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Background: This study aims to evaluate the clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS) when used as an add-on therapy for individuals with persistent postural-perceptual dizziness (PPPD). Methods: In this randomized controlled, double-blind trial conducted at Shangluo Central Hospital, patients with PPPD diagnosed in the neurology departments were included. Participants were randomized into a rTMS treatment group and a control group in a 1:1 ratio by the randomized grouping method. Patients in both groups received conventional treatment, with the rTMS treatment group underwent daily rTMS sessions, whereas the control group received sham rTMS treatments following the same schedule. The effectiveness of the treatments was primarily assessed using the Dizziness Handicap Inventory (DHI), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD), which measured symptoms of vertigo, anxiety, and depression at baseline, after two weeks, and at the end of four weeks. Findings: Of the 46 participants recruited, 2 were excluded due to contraindications, 22 were randomly assigned to the rTMS treatment group, and 22 were assigned to the control group. Ultimately, 2 withdrew for personal reasons, and data from 42 participants were included in the outcome analysis. HAMA, HAMD and DHI scores were significantly lower in the rTMS treatment group than in the control group after 4 weeks of treatment (p

Daphnetin, a coumarin derivative isolated from Daphne odorifera, has anti-tumor effects. The MAPK, STAT3, and NF-κB signaling pathways are closely related to the pathogenesis of lung cancer. To investigate the effect of daphnetin on anti-lung adenocarcinoma A549 cells and its mechanism. The anti-tumor effects of daphnetin on the proliferation, clone formation, migration, and invasion of A549 lung adenocarcinoma cells were investigated. The results showed that daphnetin inhibited the proliferation, colony formation, migration, and invasion of A549 cells through the MAPK/STAT3/NF-KB pathway, and mainly inhibited the clonal formation and migration of A549 cells through the JNK pathway. These results provide a new research direction and theoretical basis for the use of daphnetin in the inhibition of lung adenocarcinoma.

Abstract Knee osteoarthritis (KOA) combined with depressive symptoms is prevalent and leads to poor outcomes and significant financial burdens. However, practical tools for identifying at-risk patients remain limited. A robust prediction model is needed to address this gap. This study aims to develop and validate a predictive model to identify KOA patients at risk of developing depressive symptoms. The China Health and Retirement Longitudinal Survey (CHARLS) data were used for model development and the Osteoarthritis Initiative (OAI) for external validation. 18 potential predictors were selected using LASSO regression. 4 machine learning models—logistic regression, decision tree, random forest, and artificial neural network—were developed. Model performance was assessed using the area under the operating characteristic curve (AUC), calibration curves, and decision curve analysis. The most important features were extracted from the optimal model on external validation. A total of 469 individuals were included, with 70% used for training and 30% for testing. The random forest model achieved the best performance, with an AUC of 0.928 in the test set, outperforming logistic regression (AUC 0.622), decision tree (AUC 0.611), and neural network models (AUC 0.868). External validation revealed an AUC of 0.877 (95% CI: 0.864–0.889) for the adjusted random forest model. Pain severity was the most significant predictor, followed by the five-time sit-to-stand test (FTSST) and sleep problems. This study is the first in China to apply a predictive model for depressive symptoms in KOA patients, offering a practical tool for early risk identification using routinely available data.

Abstract Optical skyrmions are an emerging class of structured light with sophisticated particle-like topologies with great potential for revolutionizing modern informatics. However, the current generation of optical skyrmions involves complex or bulky systems, hindering the development of practical applications. Here, exploiting the emergent “lab-on-fiber” technology, we demonstrate the design of a metafiber-integrated photonic skyrmion generator. We not only successfully generate high-quality optical skyrmions from metafibers, but also verify their remarkable properties, such as topology switchability and topology stability with subwavelength polarization features beyond the diffraction limits. Our flexible fiber-integrated optical skyrmions platform paves the avenue for future applications of topologically-enhanced remote super-resolution microscopy and robust information transfer.

Abstract Despite the significant potential of generative models, low synthesizability of many generated molecules limits their real-world applications. In response to this issue, we develop ClickGen, a deep learning model that utilizes modular reactions like click chemistry to assemble molecules and incorporates reinforcement learning along with inpainting technique to ensure that the proposed molecules display high diversity, novelty and strong binding tendency. ClickGen demonstrates superior performance over the other reaction-based generative models in terms of novelty, synthesizability, and docking conformation similarity for existing binders targeting the three proteins. We then proceeded to conduct wet-lab validation on the ClickGen’s proposed molecules for poly adenosine diphosphate-ribose polymerase 1. Due to the guaranteed high synthesizability and model-generated synthetic routes for reference, we successfully produced and tested the bioactivity of these novel compounds in just 20 days, much faster than typically expected time frame when handling sufficiently novel molecules. In bioactivity assays, two lead compounds demonstrated superior anti-proliferative efficacy against cancer cell lines, low toxicity, and nanomolar-level inhibitory activity to PARP1. We demonstrate that ClickGen and related models may represent a new paradigm in molecular generation, bringing AI-driven, automated experimentation and closed-loop molecular design closer to realization.

Abstract Background The relationship between hepatocellular carcinoma (HCC) metastasis and cancer metabolism reprogramming is becoming increasingly evident. Ubiquitin-specific protease 11 (USP11), a member of the deubiquitinating enzyme family, has been linked to various cancer-related processes. While USP11 is known to promote HCC metastasis and proliferation, the precise mechanisms, especially those related to cancer metabolism, remain unclear. Methods Through mass spectrometry, co-immunoprecipitation, immunofluorescence, and ubiquitination assays, we identified USP11 as the key deubiquitinase for SREBF1.Lipogenesis was evaluated using Oil Red O and Nile Red staining, along with the detection of triglycerides and cholesterol. To assess HCC cell proliferation, migration, and invasion in vitro, Transwell assays, EDU, colony formation, and CCK-8 were conducted. Xenograft models in nude mice were developed to verify the role of the USP11/SREBF1 axis in lipogenesis and tumor growth in vivo. Results USP11 directly interacts with SREBF1, and its silencing leads to the disruption of SREBF1 stabilization through K48-linked deubiquitination and degradation. Importantly, the truncated mutant USP11 (503–938 aa) interacts with the truncated mutant SREBF1 (569–1147aa), with K1151 playing a crucial role in this interaction. Higher levels of USP11 enhance lipogenesis, proliferation, and metastasis in HCC cells. Importantly, the knockdown of SREBF1 weakened the effects of USP11 in enhancing lipogenesis and tumorigenesis. Futhermore, the elevated expression of USP11 and SREBF1 in HCC tissue serves as an indicator of poor prognosis in HCC patients. Conclusions In summary, our study reveals that USP11 promotes HCC proliferation and metastasis through SREBF1-induced lipogenesis. These findings provide a foundation for novel therapies targeting lipid metabolism in HCC.

Abstract Histone deacetylase inhibitors (HDACis) have shown a significant antitumor effect in clinical studies, and PXD101 is a novel HDACi which can cross the blood–brain barrier. In this study, we showed that PXD101 could significantly inhibit the proliferation and invasion of glioblastoma (GBM) cells, while promoting their apoptosis and radiosensitivity. Furthermore, it was found that PXD101 exerted its antitumor function by upregulating the expression of the growth arrest and DNA damage inducible protein α (GADD45A). Mechanistically, PXD101 promoted the transcription of GADD45A by directly acetylating the histones H3 and H4, and GADD45A enhanced apoptosis and radiosensitivity through the activation of P38 in the GBM cells. In vivo experiments also showed that PXD101 combined with radiotherapy could significantly inhibit the growth of GBM. This study provides experimental evidence for application of the novel HDACi PXD101 in the treatment of GBM, as well as new molecular markers and potential intervention targets that may be used in preventing GBM malignant progression and radioresistance.

Two new Cordyceps-like species, Perennicordyceps zongqii and Purpureocillium zongqii, isolated from a larva and soil, are introduced. Morphological comparisons and phylogenetic analyses based on multigene datasets (ITS, LSU, RPB2 and TEF) support the establishment of the new species. Moreover, new species in the families Polycephalomycetaceae and Ophiocordycipitaceae were introduced into Tiankeng and the valley for the first time. Further attention needs to be paid to the diversity of other Cordyceps-like fungi in the special eco-environment of the karst region.

Abstract Coenzyme Q10 (CoQ10) is the most consumed dietary supplement and mainly biosynthesized by aerobic fermentation of Rhodobacter sphaeroides (R. sphaeroides). Oxygen supply was identified as a bottleneck for improving CoQ10 yield in R. sphaeroides. In this study, a precise regulation strategy based on dielectric spectroscopy (DS) was applied to further improve CoQ10 biosynthesis by R. sphaeroide. First, a quantitative response model among viable cells, cell morphology, and oxygen uptake rate (OUR) was established. DS could be used to detect viable R. sphaeroides cells, and the relationship among cell morphology, CoQ10 biosynthesis, and OUR was found to be significant. Based on this model, the online specific oxygen consumption rate (QO2) control strategy was successfully applied to the CoQ10 fermentation process. QO2 controlled at 0.07 ± 0.01 × 10− 7mmol/cell/h was most favorable for CoQ10 biosynthesis, resulting in a 28.3% increase in CoQ10 production. Based on the multi-parameters analysis and online QO2 control, a precise online nutrient feeding strategy was established using conductivity detected by DS. CoQ10 production was improved by 35%, reaching 3384 mg/L in 50 L bioreactors. This online control strategy would be effectively applied for improving industrial CoQ10 production, and the precise fermentation control strategy could also be applied to other fermentation process.

Abstract Background With increasing age, the social and economic burdens of postmenopausal osteoporosis are steadily increasing. This study aimed to investigate the factors that influence the development of postmenopausal osteoporosis. Methods Postmenopausal women at the Affiliated Hospital of Jiangnan University from January 2023 to December 2023 were recruited for BMD examination. The patients were divided into a normal group, an osteopenia group and an osteoporosis group according to their T value. Questionnaires, including the Gastrointestinal Symptom Rating Scale and Short Form 12, were administered through face-to-face interviews. Bone turnover markers and serum protein levels of Fasting venous blood were detected. Results A total of 222 postmenopausal women met the inclusion criteria were recruited. Univariate analysis revealed statistically significant differences in age, education, BMI, supplementation with soy products, supplementation with dairy products, supplementation with other nutritional supplements, exercise frequency, gastrointestinal symptom score, quality of life, 25(OH)D, total protein, albumin and prealbumin among the three groups (P

Abstract The bidirectional relationship between sleep duration and pain during the COVID-19 pandemic remains poorly understood. This study explores these interactions and the mediating roles of depression and chronic diseases using data from the China Health and Retirement Longitudinal Study (CHARLS) cohort. A cross-sectional analysis was conducted on 15,979 participants aged 45 and older. Sleep duration was self-reported, and pain was assessed using validated anatomical charts. Depression symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10), and chronic diseases were self-reported. Personal activity during the pandemic was measured using the Personal Activity Score during COVID-19 (PAS-COVID-19). The results showed a significant association between deviations from optimal sleep duration and increased pain frequency. Participants with both shorter and longer sleep durations reported higher pain levels, with depression and chronic diseases acting as significant mediators. However, personal activity did not significantly mediate the association between sleep duration and pain. These findings underscore the complex interplay among sleep duration, pain, depression, and chronic diseases during the COVID-19 pandemic, emphasizing the importance of integrated interventions to manage these interconnected health issues.

Abstract Background This study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during disease progression. Methods Pathological features and serum lipid profiles of 179 patients with stage III-IV gastric adenocarcinoma were analyzed. Lipid parameters examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein AI (Apo AI), apolipoprotein B (Apo B), lipoprotein(a) (Lp(a)), among others. The total cholesterol-lymphocyte score (TL score) and BMI were also calculated. The association between lipid parameters and clinicopathological characteristics such as age, gender, family history, and metastasis sites was assessed. Results In GC patients, females had higher TG levels than males. Patients with peritoneal metastasis had significantly lower levels of TC, LDL-C, Apo B, and B/A ratio. Those with lung metastasis exhibited higher LDL-C levels and lower levels of VLDL-C. No significant associations were found between lipid levels and metastasis to distant lymph nodes, liver, or bone. Female patients with ovarian metastasis had significantly lower VLDL-C levels. Multivariate analysis revealed low TC as an independent risk factor for peritoneal metastasis, high LDL-C and low VLDL-C levels for lung metastasis, and younger age and low VLDL-C for ovarian metastasis. Conclusion Specific blood lipid levels are significantly associated with metastatic sites in advanced gastric cancer. Lipid profiles could serve as potential biomarkers for predicting metastatic sites in GC patients.

Abstract Background The prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM. Methods Inpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1. Results Of the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P

Abstract The twin boundaries and inherent lattice strain of five-fold twin (5-FT) structures offer a promising and innovative approach to tune nanocrystal configurations and properties, enriching nanomaterial performance. However, a comprehensive understanding of the nonclassical growth models governing 5-FT nanocrystals remains elusive, largely due to the constraints of their small thermodynamically stable size and complex twin configurations. Here, we conducted in situ investigations to elucidate the atomic-scale mechanisms driving size-dependent and twin configuration-related aggregation phenomena between 5-FT and other nanoparticles at the atomic scale. Our results reveal that surface diffusion significantly shapes the morphology of aggregated nanoparticles, promoting the symmetrical formation of 5-FT, especially in smaller nanoparticles. Moreover, the inherent structural characteristics of 5-FT mitigate the dominance of surface diffusion in its morphological evolution, retarding the aggregation evolution process and fostering intricate twin structures. These findings contribute to advancing our capacity to manipulate the configuration of twinned particles, enabling more predictable synthesis of functional nanomaterials for advanced engineering applications.

Abstract The quality of images we perceive visually is heavily impacted by the settings used for camera exposure. When these settings are imbalanced, it can result in an undesired prominent phenomenon known as blur effects. To address this problem, an ExposureNet project has been undertaken, which aims to develop an autonomous camera exposure settings control system for blur effects prevention. The proposed ExposureNet model is a CNN/Transformer hybrid neural structure, created and trained in a comprehensive manner to effectively predict the ideal exposure settings based on the semantic features of the scene being captured. This system is designed to learn the necessary steps for processing, such as identifying relevant scene features, using only two camera exposure parameters (shutter speed (SHS) and ISO) as training signals. As a result, this system can associate the semantic features of a scene with the appropriate exposure parameter adjustments, customized to the scene's dynamics and lighting conditions. By simultaneously optimizing all processing steps and bypassing traditional post‐processing stages, the proposed system is designed to achieve faster performance, reduced computational cost, and lower power consumption. Experimental results demonstrate that the proposed system significantly outperforms existing methods and achieves cutting‐edge performance.

Purpose – The purpose of this study is to address the deficiency in safety monitoring technology for 27.5 kV high-voltage cables within the railway traction power supply by analyzing the grounding methods employed in high-speed railways and developing an effective monitoring solution. Design/methodology/approach – Through establishing a mathematical model of induced potential in the cable sheath and analyzing its influencing factors, the principle of grounding current monitoring is proposed. Furthermore, the accuracy of data collection and alarm function of the monitoring equipment were verified through laboratory simulation experiments. Finally, through practical application in the traction substation of the railway bureau on site, a large amount of data were collected to verify the stability and reliability of the monitoring system in actual environments. Findings – The experimental results show that the designed monitoring system can effectively monitor the grounding current of high-voltage cables and respond promptly to changes in cable insulation status. The system performs excellently in terms of data collection accuracy, real-time performance and reliability of alarm functions. In addition, the on-site trial results further confirm the accuracy and reliability of the monitoring system in practical applications, providing strong technical support for the safe operation of high-speed railway traction power supply systems. Originality/value – This study innovatively develops a 27.5kV high-voltage cable grounding current monitoring system, which provides a new technical means for evaluating the insulation status of cables by accurately measuring the grounding current. The design, experimental verification and application of this system in high-speed railway traction power supply systems have demonstrated significant academic value and practical significance, contributing innovative solutions to the field of railway power supply safety monitoring.

Abstract Background Inter-generational interaction is a carrier of Chinese traditional culture, and it can exert important influence on the depressive symptoms on Chinese older adults. The study aims to analyze gender differences in the association between inter-generational interaction and depressive symptoms among Chinese older adults and explore factors contributing to the differences. Method Data from China Family Panel Studies in 2020 were used. Depressive symptoms were assessed using the 8-item Center for Epidemiologic Studies Depression Scale. The latent class analysis was applied to identify patterns of inter-generational interaction of older adults (aged 60 and above). Before the comparison between older man and older woman, we used Coarsened Exact Matching to control confounding factors and improve causal inferences. Multiple linear regression was conducted to explore the association between inter-generational interaction and depression symptoms. Oaxaca-blinder decomposition method was used to analyze the gender difference and the sources. Result Our study identified three types of inter-generational interaction: detached, nearby but discordant and two-way tight-knit. Analysis indicated that most of older man (54.39%) and older woman (49.78%) were in the type of nearby but discordant. Older man and older woman who in detached type had higher depression scores than other types, and the depression score of two-way tight-knit type accounted for 12.42 and 13.77 respectively. Our findings demonstrated that two-way tight-knit type (-11.89%) significantly decreased the gender differences in the depression symptoms. Other major contributors also included living without spouse (20.56%), primary school and junior middle school (15.95%), higher middle school and above (9.50%) and no illness for two weeks (47.70%). Conclusion Our study highlighted three patterns of inter-generational interaction, and most of older man and older woman were in the pattern of nearby but discordant. In addition, the two-way tight-knit pattern significantly can decrease gender differences in depression symptoms. The contributors should be taken into account in more targeted intervention strategies for narrowing gender differences in the depression symptoms, which could achieve a gender dividend in the era of China's aging population.

Abstract Background Inorganic polyphosphate (polyP)-targeted polyphosphate kinase 1 (PPK1) has attracted much attention by virtue of its importance in bacterial pathogenicity and persistence, as well as its exclusive presence in microorganisms. However, only very few drugs have been found to be efficacious in inhibiting the Acinetobacter baumannii (A. baumannii) PPK1 protein. Results In this study, we identified Scutellarein (Scu), a potent PPK1 inhibitor that could significantly influence PPK1-regulated motility, biofilm formation, and bacterial persistence, which was further validated by the results of transcriptome analysis. Mechanistic explorations revealed that Scu achieved its enzyme inhibitory activity predominantly through direct engagement with the active center of PPK1. Moreover, the survival rate of Galleria mellonella larvae was increased by about 35% with 20 mg/kg of Scu treatment. The remarkable therapeutic benefits of Scu were also observed in the mouse pneumonia model, shown mainly by reduced bacterial colonization, pathological lesions, and inflammatory factors. Conclusion Our results revealed that Scu could attenuate the pathogenicity and persistence of A. baumannii by interfering with its important kinase PPK1.

Two new species, Chlorocillium sinense and Calcarisporium guizhouense, isolated from a spider and fruiting body of Cordyceps sp., are introduced. Morphological comparisons and phylogenetic analyses based on multigene datasets (ITS+LSU+RPB2+tef-1alpha) support the establishment of the new species. A combined dataset of ITS, LSU, RPB2, and tef-1alpha showed the taxonomic placement of Chlorocillium in Clavicipitaceae for the first time. Pseudometarhizium is regarded as a synonym of Chlorocillium and two Pseudometarhizium species are transferred into the latter based on the phylogenetic analysis and morphological characteristics.

Abstract This study developed a postbiotic fermentation solution for fresh oyster preservation with the use of food waste soy whey. Lactiplantibacillus plantarum 299V was able to proliferate in soy whey within 24 h without any supplementation. Pacific oysters (Magallana gigas) were immersed in the postbiotic fermentation solution and stored at 4 °C for 12 days. Pathogenic bacteria Vibrio parahaemolyticus and Salmonella enterica introduced by bioaccumulation were suppressed to levels below the detection limit (60%). Overall, the postbiotic fermentation solution reported in this study enhanced the shelf life and safety of oysters in a sustainable way and could also be recognized as an innovative probiotic vehicle with potential implications for human health promotion.

Abstract Background The global rise in developmental delays underscores the critical need for a thorough understanding and timely interventions during early childhood. Addressing this issue, the Chinese Baby Connectome Project (CBCP)’s behavior branch is dedicated to examining language acquisition, social-emotional development, and environmental factors affecting Chinese children. The research framework is built around three primary objectives: developing a 0–6 Child Development Assessment Toolkit, implementing an Intelligent Coding System, and investigating environmental influence. Methods Utilizing an accelerated longitudinal design, the CBCP aims to enlist a minimum of 1000 typically developing Chinese children aged 0–6. The data collected in this branch constitutes parental questionnaires, behavioral assessments, and observational experiments to capture their developmental milestones and environmental influences holistically. The parental questionnaires will gauge children’s developmental levels in language and social-emotional domains, alongside parental mental well-being, life events, parenting stress, parenting styles, and family relationships. Behavioral assessments will involve neurofunctional developmental evaluations using tools such as the Griffiths Development Scales and Wechsler Preschool and Primary Scale of Intelligence. Additionally, the assessments will encompass measuring children’s executive functions (e.g., Head-Toe-Knee-Shoulder), social cognitive abilities (e.g., theory of mind), and language development (e.g., Early Chinese Vocabulary Test). A series of behavior observation. experiments will be conducted targeting children of different age groups, focusing primarily on aspects such as behavioral inhibition, compliance, self-control, and social-emotional regulation. To achieve the objectives, established international questionnaires will be adapted to suit local contexts and devise customized metrics for evaluating children’s language and social-emotional development; deep learning algorithms will be developed in the observational experiments to enable automated behavioral analysis; and statistical models will be built to factor in various environmental variables to comprehensively outline developmental trajectories and relationships. Discussion This study’s integration of diverse assessments and AI technology will offer a detailed analysis of early childhood development in China, particularly in the realms of language acquisition and social-emotional skills. The development of a comprehensive assessment toolkit and coding system will enhance our ability to understand and support the development of Chinese children, contributing significantly to the field of early childhood development research. Trial registration This study was registered with clinicaltrials.gov NCT05040542 on September 10, 2021.

Background: This study examined the impact of apolipoprotein ɛ4 (APOEɛ4) allele frequency and sex on the phenotype of Alzheimer’s disease (AD). Methods: This post hoc study evaluated the baseline characteristics, cerebrospinal fluid (CSF) and neuroimaging biomarkers, and cognition scores collected from 45 patients aged 50–74 years with CSF-biomarker-confirmed mild cognitive impairment or mild dementia due to AD from clinical trial NCT03186989. Results: A phenotypic spectrum was observed from a predominant amyloid and limbic–amnestic phenotype in male APOEɛ4 homozygotes to a predominantly tau, limbic-sparing, and multidomain cognitive impairment phenotype in female APOEɛ4 noncarriers. Amyloid pathology was inversely correlated with tau pathophysiology, glial activation, and synaptic injury, with the strongest associations observed in male APOEɛ4 carriers. Tau pathophysiology was correlated with glial activation, synaptic injury, and neuroaxonal damage, with the strongest correlation observed in female APOEɛ4 noncarriers. Conclusions: These data support the hypothesis that functional glial activation is influenced by apoE isoform and sex and might explain much of the biological and clinical heterogeneity in early clinical AD in those aged 50–74 years. Conclusions are limited because of the retrospective nature and small sample size. Trial Registration: Clinical Trial NCT03186989.

Abstract Background Intensive Care Unit nurses are related to the medical quality and life outcome of critically ill patients. In the context of nurse shortage, it is of great significance to reduce the turnover intention of Intensive Care Unit nurses. Inclusive Leadership, organizational-based self-esteem and Interactional Justice are important factors affecting the turnover intention of Intensive Care Unit nurses. However, for the special group of Intensive Care Unit nurses, there are few studies that explore the associations between these factors. This study explores the effect of inclusive leadership on the turnover intention of Intensive Care Unit nurses and the potential mediation through organizational-based self-esteem and interactional justice. Method A cross-sectional study design was used to investigate 460 Intensive Care Unit nurses in 4 general hospitals in northern China. The scales used in this study include the inclusive leadership scale, the organization-based self-esteem scale, the interactional justice scale and the turnover intention scale. SPSS 27.0 was used for descriptive analysis and Pearson correlation analysis. AMOS 25.0 was used to construct structural equation model and Bootstrap test. Results The results showed that the turnover intention of Intensive Care Unit nurses was higher (2.05 ± 0.67). Inclusive leadership had a negative predictive effect on turnover intention (β=-0.27, P

ObjectiveTo investigate the association of sleep duration and sleep quality with chronic disease and comorbidity among the elderly in China, providing a reference for developing chronic disease prevention and control strategies for the elderly population in China. MethodsData on 11 529 the elderly aged ≥ 60 years old from 23 provinces (autonomous regions and municipalities) across China were collected from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2018. The association of sleep duration and sleep quality with chronic disease and comorbidity among the elderly in China was analyzed. ResultsAmong the 11 529 the elderly aged ≥ 60 years in China, 2 115 (18.35%), 6 362 (55.18%), and 3 052 (26.47%) had a sleep duration of < 6 h/d, 6 – 8 h/d, and >8 h/d, respectively; 6 201 (53.78%), 3 629 (31.48%), and 1 699 (14.74%) had good, fair, and poor sleep quality, respectively. There were 6 457 cases of chronic disease and 2 682 cases of chronic disease comorbidity, with prevalence rates of 56.01% and 23.26%, respectively. After adjusting for confounding factors such as gender, age, marital status, smoking status, drinking status, and body mass index, multivariate unconditional logistic regression analysis showed that the risk of chronic disease in Chinese the elderly with a sleep duration of < 6 h/d was 1.25 times that of those with a sleep duration of 6 – 8 h/d (OR = 1.25, 95%CI: 1.13 – 1.39). The risk of chronic disease in Chinese the elderly with good and fair sleep quality was 0.62 times (OR = 0.62, 95%CI: 0.55 – 0.70) and 0.72 times (OR = 0.72, 95%CI: 0.64 – 0.81) that of those with poor sleep quality, respectively. The risk of chronic disease comorbidity in Chinese the elderly with a sleep duration of < 6 h/d was 1.34 times that of those with a sleep duration of 6 – 8 h/d (OR = 1.34, 95%CI: 1.19 – 1.51). The risk of chronic disease comorbidity in Chinese the elderly with good and fair sleep quality was 0.54 times (OR = 0.54, 95%CI: 0.48 – 0.62) and 0.65 times (OR = 0.65, 95%CI: 0.57 – 0.74) that of those with poor sleep quality, respectively. ConclusionShort sleep duration can increase the risk of chronic disease and comorbidity in Chinese the elderly, while better sleep quality can reduce the risk of chronic disease and comorbidity in Chinese the elderly.

Abstract Background This study investigates the molecular mechanisms of CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and sorafenib (SF) for improving hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). Methods A dataset of 44 HBV-HCC patients and their survival information was selected from the TCGA database. Immune genes related to survival status were identified using the ImmPort database and WGCNA analysis. A prognostic risk model was constructed and analyzed using Lasso regression. Differential analysis was performed to screen key genes, and their significance and predictive accuracy for HBV-HCC were validated using Kaplan–Meier survival curves, ROC analysis, CIBERSORT analysis, and correlation analysis. The correlation between AC099850.3 and the gene expression matrix was calculated, followed by GO and KEGG enrichment analysis using AC099850.3 and its co-expressed genes. HepG2.2.15 cells were selected for in vitro validation, and lentivirus interference, cell cycle determination, CCK-8 experiments, colony formation assays, Transwell experiments, scratch experiments, and flow cytometry were performed to investigate the effects of key genes on HepG2.2.15 cells. A subcutaneous transplanted tumor model in mice was constructed to verify the inhibitory effect of key genes on HBV-HCC tumors. Subsequently, pH-triggered drug release NPs (CC@AC&SF@PP) were prepared, and their therapeutic effects on HBV-HCC in situ tumor mice were studied. Results A prognostic risk model (AC012313.9, MIR210HG, AC099850.3, AL645933.2, C6orf223, GDF10) was constructed through bioinformatics analysis, showing good sensitivity and specificity in diagnostic prediction. AC099850.3 was identified as a key gene, and enrichment analysis revealed its impact on cell cycle pathways. In vitro cell experiments demonstrated that AC099850.3 promotes HepG2.2.15 cell proliferation and invasion by regulating immune checkpoint CD276 expression and cell cycle progression. In vivo, subcutaneously transplanted tumor experiments showed that AC099850.3 promotes the growth of HBV-HCC tumors in nude mice. Furthermore, pH-triggered drug release NPs (CC@AC&SF@PP) loaded with AC099850.3 siRNA and SF were successfully prepared and delivered to the in situ HBV-HCC, enhancing the effectiveness of combined therapy for HBV-HCC. Conclusions AC099850.3 accelerates the cell cycle progression and promotes the occurrence and development of HBV-HCC by upregulating immune checkpoint CD276 expression. CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and SF improve the effectiveness of combined therapy for HBV-HCC.

Abstract Hydrogen oxidation reaction in alkaline media is critical for alkaline fuel cells and electrochemical ammonia compressors. The slow hydrogen oxidation reaction in alkaline electrolytes requires large amounts of scarce and expensive platinum catalysts. While transition metal decoration can enhance Pt catalysts’ activity, it often reduces the electrochemical active surface area, limiting the improvement in Pt mass activity. Here, we enhance Pt catalysts’ activity without losing surface-active sites by using a Pd-Ru pair. Utilizing a mildly catalytic thermal pyrolysis approach, Pd-Ru pairs are decorated on Pt, confirmed by extended X-ray absorption fine structure and high-angle annular dark-field scanning transmission electron microscopy. Density functional theory and ab-initio molecular dynamics simulations indicate preferred Pd and Ru dopant adsorption. The Pd-Ru decorated Pt catalyst exhibits a mass-based exchange current density of 1557 ± 85 A g−1 metal for hydrogen oxidation reaction, demonstrating superior performance in an ammonia compressor.

Abstract Next-generation sequencing (NGS) has revolutionized genomic research by enabling high-throughput, cost-effective genome and transcriptome sequencing accelerating personalized medicine for complex diseases, including cancer. Whole genome/transcriptome sequencing (WGS/WTS) provides comprehensive insights, while targeted sequencing is more cost-effective and sensitive. In comparison to short-read sequencing, which still dominates the field due to high speed and cost-effectiveness, long-read sequencing can overcome alignment limitations and better discriminate similar sequences from alternative transcripts or repetitive regions. Hybrid sequencing combines the best strengths of different technologies for a more comprehensive view of genomic/transcriptomic variations. Understanding each technology’s strengths and limitations is critical for translating cutting-edge technologies into clinical applications. In this study, we sequenced DNA and RNA libraries of reference samples using various targeted DNA and RNA panels and the whole transcriptome on both short-read and long-read platforms. This study design enables a comprehensive analysis of sequencing technologies, targeting protocols, and library preparation methods. Our expanded profiling landscape establishes a reference point for assessing current sequencing technologies, facilitating informed decision-making in genomic research and precision medicine.

Abstract Background Poor mood states pose the most frequent mental health, creating a considerable burden to global public health. Sedentary behavior is an essential factor affecting mood states, however, previous measures to reduce sedentary time in Chinese young adults have focused only on increasing physical activity (PA). Sedentary, PA, and sleep make up a person’s day from the standpoint of time use. It is not known whether reallocating sedentary time to different types of PA (e.g. daily PA and structured PA) or sleep during an epidemic has an effect on mood states. Therefore, this study aimed to examine the association between replacing sedentary time with different types of PA or sleep during the pandemic and the mood states of Chinese young adults and to further examine whether this association varies across sleep populations and units of replacement time. Method 3,579 young adults aged 18 to 25 years living in China and self-isolating at home during the COVID-19 outbreak were invited to complete an online questionnaire between February from 23 to 29, 2020. Subjects’ PA, sedentary time, and mood states were assessed using the International Physical Activity Questionnaire and the Chinese version of the Profile of Mood States, respectively. Participants also reported sleep duration and some sociodemographic characteristics. Participants were divided into short sleepers ( 9 h/d) based upon their reported sleep duration. Relevant data were analyzed using Pearson correlation analysis and isotemporal substitution model (ISM). Results Sedentary time was negatively associated with mood states in Chinese young adults during the pandemic (r = 0.140) and correlated strongest among short sleepers (r = 0.203). Substitution of sedentary time with structured PA was associated with good mood states (β=-0.28, 95% CI: -0.49, -0.08). Additionally, substituting sedentary time with daily PA (e.g. occupational PA, household PA) was also associated with good mood states among normal sleepers (β=-0.24, 95% CI: -0.46, -0.02). The substitution of sedentary time with sleep could bring mood benefits (β=-0.35, 95% CI: -0.47, -0.23). This benefit was particularly prominent among short sleepers. Furthermore, for long sleepers, replacing sedentary time with sleep time also resulted in significant mood benefits (β=-0.41, 95% CI: -0.69, -0.12). The longer the duration of replacing sedentary behavior with different types of PA or sleep, the greater the mood benefits. Conclusions A reallocation of as little as 10 min/day of sedentary time to different types of PA or sleep is beneficial for the mood states of young adults. The longer the reallocation, the greater the benefit. Our results demonstrate a feasible and practical behavior alternative for improving mood states of Chinese young adults.

Abstract The limitations associated with conventional cancer treatment modalities, particularly for breast cancer, underscore the imperative for developing safer and more productive drug delivery systems. A promising strategy that has emerged is the combination of chemotherapy with gas therapy. We synthesized curcumin-loaded amorphous calcium carbonate nanoparticles (Cur-CaCO3) via a gas diffusion reaction in the present study. Subsequently, a "one-step" ethanol injection method was employed to fabricate lipid-coated calcium carbonate nanoparticles (Cur-CaCO3@LA-Lip) loaded with L-arginine, aimed at harnessing the synergistic effects of chemotherapy and nitric oxide to enhance antitumor efficacy. Transmission electron microscopy analysis revealed that Cur-CaCO3@LA-Lip nanoparticles were subspherical with a distinct lipid layer encapsulating the periphery. Fourier transform infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry results confirmed the successful synthesis of Cur-CaCO3@LA-Lip. The nanoparticles exhibited significant drug loading capacities of 8.89% for curcumin and 3.1% for L-arginine. In vitro and in vivo assessments demonstrated that Cur-CaCO3@LA-Lip nanoparticles facilitated sustained release of curcumin and exhibited high cellular uptake, substantial tumor accumulation, and excellent biocompatibility. Additionally, the nanoparticles showed robust cytotoxicity and potent antitumor efficacy, suggesting their potential as a formidable candidate for breast cancer therapy.

Abstract Purpose To investigate the role of prognostic genes related to cisplatin resistance in ovarian cancer during disease progression. Method The gene expression profile of the NCI-60 cell line was acquired through comprehensive analysis of the GEO database accession GSE116439. We performed a thorough analysis of gene expression differences in samples from seven individuals exposed to cisplatin concentrations of 0 nM compared to seven samples exposed to 15000 nM over a 24-h period. Key genes were initially identified through LASSO regression, followed by their enrichment through differential gene function analysis (GO) and pathway enrichment analysis (KEGG). Subsequently, a prognostic risk model was established for these key genes. The prognostic model's performance was assessed through K-M survival curves and ROC curves. To examine the variance in immune cell infiltration between the high and low-risk groups, CIBERSORTx analysis was employed. Finally, validation of prognostic gene expression in cisplatin-resistant ovarian cancer was carried out using clinical samples, employing RT-qPCR and Western Blot techniques. Results A total of 132 differential genes were found between cisplatin resistance and control group, and 8 key prognostic genes were selected by analysis, namely VPS13B, PLGRKT, CDKAL1, TBC1D22A, TAP1, PPP3CA, CUX1 and PPP1R15A. The efficacy of the risk assessment model derived from prognostic biomarkers, as indicated by favorable performance on both Kaplan–Meier survival curves and ROC curves. Significant variations in the abundance of Macrophages M1, T cells CD4 memory resting, T cells follicular helper, and T cells gamma delta were observed between the high and low-risk groups. To further validate our findings, RT-qPCR and Western Blot analyses were employed, confirming differential expression of the identified eight key genes between the two groups. Conclusion VPS13B, TBC1D22A, PPP3CA, CUX1 and PPP1R15A were identified as poor prognostic genes of cisplatin resistance in ovarian cancer, while PLGRKT, CDKAL1 and TAP1 were identified as good prognostic genes. This offers a novel perspective for future advancements in ovarian cancer treatment, suggesting potential avenues for the development of new therapeutic targets.

Abstract Background Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. Objective To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. Method In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. Results Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. Conclusion These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. Trial registration The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).

We study the almost everywhere pointwise convergence of the Boussinesq operator along sequences $ \{t_n\}_{n = 1}^\infty $ with $ \lim\limits_{n\rightarrow \infty} t_n = 0 $ in one dimension. We obtain a characterization of convergence almost everywhere when $ \{t_n\}\in l^{r, \infty}(\mathbb{N}) $ for all $ f\in H^s(\mathbb{R}) $ provided $ 0 < s < \frac12 $.

Objective: This study aimed to optimize the preparation process of blueberry juice and improve its antioxidant activity. Methods: Blueberry juice was prepared using a wet ultrafine grinding process and compound enzymolysis method. Response surface methodology was used to optimize the process parameters and analyze the antioxidant activity of blueberry juice. Results: There were significant differences in the juice yield and active substance content of blueberry juice under different solid-liquid ratios, crushing times, compound enzyme contents, and enzymatic hydrolysis times, with enzymatic hydrolysis time having the most significant impact on juice yield and anthocyanin content. The optimal process parameters for the wet ultrafine grinding process and compound enzymolysis method are solid-liquid ratio of 1∶1.7 (g/g), pulverization time of 8.00 min, compound enzyme content of 0.15%, and enzymatic hydrolysis time of 127 min. Under the control of these process conditions, the blueberry juice yield was 87.89%, with the contents of anthocyanin, total flavonoid and total phenol were 612.04 mg/L, 2.96 g/L and 3.43 g/L, respectively, and its antioxidant capacity was equivalent to 0.3% vitamin C when the addition amount is 1.6 mL. Conclusion: The wet ultrafine grinding process and compound enzymolysis method can improve the juice yield of blueberry juice, maximize the retention of its active substances, and enhance its antioxidant capacity.

Abstract Glioblastoma (GBM) is a highly aggressive, infiltrative malignancy that cannot be completely cured by current treatment modalities, and therefore requires more precise molecular subtype signatures to predict treatment response for personalized precision therapy. Expression subtypes of GBM samples from the Cancer Genome Atlas (TCGA) were identified using BayesNM and compared with existing molecular subtypes of GBM. Biological features of the subtypes were determined by single-sample gene set enrichment analysis. Genomic and proteomic data from GBM samples were combined and Genomic Identification of Significant Targets in Cancer analysis was used to screen genes with recurrent somatic copy-number alterations phenomenon. The immune environment among subtypes was compared by assessing the expression of immune molecules and the infiltration of immune cells. Molecular subtypes adapted to immunotherapy were identified based on Tumor Immune Dysfunction and Exclusion (TIDE) score. Finally, least absolute shrinkage and selection operator (LASSO) logistic regression was performed on the expression profiles of S2, S3 and S4 in TCGA-GBM and RPPA to determine the respective corresponding best predictive model. Four novel molecular subtypes were classified. Specifically, S1 exhibited a low proliferative profile; S2 exhibited the profile of high proliferation, IDH1 mutation, TP53 mutation and deletion; S3 was characterized by high immune scores, innate immunity and adaptive immune infiltration scores, with the lowest TIDE score and was most likely to benefit from immunotherapy; S4 was characterized by high proliferation, EGFR amplification, and high protein abundance, and was the most suitable subtype for bevacizumab. LASSO analysis constructed the best prediction model composed of 13 genes in S2 with an accuracy of 96.7%, and the prediction model consisting of 17 genes in S3 with an accuracy of 86.7%, and screened 14 genes as components of the best prediction model in S4 with an accuracy of 93%. To conclude, our study classified reproducible and robust molecular subtypes of GBM, and these findings might contribute to the identification of patients responding to immunotherapy, thereby improving GBM prognosis.

A method of gas chromatography-mass spectrometry (GC-MS) was established to determine the migration of dibutyl sebacate, dioctyl sebacate, diisooctyl sebacate, decanedioic acid bis(2,2,6,6-tetramethyl-4-piperidinyl)ester in water-based, acidic and alcoholic food simulants, and olive oil and chemical alternative solvents. The 95% ethanol and isooctane chemical substitution solutions were directly analyzed by GC-MS. The olive oil samples were extracted with acetonitrile followed by QuEChERS purification, and then analyzed by GC-MS. Other simulants (water, 4% acetic acid, 10% ethanol, 20% ethanol, and 50% ethanol) were extracted with n-hexane and then determined by GC-MS. The results showed that the method is well performed under optimized conditions, with the correlation coefficient (r2) greater than 0.995. The limits of detection and the limits of quantitation of the four sebacic acid ester compounds in water, 4% acetic acid, 10% ethanol, 20% ethanol, 50% ethanol, 95% ethanol, isooctane, and olive oil simulants are 0.1-0.2 mg/kg, 0.3-0.5 mg/kg, respectively. Migration experiments on plastic samples were conducted, and spiking experiments at three concentration levels of 0.30, 2.0, 4.0 mg/kg in water, 4% acetic acid, 10% ethanol, 20% ethanol, 50% ethanol, 95% ethanol, and isooctane food simulants, and three concentration levels of 0.50, 2.0, 4.0 mg/kg in olive oil food simulants were carried out. The spiking recoveries range from 92.5% to 108%, and the relative standard deviations (RSDs) are 2.4%-8.8%. The method solves the problem that decanedioic acid bis(2,2,6,6-tetramethyl-4-piperidinyl)ester cannot be extracted into n-hexane in 4% acetic acid by adjusting pH value using ammonium hydroxide, the optimal pH range was determined by comparing the responses of four targets at different pH values. QuEChERS was firstly used for migration experiments of sebacic acid esters in food contact materials to solve the turbidity and partial oil precipitation of olive oil simulants in the concentration process after extraction. By optimizing the QuEChERS filling material, the interference of organic acids, fatty acids, sugar and other impurities on the targets were reduced, producing greater separation effect of the targets. The separation efficiency of four chromatographic columns with different polarity was compared, and the DB-17HT column was selected to detect the four sebacic acid esters simultaneously. Plastics such as polypropylene, polyethylene terephthalic acid terephthalate, polyvinyl chloride, composite membranes, paper cups, recycled PET and recycled PVC were collected and migration experiments were carried out, the migration of sebacic acid esters in these plastics materials was investigated. This method is highly sensitive, precise, and accurate, fully meeting the requirement for determining the migration of the sebacic acid esters in food contact materials and their products.

Regular physicochemical and microbiological properties and volatile flavors of Sichuan Wu xiang-style sausages collected from Chengdu City were analyzed and used to reveal the quality characteristics of Sichuan Wu xiang-style sausage. The results showed that moisture content was 11.73%±1.64%, pH value was 5.68±0.06, TBARS value was 1.47±0.48 mg/kg, nitrite content was 1.31±0.12 mg/kg, and L*, a*, and b* was 48.12±1.46, 16.08±0.91, 18.31±0.73 respectively. The aerobic plate count, suspected staphylococci count, suspected lactic acid bacteria count, and Enterobacteriaceae count was 7.09±0.14, 5.74±0.23, 7.64±0.14 and 4.27±0.15 lg CFU/g, respectively. 97 kinds of volatile compounds were totally detected from Sichuan Wu xiang-style sausage samples, and 22 shared volatile compounds with odor activity value (OAV) greater than 1 were regarded as the main volatile flavors. Furthermore, it was showed that (+)-limonene, linalool and artemisia brain contributed most to the typical flavor of Wu xiang-style sausage through the loading plot of principal component analysis, imparting citrus, mint, floral, lavender, liquorice, and aniseed odors. The results obtained revealed the main volatile compounds and typical flavor characteristics of Sichuan Wu xiang-style sausage, and laid foundations for further researches on the flavor characteristics of Sichuan Wu xiang-style sausage.

Abstract Objective To investigate the physical fitness level and health behavior status of preschool children in China, explore the relationship between physical fitness and health behavior, and further reveal the main factors affecting health behavior, to provide a reference for improving the physical fitness level of preschool children and maintaining healthy behavior. Methods A total of 755 preschool children (394 boys and 361 girls, aged 4.52 ± 1.11 years) were selected from Chongqing and Liupanshui in China by cluster random sampling method for questionnaire survey and physical monitoring, and SPSS21.0 software was used to process and analyze the data. Results (1) Heart rate (p = 0.015), protein content (p

Background: The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. Objective: To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. Methods: The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10–20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. Results: A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. Conclusion: The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

In order to solve the enzymatic browning phenomenon in the pulping unit of Lonicera caerulea fruits and improve its utilization value. The main phenolic substrates involved in the enzymatic browning reaction in the pulping process of Lonicera caerulea fruits and the inhibition ability were investigated, and the interactions between phenolic substrates and epicatechin on the reaction of polyphenol oxidase (PPO) were analyzed and its mechanism of enzymatic browning was also determined. The three most effective inhibitors were further selected by comparing the effects of ascorbic acid, L-cysteine, calcium chloride, EDTA-2Na, and citric acid additions on the browning inhibition rate. The results showed that epicatechin was the primary influencing factor involved in enzymatic browning in the pulping process of Lonicera caerulea fruits, and the quenching mechanism of epicatechin on PPO was static quenching. The response surface optimization test determined the optimal combination of composite inhibitors as 0.11% ascorbic acid, 0.11% L-cysteine, and 0.08% EDTA-2Na, and the browning inhibition rate of Lonicera caerulea fruits juice under this condition was 93.17%. It indicates that the above composite inhibitors can inhibit the enzymatic browning in the pulping process of Lonicera caerulea fruits.

Liver regeneration is a complex process that involves the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs). Pregnane X receptor (PXR), also known as NR1I2, is an important regulator for liver enlargement and regeneration. However, the role of PXR activation in hematopoiesis during liver regeneration remains unclear. This study investigates the effects of PXR activation on HSPCs and hematopoiesis during liver regeneration, as well as the underlying mechanisms involved. Using a 70 % partial hepatectomy (PHx) on C57BL/6 wild-type (WT) and Pxr-null mice, we observed a significant correlation between the changes in HSPCs numbers in BM and the process of liver regeneration. PXR activation significantly increased the population of Lineage- Sca-1+ c-Kit+ (LSK) cells in the BM, which are key HSPCs involved in hematopoiesis. Additionally, PXR activation increased serum levels of thrombopoietin (TPO) and erythropoietin (EPO), factors known to support HSPCs proliferation and hematopoiesis in the process of liver regeneration. PXR activation does not affect the hematopoietic function of normal mice. Furthermore, mice subjected to irradiation or busulfan-induced hematopoietic dysfunction exhibited impaired liver regeneration, which was alleviated by PXR activation. Importantly, in Pxr-null mice, the promotive effects of PXR activation on liver regeneration and increase of HSPCs were markedly diminished. Moreover, liver-specific Pxr silencing using AAV-Pxr shRNA attenuated the PXR activation-mediated liver regeneration and increase in BM LSK cells, confirming the critical role of hepatic PXR in hematopoiesis during liver regeneration. Collectively, these findings reveal that PXR activation promotes HSPCs proliferation and hematopoiesis during liver regeneration, providing new insights into the molecular mechanisms underlying the role of PXR in liver regeneration and hematopoiesis.

The E6 and E7 oncoproteins of human papillomavirus (HPV) are considered promising targets for HPV-related cancers. In this study, we evaluated novel T cell receptor mimic (TCRm) nanobodies targeting the E629-38 peptide complexed with human leukocyte antigen (HLA)-A∗02:01 in the chimeric antigen receptor (CAR) format. We isolated two dromedary camel nanobodies, F5 and G9, through phage display screening. F5 bound more efficiently to the complex expressed on cells, including peptide-pulsed T2, overexpressed 293E6, and cervical cancer lines CaSki and SS4050, compared to G9. CAR-T cells based on the F5 nanobody specifically killed target cells, including 293E6, CaSki, and SS4050 in vitro, through activation of nuclear factor of activated T cells (NFAT) and nuclear factor κB (NF-κB) signaling. Importantly, F5 CAR-T cells inhibited the growth of CaSki and SS4050 tumor xenografts in mice. These findings demonstrate that HPV-16+ cervical cancer can be targeted by F5 nanobody-based CAR-T cells, offering a valuable alternative strategy for treating HPV-16+ malignancies.

Background and purpose Several clinical studies have demonstrated the potential of molecular-targeted agents for the treatment of recurrent or metastatic adenoid cystic carcinoma (R/M ACC). However, there is currently no consensus regarding the efficacy of molecular-targeted agents for patients with R/M ACC. This study aimed to evaluate the therapeutic efficacy and safety of molecular-targeted agents in patients with R/M ACC and provide insights to guide clinical decision-making.Materials and methods Five databases (PubMed, Embase, Cochrane, ProQuest, and Scopus) were searched based on the search strategy and selection criteria. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS), metastatic sites, and adverse events (AE). Pooled estimates were calculated using a random-effects meta-analysis.Results Finally, 28 studies, involving 849 patients, were included. The most common metastatic sites were the lungs, bones, liver, lymph nodes, and kidneys. The pooled ORR was 4.0% (95% CI, 0.7–8.8%), the pooled DCR was 80.5% (95% CI, 72.2%–87.7%). Compared with other-target drugs, multiple kinase inhibitors (MKIs) improved the ORR (pooled ORR for single-target drugs vs. MKIs: 5.9% vs. 0%). The combination of MKIs and immune checkpoint inhibitors (ICIs) had a significantly higher ORR (17.9% in the axitinib + avelumab group). The pooled median PFS and OS were 8.35 and 25.62 months, respectively. MKIs improved the median PFS compared to other-target drugs (9.43 months vs 5.06 months). In addition, the most common adverse events (AEs) were fatigue (51.6%), hypertension (44.2%), and nausea (40.0%), followed by hand-foot skin syndrome (36.8%), diarrhoea (34.4%), weight loss (34.2%), anorexia (31.8%), rash (31.7%), and headache (29.0%).Conclusion The findings of this study suggest that MKIs have a better therapeutic efficacy than single-target drugs in patients with R/M ACC. Future studies are warranted to verify the synergistic role of the combination strategy of MKIs plus ICIs, given the limited number of studies on this topic conducted and published to date.

Background To estimate the predictors, prevalence and prognostic role of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) using meta-analysis.Methods The PubMed, EmBase, and the Cochrane library were systematically searched for eligible studies from inception till May 2024. All of pooled analyses were performed using the random-effects model.Results Fifty observational studies involving 17,558 CKD patients were selected. The prevalence of PH in CKD patients was 38% (95% confidence interval [CI]: 33%–43%), and the prevalence according to CKD status were 31% (95% CI: 20%–42%) for CKD (I-V), 39% (95% CI: 25%–54%) for end stage kidney disease (ESKD) (predialysis), 42% (95% CI: 35%–50%) for ESKD (hemodialysis), and 26% (95% CI: 19%–34%) for renal transplant. We noted the risk factors for PH in CKD included Black individuals (relative risk [RR]: 1.39; 95% CI: 1.18–1.63; p

ABSTRACTEmerging evidence has revealed the novel role of gut microbiota in the development of cancer. The characteristics of function and composition in the gut microbiota of patients with breast cancer patients has been reported, however the detailed causation between gut microbiota and breast cancer remains uncertain. In the present study, 16S rRNA sequencing revealed that Prevotella, particularly the dominant species Prevotella copri, is significantly enriched and prevalent in gut microbiota of breast cancer patients. Prior-oral administration of P. copri could promote breast cancer growth in specific pathogen-free mice and germ-free mice, accompanied with sharp reduction of indole-3-pyruvic acid (IPyA). Mechanistically, the present of excessive P. copri consumed a large amount of tryptophan (Trp), thus hampering the physiological accumulation of IPyA in the host. Our results revealed that IPyA is an intrinsic anti-cancer reagent in the host at physiological level. Briefly, IPyA directly suppressed the transcription of UHRF1, following by the declined UHRF1 and PP2A C in nucleus, thus inhibiting the phosphorylation of AMPK, which is just opposite to the cancer promoting effect of P. copri. Therefore, the exhaustion of IPyA by excessive P. copri strengthens the UHRF1-mediated negative control to inactivated the energy-controlling AMPK signaling pathway to promote tumor growth, which was indicated by the alternation in pattern of protein expression and DNA methylation. Our findings, for the first time, highlighted P. copri as a risk factor for the progression of breast cancer.

ABSTRACTAdherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn’s disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.

ABSTRACTThe insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis. We discovered a set of genera in early-life associated with CTS and defined a 16-genus signature that accurately predicted CTS, the majority of which were correlated with human CRCs. We identified 547 SNPs associated with abundances of these genera. Mediation analysis revealed GM as mediators partially exerting the effect of SNP UNC3869242 within Duox2 on CTS. Intestine cell-specific depletion of Duox2 altered GM composition and contribution of Duox2 depletion to CTS was significantly influenced by GM. Our findings provide potential novel targets for personalized CRC prevention and treatment.

AbstractSurveys were conducted on sociodemographic characteristics, family, home- and school-related factors, and sugar-sweetened beverage (SSB) intake to identify factors associated with SSB consumption in children. In total, 2700 valid questionnaires were returned. Mean age was 10.4 ± 2.23 years and 49.3% were male. Multivariate logistic analysis showed that the frequency of SSB dinking by fathers and peers, the frequency of SSB purchasing at home and school, and the duration of daily TV and video watching were significantly independent factors affecting SSB intake, suggesting that interventions targeting children’s SSB intake should incorporate government policies, educational programs and parental engagement.