients and those residing in rural areas. Conclusion The present study found that gender differences should be taken into account in the development of suicide prevention programs for people with schizophrenia, and future research is still required to verify our preliminary results.

Abstract Background Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment. Methods Keywords such as “prostate cancer”, “tumor microenvironment”, “immune cells”, “vascular system”, “stromal cells”, and “microbiota” were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment. Results The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment. Conclusions A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation. Graphical Abstract

Abstract Background Mental health literacy is a predictor of health outcomes in psychological distress. However, limited research has explored whether low mental health literacy is associated with recent depression and anxiety. Methods We used data from the Guangdong Mental Health Survey, a provincial representative and a population-based survey with a multistage stratified cluster random sampling method. We included adults aged 18 and above living in communities from September to December 2021 in Guangdong, China. Eligible participants were those who completed the mental health literacy questionnaire and assessments for depression and anxiety symptoms. We assessed the proportion of individuals with low mental health literacy by categories of psychological symptoms and whether low mental health literacy was associated with depressive and anxiety symptoms in the general population and subgroups. Results A total of 16,715 adults were included. We found that individuals with more severe symptoms had a greater proportion of low mental health literacy- it went from 89.4% in participants without depression or anxiety to 96.2% in people who co-occurred with depression and anxiety (x2 = 21.457, P

We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia (iNOA). We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction. The Chi-square test and Mann–Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons. A logistic regression analysis was conducted to identify predictors of retrieval failure. Area under the receiver operating characteristic curve for each variable was evaluated, and the net clinical benefit was calculated using a clinical decision curve. Patients with iNOA had a lower sperm retrieval rate than those with known causes. Moreover, testicular volume was an independent factor affecting sperm extraction outcomes (odds ratio = 0.79, P < 0.05). The testicular volume cut-off value was 6.5 ml (area under the curve: 0.694). The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed. The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution. There was also a significant association between a uniform tubule distribution and testicular volume. In conclusion, a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 (LRRC23; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband’s spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%–46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: −2.70; 95% CI: −3.94–−1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.

The exposure of ethanol increases the risk of head and neck inflammation and tumor progression. However, limited studies have investigated the composition and functionality of laryngeal microbiota under ethanol exposure. We established an ethanol-exposed mouse model to investigate the changes in composition and function of laryngeal microbiota using Metagenomic shotgun sequencing. In the middle and late stages of the experiment, the laryngeal microbiota of mice exposed to ethanol exhibited obvious distinguished from that of the control group on principal-coordinate analysis (PCoA) plots. Among the highly abundant species, Salmonella enterica and Mycobacterium marinum were likely to be most impacted. Our findings indicated that the exposure to ethanol significantly increased their abundance in larynxes in mice of the same age, which has been confirmed through FISH experiments. Among the species-related functions and genes, metabolism is most severely affected by ethanol. The difference was most obvious in the second month of the experiment, which may be alleviated later because the animal established tolerance. Notable enrichments concerning energy, amino acid, and carbohydrate metabolic pathways occurred during the second month under ethanol exposure. Finally, based on the correlation between species and functional variations, a network was established to investigate relationships among microbiota, functional pathways, and related genes affected by ethanol. Our data first demonstrated the continuous changes of abundance, function and their interrelationship of laryngeal microbiota under ethanol exposure by Metagenomic shotgun sequencing. Importance: Ethanol may participate in the inflammation and tumor progression by affecting the composition of the laryngeal microbiota. Here, we applied the metagenomic shotgun sequencing instead of 16 S rRNA sequencing method to identify the laryngeal microbiota under ethanol exposure. Salmonella enterica and Mycobacterium marinum are two dominant species that may play a role in the reconstruction of the laryngeal microenvironment, as their local abundance increases following exposure to ethanol. The metabolic function is most evidently impacted, and several potential metabolic pathways could be associated with alterations in microbiota composition. These findings could help us better understand the impact of prolonged ethanol exposure on the microbial composition and functionality in the larynx.

Abstract Background Although national policies in China are comprehensive and instructive, a wide disparity exists between different cities. The current status of public mental health services by region in China remains unclear. This study aimed to investigate policies related to public mental health services, the contact coverage of public mental health services and outcomes of service users. Methods A cross-sectional study was carried out in Southern China, between April 2021 and March 2022. Considering the geographical location, socioeconomic development levels, and prevalence of severe mental illness, four cities including Wuhan, Changsha, Guangzhou, and Shenzhen were selected. Relevant service providers were asked to report data on mental health policies and facility-related information, including mental health resources, registration rates of patients, management rates of patients, and medication rates of patients. Eligible patients were invited to report service user-related data, including contact coverage of public mental health services and their outcomes. SPSS 26.0 was used for data analysis. Results The four cities in Southern China have made different efforts to develop public mental health services, primarily focusing on socio-economically disadvantaged individuals. Community health centers in Guangzhou and Shenzhen reported having more professional human resources on mental health and higher mental health budgets for patients. The contact coverage rates of most public mental services were higher than 80%. Patients in Changsha (B = 0.3; 95%CI: 0.1–0.5), Guangzhou (B = 0.2; 95%CI: 0.1–0.3), and Shenzhen (B = 0.3; 95%CI: 0.1–0.4) who received social medical assistance services reported higher levels of medication adherence. Patients in Wuhan (B = -6.5; 95%CI: -12.9--0.1), Guangzhou (B = -2.8; 95%CI: -5.5--0.1), and Shenzhen who received community-based rehabilitation services reported lower levels of disability (B = -2.6; 95%CI: -4.6--0.5). Conclusions There have been advances in public mental health services in the four Southern cities. The contact coverage rates of most public mental health services were higher than 80%. Patients’ utilization of public mental services was associated with better health outcomes. To improve the quality of public mental health services, the government should try to engage service users, their family members, and supporters in the design, delivery, operationalization, and evaluation of these public mental health services in the future.

Abstract Background Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined. Methods 57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR. Results This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P

The traditional filter weighing method has a cumbersome operation process, a long detection cycle, and a low degree of automation. Although it has high accuracy, it cannot meet the needs of real-time detection of dust concentration. An automatic dust mass concentration detection device was designed, and the temperature and humidity compensation model was established to replace the steps of filter membrane drying after sampling in the manual weighing method, so as to further reduce the dust concentration detection time and the volume of the dust concentration detection device. The prototype device was built and the experiment was conducted. The test results showed that the standard deviation of the CCZ-20A dust sampler commonly used in coal mines and the converted concentration of dust detected by this device was within 5%, and the fitting correlation of the experimental data under the univariate linear regression fitting analysis was good. In order to further improve the detection accuracy of the device, an error compensation method based on the combination of Fourier series, linear fitting and periodic fitting was studied, and the concentration calculation process of the device was established and brought into the original data, and the detection concentration error of the device was concentrated from the original (−7.20%, −1.26%) to (−3.64%, 3.65%). After the introduction of the device concentration calculation process, several comparative experiments were carried out, and the experimental results showed that the detection errors of the device concentration were within this range, which verified the reliability of the device concentration calculation process. The device shortens the time required for dust concentration detection, and at the same time controls the detection error within a reasonable range, which provides a reference for the research of filter membrane weighing method in the online monitoring of dust concentration.

Currently spray dust reduction is one of the most widely used dust removal methods in coal mines. The wetting performance of water on coal has a direct impact on spray dust reduction, therefore, adding wetting agents such as surfactants in water can improve the wetting performance of water on coal. In order to investigate the effect of various surfactants on the wettability of bituminous coal dust, four types of surfactants, namely, Rapid Penetrant T, 1227, BS-12 and APG, were used to investigate the wettability of bituminous coal by combining molecular simulation techniques and laboratory experiments. On the one hand, the interfacial system of surfactant aqueous solution was constructed by means of molecular simulation, the hydrophilicity of surfactant itself was analyzed based on the theory of the number of hydrogen bond formation and the radial distribution function, and the surface tension experiments of 4 reagents were carried out, and it was found that the Rapid Penetrant T reagent forms the most number of hydrogen bonds being 398, and the radial distribution function curve peaks at 1.99 ×10−10 m at the earliest time, which is the easiest to be adsorbed with H2O molecules, and the experimental results also showed that the Rapid Penetrant T reagent has the strongest weakening of the surface tension of the water, i.e., the smallest surface tension, which is 24.4 mN/m. On the other hand, through the electrostatic potential calculation, combined with the constructed surfactant/water/bituminous coal ternary adsorption system interaction energy analysis, the effect of four surfactants on the wettability of bituminous coal was investigated, and the experiments on the settlement and contact angle of bituminous coal in 4 reagents were carried out respectively. The results showed that the potential difference between the site and the water molecules after the Rapid Penetrant T molecules combined with the bituminous coal molecules is the largest, being 6.8535 eV, and the interaction energy between it and the bituminous coal is also the largest, being −2705.12 kJ/mol, and the experimental results also showed that the two kinds of bituminous coal have the smallest settling time in the Rapid Penetrant T reagent being 26.3 and 10.22 s respectively, and the smallest contact angle are 25.8° and 21.7° respectively. Thus, the study shown that the molecular simulation results are in agreement with the experimental results, and all of them validate that the anionic surfactant Rapid Penetrant T has the best wettability performance on bituminous coal.

Abstract Background This systematic review and meta-analysis aimed to evaluate the efficiency and safety of percutaneous nephrolithotomy (PCNL) between flank position and prone position for the treatment of renal stones. Methods PubMed, Embase, OVID, and Cochrane Library were comprehensively searched from their inception to Jul 2024. Randomized and nonrandomized trials evaluating renal calculi patients who underwent PCNL via flank position or prone position were included. Data extraction and quality assessment were conducted by two independent reviewers. The outcomes and complications of both groups were compared in this meta-analysis. Results This review involved five articles (554 patients). Specifically, four articles were randomized controlled trials, and the remaining publication was prospective cohort study. No significant difference was found in stone-free rate between the flank group and prone group after the PCNL procedure. Similarly, the percutaneous access time, operative time, and hospital stay of flank position had no significant difference compared with the prone group. There was no significant difference in the comparison of complication rates between the flank group and the prone group. Although further analysis indicated that patients in the prone position suffered more hemoglobin drop than the flank group, no significant difference was found in the hemorrhage and blood transfusion rates. Conclusions Both surgical positions were appropriate for most PCNL procedures and had shown similar efficacy and safety. In practice, the optimal choice should be made according to the patients’ conditions and urologists’ acquaintance.

Since their clinical application in the 1840s, the greatest mystery surrounding general anesthesia (GA) is how different kinds of general anesthetics cause reversible unconsciousness, and the precise neural mechanisms underlying the processes. Over past years, although many studies revealed the roles of cortex, thalamus, brainstem, especially the sleep-wake circuits in GA-induced loss of consciousness (LOC),the full picture of the neural circuit mechanism of GA is still largely unknown. Recent studies have focused on the importance of other brain regions. Here, we report that the activity of glutamatergic (Glu) neurons in the piriform cortex (PC), a critical brain region for odor encoding, began to increase during the LOC of GA and gradually recovered after recovery of consciousness. Chemical lesions of the anterior PC (APC) neurons accelerated the induction time of isoflurane anesthesia. Chemogenetic and optogenetic activation of APCGlu neurons prolonged isoflurane and sevoflurane anesthesia induction, whereas APCGlu neuron inhibition displayed the opposite effects. Moreover, the modification of APCGlu neurons did not affect the induction or emergence time of propofol GA. In addition, odor processing may be partially involved in the induction of isoflurane and sevoflurane GA regulated by APCGlu neurons. In conclusion, our findings reveal a critical role of APCGlu neurons in inhalational GA induction.

Abstract Acute kidney injury (AKI) is one of the most important lethal factors for patients admitted to intensive care units (ICUs), and timely high-risk prognostic assessment and intervention are essential to improving patient prognosis. In this study, a stacking model using the MIMIC-III dataset with a two-tier feature selection approach was developed to predict the risk of in-hospital mortality in ICU patients admitted for AKI. External validation was performed using separate MIMIC-IV and eICU-CRD. The area under the curve (AUC) was calculated using the stacking model, and features were selected using the Boruta and XGBoost feature selection methods. This study compares the performance of a stacking model using two-tier feature selection with a model using single-tier feature selection (XGBoost: 85; Boruta: 83; two-tier: 0.91). The predictive effectiveness of the stacking model was further validated by using different datasets (Validation 1: 0.83; Validation 2: 0.85) and comparing it with a simpler model and traditional clinical scores (SOFA: 0.65; APACH IV: 0.61). In addition, this study combined interpretable techniques and causal inference to analyze the causal relationship between features and predicted outcomes.

Abstract Objective The aim of this study is to identify risk factors associated with acute complicated appendicitis (CA) in children aged three years or younger, providing a theoretical foundation for the management and treatment of acute appendicitis (AA). Methods A retrospective analysis was conducted on 135 pediatric patients with AA, admitted to the Department of General Surgery at Anhui Children’s Hospital between December 2020 and December 2023, who underwent successful surgical treatment. Based on the intraoperative and postoperative pathological findings, patients were categorized into two groups: complicated appendicitis (CA) (n = 97 cases) and uncomplicated appendicitis (UA) (n = 38 cases). Clinical data including gender, age, weight, disease duration, preoperative white blood cell count (WCC), neutrophil granulocyte (NEUT) count, C-reactive protein (CRP) levels, total bilirubin (TBil) levels, procalcitonin (PCT) levels, calprotectin (Cal) levels, preoperative ultrasound results indicating the presence or absence of fecaliths, maximum appendix diameter, and pediatric appendicitis sore (PAS) were collected and analyzed. Comparative analysis was performed to investigate the differences between the groups and identify risk factors of CA. Results The CA group exhibited significantly higher values in disease duration, CRP levels, PCT, Cal, presence of appendiceal fecaliths, maximum appendix diameter, and PAS compared to the UA group (P

Abstract Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

An iterative evaluation method for testability of avionics electronic system in field is proposed to improve the accuracy of testability evaluation and solve the problems of few testability evaluation samples and low evaluation accuracy of avionics electronic system after aircraft service. Firstly, the idea of field testability evaluation based on Bayesian framework is expounded. Secondly, according to the prior information, the maximum entropy method, combined with PSO algorithm, is used to find hyper-parameters in the prior distribution of fault detection rate, and hyper-parameters consistency check is carried out. Then, the posterior distribution is obtained by Bayes formula, and the iterative estimation results of fault detection rate are obtained. Combined with the example, the comparison and analyses between this method and existing method further proved the correctness and advantages of the proposed method.

This study aimed to clarify the oxidative damage in human skin fibroblasts (HSF) treated with trimethylamine oxide (TMAO) and to elucidate its pro-aging effect in skin cells in terms of antioxidant indicators, levels of inflammatory cytokines, levels of collagen and matrix metalloproteinases, and mRNA expression of related genes. The results showed that TMAO treatment significantly increased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and decreased the content of reduced glutathione, superoxide dismutase (SOD) activity, and total antioxidant capacity (TAC) in HSF cells (P < 0.05). TMAO treatment was found to significantly elevate the mRNA levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and matrix metalloproteinase-1 (MMP-1), and decrease the mRNA transcript levels of collagen synthesis-related genes and the inducible nitric oxide synthase (iNOS) gene by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Western blot analysis showed that the protein expression level of phosphorylated p65 (p-p65) significantly increased (P < 0.05). Vitamin C (VC) was able to protect against TMAO-induced oxidative stress in HSF cells, and reduce inflammation and collagen loss. These results indicated that TMAO can produce oxidative stress in HSF cells, which may activate the signaling pathway of nuclear factor kappa-B (NF-κB), promote NF-κB phosphorylation in HSF cells, induce inflammatory responses, reduce collagen synthesis, and accelerate collagen degradation, thus possibly promoting skin cell aging.

Abstract Purpose The purpose of this study was to analyse the difference between arthroscopic fixation and open reduction internal fixation (ORIF) of posterior cruciate ligament (PCL) tibial avulsion fractures. Methods This retrospective study analysed patients with an acute PCL tibial avulsion fracture who underwent surgical treatment at our hospital and follow-up for at least 24 months. Variables based on sex, age, Meyers–McKeever type, surgical method, meniscus tear, external fixation, labour or sports, Lysholm knee score, IKDC score, and KT-1000 value were also recorded. Multifactor unconditional logistic regression and Student’s t test with 1:1 propensity score matching (PSM) to remove confounding factors were used for analysis. Results Sixty-five cases achieved knee function graded as “good” or better, and 9 cases not. Single-factor analysis indicated that Meyers–McKeever type (χ 2 = 4.669, P = 0.031) and surgical approach (χ 2 = 9.428, P = 0.002) are related to functional outcomes. Multifactorial logistic regression analysis further confirmed that Meyers–McKeever typing (OR = 10.763, P = 0.036, [95% CI 1.174–98.693]) and surgical approach (OR = 9.274, P = 0.008, [95% CI 1.794–47.934]) are independent risk factors affecting prognosis. In addition, PSM verified significant differences in the Lysholm score (t = 3.195, P = 0.006), IKDC score (t = 4.703, P = 0.000) and A-KT/H-KT (t = 2.859, P = 0.012). However, the affected-side KT-1000 value (A-KT, mm, t = 1.225, P = 0.239) and healthy-side KT-1000 value (H-KT, mm, t = 1.436, P = 0.172) did not significantly differ between the two groups. The proportions of cases in which the Lysholm score, IKDC and A-KT/H-KT exceeded the minimal clinically important difference (MCID) were 62.5% (20/32), 62.5% (20/32) and 93.75% (30/32), respectively. Conclusion Compared with ORIF, an arthroscopic approach for PCL tibial avulsion fractures achieves better results. Level of evidence: Retrospective cohort study; Level II.

Abstract This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

Abstract Nicotine, a crucial constituent of tobacco smoke, can bind to and activate nicotinic acetylcholine receptors (nAChRs), thereby regulating various biological functions. However, the specific mechanisms through which nicotine mediates nAChRs to regulate the metastasis of laryngeal squamous cell carcinoma (LSCC) remain elusive. In this study, smoking status was found to be closely associated with metastasis in patients with LSCC. In addition, nicotine exposure potentiated the hematogenous and lymphatic metastatic capacity of LSCC cells. Nicotine activates membrane-bound CHRNA5, promoting cell migration and invasion, EMT and cell–ECM adhesion in LSCC. Furthermore, this study demonstrated that the Ras superfamily protein RABL6 directly interacted with CHRNA5, which preferentially binds to the RABL6-39-279aa region, and this interaction was enhanced by nicotine. Nicotine-mediated activation of CHRNA5 enhanced its interaction with RABL6, triggering the JAK2/STAT3 signalling pathway and eventually augmenting the metastatic potential of LSCC cells. This study reveals a novel mechanism through which nicotine-mediated CHRNA5–RABL6 interaction promotes the metastasis of LSCC. The findings of this study may help to develop effective strategies for improving the outcome of patients with LSCC in clinical settings.

Abstract Anthropogenic climate warming is predicted to increase the intensity of global tropical cyclones (TCs) on decadal timescales, known as the ‘temperature-TC intensity’ paradigm. However, no proxy is currently available to directly quantify TC intensity in the northwestern Pacific region over centennial to millennial timescales. Here, we reconstruct the intensity of past TCs inferred from event-beds detected in two sedimentary systems in eastern China spanning approximately 1910 to 645 yr BP using an instrumental-calibrated technique, thereby encompassing a sufficiently wide range of temperatures to test the paradigm in the time domain. Intriguingly, our two intensity indices, based on flooding depth and wind speed, provide the initial quantitative evidence that TC intensity in eastern China has been anomalously weak since around 1485 ± 45 yr BP, with a reduction of approximately 30 ± 8% in intensity, despite no concurrent temperature shift. This reduction appears to have been pre-conditioned by a combined influence of a weaker El Niño-Southern Oscillation, a stronger Atlantic Meridional Overturning Circulation, and an increased level of Saharan dust. We suggest that the magnitudes of these factors may have crossed a tipping point and have not reverted to their pre-shift levels since that time, resulting in their impact on TC intensity exceeding that of temperature by triggering changes in the oceanic and atmospheric state within the tropical Pacific region where TCs originate.

Abstract Background There is an urgent need to find a reliable and effective imaging method to evaluate the therapeutic efficacy of immunochemotherapy in advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the capability of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis based on different region of interest (ROI) selection methods for predicting treatment response to chemoimmunotherapy in advanced NSCLC. Methods Seventy-two stage III or IV NSCLC patients who received chemoimmunotherapy were enrolled in this study. IVIM and DKI were performed before treatment. The patients were classified as responders group and non-responders group according to the Response Evaluation Criteria in Solid Tumors 1.1. The histogram parameters of ADC, Dslow, Dfast, f, Dk and K were measured using whole tumor volume ROI and single slice ROI analysis methods. Variables with statistical differences would be included in stepwise logistic regression analysis to determine independent parameters, by which the combined model was also established. And the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of histogram parameters and the combined model. Results ADC, Dslow, Dk histogram metrics were significantly lower in the responders group than in the non-responders group, while the histogram parameters of f were significantly higher in the responders group than in the non-responders group (all P

Power infrastructure projects are characterized by complex supply chain structures and numerous stakeholders, presenting significant challenges in maintaining data integrity and ensuring seamless integration of project information. Previous Digital Twins (DTs) and Building Information Modeling (BIM) collaboration methods lack robust mechanisms for data traceability and immutable storage, leading to potential risks such as data loss or tampering. Furthermore, existing project information exchange and data management methods do not adequately integrate diverse data types, such as project documentation, onsite environment monitoring IoT sensor readings and CAD/BIM-based design information. This research introduces a novel DT data platform prototype, utilizing Blockchain and Semantic Web technologies, to establish a trustworthy DT data environment for power infrastructure projects. This system collects heterogeneous data, including manual inputs and IoT-generated data, and processes them into RDF format on dedicated devices. The integrated data is then stored on a Permissioned Blockchain, ensuring traceability and immutability. The framework incorporates Distributed File Systems to enhance storage efficiency and features a semantic gateway that transforms heterogeneous data into RDF graphs, fostering interoperability and the potential for automated data linkage. The efficacy of this prototype was demonstrated through a case study, testing data consistency and showcasing prototype queries enhanced by Semantic Web, thus substantiating the platform’s capacity to support multidisciplinary project management.

Autoimmune diseases encompass over 80 distinct types, affecting approximately 7.6–9.4 % of the population globally. The intricate interplay between genetic predispositions and environmental triggers complicates early diagnosis and intervention. Abnormal macrophage differentiation and proliferation have been identified as key contributors to the pathogenesis of these conditions, though the precise molecular pathways remain poorly understood. Recent studies suggest that cereblon (CRBN), a target for immunomodulatory drugs like thalidomide, lenalidomide, and pomalidomide, may offer therapeutic potential for autoimmune diseases such as systemic lupus erythematosus. In this study, quantitative proteomics revealed that CRBN downregulated the calpain regulatory subunit, calpain small subunit 1 (CAPNS1), in macrophages. Subsequent biochemical assays demonstrated that CRBN modulated calpain activity, impacting autophagy processes during macrophage differentiation and microglial phagocytosis. Histological evaluation of CRBN-deficient mice indicated a marked increase in microglial populations in the brain. These findings highlight potential therapeutic targets and present new avenues for the treatment of autoimmune diseases.

The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, cell type specific dysregulation of transposable elements was observed in Severe COVID-19 patients. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.

Objectives Previous research has extensively explored the factors associated with psychotic-like experiences (PLEs). However, the characteristics and associated factors of remitted PLEs, which refer to the absence of current PLEs following previous PLEs, remain unclear. Therefore, this study aims to describe the characteristics of adolescents who reported remitted PLEs.Design Cross-sectional study.Setting The survey was conducted from October to December 2020 in three colleges located in Guangzhou, China.Participants A total of 4208 college freshmen aged from 15 to 24 participated in our survey.Primary and secondary outcome measures The 15-item positive subscale of the Community Assessment of the Psychic Experience was used to assess both lifetime and current PLEs. Multivariate logistic regression models were used to examine the associations between remitted PLEs and a range of demographic factors, lifestyle, psychosocial factors, lifetime affective symptoms and sleep problems.Results Three groups of PLEs were observed: non-PLEs (47.27% of the sample), remitted PLEs (40.42%) and current PLEs (12.31%). Several factors have been identified as shared correlates of remission and absence of PLEs, including fewer recent adverse life events, greater resilience, fewer symptoms of depression and anxiety, and early waking. Furthermore, higher levels of social support (OR 1.48, 95% CI 1.01 to 2.17; OR 1.53, 95% CI 1.18 to 1.97) was a specific factor associated with the remission of PLEs. Compared with individuals without PLEs, those with remitted PLEs were more likely to be female (OR 1.50, 95% CI 1.28 to 1.75), less likely to be younger (OR 0.88, 95% CI 0.81 to 0.95) and prone to have more chronic physical illness (OR 1.67, 95% CI 1.29 to 2.16), habitual alcohol intake (OR 1.85, 95% CI 1.19 to 2.88), more childhood trauma (OR for low vs high=0.72, 95% CI 0.57 to 0.91) and the sleep problems of waking up easily (OR 1.36, 95% CI 1.12 to 1.65).Conclusion These findings suggest that remitted PLEs play a vital, unique role among three groups and provide preliminary targets for the intervention for adolescents at risk of mental health problems. Further investigation may shed light on the causality of the relationship between remitted PLEs and associated factors.

Abstract Three dinuclear Pd(II) complexes (1, 2, and 3) with intense red phosphorescence at room temperature are here synthesized using strong ligand field strength compounds. All three complexes are characterized by nuclear magnetic resonance, high‐resolution mass spectrometry, and elemental analyses. Complexes 2 and 3 are characterized by single‐crystal X‐ray diffraction. The crystalline data of 2 and 3 reveal complex double‐layer structures, with Pd–Pd distances of 2.8690(9) Å and 2.8584(17) Å, respectively. Furthermore, complexes 1, 2, and 3 show phosphorescence at room temperature in their solid states at the wavelengths of 678, 601, and 672 nm, respectively. In addition, they show phosphorescence at 634, 635, and 582 nm, respectively, in the 2 wt.% (PMMA) films, and phosphorescence at 670, 675, and 589 nm, respectively, in the deoxygenated CH2Cl2 solutions. Among three complexes, complex 1 shows red emission at 634 nm with phosphorescent quantum yield Ф = 67% in the 2 wt.% PMMA film. Furthermore, complex 1‐based organic light‐emitting diode is fabricated using a vapor‐phase deposition process, and their maximum external quantum efficiency reaches 20.52%, which is the highest percentage obtained by using the dinuclear Pd(II) complex triplet emitters with the CIE coordinates of (0.62, 0.38).

This study explores the thermal behavior of graphite-enhanced expanded polystyrene (GEPS) both with and without a rendering cover during cone calorimeter testing. We designed a sample holder with inserted thermocouples to capture temperature variations at different levels. Without a cover, the sample remained unignited under radiant intensity of 25 kW m−2, experiencing a brief temperature rise followed by stabilization. At 50 kW m−2, ignition occurred after a period of steady temperature. However, at 75 kW m−2, the temperature soared rapidly without a stable phase, leading to swift ignition. With a cover, the temperatures for all tested scenarios ultimately stabilized without ignition, even though the recorded values exceeded the ignition point under high heat fluxes. This indicates that the protective mechanism of render lies mainly in isolating mass transfer. Increasing the render's thickness from 3 mm to 5 mm delayed and slowed the initial temperature rise but had little impact on the final steady temperatures. Based on the energy conservation principles, a steady temperature prediction model for liquified GEPS and rendering cover was established. Notably, the calculated outcomes closely align with the measured temperatures. These findings provide valuable insights into the fire safety characteristics of GEPS and the protective effects of rendering covers.

Abstract Background Steroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid receptor (GR) mediates the intracellular signaling of inhaled corticosteroids (ICS) by interacting with transcription factors and histone deacetylases (HDACs). The aim of this study was to assess if COPD patients’ response to ICS in vivo, may be associated with the expression of GR, the complex of GR with transcription factors, and the expression of various HDACs in vitro. Methods Primary airway smooth muscle cells (ASMC) were established from endobronchial biopsies obtained from patients with asthma (n = 10), patients with COPD (n = 10) and subjects that underwent diagnostic bronchoscopy without pathological findings and served as controls (n = 6). ASMC were also established from 18 COPD patients, 10 responders and 8 non-responders to ICS, who participated in the HISTORIC study, an investigator-initiated and driven clinical trial that proved the hypothesis that COPD patients with high ASMC in their endobronchial biopsies respond better to ICS than patients with low ASMC. Expression of GR and its isoforms GRα and GRβ and HDACs was investigated in primary ASMC in the absence or in the presence of dexamethasone (10− 8M) by western blotting. The complex formation of GR with transcription factors was assessed by co-immunoprecipitation. Results Expression of GR and its isoform GRα but not GRβ was significantly reduced in ASMC from COPD patients as compared to controls. There were no significant differences in the expression of GR, GRα and GRβ between responders and non-responders to ICS. However, treatment with dexamethasone upregulated the expression of total GR (p = 0.004) and GRα (p = 0.005) after 30 min in responders but not in non-responders. Τhe formation of the complex GR-c-Jun was increased 60 min after treatment with dexamethasone only in responders who exhibited significantly lower expression of HDAC3 (p = 0.005) and HDAC5 (p

Abstract Background For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. Methods 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th–95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a

Abstract High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.

Abstract Benign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor β (TGF-β)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-β/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-β/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH. Graphical Abstract

Objective: Flexible ureteroscopy (fURS) has become a widely accepted and effective technique for treating kidney stones. With the development of new laser systems, the fURS approach has evolved significantly. This literature review aims to examine the current state of knowledge on fURS treatment of kidney stones, with a particular focus on the impact of the latest laser technologies on clinical outcomes and patient safety. Methods: We conducted a search of the PubMed/PMC, Web of Science Core Collection, Scopus, Embase (Ovid), and Cochrane Databases for all randomized controlled trial articles on laser lithotripsy in September 2023 without time restriction. Results: We found a total of 22 relevant pieces of literature. Holmium laser has been used for intracavitary laser lithotripsy for nearly 30 years and has become the golden standard for the treatment of urinary stones. However, the existing holmium laser cannot completely powder the stone, and the retropulsion of the stone after the laser emission and the thermal damage to the tissue have caused many problems for clinicians. The introduction of thulium fiber laser and Moses technology brings highly efficient dusting lithotripsy effect through laser innovation, limiting pulse energy and broadening pulse frequency. Conclusion: While the holmium:yttrium-aluminum-garnet laser remains the primary choice for endoscopic laser lithotripsy, recent technological advancements hint at a potential new gold standard. Parameter range, retropulsion effect, laser fiber adaptability, and overall system performance demand comprehensive attention. The ablation efficacy of high-pulse-frequency devices relies on precise targeting, which may pose practical challenges.