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Abstract Background Diabesity, a co-occurrence of diabetes and obesity, is a growing public health concern globally. The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been associated with various metabolic disorders. This study aimed to investigate the association between TyG index and new-onset diabesity in a national longitudinal study. Methods We utilized data from the China Health and Retirement Longitudinal Study (CHARLS). Baseline data from the first wave (2011) and follow-up data from the third wave (2015) were analyzed. A Competing risks model based on Fine and Gray’s subdistribution hazard approach was employed to examine the association between the TyG index and developing of three mutually exclusive outcomes: remaining free of diabetes and obesity, diabetes alone, and new-onset diabesity (co-occurrence of diabetes and obesity). Results A total of 6,976 participants were included in the analysis. During a mean follow-up period of 4.0 years, a total of 557 diabetes and 155 diabesity were recorded, respectively. After adjusting for socio-demographic information, lifestyle and comorbidities, compared with participants in the lowest quartile of TyG, the corresponding adjusted subdistribution hazard ratios (HRs) with 95% confidence intervals (95% CIs) for participants in the second, third, and fourth quartiles were 2.112 (95% CI: 1.047–4.259; P-value = 0.037), 2.911 (95% CI: 1.481–5.722, P-value = 0.002), and 4.305 (95% CI: 2.220–8.346, P-value

Abstract Objective The objectives of this study were to explore emotional behavioral problems (EBP) associated with learning burnout (LB) among returned migrant middle school students. In addition, the mediating mechanism of internet addiction (IA) and social support (SS) in this relationship was investigated. We also verified the chain-mediating effect of IA and SS on the EBP of returned migrant middle school students and LB. Methods This study used the sample data collected from the “Health Status Survey of Middle School Students in Guizhou Province, China” conducted by the research group. The baseline survey of 36 secondary schools from December 2021 to January 2022 in Guizhou Provine, China. Based on this sample data, middle school students who met the following conditions were selected as study subjects. 2020 returned migrant secondary school students were finally obtained as the subjects of this study. The Strength and Difficulty Questionnaire (SDQ), Adolescent Student Burnout Scale (ASBI), Internet Addiction Test (IAT), and Social Support Scale (SSS) were used to assess EBP, LB, IA, and SS among returned migrant secondary school students. Serial multiple mediation analysis and the bootstrap method were used to investigate the mediation effects of IA and SS (PROCESS model 6). Results Prevalence of EBP was classified in the abnormal (11.9%) or borderline (17.1%) categories based on the total difficulties scores among returned migrant middle school students. A serial multiple mediation model was generated. The mediation effect of IA and SS on the pathway from LB to EBP was 31.25% (direct effect = 0.373, total indirect effect = 0.170). The association between LB and SS was partially mediated by IA (direct effect=-0.356, indirect effect=-0.065). The proposed model fits the data well. Conclusion This study found that lower IA and higher SS can effectively reduce EBP caused by LB among returned migrant middle school students. It is suggested that parents, schools, and government departments pay attention to IA and SS problems caused by LB in returned migrant middle school students, and prevent and avoid EBP. Returned migrant middle school students should take the initiative to identify the factors that harm their physical and mental health for self-regulation, and establish reliable SS, rather than meet psychological needs through IA, to reduce the occurrence of EBP.

Abstract This article proposes a method for evaluating the dominant factors of grid‐connected inverters based on impedance models, which can achieve quantitative calculation of the dominant factors of system stability. First, an impedance model was established, and an analysis method based on the impedance model was proposed to calculate the absolute sensitivity. The control and circuit parameters of the grid‐connected inverter were calculated, and the impact trend of each parameter on system stability was obtained. Then, in order to eliminate the influence of dimensions between various parameters and achieve traceability of the dominant factors of stability, an absolute sensitivity stability analysis method was proposed to analyze the influencing factors of different frequency bands, and based on this, a suppression scheme of harmonic resonance is proposed. Finally, the accuracy of the method was verified through impedance sweep based on grid‐connected inverters.

Introduction: Cell transplantation is an emerging and effective therapeutic approach for enhancing uterine adhesions caused by endometrial damage. Currently, human umbilical cord blood mononuclear cells (HUCBMCs) have been extensively for tissue and organ regeneration. However, their application in endometrial repair remains unexplored. Our investigation focuses on the utilization of HUCBMCs for treating endometrial injury. Methods: The HUCBMCs were isolated from health umbilical cord blood, and co-cultured with the injured endometrial stromal cells and injured endometrial organoids. The cell proliferation and apoptosis were measured by cck8 assays and flow cytometry. Western blotting was used to detect the expression of PTEN, AKT and p-AKT. Immunofluorescence assay revealed expression levels of epithelial-mesenchymal transition (EMT) -related markers such as E-cadherin, N-cadherin, and TGF-β1. The endometrial thickness, fibrosis level, and glandular number were examined after the intravenous injection of HUCBMCs in mouse endometrial models. Immunohistochemistry was employed to assess changes in growth factors vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) as well as fibrosis markers α-SMA and COL1A1. Additionally, expressions of EMT-related proteins E-cadherin and N-cadherin were evaluated. Results: HUCBMCs significantly improved the proliferation and reduced the apoptosis of damaged endometrial stromal cells (ESCs), accompanied by up-regulation of phospho-AKT expression. HUCBMCs increased endometrial thickness and glandular count while decreasing fibrosis and EMT-related markers in mouse endometrial models. Furthermore, EMT-related markers of ESCs and endometrial organoids were significantly decreased. Conclusions: Our findings suggest that HUCBMCs plays a pivotal role in mitigating endometrial injury through the attenuation of fibrosis. HUCBMCs may exert a reverse effect on the EMT process during the endometrium reconstruction.

Abstract Background Absent in melanoma 2 (AIM2) inflammasome-dependent pyroptosis and neutrophil extracellular traps (NETs) have been implicated in chronic liver disease (CLD). However, the specific intrahepatic cell type that undergoes AIM2 inflammasome-dependent pyroptosis and how their interaction augments hepatic inflammation/fibrosis remains unclear. Methods The expression and correlation of AIM2 inflammasome-dependent pyroptosis-related indicators and NETs were analyzed in biopsy tissue and blood specimens from chronic hepatitis patients (CHs). Cell-based experiments were conducted to investigate their interaction. In vitro and in vivo experiments were used to analyze their effects on the progression of hepatic inflammation/fibrosis as well as their clinical importance. Results Elevated levels of AIM2 inflammasome-dependent pyroptosis indicators and NETs were detected in biopsy tissue and blood specimens. Circulating NETs were positively correlated with pyroptosis-related indicators, and both were related with disease severity. Confocal imaging revealed that AIM2 was mainly localized to hepatic macrophages, indicating that hepatic macrophages were the major cell type that underwent pyroptosis. NETs were directly engulfed by macrophages and then stimulated AIM2 inflammasome-dependent macrophage pyroptosis in vitro, which amplified the activation of hepatic stellate cells (HSCs) and increased collagen deposition. Administration of the NETs degradation agent DNase I or the AIM2 inflammasome activation inhibitor ODN A151 effectively alleviated chronic liver inflammation/fibrosis progression in vivo. Conclusions NETs-induced AIM2 inflammasome-dependent pyroptosis in macrophages facilitates liver inflammation/fibrosis progression. The identified NET–AIM2 inflammasome cascade could serve as a novel therapeutic target for hepatic inflammation/fibrosis progression.

Abstract Arid and semi-arid regions, which account for more than 30% of the Earth's land area, increasingly dominate the spatiotemporal trends in global carbon fluxes. The Horqin Sandy Land is a typical semi-arid fragile ecosystem in northern China. Understanding the components of the carbon budget in ecosystems under conditions of extreme soil moisture limitations provides a foundation for comprehending the carbon balance in semi-arid ecosystems. The seasonal and diurnal variations in soil respiration (R s) in semi-mobile dune (SD) and meadow wetland (MW) ecosystems of the Horqin Sandy Land were examined, and the sources of CO2 emissions from R s were identified using stable carbon isotopes. The responses of R s and ecosystem respiration (R eco) to environmental temperature, moisture and leaf area index (LAI) were revealed. The results showed that on a seasonal scale, in SD with soil moisture content (M s) below field capacity (FC), M s had a greater influence on R s than soil temperature (T s) during the growing season. Changes in the LAI during the middle and late growth period affected R s by altering root carbon supply. In MW, the most favorable M s for R s was near FC. The increase in LAI before mowing could effectively promote root and soil microbial respiration, and the decomposition of litter driven by T s was the main form of R s at this time. After mowing, root respiration and soil microbial respiration were the main processes contributing to CO2 emissions. On a daily scale, relative humidity (RH) dominated the R s variation under dry conditions, whereas in other conditions, the R s was adequately explained by temperature in SD and MW. The overall R eco was larger than R s, but occasionally R s was greater than R eco. The effects of temperature, moisture and LAI on R eco and R s varied with growing season. Adding factors, such as ecosystem type, vegetation growth, water, and heat, to the carbon cycle model can improve predictions of carbon emissions, and aid in further management decisions in arid and semi-arid areas.

Abstract Background In China, the problem of HIV infection among the older people has become increasingly prominent. This study aimed to analyze the pattern and influencing factors of HIV transmission based on a genomic and spatial epidemiological analysis among this population. Methods A total of 432 older people who were aged ≥ 50 years, newly diagnosed with HIV-1 between January 2018 and December 2021 and without a history of ART were enrolled. HIV-1 pol gene sequence was obtained by viral RNA extraction and nested PCR. The molecular transmission network was constructed using HIV-TRACE and the spatial distribution analyses were performed in ArcGIS. The multivariate logistic regression analysis was performed to analyze the factors associated with clustering. Results A total of 382 sequences were successfully sequenced, of which CRF07_BC (52.3%), CRF01_AE (32.5%), and CRF08_BC (6.8%) were the main HIV-1 strains. A total of 176 sequences entered the molecular network, with a clustering rate of 46.1%. Impressively, the clustering rate among older people infected through commercial heterosexual contact was as high as 61.7% and three female sex workers (FSWs) were observed in the network. The individuals who were aged ≥ 60 years and transmitted the virus by commercial heterosexual contact had a higher clustering rate, while those who were retirees or engaged other occupations and with higher education degree were less likely to cluster. There was a positive spatial correlation of clustering rate (Global Moran I = 0.206, P

Abstract Introduction Early prediction and timely treatment are essential for minimizing the risk of visual loss or blindness of retinopathy of prematurity, emphasizing the importance of ROP screening in clinical routine. Objective To establish predictive models for ROP occurrence based on the risk factors using artificial neural network. Methods A cohort of 591 infants was recruited in this retrospective study. The association between ROP and perinatal factors was analyzed by univariate analysis and multivariable logistic regression. We developed predictive models for ROP screening using back propagation neural network, which was further optimized by applying genetic algorithm method. To assess the predictive performance of the models, the areas under the curve, sensitivity, specificity, negative predictive value, positive predictive value and accuracy were used to show the performances of the prediction models. Results ROP of any stage was found in 193 (32.7%) infants. Twelve risk factors of ROP were selected. Based on these factors, predictive models were built using BP neural network and genetic algorithm-back propagation (GA-BP) neural network. The areas under the curve for prediction models were 0.857, and 0.908 in test, respectively. Conclusions We developed predictive models for ROP using artificial neural network. GA-BP neural network exhibited superior predictive ability for ROP when dealing with its non-linear clinical data.

ObjectiveThis study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.MethodsMale Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test.ResultsOVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions.ConclusionThe retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.

Rapid urbanization intensifies the challenges of achieving satisfaction and equity in ecosystem services (ESs). Beginning with a theoretical overview, we identify five pivotal challenges in managing urban ESs, forming the basis for our integrative analysis. Employing a multi-level analytical perspective, our research quantifies ESs satisfaction through supply–demand ratios and evaluates ESs equity via supply–demand Gini coefficient. Simultaneously explored the driving force relationship between these two dimensions. This study uses Guangdong Province, a typical urbanized area in China, as a case study to assess the supply and demand relationships of four regulating ESs: water retention, soil retention, carbon storage, and water purification. Our results highlight the disparity in ESs management effectiveness across different scales while the overall assessments might suggest adequate or equitable ESs, localized assessments within cities and regions often uncover specific ESs issues. A pivotal aspect is that single-factor critical to ESs satisfaction or equity dimension may have limited or opposing importance in another, but interactive effects of multiple factors can effectively mitigate these divergent impacts through non-linear synergies. These insights not only reveal the multiplex impacts of natural–social–economic drivers on urban expansion but also guide the targeted development in different management scale, multi-dimensional management strategies to address these disparities. This approach enriches the discourse on sustainable urban development and provides a robust framework for addressing the nuanced challenges of urban ESs management.

IntroductionWith the continuous development of the global aging trend, the mental health of older adults has been a concern by the world. The living space of older adults is limited due to the decline of their activity function. Neighborhood environment, especially the neighborhood social environment, has become an important factor affecting the mental health of older adults. Therefore, this study explores the mechanism that influences the social environment of the neighborhood and the mental health of older adults, the mediating effect of subjective well-being (SWB), and the moderating effect of green space.MethodsBased on the 2018 China Labor Dynamics Survey, this study used the structural equation model to explore the mediating effect of neighborhood social environment (neighborhood ties, social trust, community security) on the mental health of older adults through SWB and the moderating effect of green space.ResultsSocial trust and community security are both directly and positively associated with older adults’ mental health. At the same time, neighborhood ties, social trust, and community security can promote the mental health of older adults by positively affecting SWB, while green space has an enhanced moderating effect between neighborhood ties and mental health.DiscussionThis study enriches the empirical research on neighborhood social environment and mental health. First of all, older adults living in communities with good safety conditions and high social trust are less affected by negative emotions and tend to have good mental health. Second, deeper neighborhood ties, higher social trust, and safer community environments help older adults to be less disturbed by negative situations, have a positive effect on their SWB, and indirectly promote mental health. At the same time, green space can provide a place for older adults to socialize, enhance the positive impact of neighborhood ties on SWB, and further promote the mental health of older adults. Finally, this study suggests that the government and community managers pay attention to the construction of neighborhood social environment and green space, and provide support for “healthy community” and “healthy aging” planning.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI), with gender-specific differences in susceptibility. However, the mechanism underlying this phenomenon remains unclear. Our study reveals that the gender-specific differences in susceptibility to APAP-induced hepatotoxicity are due to differences in the gut microbiota. Through microbial multi-omics and cultivation, we observed increased gut microbiota-derived deguelin content in both women and female mice. Administration of deguelin was capable of alleviating hepatotoxicity in APAP-treated male mice, and this protective effect was associated with the inhibition of hepatocyte oxidative stress. Mechanistically, deguelin reduced the expression of thyrotropin receptor (TSHR) in hepatocytes with APAP treatment through direct interaction. Pharmacologic suppression of TSHR expression using ML224 significantly increased hepatic glutathione (GSH) in APAP-treated male mice. These findings suggest that gut microbiota-derived deguelin plays a crucial role in reducing APAP-induced hepatotoxicity in female mice, offering new insights into therapeutic strategies for DILI.

ObjectiveThis study aims to analyze the lipid metabolism patterns and identify risk factors for dyslipidemia in Wilson’s Disease (WD), offering novel insights into diagnosis and treatment strategies for unexplained dyslipidemia.MethodsData from Wilson’s disease patients hospitalized at the First People’s Hospital of Shanghai from December 2008 to February 2015 were collected. Patients were categorized into normal lipid (46 cases) and dyslipidemia (42 cases) groups based on lipid levels. Group analyzes were conducted using t-tests, chi-square analysis, and rank sum tests. Spearman correlation, multiple linear regression, or Logistic regression were employed to identify relevant influencing factors.Results1. The incidence of abnormal blood lipids in a series of Wilson’s disease patients was 47.73% (25.12 ± 1.29 years old), and the incidence of control healthy group was 27.40%, with proportions of hypercholesterolemia, hypertriglyceridemia, and low-density lipoprotein cholesterol being 14.77, 30.68, and 29.63%, respectively; 2. Significant differences were observed between the dyslipidemia and normal WD groups in AST/ALT ratio, liver parenchymal echo, liver surface, spleen area, and ultrasound total score.3. Low-and high-density lipoprotein cholesterols (LDL-c and HDL-c) showed no significant correlation with these indicators. Triglyceride (TG) exhibited moderately negative correlation with AST/ALT, liver parenchymal echo, spleen area, and ultrasound score. Total cholesterol (TC) displayed low negative correlation with these factors.Conclusion1. Dyslipidemia incidence in Wilson’s disease patients may exceed that of the normal population, especially in adolescents with unexplained abnormal lipid metabolism; 2. Patients with mild to moderate liver damage are predisposed to elevated triglycerides and total cholesterol, reflecting liver damage impact on lipid metabolism; 3. Glucose metabolism is not implicated in WD-related dyslipidemia; 4. No significant correlation was found between abnormal lipid metabolism and blood concentration of trace elements in WD patients.

Abstract Objective The objective of this study was to conduct a comprehensive analysis of the molecular transmission networks and transmitted drug resistance (TDR) patterns among individuals newly diagnosed with HIV-1 in Nanjing. Methods Plasma samples were collected from newly diagnosed HIV patients in Nanjing between 2019 and 2021. The HIV pol gene was amplified, and the resulting sequences were utilized for determining TDR, identifying viral subtypes, and constructing molecular transmission network. Logistic regression analyses were employed to investigate the epidemiological characteristics associated with molecular transmission clusters. Results A total of 1161 HIV pol sequences were successfully extracted from newly diagnosed individuals, each accompanied by reliable epidemiologic information. The analysis revealed the presence of multiple HIV-1 subtypes, with CRF 07_BC (40.57%) and CRF01_AE (38.42%) being the most prevalent. Additionally, six other subtypes and unique recombinant forms (URFs) were identified. The prevalence of TDR among the newly diagnosed cases was 7.84% during the study period. Employing a genetic distance threshold of 1.50%, the construction of the molecular transmission network resulted in the identification of 137 clusters, encompassing 613 nodes, which accounted for approximately 52.80% of the cases. Multivariate analysis indicated that individuals within these clusters were more likely to be aged ≥ 60, unemployed, baseline CD4 cell count ≥ 200 cells/mm3, and infected with the CRF119_0107 (P

Typhoon disaster factors show multiplicity, so the risk assessment of typhoon-related disasters is more difficult than other hazards. Using the typhoon precipitation and maximum wind speed data of 81 national meteorological stations and 1 035 regional automatic meteorological stations in Anhui Province, a comprehensive typhoon wind and rain intensity index is first constructed. Then the typhoon wind and rain intensity index and disaster pregnant environment impact coefficient are used to assess the risk of typhoon disasters. According to the theory of natural disaster risk assessment, the risk assessment of housing damage by typhoon disaster in Anhui Province is conducted by integrating disaster-causing hazards, exposure level and vulnerability of disaster-bearing bodies. The results show that Anhui Province is affected by about 1.9 typhoons per year on average, with a duration of 2-4 days. The results are as follows. The southern part and mountainous areas usually have more typhoon precipitation than the northern part and plain areas. The high-hazard region caused by typhoon disasters is mainly located in the southern mountainous and Dabie Mountains in Anhui Province, with the relatively high-hazard region in the east of Jianghuai region, and the low-hazard area in most of the regions to the north of the Huaihe River and in the northwest of Jianghuai region. The high and relatively high-risk area of housing damage caused by typhoon disasters is located in the Dabie Mountains, the eastern part of the Jianghuai region, and the southern mountainous area in Anhui Province. These areas are generally high in elevation, and easily suffer from geological disasters and mountain floods during typhoon transit. In addition, the vulnerability of houses is high, which further causes a high risk of house collapse and damage. The medium-risk region is scattered in the Huaihe River region and Jiangnan region. Lower and low-risk areas are located in the central and western parts to the north of the Huaihe River, regions along the Yangtze River, and main urban areas. Using reports on house damage caused by typhoons from different counties in Anhui Province, the zoning results are verified through spatial consistency and scatter correlation. A high degree of spatial consistency between the risk zoning results and the actual damage, with scatter correlation between them passing a significance test of 0.01, indicating that the risk zoning results of housing damage by typhoon disaster in Anhui Province are basically consistent with the actual situation.

Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls. They release inflammatory molecules that attract additional immune cells, leading to further macrophage recruitment and plaque development. In this study, we develop an osteopontin (OPN) antibody-conjugated niobium carbide (Nb2C-aOPN) MXenzyme designed to selectively target and mildly ablate foam cells while reducing inflammation in the plaque microenvironment. This approach utilizes photonic hyperthermia to decrease plaque size by enhancing cholesterol regulation through both passive cholesterol outflow and positive cholesterol efflux. Nb2C-aOPN MXenzyme exhibits multiple enzyme-mimicking properties, including catalase, superoxide dismutase, peroxidase and glutathione peroxidase, and acts as a scavenger for reactive oxygen and nitrogen species. The inhibition of reactive oxygen and nitrogen species synergizes with photothermal ablation to promote positive cholesterol efflux, leading to reduced macrophage recruitment and a shift in macrophage phenotype from M1 to M2. This integrative strategy on cholesterol regulation and anti-inflammation highlights the potential of multifunctional 2D MXenzyme-based nanomedicine in advancing atherosclerotic regression.

Purpose This cross-sectional cohort-comparison observational study investigated the value of high-frame-rate vector flow (V Flow) imaging for evaluating differences in carotid plaque shape and biomechanical parameters in patients with mild stenosis according to a recent history of ipsilateral ischemic stroke. Methods The present study included 352 patients from February 2023 to October 2023, who were categorized as symptomatic or asymptomatic based on a history of recent ischemic stroke and ipsilateral ischemic lesions detected on head computed tomography or magnetic resonance imaging. A Mindray Resona R9 system was used for B-mode ultrasonography and V Flow imaging. The upstream and downstream surfaces of the plaques were examined at the carotid bifurcation for wall shear stress (WSS), oscillatory shear index (OSI), and turbulence index, which performed peri-plaque biomechanical condition. Multivariable logistic regression models were used to determine associations between plaque shape, V Flow parameters, and ischemic stroke. Results Symptomatic patients exhibited higher WSS values for the upstream and downstream surfaces of carotid plaque, as well as higher OSI and turbulence index values for the downstream surface. Type Ⅲ plaques and higher WSS and OSI values for the downstream surface of the plaque were significantly associated with ischemic stroke. Type Ⅲ plaques were more prevalent in symptomatic patients and demonstrated much higher WSS and OSI values for the downstream plaque surface in both groups. Conclusion High-frame-rate V Flow imaging could assess peri-plaque biomechanical forces and may provide effective imaging biomarkers for early prediction of ischemic stroke in patients with mild stenosis.

Abstract The presence of dysbiotic cervicovaginal microbiota has been observed to be linked to the persistent development of cervical carcinogenesis mediated by the human papillomavirus (HPV). Nevertheless, the characteristics of the cervical microbiome in individuals diagnosed with cervical cancer (CC) are still not well understood. Comprehensive analysis was conducted by re-analyzing the cervical 16S rRNA sequencing datasets of a total of 507 samples from six previously published studies. We observed significant alpha and beta diversity differences in between CC, cervical intraepithelial neoplasia (CIN) and normal controls (NC), but not between HPV and NC in the combined dataset. Meta-analysis revealed that opportunistic pernicious microbes Streptococcus, Fusobacterium, Pseudomonas and Anaerococcus were enriched in CC, while Lactobacillus was depleted compared to NC. Members of Gardnerella, Sneathia, Pseudomonas, and Fannyhessea have significantly increased relative abundance compared to other bacteria in the CIN group. Five newly identified bacterial genera were found to differentiate CC from NC, with an area under the curve (AUC) of 0.8947. Moreover, co-occurrence network analysis showed that the most commonly encountered Lactobacillus was strongly negatively correlated with Prevotella. Overall, our study identified a set of potential biomarkers for CC from samples across different geographic regions. Our meta-analysis provided significant insights into the characteristics of dysbiotic cervicovaginal microbiota undergoing CC, which may lead to the development of noninvasive CC diagnostic tools and therapeutic interventions.

Abstract Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.

Olmsted syndrome (OS) is a rare congenital skin disorder, typically characterized by symmetrical, severe palmoplantar and periorificial keratoderma, often accompanied by alopecia, and onychodystrophy, with varying degrees of pruritus and pain. Gain-of-function variants of the transient receptor potential cation channel subfamily V member 3 (TRPV3) were described as a cause of OS. Here, we report an atypical case of OS caused by a novel mutation in the TRPV3 gene that has not been described before in OS. The patient presented with disabling, bilateral palmoplantar keratoderma, and subsequently developed squamous cell carcinoma on the right sole. Genetic analysis identified a novel heterozygous p.Val306Met missense mutation in the exon 8 of TRPV3. Our findings expand the phenotypic spectrum of TRPV3-related OS and underscore the need for vigilant long-term monitoring of these patients.

China is currently undergoing a phase of high-quality development, with increasing emphasis on the circular economy, energy conservation, and environmental protection by both the government and enterprises. This paper examines a secondary supply chain comprising manufacturers and retailers, focusing on three supply chain decision-making models: one where the manufacturer is the channel leader, one where the retailer is the channel leader, and one where both parties have equal power. The study investigates the impact of manufacturers misrepresenting their Corporate Social Responsibility (CSR) information and the challenges associated with recycling efforts on the optimal performance of the supply chain. The findings reveal that when manufacturers lead the supply chain, they do not misrepresent their private information. However, when retailers dominate, manufacturers tend to underreport their CSR levels and the difficulty of recycling efforts. In scenarios where manufacturers and retailers have equal power, manufacturers do not misreport the difficulty of recycling but do underreport their CSR levels. This misreporting benefits the manufacturers at the expense of retailers and overall supply chain profitability, while also discouraging the recycling of used products. Across all three power structures, the study shows that retailers’ marketing efforts decrease as the misrepresentation of recycling difficulty increases, and increase as the misrepresentation of CSR levels increases. To mitigate the effects of manufacturers’ misreporting under information asymmetry, the paper proposes revenue-sharing contracts and two-part pricing contracts to coordinate the closed-loop supply chain under different power structures. Both contracts are shown to achieve Pareto improvements within the supply chain. This research provides valuable insights for enterprises operating within closed-loop supply chains, highlighting the importance of enhancing communication and cooperation to bridge information gaps and ensuring the coordina.

Continuous glucose monitoring (CGM) using implantable glucose sensors is a critical tool in the management of diabetes. Unfortunately, current commercial glucose sensors have limited performance and lifespans in vivo, considered to be due to sensor-induced tissue reactions (inflammation, fibrosis, and vessel regression). Previously, our laboratory utilized monocyte/macrophage (Mo/MQ) deficient and depleted mice to establish a causal relationship between Mo/MQ accumulation and inflammation in glucose sensor performance in vivo. Using C–C chemokine ligand-2 (CCL2) and C–C chemokine receptor-2 (CCR2) knockout mice, we next established that deletion of this Mo/MQ chemokine family, suppressed inflammation at the sensor-tissue interface in these mice, while improving sensor performance over a 4-week post-sensor implantation, compared to normal mice. These studies underscore the importance of the CCL2 family of chemokines and receptors in Mo/MQ recruitment/activation, and sensor performance in vivo. In the present study, we systemically administered Bindarit, a CCL2 synthesis inhibitor, to assess the role of CCL2 chemokines, Mo/MQ recruitment and inflammation at sensor implantation sites, on CGM performance in vivo. These studies demonstrate that systemic administration of Bindarit substantially reduced sensor-induced inflammation, particularly MQ recruitment, preventing sensor biofouling in our CGM mouse model. These results not only confirm the major role monocytes/macrophages play, but directly demonstrate that CCL2 drives Mo/MQ recruitment and biofouling of glucose sensors in vivo. These findings support future studies incorporating Mo/MQ migration/chemotaxis inhibitors, like CCL2, on sensor coatings to improve glucose sensor accuracy and lifespan in vivo.

Abstract In order to realize the intelligent monitoring of the high-precision positioning of the hole position and the real-time control of the verticality of the pile, an intelligent monitoring system was developed based on the combination positioning technology of BDS and UWB and the biaxial tilt sensor, and the numerical simulation and comparative analysis of the verticality of the pile were carried out by abaqus. The deviation of pile foundation in different directions and the deviation of pile body are controlled by the monitoring system, and abnormal warning is made when the deviation exceeds the permissible range.Through the application of intelligent monitoring system in the pile foundation engineering area of Changshui Airport, it is found that the plane offset and perpendicularity of all piles meet the standard requirements and the construction error is controlled at a small value. The results show that the application of intelligent inspection system can not only ensure the construction quality of pile foundation, but also meet and improve the level of digitization and information technology of smart construction site.

Abstract Background Inaccurate colposcopy diagnosis may lead to inappropriate management and increase the incidence of cervical cancer. This study aimed to evaluate the diagnostic accuracy of colposcopy in the detection of histologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with transformation zone type 3 (TZ3). Methods Records from 764 patients with TZ3 who underwent colposcopy-directed biopsy and/or endocervical curettage in Putuo Hospital China between February 2020 and March 2023 were retrospectively collected. Colposcopy was carried out based on 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) and Colposcopy nomenclature. The diagnostic performance of colposcopy for identifying CIN2 + was evaluated compared with biopsies. The Kappa and McNemar tests were used to perform statistical analyses. Results Among the study population, 11.0% had pathologic CIN2+. The relative sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of colposcopy for histologic CIN2 + were 51.2%, 96.5%, 64.2% and 94.1%, respectively. The senior colposcopists (80.6%) had a higher colposcopic accuracy to diagnose histologic CIN2 + than junior colposcopists (68.6%). In subgroup analyses, age group ≥ 60 years (70.3%) showed lowest diagnostic accuracy when compared with age groups of

Selenium (Se) is an essential trace element that is crucial for human health. As a key component of various enzymes and proteins, selenium primarily exerts its biological functions in the form of selenoproteins within the body. Currently, over 30 types of selenoproteins have been identified, with more than 20 of them containing selenocysteine residues. Among these, glutathione peroxidases (GPXs), thioredoxin reductases (TrxRs), and iodothyronine deiodinases (DIOs) have been widely studied. Selenium boasts numerous biological functions, including antioxidant properties, immune system enhancement, thyroid function regulation, anti-cancer effects, cardiovascular protection, reproductive capability improvement, and anti-inflammatory activity. Despite its critical importance to human health, the range between selenium’s nutritional and toxic doses is very narrow. Insufficient daily selenium intake can lead to selenium deficiency, while excessive intake carries the risk of selenium toxicity. Therefore, selenium intake must be controlled within a relatively precise range. This article reviews the distribution and intake of selenium, as well as its absorption and metabolism mechanisms in the human body. It also explores the multiple biological functions and mechanisms of selenium in maintaining human health. The aim is to provide new insights and evidence for further elucidating the role of selenium and selenoproteins in health maintenance, as well as for future nutritional guidelines and public health policies.

To achieve efficient and accurate thick plate welding, as well as to precisely extract and plan the paths of complex three-dimensional weld seams in large steel structures, this study introduces a novel vision-guided approach for robotic welding systems utilizing a constant-focus laser sensor. This methodology specifically targets and mitigates several critical shortcomings inherent in conventional vision-guided welding techniques, including limited detection ranges, diminished precision in both detection and tracking, and suboptimal real-time performance. For preprocessed weld images, an improved grayscale extreme centroid method was developed to extract the center of the light stripe. Furthermore, a sophisticated feature point extraction algorithm, which integrates a maximum distance search strategy with a least-squares fitting procedure, was developed to facilitate the precise and timely identification of weld seam characteristic points. To further optimize the outcomes, a cylindrical filtering mechanism was employed to eliminate substantial discrepancies, whereas local Non-Uniform Rational B-Spline (NURBS) curve interpolation was utilized for the generation of smooth and accurate trajectory plans. A spatial vector-based pose adjustment strategy was then implemented to provide robust guidance for the welding robot, ensuring the successful execution of the welding operations. The experimental results indicated that the proposed algorithm achieved a tracking error of 0.3197 mm for welding workpieces with a thickness of 60 mm, demonstrating the method’s substantial potential in the manufacturing sector, especially in the domain of automated welding.

Fire and smoke detection technologies face challenges in complex and dynamic environments. Traditional detectors are vulnerable to background noise, lighting changes, and similar objects (e.g., clouds, steam, dust), leading to high false alarm rates. Additionally, they struggle with detecting small objects, limiting their effectiveness in early fire warnings and rapid responses. As real-time monitoring demands grow, traditional methods often fall short in smart city and drone applications. To address these issues, we propose FireNet, integrating a simplified Vision Transformer (RepViT) to enhance global feature learning while reducing computational overhead. Dynamic snake convolution (DSConv) captures fine boundary details of flames and smoke, especially in complex curved edges. A lightweight decoupled detection head optimizes classification and localization, ideal for high inter-class similarity and small targets. FireNet outperforms YOLOv8 on the Fire Scene dataset (FSD) with a mAP@0.5 of 80.2%, recall of 78.4%, and precision of 82.6%, with an inference time of 26.7 ms. It also excels on the FSD dataset, addressing current fire detection challenges.

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 ( MET ex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, MET ex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1–56.3%], the DCR was 81.3% (95% CI: 63.6–92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6–9.7) and 17.0 month (95% CI: 10.3–not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

In the Horqin Sandy Land, the dynamics of the soil-plant-atmosphere-water system and changes in plant water availability significantly impact water resources management and vegetation restoration. This study determined the hydrogen and oxygen isotopic compositions (δD and δ18O) of precipitation, plant water, soil water, and groundwater as well as carbon isotopes of plant leaves during the growing season and different precipitation events (8.9 mm, 18.1 mm, and 28.3 mm) in 2020. Target areas included a semimobile dune with Artemisia halodendron communities (SMAH), a meadow corn field (MCF), and a meadow wetland dominated by Phragmites australis (MPA). The water uptake patterns of the three typical plants were determined using the Iso-Source model. The results showed significant differences in the seasonal variations of δD and δ18O in precipitation, plant water, soil water, and groundwater among SMAH, MCF, and MPA throughout the water cycle, which was attributed to the different origins, distribution, and evaporation mechanisms of water. The influence of precipitation on soil water transport processes varied with the change and transformation of rainfall intensity and ecosystem type. Water conditions and root distribution determined seasonal water use patterns of three plants. The water use efficiency (WUE) of the three typical plants followed the order: corn > Phragmites australis > Artemisia halodendron. And their seasonal WUE were not only consistent with the contribution rate of deep soil water, but also affected by the water use strategies adopted. However, the response of their WUE to rainfall pulses was not significant on the whole. Rainfall intensity, pre-rain mass soil moisture content characteristics and vegetation characteristics are important factors affecting the contribution distribution of different water sources to plants under rainfall events. Artemisia halodendron displays ecological plasticity against seasonal water deficit, facilitating its extensive colonization in dune ecosystem and further promoting the process of dune fixation. The distribution pattern of vegetation water use in the meadow ecosystem is not very ideal at present, and water-carbon processes would gradually become imbalanced in the long run. The research results will provide a reference for sustainable water resource utilization in semi-arid areas through ecohydrological processes.

Quantifying the impacts of climate change, vegetation greening and human activities (CVH) on evapotranspiration (ET), surface drought intensity (ET divided by precipitation, SDI), and vegetation available water (precipitation minus ET, VAW) would improve our understanding of water cycle processes. The Yellow River Basin (YRB) is a significant climate-sensitive region in China, resulting in an obvious spatiotemporal heterogeneity of ET, SDI, and VAW in response to driving variables. In this study, we analysed the spatiotemporal variation characteristics of ET, SDI, and VAW in the YRB from 1984 to 2018. We also quantified the direct and indirect contributions of the CVH to the changes in ET, SDI, and VAW, and revealed the influence mechanism of each link. Finally, water resource risks were assessed from a probabilistic perspective. The results indicated that vegetation greening was the primary driver of ET with an increase rate of 1.60 mm/a, which was also the most important influencing factor of SDI increase and VAW decrease. Leaf area index (LAI) and relative humidity (RH) jointly dominated the ET changes in 66 % of the YRB, temperature (Temp) dominated the SDI changes in nearly half of the basin, precipitation (Pre) and LAI jointly dominated the VAW changes in 66 % of the YRB. Temp indirectly influenced ET primarily through LAI, whereas LAI primarily influenced ET directly. Temp had a significant direct impact on SDI, while LAI mainly influenced SDI through RH and wind speed (WS). Temp exhibited the most substantial negative influence on VAW. LAI was identified as the primary factor contributing to water resource risks, with a probability reaching 0.8, while the probabilities associated with other factors inducing such risks were similar at the basin level, but disparities existed among different land use types. The findings of the study significantly enhanced our understanding of the role that the CVH played in hydrological processes, serving as a crucial foundation for achieving a balance between ecological restoration and socio-economic development in the YRB.

We report electrochemical metallization (ECM) resistive switching in polycrystalline YMnO3 memristive devices using Al as an active electrode. Al/YMnO3/Pt devices exhibit bipolar resistive switching with a high ROFF/RON ratio of 104, low operational voltages of VSet ≈ 1.7 V and VReset ≈ −0.36 V and good retention properties. The resistive switching is intimately linked to the coexistence of the orthorhombic and hexagonal YMnO3 phases. The characterization of these two nanocrystalline phases is realized not only by X‐ray diffraction – which is shown to be unable to reveal the presence of the orthorhombic phase – but also by a set of correlative microscopy and spectroscopy methods (scanning electron microscopy, optical microscopy, Raman spectroscopy and conductive atomic force microscopy). The origin of resistive switching is ascribed to an Al filament‐based electrochemical metallization mechanism that likely occurs along an oxygen‐deficient grain boundary between the hexagonal and orthorhombic nanocrystalline YMnO3 phases. The unique microstructure provided by the mixed polycrystalline phase films allows to use Al as an active electrode in YMnO3‐based ECM cells, and gives perspective for further miniaturization of the devices.

The sphincter of Oddi is a delicate neuromuscular structure located at the junction of the biliary-pancreatic system and the duodenum. Sphincter of Oddi Dysfunction (SOD) can result in various clinical manifestations, including biliary-type pain and recurrent idiopathic pancreatitis. The management of SOD has been challenging. With the publication of the landmark Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial and the Rome IV consensus, our clinical practice in the treatment of SOD has changed significantly in recent years. Currently, the management of type II SOD remains controversial and there is a lack of non-invasive therapy options, particularly for patients not responding to endoscopic treatment. In this mini review, we aimed to discuss the current knowledge on the treatment of biliary SOD.

To solve the problem of insufficient low-carbon operational motivation among cold chain logistics enterprises due to the high investment costs of low-carbon assets and considering the promotional effect of environmental regulatory policies and green credit, an evolutionary game model was constructed for the government, cold chain logistics enterprises, and financial institutions. The stability strategies of each participating entity and the stability of the system equilibrium point were analyzed, and the relevant conclusions were verified through numerical simulations. The research results indicated the following: (1) the initial willingness of the three parties to participate increased, the low-carbon operation of cold chain logistics enterprises and the speed of green credit services provided by financial institutions accelerated, and the rate of strict government regulation slowed down. (2) Moderate subsidies and taxes were conducive to the joint participation of the three parties. (3) Increasing the subsidy for green credit provided positive incentives for financial institutions to provide green credit services, while reducing credit interest rates accelerated the low-carbon operation rate of cold chain logistics enterprises.

Abstract Background Prunella vulgaris polysaccharide extracted by hot water and 30% ethanol precipitation (PVE30) was reported to possess potent antiviral effects against herpes simplex virus (HSV) infection. However, its anti-HSV mechanism has not yet been fully elucidated. Purpose This study aimed to investigate the potential mechanisms of PVE30 against HSV infection. Methods Antiviral activity was evaluated by a plaque reduction assay, and the EC50 value was calculated. Immunofluorescence staining and heparin bead pull-down assays confirmed the interactions between PVE30 and viral glycoproteins. Real-time PCR was conducted to determine the mRNA levels of viral genes, including UL54, UL29, UL27, UL44, and US6, and the proinflammatory cytokines IL-6 and TNF-α. The protein expression of viral proteins (ICP27, ICP8, gB, gC, and gD), the activity of the TLR-NF-κB signalling pathway, and necroptotic-associated proteins were evaluated by Western blotting. The proportion of necroptotic cells was determined by flow cytometric analysis. Results The P. vulgaris polysaccharide PVE30 was shown to compete with heparan sulfate for interaction with HSV surface glycoprotein B and gC, thus strongly inhibiting HSV attachment to cells. In addition, PVE30 downregulated the expression of IE genes, which subsequently downregulated the expression of E and L viral gene products, and thus effectively restricted the yield of progeny virus. Further investigation confirmed that PVE30 inhibited TLR2 and TLR3 signalling, leading to the effective suppression of NF-κB activation and IL-6 and TNF-α expression levels, and blocked HSV-1-induced necroptosis by reducing HSV-1-induced phosphorylation of MLKL. Conclusion Our results demonstrate that the P. vulgaris polysaccharide PVE30 is a potent anti-HSV agent that blocks TLR-mediated NF-κB activation. Graphical Abstract

This study utilized the U-Net deep learning model to automate the segmentation of three-dimensional after-loaded metal source applicators, aiming to expedite treatment planning, reduce patient wait times, and enhance the treatment process. Using CT images from cervical cancer patients treated between December 2020 and August 2023, 27 images formed the training set, 3 were for validation, and 10 for testing. The model’s performance was evaluated against expert delineations using metrics like the Dice similarity coefficient (DSC), Hausdorff distance 95% (HD95), and others. The results were integrated into an after-loading planning system to locate applicator pathways and assess dose accuracy and feasibility. For the test group, the DSC ranged from 0.90 to 0.93, HD95 from 0.79 to 0.80 mm, and ASSD from 0.03 to 0.22 mm, with an average segmentation time of 65 seconds, significantly faster than manual delineation. The automatic pathways closely matched the original plan’s dosimetric parameters (P >0.05), indicating the system’s potential for safe application in after-loading planning for cervical cancer treatment. The U-Net-based region-growing method shows promise in improving the efficiency and accuracy of after-loaded applicator segmentation.

AbstractContext Slow transit constipation (STC), the most common type of constipation, seriously affects the life of patients. Zhizhu decoction (ZZD), a traditional Chinese medicine compound, has is effective against functional constipation, but the mechanism is still unclear.Objective This research explores the mechanism of ZZD on STC from the perspective of metabolomics and gut microbiota.Materials and methods Fifty-four C57BL/6 mice were randomly divided into six groups (n = 9): control (control); STC (model); positive control (positive); low-dose (5 g/kg; L-ZZD), medium-dose (10 g/kg; M-ZZD), and high-dose (20 g/kg; H-ZZD) ZZD treatment. Following treatment of mice with ZZD for two weeks, the changes in intestinal motility, colon histology, intestinal neurotransmitters, and aryl hydrocarbon receptor (AHR) pathway determined the effects of ZZD on the pathophysiology of STC. LC-MS targeting serum metabolomics was used to analyze the regulation of ZZD on neurotransmitters, and 16S rRNA high-throughput sequencing was used to detect the regulation of the gut microbiome.Results ZZD had the highest content of naringin (6348.1 mg/L), and could significantly increase the 24 h defecations (1.10- to 1.42-fold), fecal moisture (1.14-fold) and intestinal transport rate (1.28-fold) of STC mice, increased the thickness of the mucosal and muscular tissue (1.18- to 2.16-fold) and regulated the neurotransmitters in the colon of STC mice. Moreover, ZZD significantly activated the AHR signaling pathway, and also affected the composition of gut microbiota in STC mice.Discussion and conclusions The beneficial effect and the possible mechanism of ZZD on STC could provide a theoretical basis for the broader clinical application of ZZD.

Within the Earth’s terrestrial environment, evapotranspiration significantly contributes to the hydrological cycle, accounting for around 80% of the precipitation on landmasses to be reintroduced into the atmosphere. This mechanism profoundly affects the distribution and availability of surface water resources throughout the ecosystem. Gaining insight into the factors influencing local evapotranspiration fluctuations in response to varying climatic and vegetative scenarios is crucial for effective water management strategies and rehabilitating ecosystem resilience. To this end, our study focuses on the Jing River Basin in the Loess Plateau, utilizing multi-source remote sensing data and climatic information to investigate the spatiotemporal dynamics of evapotranspiration from 1984 to 2018 through the application of the Priestley–Taylor Jet Propulsion Laboratory (PT-JPL) model. Our research results indicate a general ascending tendency in evapotranspiration across the investigated region, demonstrating a notably discernible escalation at a pace of approximately 3.11 mm/year (p < 0.01), with an annual vegetation ET volume reaching 533.88 mm. Across different vegetation types in the Jing River Basin between 1984 and 2018, the mean yearly ET was observed to be highest in forests (572.88 mm), followed by croplands (564.74 mm), shrublands (536.43 mm), and grasslands (503.42 mm). The leaf area index (LAI) demonstrated the strongest partial correlation with ET (r = 0.35) and contributed the most significantly to the variation in ET within the Jing River Basin (0.41 mm/year). Additionally, LAI indirectly influences ET through its impact on vapor pressure deficit (VPD), precipitation (Pre), and temperature (Temp). Radiation is found to govern most ET changes across the region, while radiation and precipitation notably affected ET by modulating air temperature. In summary, these radiant energy changes directly affect the evaporation rate and total evapotranspiration of surface water. It provides important support for understanding how evapotranspiration in the Jing River Basin is adjusting to climate change and increased vegetation cover. These findings serve as a theoretical foundation for devising sustainable vegetation restoration strategies to optimize water resource utilization within the region.

Terrain correction is a key step to ensure the accuracy of risk zoning for hail disasters. This study utilizes the hail observations from 81 national meteorological stations in Anhui Province spanning from 1978 to 2020, along with geographic information data, gross domestic product (GDP), and historical disaster data, to identify causative factors for hail disasters and calculate the hazard-inducing intensity indices by employing statistical methods of correlation analysis and regression analysis. Then, a terrain-involved correction method for hail frequency is established, with the combination of hazard-inducing intensity and frequency, to conduct disaster risk evaluation. According to the theory of natural disaster risk assessment, the Geographic Information System-based economic risk zonation of hail disaster is performed by integrating the hazard-inducing factors and vulnerability factors. The feasibility of zoning results is further verified through the direct economic losses caused by hail disasters. The results show that: (1) the maximum hail diameter and duration of hailfall can be used as hail hazard-inducing factors, as both are significantly correlated with the damage index of hail disaster. The terrain-corrected spatial distributions of hail frequency are well consistent with the actual observations, which better represent spatial distribution variations in high-altitude mountainous areas. (2) the hail-prone areas, as well as the high-risk areas, are located in several regions along the main paths of hail disaster, such as to the north of the Huaihe River, in the eastern regions between the Yangtze River and Huai River, as well as in the mountainous areas of Dabie Mountains and the south part in Anhui Province. (3) The overall economic risk of hail disasters gradually decreases from north to south. The validation by direct economic losses suggests that the correlation coefficient between the economic risk index of hail disaster and the average of direct economic losses over multiple years in Anhui province has passed the significance test with a confidence level of 99%, and the zoning results agree well with the true situations.

Abstract C9ORF72 hexanucleotide repeat expansion is the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One pathogenic mechanism is the accumulation of toxic dipeptide repeat (DPR) proteins like poly-GA, GP and GR, produced by the noncanonical translation of the expanded RNA repeats. However, how different DPRs are synthesized remains elusive. Here, we use single-molecule imaging techniques to directly measure the translation dynamics of different DPRs. Besides initiation, translation elongation rates vary drastically between different frames, with GP slower than GA and GR the slowest. We directly visualize frameshift events using a two-color single-molecule translation assay. The repeat expansion enhances frameshifting, but the overall frequency is low. There is a higher chance of GR-to-GA shift than in the reversed direction. Finally, the ribosome-associated protein quality control (RQC) factors ZNF598 and Pelota modulate the translation dynamics, and the repeat RNA sequence is important for invoking the RQC pathway. This study reveals that multiple translation steps modulate the final DPR production. Understanding repeat RNA translation is critically important to decipher the DPR-mediated pathogenesis and identify potential therapeutic targets in C9ORF72-ALS/FTD.

Abstract Background HPV screening tests may improve cervical cancer risk stratification and better guide decisions about follow-up with colposcopy/biopsy. This study aimed to estimate the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with oncogenic HPV types and evaluate the performance of colposcopy in the diagnosis of histologic CIN2 + at Putuo Hospital, Shanghai, China. Methods This cross-sectional survey was conducted from February 2020 to December 2022 among women who were referred to colposcopy. Women with high-risk (HR) HPV-positive, cytology testing and colposcopy-directed biopsy were included. Results Univariate and multivariate analysis indicated that high-grade colposcopic impression ((OR, 17.61%, 95%CI: 11.54–26.85%) was associated with the highest risk for detecting CIN2+, followed by HSIL + cytology (OR, 6.90%, 95%CI: 3.56–13.37%) and HPV16/18 positive (OR, 2.91%, 95%CI: 2.12–3.99%). Overall, CIN2 + was detected in 14.6% of 2007 women. HPV16/18 had higher CIN2 + risks than other HR-HPV genotypes (30.1% vs. 10.2%, P 0.05). The diagnostic performance of colposcopy in diagnosis of CIN2 + by senior and junior colposcopists was comparable. Conclusions The results indicated that referral to colposcopy is recommended in managing women with HR-HPV positive, and colposcopic impressions provide key clues for identification CIN2+.

Bian-Se-Tong mixture (BSTM) is an optimized formulation based on the classical prescription “Zhizhu pill”, which is widely used in the clinical treatment of slow-transit constipation (STC). The potential molecular mechanism of BSTM therapy for STC was investigated by network pharmacology prediction combined with animal experiments. The active components of BSTM were screened via the TCMSP platform. The GeneCards, OMIM and DrugBank databases were used to search for STC targets. With the help of the Biogenet tool, a protein interaction network between drugs and disease targets was constructed, and the intersection network of the two was extracted to obtain the key targets of BSTM in the treatment of STC. GO and KEGG enrichment analyses of key targets were carried out with Metascape. Loperamide hydrochloride was used to establish an STC rat model, and the key targets and related pathways were preliminarily verified. The important signaling pathways included the PI3K-Akt, MAPK, IL-17, cAMP, and cell cycle signaling pathways. The experimental results showed that BSTM treatment increased the body weight of STC rats and increased the fecal particle number, fecal water content and intestinal carbon ink promotion rate within 24 h. Further pathological changes in the colon of the rats were also observed. In-depth mechanistic studies have shown that BSTM can significantly reduce the apoptosis of intestinal Cajal cells, downregulate the expression of Bax and c-Caspase 3, upregulate the expression of Bcl-2 and c-kit, and promote the phosphorylation of AKT. The results showed that BSTM can significantly relieve constipation in STC rats via a mechanism related to activating the PI3K-Akt signaling pathway and improving Cajal cell apoptosis.

IntroductionWith China embracing a new people-centered urbanization stage, the problem of migrants “flowing without moving” has become increasingly prominent, and settlement intention has gradually garnered attention.MethodsOur research, based on questionnaire data from the China Labor Force Dynamic Survey 2016, uses a multilevel linear regression model to explore the influence of mobility, social environment, built environment, and demographics characteristics on settlement intention in the migrants and discusses differences between settlement intention of new and old generations and their internal influence mechanism.ResultsThe findings are as follows: (1) Compared to the old generation, the new migrant generation generally has higher settlement intention. (2) The migrants’ settlement intention is influenced mainly by mobility, social environment, built environment, and demographic characteristics. (3) For the new migrant generation, social and demographic characteristics significantly influence their settlement intention. (4) The floating and built environment of the old generation significantly influence their settlement intention.DiscussionFinally, this paper argues that there are differences in the influence mechanism of the same factors on the settlement intention of the new and old generations of migrants. It proposes differentiated policy suggestions for the migrants to promote city social integration. Finally, this paper argues that there are differences in the influence mechanism of the same factors on the settlement intention of the new and old generations of migrants. It proposes differentiated policy suggestions for the migrants to promote city social integration.

Purpose: The controlling nutritional status (CONUT) score is an important tool for predicting the prognosis of colorectal cancer (CRC); however, its effectiveness is relatively insufficient. This study aimed to screen for more effective clinical indicators as supplements to the CONUT scoring system and improve the predictive value of CRC prognosis. Patients and methods: Between 2014 and 2020, the clinical information of all CRC patients in our unit was retrospectively collected, and the CONUT scores were calculated based on the levels of serum albumin (ALB), lymphocytes (LC), and total cholesterol. The included patients were divided into the following three groups: normal nutrition (0–1), mild malnutrition (2–4), and moderate-to-severe malnutrition (5–12). The correlations between the CONUT score and baseline characteristics and clinical indicators were evaluated. Results: This study ultimately included 5014 CRC patients. The nutritional status of patients with colon cancer (CC) was worse than that of rectal cancer (RC). The nutritional status was worse in men than in women. The older the patient, the poorer the nutritional status, and the poorer the nutritional status, the longer the hospital stay. In addition, poor nutritional status in patients is indicated by higher values of neutrophils (NE), monocytes (MC), eosinophils (EOS), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), carcinoembryogenic antigen (CEA), and lower values of white blood cells (WBC), basophils (BAS), haemoglobin (HB), total protein (TP), triglycerides (TG), low density lipoprotein (LDL), aspartate transaminase (AST), and blood urea nitrogen (BUN), which was statistically significant (P

Summary: Oligodendrocyte progenitor cells (OPCs) differentiate into myelin-producing cells and modulate neuronal activity. Defects in OPC development are associated with neurological diseases. N6-methyladenosine (m6A) contributes to neural development; however, the mechanism by which m6A regulates OPC development remains unclear. Here, we demonstrate that PRRC2B is an m6A reader that regulates OPC development and myelination. Nestin-Cre-mediated Prrc2b deletion affects neural stem cell self-renewal and glial differentiation. Moreover, the oligodendroglia lineage-specific deletion of Prrc2b reduces the numbers of OPCs and oligodendrocytes, causing hypomyelination and impaired motor coordination. Integrative methylated RNA immunoprecipitation sequencing, RNA sequencing, and RNA immunoprecipitation sequencing analyses identify Sox2 as the target of PRRC2B. Notably, PRRC2B, displaying separate and cooperative functions with PRRC2A, stabilizes mRNA by binding to m6A motifs in the coding sequence and 3′ UTR of Sox2. In summary, we identify the posttranscriptional regulation of PRRC2B in OPC development, extending the understanding of PRRC2 family proteins and providing a therapeutic target for myelin-related disorders.

Objective: This research aims to examine the involvement of lymphocyte subsets and inflammatory cytokines in the development and progression of COVID-19. Methods: 164 COVID-19 patients were admitted to hospital between December 2022 and January 2023. Based on lung CT scans and whether it is necessary for intensive care unit (ICU) admission, they were categorized into: severe groups (84) and mild disease groups (80). Peripheral blood were also collected from 101 healthy examinees and 164 patients. Flow cytometry (FCM) was used to measure the absolute and relative counts of lymphocyte subsets, while chemiluminescence was used to detect the level of inflammatory cytokines. Results: The COVID-19 patient group exhibited lower count of lymphocytes subsets than healthy control group. Moreover, COVID-19 patient case presented higher content of cytokines (IL-6, IL-4, IL-8, IL-10, and TNF-α) expression compared to healthy control case. Within the COVID-19 patient group, individuals with severe disease showed lower counts of lymphocytes subsets than the mild disease case. Furthermore, IL-6 levels in severe case were higher than the mild disease patients case. Multi-variate logistic regression analysis confirmed IL-6 (odds ratio: 0.985 [0.977–0.993]), CD3+ T cells (odds ratio:1.007 [1.004–1.010]), CD8+ T cells (odds ratio:1.016 [1.009–1.023]), and CD19+ B cells (odds ratio:1.011 [1.002–1.020]) independently predicted severe progression. ROC curve results indicated AUC for lymphocytes in patients with severe COVID-19 was 0.8686 (0.8112–0.9260), CD3+ T cells was 0.8762 (0.8237–0.9287), CD8+ T cells was 0.7963 (0.7287–0.8638), CD4+ T cells was 0.8600 (0.8036–0.9164), CD19+ B cells was 0.7217 (0.6434–0.8001), NK cells was 0.6492 (0.5627–0.7357), age was 0.6699 (0.5877–0.7521), diabetes was 0.5991 (0.5125–0.6857), and IL-6 was 0.7241 (0.6479–0.8003). Furthermore, the ROC curves for different factors (CD3+ T cells, age, IL-6) yielded an AUC of 0.9031 (0.8580–0.9483). Conclusions: The research indicated that COVID-19 patients experience a decrease in lymphocytes subset and an increase in the inflammatory factor IL-6, particularly in the severe case group. As a result, the count of lymphocyte subset (CD3+ T cells) and the content of inflammatory cytokine (IL-6) can serve as predictive markers for assessing the severity of COVID-19 and developing treatment plans efficacy.

Objectives Emmetropia depends on the precise coordination of ocular biometry, including axial length (AL), corneal curvature, lens thickness and anterior chamber depth (ACD). Disruption of this coordination leads to refractive errors such as myopia. This article aimed to determine the factors affecting ocular biometry and myopia development in young children.Design A cross-sectional study.Setting This study was conducted in a primary school in the Yanqing district of Beijing, China.Participants 792 students in grades 1–3 without hyperopia (>+2.00 D), strabismus, or amblyopia were selected. Exclusions: students had conditions affecting best corrected visual acuity and whose guardians refused to provide informed consent. Ocular biometric measurements and non-cycloplegia autorefraction were performed. The questionnaire addressed factors such as perinatal factors and environmental factors.Interventions None.Primary and secondary outcomes Ocular biometry and myopia.Results According to the multivariate logistic regression analysis, electronic screen use >2 hours/day (OR=2.175, p=0.013), paternal myopia (OR=1.761, p=0.002), maternal myopia (OR=1.718, p=0.005), taller height (OR=1.071, p2 hours each day (OR=3.596, p2 hours each day (OR=0.431, p=0.001) influenced ACD incidence. Central corneal thickness (CCT) was associated with older age (OR=1.113, p=0.008), paternal education (OR=1.474, p=0.007), premature birth (OR=0.494, p=0.031), history of blue light therapy in infancy (OR=0.636, p=0.041) and history of incubator therapy in infancy (OR=0.263, p=0.009). Only sex influenced corneal curvature.Conclusions The factors associated with myopia were partly related to ACD and AL, and perinatal factors were associated with myopia and CCT.Trial registration number ChiCTR2200065398.

Abstract Background Insomnia disorder remains one of the most common sleep disorders in the elderly, with high prevalence and substantial consequences for patients’ general health. Despite that increasing clinical trials have indicated that acupuncture seems to be effective for insomnia disorder in the elderly, comparative efficacy and safety of different acupuncture methods for elderly individuals with insomnia disorder has been unclear. Therefore, this protocol outlined a plan to evaluate and rank the efficacy and safety of various acupuncture approaches for insomnia disorder in the elderly. Methods A systematic search of 8 bibliographic databases will be conducted from their inception to 18 June 2023, including Cochrane Library, MEDLINE (via PubMed), Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and Chinese Biomedical Literature Database (CBM). Randomized controlled trials investigating acupuncture methods for insomnia disorder in the elderly, published in English or Chinese will be included. The primary outcome is sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). Two reviewers will independently perform study selection, data extraction and risk assessment of bias. The quality of included literatures will be appraised using Cochrane risk-of-bias tool (ROB 2.0). ADDIS (Aggregate Data Drug Information System) V.1.16.8 will be used to conduct Bayesian network meta-analysis. The quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation System (GRADE). Discussion In this study, the results will provide credible evidence to assess the efficacy and safety of acupuncture therapies for elderly patients with insomnia disorder, assisting patients, physicians and clinical research investigators to select the most appropriate acupuncture method. Systematic review registration The protocol has been registered at OSF ( https://osf.io/3kjpq/ ) with a registration number https://doi.org/10.17605/OSF.IO/3KJPQ .

Abstract Background This study aimed to apply near-infrared spectroscopy (NIRS) to monitor cerebral oxygen saturation (SrO2) level in neonates before and after the change of mechanical ventilation mode, and thus, the effects of the change of mechanical ventilator mode on SrO2 level in neonates were assessed. Methods This trial was designed as an observational study .A total of 70 neonates who were admitted to the Department of Neonatology of Beijing Luhe Hospital Affiliated to Capital Medical University (Beijing, China) between September 2019 and October 2021 and required respiratory support were included. The variations of SrO2 level before and after the change of mechanical ventilation mode, including changing from Synchronized intermittent mandatory ventilation (SIMV) to noninvasive ventilation (NIV, group 1), and from NIV to oxygen inhalation (group 2), were monitored by Enginmed EGOS-600 A. The changes of SrO2 level at 30 min before and 1 h after the change of ventilation mode were compared between the two groups. Results The SrO2 level in the group 1 30 min before, as well as 10 min, 30 min, and 1 h after the change of ventilation mode was 62.54 ± 3.36%, 65.43 ± 3.98%, 64.38 ± 4.23%, and 64.63 ± 3.71%, respectively. The SrO2 level at all the points after the change of ventilation mode increased compared with 30 min before the change (P

Abstract Background Pancreatic cancer (PAC), a malignancy that is fatal and commonly diagnosed at a late stage. Despite considerable advancements in cancer treatment, the survival rate of PAC remains largely consistent for the past 60 years. The traditional Chinese medicine formula Pulsatilla Decoction (PD) has been clinically used to treat inflammatory diseases for millennia and recently as a supplementary anti-cancer treatment in China. However, the bioactive ingredients and mechanisms underlying its anti-cancer effect remains unclear. Methods The composition and quality control of PD were verified through analysis by high performance liquid chromatography. Cell viability was determined using Cell Counting Kit-8 assay. The cell cycle distribution was analyzed through PI staining and flow cytometry analysis, while apoptotic cells were measured by double staining with Annexin V-FITC and PI. We used immunoblotting to examine protein expressions. The in vivo effects of β-peltatin and podophyllotoxin were evaluated on a subcutaneously-xenografted BxPC-3 cell nude mice model. Results The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. Four herbal PD formula was then disassembled into 15 combinations of herbal ingredients and a cytotoxicity assay showed that the Pulsatillae chinensis exerted the predominant anti-PAC effect. Further investigation indicated that β-peltatin was potently cytotoxic with IC50 of ~ 2 nM. β-peltatin initially arrested PAC cells at G2/M phase, followed by apoptosis induction. Animal study confirmed that β-peltatin significantly suppressed the growth of subcutaneously-implanted BxPC-3 cell xenografts. Importantly, compared to podophyllotoxin that is the parental isomer of β-peltatin but clinically obsoleted due to its severe toxicity, β-peltatin exhibited stronger anti-PAC effect and lower toxicity in mice. Conclusions Our results demonstrate that Pulsatillae chinensis and particularly its bioactive ingredient β-peltatin suppress PAC by triggering cell cycle arrest at G2/M phase and apoptosis.