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Abstract Floods are becoming more frequent and severe in the context of climate change, with major impacts on human health. However, their effect on infant mortality remains unknown, particularly in low- and middle-income countries. We conducted a sibling-matched case-control study using individual-level data from Demographic and Health Surveys in Africa during 1990–2020. Individual flood experience was determined by matching the residential coordinates with flood events from the Dartmouth Flood Observatory database. Using data from 514,760 newborns, we found increased risks of infant mortality associated with flood exposure across multiple periods, with the risks remaining elevated for up to four years after the flood event. Overall, flood exposure was associated with 3.42 infant deaths per 1000 births in Africa from 2000 to 2020, approximately 1.7 times the burden associated with life-period exposure. This multi-country study in Africa provides novel evidence that flood events may increase infant mortality risk and burden, even over years after exposure.

Abstract Patients with rare diseases often experience prolonged diagnostic delays. Ordering appropriate genetic tests is crucial yet challenging, especially for general pediatricians without genetic expertise. Recent American College of Medical Genetics (ACMG) guidelines embrace early use of exome sequencing (ES) or genome sequencing (GS) for conditions like congenital anomalies or developmental delays while still recommend gene panels for patients exhibiting strong manifestations of a specific disease. Recognizing the difficulty in navigating these options, we developed a machine learning model trained on 1005 patient records from Columbia University Irving Medical Center to recommend appropriate genetic tests based on the phenotype information. The model achieved a remarkable performance with an AUROC of 0.823 and AUPRC of 0.918, aligning closely with decisions made by genetic specialists, and demonstrated strong generalizability (AUROC:0.77, AUPRC: 0.816) in an external cohort, indicating its potential value for general pediatricians to expedite rare disease diagnosis by enhancing genetic test ordering.

Abstract Spotted sea bass (Lateolabrax maculatus) is a species of significant economic importance in aquaculture. However, genetic degeneration, such as declining growth performance, has severely impeded industry development, necessitating urgent genetic improvement. Here, we conducted a genome‐wide association study (GWAS) and genomic prediction for growth traits using insertion and deletion (InDel) markers, and systematically compared the results with our previous studies using single nucleotide polymorphism (SNP) markers. A total of 97 significant InDels including a 6 bp insertion in an exon region were identified. It is worth noting that only 5 and 1 candidate genes for DY and TS populations were also detected in previous GWAS using SNPs, and numerous novel genes including c4b, fgf4, and dnajb9 were identified as vital candidate genes. Moreover, several novel growth‐related procedures, such as the growth and development of the bone and muscle, were also detected. These findings indicated that InDel‐based GWAS can provide valuable complement to SNP‐based studies. The comparison of genomic predictive performance for total length trait under different marker selection strategies and genomic selection models indicated that GWAS selection strategy exhibits more stable predictive performance compared to the evenly selection strategy. Additionally, support vector machine model demonstrated better predictive accuracy and efficiency than traditional best linear unbiased prediction and Bayes models. Furthermore, the superior predictive performance using InDel markers compared to SNP markers highlighted the potential of InDels to enhance genomic predictive accuracy and efficiency. Our results carry significant implications for dissecting genetic mechanisms and contributing genetic improvement of growth traits in spotted sea bass through genomic resources.

In this work, the environmental fracture behavior of marine steel and its welding joint were compared in artificial seawater. The electrochemical measurement, slow strain rate tensile test, and low-frequency cyclic loading test were conducted. The results showed that the corrosion current density and stress corrosion cracking susceptibility of welding joints were higher than those of base metal, caused by high dislocation density and residual stress in the heat-affected zone. The acidification and ion concentration occurred at the crack tip of the welding joint and basic metal. pH value and Cl− concentration at the crack tip reached 4.1 and 3.8 mol/L, respectively. The crack growth rate of the welding joint was higher than that of base metal. The crack growth behavior was controlled by the mechano-electrochemical effect at the crack tip, and hydrogen embrittlement was the main factor.

Abstract Intestinal stem cells (ISCs) are responsible for intestinal homeostasis and are important for the regeneration of damaged intestine. We established an ionizing radiation (IR)-induced intestinal injury model and observed that Gelsolin KO mice had increased radiosensitivity. The deletion of Gelsolin aggravated intestinal damage and reduced the number of ISCs after lethal IR. The intestinal organoid experiments showed that Gelsolin deletion inhibited ISCs function after IR. Notably, RNA sequencing and RT-PCR results showed IL-17 signaling pathway was down-regulated and Th17 cells differentiation was inhibited in Gelsolin KO mice. Moreover, recombinant IL-17 A ameliorated IR-induced intestinal injury and promoted ISCs regeneration. To figure out the role of Gelsolin in Th17 cells differentiation, flow cytometry was used and we found that Gelsolin targets Th17 cells functionality via the p-STAT3/RORγt axis. By establishing the co-culture system, we proved that Th17 cells promoted self-renewal and budding abilities in Gelsolin-deficient organoids. Finally, we found that Gelsolin was protective against DSS-induced colitis and that this protective effect was not specific or limited to the IR induced intestinal injury model. Based on these results, we proved Gelsolin maintained the regeneration of ISCs by sustaining Th17 cells functions via the p-STAT3/RORγt axis. Graphical abstract

Abstract Background Marchiafava-Bignami disease (MBD) is an exceptionally rare condition, a fact that should pique the professional curiosity of medical practitioners. In recent years, case reports of this disease have been infrequent, and no comprehensive analysis or summary of the characteristics of the published cases has been conducted. Methods We collected the medical records of three patients treated at our hospital from March 2022 to March 2023. Furthermore, we searched PubMed for “case reports” from January 2017 to March 2023 and included 30 cases. By retrospectively analyzing these 33 cases, we summarized the characteristics of the disease. Results Based on our analysis, we found that MBD primarily affects middle-aged men and typically has an acute or subacute onset, with the primary clinical manifestations being disturbances of consciousness, speech disorders, cognitive impairment, and psychiatric or behavioral abnormalities, often leading to misdiagnosis of psychiatric disorders. Most patients have a history of alcohol consumption or malnutrition. Head CT or MRI revealed symmetric lesions in the corpus callosum, with the splenium being the most commonly affected area. Lesions might also involve white matter outside the corpus callosum, and a wider range of lesions suggested a poor prognosis. However, the prognosis is generally favorable with timely and adequate administration of B vitamins, providing reassurance to medical professionals and patients alike. Conclusion The early recognition and treatment of Marchiafava-Bignami disease are paramount, as they can significantly improve the prognosis. This underscores the critical need for prompt clinical intervention in the early stages of the disease, instilling a sense of urgency and significance in the work of medical professionals.

Abstract Background Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. Methods The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. Results As parameterized in tertiles, titanium showed positive dose–response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. Conclusions In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk. Graphical Abstract

Abstract To address the prominent problem of collapse instability in shallow buried soft ground tunnels, a non-invasive stochastic finite element method was introduced. Taking Fujian Puyan Wenbishan tunnel as the background project, ABAQUS finite element software was used to analyze the tunnel excavation mechanics and parameter sensitivity. And developed the software interface program based on Python to output explicit limit state equation for the key mechanical indexes of the tunnel, so as to evaluate the tunnel reliability under different excavation methods, quantitatively. Study results show a significant improvement in efficiency and accuracy when calculating the probability of failure in tunnel excavation by the non-invasive stochastic finite element method. The maximum displacement monitoring points for the Wenbishan tunnel portal section were all vault settlement, with displacements of 33.6 mm, 30.2 mm, and 25.3 mm, respectively, using the annular retained core soil method, single sidewall guide pit and double sidewall guide pit method, with probabilities of failure of 36.11%, 28.03%, and 20.02%. It is found that the reliability of the tunnel is mainly determined by the geotechnical weight, elastic modulus and cohesion of the weak sandy soil layer, which can provide ideas for this type of engineering researches.

Abstract The cortical cytoskeleton of subpellicular microtubules (SPMTs) supports the Plasmodium ookinete morphogenesis during mosquito transmission of malaria. SPMTs are hypothesized to function as the cytoskeletal tracks in motor-driven cargo transport for apical organelle and structure assembly in ookinetes. However, the SPMT-based transport motor has not been identified in the Plasmodium. The cytoplasmic dynein is the motor moving towards the minus end of microtubules (MTs) and likely be responsible for cargo transport to the apical part in ookinetes. Here we screen 7 putative dynein heavy chain (DHC) proteins in the P. yoelii and identify DHC3 showing peripheral localization in ookinetes. DHC3 is localized at SPMTs throughout ookinete morphogenesis. We also identify five other dynein subunits localizing at SPMTs. DHC3 disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection of Plasmodium. The DHC3-deficient ookinetes display defective formation or localization of apical organelles and structures. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, likely functioning as the receptors for the cargoes driven by SPMT-dynein. Disturbing Rab11A or Rab11B phenocopies DHC3 deficiency in ookinete morphogenesis. Our study reveals an SPMT-based dynein motor driving the transport of Rab11A- and Rab11B-labeled cargoes in the ookinete morphogenesis of Plasmodium.

Abstract Background The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring. Methods Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring. Results Compared with “low IPAI” group, offspring with “high IPAI” have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted β were − 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and − 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among “high IPAI” group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72). Conclusions Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Abstract Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio

Abstract Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are implicated in the development and progression of various tumors. The aim of this study was to investigate the effects of circ_SMA4 in Gastrointestinal Stromal Tumors (GISTs) malignant progression. Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in GISTs. The effect of circ_SMA4 on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo settings. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_SMA4/miR-494-3p/ KIT axis. The results revealed that circ_SMA4 was significantly upregulated in GISTs, and exhibited high diagnostic efficiency with an AUC of 0.9824 (P

In this paper, alkali protease was used to enzymatically hydrolyze wheat germ proteins grown in the Hetao region. A univariate analysis and an orthogonal experiment were conducted to optimize the enzymatically hydrolyze process conditions of wheat germ proteins, with the degree of hydrolysis taken as the indicator. Moreover, the in vitro hypolipidemic effect of wheat germ polypeptides was investigated. The results showed that the degree of hydrolysis of wheat germ proteins was 37.18%±0.25% achieved by the following conditions, substrate concentration of 6.0%, temperature at 50 ℃, pH of 10.5 and protease amount of 12000 U/g. When the concentration of wheat germ polypeptides was 5 mg/mL, the rate of inhibiting cholesterol solubilisation into micelles was 27.11%±0.36%, the pancreatic lipase activity inhibition rate was 33.54%±0.57%, and cholesterol esterase activity inhibition rate was 38.13%±0.29%. Moreover, after ultrafiltration, the relative molecule weight of polypeptides less than 1 kDa accounted for 54.30%±0.32% of all polypeptides, indicating that low-molecular-weight wheat germ polypeptides might yield superior hypolipidemic effects. The work provides a theoretical foundation for further exploring the mechanism between Hetao wheat germ polypeptides and hypolipidemic effect.

Abstract RNase H1 has been acknowledged as an endoribonuclease specializing in the internal degradation of the RNA moiety within RNA–DNA hybrids, and its ribonuclease activity is indispensable in multifaceted aspects of nucleic acid metabolism. However, the molecular mechanism underlying RNase H1-mediated hybrid cleavage remains inadequately elucidated. Herein, using single-molecule approaches, we probe the dynamics of the hybrid cleavage by Saccharomyces cerevisiae RNase H1. Remarkably, a single RNase H1 enzyme displays 3′-to-5′ exoribonuclease activity. The directional RNA degradation proceeds processively and yet discretely, wherein unwinding approximately 6-bp hybrids as a prerequisite for two consecutive 3-nt RNA excisions limits the overall rate within each catalytic cycle. Moreover, Replication Protein A (RPA) reinforces RNase H1’s 3′-to-5′ nucleolytic rate and processivity and stimulates its 5′-to-3′ exoribonuclease activity. This stimulation is primarily realized through the pre-separation of the hybrids and consequently transfers RNase H1 to a bidirectional exoribonuclease, further potentiating its cleavage efficiency. These findings unveil unprecedented characteristics of an RNase and provide a dynamic view of RPA-enhanced processive hybrid cleavage by RNase H1.

Abstract Background Although WD repeat domain 45 (WDR45) mutations have been linked to $$\upbeta$$ β -propeller protein-associated neurodegeneration (BPAN), the precise molecular and cellular mechanisms behind this disease remain elusive. This study aims to shed light on the impacts of WDR45-deficiency on neurodegeneration, specifically axonal degeneration, within the midbrain dopaminergic (DAergic) system. We hope to better understand the disease process by examining pathological and molecular alterations, especially within the DAergic system. Methods To investigate the impacts of WDR45 dysfunction on mouse behaviors and DAergic neurons, we developed a mouse model in which WDR45 was conditionally knocked out in the midbrain DAergic neurons (WDR45 cKO ). Through a longitudinal study, we assessed alterations in the mouse behaviors using open field, rotarod, Y-maze, and 3-chamber social approach tests. We utilized a combination of immunofluorescence staining and transmission electron microscopy to examine the pathological changes in DAergic neuron soma and axons. Additionally, we performed proteomic and lipidomic analyses of the striatum from young and aged mice to identify the molecules and processes potentially involved in the striatal pathology during aging. Further more, primary midbrain neuronal culture was employed to explore the molecular mechanisms leading to axonal degeneration. Results Our study of WDR45 cKO mice revealed a range of deficits, including impaired motor function, emotional instability, and memory loss, coinciding with the profound reduction of midbrain DAergic neurons. The neuronal loss, we observed massive axonal enlargements in the dorsal and ventral striatum. These enlargements were characterized by the accumulation of extensively fragmented tubular endoplasmic reticulum (ER), a hallmark of axonal degeneration. Proteomic analysis of the striatum showed that the differentially expressed proteins were enriched in metabolic processes. The carbohydrate metabolic and protein catabolic processes appeared earlier, and amino acid, lipid, and tricarboxylic acid metabolisms were increased during aging. Of note, we observed a tremendous increase in the expression of lysophosphatidylcholine acyltransferase 1 (Lpcat1) that regulates phospholipid metabolism, specifically in the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine (PC) in the presence of acyl-CoA. The lipidomic results consistently suggested that differential lipids were concentrated on PC and LPC. Axonal degeneration was effectively ameliorated by interfering Lpcat1 expression in primary cultured WDR45-deficient DAergic neurons, proving that Lpcat1 and its regulated lipid metabolism, especially PC and LPC metabolism, participate in controlling the axonal degeneration induced by WDR45 deficits. Conclusions In this study, we uncovered the molecular mechanisms underlying the contribution of WDR45 deficiency to axonal degeneration, which involves complex relationships between phospholipid metabolism, autophagy, and tubular ER. These findings greatly advance our understanding of the fundamental molecular mechanisms driving axonal degeneration and may provide a foundation for developing novel mechanistically based therapeutic interventions for BPAN and other neurodegenerative diseases.

Formaldehyde is an important carcinogen commonly found indoors. Its indoor sources have been intensively investigated. But study on outdoor formaldehyde concentration, which is potentially an important source to indoors, remains scarce. This study attempts to characterize temporal and spatial distribution of the atmospheric formaldehyde concentration in Chinese cities. Diurnal variation of ambient formaldehyde was examined in 6 cities and peak hours were identified between 12:00 pm and 3:00 pm. Consequently, outdoor formaldehyde concentrations were measured in the peak hours in 30 cities during the summer months of Jul.-Aug., 2022. The formaldehyde concentrations in the peak hours fell into a range of 0.005–0.087 mg/m3 (median value is 0.027 mg/m3), 87.7% of which have exceeded the chronic reference exposure criteria of 0.009 mg/m3 set by Office of Environmental Health Hazard Assessment. Health risk analysis suggests that exposure to ambient formaldehyde could cause a median carcinogenic risk of 1.9 × 10−5 (3.17×10−6–6.13×10−5), higher than threshold limit of 10−6. Pearson correlation analysis of the 30 cities shows that ambient summertime atmospheric formaldehyde concentrations of the city are positively correlated with its Gross Domestic Product (r = 0.48). We also found that the outdoor formaldehyde concentrations in urban areas (median: 0.017 mg/m3) is slightly higher than those in suburban areas (median: 0.013 mg/m3). Results here prove that outdoor formaldehyde is ubiquitous in Chinese cities and reduces effectiveness of ventilation in dilution indoor concentrations. Neglecting it would underestimate air cleaner capacity needed by a factor of about two. It should be accounted for in health analysis and air quality engineering control design of built environment in the future.

Abstract Translating RNA-seq into clinical diagnostics requires ensuring the reliability and cross-laboratory consistency of detecting clinically relevant subtle differential expressions, such as those between different disease subtypes or stages. As part of the Quartet project, we present an RNA-seq benchmarking study across 45 laboratories using the Quartet and MAQC reference samples spiked with ERCC controls. Based on multiple types of ‘ground truth’, we systematically assess the real-world RNA-seq performance and investigate the influencing factors involved in 26 experimental processes and 140 bioinformatics pipelines. Here we show greater inter-laboratory variations in detecting subtle differential expressions among the Quartet samples. Experimental factors including mRNA enrichment and strandedness, and each bioinformatics step, emerge as primary sources of variations in gene expression. We underscore the profound influence of experimental execution, and provide best practice recommendations for experimental designs, strategies for filtering low-expression genes, and the optimal gene annotation and analysis pipelines. In summary, this study lays the foundation for developing and quality control of RNA-seq for clinical diagnostic purposes.

Abstract Background Seed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson’s disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation. Methods We introduced a modified form of SAA, known as Quiescent SAA (QSAA), and evaluated biopsy and autopsy samples from individuals clinically diagnosed with PD and those without synucleinopathies (control group). Brain biopsy samples were obtained from 14 PD patients and 6 controls without synucleinopathies. Additionally, skin samples were collected from 214 PD patients and 208 control subjects. Data were analyzed from April 2019 to May 2023. Results QSAA successfully amplified αSyn aggregates in brain tissue sections from mice inoculated with pre-formed fibrils. In the skin samples from 214 PD cases and 208 non-PD cases, QSAA demonstrated high sensitivity (90.2%) and specificity (91.4%) in differentiating between PD and non-PD cases. Notably, more αSyn aggregates were detected by QSAA compared to immunofluorescence with the pS129-αSyn antibody in consecutive slices of both brain and skin samples. Conclusion We introduced the new QSAA method tailored for in situ amplification of αSyn aggregates in brain and skin samples while maintaining tissue integrity, providing a streamlined approach to diagnosing PD with individual variability. The integration of seeding activities with the location of deposition of αSyn seeds advances our understanding of the mechanism underlying αSyn misfolding in PD.

Abstract To systematically evaluate the intervention effect of music therapy on anxiety and depression in breast cancer patients. Randomised controlled trial (RCT) on music therapy for anxiety and depression in breast cancer patients was searched from 7 major databases, PubMed, Embase, the Cochrane Library, WOS, CNIC, Wanfang, and Wipro, spanning the period of library construction to 23 October 2023, and the literature screening of music therapy for anxiety or depression in breast cancer patients was carried out by 2 experimentalists, each of whom conducted a literature screening RCT independently of the other anxiety or depression in a RCT. Methodological quality was evaluated using the PEDro scale; GRADE profiler software for quality of evidence; and RevMan 5.4 was used for effect size merging and forest plots; publication bias tests and sensitivity analyses were performed using Stata 17.0; and standardized mean difference (SMD) and 95% CI were used as the effect statistics. A total of 13 RCTs with 1326 subjects (aged 18–70 years) were included in the literature, with a mean PEDro score of 6.8, and the literature was overall of good methodological quality. Meta-analysis showed that music therapy improved anxiety in breast cancer patients (841 cases), with a combined effect size (SMD = − 0.82, 95% CI [− 1.03, − 0.61] and P

Abstract Background Parent-child separation poses a significant challenge for left-behind children (LBC). However, limited empirical evidence exists regarding the correlation between left-behind characteristics and the psychological symptoms of LBC. This study investigated psychological symptoms among LBC and explored associations between left-behind characteristics and those symptoms. Methods Using stratified cluster sampling, 1,832 LBC aged 13–18 years from three cities in East China were selected for analysis. Participants’ depression and anxiety symptoms were assessed with the Patient Health Questionnaire 9 and the General Anxiety Disorder 7, respectively. Chi-square tests were used to compare differences in detection rates of psychological symptoms among LBC in different groups. Binary logistic regression analysis was used to infer associations between left-behind characteristics and psychological symptoms. Results Depression and anxiety symptoms were detected in 32.86% and 33.24%, respectively, of participating LBC. Univariate analysis showed statistically significant differences in detection rates of depression symptoms by sex, grade, and timing of parent-child separation. Statistically significant differences were observed in anxiety symptom rates by sex, grade, type of caregiver, and timing of mother-child separation. Multivariate analysis indicated a positive association between LBC’s anxiety symptoms and mother-child separation that occurred during post-primary school, and type of caregiver (father only or mother only). Our findings confirm a positive association between left-behind characteristics and anxiety symptoms among LBC. Conclusion The timing of mother-child separation and type of caregiver are potential risk factors for the development of anxiety symptoms in this population.

Abstract Background The Triglyceride-glucose (TyG) index is a marker of insulin resistance, but its role in sarcopenia is controversial. The purpose of this study was to investigate the association of the TyG index with sarcopenia. Methods 4030 participants aged 20 years and above were selected from National Health and Nutrition Examination Survey for cross sectional study. Weighted logistic regression model was used to estimate the association between TyG index and sarcopenia. Threshold effect analysis and restricted cubic spline were employed to describe nonlinear link, with interaction tests and subgroup analyses performed. Results It was found in the fully adjusted model that the TyG index was positively associated with sarcopenia (per 1-unit increase in the TyG index: OR = 1.31, 95%CI: 1.07, 1.60). This association was further highlighted in groups characterized by the absence of MetS or diabetes, as well as the absence of vigorous or moderate work activity. Furthermore, analysis of the curve fitting and threshold effects indicated a nonlinear relationship, which exhibited a turning point at 9.14. Conclusion The study results indicated that the TyG index was positively associated with sarcopenia. Enhancing the management of insulin resistance could help reduce the risk of developing sarcopenia.

Abstract In pursuit of the highest possible energy density, researchers shift their focus to the ultimate anode material, lithium metal (Li0), and high‐capacity cathode materials with high nickel content (Ni > 80%). The combination of these aggressive electrodes presents unprecedented challenges to the electrolyte. Here, we report a hybrid electrolyte consisting of a highly fluorinated ionic liquid and a weakly solvating fluorinated ether, whose hybridization structure enables the reversible operation of a battery chemistry based on Li0 and LiNiO2 (Ni = 100%), delivering nearly theoretical capacity of the latter (up to 249 mAh g−1) for >300 cycles with retention of 78.6% and in absence of unwanted morphological changes in both electrodes. Extensive characterization assisted by molecular dynamic simulation and density functional theory calculations reveals the function of the fluorinated ether to be far more profound than simple dilution and viscosity reduction. Instead, it induces drastic changes in Li+‐solvation environment, the consequence of which engenders simultaneous stabilization of electrode/electrolyte and interfacing via formation of respective interfacial chemistries. This study further unlocks fundamental knowledge underneath the prevailing “diluent strategy” that is extensively applied by the electrolyte researchers and opens more design space for the next‐generation electrolytes and interphases for these coveted battery chemistries.

Objective We aim to evaluate the efficacy and safety of blinatumomab for the treatment of post-transplant relapse patients with acute lymphoblastic leukemia (ALL).Methods The search was conducted using several databases including the PubMed, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang Data Knowledge Service Platform to collect clinical studies related to blinatumomab. The primary outcome measures were complete remission (CR), 1-year overall survival (OS), 2-year OS, median OS and adverse events (AEs). Grade ≥3 AEs were mainly analyzed for safety, including anemia, thrombocytopenia, neutropenia, encephalopathy, peripheral paresthesia, tremor and cytokine release syndrome (CRS).Results A total of 7 studies, involving a total of 292 patients were included in the analysis. The analysis results showed CR rate of 48%, 1-year OS rate of 40% 2-year OS rate of 21%, median OS 7.47. For safety analysis, the incidence of grade ≥3 AEs, including the incidence of grade ≥3 anemic toxicity was 13% , the incidence of grade ≥3 thrombocytopenia toxicity was 7% , the incidence of grade ≥3 neutropenia toxicity 24%, the incidence of grade ≥3 encephalopathic toxicity was 4% , the incidence of grade ≥3 peripheral paresthesia toxicity 4%, the incidence of grade ≥3 tremor toxicity 8% , the incidence of grade ≥3 CRS toxicity was 4%.Conclusion Blinatumomab may be a safe and an effective treatment approach for post-transplant relapse patients with ALL, but its long-term efficacy is still a big challenge. In regard to Regarding AEs, serious CRS and neurological events were infrequent and manageable.

ABSTRACT: The high-yielding Houdan chicken (GGF) is characterized by high egg production and disease resistance. This study conducted whole genome resequencing of the GGF population and compared it to data from other breeds. Genetic diversity analysis revealed higher observed heterozygosity (Ho), Polymorphism information content (PIC), number of runs of homozygosity (ROH), and inbreeding coefficient (FROH) in GGF. Linkage disequilibrium (LD) decay was slowest in GGF, indicating intensive inbreeding and strong selection. These findings suggest a need for appropriate strategies to enhance genetic diversity conservation in this breed. Population structure analysis demonstrated that GGF was genetically distinct from both the red jungle fowl (RJF) and Chinese indigenous chicken (CIC) populations, highlighting GGF as a unique genetic resource warranting intensive protection and utilization. Selective sweep analysis identified genes under selection in GGF, primarily enriched in signaling pathways related to oocyte meiosis and progesterone-mediated oocyte maturation. Key candidate genes included: CCNE1, SKP1, CDC20, CDK2, ADCY8, RPS6KA6, PPP3CB, PDE3B, HSP90AB1, and AKT3. These findings provide a theoretical foundation for their potential application in poultry breeding. Additionally, this study combined bioinformatics analysis with PCR amplification and Sanger sequencing to identify 4 SNPs that can serve as a molecular identity card (ID) for GGF: SNP1 (Chr2: 136130976), SNP3 (Chr4:11705164), SNP4 (Chr4: 63255588), and SNP5 (Chr24: 3271008). This study provides a scientific basis for effective management and conservation of GGF genetic resources, and establishes a simple, economical, and accurate set of molecular IDs to combat the proliferation of inferior breeds and protect genetic resources.

Influence mechanism of various ion chelators on the mechanical, transport, and microstructure properties of cement-based materials was explored. The ion chelators included pentasodium diethylenetriamine pentaacetate, tetrasodium ethylenediaminetetraacetate, sodium hexametaphosphate and tetrasodium glutamate diacetate, with a dosage of 1 % of the cement mass. The effect of ion chelators on the mechanical, transport, and pore structure properties was evaluated by compressive, sorptivity, and mercury intrusion porosimetry (MIP) tests. The composition and microstructure of hydration products were studied by scanning electron microscope (SEM) and X-ray diffractometer (XRD). Test results indicated that four ion chelators reduced the mechanical and transport properties, and increased the porosity of specimens at 3 d and 7 d. And four ion chelators improved the mechanical and transport properties, and reduced porosity at 28 d and 56 d. The fundamental reason for the differences in the basic properties of cement-based materials caused by the types of ion chelators is that different ion chelators possess various calcium chelating capacities and stability of calcium complexes, which leads to different impact on the complexation substitution reaction process. Moreover, compared to the stability of calcium complexes, the influence of calcium chelating ability on the basic properties of specimens is more significant in the early curing ages.

Background Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients’ condition.Methods An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided.Results A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP.Conslusions Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.

For over 50 years, the Xianyang city on the Chinese loess plateau, has been deeply affected by land subsidence and its associated ground fissures. In this study, 67 Sentinel-1A images from 2015 to 2022 were analysed to obtain the spatio-temporal evolution of land subsidence. Subsidence centers identified in Yunyang town and Luqiao town exhibit annual subsidence rates of −31 mm/a and −26.7 mm/a, respectively, culminating in total subsidence of −258 mm in Yunyang town and −139 mm in Luqiao town. Moreover, time series analysis revealed that both towns exhibit pronounced seasonal subsidence patterns. It is believed that human cultivation and groundwater overuse, combined with the effects of active faults, have led to uneven land subsidence. Then, the gradient of land subsidence and its potential relation to ground fissure hazards were evaluated. The results highlight a strong spatial correlation between high subsidence gradient areas and dense ground fissure distribution. Therefore, we proposed for the first time to introduce the land subsidence gradient factors for the susceptibility mapping of ground fissures using the artificial neural network algorithm. The susceptibility zonation results show that integrating the gradient factor can improve the rationality of the susceptibility evaluation. The above understanding provides valuable support for disaster prevention and mitigation in urban areas affected by land subsidence and ground fissures in loess regions.

Objective This article conducts a systematic review of eltrombopag combined with immunosuppressive therapy for the treatment of aplastic anemia (AA), to demonstrate the effectiveness and safety of eltrombopag.Methods PubMed, Cochrane Library, Embase, OVID, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched. Studies that met the inclusion criteria were collected, ranging from the establishment of the database to August 2023. Two reviewers performed meta-analyses using the Cochrane systematic review method and RevMan 5.3 software.Results This meta-analysis enrolled 5 studies with a total of 542 AA patients, including 274 in the experimental group and 268 in the control group. Meta-analyses were performed for efficacy and adverse reactions. The endpoint of effects included 6-month complete response (CR), 6-month partial response (PR), and 6-month overall response (OR). Eltrombopag combined with immunotherapy showed significant improvements in 6-month CR (OR: 2.20; 95% CI;1.54–3.12; P

Abstract The incorporation of defects and cocatalysts is known to be effective in improving photocatalytic activity, yet their coupled contribution to the photocatalytic hydrogen evolution process has not been well‐explored. In this study, We demonstrate that the incorporation of S vacancies and NiSe can contribute to the improvement of charge separation efficiency via the formation of a strong electric field within the bulk ZnIn2S4 (ZIS) and on its surface. More importantly, We also demonstrate that the synergy of S vacancies and NiSe benefits the overall hydrogen evolution activity by facilitating the H2O adsorption and dissociation process. This is particularly important for hydrogen evolution taking place under alkaline conditions where the proton concentration is low, allowing ZISv‐NiSe (containing abundant S vacancies) to outperform ZIS‐NiSe under alkaline conditions. In contrast, under acid conditions, since there are already sufficient amounts of protons available for reaction, the hydrogen evolution activity became governed by the hydrogen adsorption/desorption process rather than the H2O dissociation process. This leads to ZIS‐NiSe exhibiting higher activity than ZISv‐NiSe due to its more favorable hydrogen adsorption energy. The findings thus provide insights into how defect and cocatalyst modification strategies can be tailor‐made to improve hydrogen evolution activity under different pH conditions.

Background With the ageing of people living with HIV/AIDS (PLWHA), the prevalence of chronic comorbidities, especially hyperglycaemia, is increasing among elderly PLWHA. Antiretroviral therapy (ART) is associated with fasting plasma glucose (FPG) levels. This study aimed to investigate both short-term and long-term FPG characteristics and trends across different ART regimens in elderly Chinese PLWHA.Methods This retrospective cohort study, based on hospital treatment information, classified ART regimens as this retrospective cohort study used hospital treatment data. ART regimens are classified into three categories: non-nucleoside reverse transcriptase inhibitors (NNRTIs) based, protease inhibitors (PIs) based and integrase strand transfer inhibitor (INSTIs) based. Propensity score matching was applied to control for confounding factors. Follow-up FPG characteristics were then described, and a generalised linear mixed model was employed to estimate FPG trends under different regimens within 1-year and 5-year periods following ART initiation.Results Participants had an average age of 58.28 years, with 75.02% male. FPG increased following ART initiation, with the most significant rise within 1 year of ART, followed by stabilisation. The FPG increase within 1 year was slower in the PIs-based group compared with the NNRTIs-based group (β=−0.08, 95% CI −0.15 to –0.01), while there was a higher prevalence of diabetes within 5 years of ART (31.55% vs 22.33%, standardised difference=0.357). The FPG increase within 1 year of ART did not differ between NNRTIs-based and INSTIs-based groups (β=−0.01, 95% CI −0.20, 0.18).Conclusion Our study highlights that elderly Chinese PLWHA experience an increase in FPG levels, particularly during the first year of ART, with variations observed across different ART regimens. The higher long-term prevalence of diabetes in the PIs-based regimen group emphasises the need for tailored glucose management strategies. Routine glucose monitoring and proactive management are crucial for preventing and controlling diabetes in this population, particularly given the long-term metabolic risks associated with ART.

BackgroundInfertility is increasingly recognized as a global health issue affecting couples of reproductive age, with male factors contributing to approximately 50% of infertility cases. However, the association between depression and anxiety-two of the most prevalent mental health conditions-and impaired male fertility remains a subject of ongoing debate.MethodsIn this cross-sectional study, male participants seeking fertility counseling at an IVF clinic were recruited. Symptoms of depression and anxiety were assessed using the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. Generalized linear regression models (GLMs) were employed to investigate the relationships between mental health status and semen parameters.ResultsStatus of depression was negatively associated with semen quality parameters, whereas no statistically significant association was recognized between anxiety and semen quality except that sperm concentration was decreased by 25.60 (95% CI, 1.226 to 49.965, P=0.040) ×106/ml in moderate to severe anxiety group referring to normal group. Furthermore, when stratified by sleep duration, moderate to severe depression group showed a great decrease in progressive motility (PR), total motility, concentration and total sperm count (TSC) as referred to normal group in participants with sleep duration less than 7 hours.ConclusionThe present study revealed that depression rather than anxiety was a negative factor that affected semen quality, especially in individuals with shorter sleep duration.

Limited evidence was available on ambient air pollution and pediatric atopic dermatitis (AD). The study aimed to evaluate the associations between short-term exposure to air pollutants and outpatient visits for pediatric AD. From 2016–2018, we collected data on six criteria air pollutants (PM2.5, PM10, NO2, SO2, CO and O3) and daily outpatient visits for pediatric AD in 66 hospitals, covering all districts in Shanghai, China. The over-dispersed Poisson generalized additive model (GAM) was applied to fit the associations of criteria air pollutants with hospital visits. Two-pollutant models were fitted and stratified analyses by sex, age and season were conducted. We identified 477,833 outpatient visits for pediatric AD. Each interquartile range (IQR) increase in PM2.5 (IQR: 30.9 μg/m3), PM10 (8.9 μg/m3), NO2 (25.5 μg/m3), SO2 (5.8 μg/m3) and CO (0.283 mg/m3) on the concurrent day was significantly associated with increments of 2.08 % (95 % CI: 0.53 %, 3.65 %), 2.53 % (95 % CI: 0.87 %, 4.22 %), 8.14 % (95 % CI: 6.24 %, 10.08 %), 5.67 % (95 % CI: 3.58 %, 7.80 %), and 2.27 % (95 % CI: 0.70 %, 3.87 %) in pediatric AD outpatient visits, respectively. The effects of NO2 remained robust after adjustment for other air pollutants. The exposure-response curves for PM2.5 and PM10 were steeper for moderate-lower concentrations, with a flatten curves at high concentration; nearly linear relationships were found for NO2. Higher associations of NO2 exposure on AD were detected in children under 6 years old (p=0.01); and we observed larger effect of air pollutants in cool seasons (p

Background: This study aims to investigate the association between sleep duration, sleep quality, and the risk of low back pain (LBP) among middle-aged and elderly individuals in China. Methods: Utilizing data from the China Health and Retirement Longitudinal Study spanning 2011 to 2020, we categorized sleep duration into long, medium, and short categories, and sleep quality into good, fair, and poor levels. LBP status was determined based on self-reported information by participants. Multivariable logistic regression analysis was employed to assess the relationship between sleep duration, sleep quality, with the risk of LBP. Results: A total of 6750 individuals were included in the longitudinal study. After 9 years of follow-up, the prevalence of LBP was 25.69 %. In the fully adjusted model, compared to individuals with medium sleep duration, those with short sleep duration had a 28 % increased risk of developing LBP (OR = 1.28, 95%CI: 1.12, 1.46). Additionally, when compared to individuals with good sleep quality, those with fair and poor sleep quality had a 35 % (OR = 1.35, 95%CI: 1.19, 1.54) and 33 % (OR = 1.33, 95%CI: 1.12, 1.58) increased risk of LBP, respectively. Joint analysis of both factors revealed that individuals with poor sleep quality and short sleep duration had the highest risk of LBP. Conclusion: Among middle-aged and elderly individuals in China, short sleep duration and poor sleep quality were associated with an increased risk of LBP. Future studies should further explore the mechanisms underlying this association and validate the findings through randomized controlled trials.

ABSTRACT Globally, appetite disorders have become an increasingly prominent public health issue. While short-term appetite loss may seem relatively harmless, prolonged instances can lead to serious physical and mental damage. In recent years, numerous studies have highlighted the significant role of the “microbiota-gut-brain” axis in the regulation of feeding behavior in organisms, suggesting that targeting the gut microbiota may be a novel therapeutic strategy for appetite disorders. However, the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between the two remain unclear. Based on this, we conducted 16S rRNA sequencing to analyze the gut microbiota of rabbits with high and low feed intake, followed by fecal microbiota transplantation (FMT) and metabolite gavage experiments to elucidate the underlying mechanisms. Our research indicates that the high feed intake group exhibited significant enrichment of the g__Bacteroides and gamma-aminobutyric acid (GABA), and intragastric administration of GABA effectively promoted the host’s feeding behavior. The underlying mechanism involves GABA derived from the gut microbiota inhibiting the secretion of satiety hormones to enhance the host’s feeding behavior. Furthermore, the results of FMT suggest that differences in gut microbiota composition may be a contributing factor to varying levels of feed intake in the host. In conclusion, these findings emphasize the role of the gut microbiota-derived GABA, in increasing host feed intake, offering a new target for the treatment of appetite disorders from the perspective of gut microbiota.IMPORTANCEThe incidence of anorexia is rapidly increasing and has become a global burden. Gut microbiota can participate in the regulation of host feeding behavior, yet the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between them remain unclear. In this study, we utilized 16S rRNA sequencing to investigate the composition of the gut microbiota in rabbits with varying levels of feed intake and employed fecal microbiota transplantation and gastric infusion experiments with gamma-aminobutyric acid (GABA) to elucidate the potential mechanisms involved. GABA derived from the gut microbiota can effectively enhance the host’s feeding behavior by inhibiting the secretion of satiety hormones. This discovery underscores the pivotal role of the gut microbiota in modulating host appetite, offering novel research avenues and therapeutic targets for appetite disorders.

We study the collective stimulus response in two classical nonlinear dynamical models, the globally coupled bistable oscillators and the excitable FitzHugh-Nagumo neurons, where the coupling strength among the units are randomly distributed with fixed mean and varying variance. We find theoretically and numerically that in both models the ensemble response to a weak periodic stimulus exhibits a bell-shaped amplification manifesting a different type of resonance mechanism, namely, coupling-disorder-induced resonance, as the quenched disorder of coupling increases. Of particular interest is that the optimal collective response emerges near the order-chaos transition point, i.e., at the edge of chaos. As a promising application, we discuss briefly the potential reasonability for exploiting such a type of chaotic resonance to explain the optimal mutual information in the realistic inferior olive. Our results provide explicitly a clue that the disorderly coupled elements may utilize the coupling-disorder-induced chaos to optimize their stimulus response.

Non-optimal temperature is a leading risk factor for global disease burden. Most epidemiological studies assessed only outdoor temperature, with important uncertainties on personal exposure misclassification. The CKB-Air study measured personal, household (kitchen and living room), and outdoor temperatures in the summer (MAY-SEP 2017) and winter (NOV 2017-JAN 2018) in 477 participants in China. After data cleaning, ∼88,000 person-hours of data were recorded across each microenvironment. Using multivariable linear regression (MLR) and random forest (RF) models, we identified key predictors and constructed personal temperature exposure prediction models. We used generalised additive mixed effect models to examine the relationships of personal and outdoor temperatures with heart rate. The 24-hour mean (SD) personal and outdoor temperatures were 29.2 (3.8) °C and 27.6 (6.4) °C in summer, and 12.0 (4.0) °C and 7.5 (4.2) °C in winter, respectively. The temperatures across microenvironments were strongly correlated (Spearman’s ρ: 0.86–0.92) in summer. In winter, personal temperature was strongly related to household temperatures (ρ: 0.74–0.79) but poorly related to outdoor temperature (ρ: 0.30). RF algorithm identified household and outdoor temperatures and study date as top predictors of personal temperature exposure for both seasons, and heating-related factors were important in winter. The final MLR and RF models incorporating questionnaire and device data performed satisfactorily in predicting personal exposure in both seasons (R2summer: 0.92; R2winter: 0.68–0.70). We found consistent U-shaped associations between measured and predicted personal temperature exposures and heart rate (lowest at ∼ 14.5 °C), but a weak positive linear association with outdoor temperature. Personal and outdoor temperatures differ substantially winter, but prediction models incorporating household and outdoor temperatures and questionnaire data performed satisfactorily. Exposure misclassification from using outdoor temperature may produce inappropriate epidemiological findings.

Since the wave is accompanied by the transfer of energy in the process of transmission, and the energy density at the node directly affects the bearing capacity and service performance of the steel truss cable-stayed bridge members and joints, this paper quantitatively studies the energy density at the key nodes of the long-span steel truss cable-stayed bridge from the perspective of the wave response of the structure. Firstly, according to the drawings of Xiangshan Bridge, a local finite element model of the steel truss cable-stayed bridge is established, and by changing the angle between the cable and the steel truss girder and the bending stiffness of the cable, the variation law of energy density at the connection node between the cable and the steel truss girder is obtained by changing the angle between the cable and the steel truss girder and the bending stiffness of the cableway. Due to the limitations of finite element wave analysis, from the perspective of theoretical analysis, this paper establishes the local scattering matrix at the node, proves the obtained law to a certain extent, and uses the return wave-light matrix method to analyze and solve the energy density at the connection node between the cable bar and the steel truss girder, and the final analytical solution is in good agreement with the numerical solution, which proves that the law obtained by numerical analysis is correct.

Abstract Algorithmic recommendation technology, including news apps, social networking services (SNSs), and video or short-video apps, and is widely embedded in various mobile applications (apps), has raised concerns about potential addiction. This study constructs a model linking the uses and gratifications of algorithmic recommendation apps with algorithmic dependence, with a particular focus on fatigue as a key mediator in explaining the psychological mechanism behind the formation of algorithmic app dependence. Snowball sampling was employed for data collection, and a total of 354 valid questionnaires were collected via the online survey tool (i.e., WJX platform). The results show that the use of algorithmic recommendation apps has a direct positive effect on algorithmic app dependence. While all three types of user gratification obtained (i.e., information gratification, entertainment gratification, and expression gratification) are positively related to algorithmic app dependence, the mediating role of fatigue varies: entertainment gratification indirectly reduces algorithmic app dependence by increasing fatigue, whereas expression gratification indirectly increases algorithmic app dependence by reducing fatigue. The theoretical contributions and practical implications of the research findings are discussed.

Abstract The home-rearing environment (HRE) is significantly related to preschoolers’ academic and behavioral development. Children’s screen time has become an increasingly important aspect of the family environment in today’s digital age. However, few studies explored screen time’s indirect role in the relationships between HRE and children’s development. This study was conducted in three provinces of China, and 825 child-parent dyads participated. The results indicated that a high-quality HRE is directly associated with better language and cognitive skills, self-regulation, self-efficacy, and fewer problem behaviors in children. Screen time has an indirect role in this relationship, suggesting that a better HRE associated with lower screen time improves children’s outcomes. However, the HRE did not show a significant indirect role through screen time related to children’s problem behavior, indicating other factors may play a role. The study highlights the importance of fostering enriching home environments and managing screen time to support children’s development.

Introduction Cigarette smoking is one of the most important causes of COPD and could induce the apoptosis of pulmonary microvascular endothelial cells (PMVECs). The conditional knockout of LRG1 from endothelial cells reduced emphysema in mice. However, the mechanism of the deletion of LRG1 from endothelial cells rescued by cigarette smoke (CS) induced emphysema remains unclear. This research aimed to demonstrate whether LRG1 promotes the apoptosis of PMVECs through KLK10 in COPD. Methods Nineteen patients were divided into three groups: control non-COPD (n=7), smoker non-COPD (n=7), and COPD (n=5). The emphysema mouse model defined as the CS exposure group was induced by CS exposure plus cigarette smoke extract (CSE) intraperitoneal injection for 28 days. Primary PMVECs were isolated from the mouse by magnetic bead sorting method via CD31-Dynabeads. Apoptosis was detected by western blot and flow cytometry. Results LRG1 was increased in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. KLK10 was over-expressed in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. LRG1 promoted apoptosis in PMVECs. LRG1 knockdown reversed CSE-induced apoptosis in PMVECs. The mRNA and protein expression of KLK10 were increased after over-expressed LRG1 in PMVECs isolated from mice. Similarly, both the mRNA and protein levels of KLK10 were decreased after LRG1 knockdown in PMVECs. The result of co-immunoprecipitation revealed a protein-protein interaction between LRG1 and KLK10 in PMVECs. KLK10 promoted apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. KLK10 knockdown could reverse CSE-induced apoptosis in PMVECs. Conclusions LRG1 promotes apoptosis via up-regulation of KLK10 in PMVECs isolated from mice. KLK10 promotes apoptosis via the down-regulation of Bcl-2/ Bax in PMVECs. There was a direct protein-protein interaction between LRG1 and KLK10 in PMVECs. Our novel findings provide insights into the understanding of LRG1/KLK10 function as a potential molecule in COPD.

Abstract Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson’s disease and related α-synucleinopathies.

Abstract Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants with significant adverse effects on human health, particularly concerning fetal development during pregnancy. This study investigates the relationship between maternal exposure to particulate matter-bound (PM-bound) PAHs and potential alterations in fetal renal function. A cross-sectional investigation was conducted on 450 mother-pair newborns from June 2019 to August 2021. Exposure to PM-bound PAHs was estimated at the residential address using spatiotemporal models based on data from 30 monitoring stations across the study area. Umbilical cord blood samples were collected post-delivery for biochemical analysis of renal function markers, including creatinine (Cr), blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR). Multivariable regression models were used to assess the relationship between exposure to each PAHs compound and fetal renal function. Moreover, the mixture effects of exposure to PAHs on fetal renal function were assessed using quantile g-computation analysis. Increased concentrations of various PAH compounds at the residential address correlated with raised levels of umbilical BUN and Cr, suggesting potential renal impairment. Notably, exposure to certain PAHs compounds demonstrated statistically negative significant associations with eGFR levels. An increment of one quartile in exposure to PAHs mixture was correlated with a rise of 1.08 mg/dL (95% CI 0.04, 2.11, p = 0.04) and 0.02 mg/dL (95% CI − 0.00, 0.05, p = 0.05) increase in BUN and Cr, respectively. Moreover, a one-quartile increase in PAHs mixture exposure was associated with − 1.09 mL/min/1.73 m2 (95% CI − 2.03, − 0.14, p = 0.02) decrease in eGFR. These findings highlight the potential impact of PAH exposure on fetal renal function and underscore the importance of considering environmental exposures in assessing neonatal renal health outcomes.

Abstract TDP-43 is implicated in the dynamic formation of nuclear bodies and stress granules through phase separation. In diseased states, it can further condense into pathological aggregates in the nucleus and cytoplasm, contributing to the onset of amyotrophic lateral sclerosis. In this study, we evaluate the effect of graphene quantum dots (GQDs) with different functional groups on TDP-43’s phase separation and aggregation in various cellular locations. We find that halogen atom-doped GQDs (GQDs-Cl, Cl-GQDs-OH) penetrate the nuclear envelope, inhibiting the assembly of TDP-43 nuclear bodies and stress granules under oxidative stress or hyperosmotic environments, and reduce amyloid aggregates and disease-associated phosphorylation of TDP-43. Mechanistic analysis reveals GQDs-Cl and Cl-GQDs-OH modulate TDP-43 phase separation through hydrophobic and electrostatic interactions. Our findings highlight the potential of GQDs-Cl and Cl-GQDs-OH in modulating nuclear protein condensation and pathological aggregation, offering direction for the innovative design of GQDs to modulate protein phase separation and aggregation.

The changing climate poses a growing challenge to the population health. The objective of this study was to assess the association between ambient temperature and cause-specific mortality in Suzhou. Based on the non-accidental mortality data collected during 2008–2022 in Suzhou, China, this study utilized an individual-level case-crossover design to evaluate the associations of temperature with cause-specific mortality. We applied a distributed lag nonlinear model with a maximum lag of 14 days to account for lag effects. Mortality risk due to extreme cold (97.5th percentile) was analyzed. A total of 634,530 non-accidental deaths were analyzed in this study. An inverse J-shaped exposure-response relationship was observed between ambient temperature and non-accidental mortality, with the minimum mortality temperature (MMT) at 29.1℃. The relative risk (RR) of mortality associated with extreme cold (2.5th percentile) was 1.37 [95 % confidence interval (CI): 1.30, 1.44], higher than estimate of 1.09 (95 %CI: 1.07, 1.11) for extreme heat (97.5th percentile) relative to the MMT. Heat effect lasted for 2–3 days, while cold effect could persist for almost 14 days. Higher mortality risk estimates were observed for cardiorespiratory deaths compared to total deaths, with statistically significant between-group differences. Consequently, this study provides first-hand evidence on the associations between ambient temperatures and mortality risks from various causes, which could help local government and policy-makers in designing targeted strategies and public health measures against the menace of climate change.

Background This article aims to systematically evaluate the intervention effect of exercise on working memory in patients with depression. Methods Six Chinese and English databases were searched for randomized controlled trials (RCTs) about exercise on working memory in patients with depression. PEDro scale was adopted to evaluate the methodological quality of the included articles, GRADEpro scale was employed to evaluate the level of evidence for outcomes, and the Metafor Package in R 4.4.1 was used to analyze the combined effect size, subgroup analyses and publication bias. Results A total of 15 studies were included. The meta-analysis indicated that exercise had a statistically significant effect on working memory in patients with depression, with an effect size of 0.16 (95% CI [0.03–0.28], p = 0.02). Exercise type (F(3,34) = 1.99, p = 0.13), intervention content (F(1,36) = 1.60, p = 0.22), and exercise duration (F(1,36) = 0.05, p = 0.83) did not moderate the effect, whereas exercise intensity showed a moderating effect (F(2,35) = 8.83, p < 0.01). There was evidence of publication bias in the study results (t = 2.52, p = 0.02). Conclusion Exercise can improve the working memory of patients with depression, and its moderating effect is the best when having low-intensity and moderate-intensity. Research plan was registered in international system evaluation platform PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) (CRD42023475325).

Summary: The origin and evolution of trilobated body plan of the Artiopoda, a group of epibenthic euarthropods from Cambrian Lagerstätten, remain unclear. Here we examine old and new specimens of Urokodia aequalis, one of euarthropods from the Chengjiang biota, revealing new morphological details and revising its taxonomy. Urokodia possesses an elongate body with a five-segmented head, a thorax with 13–15 tergites, and a three-segmented pygidium with well-defined axial region. The ventral morphology includes paired stalked eyes, one fleshy antenna pair, the following homogeneous head and thoracic appendages, each with an annular proximal-element, an articulated stenopodous branch and a lamellar flap, and the pygidial appendages solely consisting of lamellar flaps. Cladistic analyses resolved Urokodia as the basal-most member of the Artiopoda, offering a hypothesis of the initial origin of trilobation in the pygidium. The new data, in conjunction with the presence of the elongated body plan across major lineages of euarthropods, suggest a convergent evolution of this trait.

ObjectiveThe oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM).MethodsThis cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results.ResultsA total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found.ConclusionHigher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with diabetes.

In order to reveal the correlation between the accelerated corrosion test of epoxy polysiloxane coating and the real sea environmental test, the real sea environmental test was carried out in the atmosphere and tidal range area of Zhairuoshan Island in the East China Sea, and the multi-factor coupling test I (Cycle of 7-day xenon lamp aging test + 7-day Wetting-drying test) and test II (Cycle of 7-day xenon lamp aging test + 3-day damp heat test + 4-day salt spray test) were designed with reference to the environment of the East China Sea. The correlation between indoor accelerated corrosion test and real sea environmental test was analyzed by using Grey Relation Analysis, Spearman's rank correlation coefficient and Acceleration factor conversion method. The results show that both the indoor accelerated corrosion test and the real sea environmental test have corrosive effects on the epoxy polysiloxane coating of concrete. In the indoor accelerated corrosion test, it was found that the Wetting-drying test caused the highest loss of light rate. In the real sea environmental test, the loss of light rate of the coating in the atmosphere is higher than that in the tidal area, and the color difference is slightly lower. When the loss of light rate is used as the criterion, the grey correlation coefficient between the multi-factor coupling test I and the tidal range test is 0.63, and the maximum acceleration factor during the test is 5.3, indicating a good correlation between the two tests. Through this study, an effective indoor accelerated corrosion test method with good correlation and acceleration characteristics to the loss of light rate of concrete epoxy polysiloxane coating in a real sea environment was obtained.