The clinical utility of next generation sequencing in endometrial cancer: focusing on molecular subtyping and lynch syndrome.

Objective: To investigate the clinical utility of Next Generation Sequencing (NGS) in molecular typing of endometrial carcinoma and its combined screening for Lynch Syndrome (LS). Methods: 90 patients diagnosed with endometrial carcinoma (EC) and receiving treatment at the Third Affiliated Hospital of Zhengzhou University between March 2022 and December 2023 were included in this study. Molecular typing and germline evaluation for LS were conducted using NGS on the Illumina platform. A retrospective analysis was performed to examine the clinical pathological characteristics, molecular mutation spectrum, and LS screening outcomes among patients with four distinct molecular subtyping categories. Results: Among the 90 cases of EC, 11 cases (12.2%) of POLE mut type, 19 cases (21.1%) of MMRd type, 6 cases (6.7%) of p53 abn type, and 54 cases (60%) of NSMP type were detected, with detailed analysis of their respective molecular characteristics. LS screening identified 9 cases (10%) of pathogenic germline mutations in MMR genes, including 3 cases of MLH1 germline mutations, 2 cases of PMS2, 2 of MSH2, and 2 of MSH6. Of the 9 LS patients, 7 were MMRd type and 2 NSMP type, with 7 cases showing abnormal MMR protein expression. Additionally, 6 cases with germline variants of uncertain significance in MMR genes were detected, including 2 MLH1, 1 MSH6, 2 MSH6, 1 PMS2, and 1 EPCAM. Conclusion: NGS enables precise molecular typing of endometrial carcinoma through the identification of mutations in the POLE, TP53, and MMR genes. Conducting germline mutation testing for MMR genes in all patients with endometrial carcinoma can effectively prevent instances of overlooked LS diagnoses. Nevertheless, the extensive expenses associated with NGS necessitate additional validation and investigation before its clinical implementation can be fully endorsed.

Deciphering the mechanisms of the IL-6/CXCL1 and NOD-like receptor signaling pathways in otitis media with effusion in rodents.

BACKGROUND: Otitis media with effusion (OME) often leads to pediatric hearing loss and is influenced by innate and adaptive immune responses. Innate immunity serves as the non-specific first line of defense against OME. METHODS: We induced OME in rats using ovalbumin. We administered IL-6 monoclonal antibodies intranasally to inhibit IL-6, and we injected an NF-κB inhibitor intraperitoneally to explore the role of IL-6 in innate immunity and its interaction with the NOD-like receptor signaling pathway. We analyzed RNA-sequencing data with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways to assess signaling pathways involved in OME. We also utilized Western blot, quantitative real-time PCR, and immunohistochemistry on middle ear samples and used microscopy to identify immune cells in ear wash fluids. RESULTS: Our study suggests a pivotal role for IL-6 in the immune pathways of rats with OME via the regulation of CXCL1-mediated pathways. Increased levels of IL-6 and CXCL1 were observed in the middle ear tissues, and activation of the NLRP3 inflammasome in OME rats led to an immune response via NF-κB, thus promoting IL-6 and CXCL1 production, which was reduced by IL-6 antibody treatment. CONCLUSIONS: Our findings confirm that IL-6 and CXCL1 play significant roles in the innate immune response in OME in rodents, predominantly via the NOD-like receptor signaling pathway and NLRP3 inflammasome activation. This research sheds light on OME pathogenesis and its immune-related mechanisms.

Projections of Socioeconomic Costs for Individuals with Dementia in China 2020-2050: Modeling Study.

Background: Previous estimates on future socioeconomic costs of dementia in China are inconsistent, and the main drivers of these costs are unclear. Objective: This study projected future socioeconomic costs (healthcare, formal social care, and informal care costs) and value of quality adjusted life years (QALYs) lost to dementia in China and assessed drivers of socioeconomic costs. Methods: Based on our prior projection on dementia cases to 2050 by a Markov model, we forecasted future socioeconomic costs and the value of QALYs from a societal perspective, utilizing the China Health and Retirement Longitudinal Study and the Chinese Longitudinal Healthy Longevity Survey. In our main analysis, dementia incidence increased by 2.9% annually, while sensitivity analyses considered a flat or 1.0% annual decrease in the temporal trend of dementia incidence. Furthermore, we decomposed socioeconomic costs changes (2018 US$) into population growth, population aging, dementia prevalence and average socioeconomic costs per case. Results: The annual socioeconomic costs and value of QALYs lost to dementia will reach $1,233 billion and $702 billion by 2050. If dementia incidence stays constant or decreases by 1.0% annually, the costs and QALYs would respectively decrease by 34% or 43% in 2050. Informal care is currently, and projected to remain, the largest share of socioeconomic costs. Population aging and rising dementia prevalence will mainly drive the growth in socioeconomic costs through 2050. Conclusions: Dementia casts an increasingly large economic burden on Chinese society, mainly driven by fast aging population and growing dementia prevalence.

Decoding 11-oxygenated androgen synthesis: insights from enzyme gene expression and LC-MS/MS quantification.

BACKGROUND: Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited. METHODS: We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes. To validate the findings, immunohistochemical and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques were employed. RESULTS: Our investigation revealed that the gene expression levels of the enzymes HSD11B2 and AKR1C3 were notably elevated in the kidney and intestines. Intriguingly, within these organs, we observed an increasing trend in enzyme expression with age in women, while a decreasing trend was apparent in men. scRNA analysis revealed that HSD11B2 was predominantly expressed in collecting duct principal cells in the kidney, while AKR1C3 was primarily expressed in the proximal tubules. Intriguingly, nearly all epithelial cells in the intestine expressed these key enzymes. Further analysis using LC-MS/MS revealed that the kidney exhibited the highest levels of 11-ketoandrostenedione (11KA4) and 11-ketotestosterone (11KT) among the seven tissues examined, and substantial synthesis of 11KA4 and 11KT was also observed in the intestine. Finally, we developed the TransMap website (http://gxmujyzmolab.cn:16245/TransMap/) to provide comprehensive visualization of all currently available transcriptome data. CONCLUSION: This study offers an overarching perspective on tracing the synthesis of 11-oxygenated androgens in peripheral tissues, thereby providing valuable insights into the potential role of these androgens in humans.

Origin of ultrahigh-performance barium titanate-based piezoelectrics: Stannum-induced intrinsic and extrinsic contributions.

Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

Ecological environmental flow estimation for rivers with complicated hydraulic conditions.

Estimating ecological environmental flow in tidal rivers is one of the major challenges for sustainable water resource management in estuaries and river basins. This paper presents an ecological environmental flow framework that was developed to accommodate highly dynamic medium tidal estuaries found along the Yellow Sea coast of China. The framework not only proposes a method of water quality-based ecological flow for tidal gate-controlled rivers but also proposes a method of water demand for scouring and silting to protect ports in coastal viscous sediment environments. The framework integrates the instream water requirements of water quality, sediment and basic ecological flow, and considers the temporal and spatial variation differences for the environmental flow requirements of tidal rivers. This study emphasizes the significance and necessity of continuous monitoring of ecological data in determining the environmental flow of tidal rivers. The output of this study could provide vital references for decision-making and management of the water resource allocation and ecological protection in tidal rivers.

Hierarchical Branched TiO2 Photo/Photoelectrocatalyst with Directed Charge Transfer for Efficient Hydrogen Production from Seawater.

The directed electron transport channel design in semiconductors, which could promote charge utilization, is attractive but rarely reported. Hierarchical branched titanium dioxide (HB-TiO2), possessing a charge cascade transfer channel, was constructed by assembling titanium-defected TiO2 nanobranches on oxygen-defected TiO2 nanobelts. The interfacial Ti/O vacancies have been detected by X-ray photoelectron and electron paramagnetic resonance spectroscopies, and the vacancies act as the "bridge" of photogenerated carrier transport. This structure maintained high photoactivity in H2 production in different mass fractions of NaCl solutions. The photocurrent density of the HB-TiO2 photoanode in natural seawater is 3.9, 2.1, and 2.6 times that of oxygen-defected TiO2 nanobelts, titanium-defected TiO2 nanobranches, and their mixture, respectively. Besides, the charge transport mechanism from the inner lattice to the TiO2 surface is proposed.

Efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer: a systematic review and meta-analysis.

Background: Various trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. Methods: We utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR). Results: Four trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9-36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1-70.2) for dMMR group and 33.1% (95% CI: 25.7-40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3-78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5-97.6) for the dMMR group and 76.3% (95% CI: 66.3-86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5-100.0) and 80.2% (95% CI: 59.9-100.0), respectively. Conclusion: Lenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.

The therapeutic use of exosomes in children with adenoid hypertrophy accompanied by otitis media with effusion (AHOME): a protocol study.

BACKGROUND: The adenoids act as a reservoir of bacterial pathogens and immune molecules, and they are significantly involved in children with otitis media with effusion (OME). As an essential carrier of intercellular substance transfer and signal transduction, exosomes with different biological functions can be secreted by various types of cells. There remains significant uncertainty regarding the clinical relevance of exosomes to OME, especially in its pathophysiologic development. In this study, we will seek to determine the biological functions of exosomes in children with adenoid hypertrophy accompanied by OME (AHOME). METHODS: The diagnostic criteria for OME in children aged 4-10 years include a disease duration of at least 3 months, type B or C acoustic immittance, and varying degrees of conductive hearing loss. Adenoidal hypertrophy is diagnosed when nasal endoscopy shows at least 60% adenoidal occlusion in the nostrils or when nasopharyngeal lateral X-ray shows A/N > 0.6. Children who meet the indications for adenoidectomy surgery undergo adenoidectomy. Peripheral blood, nasopharyngeal swab, and adenoid tissue will be collected from patients, and the exosomes will be isolated from the samples. Following the initial collection, patients will undergo adenoidectomy and peripheral blood and nasopharyngeal swabs will be collected again after 3 months. EXPECTED RESULTS: This study aims to identify differences in exosomes from preoperative adenoid tissue and peripheral blood samples between children with AHOME and those with adenoid hypertrophy alone. Additionally, it seeks to determine changes in microbial diversity in adenoid tissue between these groups. CONCLUSIONS: The findings are expected to provide new insights into the diagnosis and treatment of OME, to identify novel biomarkers, and to enhance our understanding of the pathophysiology of OME, potentially leading to the development of innovative diagnostic and therapeutic approaches.

Projection for dementia burden in China to 2050: a macro-simulation study by scenarios of dementia incidence trends.

Background: It is unclear how temporal trends in dementia incidence, alongside fast-changing demography, will influence China's future dementia burden. We developed a Markov model that combines population trends in dementia, mortality, and dementia-related comorbidities, to forecast and decompose the burden of dementia in China to 2050. Methods: Population-based Chinese ageing cohorts provided input data for a 10-health-state Markov macrosimulation model, IMPACT-China Ageing Model (CAM), to predict sex- and age-specific dementia prevalence among people aged 50+ by year to 2050. We assumed three potential future scenarios representing the range of likely dementia incidence trends: upward (+2.9%), flat (0%) or downward (-1.0%). Sensitivity analyses were conducted to examine uncertainty associated with trends in mortality rates and CVD incidence. The projected dementia burden was decomposed into population growth, population ageing, and changing dementia prevalence corresponding to the three incidence trend scenarios. Findings: Under the upward trend scenario, the estimated number of people living with dementia is projected to rise to 66.3 million (95% uncertainty interval (UI) 64.7-68.0 million), accounting for 10.4% of the Chinese population aged 50+ by 2050. This large burden will be lower, 43.9 (95% UI 42.9-45.0) million and 37.5 (95% UI 36.5-38.4) million, if dementia incidence remains constant or decreases. Robustness of the projection is confirmed by sensitivity analyses. Decomposition of the change in projected dementia cases indicates dominate effects of increasing dementia prevalence and population ageing, and a relatively minor contribution from negative population growth. Interpretation: Our findings highlight an impending surge in dementia cases in China in the forthcoming decades if the upward trend in dementia incidence continues. Public health interventions geared towards dementia prevention could play a pivotal role in alleviating this burgeoning disease issue. Funding: National Science Foundation of China/UK Economic and Social Research Council.

Design and synthesis of an environment-sensitive 3-methyleneisoindolin-1-one fluorophore for labeling DNA-interacting proteins.

We designed 6-dimethylamino 3-methyleneisoindolin-1-one as an environment-sensitive fluorophore, examining its applications for protein labeling. Synthesized 3-methyleneisoindolin-1-one exhibits solvatochromic fluorescence (λemmax; 472 nm in 2-PrOH, 512 nm in H2O). A positive linear dependence between λemmax and solvent dielectric constant (DC), as well as between Stokes shift and DC, and a negative correlation between fluorescence quantum yield and DC are observed in protic solvents. These properties are similar to those of the oxygen isosteric fluorophore, 4-dimethylaminophthalimide, a slovatochromic fluorophore utilized for labeling oligodeoxynucleotides (ODNs) and peptides. Notably, fluorescence intensity of 3-methyleneisoindolin-1-one is higher than the phthalimide in protic solvents used in this study. The 3-methyleneisoindolin-1-one demonstrated the higher stability in pH 8 solution than in pH 6 solution in contrast to the stability profile of the phthalimide, which was stable at pH 6 but was hydrolyzed at pH 8. We also synthesized an o-keto benzaldehyde derivative that converts a primary amine to 6-dimethylamino 3-methyleneisoindolin-1-one under biocompatible conditions and introduced it into ODNs for turn-on fluorescent protein labeling. The synthesized ODN with a protein-binding sequence of Escherichia coli DnaA was employed to modify the DNA-binding domain of DnaA, and the fluorescent properties of the modified protein were investigated.

How the Degree of Anthropomorphism of Human-like Robots Affects Users' Perceptual and Emotional Processing: Evidence from an EEG Study.

Anthropomorphized robots are increasingly integrated into human social life, playing vital roles across various fields. This study aimed to elucidate the neural dynamics underlying users' perceptual and emotional responses to robots with varying levels of anthropomorphism. We investigated event-related potentials (ERPs) and event-related spectral perturbations (ERSPs) elicited while participants viewed, perceived, and rated the affection of robots with low (L-AR), medium (M-AR), and high (H-AR) levels of anthropomorphism. EEG data were recorded from 42 participants. Results revealed that H-AR induced a more negative N1 and increased frontal theta power, but decreased P2 in early time windows. Conversely, M-AR and L-AR elicited larger P2 compared to H-AR. In later time windows, M-AR generated greater late positive potential (LPP) and enhanced parietal-occipital theta oscillations than H-AR and L-AR. These findings suggest distinct neural processing phases: early feature detection and selective attention allocation, followed by later affective appraisal. Early detection of facial form and animacy, with P2 reflecting higher-order visual processing, appeared to correlate with anthropomorphism levels. This research advances the understanding of emotional processing in anthropomorphic robot design and provides valuable insights for robot designers and manufacturers regarding emotional and feature design, evaluation, and promotion of anthropomorphic robots.

Novel Chemical Routes for Carbon Dioxide and Methane Production from Lignin Photodegradation: The Role of Environmental Free Radicals.

Sunlight irradiation significantly mediates plant litter's carbon dynamics and volatile carbon release in semi-arid and arid ecosystems. In this process, carbon loss is controlled by lignin, but the mechanisms of production of CO2 and CH4 during lignin photolysis are ambiguous. In this study, the photomineralization of plant litter and the lignocellulosic component collectively indicate that lignin is a major source of CO2 and CH4 emissions. Characterization and free radical analysis reveal that the production of CO2 is due to the oxidation and ring-opening reaction of the coniferyl alcohol unit, with the subsequent decarboxylation of carboxylic acid as an oxidation product. This reaction involves o-quinone formation by the reactions between O2, superoxide radical (O2·-), and persistent free radicals (PFRs)-bearing lignin. Of this, O2·- contributes to 43.2% of the photogenerated CO2, as a new pathway, derived from the electron transfer from PFRs to O2. Interestingly, photoinduced demethylation of the dimethoxybenzene-type compounds as the photolysis products of lignin results in a never-before-reported CH4 formation chemical route independent of that of O2. This mechanistic insight into the role of lignin in volatile carbon production from the irradiative plant litter will contribute to a deeper understanding of carbon balance in water-limited ecosystems.

Identifying genetic determinants of sarcopenia-related traits: a Mendelian randomization study of druggable genes.

BACKGROUND: Sarcopenia, characterized by progressive muscle mass and function loss, particularly affects the elderly, and leads to severe consequences such as falls and mortality. Despite its prevalence, targeted pharmacotherapies for sarcopenia are lacking. Utilizing large-sample genome-wide association studies (GWAS) data is crucial for cost-effective drug discovery. METHODS: Herein, we conducted four studies to understand the putative causal effects of genetic components on muscle mass and function. Study 1 employed a two-sample Mendelian randomization (MR) on 15,944 potential druggable genes, investigating their potential causality with muscle quantity and quality in a European population (N up to 461,089). Study 2 validated MR results through sensitivity analyses and colocalization analyses. Study 3 extended validation across other European cohorts, and study 4 conducted quantitative in vivo verification. RESULTS: MR analysis revealed significant causality between four genes (BLOC-1 related complex subunit 7, BORCS7; peptidase m20 domain containing 1, PM20D1; nuclear casein kinase and cyclin dependent kinase substrate 1, NUCKS1 and ubiquinol-cytochrome c reductase complex assembly factor 1, UQCC1) and muscle mass and function (p-values range 5.98 × 10-6 to 9.26 × 10-55). To be specific, BORCS7 and UQCC1 negatively regulated muscle quantity and quality, whereas enhancing PM20D1 and NUCKS1 expression showed promise in promoting muscle mass and function. Causal relationships remained robust across sensitivity analyses, with UQCC1 exhibiting notable colocalization effects (PP·H4 93.4 % to 95.8 %). Further validation and in vivo replication verified the potential causality between these genes and muscle mass as well as function. CONCLUSIONS: Our druggable genome-wide MR analysis identifies BORCS7, PM20D1, NUCKS1, and UQCC1 as causally associated with muscle mass and function. These findings offer insights into the genetic basis of sarcopenia, paving the way for these genes to become promising drug targets in mitigating this debilitating condition.

The Effects of Climate Change on the Distribution Pattern of Species Richness of Endemic Wetland Plants in the Qinghai-Tibet Plateau.

Wetland ecosystems in the Qinghai-Tibet Plateau (QTP), the region with the richest biodiversity and the most important ecological barrier function at high altitudes, are highly sensitive to global change, and wetland plants, which are important indicators of wetland ecosystem structure and function, are also threatened by wetland degradation. Therefore, a comprehensive study of changes in the geographical distribution pattern of plant diversity, as well as species loss and turnover of wetlands in the QTP in the context of global climate change is of great importance for the conservation and restoration of wetland ecosystems in the QTP. In this study, species turnover and loss of 395 endemic wetland plants of the QTP were predicted based on the SSP2-4.5 climate change scenarios. The results showed that there were interspecific differences in the effects of climate change on the potential distribution of species, and that most endemic wetland plants would experience range contraction. Under the climate change scenarios, the loss of suitable wetland plant habitat is expected to occur mainly in parts of the southern, north-central and north-western parts of the plateau, while the gain is mainly concentrated in parts of the western Sichuan Plateau, the Qilian Mountains, the Three Rivers Source Region and the northern Tibetan Plateau. Overlaying the analysis of priority protected areas with the established protected areas in the QTP has resulted in the following conservation gaps: the eastern Himalayan region, midstream of the Yarlung Zangbo River, the transition zone between the northern Tibetan Plateau and the Hengduan Mountains, Minshan-Qionglai mountain, Anyemaqen Mountains (southeast) to Bayankala (southeast) mountains, the southern foothills of the Qilian Mountains and the northern Tibetan Plateau region. In the future, the study of wetland plant diversity in the QTP and the optimisation of protected areas should focus on the conservation gaps. This study is of great importance for the study and conservation of wetland plant diversity in the QTP, and also provides a scientific basis for predicting the response of wetland plants to climate change in the QTP.

Validity of the Chinese multimorbidity-weighted index in measuring disease burden using health check-ups data in primary care.

BACKGROUND: As multimorbidity becomes common that imposes a considerable burden to patients, but the extent to which widely-used multimorbidity indexes can be applied to quantify disease burden using primary care data in China is not clear. We applied the Chinese Multimorbidity-Weighted Index (CMWI) to health check-ups data routinely collected among older adults by primary care, to examine its validity in measuring multimorbidity associated risks of disability and mortality in annual follow-ups. METHODS: The study utilized data from annual health check-ups of older adults, which included information on individual age, sex, and 14 health conditions at primary care in a district of Guangzhou, Guangdong, China. The risk of CMWI for mortality was analysed in a total sample of 45,009 persons 65 years and older between 2014 and 2020 (average 2.70-year follow-up), and the risk for disability was in a subsample of 18,320 older adults free of physical impairment in 2019 and followed-up in 2020. Risk of death and disability were assessed with Cox proportional hazard regression and binary logistic regression, respectively, with both models adjusted for age and sex variables. The model fit was assessed by the Akaike information criterion (AIC), and C-statistic or the area under the receiver operating characteristic curve (AUC). RESULTS: One unit increase in baseline-CMWI (Median= 1.70, IQR: 1.30-3.00) was associated with higher risk in subsequent disability (OR = 1.12, 95%CI = 1.05,1.20) and mortality (OR = 1.18, 95%CI = 1.14, 1.22). Participants in the top tertile of CMWI had 99% and 152% increased risks of disability and mortality than their counterparts in the bottom tertile. Model fit was satisfied with adequate AUC (0.84) or C-statistic (0.76) for both outcomes. CONCLUSIONS: CMWI, calculated based on primary care's routine health check-ups data, provides valid estimates of disability and mortality risks in older adults. This validated tool can be used to quantity and monitor older patients' health risks in primary care.

Global leaf sulfur stoichiometry and the relationships with nitrogen and phosphorus: phylogeny, growth form and environmental controls.

Sulfur (S) is an essential bioelement with vital roles in serving regulatory and catalytic functions and tightly coupled with N and P in plants. However, globally stoichiometric patterns of leaf S and its relationships to leaf N and P are less well studied. We compiled 31 939 records of leaf-based data for 2600 plant species across 6652 sites worldwide. All plant species were divided into different phylogenetic taxa and growth forms. Standard major axis analysis was employed to fit the bivariate element relationships. A phylogenetic linear mixed-effect model and a multiple-regression model were used to partition the variations of bioelements into phylogeny and environments, and then to estimate the importance of environmental variables. Global geometric mean leaf S, N and P concentrations were 1.44, 15.70 and 1.27 mg g-1, respectively, with significant differences among plant groups. Leaf S-N-P positively correlated with each other, ignoring plant groups. The scaling exponents of LN-LS, LP-LS and LN-LP were 0.64, 0.76 and 0.79, respectively, for all species, but differed among plant groups. Both phylogeny and environments regulated the bioelements. The variability, rather than mean temperature, controlled the bioelements. Phylogeny explained more for the concentrations of all the three bioelements than environments, of which S was the one most affected by phylogenetic taxa.

Integrative proteome and metabolome unveil the central role of IAA alteration in axillary bud development following topping in tobacco.

Axillary bud is an important aspect of plant morphology, contributing to the final tobacco yield. However, the mechanisms of axillary bud development in tobacco remain largely unknown. To investigate this aspect of tobacco biology, the metabolome and proteome of the axillary buds before and after topping were compared. A total of 569 metabolites were differentially abundant before and 1, 3, and 5 days after topping. KEGG analyses further revealed that the axillary bud was characterized by a striking enrichment of metabolites involved in flavonoid metabolism, suggesting a strong flavonoid biosynthesis activity in the tobacco axillary bud after topping. Additionally, 9035 differentially expressed proteins (DEPs) were identified before and 1, 3, and 5 days after topping. Subsequent GO and KEGG analyses revealed that the DEPs in the axillary bud were enriched in oxidative stress, hormone signal transduction, MAPK signaling pathway, and starch and sucrose metabolism. The integrated proteome and metabolome analysis revealed that the indole-3-acetic acid (IAA) alteration in buds control dormancy release and sustained growth of axillary bud by regulating proteins involved in carbohydrate metabolism, amino acid metabolism, and lipid metabolism. Notably, the proteins related to reactive oxygen species (ROS) scavenging and flavonoid biosynthesis were strongly negatively correlated with IAA content. These findings shed light on a critical role of IAA alteration in regulating axillary bud outgrowth, and implied a potential crosstalk among IAA alteration, ROS homeostasis, and flavonoid biosynthesis in tobacco axillary bud under topping stress, which could improve our understanding of the IAA alteration in axillary bud as an important regulator of axillary bud development.

Association between stress hyperglycemia ratio and in-hospital outcomes: findings from the improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) Project.

BACKGROUND: Stress hyperglycemia ratio (SHR) could provide accurate information on the acute status of hyperglycemia. The relationship between SHR and acute coronary syndrome (ACS) prognosis remains unclear. This study was conducted to identity the association between SHR and in-hospital outcomes in patients with ACS. METHODS: A total of 12,010 patients were eventually enrolled in the study. The relationship between SHR and in-hospital major adverse cardiovascular events (MACEs) was then modeled by restricted cubic spline (RCS) curves, and all patients were divided into three groups according to the results. The multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes, described as odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were also performed on different diseases. RESULTS: The median age of this cohort was 63 (54, 71) years old, and 8942 (74.5%) were male. Group 1 was defined as SHR < 0.6 (n = 426), Group 2 was defined as SHR between 0.6 and 1 (n = 5821), and Group 3 was defined as SHR > 1 (n = 5763). Compared with Group 2, Group 1 (OR = 1.891, 95% CI: 1.028-3.479, P < 0.001) and Group 3 (OR = 1.868, 95% CI: 1.434-2.434, P < 0.001) had higher risks of suffering from in-hospital MACEs. SHR was associated with higher risks of in-hospital MACEs in the subgroups of DM [OR = 2.282, 95% CI: 1.477-3.524). CONCLUSIONS: Both low and high SHR levels were independently associated with in-hospital MACEs. Young males with DM, hypertension, and decreased renal function had much higher risks of suffering from SHR-correlated MACEs.

Geographical variation in dementia prevalence across China: a geospatial analysis.

Background: Dementia poses great health and social challenges in China. Dementia prevalence may vary across geographic areas, while comparable estimations on provincial level is lacking. This study aims to estimate dementia prevalence by provinces across China, taking into account risk factors of individual level and potential spatial correlation of provinces. Methods: In this study, 17,176 adults aged 50 years or older were included from the fourth wave of the China Health and Retirement Longitudinal Study (CHARLS 2018), covering 28 provinces, autonomous regions and municipalities. To improve provincial representativeness, we constructed provincial survey weights based on China 7th census (2020). The prevalence of dementia and 95% Bayesian credible intervals (BCIs) were estimated using a Bayesian conditional autoregressive (CAR) model with spatially varying coefficients of covariates. Findings: The weighted prevalence of dementia at provincial level in China in 2018 ranged from 2.62% (95%BCI: 1.70%, 3.91%) to 13.53% (95%BCI: 8.82%, 20.93%). High dementia prevalence was concentrated in North China, with a prominent high-high cluster, while provinces of low prevalence were concentrated on East and South China, characterized by a low-low cluster. Ordered by the median estimation of prevalence, the top 10% of provinces, include Xinjiang, Jilin, and Beijing. Meanwhile, Fujian, Zhejiang, and Guangdong rank among the last. The association between dementia prevalence and drinking, smoking, social isolation, physical inactivity, hearing impairment, hypertension, and diabetes exhibits provincial variation. Interpretation: Our study identifies a geospatial disparity in dementia prevalence and risk factor effects across China's provinces, with high-high and low-low clusters in some northern and southern provinces, respectively. The findings emphasize the need for targeted strategies, such as addressing hypertension and hearing impairment, in specific regions for more effective dementia prevention and treatment. Funding: National Science Foundation of China/the Economic and Social Research Council, UK Research and Innovation joint call: Understanding and Addressing Health and Social Challenges for Ageing in the UK and China. UK-China Health And Social Challenges Ageing Project (UKCHASCAP): present and future burden of dementia, and policy responses (grant number 72061137003, ES/T014377/1).