Designing electrolytes with high solubility of sulfides/disulfides for high-energy-density and low-cost K-Na/S batteries.

Alkaline metal sulfur (AMS) batteries offer a promising solution for grid-level energy storage due to their low cost and long cycle life. However, the formation of solid compounds such as M2S2 and M2S (M = Na, K) during cycling limits their performance. Here we unveil intermediate-temperature K-Na/S batteries utilizing advanced electrolytes that dissolve all polysulfides and sulfides (K2Sx, x = 1-8), significantly enhancing reaction kinetics, specific capacity, and energy density. These batteries achieve near-theoretical capacity (1655 mAh g-1 sulfur) at 75 °C with a 1 M sulfur concentration. At a 4 M sulfur concentration, they deliver 830 mAh g-1 at 2 mA cm-2, retaining 71% capacity after 1000 cycles. This new K-Na/S battery with specific energy of 150-250 Wh kg-1 only employs earth-abundant elements, making it attractive for long-duration energy storage.

Unsupervised Transfer Learning Method via Cycle-Flow Adversarial Networks for Transient Fault Detection under Various Operation Conditions.

The efficient fault detection (FD) of traction control systems (TCSs) is crucial for ensuring the safe operation of high-speed trains. Transient faults (TFs) can arise due to prolonged operation and harsh environmental conditions, often being masked by background noise, particularly during dynamic operating conditions. Moreover, acquiring a sufficient number of samples across the entire scenario presents a challenging task, resulting in imbalanced data for FD. To address these limitations, an unsupervised transfer learning (TL) method via federated Cycle-Flow adversarial networks (CFANs) is proposed to effectively detect TFs under various operating conditions. Firstly, a CFAN is specifically designed for extracting latent features and reconstructing data in the source domain. Subsequently, a transfer learning framework employing federated CFANs collectively adjusts the modified knowledge resulting from domain alterations. Finally, the designed federated CFANs execute transient FD by constructing residuals in the target domain. The efficacy of the proposed methodology is demonstrated through comparative experiments.

Cardiac intravoxel incoherent motion diffusion-weighted imaging to assess myocardial microcirculation dysfunction in hypertension.

Background: Myocardial microcirculation dysfunction is the most potent predictor of adverse cardiovascular events in hypertension. The current study aimed to apply intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to assess hypertension-related microcirculation dysfunction. Methods: In this prospective study, 102 participants were recruited from our hospital and underwent cardiac magnetic resonance (CMR) examination on a 3T scanning system. Hypertensive patients were divided into 3 subgroups based on blood pressure (BP) types. Two experienced CMR radiologists independently analyzed all images, and Bland-Altman analysis was applied to assess intra- and inter-observer reproducibility. Cardiac function indexes and IVIM-DWI parameters were compared between the hypertension and healthy control groups, as well as among the three hypertension subgroups. Results: Totally 62 participants with hypertension and 27 healthy controls were included. 13 participants were excluded for poor quality of IVIM-DWI images. Significantly higher maximal left ventricular wall thickness (10.3±2.0 vs. 8.6±1.4 mm, P<0.001) and left ventricular mass index (49.0±9.1 vs. 42.1±7.5 g/m2, P<0.05) were observed inhypertension group compared with healthy control group. There were significant statistical differences in pseudo diffusion (D*) between them (81.3±16.3 vs. 111.8±18.9 mm2/s, P<0.001), as well as among the three hypertension subgroups (99.4±13.9 vs. 79.7±10.6 vs. 67.1±6.6 mm2/s, P<0.001). Participants with poor quality of IVIM-DWI images had higher heart rates (72.2±10.0 vs. 62.0±8.1 bpm, P<0.001). Conclusions: IVIM-DWI is feasible for quantitatively evaluating myocardial microcirculation dysfunction in hypertension. The D* parameter has a potential value for assessing the severity of microcirculation dysfunction in different BP categories.

Correlates of feeding difficulties among children of Chinese transgender parents.

Background: Ensuring proper early feeding for young children is crucial, as encountering feeding difficulties (FD) during this stage can give rise to a cascade of health problems, the repercussions of which may endure into late childhood and adolescence. Children raised by transgender parents may be at risk of encountering FD, however, there is no research conducted on Chinese transgender families. Methods: We designed a cross-sectional survey in which the rate of FD and its influencing factors were investigated among transgender parents in China. A total of 446 Chinese transgender parents (average age 30.39 years) were included in the analysis. Logistic regression models were applied to investigate the influencing factors of FD among children of transgender parents. We also established structural equation modeling (SEM) to explore the possible pathways among these factors and FD. Results: The rate of FD in children of Chinese transgender parents is 55.4%, with 34.5% having severe FD. Coming out after having a child (AOR = 2.26, 95%CI = 1.33 ∼ 3.91), family violence (AOR = 1.06, 95%CI = 1.04 ∼ 1.09), partner violence (AOR = 1.11, 95%CI = 1.08 ∼ 1.15), no feeding education (accepting feeding education: AOR = 0.43, 95%CI = 0.25 ∼ 0.74), being discriminated during seeking of childbearing health care (AOR = 1.99, 95%CI = 1.3 ∼ 3.05), and poor relationship with partner (fair: AOR = 0.09, 95%CI = 0.03 ∼ 0.22; good: AOR = 0.06, 95%CI = 0.02 ∼ 0.15) are significantly associated with higher FD. Furthermore, through the pathway analysis, the indirect effects of education level (ß=-0.151), feeding education (ß = 0.145), and relationship with partner (ß=-0.196) on FD are observed. Conclusions: Children of Chinese transgender parents showed a high FD rate. It is crucial to help build a better family and social environment for transgender families to reduce the FD and improve children's and adolescents' health.

Comparative analysis of atherosclerotic cardiovascular disease burden between ages 20-54 and over 55 years: insights from the Global Burden of Disease Study 2019.

BACKGROUND: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. METHODS: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. RESULTS: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. CONCLUSIONS: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

ChRIPK1 caused necroptosis signaling pathway deficiency in Crassostrea hongkongensis.

RIPK1/TAK1 are important for programmed cell death, including liver death, necroptosis and apoptosis. However, there have been few published reports on the functions of RIPK1/TAK1 in invertebrates. In this study, full-length ChRIPK1 and ChTAK1 were cloned from C. hongkongensis through the rapid amplification of cDNA ends (RACE) technology. ChRIPK1 has almost no homology with human RIPK1 and lacks a kinase domain at the N-terminus but has a DD and RHIM domain. ChTAK1 is conserved throughout evolution. qRT‒PCR was used to analyze the mRNA expression patterns of ChRIPK1 in different tissues, developmental stages, and V. coralliilyticus-infected individuals, and both were highly expressed in the mantle and gills, while ChRIPK1 was upregulated in hemocytes and gills after V. coralliilyticus or S. aureus infection, which indicates that ChRIPK1 is involved in immune regulation. Fluorescence assays revealed that ChRIPK1 localized to the cytoplasm of HEK293T cells in a punctiform manner, but the colocalization of ChRIPK1 with ChTAK1 abolished the punctiform morphology. In the dual-luciferase reporter assay, both ChRIPK1 and ChRIPK1-RIHM activated the NF-κB signaling pathway in HEK293T cells, and ChTAK1 activated ChRIPK1 in the NF-κB signaling pathway. The apoptosis rate of the hemocytes was not affected by the necroptosis inhibitor Nec-1 but was significantly decreased, and ChRIPK1 expression was knocked down in the hemocytes of C. hongkongensis. These findings indicated that ChRIPK1 induces apoptosis but not necroptosis in oysters. This study provides a theoretical basis for further research on the molecular mechanism by which invertebrates regulate the programmed cell death of hemocytes in oysters.

Comparative safety of monoclonal antibodies in chronic inflammatory airway diseases (chronic sinusitis with nasal polyposis and asthma): A network meta-analysis.

OBJECTIVE: Several monoclonal antibodies (MoAbs) targeting specific type 2 immune reactions have been developed as innovative therapeutic approaches for chronic inflammatory airway diseases, such as chronic sinusitis with nasal polyps (CRSwNP) and asthma. However, the clinical safety of these MoAbs and how to choose them are not clear. Therefore, we aimed to assess the systemic drug- and dose-based safety of MoAbs in chronic airway inflammation using network meta-analysis (NMA). METHODS: Electronic databases were systematically searched for relevant studies published in English between January 2009 and December 2022. Eligible studies must have clearly reported adverse events (AEs) among the MoAbs' safety data. RESULTS: 1). Regarding serious AEs, mepolizumab was significantly safer than placebo; in terms of permanent treatment discontinuation, reslizumab and dupilumab were significantly safer than benralizumab. 2). Regarding asthma worsening, dupilumab was associated with the best safety profile; was safer than dupilumab/300 mg/q2-4w. 3). In terms of injection-site reactions, dupilumab posed a higher risk than placebo; dupilumab/300 mg/qw posed a higher risk than dupilumab/300 mg/q2w and dupilumab/300 mg/q2-4w; lebrikizumab/250 mg/q4w posed a higher risk than lebrikizumab/37.5 mg/q4w; mepolizumab/100 mg/q4w posed a higher risk than mepolizumab/75 mg/q4w; benralizumab/30 mg/q4-8w posed a higher risk than benralizumab/20 mg/q4-8w. 4) In CRSwNP patients combined with asthma, the risks of experiencing AEs were not increased. CONCLUSION: Overall, biologics are safe and well tolerated in chronic inflammatory airway disease. This drug- and dose-based NMA provides further evidence on the different safety profiles of different emerging MoAbs. This information may help guide rational drug use and provide clinical recommendations for choosing MoAbs. TRIAL REGISTRATION: SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42023387610).

Changes of cardiac function: cardiac adaptation in patients with hypothyroidism assessed by cardiac magnetic resonance-a meta-analysis.

Objective: The meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance. Research methods and procedures: Databases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114. Results: Six studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], P=0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity (P = 0.08, I² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], P=0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], P=0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], P=0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], P=0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], P=0.05)], and there was no difference from the healthy controls. Conclusion: Hypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function. Systematic review registration: https://inplasy.com, identifier (INPLASY202440114).

Genetically predicted 91 circulating inflammatory proteins in relation to risk of urological malignancies: a Mendelian randomization study.

BACKGROUND: Urological malignancies, including kidney, bladder, and prostate cancer, are major health concerns worldwide. Inflammation has been implicated in the pathogenesis of these cancers, and circulating inflammatory proteins may play a role in their development. However, the causal relationship between specific plasma proteins and urological malignancies remains unclear. METHODS: We performed a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS). Instrumental variables representing genetic variants associated with circulating inflammatory proteins were used to infer causality on the risk of kidney, bladder, and prostate cancer. Four MR methods were utilized to provide robust effect estimates. RESULTS: Our analysis identified several plasma proteins associated with a lower risk of kidney and bladder cancer, including Eukaryotic translation initiation factor 4E-binding protein 1, Caspase 8, Natural killer cell receptor 2B4, and Tumor necrosis factor ligand superfamily member 12. However, after adjusting for multiple testing, these associations did not remain statistically significant. For prostate cancer, CUB domain-containing protein 1 and Interleukin-10 receptor subunit beta were found to be protective, while Glial cell line-derived neurotrophic factor and SIR2-like protein 2 were identified as risk factors. After FDR adjustment, none of the inflammatory proteins were found to be significantly associated with a lower risk of prostate cancer. CONCLUSION: Our findings suggest that certain plasma proteins may be involved in the development of urological malignancies. Mendelian randomization provides a useful framework for investigating causal relationships between inflammatory proteins and urological cancers, offering potential insights into their underlying biology and therapeutic targets.

Synergistic and stepwise treatment of resveratrol and catechol in Haematococcus pluvialis for the overproduction of biomass and astaxanthin.

To increase the production of biomass and astaxanthin from Haematococcus pluvialis to meet the high market demand for astaxanthin, this study recruited two typical and negligible phytohormones (namely resveratrol and catechol) for the stepwise treatments of H. pluvialis. It was found that the hybrid and sequential treatments of resveratrol (200 µmol) and catechol (100 µmol) had achieved the maximum astaxanthin content at 33.96 mg/L and 42.99 mg/L, respectively. Compared with the hybrid treatment, the physiological data of H. pluvialis using the sequential strategy revealed that the enhanced photosynthetic performance via the Calvin cycle by RuBisCO improved the biomass accumulation during the macrozooid stage; meanwhile, the excessive ROS production had occurred to enhance astaxanthin production with the help of NADPH overproduction during the hematocyst stage. Overall, this study provides improved knowledge of the impacts of phytohormones in improving biomass and astaxanthin of H. pluvialis, which shed valuable insights for advancing microalgae-based biorefinery.

[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

Triceps skinfold thickness trajectories and the risk of all-cause mortality: A prospective cohort study.

BACKGROUND: The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated. AIM: To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality. METHODS: This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors. RESULTS: Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort. CONCLUSION: In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials.

BACKGROUND: Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. AIM: To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS: Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. RESULTS: The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. CONCLUSION: This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Plant polysaccharide-derived edible film packaging for instant food: Rapid dissolution in hot water coupled with exceptional mechanical and barrier characteristics.

A comprehensive multiscale analysis was conducted to explore the effects of different ratios of these materials on its properties. The results show that KC played a crucial role in controlling solution viscosity and gel and sol temperatures. The dissolution time at high water temperatures primarily decreased with an increase in SA content. Higher KC and CS content increased tensile strength (TS) and elongation at break (ε), while also exhibiting better thermal stability. Water vapor transmission (WVT) and permeability (PV) initially decreased, then increased with the increase of SA and CS contents. Finally, an SA:KC:CS ratio of 1:3:2 showed optimal comprehensive properties, with a dissolution time of about 60.0 ± 3.8 s, TS of 23.80 ± 0.29 MPa, ε of 18.61 ± 0.34 %, WVT of 21.74 ± 0.62 g/m2·24h, and PV of 5.39 ± 0.17 meq/kg. Meanwhile, the SA:KC:CS edible food packaging only introduced minimal effects on food after dissolution, and the total bacterial count met regulatory standards.

Preparation, antibacterial activity, and structure-activity relationship of low molecular weight κ-carrageenan.

κ-Carrageenan (KC) is a polysaccharide widely used in food industry. It has been widely studied for its excellent physicochemical and beneficial properties. However, the high molecular weight and high viscosity of KC make it difficult to be absorbed and to exert its' biological activities, thus limit its extensive industrial application. In order to solve this problem, five low molecular weight κ-carrageenans (DCPs) were prepared by the degradation of KC using hydrogen peroxide (H2O2) and ascorbic acid (AH2). The chemical compositions and structure characteristics of the DCPs were then determined. The results showed that H2O2 and AH2 could effectively degrade KC to DCPs, and DCPs remained the basic skeletal structure of KC. DCPs showed good antibacterial activities against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis. The Minimum Inhibitory Concentration (MIC) of DCPs with the highest antibacterial effects were 5.25, 4.5, 5.25, and 4.5 mg/mL, respectively. This is due to the underlying mechanism of DCPs that bind to the bacterial membrane proteins and change the membrane permeability, thus exerting antibacterial activity. In addition, Spearman's rank correlation and Ridge regression analysis revealed that the molecular weight and the contents of 3,6-anhydro-D-galactose, aldehyde group, carboxyl, and sulfate were the main structural characteristics affecting the antibacterial activity. Our findings reveal that the H2O2-AH2 degradation treatment could significantly improve the antibacterial activity of KC and provide insights into the quantitative structure-activity relationships of the antibacterial activity of DCPs.

Sarcopenic obesity is part of obesity paradox in dementia development: evidence from a population-based cohort study.

BACKGROUND: Sarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia risk and its onset. METHODS: We included 208,867 participants from UK biobank, who aged 60 to 69 years at baseline. Dementia diagnoses were identified using hospital records and death register data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to evaluate the associations of obesity, sarcopenia, and sarcopenic obesity with dementia risk, stratified by sex. Stratified analyses were performed across dementia-related polygenic risk score (PRS). Restricted mean survival time models were established to estimate the difference and 95%CIs of dementia onset across different status. Additionally, linear regression models were employed to estimate associations of different status with brain imaging parameters. The mediation effects of chronic diseases were also examined. RESULTS: Obese women with high PRS had a decreased risk (HR = 0.855 [0.761-0.961]), but obese men with low PRS had an increased risk (HR = 1.223 [1.045-1.431]). Additionally, sarcopenia was associated with elevated dementia risk (HRwomen = 1.323 [1.064-1.644]; HRmen = 2.144 [1.753-2.621]) in those with low PRS. Among those with high PRS, however, the association was only significant in early-life (HRwomen = 1.679 [1.355-2.081]; HRmen = 2.069 [1.656-2.585]). Of note, sarcopenic obesity was associated with higher dementia risk (HRwomen = 1.424 [1.227-1.653]; HRmen = 1.989 [1.702-2.323]), and results remained similar stratified by PRS. Considering dementia onset, obesity was associated with dementia by 1.114 years delayed in women, however, 0.170 years advanced in men. Sarcopenia (women: 0.080 years; men: 0.192 years) and sarcopenic obesity (women: 0.109 years; men: 0.511 years) respectively advanced dementia onset. Obesity, sarcopenia, and sarcopenic obesity were respectively related to alterations in different brain regions. Association between sarcopenic obesity and dementia was mediated by chronic diseases. CONCLUSIONS: Sarcopenic obesity and sarcopenia were respectively associated with increased dementia risk and advanced dementia onset to vary degree. The role of obesity in dementia may differ by sex and genetic background.

Atomic Defect Quantification by Lateral Force Microscopy.

Atomic defects in two-dimensional (2D) materials impact electronic and optoelectronic properties, such as doping and single photon emission. An understanding of defect-property relationships is essential for optimizing material performance. However, progress in understanding these critical relationships is hindered by a lack of straightforward approaches for accurate, precise, and reliable defect quantification on the nanoscale, especially for insulating materials. Here, we demonstrate that lateral force microscopy (LFM), a mechanical technique, can observe atomic defects in semiconducting and insulating 2D materials under ambient conditions. We first improve the sensitivity of LFM through consideration of cantilever mechanics. With the improved sensitivity, we use LFM to locate atomic-scale point defects on the surface of bulk MoSe2. By directly comparing LFM and conductive atomic force microscopy (CAFM) measurements on bulk MoSe2, we demonstrate that point defects observed with LFM are atomic defects in the crystal. As a mechanical technique, LFM does not require a conductive pathway, which allows defect characterization on insulating materials, such as hexagonal boron nitride (hBN). We demonstrate the ability to observe intrinsic defects in hBN and defects introduced by annealing. Our demonstration of LFM as a mechanical defect characterization technique applicable to both conductive and insulating 2D materials will enable routine defect-property determination and accelerate materials research.

Predictive modeling for eosinophilic chronic rhinosinusitis: Nomogram and four machine learning approaches.

Eosinophilic chronic rhinosinusitis (ECRS) is a distinct subset of chronic rhinosinusitis characterized by heightened eosinophilic infiltration and increased symptom severity, often resisting standard treatments. Traditional diagnosis requires invasive histological evaluation. This study aims to develop predictive models for ECRS based on patient clinical parameters, eliminating the need for invasive biopsy. Utilizing logistic regression with lasso regularization, random forest (RF), gradient-boosted decision tree (GBDT), and deep neural network (DNN), we trained models on common clinical data. The predictive performance was evaluated using metrics such as area under the curve (AUC) for receiver operator characteristics, decision curves, and feature ranking analysis. In a cohort of 437 eligible patients, the models identified peripheral blood eosinophil ratio, absolute peripheral blood eosinophil, and the ethmoidal/maxillary sinus density ratio (E/M) on computed tomography as crucial predictors for ECRS. This predictive model offers a valuable tool for identifying ECRS without resorting to histological biopsy, enhancing clinical decision-making.

Impact of a dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta-analysis.

AIMS: To evaluate the impact of a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide (TZP), and its potential dose-response effect, on heart rate. METHODS: Articles were searched from PubMed, Web of Science, Embase, Cochrane Library, and clinical trials registries (ClinicalTrials.gov) databases. Randomized controlled trials (RCTs) comparing TZP at doses of 5, 10 and 15 mg in adults with type 2 diabetes were included. Six study arms were summarized from original research (TZP 5, 10 and 15 mg, GLP-1 receptor agonists [GLP-1RAs], insulin, placebo). The GLP-1RA and non-GLP-1RA groups were combined to form a control group. Two reviewers independently extracted data and assessed the quality of each study. Mean differences (MDs) were calculated as effect estimates for continuous outcomes. Pairwise meta-analyses and network meta-analyses were conducted. The study protocol was prospectively registered (PROSPERO ID: CRD42023418551). RESULTS: Eight articles were included in this systematic review and meta-analysis. The mean baseline heart rate ranged from 65.2 to 75.7 beats per minute. Pairwise meta-analysis showed that, compared with combined the control group, there were significantly greater increases in heart rates in the TZP group (MD 1.82, 95% confidence interval [CI] 0.75, 2.89). Similar significant rises were identified when comparing TZP with GLP-1RAs and non-GLP-1RAs (GLP-1 RAs: MD 2.29, 95% CI 1.00, 3.59; non-GLP-1RAs: MD 1.58, 95% CI 0.26, 2.91). TZP 5 mg was associated with smaller increases in heart rates compared to TZP 10 mg and TZP 15 mg (TZP 10 mg: MD -0.97, 95% CI -1.79, -0.14; TZP 15 mg: MD -2.57, 95% CI -3.79, -1.35). TZP 10 mg increased heart rate less than TZP 15 mg (MD -1.5, 95% CI -2.38, -0.82). Network meta-analysis indicated that TZP 15 mg was associated with significant increases in heart rate compared with TZP 5 mg (MD 2.53, 95% CI 1.43, 3.62), TZP 10 mg (MD 1.44, 95% CI 0.35, 2.53), GLP-1RAs (MD 3.46, 95% CI 1.67, 5.25), insulin (MD 2.86, 95% CI 1.32, 4.41) and placebo (MD 2.96, 95% CI 1.36, 4.57). CONCLUSIONS: Our study showed not only that there was a greater increase in heart rate in the TZP group than in the control, GLP-1RA and non-GLP-1RA groups, but also that the 15-mg dose of TZP had the strongest impact on increasing heart rates compared with the other five inventions, with a TZP dose-response impact on heart rate. Further research on the effects of TZP treatment-related increases in heart rate is required.

STAB2: an updated spatio-temporal cell atlas of the human and mouse brain.

The brain is constituted of heterogeneous types of neuronal and non-neuronal cells, which are organized into distinct anatomical regions, and show precise regulation of gene expression during development, aging and function. In the current database release, STAB2 provides a systematic cellular map of the human and mouse brain by integrating recently published large-scale single-cell and single-nucleus RNA-sequencing datasets from diverse regions and across lifespan. We applied a hierarchical strategy of unsupervised clustering on the integrated single-cell transcriptomic datasets to precisely annotate the cell types and subtypes in the human and mouse brain. Currently, STAB2 includes 71 and 61 different cell subtypes defined in the human and mouse brain, respectively. It covers 63 subregions and 15 developmental stages of human brain, and 38 subregions and 30 developmental stages of mouse brain, generating a comprehensive atlas for exploring spatiotemporal transcriptomic dynamics in the mammalian brain. We also augmented web interfaces for querying and visualizing the gene expression in specific cell types. STAB2 is freely available at https://mai.fudan.edu.cn/stab2.