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Abstract Background Kinesiophobia, an irrational fear-avoidance behaviour, can significantly impact the quality of life and prognosis of peritoneal dialysis patients. This study aimed to assess the prevalence of kinesiophobia in patients undergoing peritoneal dialysis and to analyse its influencing factors. Methods A total of 291 patients who visited the outpatient and ward of peritoneal dialysis in 7 tertiary hospitals in Jiangsu Province from December 2023 to March 2024 were selected as research subjects via the convenience sampling method. A cross-sectional survey was conducted using a general data questionnaire, the Tampa Kinesiophobia-11 Scale, the Chinese Version of the Multidimensional Fatigue Symptom Scale, and the Simplified Coping Style Questionnaire. Results The score obtained using the Tampa Scale for kinesiophobia in patients with peritoneal dialysis was 22.44 ± 7.46, with a prevalence rate of 69.1%. Binary logistic regression analysis revealed that no complications, daily exercise before illness, and positive coping styles were protective factors (p

Abstract To explore diagnostic and prognostic biomarkers in the progression of oral squamous cell carcinoma (OSCC) and to reveal their regulatory mechanisms in key pathways. A RayBiotech protein chip was used to screen differentially expressed serum proteins in OSCC, oral leukoplakia (OLK), and healthy participants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to determine the pathways enriched by characteristic differential proteins. Immunohistochemical analysis and western blotting were used to verify the expression of characteristic differential proteins and key regulatory factors in human tissues and in a nude mouse model. Fibroblast growth factor 6 (FGF6) was identified as a key differential protein and was weakly expressed in OSCC tissues. The mitogen-activated protein kinases (MAPK) and PI3K-AKT pathways were identified as key signaling pathways. The results showed that pERK, Cyclin D1, pAKT, and BCL2 were highly expressed in OSCC, Caspase9 was lowly expressed in OSCC. With an increase in FGF6 expression in nude mice, the expression of FGFR4, pERK, Cyclin D1, pAKT, BCL2, GPX4, and ACSL4 increased, and the expression of Caspase9 decreased. FGF6 may change the expression of apoptosis-related proteins and proliferation factors by binding to FGFR4 in the PI3K-AKT/MAPK pathway and may inhibit the ferroptosis of OSCC, thereby possibly participating in the process of inhibiting OSCC.

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

We prepared biocompatible and environment-friendly zinc oxide nanoparticles (ZnO NPs) with upconversion properties and catalase-like nanozyme activity. Photodynamic therapy (PDT) application is severely limited by the poor penetration of UV–Visible light and a hypoxic tumor environment. Here, we used ZnO NPs as a carrier for the photosensitizer chlorin e6 (Ce6) to construct zinc oxide–chlorin e6 nanoparticles (ZnO-Ce6 NPs), simultaneously addressing both problems. In terms of penetration, ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6, achieving deep-penetrating photodynamic therapy under long-wavelength light. Interestingly, the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles. As nanozymes, ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors, providing oxygen for photodynamic action and relieving hypoxia. The enhanced photodynamic action produces a large amount of reactive oxygen species, which overactivate autophagy and trigger immunogenic cell death (ICD), leading to antitumor immunotherapy. In addition, even in the absence of light, ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects.

Abstract Alternative splicing is an important process that contributes to highly diverse transcripts and protein products, which can affect the development of disease in various organisms. Cardiovascular disease (CVD) represents one of the greatest global threats to humans, particularly acute myocardial infarction (MI) and subsequent ischemic reperfusion (IR) injury, which involve complex transcriptomic changes in heart tissues associated with metabolic reshaping and immunological response. In this study, we used a newly developed ONT full-length transcriptomic approach and performed transcript-resolved differential expression profiling in murine models of MI and IR. We built an analytical pipeline to reliably identify and quantify alternative splicing products (isoforms), expanding on the currently available catalog of isoforms described in mice. The updated alternative splicing landscape included transcripts, genes, and pathways that were differentially regulated during IR and MI. Our study establishes a pipeline to profile highly diverse isoforms using state-of-the-art long-read sequencing, builds a landscape of alternative splicing in the mouse heart during MI and IR.

Abstract Background Prompt identification of fracture healing is crucial for medical decision-making and clinical research. This study aims to assess the effectiveness of the Radiographic Union Score for Hip (RUSH) in subtrochanteric fractures and determine the optimal scoring threshold for fracture healing. Methods We obtained 94 sets of X-ray films from the postoperative follow-up of 35 patients who underwent intramedullary nail fixation for subtrochanteric fractures. Six orthopedic trauma surgeons evaluated the imaging data and determined fracture healing based on subjective judgment. They then scored the X-ray images using the RUSH form. After four weeks, the same observers re-evaluated 47 randomly selected sets of radiographs. Subsequently, the observers and study designer conducted a consensus meeting where they agreed on whether the fractures had healed. We used Fleiss kappa to evaluate agreement among observers based on subjective impressions, and the intraclass correlation coefficient assessed RUSH score consistency. Regression analysis examined the relationship between scores and fracture healing consensus using a receiver operator characteristic (ROC) curve. Results Based on overall impressions, the agreement level among orthopedic trauma surgeons for determining the healing status of subtrochanteric fractures was moderate (Kappa = 0.564, 95% CI: 0.511–0.616). However, utilizing the RUSH scoring system can improve the consistency to a substantial level of agreement (ICC = 0.748, 95% CI: 0.663–0.817). Regarding intraobserver reliability, there were significant differences among orthopedic trauma surgeons in judging fracture healing based on overall impressions. However, using the RUSH scoring form, the attending group achieved better intraobserver consistency than the resident group. Regression analysis and ROC curve analysis revealed a strong correlation between the RUSH total score, cortical bone score, cancellous bone score, and consensus on fracture healing. The AUC values are 0.769 (95% CI: 0.670–0.868), 0.779 (95% CI: 0.681–0.876), and 0.771 (95% CI: 0.674–0.867), respectively. Conclusions Our study highlights the effectiveness of the RUSH scoring system in enhancing interobserver agreement and intraobserver consistency when evaluating subtrochanteric fracture healing in orthopedic trauma surgeons. We propose setting 21 points as the threshold for the simplified RUSH scoring system to determine fracture healing. This system includes only eight items related to cortical bone, with a total score of 24 points.

Abstract Background SHR-1707 is a novel humanized anti-Aβ IgG1 monoclonal antibody that binds to Aβ fibrils and monomers to block the formation of Aβ plaques or to promote the microglial phagocytosis of Aβ. Preclinical studies showed that SHR-1707 reduced brain Aβ deposition in 5xFAD transgenic mice. Herein, we conducted two phase 1 studies to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous dose of SHR-1707 in healthy adult subjects. Methods Two randomized, double-blind, single-ascending-dose, phase 1 studies were conducted in China (Study CHN) and Australia (Study AUS). Study CHN consisted of 2 parts. In Part 1, eligible healthy young adults (18–45 years) were sequentially randomized 8:2 to receive SHR-1707 (five cohorts: 2, 6, 20, 40, and 60 mg/kg) or placebo in each cohort; in Part 2, elderly subjects (55–80 years) were randomized 8:4 to receive SHR-1707 (20 mg/kg) or placebo. A similar design was used in Study AUS, but with only healthy young adults enrolled across three dosing cohorts (2, 20, and 60 mg/kg). Results Sixty-two (part 1/2, n = 50/12; age range, 18–42/55–63 years) and 30 subjects (age range, 18–42 years) received SHR-1707 or placebo in Study CHN and Study AUS, respectively. In Study CHN, all treatment-related adverse events (TRAEs) were mild, with the most common being transient laboratory abnormalities. In Study AUS, TRAEs were mostly mild (1 moderate event each with SHR-1707/placebo); the most common TRAEs with SHR-1707 were dysgeusia and fatigue (8.3% each). In both studies, the exposure of SHR-1707 increased in a slightly greater than dose-proportional manner over the dose range of 2–60 mg/kg in young adults; there was a dose-dependent increase in plasma Aβ42 concentration following SHR-1707 administration compared with the placebo group. The safety and PK and PD profiles of SHR-1707 in the elderly subjects were consistent with the younger counterpart at the same dose level. No ethnic difference in safety, PK and PD of SHR-1707 was observed. Conclusions A single intravenous dose of SHR-1707 at 2–60 mg/kg was safe and well tolerated in healthy young adult and elderly subjects. The PK and PD profiles are supportive for further clinical development. Trial registration NCT04973189 (retrospectively registered on Jul.21, 2021) and NCT04745104 (registered on Feb.6, 2021) on clinicaltrials.gov.

Abstract Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors.

The effectiveness of AI-driven drug discovery can be enhanced by pretraining on small molecules. However, the conventional masked language model pretraining techniques are not suitable for molecule pretraining due to the limited vocabulary size and the non-sequential structure of molecules. To overcome these challenges, we propose FragAdd, a strategy that involves adding a chemically implausible molecular fragment to the input molecule. This approach allows for the incorporation of rich local information and the generation of a high-quality graph representation, which is advantageous for tasks like virtual screening. Consequently, we have developed a virtual screening protocol that focuses on identifying estrogen receptor alpha binders on a nucleus receptor. Our results demonstrate a significant improvement in the binding capacity of the retrieved molecules. Additionally, we demonstrate that the FragAdd strategy can be combined with other self-supervised methods to further expedite the drug discovery process.

Abstract To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P

Abstract Reuse and recycling of retired electric vehicle (EV) batteries offer a sustainable waste management approach but face decision-making challenges. Based on the process-based life cycle assessment method, we present a strategy to optimize pathways of retired battery treatments economically and environmentally. The strategy is applied to various reuse scenarios with capacity configurations, including energy storage systems, communication base stations, and low-speed vehicles. Hydrometallurgical, pyrometallurgical, and direct recycling considering battery residual values are evaluated at the end-of-life stage. For the optimized pathway, lithium iron phosphate (LFP) batteries improve profits by 58% and reduce emissions by 18% compared to hydrometallurgical recycling without reuse. Lithium nickel manganese cobalt oxide (NMC) batteries boost profit by 19% and reduce emissions by 18%. Despite NMC batteries exhibiting higher immediate recycling returns, LFP batteries provide superior long-term benefits through reuse before recycling. Our strategy features an accessible evaluation framework for pinpointing optimal pathways of retired EV batteries.

AIM: To assess the clinical presentations and outcomes of idiopathic orbital inflammatory pseudotumor (IOIP) patients with orbital wall bone destruction (OWBD) and to propose an expanded classification system that includes bone destruction. METHODS: The study retrospectively reviewed clinical presentations, imaging findings, treatment modalities, and outcomes of six patients diagnosed histopathologically with IOIP and OWBD at the Beijing Tongren Hospital, Capital Medical University between October 2018 and June 2021. RESULTS: Over two years, 6 (10%) of 60 IOIP patients at our hospital exhibited OWBD, but this may overrepresent severe cases. The cohort consisted of three men and three women, aged 17 to 60y (mean 35.5±16.1y). Presenting symptoms included proptosis, eyelid swelling, decreased visual acuity with pain, and palpable mass. Imaging revealed multiple anatomical structures involved with the medial wall being the most common site of bone destruction. Histopathological examination showed classic type in five patients and sclerosing type in one patient. All patients underwent surgical resection followed by methylprednisolone treatment. Follow-up (mean 30.3±3.1mo) indicated three patients had no recurrence, while others had varying degrees of symptom persistence or recurrence. CONCLUSION: IOIP with bone destruction is a rare but significant subtype that mimics malignancy, leading to potential diagnostic and therapeutic challenges. Our findings suggest that complete surgical resection combined with adjunctive glucocorticoid therapy can yield favorable outcomes. However, larger-scale studies are needed to further optimize therapeutic approaches.

Identifying novel compound–protein interactions (CPIs) plays a pivotal role in target identification and drug discovery. Although the recent multimodal methods have achieved outstanding advances in CPI prediction, they fail to effectively learn both intra-modality and inter-modality dynamics, which limits their prediction performance. To address the limitation, we propose a novel multimodal tensor fusion CPI prediction framework, named MMTF-CPI, which contains three unimodal learning modules for structure, heterogeneous network and transcriptional profiling modalities, a tensor fusion module and a prediction module. MMTF-CPI is capable of focusing on both intra-modality and inter-modality dynamics with the tensor fusion module. We demonstrated that MMTF-CPI is superior to multiple state-of-the-art multimodal methods across seven datasets. The prediction performance of MMTF-CPI is significantly improved with the tensor fusion module compared to other fusion methods. Moreover, our case studies confirmed the practical value of MMTF-CPI in target identification. Via MMTF-CPI, we also discovered several candidate compounds for the therapy of breast cancer and non-small cell lung cancer.

Abstract The kidney is vulnerable to ischemia and reperfusion (I/R) injury that can be fatal after major surgery. Currently, there are no effective treatments for I/R-induced kidney injury. Trimethylamine N-oxide (TMAO) is a gut-derived metabolite linked to many diseases, but its role in I/R-induced kidney injury remains unclear. Here, our clinical data reveals an association between preoperative systemic TMAO levels and postoperative kidney injury in patients after post-cardiopulmonary bypass surgery. By genetic deletion of TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) and dietary supplementation of choline to modulate TMAO levels, we found that TMAO aggravated acute kidney injury through the triggering of endoplasmic reticulum (ER) stress and worsened subsequent renal fibrosis through TGFβ/Smad signaling activation. Together, our study underscores the negative role of TMAO in I/R-induced kidney injury and highlights the therapeutic potential through the modulation of TMAO levels by targeting FMO3, thereby mitigating acute kidney injury and preventing subsequent renal fibrosis.

Abstract Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.

Abstract Objectives To retrospectively investigate clinical characterization and the long-term postoperative outcomes of retinoblastoma (RB) patients receiving enucleation with primary orbital implantation in early infancy (0–6 months old). Methods The clinical and follow-up data of 42 RB patients receiving enucleation with primary orbital implantation in early infancy at Beijing Tongren Hospital from December 2009 to January 2020 were analysed. The average follow-up time was 83 months. The patient group included 24 males and 18 females, 30 unilateral and 12 bilateral cases. A total of 44 eyes with 10 in stage D and 34 in stage E underwent 40 unilateral and 2 bilateral surgeries. 17 RB eyes received hydrogel and 27 RB eyes received hydroxyapatite implants. This study was performed by following the guideline of STROBE. Results Enucleation combined with primary orbital implantation promoted survival and was safe with few and minor complications such as increased secretion, upper eyelid ptosis, and sunken eye sockets which were not affected by stages, lateralities, or implant materials. 55-80% RB patients exhibited satisfactory appearance and obvious or moderate motility of orbital implants according to the evaluation by doctors and family members. Family members were likely more optimistic about the appearance and more pessimistic about motility of the orbital implantation than doctors did.The quality of life was high as indicated by PedsQL3.0 or PedsQL4.0 scores ( ≧ 90 for > 75% patients). It was not affected by the stages, laterality, and implant materials, nor affected by the appearance and motility of the implants. Conclusions The outcomes of the combination of enucleation and primary orbital implantation for pertinent RB patients in early infancy are generally satisfactory with few and minor complications, high safety, appearance, and overall quality of life. Enucleation combined with primary orbital implantation in early infancy benefits pertinent RB patients in appearance, survival, and quality of life.

Abstract LLC series resonant converter (LLC‐SRC) has attracted much attention due to its simple circuit structure and easy realization of soft‐switching. To get a better efficiency, rectifier stage can be realized by the active switches instead of the diodes. Meanwhile, more control variables can be selected besides the switching frequency, such as single phase shifted (SPS) angle, dual phase shifted (DPS) angle, and extended phase shifted (EPS) angle. Considering the simplicity of the implementation of the control strategy, this paper focused on the converter model with frequency and SPS control. Different from the common modelling method with the Fundamental Harmonic Approximation (FHA), the precise time‐domain mathematic model is built. By a comparison between the two modelling results, it can be proved the FHA model may be failure in some operating condition while the proposed time‐domain model can still show a good accuracy. According to the proposed model, two simple fixed‐frequency SPS control strategies are proposed. The first one can realize infinite soft‐switching margin with no restrictions on the transformer magnetizing inductance. The second one can greatly improve the efficiency of the converter. All the theoretical results are verified by a 1‐kW experiment prototype.

Abstract Background Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels. Methods Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration. Results The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p

Objective: To develop and evaluate a Chinese version of the Symptom Questionnaire for Visual Dysfunctions (CSQVD) to quantify visual dysfunction symptoms in school-age children with various eye diseases, and to explore the relationship between ophthalmological disorders and visual dysfunction symptoms. Methods: Following standard scale adaptation procedures, the Symptom Questionnaire for Visual Dysfunctions (SQVD) was translated into Chinese (CSQVD). We employed random sampling to survey 198 outpatients aged 7–18 to assess the psychometric properties of the CSQVD. Using the reliable and validated questionnaire, we evaluated the determinants of visual dysfunction symptoms among 406 school-age patients at an eye center. The CSQVD scores were correlated with demographic and clinical variables, including gender, age, eye position, refractive power, and best-corrected visual acuity. Univariate analysis identified potential risk factors, followed by binary logistic regression and multiple linear regression analysis on factors with a P-value

Abstract Background Insulin resistance (IR) and arthritis are strongly associated, and the triglyceride–glucose (TyG) index combinations with obesity indicators [including TyG–BMI (glucose triglyceride–body mass index), TyG–WC (glucose triglyceride–waist circumference), and TyG–WHtR (glucose triglyceride–waist height ratio)] has recently been recognized as a more effective indicator for assessing IR. However, there is a lack of research on its association with arthritis, and it is also important to assess in different populations. Methods The analysis utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and the National Health and Nutrition Examination Survey (NHANES). Arthritis diagnosis relied on self-reporting confirmed by physicians. The association of TyG–BMI, TyG–WC, and TyG–WHtR with arthritis was analyzed through weighted logistic regression models, and exploring nonlinear effects with restricted cubic spline (RCS) models. Secondary and sensitivity analyses included receiver operating characteristic curve (ROC) analysis, comparisons of z score-related odds ratios, subgroup analyses, and multiple imputation. Results The study involved 6141 CHARLS participants and 17,091 NHANES participants. Adjusting for confounding variables, TyG–BMI and TyG–WHtR demonstrate a positive correlation with arthritis prevalence in both CHARLS (TyG–BMI: OR = 1.02, 95% CI 1.00–1.04; TyG–WHtR: OR = 1.13, 95% CI 1.03–1.24) and NHANES (TyG–BMI: OR = 1.07, 95% CI 1.06–1.08; TyG–WHtR: OR = 1.50, 95% CI 1.40–1.60). RCS regression analysis demonstrated a significant nonlinear association. ROC analysis indicated that TyG–BMI and TyG–WHtR were superior to TyG for the diagnosis of arthritis in both CHARLS and NHANES. Conclusions TyG–BMI and TyG–WHtR demonstrate a positive correlation with arthritis prevalence in both Chinese and the U.S. populations, displaying superior diagnostic relevance compared to TyG.

Abstract Mutations in the Cockayne Syndrome group B (CSB) gene cause cancer in mice, but premature aging and severe neurodevelopmental defects in humans. CSB, a member of the SWI/SNF family of chromatin remodelers, plays diverse roles in regulating gene expression and transcription-coupled nucleotide excision repair (TC-NER); however, these functions do not explain the distinct phenotypic differences observed between CSB-deficient mice and humans. During investigating Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism that involves elongating RNA polymerase II (RNAPII) undergoing transient pauses at internal T-runs where CSB is required to propel RNAPII forward. Consequently, CSB deficiency retards RNAPII elongation in these regions, and when coupled with G-rich sequences upstream, exacerbates genome instability by promoting R-loop formation. These R-loop prone motifs are notably abundant in relatively long genes related to neuronal functions in the human genome, but less prevalent in the mouse genome. These findings provide mechanistic insights into differential impacts of CSB deficiency on mice versus humans and suggest that the manifestation of the Cockayne Syndrome phenotype in humans results from the progressive evolution of mammalian genomes.

Abstract Myeloid cells are vital components of the immune system and have pivotal functions in orchestrating immune responses. Understanding their functions within the tumor microenvironment and their interactions with tumor-infiltrating lymphocytes presents formidable challenges across diverse cancer types, particularly with regards to cancer immunotherapies. Here, we explore tumor-infiltrating myeloid cells (TIMs) by conducting a pan-cancer analysis using single-cell transcriptomics across eight distinct cancer types, encompassing a total of 192 tumor samples from 129 patients. By examining gene expression patterns and transcriptional activities of TIMs in different cancer types, we discern notable alterations in abundance of TIMs and kinetic behaviors prior to and following immunotherapy. We also identify specific cell-cell interaction targets in immunotherapy; unique and shared regulatory profiles critical for treatment response; and TIMs associated with survival outcomes. Overall, our study illuminates the heterogeneity of TIMs and improves our understanding of tissue-specific and cancer-specific myeloid subsets within the context of tumor immunotherapies.

Abstract To explore complex biological questions, it is often necessary to access various data types from public data repositories. As the volume and complexity of biological sequence data grow, public repositories face significant challenges in ensuring that the data is easily discoverable and usable by the biological research community. To address these challenges, the National Center for Biotechnology Information (NCBI) has created NCBI Datasets. This resource provides straightforward, comprehensive, and scalable access to biological sequences, annotations, and metadata for a wide range of taxa. Following the FAIR (Findable, Accessible, Interoperable, and Reusable) data management principles, NCBI Datasets offers user-friendly web interfaces, command-line tools, and documented APIs, empowering researchers to access NCBI data seamlessly. The data is delivered as packages of sequences and metadata, thus facilitating improved data retrieval, sharing, and usability in research. Moreover, this data delivery method fosters effective data attribution and promotes its further reuse. This paper outlines the current scope of data accessible through NCBI Datasets and explains various options for exploring and downloading the data.

Abstract Background The mortality of pneumonia in older adults surpasses that of other populations, especially with the prevalence of coronavirus disease 2019 (COVID-19). Under the influence of multiple factors, a series of geriatric syndromes brought on by age is one of the main reasons for the poor prognosis of pneumonia. This study attempts to analyze the impact of geriatric syndrome on the prognosis of pneumonia. Methods This is a prospective cross-sectional study. Patients over 65 years old with COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) were included in the research. General characteristics, laboratory tests, length of stay (LOS), and comprehensive geriatric assessment (CGA) were collected. Multivariate regression analysis to determine the independent predictors of the severity, mortality, and LOS of COVID-19. At the same time, the enrolled subjects were divided into three categories by clustering analysis of 10 CGA indicators, and their clinical characteristics and prognoses were analyzed. Results A total of 792 subjects were included in the study, including 204 subjects of SN-CAP (25.8%) and 588 subjects (74.2%) of COVID-19. There was no significant difference between non-severe COVID-19 and SN-CAP regarding mortality, LOS, and CGA (P > 0.05), while severe COVID-19 is significantly higher than both (P

Abstract Ferroptosis is an iron-dependent cell death that was discovered recently. For beneficial microbes to establish mutualistic relationships with hosts, precisely controlled cell death in plant cells is necessary. However, whether ferroptosis is involved in the endophyte‒plant system is poorly understood. Here, we reported that endophytic Streptomyces hygroscopicus OsiSh-2, which established a sophisticated and beneficial interaction with host rice plants, caused ferroptotic cell death in rice characterized by ferroptosis- and immune-related markers. Treatments with ferroptosis inhibitors and inducers, different doses of OsiSh-2, and the siderophore synthesis-deficient mutant ΔcchH revealed that only moderate ferroptosis induced by endophytes is essential for the establishment of an optimal symbiont to enhance plant growth. Additionally, ferroptosis involved in a defence-primed state in rice, which contributed to improved resistance against rice blast disease. Overall, our study provides new insights into the mechanisms of endophyte‒plant interactions mediated by ferroptosis and suggests new directions for crop yield promotion.

BackgroundMalignant ureteral obstruction (MUO) has the potential to result in a range of outcomes, including varying degrees of hydronephrosis and renal impairment. Allium covered metal stents have provided a new, highly effective treatment option for MUO. Our objective was to evaluate the safety and efficacy of the Allium covered metallic stent for the treatment of malignant ureteral obstruction.MethodsClinical data of 29 patients who underwent endoscopic insertion of an Allium ureteral stent between October 2019 and August 2021 at Yongchuan Hospital, affiliated with Chongqing Medical University, were analyzed retrospectively. At one, three, six and 12 months after insertion, serum creatinine was measured, the width of the renal pelvis was rechecked under ultrasound guidance, and the position and shape of the stent were checked by abdominal x-ray. Data on long-term stent patency, incidence of complications, changes in renal function and hydronephrosis grade were collected and analyzed. Ureteral stent symptom questionnaire (USSQ) was administered preoperatively and after six months in 22 patients with previous stent history.ResultsAllium covered metal stents (n = 33) were implanted successfully in 29 patients who were followed for three to 22 months, with 32/33 stents remaining patent. Serum creatinine levels decreased in 17 patients (p

IntroductionThe integration of artificial intelligence (AI) in pathogenic microbiology has accelerated research and innovation. This study aims to explore the evolution and trends of AI applications in this domain, providing insights into how AI is transforming research and practice in pathogenic microbiology.MethodsWe employed bibliometric analysis and topic modeling to examine 27,420 publications from the Web of Science Core Collection, covering the period from 2010 to 2024. These methods enabled us to identify key trends, research areas, and the geographical distribution of research efforts.ResultsSince 2016, there has been an exponential increase in AI-related publications, with significant contributions from China and the USA. Our analysis identified eight major AI application areas: pathogen detection, antibiotic resistance prediction, transmission modeling, genomic analysis, therapeutic optimization, ecological profiling, vaccine development, and data management systems. Notably, we found significant lexical overlaps between these areas, especially between drug resistance and vaccine development, suggesting an interconnected research landscape.DiscussionAI is increasingly moving from laboratory research to clinical applications, enhancing hospital operations and public health strategies. It plays a vital role in optimizing pathogen detection, improving diagnostic speed, treatment efficacy, and disease control, particularly through advancements in rapid antibiotic susceptibility testing and COVID-19 vaccine development. This study highlights the current status, progress, and challenges of AI in pathogenic microbiology, guiding future research directions, resource allocation, and policy-making.

Ovarian cancer is one of the most common gynecological malignancies. The current first-line treatment strategies for advanced ovarian cancer include surgery, chemotherapy, and maintenance therapy. Bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) are primary maintenance treatments for advanced ovarian cancer. Previously, many patients declined these therapies before medicare coverage because of high costs. Bevacizumab and apatinib are anti-tumor angiogenic agents. In this case study, we describe a patient with advanced ovarian cancer who underwent neoadjuvant chemotherapy, interval debulking surgery, and adjuvant chemotherapy. She declined bevacizumab and PARPi maintenance therapy owing to the prohibitive expenses. The patient was administered off-label apatinib and achieved a progression-free survival of 54 months. Thus, apatinib may offer substantial therapeutic value as a first-line maintenance therapy in advanced ovarian cancer.

IntroductionThis study explores the intricate relationships among psychological capital, emotional intelligence, psychological safety, and knowledge sharing among e-commerce practitioners. Grounded in social exchange theory, the research aims to fill a gap in the literature by focusing on the psychological and emotional factors influencing knowledge sharing in a fast-paced and highly competitive industry.MethodsThis study used snowball and purposive sampling to collect 439 valid online questionnaires from e-commerce professionals in Guangdong, Zhejiang, and Jiangsu, China. The survey, conducted from October to November 2023, explored the relationships between psychological capital, emotional intelligence, psychological safety, and knowledge sharing. Data were analyzed using structural equation modeling (SEM) with AMOS 26.0.ResultsThe structural path model revealed significant positive correlations between psychological capital and both emotional intelligence (β = 0.494, p

Abstract Study objective The aim of our study was to elucidate differences in brain activity patterns among obstructive sleep apnea (OSA) patients, OSA patients with depressive symptoms, and healthy controls (HCs). We also investigated the relationship between brain function and depression in OSA patients. Methods A total of 95 subjects were included in the study, including 34 OSA patients without depressive symptoms, 31 OSA patients with depressive symptoms, and 30 HCs. The 53‐channel functional near‐infrared spectroscopy (fNIRS) was used to monitor the concentration of oxy‐hemoglobin (Oxy‐Hb) in the brain, whereas the participants performed the verbal fluency task, and the degree of depression was scored using the 17‐item Hamilton Rating Scale for Depression (HAMD‐17). Hierarchical regression models were conducted to analyze the association of fNIRS features with depressive symptom. Results The Oxy‐Hb changes of the three groups were significantly different in Channels 25 (H = 9.878, p = .007) and 43 (H = 6.957, p = .031). Inter‐group comparisons showed that the Oxy‐Hb change of Channel 25 (located in the dorsolateral prefrontal cortex [DLPFC]) in OSA group was less than that in HC group (p = .006), and the Oxy‐Hb change of Channel 43 (located in the right frontal polar region) in OSA group with depression was less than that in OSA group (p = .025). Spearman's test showed that there was a significant negative correlation between HAMD‐17 scores and mean Oxy‐Hb changes in Channel 43 (r = −.319, p

Recurrent miscarriage (RM) is currently difficult to prevent and treat due to a lack of comprehensive understanding of its molecular mechanisms. The aim of this study was to identify genes potentially involved in the pathogenesis of RM and to observe their expression in the decidual tissues of RM patients. A total of 1823 differentially expressed genes (DEGs) and 148 differentially expressed proteins (DEPs) in decidual tissues between RM and control groups were identified. Subsequently, DCN, DPT, LUM, MFAP4, and ISG15 were identified from the DEGs/DEPs as RM-related hub genes through systematic bioinformatics analysis. Bioinformatics analysis of the single-cell dataset GSE214607 revealed that the expression of these five hub genes in the decidual stromal cells of RM patients appeared to be upregulated, while the RT-qPCR assay showed that their decidual expression levels were significantly increased in RM patients. Uterine Isg15expression was significantly increased, whereas the uterine expression of Dcn, Dpt, Lum, and Mfap4 was decreased in LPS-induced early pregnancy loss mice. MiR-16-5p, -21-3p, -27a-3p, and -941 were identified as potentially involved in the regulation of these five hub genes, and their decidual expression levels were significantly decreased in RM patients. The abnormally increased ISG15 expression in the decidual tissues of RM patients and uterine tissues of LPS-induced mice was validated by WB analysis. ISG15 expression was significantly reduced during the in vitro decidualization of human endometrial stromal cells (hESCs). Collectively, DCN, DPT, LUM, MFAP4, and ISG15 were identified as RM-related hub genes, and their expression in the decidual tissues of RM patients was significantly increased. The decidualization of hESCs was accompanied by reduced ISG15 expression, suggesting that increased decidual ISG15 expression might lead to early pregnancy loss by disrupting the decidualization process.

Abstract Gliomas are highly heterogenous diseases with poor prognosis. Precise survival prediction could benefit further clinical decision‐making, clinical trial incursion, and health economics. Recent research has emphasized the prognostic value of magnetic resonance imaging, pathological specimens, and circulating biomarkers. However, the integrative potential and efficacy of these modalities require to be further validated. After incorporating 218 patients of The Cancer Genome Atlas glioma datasets of and 54 patients of the Huashan cohort with complementary prognostic information, we established a squeeze‐and‐excitation deep learning feature extractor for T1‐contrast enhanced images and histological slides and explored to screen significant circulating 5‐hydroxymethylcytosines (5hmC) profiles for glioma survival by least absolute shrinkage and selection operator‐Cox regression. Therefore, a prognostication predictive model with high efficiency was obtained through survival support vector machine multimodal integration of radiologic imaging, histopathologic imaging features, genome‐wide 5hmC in circulating cell‐free DNA and clinical variables, suggesting a valid strategy (concordance‐index = 0.897; Brier score = 0.118) for improved survival risk stratification of glioma patients.

BackgroundThe cardiometabolic index (CMI) has emerged as a novel marker for evaluating the distribution and dysfunction of visceral adipose tissue, yet its correlation with numerous diseases, particularly new-onset chronic conditions, remains underexplored. Therefore, we aim to explore the association of cardiometabolic index (CMI) and new-onset chronic diseases.MethodsThe analysis utilized data from the China Health and Retirement Longitudinal Study, with a baseline in 2011 and follow-ups biennially until 2020. Fourteen new-onset chronic diseases were diagnosed based on self-report, and separate cohorts were created for each disease. CMI was calculated as triglycerides/high-density lipoprotein cholesterol multiplied by the waist-to-height ratio. Cox proportional hazards models were used to assess the association between CMI and new-onset chronic diseases, while restricted cubic spline (RCS) models were employed to explore potential nonlinear effects. Additional and sensitivity analyses included Kaplan-Meier survival curves, subgroup analyses, multiple imputations, and exclude outcome events at the first follow-up.ResultsHigher levels of CMI were associated with an increased risk of new-onset hypertension (HR=1.05, 95% CI=1.04-1.06, P

The study aimed to screen for the possible presence of lactic acid bacteria (LAB) in cat milk in order to evaluate their probiotic properties. The isolates were characterized by biochemical identification, morphological tests and 16S rDNA sequencing. Afterward, gastrointestinal passage, in vitro safety and probiotic properties were evaluated. The results showed that the isolates had 10 strains of Pediococcus acidilactici permitted in the feed additive catalog. The high survival rate in the acid and bile salt resistance test reflected the good strain tolerance of the isolates to the simulated gastrointestinal conditions of the host in vitro. The mean inhibitory diameters of the 10 strains against chloramphenicol and tetracycline were 23.6 mm and 17.4 mm, respectively; none of the hemolytic tests showed α/β hemolytic ring. The bacteriostatic test showed that P. acidilactici YH-9, YH-14 and YH-15 had inhibitory effects on four common pathogenic bacteria, including Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Streptococcus. The adhesion test showed that P. acidilactici YH-15 had good adhesion to HT-29 cells. Based on these results, we concluded that P. acidilactici YH-15 extracted from cat milk has potential application as a clinical probiotic therapy and health care product.

BackgroundSeizures have been identified in most patients with CSNK2B-related Poirer-Bienvenu Neurodevelopment syndrome (POBINDS). Detailed descriptions of seizure phenotypes, various genotypes, and long-term follow-up visits are required for clinicians to provide reasonable clinical management for such patients.Case summaryWe report two new Chinese patients with varying sizes of 6p21.33 deletions encompassing the CSNK2B gene who presented with intellectual disability and seizures. Furthermore, we conducted a literature review of previously reported patients with 6p21.33 deletions or CSNK2B variants. We summarized and analyzed the clinical characteristics of these patients with seizures. The occurrence of a biphasic pattern of epilepsy and pharmacoresistant epilepsy in patients with CSNK2B variants is severely underestimated. One of our patients underwent a long follow-up period and presented with comprehensive disease progression.ConclusionOur data suggest that the CSNK2B variant or 6p21.33 deletion should be considered in patients with intellectual disability and epilepsy, especially those characterized by biphasic patterns and digital anomalies.

Objectives Metabolic and bariatric surgery (MBS) for obstructive sleep apnoea syndrome (OSAS) has garnered significant research interest. The main aim of this study was to analyse the unique characteristics of publications centred around MBS for OSAS. We aimed to provide valuable insights into the present status of the field and offer predictions regarding future trends.Design Bibliometric analysis through science mapping and performance analysis methods.Data sources Scientific articles.Data extraction and synthesis A comprehensive search was conducted in the Web of Science database to retrieve publications on MBS for OSAS within the time frame of 1999–2023. The search was performed using keywords such as “Obstructive Sleep Apnea syndrome”, “OSAS”, “metabolic surgery” and “bariatric surgery” to identify relevant papers. To analyse the bibliometric characteristics of these publications, VOSviewer and R software were used. This analysis encompassed various aspects, including the number of publications, contributions by different countries and institutions, the most cited author, journal publications, citation frequency and the identification of keywords related to popular scientific fields.Results 1264 papers on MBS for OSAS were identified and are currently in a stage of rapid growth. The relevant study involved 1230 institutions from 53 different countries, with the USA topping the field with 465 publications contributed. Assistance Publique Hopitaux Paris proved to be the most productive institution, with De Vries N posting the highest number of papers (n=24). The most prolific journal was Obesity Surgery, with 241 publications. Keywords “Bariatric surgery”, “Obstructive sleep apnea”, “Obesity”, “Weight loss” and “Morbid obesity” have the highest frequency of occurrence.Conclusions The relationship between obesity and OSAS, various metabolic surgical techniques, and the mechanism of MBS for OSAS will continue to be related areas of frontiers. Furthermore, while there has been a gradual increase in basic research, the mechanisms involved and the long-term efficacy of bariatric MBS for OSAS still require further investigation. It is anticipated that these research areas may emerge as potential hot topics in the future.

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), with repeated infections and airflow limitation leading to endothelial dysfunction. The objective of this study was to retrospectively investigate the clinical significance of serum hypoxia-inducible factor 1-alpha (HIF-1α), plasma endothelin-1 (ET-1), and nitric oxide (NO) as non-invasive blood biomarkers for diagnosing patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 230 AECOPD patients were assessed for serum HIF-1α, plasma ET-1, and NO levels using Doppler echocardiography and blood tests. Clinical characteristics, including age, COPD duration, and comorbidities, were compared between patients with and without PH. The diagnostic value was determined through ROC analysis. Pearson correlation and multivariate logistic analyses explored the correlation of biomarkers in AECOPD with PH. Serum HIF-1α, plasma ET-1, and NO levels showed significant differences between COPD patients with and without PH. The combination model (0.027 * HIF-1α + 0.028 * ET-1 - 0.049 * NO) demonstrated an AUC of 0.89, indicating superior diagnostic value compared to individual biomarkers. Multivariate logistic analysis identified smoking, higher GOLD grade, hypertension, and elevated levels of HIF-1α, ET-1, and NO as independent risk factors for AECOPD. Positive correlations were observed between serum HIF-1α and plasma ET-1 levels with pulmonary artery systolic pressure (PASP), while NO demonstrated a negative correlation. Serum HIF-1α, plasma ET-1, and NO were associated with AECOPD and PH, and detecting individual or combined levels of these biomarkers in the blood can predict COPD-related PH.

This research examined the impact of defatted coconut flour (DCF)-based oleogels on the quality of surimi. Microscopic analysis indicated that the dietary fiber present in DCF could act as the main structure of the oleogels network. The formation of the oleogels network primarily relies on the tensile intramolecular or intermolecular hydrogen bonds between DCF and corn oil. The oleogels displayed oil binding capacity of up to 96.95% and exhibited favorable mechanical and rheological properties. Efforts were undertaken to integrate the acquired oleogels into silver carp surimi to create oil-fortified surimi products. Adding oleogels significantly enhanced the gel strength, texture, and water-holding capacity of surimi compared to adding corn oil. Especially, oleogels containing 5.0 % (w/v) DCF concentration elevated the lipid content in the surimi and preserved the gel and texture properties. Therefore, incorporating oleogels in surimi presents a potential solution for enhancing the nutritional content of surimi products.

Peanut protein (PP)/buckwheat protein (BWP) mixture crosslinked by transglutaminase (TGase) under dual-frequency ultrasound (DFU) field was developed and its structural and functional properties were characterized. The results showed that the optimal DFU parameters for PP-BWP crosslinking were 25 kHz/40 kHz dual-frequency ultrasound working time ratio of 10:10 (s/s), a temperature of 45°C, ultrasonic power density of 125 W/L and time duration of 30 min, resulting in the degree of crosslinking (DC) of 37.7 %, which is 125 % higher than that of the control. The solubility at pH 7.0, oil-holding capacity, and emulsifying capacity of the protein aggregate (peanut protein-buckwheat protein crosslinked by TGase under dual-frequency ultrasound, U-TG-PP-BWP) was significantly (P

Abstract Flexible microwave absorber (MAR), vital in advanced applications such as wearable electronics and precision devices, are highly valued for their lightweight, exceptional electromagnetic waves (EWs), and ease of fabrication. However, optimizing the electromagnetic parameters of microwave absorption materials (MAMs) to enhance absorption ability and expand effective absorption broadband (EAB, reflection loss (RL)

Accurately predicting agricultural yields is crucial for developing adaptative strategies to ensure food security. Unmanned aerial vehicle (UAV) remote sensing equipped with portable multispectral sensors are commonly applied to acquire high temporal and spatial resolutions of remote sensing data. The vegetation indices (VIs) extracted from multispectral images are conducted for agricultural yield prediction. However, existing VIs often suffered from saturation problems when the canopy coverage is high. Integrating UAV-derived canopy height data with spectral indices holds the potential to solve saturation problem. However, this method is still at the infant stage and requires further validation. Here, we have newly proposed a multispectral-based canopy volumetric vegetation index (MSCVI) that integrates RGB-based volumetric index (VCI) and multispectral images derived VIs from UAV platform for predicting irrigated maize yields for three years (2019, 2020, and 2021). To test the stability of the proposed method, the maize was well managed and different levels of fertilizers were applied in each plot. The results using regression analysis showed the MSCVI outperformed the single adoption of VIs and VCI, and the MSCVI at reproductive growth stages was more strongly correlated with maize yields. Two commonly applied machine learning approaches: backpropagation neural network (BP) and random forest (RF) were applied for predicting maize yield. The R2 between actual maize yield and predicted maize yield using BP increased from 0.81 to 0.86 (RMSE decreased from 0.93 to 0.67 t/ha). The R2 between actual maize yield and predicted maize yield using RF increased from 0.91 to 0.94 (RMSE decreased from 0.65 to 0.42 t/ha). The robustness of the proposed model was further evaluated using data updating strategies, and results implied that the models was stable across sensors and different years. Overall, this study revealed the proposed MSCVI obtain high potential for predicting agricultural yields, and the proposed model was robust and stable when tested using data updating strategy.

Summary: Cancer cells with mitochondrial dysfunction can be rescued by cells in the tumor microenvironment. Using human adenoid cystic carcinoma cell lines and fibroblasts, we find that mitochondrial transfer occurs not only between human cells but also between human and mouse cells both in vitro and in vivo. Intriguingly, spontaneous cell fusion between cancer cells and fibroblasts could also emerge; specific chromosome loss might be essential for nucleus reorganization and the post-hybrid selection process. Both mitochondrial transfer through tunneling nanotubes (TNTs) and cell fusion “selectively” revive cancer cells, with mitochondrial dysfunction as a key motivator. Beyond mitochondrial transfer, cell fusion significantly enhances cancer malignancy and promotes epithelial-mesenchymal transition. Mechanistically, mitochondrial dysfunction in cancer cells causes L-lactate secretion to attract fibroblasts to extend TNTs and TMEM16F-mediated phosphatidylserine externalization, facilitating TNT formation and cell-membrane fusion. Our findings offer insights into mitochondrial transfer and cell fusion, highlighting potential cancer therapy targets.

It has been well acknowledged that maternal exposure to fine particulate matters (PM2.5) might lead to poor pregnancy outcomes including the intrauterine growth restriction (IUGR) by interfering with the placental development. Our previous studies have demonstrated that maternal PM2.5 exposure induces IUGR, accompanied with increased maternal circulating TNFα level and impaired extravillous trophoblast cells (EVTs) invasion in mice. In this study, HTR8/SVneo cells, the immortalized human EVTs line, were used to assess effects and the underlying molecular mechanisms of nicotinamide on the impaired EVTs invasion. Our results showed that, the placental FLT1 protein level was significantly increased whereas maternal serum nicotinamide concentration was remarkably decreased in PM2.5-exposured pregnant mice at GD17.5 (vaginal plug day=GD0.5), compared to that in normal GD17.5 pregnant mice. FLT1 expression in HTR8/SVneo cells was significantly up-regulated by TNFα treatment, and the down-regulated FLT1 expression effectively abated the inhibitory effects of TNFα on HTR8/SVneo cells migration and invasion. Meanwhile, TNFα promoted reactive oxygen species (ROS) production and NF-κB signaling pathway activation in HTR8/SVneo cells in a dose-dependent manner. Nicotinamide treatment significantly reversed the effects of TNFα on cell migration and invasion, as well as the FLT1 expression, ROS production and NF-κB pathway activation. In summary, increased TNFα induced by PM2.5 exposure inhibits EVTs invasion by activating the ROS/NF-κB/FLT1 signaling pathway, and this adverse effect could be attenuated by nicotinamide treatment, suggesting a potential application in the clinical intervention of PM2.5-induced IUGR.

Abstract Background Chronic myeloid leukemia (CML) is a common hematological malignancy, and tyrosine kinase inhibitors (TKIs) represent the primary therapeutic approach for CML. Activation of metabolism signaling pathway has been connected with BCR::ABL1-independent TKIs resistance in CML cells. However, the specific mechanism by which metabolism signaling mediates this drug resistance remains unclear. Here, we identified one relationship between glutamine synthetase (GS) and BCR::ABL1-independent Imatinib resistance in CML cells. Methods GS and PXN-AS1 in bone marrow samples of CML patients with Imatinib resistance (IR) were screened and detected by whole transcriptome sequencing. GS expression was upregulated using LVs and blocked using shRNAs respectively, then GS expression, Gln content, and cell cycle progression were respectively tested. The CML IR mice model were established by tail vein injection, prognosis of CML IR mice model were evaluated by Kaplan–Meier analysis, the ratio of spleen/body weight, HE staining, and IHC. PXN-AS1 level was blocked using shRNAs, and the effects of PXN-AS1 on CML IR cells in vitro and in vivo were tested the same as GS. Several RNA-RNA tools were used to predict the potential target microRNAs binding to both GS and PXN-AS1. RNA mimics and RNA inhibitors were used to explore the mechanism through which PXN-AS1 regulates miR-635 or miR-635 regulates GS. Results GS was highly expressed in the bone marrow samples of CML patients with Imatinib resistance. In addition, the lncRNA PXN-AS1 was found to mediate GS expression and disorder cell cycle in CML IR cells via mTOR signaling pathway. PXN-AS1 regulated GS expression by binding to miR-635. Additionally, knockdown of PXN-AS1 attenuated BCR::ABL1-independent Imatinib resistance in CML cells via PXN-AS1/miR-635/GS/Gln/mTOR signaling pathway. Conclusions Thus, PXN-AS1 promotes GS-mediated BCR::ABL1-independent Imatinib resistance in CML cells via cell cycle signaling pathway. Graphic Abstract

Abstract Objectives To develop an interactive, non-invasive artificial intelligence (AI) system for malignancy risk prediction in cystic renal lesions (CRLs). Methods In this retrospective, multicenter diagnostic study, we evaluated 715 patients. An interactive geodesic-based 3D segmentation model was created for CRLs segmentation. A CRLs classification model was developed using spatial encoder temporal decoder (SETD) architecture. The classification model combines a 3D-ResNet50 network for extracting spatial features and a gated recurrent unit (GRU) network for decoding temporal features from multi-phase CT images. We assessed the segmentation model using sensitivity (SEN), specificity (SPE), intersection over union (IOU), and dice similarity (Dice) metrics. The classification model’s performance was evaluated using the area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA). Results From 2012 to 2023, we included 477 CRLs (median age, 57 [IQR: 48–65]; 173 men) in the training cohort, 226 CRLs (median age, 60 [IQR: 52–69]; 77 men) in the validation cohort, and 239 CRLs (median age, 59 [IQR: 53–69]; 95 men) in the testing cohort (external validation cohort 1, cohort 2, and cohort 3). The segmentation model and SETD classifier exhibited excellent performance in both validation (AUC = 0.973, ACC = 0.916, Dice = 0.847, IOU = 0.743, SEN = 0.840, SPE = 1.000) and testing datasets (AUC = 0.998, ACC = 0.988, Dice = 0.861, IOU = 0.762, SEN = 0.876, SPE = 1.000). Conclusion The AI system demonstrated excellent benign-malignant discriminatory ability across both validation and testing datasets and illustrated improved clinical decision-making utility. Critical relevance statement In this era when incidental CRLs are prevalent, this interactive, non-invasive AI system will facilitate accurate diagnosis of CRLs, reducing excessive follow-up and overtreatment. Key Points The rising prevalence of CRLs necessitates better malignancy prediction strategies. The AI system demonstrated excellent diagnostic performance in identifying malignant CRL. The AI system illustrated improved clinical decision-making utility. Graphical Abstract

Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is caused by reperfusion after ischemic heart disease. LncRNA Snhg1 regulates the progression of various diseases. N6-methyladenosine (m6A) is the frequent RNA modification and plays a critical role in MIRI. However, it is unclear whether lncRNA Snhg1 regulates MIRI progression and whether the lncRNA Snhg1 was modified by m6A methylation. Methods Mouse cardiomyocytes HL-1 cells were utilized to construct the hypoxia/reoxygenation (H/R) injury model. HL-1 cell viability was evaluated utilizing CCK-8 method. Cell apoptosis, mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were quantitated utilizing flow cytometry. RNA immunoprecipitation and dual-luciferase reporter assays were applied to measure the m6A methylation and the interactions between lncRNA Snhg1 and targeted miRNA or target miRNAs and its target gene. The I/R mouse model was constructed with adenovirus expressing lncRNA Snhg1. HE and TUNEL staining were used to evaluate myocardial tissue damage and apoptosis. Results LncRNA Snhg1 was down-regulated after H/R injury, and overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization. Besides, lncRNA Snhg1 could target miR-361-5p, and miR-361-5p targeted OPA1. Overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization though the miR-361-5p/OPA1 axis. Furthermore, WTAP induced lncRNA Snhg1 m6A modification in H/R-stimulated HL-1 cells. Moreover, enforced lncRNA Snhg1 repressed I/R-stimulated myocardial tissue damage and apoptosis and regulated the miR-361-5p and OPA1 levels. Conclusion WTAP-mediated m6A modification of lncRNA Snhg1 regulated MIRI progression through modulating myocardial apoptosis, mitochondrial ROS production, and mitochondrial polarization via miR-361-5p/OPA1 axis, providing the evidence for lncRNA as the prospective target for alleviating MIRI progression.

Abstract Background With suicide as a leading cause of death, the issue of children and adolescent suicide risks is in the spotlight today. To empower teachers in primary and secondary schools to serve as gatekeepers and to ensure the safety of children and adolescents, the systematically tailored and localized Life Gatekeeper suicide prevention program was designed for Chinese schools. Objective With the ultimate goal of preventing child and adolescent suicide, we aim to outline a research protocol for examining outcomes of the recently created standardized school-based Life Gatekeeper program in reducing teachers’ stigma, increasing their knowledge, willingness to intervene, and perceived competence. Methods Participants will be recruited from eligible primary and secondary schools. Cluster sampling will be used to randomly assign each school to either the intervention group or the control group. The primary outcomes are stigma against suicide, suicide literacy, perceived competence, and willingness to intervene with suicidal individuals, which will be measured using the Stigma of Suicide Scale, the Literacy of Suicide Scale, and the Willingness to Intervene Against Suicide Questionnaire, respectively. Measurements will be taken at four time points, including pre-intervention, immediately after the intervention, 6-month follow-up, and 1-year follow-up. Conclusions The current study features innovative implementation in the real world, by using a randomized controlled trial design to examine the effectiveness of a school-based gatekeeper program among primary and secondary school teachers, following a sequence of defined and refined steps. The research will also investigate the viability of a school-based gatekeeper program for primary and secondary school teachers that could be quickly and inexpensively implemented in a large number of schools.

Abstract The brain presents age-related structural and functional changes in the human life, with different extends between subjects and groups. Brain age prediction can be used to evaluate the development and aging of human brain, as well as providing valuable information for neurodevelopment and disease diagnosis. Many contributions have been made for this purpose, resorting to different machine learning methods. To solve this task and reduce memory resource consumption, we develop a mini architecture of only 10 layers by modifying the deep residual neural network (ResNet), named ResNet mini architecture. To support the ResNet mini architecture in brain age prediction, the brain age dataset (OpenNeuro #ds000228) that consists of 155 study participants (three classes) and the Alzheimer MRI preprocessed dataset that consists of 6400 images (four classes) are employed. We compared the performance of the ResNet mini architecture with other popular networks using the two considered datasets. Experimental results show that the proposed architecture exhibits generality and robustness with high accuracy and less parameter number.