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Abstract As population aging increased globally, this study aimed to examine the relationship between leisure activity participation and cognitive function in the older Chinese population and the gender and age differences in this relationship. A total of 12526 individuals aged 60 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey were obtained for this study. Multiple linear regression analysis was used to explore the relationship. This study found productive, physical, intellectual, recreational and social activities were associated with cognitive function. Males enjoyed extra benefits from recreational activities compared with females. Females enjoyed extra benefits from productive activities and social activities compared with males. Older age enjoyed extra benefits from productive activities, physical activities, intellectual activities, recreational activities, social activities in comparison with younger age. Thus, Chinese older adults need to make efforts to increase the time and variety of leisure activities, especially for the oldest old. Compared with other types of leisure activities, it’s more important for old men to participate in recreational activities, and for old women to participate in productive activities and social activities.

Abstract Background Previous studies have shown that overall sleep quality among Chinese nurses is relatively low, with a sleep disorder prevalence rate of approximately 66.4%. Against the backdrop of healthcare reforms, China has been striving to improve the mental health and sleep quality of nurses. Stress mindset can influence how individuals respond to stress, but there is limited research on how stress mindset affects nurses’ sleep quality. This study aims to explore the impact of stress mindset on sleep quality among nurses, as well as the mediating roles of stress overload and anxiety in this relationship. Methods The study was conducted online using a questionnaire from February 18 to February 22, 2024. It utilized the Stress Mindset Measure (SMM), the Stress Overload Scale-Short (SOS-S), the Generalized Anxiety Disorder 7-item scale (GAD-7), and the Pittsburgh Sleep Quality Index (PSQI) to survey 441 nurses in three regions of China: Chongqing, Hunan, and Shandong (M = 34.39, SD = 7.82, 95.7% female). A chain mediation model was employed to examine the mediating roles of stress overload and anxiety in the relationship between stress mindset and sleep quality. Results The participants’ average sleep quality score was 7.18 ± 3.47. Nurses’ stress mindset was significantly negatively correlated with both stress overload and anxiety, and significantly positively correlated with sleep quality. Stress overload was significantly positively correlated with anxiety and significantly negatively correlated with sleep quality. Anxiety was also significantly negatively correlated with sleep quality. The direct effect of nurses’ stress mindset on sleep quality was significant (effect size = -0.10, 95% CI: -0.19 to -0.01), as were the indirect effects through stress overload (effect size = -0.05, 95% CI: -0.11 to -0.01) and anxiety (effect size = -0.09, 95% CI: -0.13 to -0.05), along with their chain mediation effect (effect size = -0.10, 95% CI: -0.14 to -0.06). Conclusion Our study demonstrates that a higher level of nurses’ stress mindset is associated with better sleep quality, with stress overload and anxiety mediating this relationship. A positive stress mindset helps nurses cope more effectively with professional challenges and reduces anxiety, leading to improved sleep quality. Healthcare institutions should therefore prioritize fostering positive stress mindsets in nurses, encouraging regular psychological training and workshops to support the development of effective coping strategies.

Abstract Background Ferroptosis is a unique mode of cell death that is iron-dependent and associated with oxidative stress and lipid peroxidation. Oxidative stress and ferroptosis are essential mechanisms leading to metabolic abnormalities in cells and have been popular areas in cancer research. Methods Initially, 76 oxidative stress and ferroptosis-related genes (OFRGs) were acquired by intersecting the gene sets from oxidative stress and ferroptosis. Afterwards, optimal OFRGs were screened using PPI networks, and individuals were separated into two OFRG subtypes (K = 2). Subsequently, we successfully constructed and verified a prognostic signature comprising SLC7A2, Cadherin 19 (CDH19), and CCN1. To further uncover potential biomarkers of gastric cancer (GC), we examined the expression level of CDH19, investigated the effects of knocking down CDH19 on the biological behavior of GC cells, and explored whether CDH19 is involved in ferroptosis and oxidative stress processes. Results According to the findings, individuals in the low-risk scoring group have less infiltration of immune suppressive cells, fewer occurrences of immune escape and dysfunction, greater efficacy in chemotherapy and immunotherapy, and better survival outcomes. The qRT-PCR assay indicated that CDH19 expression was significantly higher in GC cells. Through experiments, we demonstrated that knocking down CDH19 can affect the transcription levels of ACSL4 and GPX4, increase intracellular iron ion concentration and accumulation of reactive oxygen species (ROS), and inhibit the proliferation and migration of GC cells. Conclusion We developed an OFRG-related signature to predict the prognosis and treatment responsiveness of individuals with GC and identified CDH19 as a possible therapeutic target for GC.

Abstract The run-up velocity and jumping ground reaction force directly influence gymnasts’ ability to perform more difficult manoeuvres and win competitions on vault. However, the variables influencing them among elite female gymnasts remain inadequately understood and warrant detailed investigation. This study aimed to analyse critical variables including run-up velocity and jumping ground reaction force, and to compare these factors across different vault types while further exploring the correlations among them. The study hypothesized that there are significant differences in run-up velocity and jumping ground reaction force across vaulting types, and that these differences will affect athletes’ performance. To test this hypothesis, the study analyzed data from performance tests on 16 elite Chinese female gymnasts, focusing on vaulting run-up velocity and jumping ground reaction force. Descriptive statistics were used to summarize the data, and binary logistic regression analysis was employed to investigate the relationships between the variables. The study found significant differences in interval run-up velocities between the Front handspring vaults and the Tsukahara vaults, particularly before the last 10 m (p = 0.04) and the last 5 m (p = 0.03). Specifically, the Front handspring vaults had higher velocities before the last 10 m, while the Tsukahara vaults had higher velocities within the last 5 m. Differences were also noted in the lengths of the penultimate (p = 0.03), last (p = 0.01), and hurdle steps (p = 0.04). The jumping ground reaction force showed a strong negative correlation with run-up velocity before the last 10 m (ρ = -0.469, p

Abstract Background Chronic Kidney Disease (CKD) impacts over 10% of the global population, and recent advancements in high-throughput analytical technologies are uncovering the complex physiology underlying this condition. By integrating Genome-Wide Association Studies (GWAS), RNA sequencing (RNA-seq/RNA array), and single-cell RNA sequencing (scRNA-seq) data, our study aimed to explore the genes and cell types relevant to CKD traits. Methods GWAS summary data for end-stage renal failure (ESRD) and decreased eGFR (CKD) with or without diabetes and (micro)proteinuria were obtained from the GWAS Catalog and the UK Biobank (UKB) database. Two gene Expression Omnibus (GEO) transcriptome datasets were used to establish glomerular and tubular gene expression differences between CKD patients and healthy individuals. Two scRNA-seq datasets were utilized to obtain the expression of key genes at the single-cell level. The expression profile, differentially expressed genes (DEGs), gene-gene interaction, and pathway enrichment were analysed for these CKD risk genes. Results A total of 779 distinct SNPs were identified from GWAS across different CKD traits, involving 681 genes. While many of these risk genes are specific to the CKD traits of renal failure, decreased eGFR, and (micro)proteinuria, they share common pathways, including extracellular matrix (ECM). ECM modeling was enriched in upregulated glomerular and tubular DEGs from CKD kidneys compared to healthy controls, with the expression of relevant collagen genes, such as COL1A2, prevalent in fibroblasts/myofibroblasts. Additionally, immune responses, including T cell differentiation, were dysregulated in CKD kidneys. The late podocyte signature gene THSD7A was enriched in podocytes but downregulated in CKD. We also highlighted that the regulated risk genes of CKD are mainly expressed in tubular cells and immune cells in the kidney. Conclusions Our integrated analysis highlight the genes, pathways, and relevant cell types associational with the pathogenesis of kidney traits, as a basis for further mechanistic studies to understand the pathogenesis of CKD.

Abstract Introduction Concentrated Growth Factor (CGF), rich in CD34 + stem cells, is widely used in treatments for androgenetic alopecia and skin rejuvenation due to its immune-modulating properties. Psoriasis, a chronic inflammatory skin condition, presents significant treatment challenges, particularly for patients who cannot use biologics due to conditions such as cancer and lesions resistant to treatments. The potential of CGF in treating psoriasis is promising, given its broad immunoregulatory effects which confirmed in our previous androgenetic alopecia work. Methods We evaluated the impact of CGF on IL-17 levels in two contexts: patients treated for androgenetic alopecia and a psoriasis mouse model. Twelve patients received three monthly injections of CGF, with serum IL-17 levels measured before and after treatment. In the psoriasis mouse model, groups were treated with CGF, and outcomes were assessed using the Psoriasis Area and Severity Index (PASI), skin barrier scores, histological analysis, and RNA sequencing. Additionally, in vitro experiments applied CD34 + cells from CGF to keratinocytes to measure levels of TNF-α, IFN-γ, IL-23, and IL-17. Results In patients with androgenetic alopecia, three monthly CGF injections resulted in significantly reduced serum IL-17 levels. In the psoriatic mouse model, CGF-treated groups exhibited lower PASI scores and improved skin barrier scores compared to controls. Histological analysis revealed enhanced skin characteristics, while RNA sequencing demonstrated downregulated IL-17 and upregulated CD34 expression, as well as improved expression of barrier-related genes. In vitro, the application of CD34 + cells from CGF to keratinocytes led to a significant reduction in TNF-α, IFN-γ, IL-23, and IL-17 levels, indicating strong anti-inflammatory effects. A clinical case of a psoriasis patient unresponsive to IL-23 therapy (Guselkumab) showed significant improvement following CGF treatment. Conclusion These findings indicate that CGF could serve as an effective and versatile treatment for psoriasis, especially for patients who have already undergone biologic therapies but continue to experience resistant lesions.

Abstract Functional dyspepsia (FD) is known to be influenced by gut microbiota (GM) and circulating inflammatory proteins (CIPs), however, the causal relationship between GM, CIPs and FD haven’t been investigated. This study employed two-sample Mendelian Randomization (TSMR) to investigate their associations using data from Genome-Wide Association Studies (GWAS). In this study, Inverse-variance weighted (IVW) method was employed as the primary analysis, with supplementary approaches including weighted median, weighted mode, simple mode, and MR-Egger. Heterogeneity and pleiotropy were assessed using the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test. Totally, 196 GM traits and 91 CIPs were analyzed, and the results uncovered the causal impact of 12 GM taxa and 5 proteins on functional dyspepsia (FD). 9 GM genera were linked to a reduced risk of FD, while 3 GM genera were associated with an increased risk of FD.Additionally, reverse analysis revealed no FD-GM causation. Furthermore, IL-12, IL-10, CXCL10, CXCL9 and VEGFA were significantly correlated with FD, with CXCL9 and VEGFA acting as mediators in the association between GM traits and FD. Taken together, our findings established a link between specific GM and CIPs in the pathogenesis of FD, offering novel insights for its diagnosis and treatment.

Abstract Oocytes play a crucial role in transmitting maternal mitochondrial DNA (mtDNA), essential for the continuation of species. However, the effects of mitochondrial reactive oxygen species (ROS) on mammalian oocyte maturation and mtDNA maintenance remain unclear. We investigated this by conditionally knocking out the Sod2 gene in primordial follicles, elevating mitochondrial matrix ROS levels from early oocyte stages. Our data indicates that reproductive aging in Sod2 conditional knockout females begins at 6 months, with oxidative stress impairing oocyte quality, particularly affecting OXPHOS complex II and mtDNA-encoded mRNA levels. Despite unchanged mtDNA mutation load, mtDNA copy numbers exhibited significant variations. Strikingly, reducing mtDNA copy numbers by reducing mtSSB protein, crucial for mtDNA replication, accelerated reproductive aging onset to three months, underscoring the critical role of mtDNA copy number maintenance under oxidative stress conditions. This research provides new insights into the relationship among mitochondrial ROS, mtDNA, and reproductive aging, offering potential strategies for delaying aging-related fertility decline.

Abstract Background The neonatal outcomes across different percentiles of birth weight for gestational age are still unclear. Methods This retrospective cohort study was conducted within 57 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 25 provinces throughout China. Infants with gestational age (GA) 24+0-31+6 weeks who were admitted within 7 days after birth were included. The composite outcome was defined as mortality or any one of neonatal major morbidities, including necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (cPVL), severe retinopathy of prematurity (ROP), and sepsis. Multivariable logistic regressions using generalized estimating equation approach were conducted. Results A total of 8380 infants were included with a mean GA of 30 (28–31) weeks. Of these, 1373 (16.5%) were born at less than 28 weeks, while 6997 (83.5%) had a GA between 28 and 32 weeks. Our analysis indicated that the risk of composite outcomes was negatively associated with birth weight for gestational age, and compared to the reference group, the multiple-adjusted ORs (95%CI) of composite outcomes were 4.89 (3.51–6.81) and 2.16 (1.77–2.63) for infants with birth weight for gestational less than 10th percentile and 10th -30th percentile, respectively. The ORs (95%CI) of mortality, NEC, BPD, severe ROP, and sepsis in infants with birth weight for gestational age at 10th-30th percentile were 1.94 (1.56–2.41), 1.08 (0.79–1.47), 2.48 (2.03–3.04), 2.35 (1.63–3.39), and 1.39 (1.10–1.77), respectively. Conclusion Our study suggested that the risk of adverse neonatal outcomes increased significantly when the birth weight for gestational age was below the 30th percentile. Regular monitoring and early intervention are crucial for these high-risk infants.

With the rapid development of the electronics industry, the demand for dielectric materials with high permittivities, low losses, and excellent electrical breakdown strengths prepared via low-temperature fabrication techniques is increasing. Herein, we propose a one-step cold sintering process route to improve the comprehensive performance of BaTiO3−based ceramics by integrating polyetherimide (PEI). Dense BaTiO3–PEI nanocomposites can be prepared via a cold sintering process at 250 °C using Ba(OH)2∙8H2O and H2TiO3 as the transient liquid phase. The grain growth of BaTiO3 is inhibited, and thin PEI layers less than 10 nm in size are located at the grain boundaries. The dissolution‒precipitation process triggered by the transient liquid phase and viscous flow assisted by PEI dominates the cold sintering mechanism of the (1−x)BaTiO3–xPEI nanocomposites. The dielectric properties are stable over a broad temperature range up to 200 °C. Compared with BaTiO3, 80% BaTiO3–20% PEI has superior performance, with a relative permittivity of 163 and a low dielectric loss of 0.014, and the electrical breakdown strength is increased by 80.65% compared with BaTiO3. Overall, the cold sintering process provides a potential way to develop dielectric nanocomposites with excellent comprehensive performance.

Abstract Background Neurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear. Methods To explore their putative causalities, we conducted bidirectional two-sample Mendelian randomization (MR) using genetic variants associated with 317 human blood metabolites (n max = 215,551), g-Factor (an integrated index of multiple neurocognitive tests with n max = 332,050), and 10 different psychiatric disorders (n = 9,725 to 807,553) from the large-scale genome-wide association studies of European ancestry. Mediation analysis was used to assess the potential causal pathway among the candidate metabolite, neurocognitive trait and corresponding psychiatric disorder. Results MR evidence indicated that genetically predicted acetylornithine was positively associated with g-Factor (0.035 standard deviation units increase in g-Factor per one standard deviation increase in acetylornithine level; 95% confidence interval, 0.021 to 0.049; P = 1.15 × 10−6). Genetically predicted butyrylcarnitine was negatively associated with g-Factor (0.028 standard deviation units decrease in g-Factor per one standard deviation increase in genetically proxied butyrylcarnitine; 95% confidence interval, −0.041 to −0.015; P = 1.31 × 10−5). There was no evidence of associations between genetically proxied g-Factor and metabolites. Furthermore, the mediation analysis via two-step MR revealed that the causal pathway from acetylornithine to bipolar disorder was partly mediated by g-Factor, with a mediated proportion of 37.1%. Besides, g-Factor mediated the causal pathway from butyrylcarnitine to schizophrenia, with a mediated proportion of 37.5%. Other neurocognitive traits from different sources provided consistent findings. Conclusion Our results provide genetic evidence that acetylornithine protects against bipolar disorder through neurocognitive abilities, while butyrylcarnitine has an adverse effect on schizophrenia through neurocognition. These findings may provide insight into interventions at the metabolic level for risk of neurocognitive and related disorders.

Abstract Background Guinea pigs exhibit numerous physiological similarities to humans, yet the details of their preimplantation embryonic development remain largely unexplored. Results To address this, we conducted single-cell sequencing on the transcriptomes of cells isolated from the zygote stage through preimplantation stages in guinea pigs. This study identified seven distinct cell types within guinea pig preimplantation embryos and pinpointed the timing of zygotic gene activation (ZGA). Trajectory analysis revealed a bifurcation into two lineage-specific branches, accompanied by alterations in specific pathways, including oxidative phosphorylation and vascular endothelial growth factor (VEGF). Additionally, co-expressed gene network analysis highlighted the most enriched functional modules for the epiblast (EPI), primitive endoderm (PrE), and inner cell mass (ICM). Finally, we compared the similarities and differences between human and guinea pig epiblasts (EPIs). Conclusion This study systematically constructs a cell atlas of guinea pig preimplantation embryonic development, offering fresh insights into mammalian embryonic development and providing alternative experimental models for studying human embryonic development.

Sinamma Lin & Li, 2014 is a small tetrablemmid genus distributed in China, with three currently known species: Sinamma oxycera Lin & Li, 2014 from Guangxi Zhuang Autonomous Region and S. quadrata Tong & Li, 2022 and S. yingae Tong & Li, 2022 from Guangdong Province.While examining spider specimens obtained by sifting leaf litter from Danxiashan National Nature Reserve in Guangdong Province of China, we discovered a new species of the genus Sinamma, S. danxia sp. nov., which is described here.

Abstract This paper introduces an enhanced time synchronization method different from IEEE 1588 (PTP). The proposed algorithm employs a unique synchronous message packet structure with a fixed length of 10 bytes and the highest system priority. This design enables preemptive transmission, effectively reducing transmission and queuing delays. Additionally, it applies a Kalman filtering model to mitigate noise interference, including clock drift, network delay jitter, and network asymmetry. The algorithm also features a clock drift compensation mechanism to continuously adjust the clock, ensuring high precision and stability in time synchronization. The algorithm proposed in this paper has the characteristics of being easy to implement, requiring minimal hardware resources, and being applicable to a variety of networks. Simulation results show that, with an 80 MHz crystal oscillator, the time offset between master and slave clocks does not exceed ± 1 clock cycle in symmetric communication links. In asymmetric links, the maximum time offset is within ± 3 clock cycles. Compared to the original PTP algorithm and the Kalman filter-based time synchronization algorithm, this method reduces the time offset from several microseconds to less than 40 ns.

Abstract Background Insomnia disorder (ID) is one of the most common sleep problems, usually accompanied by anxiety and depression symptoms. Functional magnetic resonance imaging (fMRI) study suggests that both poor sleep quality and negative emotion are linked to the dysregulation of brain network related to emotion processing in ID patients. Acupuncture therapy has been proven effective in improving sleep quality and mood of ID patients, but the involved neurobiological mechanism remains unclear. We aimed to investigate the modulation effect of acupuncture on resting-state functional connectivity (rsFC) of the emotional network (EN) in patients experiencing insomnia. Methods A total of 30 healthy controls (HCs) and 60 ID patients were enrolled in this study. Sixty ID patients were randomly assigned to real and sham acupuncture groups and attended resting-state fMRI scans before and after 4 weeks of acupuncture treatment. HCs completed an MRI/fMRI scan at baseline. The rsFC values within EN were calculated, and Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy data were collected for clinical efficacy evaluation. Results Resting-state FC analysis showed abnormalities in rsFC centered on the thalamus and dorsolateral prefrontal cortex within EN of ID patients compared to HCs. After real acupuncture treatment, rsFC of the anterior cingulate cortex, hippocampus, and amygdala were increased compared with the sham acupuncture group (p

Abstract Type I CRISPR-Cas systems are widespread and have exhibited high versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems, with a total gene size smaller than that of SpCas9, can be developed for transcriptional activation in human cells. The efficiency of the engineered I-F2 tool can match or surpass that of dCas9. Additionally, we create a base editor using the I-F2 Cascade, which induces a considerably wide editing window (~30 nt) with a bimodal distribution. It can expand targetable sites, which is useful for disrupting functional sequences and genetic screening. This research underscores the application of compact type I systems in eukaryotes, particularly in the development of a base editor with a wide editing window.

Abstract Background The COVID-19 pandemic’s diverse symptomatology, driven by variants, underscores the critical need for a comprehensive understanding. Employing stochastic models, our study evaluates symptom sequences across SARS-CoV-2 variants on aggregated data, yielding essential insights for targeted interventions. Methods We conducted a meta-analysis based on research literature published before December 9, 2022, from PubMed, LitCovid, Google Scholar, and CNKI databases, to investigate the prevalence of COVID-19 symptoms during the acute phase. Registered in PROSPERO (CRD42023402568), we performed random-effects meta-analyses using the R software to estimate pooled prevalence and 95% CI. Based on our findings, we introduced the Stochastic Progression Model and Sequential Pattern Discovery using Equivalence classes (SPADE) algorithm to analyze patterns of symptom progression across different variants. Results Encompassing a total of 430,100 patients from east and southeast Asia, our results reveal the highest pooled estimate for cough/dry cough across wild-type, Delta, and Omicron variants, with fever (78.18%; 95% CI: 67–89%) being the most prominent symptom for the Alpha variant. Symptoms associated with the Omicron variant primarily manifested in upper respiratory tracts, cardiovascular, and neuropsychiatric systems. Stochastic models indicate early symptoms including dry cough and fever, followed by subsequent development of sleep disorders, fatigue, and more. Conclusion Our study underscores the evolving symptomatology across SARS-CoV-2 variants, emphasizing similarities in fever, cough, and fatigue. The Omicron variant presents a distinct profile characterized by milder symptoms yet heightened neuropsychological challenges. Advanced analytical models validate the observed sequential progression of symptoms, reinforcing the consistency of disease trajectory.

Abstract Background Colorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours. Methods 34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria. Results Five samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p

Abstract Purpose of review There are significant differences in the transmission rate and mortality rate of COVID-19 under environmental conditions such as seasons and climates. However, the impact of environmental factors on the role of the COVID-19 pandemic and the transmission mechanism of the SARS-CoV-2 is unclear. Therefore, a comprehensive understanding of the impact of environmental factors on COVID-19 can provide innovative insights for global epidemic prevention and control policies and COVID-19 related research. This review summarizes the evidence of the impact of different natural and social environmental factors on the transmission of COVID-19 through a comprehensive analysis of epidemiology and mechanism research. This will provide innovative inspiration for global epidemic prevention and control policies and provide reference for similar infectious diseases that may emerge in the future. Recent findings Evidence reveals mechanisms by which natural environmental factors influence the transmission of COVID-19, including (i) virus survival and transport, (ii) immune system damage, (iii) inflammation, oxidative stress, and cell death, and (iiii) increasing risk of complications. All of these measures appear to be effective in controlling the spread or mortality of COVID-19: (1) reducing air pollution levels, (2) rational use of ozone disinfection and medical ozone therapy, (3) rational exposure to sunlight, (4) scientific ventilation and maintenance of indoor temperature and humidity, (5) control of population density, and (6) control of population movement. Our review indicates that with the continuous mutation of SARS-CoV-2, high temperature, high humidity, low air pollution levels, and low population density more likely to slow down the spread of the virus.

Abstract Tumor neovascularization is essential for the growth, invasion, and metastasis of tumors. Recent studies have highlighted the significant role of N6-methyladenosine (m6A) modification in regulating these processes. This review explores the mechanisms by which m6A influences tumor neovascularization, focusing on its impact on angiogenesis and vasculogenic mimicry (VM). We discuss the roles of m6A writers, erasers, and readers in modulating the stability and translation of angiogenic factors like vascular endothelial growth factor (VEGF), and their involvement in key signaling pathways such as PI3K/AKT, MAPK, and Hippo. Additionally, we outline the role of m6A in vascular-immune crosstalk. Finally, we discuss the current development of m6A inhibitors and their potential applications, along with the contribution of m6A to anti-angiogenic therapy resistance. Highlighting the therapeutic potential of targeting m6A regulators, this review provides novel insights into anti-angiogenic strategies and underscores the need for further research to fully exploit m6A modulation in cancer treatment. By understanding the intricate role of m6A in tumor neovascularization, we can develop more effective therapeutic approaches to inhibit tumor growth and overcome treatment resistance. Targeting m6A offers a novel approach to interfere with the tumor’s ability to manipulate its microenvironment, enhancing the efficacy of existing treatments and providing new avenues for combating cancer progression.

Abstract There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p

Abstract Background Standardized patients (SPs) simulation training models have been widely used in various fields, the study of using SPs in Traditional Chinese medicine (TCM) is still a new filed. Previous studies have demonstrated the effectiveness of occupational SP for TCM (OSP-TCM), which has an increasingly problem of high time and financial costs. The faculty SPs for TCM (FSP-TCM) simulation training model may provide a better alternative. This study aims to test and determine whether FSP-TCM simulations are more cost-effective than OSP-TCM and traditional educational models to improve the clinical competence of TCM students. Methods This study was a single-blind, prospective, randomized controlled trial conducted between February 2023 and October 2023. The participants were randomized into FSP-TCM group, OSP-TCM group and traditionally taught group (TT group) in the ratio of 1:1:1. The duration of this training program was 12 weeks (36 credit hours). Formative and summative assessments were integrated to evaluate the effectiveness of teaching and learning. Three distinct questionnaires were utilized to collect feedback from students, SPs, and teachers at the conclusion of the course. Additionally, analysis of cost comparisons between OSP-TCM and FSP-TCM were performed in the study. Results The study comprised a total of 90 students, with no dropouts during the research. In the formative evaluation, students assigned to both the FSP-TCM and OSP-TCM groups demonstrated higher overall scores compared to those in the TT group. Notably, their performance in “physical examination” (P a = 0.01, P b = 0.04, P c = 0.93) and “comprehensive ability” (P a = 0.01, P b = 0.006, P c = 0.96) significantly exceeded that of the TT group. In the summary evaluation, both SP-TCM groups students outperforms TT group in the online systematic knowledge test (P a = 0.019, P b = 0.04, P c = 0.97), the application of TCM technology (P a = 0.01, P b = 0.03, P c = 0.93) and real-time assessment (P a= 0.003, P b = 0.01, P c = 0.93). The feedback questionnaire demonstrated that both SP-TCM groups showed higher levels of agreement for this course in “satisfaction with the course” (P a = 0.03; P b = 0.02) and “enhanced TCM clinical skills” (P a = 0.02; P b = 0.03) than TT group. The SP questionnaire showed that more FSPs than OSPs in “provided professional feedback” (FSPs: strongly agree 30%, agree 50% vs. OSPs: strongly agree 20%, agree 40%. P = 0.69), and in “gave hints” during the course (FSPs: strongly agree 10%, agree 30% vs. OSPs: strongly agree 0%, agree 10%. P = 0.42). It is noteworthy that FSP-TCM was significantly lower than the OSP-TCM in overall expense (FSP-TCM $7590.00 vs. OSP-TCM $17415.60), and teachers have a positive attitude towards the FSP-TCM. Conclusion FSP-TCM training mode showed greater effectiveness than traditional teaching method in improving clinical competence among TCM students. It was feasible, practical, and cost-effective, and may serve as an alternative method to OSP-TCM simulation.

Abstract Endometrial cancer (EC) stem cells (ECSCs) are pivotal in the oncogenesis, metastasis, immune escape, chemoresistance, and recurrence of EC. However, the specific mechanism of stem cell maintenance in EC cells (ECCs) has not been clarified. We found that WTAP and m6A levels decreased in both EC and ECSCs, and that knocking down WTAP promoted ECCs and ECSCs properties, including proliferation, invasion, migration, cisplatin resistance, and self-renewal. The downregulation of WTAP leads to a decrease in the m6A modification of EGR1 mRNA, and it is difficult for IGF2BP3, as an m6A reader, to recognize and bind to EGR1 mRNA that has lost m6A modification, resulting in a decrease in the stability of EGR1 mRNA. A decrease in the EGR1 level led to a decrease of in the expression tumor suppressor gene PTEN, resulting in deregulation and loss of cellular homeostasis and thereby fostering EC stem cell traits. Notably, the enforced overexpression of WTAP, EGR1, and PTEN inhibited the oncogenic effects of ECCs and ECSCs in vivo, and the combined overexpression of WTAP + EGR1 and EGR1 + PTEN further diminished the tumorigenic potential of these cells. Our findings revealed that the WTAP/EGR1/PTEN pathway is important regulator of EC stem cell maintenance, chemotherapeutic resistance, and tumorigenesis, suggesting a novel and promising therapeutic avenue for treating EC.

Abstract Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.

Abstract The aim of this study were to estimate associations of sarcopenic status with depressive symptoms. We used mixed-effects linear model to estimate longitudinal association between sarcopenic status and rate of change in 10-item Center for Epidemiologic Studies Depression (CES-D) scores, and used Cox regression model to estimate the association between sarcopenic status and incident depression (CES-D ≥ 10). Stratification analyses were performed when the interactions between sarcopenic status and covariates were significant. A total of 6522 participants were ultimately included. After adjusting for covariates, participants with possible sarcopenia (β = 0.117; 95% CI 0.067 to 0.166; P

Abstract Background Immunotherapies effectively treat human malignancies, but the low response and resistance are major obstacles. Neoantigen is an emerging target for tumor immunotherapy that can enhance anti-tumor immunity and improve immunotherapy. Aberrant alternative splicing is an important source of neoantigens. HNRNPA1, an RNA splicing factor, was found to be upregulated in the majority of tumors and play an important role in the tumor immunosuppressive microenvironment. Methods Whole transcriptome sequencing was performed on shHNRNPA1 SKOV3 cells and transcriptomic data of shHNRNPA1 HepG2, MCF-7M, K562, and B-LL cells were downloaded from the GEO database. Enrichment analysis was performed to elucidate the mechanisms underlying the activation of anti-tumor immunity induced by HNRNPA1 knockdown. mRNA alternative splicing was analyzed and neoantigens were predicted by JCAST v.0.3.5 and Immune epitope database. The immunogenicity of candidate neoantigens was calculated by Class I pMHC Immunogenicity and validated by the IFN-γ ELISpot assay. The effect of shHNRNPA1 on tumor growth and immune cells in vivo was evaluated by xenograft model combined with immunohistochemistry. Results HNRNPA1 was upregulated in a majority of malignancies and correlated with immunosuppressive status of the tumor immune microenvironment. Downregulation of HNRNPA1 could induce the activation of immune-related pathways and biological processes. Disruption of HNRNPA1 resulted in aberrant alternative splicing events and generation of immunogenic neoantigens. Downregulation of HNRNPA1 inhibited tumor growth and increased CD8+ T cell infiltration in vivo. Conclusion Our study demonstrated that targeting HNRNPA1 could produce immunogenic neoantigens that elicit anti-tumor immunity by inducing abnormal mRNA splicing. It suggests that HNRNPA1 may be a potential target for immunotherapy.

The purpose of this study was to investigate the protective effect and underlying mechanism of orexin A on cerebral ischemia-reperfusion injury, specifically through vasodilation mediated by the hypoxia inducible factor-1α (HIF-1α)-Endothelin-1(ET-1)/endothelial nitric oxide synthase (eNOS) pathway. A model of middle cerebral artery occlusion was established in both wild-type SD rats with exogenous orexin A intervention and in orexin A transgenic rats. Neurological deficit scores and cerebral infarction areas were assessed, and ischemic cortical blood flow was monitored. Gene and protein expression levels of HIF-1α, HIF-2α, ET-1, and three types of NOS were detected using real-time RT-qPCR and Western blot analysis, respectively. Additionally, nitric oxide (NO) levels in the cortex were analyzed through biochemical detection methods. Orexin A demonstrated a protective effect by reducing cerebral infarction and improving neurological deficits, which was achieved by increasing cortical blood flow during reperfusion. This protective mechanism was associated with upregulated HIF-1α expression, downregulated ET-1 expression, upregulated eNOS expression, and increased NO production. This study demonstrates the protective effect of orexin A on cerebral ischemia-reperfusion injury, achieved by regulating the release of vasomotor substances to enhance cortical blood flow during reperfusion. These findings suggest that orexin A may represent a potential therapeutic strategy for ischemic stroke.

Disposable electrochemical biosensors with high sensitivity are very fit for point-of-care testing in clinical diagnosis. Herein, amino-functionalized, vertically ordered mesoporous silica films (NH2-VMSF) attached to an electrochemically polarized screen-printed carbon electrode (p-SPCE) are prepared using a simple electrochemical method and then utilized to construct a gated electrochemical aptasensor for rapid and sensitive determination of carcinoembryonic antigen (CEA). After being treated with the electrochemical polarization procedure, p-SPCE has plentiful oxygen-containing groups and improved catalytic ability, which help promote the stability of NH2-VMSF on SPCE without the use of an adhesive layer and simultaneously generate a highly electroactive sensing interface. Owing to the numerous uniform and ultrasmall nanopores of NH2-VMSF, CEA-specific aptamer anchored on the external surface of NH2-VMSF/p-SPCE serves as the gatekeeper, allowing the specific recognition and binding of CEA and eventually impeding the ingress of electrochemical probes [Fe(CN)63−/4−] through the silica nanochannels. The declined electrochemical responses of Fe(CN)63−/4− can be used to quantitatively detect CEA, yielding a wide detection range (100 fg/mL to 100 ng/mL) and a low limit of detection (24 fg/mL). Moreover, the proposed NH2-VMSF/p-SPCE-based electrochemical aptasensor can be applied to detect the amount of CEA in spiked human serum samples, which extends the biological application of a disposable NH2-VMSF/p-SPCE sensor by modulating the biological recognition species.

The high metabolic requirements of cancer cells result in excess accumulation of H+ in the tumor microenvironment. Therefore, the extracellular pH of solid tumors is acidic, whereas the pH of normal tissues is more alkaline. The acidic tumor environment is correlated with tumor metastasis, immune escape, and chemoresistance, but the underlying mechanisms remain elusive. Herein, we demonstrate that sodium bicarbonate, a weakly alkaline compound, induces cytotoxicity in ovarian cancer cells and hinders cancer migration and invasion in vitro. The anti-cancer efficacy of Olaparib can be significantly augmented when combined with sodium bicarbonate. In vivo experiments suggest that the combinatorial treatment of sodium bicarbonate and Olaparib is biocompatible and more effective at inhibiting ovarian cancer growth than either treatment alone. Additionally, RNA-sequencing results reveal that the differentially expressed genes are enriched in pathways related to reactive oxygen species (ROS) generation, such as the cGMP/PKG pathway. The combined treatment increases M1 macrophage composition in tumors and reduces the accumulation of excessive ROS. These findings strongly suggest that sodium bicarbonate holds great potential as an adjuvant treatment by scavenging ROS accumulation and promoting M1 macrophage composition, thereby enhancing Olaparib’s anti-cancer activity.

Endometriosis (EMT) has a significant impact on women’s physical and mental health. In this study, high-throughput sequencing technology was employed to detect differences in gut microbiota between EMT patients and healthy individuals (CTL). Additionally, Spearman correlation analysis was utilized to analyze the correlation between different bacterial genera and EMT biomarkers (CA125 and CA199). The results demonstrated that at the phylum level, the relative abundances of Proteobacteria and Desulfobacterota_G_459546 in the EMT group were significantly higher than those in the CTL group, while the relative abundances of Bacteroidota and Firmicutes_A in the EMT group were significantly lower than those in the CTL group. At the genus level, the relative abundances of Burkholderiales and Sphingomonadales in the EMT group were significantly higher than those in the CTL group, while the relative abundances of Bacteroidales and Roseburia in the EMT group were significantly lower than those in the CTL group. The correlation analysis results show that CA125 and CA199 are significantly positively correlated with Burkholderiales and Sphingomonadales, and significantly negatively correlated with Bacteroidales, Oscillospirales, and Roseburia. The PICRUSt2 results show that the relative abundance in the cell motility and xenobiotics biodegradation and metabolism pathways in the EMT group was higher than that in the CTL group, while the relative abundance in the translation, replication and repair, folding, sorting and degradation, metabolism of terpenoids and polyketides and metabolism of cofactors and vitamins pathways in the EMT group was lower than that in the CTL group. In brief, there is a close correlation between the imbalance of gut microbiota and the onset of EMT. The intestinal microbiota has great significance broad prospects for the prevention, diagnosis and treatment of EMT.

BackgroundDyslipidemia has emerged as a significant clinical risk, with its associated complications, including atherosclerosis and ischemic cerebrovascular disease, presenting a grave threat to human well-being. Hence, it holds paramount importance to precisely predict the onset of dyslipidemia. This study aims to use ensemble technology to establish a machine learning model for the prediction of dyslipidemia.MethodsThis study included three consecutive years of physical examination data of 2,479 participants, and used the physical examination data of the first two years to predict whether the participants would develop dyslipidemia in the third year. Feature selection was conducted through statistical methods and the analysis of mutual information between features. Five machine learning models, including support vector machine (SVM), logistic regression (LR), random forest (RF), K nearest neighbor (KNN) and extreme gradient boosting (XGBoost), were utilized as base learners to construct the ensemble model. Area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to evaluate the model.ResultsExperimental results show that the ensemble model achieves superior performance across several metrics, achieving an AUC of 0.88 ± 0.01 (P < 0.001), surpassing the base learners by margins of 0.04 to 0.20. Calibration curves and DCA exhibited good predictive performance as well. Furthermore, this study explores the minimal necessary feature set for accurate prediction, finding that just the top 12 features were required for dependable outcomes. Among them, HbA1c and CEA are key indicators for model construction.ConclusionsOur results suggest that the proposed ensemble model has good predictive performance and has the potential to become an effective tool for personal health management.

Pregnancy places a metabolic burden on the body including the liver, which is responsible for ensuring adequate nutrition for the maternal and fetal systems. To gain a better understanding of liver adaptation, this study investigates metabolic shifts occurring in livers of pregnant rats. Metabolic capacities of the livers of pregnant and non-pregnant female Wistar rats were assessed using comprehensive metabolic models. Kinetic metabolic models were generated for each animal based on protein abundance data from proteomics analysis allowing for a subject-specific assessment of hepatic metabolic functions. Data are available via ProteomeXchange with identifier PXD050758. Additionally, tissue stiffness, viscosity, and water diffusion obtained from magnetic resonance imaging and elastography were correlated with metabolic capabilities to study the relationship between metabolic function and biophysical properties. Proteome profiling revealed differences in protein expression in the livers of pregnant and non-pregnant animals. Functional analysis showed significant variations in metabolic capacities. Livers of pregnant rats had reduced capacities in carbohydrate and fatty acid metabolism, along with altered urea synthesis. Additionally, there were associations between metabolic functions and biophysical properties highlighting potential links between changes in liver structure and metabolic capacities during pregnancy. In summary, our work reveals extensive hepatic metabolic changes in pregnant rats. The liver adapts its metabolic capacities to ensure whole-body metabolic homeostasis but may struggle to counteract nutritional challenges, such as hypoglycemia. The study, employing a personalized approach combining proteomics, kinetic modeling, and advanced imaging, sheds light on the intricate interplay between hepatic adaptations and medical imaging markers, providing a foundation for further investigations into the implications for maternal and fetal health.

BackgroundThe impact of COVID-19 on older adults’ personality development is essential for emergency management but under-researched. This study seeks to explore the personality profiles of older adults living in the United States and how these profiles transitioned during the pandemic.MethodsLongitudinal data were collected from 3,550 adults aged 60 and older who participated in both the 2016 and 2020 waves of the Health and Retirement Survey (61.18% female, mean age 65.85 in 2016). Personality traits were assessed using the Midlife Development Inventory. COVID-19-related experiences including pandemic concerns, restricted healthcare access, financial instability, work challenges, disrupted social connections, and mutual aid behaviors. Latent Profile Analysis and Transition Analysis were used for analysis.ResultsThree distinct personality profiles were identified: Well-adjusted, Moderate-adjusted, and Poor-adjusted. About 42% of respondents experienced personality changes during the pandemic. Higher levels of COVID-19 concern were linked to an increased likelihood of transitioning to Poor-adjusted from Moderate (OR=1.06, p

Lymphoid proliferations and lymphomas arising in post-transplantation are potentially life-threatening complications after solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT). The lymphoid proliferations and lymphomas arising in post-transplantation originating from different cell lineages in the same patient are highly unusual. Herein, we delineate a case of isolated spinal cord involvement with B cell lymphoid proliferations and lymphomas arising in post-transplantation at 11 months post-transplantation, which was successfully treated with chemotherapy and intrathecal injection. Six months later, the patient again developed lymphoma arising in post-transplantation, presenting with predominant subcutaneous tissue involvement deriving from EBV-positive NK/T cells, and received four courses of chemotherapy. Ultimately, she achieved complete remission (CR). The report further contributes to our new insights into the unusual clinical presentations of lymphoid proliferations and lymphomas arising in post-transplantation.

Rationale & Objective: The development of anuria has been linked to worse clinical outcomes in patients undergoing peritoneal dialysis (PD). Our objective was to investigate the incidence, risk factors, and associated clinical outcomes of anuria within the first year after starting PD. Study Design: Retrospective cohort study. Setting & Participants: Patients who started continuous ambulatory peritoneal dialysis at our center between 2006 and 2020 were included and followed up until January 31, 2023. Exposure: Age, sex, diabetes, temporary hemodialysis, angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs), diuretics, baseline urine volume, serum albumin, daily glucose exposure, peritonitis, and incremental PD. Outcomes: The primary outcome was early anuria, defined as 24-hour urine volume ≤100 mL within the first year of PD initiation. Secondary outcomes included all-cause mortality, cardiovascular disease mortality, technique failure, and peritonitis. Analytical Approach: Cox proportional hazards model. Results: A total of 2,592 patients undergoing continuous ambulatory peritoneal dialysis aged 46.7 ± 14.9 years were recruited. Among them, 58.9% were male, and 24.0% had diabetes. Within the first year of PD therapy, 159 (6.13%) patients developed anuria, with a median duration of 7.53 (interquartile range, 3.93-10.0) months. Higher baseline urine volume (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.90-0.97), higher serum albumin (HR, 0.92; 95% CI, 0.88-0.95), having diabetes before PD (HR, 0.57; 95% CI, 0.35-0.92), and prescribed incremental PD (HR, 0.27; 95% CI, 0.14-0.51) were associated with a reduced risk for early anuria, whereas a higher level of daily glucose exposure (HR, 1.01; 95% CI, 1.00-1.01) was identified as a risk factor for early anuria. Subgroup analyses showed that using ACEis or ARBs was linked to a lower risk of early anuria (HR, 0.25; 95% CI, 0.09-0.69) in diabetic patients. Treating early anuria as a time-dependent covariate, early anuria was associated with a higher risk for all-cause mortality (HR, 1.69; 95% CI, 1.23-2.32) and technique failure (HR, 1.43; 95% CI, 1.00-2.04) after adjusting for confounding factors. Limitations: Single-center and observational study. Conclusions: Among PD patients at a single center in China, early anuria was relatively uncommon but associated with an increased risk of mortality and PD technique failure. Incremental PD, higher baseline urine output and serum albumin, and lower daily glucose exposure were associated with a lower risk of early anuria. Clinical trials are needed to evaluate the optimal PD techniques to preserve residual kidney function and maximaze outcomes. Plain-Language Summary: The development of anuria has been linked to worse clinical outcomes in patients undergoing peritoneal dialysis (PD). However, does the development of early anuria, which is defined as 24-hour urine volume ≤100 mL, within the first year after PD initiation influence the clinical outcomes of these patients? What are the predictors of early anuria? We conducted a single-center retrospective cohort study and found lower baseline urine volume, lower serum albumin, full-dose PD start, absence of diabetes mellitus, higher daily glucose exposure, and in patients with diabetes mellitus, non-use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were associated with early anuria. Early anuria was related to a higher risk for all-cause mortality and technique failure. The results provide information for optimizing patient care and improving the prognosis of patients undergoing PD.

Abstract Mounting clinical evidence suggests that a comprised intestinal barrier contributes to the progression of nonalcoholic steatohepatitis (NASH); nevertheless, the precise mechanism remains elusive. This study unveils a significant upregulation of nuclear receptor‐binding SET domain protein 2 (NSD2) in the intestines of obese humans and mice subjected to a high‐fat cholesterol diet (HFCD). Intestine‐specific NSD2 knockout attenuated the progression of intestinal barrier impairment and NASH, whereas NSD2 overexpression exacerbated this progression. Mechanistically, NSD2 directly regulates the transcriptional activation of Ern1 by demethylating histone H3 at lysine 36 (H3K36me2), thus activating the ERN1–JNK axis to intensify intestinal barrier impairment and subsequently foster NASH progression. These findings elucidate the crucial role of NSD2‐mediated H3K36me2 in intestinal barrier impairment, suggesting that targeting intestinal NSD2 can represent a novel therapeutic approach for NASH.

Abstract Background Studies involving chronic rhinosinusitis with nasal polyps (CRSwNP) have mostly focused on bilateral cases, making unilateral CRSwNP inadequately recognized. This study examined the differences in clinical characteristics, outcomes, and risk factors for poor outcomes between unilateral and bilateral CRSwNP to facilitate a better assessment in the two groups. Methods Demographic information, tissue and blood cells, endoscopic scores, Lund‐Mackay scores, recurrence rates, and disease control conditions were compared between 310 unilateral and 596 bilateral CRSwNP patients. Furthermore, the stepwise regression multivariate Cox proportional hazard models were performed to generate risk factors for poor outcomes in the two groups. Results Bilateral cases exhibited higher rates of smoking, AR, and asthma comorbidities, along with higher numbers of tissue eosinophils and blood inflammatory cells when compared to unilateral patients. Endoscopic nasal polyp score, total computed tomography (CT) score (with scores for each sinus cavity), and adjusted CT scores were significantly higher in the bilateral group, except for a markedly higher adjusted maxillary score in the unilateral group. Furthermore, significantly higher proportions of bilateral patients experienced nasal polyp recurrence, uncontrolled status, and most disease control‐related symptoms at follow‐up. The primary risk factors for poor outcomes were asthma, tissue eosinophils, and total CT score in the bilateral group and blood basophils in the unilateral group. Conclusions Bilateral CRSwNP patients experience worse disease severity and outcomes than their unilateral counterparts. Primarily, asthma, tissue eosinophils, and total CT score were risk factors for poor outcomes in bilateral CRSwNP patients, with blood basophils in unilateral cases.

Demand Response Transit (DRT) services (e.g., dial-a-ride) play a crucial part in supporting transportation systems in small urban and more rural areas. However, the exploration of DRT trip patterns and accessibility, particularly the differences tied to demographics such as gender and age, remains an underdeveloped field. This study begins to fill this research gap by statistically and spatially analyzing real-world DRT trip data from Tennessee. DRT trip purposes were identified based on origin and destination land uses. Statistical analysis was conducted to evaluate DRT travel patterns for passengers of different demographic groups, particularly women and the elderly. Spatial analysis identified areas with higher DRT trip demand and limited DRT accessibility as potential essential destination deserts. The results show that women took more DRT trips across all purposes (e.g., Home-Healthcare, Home-Home, and Home-Leisure) except for Home-Work. About 36.8% of the DRT trips were made by the elderly, primarily for Home-Healthcare trips (67%), and they preferred shorter DRT trips. Spatial analysis revealed disparities in potential essential destination deserts for the elderly and females, as well as differences in possible deserts by trip purpose (e.g., healthcare-related trips). This study contributes to the literature by proposing a methodological framework for assessing DRT travel patterns and accessibility, which has been excluded from most of the prior literature on accessibility.

Abstract Periodontal disease is a prevalent inflammatory condition affecting the tissues and bone surrounding the teeth, posing significant challenges to oral health. Current treatments often fall short due to incomplete removal of bacteria and plaque, irreversible damage to gums and bone, and their cost and time‐consuming nature. Stem cell therapy offers a promising alternative that potentially addresses these limitations. This review delves into the biology, mechanisms, and applications of dental stem cells (DSCs) in alveolar bone and periodontal regeneration. We begin with an overview of various stem cell types and their characteristics, highlighting their role in tissue regeneration and the mechanisms involved. Subsequently, we examine preclinical and clinical studies that demonstrate the efficacy and safety of DSC therapy, showcasing their potential in restoring periodontal health. The discussion also extends to the critical challenges and future directions in the field, emphasizing the necessity for standardized protocols and rigorous research to fully integrate DSC‐based therapies into routine clinical practice. This review underscores the transformative potential of DSCs in regenerative dentistry, aiming to provide a comprehensive understanding that can propel further advancements and ultimately improve patient outcomes in periodontal therapy.

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in‐depth exploration within this scientific domain.

Hypertrophic scarring (HS) is a complication of wound healing that causes physiological and psychological distress in patients. However, the possible mechanism underlying HS is not fully understood, and there is no gold standard for its treatment. Natural products are more effective, economical, convenient, and safe than existing drugs, and they have a wide application prospect. However, there is a lack of literature on this topic, so we reviewed in vivo, in vitro, and clinical studies and screened natural products showing beneficial effects on HS that can become potential therapeutic agents for HS to fill in the gaps in the field. In addition, we discussed the drug delivery systems related to these natural products and their mechanisms in the treatment of HS. Generally speaking, natural products inhibit inflammation, myofibroblast activation, angiogenesis, and collagen accumulation by targeting interleukins, tumor necrosis factor-α, vascular endothelial growth factors, platelet-derived growth factors, and matrix metalloproteinases, so as to play an anti-HS effects of natural products are attributed to their anti-inflammatory, anti-proliferative, anti-angiogenesis, and pro-apoptotic (enhancing apoptosis and autophagy) roles, thus treating HS. We also screened the potential therapeutic targets of these natural compounds for HS through network pharmacology and constructed a protein-protein interaction (PPI) network, which may provide clues for the pharmacological mechanism of natural products in treating this disease and the development and application of drugs.

Objective To explore circular RNAs(circRNAs) that regulate ferroptosis in cervical cancer,in the development of new therapeutic targets. Methods The differentially expressed circRNAs(DEcircRNAs),differentially expressed microRNAs(DEmiRNAs) and differentially expressed mRNAs(DEmRNAs) between cervical cancer and control groups were analyzed based on GSE102686,TCGA,GSE9750.circRNAs and mRNAs with targeted regulatory relationships with DEmiRNAs were predicted by the Starbase database and compared with differential analysis results.Enrichment analysis of mRNAs was performed to identify mRNAs associated with cell death(cell cycle,apoptosis,and iron death) and to construct relevant competitive endogenous RNAs(ceRNAs) regulatory networks.Univariate Cox regression analysis was performed to identify miRNAs and mRNAs that significantly affect patient outcomes.Cervical cancer tissues and distant control cervical tissue samples from 12 patients with cervical cancer were collected to detect gene expression using quantitative reverse transcription polymerase chain reaction(qRT-PCR) and Western blot,and targeted binding of genes was detected using a dual-luciferase reporter. Results A total of 179 DEcircRNAs,93 DEmiRNAs,and 739 DEmRNAs were identified between cervical cancer and controls,and 160 DEcircRNAs were found,and 565 DEmRNAs were targeted to DEmiRNAs.The ceRNAs regulatory network of circ_0001461/miR-145-5p/transferrin receptor(TFRC) was finally identified to be associated with ferroptosis.circ_0001461 and TFRC were significantly upregulated and miR-145-5p was downregulated in cervical cancer tissues(P

Abstract Morchella spongiola is a highly prized mushroom for its delicious flavor and medical value and is one of the most flourishing, representative, and dominant macrofungi in the Qilian Mountains of the Qinghai-Tibet Plateau subkingdoms (QTPs). However, the understanding of M. spongiola remains largely unknown, and its taxonomy is ambiguous. In this study, we redescribed a unique species of M. spongiola, i.e., micromorphology, molecular data, genomics, and comparative genomics, and the historical biogeography of M. spongiola were estimated for 182 single-copy homologous genes. A high-quality chromosome-level reference genome of M. spongiola M12-10 was obtained by combining PacBio HiFi data and Illumina sequencing technologies; it was approximately 57.1 Mb (contig N50 of 18.14 Mb) and contained 9775 protein-coding genes. Comparative genome analysis revealed considerable conservation and unique characteristics between M. spongiola M12-10 and 32 other Morchella species. Molecular phylogenetic analysis indicated that M. spongiola M12-10 is similar to the M. prava/Mes-7 present in sandy soil near rivers, differentiating from black morels ~ 43.06 Mya (million years ago), and diverged from M. parva/Mes-7 at approximately 12.85 Mya (in the Miocene epoch), which is closely related to the geological activities in the QTPs (in the Neogene). Therefore, M. spongiola is a unique species rather than a synonym of M. vulgaris/Mes-5, which has a distinctive grey-brown sponge-like ascomata. This genome of M. spongiola M12-10 is the first published genome sequence of the species in the genus Morchella from the QTPs, which could aid future studies on functional gene identification, germplasm resource management, and molecular breeding efforts, as well as evolutionary studies on the Morchella taxon in the QTPs.

Abstract Background Mindfulness-based interventions have been tested to be the effective approach for preventing/reducing burnout in medical students. Therefore, this systematic review and meta-analysis aimed to synthesize the scientific evidence and quantify the pooled effect of MBIs on the burnout syndrome in medical students. Methods A comprehensive literature search was conducted in the databases, including PubMed, Embase, ERIC, PsycINFO, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), China National knowledge Information Database (CNKI) and WanFang Database from database inception to February 2023 using the terms of “mindfulness”, “burnout” and “medical students”. Two reviewers independently reviewed the studies, and extracted the data of the eligible studies, as well as assessed the risk of bias. A random-effects model was employed to calculate the standardized mean differences (SMD) with 95% confidence intervals (CI) of overall burnout and its sub-domains of burnout (i.e., emotional exhaustion, cynicism, and academic efficacy). Results Of 316 records in total, nine studies (with 810 medical students) were ultimately included. The four RCT studies demonstrated an overall judgment of some concerns risk of bias, and the overall risk of biases of the five qRCT studies were judged as serious. In term of the SORT, the RCT and qRCT studies were evaluated as level 2 evidence, and the overall strength of recommendation was classified as B (limited-quality patient-oriented evidence). The pooled analysis showed that MBIs were associated with significant small to moderate improvements for medical students’ overall burnout (SMD=-0.64; 95% CI [-1.12, -0.16]; P = 0.009) in the included four RCTs, emotional exhaustion (SMD=-0.27; 95% CI [-0.50, -0.03]; P = 0.03) and academic efficacy (SMD = 0.43; 95% CI [0.20, 0.66]; P

Abstract Introduction This study aimed to analyze the risk factors associated with isoniazid-resistant and rifampicin-susceptible tuberculosis (Hr-TB) in adults. Method The clinical data of 1,844 adult inpatients diagnosed with culture-positive pulmonary tuberculosis (PTB) in Nanjing Second Hospital from January 2019 and December 2021 were collected. All culture positive strain from the patient specimens underwent drug susceptibility testing (DST). Among them, 166 patients with Hr-TB were categorized as the Hr-TB group, while the remaining 1,678 patients were classified as having drug-susceptible tuberculosis (DS-TB). Hierarchical logistic regression was employed for multivariate analysis to identify variables associated with Hr-TB. Results: Multivariate logistic regression analysis revealed that individuals with diabetes mellitus (DM) (OR 1.472, 95% CI 1.037–2.088, p = 0.030) and a history of previous tuberculosis treatment (OR 2.913, 95% CI 1.971–4.306, p = 0.000) were at higher risk of developing adult Hr-TB, with this risk being more pronounced in male patients. Within the cohort, 1,640 patients were newly treated, and among them, DM (OR 1.662, 95% CI 1.123–2.461, p = 0.011) was identified as risk factors for Hr-TB. Conclusions: Diabetes mellitus is a risk factor for Hr-TB in adults, and the contribution of diabetes as a risk factor was more pronounced in the newly treatment or male subgroup. And previous TB treatment history is also a risk factor for Hr-TB in adults.

Abstract This study explores the detonation characteristics and compositional changes of pulverized coal, focusing on its use in Rotary Detonation Wave (RDW) technologies. While pulverized coal has shown high fuel efficiency in RDW settings, transitioning from theory to practical detonation engineering presents substantial scientific and technical hurdles. A key issue is the reprocessing of detonation byproducts for in-situ coal mine gob filling, a topic that has received little attention. Utilizing advanced methods like X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), this paper investigates the micro-morphology, composition, and aromatic structures of gas–solid products pre and post-detonation at the Tashan Coal Mine's 2305 working face. Results indicate that coal dust from the underground mining face has enhanced detonation characteristics, with the addition of coal powder fuel extending the gas detonation limits. This benefits economic aspects by reducing reliance on gas fuel and lowering detonation fuel costs. The highest recorded detonation wave velocity was 2450 m/s, 14.8% greater than that of coal dust from external sources, suggesting more effective energy release and pressure gain. Furthermore, the study links detonation combustion intensity to coal's aromatic properties, noting a post-detonation aromaticity index (I) of 0.4941. This indicates an improvement in the aromatic structure under high-temperature conditions, vital for coal's reactivity and energy efficiency in RDW applications. This research not only deepens the understanding of coal dust combustion mechanisms but also advances clean coal utilization and deep coal fluidization mining, addressing significant RDW technological challenges.

Abstract Background Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Methods Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. Results In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p