Copeptin associates with major adverse cardiovascular events in patients on maintenance hemodialysis.

BACKGROUND: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. OBJECTIVE: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. METHODS: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. RESULTS: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. CONCLUSION: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.

Zebra-Patterned Stretchable Helical Yarn for Triboelectric Self-Powered Multifunctional Sensing.

Smart textiles capable of both energy harvesting and multifunctional sensing are highly desirable for next-generation portable electronics. However, there are still challenges that need to be conquered, such as the innovation of an energy-harvesting model and the optimization of interface bonding between fibers and active materials. Herein, inspired by the spiral structure of natural vines, a highly stretchable triboelectric helical yarn (TEHY) was manufactured by twisting the carbon nanotube/polyurethane nanofiber (CNT/PU NF) Janus membrane. The TEHY had a zebra-stripe-like design that was composed of black interval conductive CNTs and white insulative PU NFs. Due to the different electron affinity, the zebra-patterned TEHY realized a self-frictional triboelectric effect because the numerous microscopic CNT/PU triboelectric interfaces generated an alternating current in the external conductive circuit without extra external friction layers. The helical geometry combined with the elastic PU matrix endowed TEHY with superelastic stretchability and outstanding output stability after 1000 cycles of the stretch-release test. By virtue of the robust mechanical and electrical stability, the TEHY can not only be used as a high-entropy mechanical energy harvester but also serve as a self-powered sensor to monitor the stretching or deforming stimuli and human physiological activities in real time. These merits manifested the versatile applications of TEHY in smart fabrics, wearable power supplies, and human-machine interactions.

Differences in archaeal diversity and potential ecological functions between saline and hypersaline lakes on Qinghai-Tibet Plateau were driven by multiple environmental and non-environmental factors beyond the salinity.

BACKGROUND: Saline lakes are home to various archaea that play special and crucial roles in the global biogeochemical cycle. The Qinghai-Tibet Plateau hosts a large number of lakes with diverse salinity ranging from 0.1 to over 400 g/L, harboring complex and diverse archaea. To the best of our knowledge, the formation mechanisms and potential ecological roles of archaea in Qinghai-Tibetan Plateau saline lakes remain largely unknown. RESULTS: Using High-throughput Illumina sequencing, we uncovered the vastly distinct archaea communities between two typical saline lakes with significant salinity differences on the Qinghai Tibet Plateau (Qinghai saline lake and Chaka hypersaline lake) and suggested archaea played different important roles in methanogenesis-related and nitrate reduction-related functions of these two lakes, respectively. Rather than the individual effect of salinity, the composite effect of salinity with diverse environmental parameters (e.g., temperature, chlorophyll a, total nitrogen, and total phosphorus) dominated the explanation of the variations in archaeal community structure in different habitats. Based on the network analysis, we further found the correlations between dominant archaeal OTUs were tight but significantly different between the two habitats, implying that archaeal interactions may also largely determine the shape of archaeal communities. CONCLUSION: The present study improved our understanding of the structure and function of archaea in different saline lakes on the Qinghai-Tibet Plateau and provided a new perspective on the mechanisms underlying shaping their communities.

Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. METHODS: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02-1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12-1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42-2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52-3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532. CONCLUSIONS: Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.

Longitudinal Trajectories of Social Mobility Beliefs among Chinese Adolescents: The Protective Roles of Parental Academic Involvement and Adolescent Future Orientation.

Social mobility beliefs play a significant role in shaping adolescents' adaptive developmental outcomes, including well-being and academic functioning. Nevertheless, existing research may not cast light on the distinct trajectories and potential protective factors of social mobility beliefs. The present study aims to identify heterogeneity in trajectory patterns of social mobility beliefs among Chinese adolescents (Mage = 12.45, SDage = 2.60; 55.1% boys; 40.0% rural adolescents) in a four-wave (i.e., fall 2017, fall 2018, spring 2019, and fall 2019) longitudinal design, and examines the protective roles of parental academic involvement and adolescent future orientation. Three distinct trajectories of social mobility beliefs were identified: high-increasing (35.1%; a positive trajectory with the best developmental outcomes, including the lowest problem behaviors and depression symptoms, and the highest life satisfaction and academic competence), moderate-stable (49.8%), and low-decreasing (15.1%; a negative trajectory with the worst developmental outcomes, including the highest problem behaviors and depression symptoms, and the lowest life satisfaction and academic competence). Apart from the main effects of parental academic involvement and future orientation, a significant interaction effect of these two protective factors and adolescent group was detected, and only rural adolescents who reported both high levels of parental academic involvement and future orientation have a greater chance of being placed in the high-increasing trajectory than the low-decreasing trajectory. These findings highlight the significance of clarifying individual differences in the dynamic process of social mobility beliefs during adolescence, and elucidate rural-urban disparities in the influences of protective factors on social mobility beliefs trajectories, and inform individualized intervention strategies.

Refrigerated storage stimulates isoflavone and γ-aminobutyric acid accumulation in germinated soybeans.

This study aims to investigate the quality changes of germinated soybeans during refrigerated storage (4 °C), with an emphasis on the stimulatory effect of refrigeration on their special functional compounds. After germinating for two days, germinated soybeans were stored at 4 °C for seven days, while the germinated soybeans stored at 25 °C served as control group. The results showed that refrigerated storage significantly affected the physiological changes in germinated soybeans. The weight loss rate, browning rate, malondialdehyde (MDA) content and H2O2 content all decreased dramatically during refrigerated storage compared to the control group. The total phenolic and total flavonoid contents of germinated soybeans under refrigeration exhibited a trend of increasing and then decreasing over time. Additionally, during refrigerated storage, the total isoflavone content reached a peak of 8.72 g/kg on the fifth day, in which the content of daidzein and glycitin increased by 45% and 49% respectively, when compared with the control group. Moreover, the content of γ-aminobutyric acid (GABA) peaked on the first day, and kept a high level during storage. In which, the refrigerated group was 2.35-, 2.88-, 1.67-fold respectively after storage for three to seven days. These results indicated that refrigeration stimulated the biosynthesis of isoflavones and GABA in germinated soybeans during storage. More importantly, there was a sequential difference in the timing of the stimulation of the two functional components under refrigeration.

The Construction of Three-Layered Biomimetic Arterial Graft Balances Biomechanics and Biocompatibility for Dynamic Biological Reconstruction.

The process of reconstructing an arterial graft is a complex and dynamic process that is subject to the influence of various mechanical factors, including tissue regeneration and blood pressure. The attainment of favorable remodeling outcomes is contingent upon the biocompatibility and biomechanical properties of the arterial graft. A promising strategy involves the emulation of the three-layer structure of the native artery, wherein the inner layer is composed of polycaprolactone (PCL) fibers aligned with blood flow, exhibiting excellent biocompatibility that fosters endothelial cell growth and effectively prevents platelet adhesion. The middle layer, consisting of PCL and polyurethane (PU), offers mechanical support and stability by forming a contractile smooth muscle ring and antiexpansion PU network. The outer layer, composed of PCL fibers with an irregular arrangement, promotes the growth of nerves and pericytes for long-term vascular function. Prioritizing the reconstruction of the inner and outer layers establishes a stable environment for intermediate smooth muscle growth. Our three-layer arterial graft is designed to provide the blood vessel with mechanical support and stability through nondegradable PU, while the incorporation of degradable PCL generates potential spaces for tissue ingrowth, thereby transforming our graft into a living implant.

Predicting the impact of rare variants on RNA splicing in CAGI6.

Variants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict a variant's impact on splicing are needed to interpret the growing number of variants of unknown significance (VUS) identified by exome and genome sequencing. Here, we present the results of the CAGI6 Splicing VUS challenge, which invited predictions of the splicing impact of 56 variants ascertained clinically and functionally validated to determine splicing impact. The performance of 12 prediction methods, along with SpliceAI and CADD, was compared on the 56 functionally validated variants. The maximum accuracy achieved was 82% from two different approaches, one weighting SpliceAI scores by minor allele frequency, and one applying the recently published Splicing Prediction Pipeline (SPiP). SPiP performed optimally in terms of sensitivity, while an ensemble method combining multiple prediction tools and information from databases exceeded all others for specificity. Several challenge methods equalled or exceeded the performance of SpliceAI, with ultimate choice of prediction method likely to depend on experimental or clinical aims. One quarter of the variants were incorrectly predicted by at least 50% of the methods, highlighting the need for further improvements to splicing prediction methods for successful clinical application.

Scutellarin Alleviates Ovalbumin-Induced Airway Remodeling in Mice and TGF-ß-Induced Pro-fibrotic Phenotype in Human Bronchial Epithelial Cells via MAPK and Smad2/3 Signaling Pathways.

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. Epithelial-mesenchymal transition (EMT) is an essential player in these alterations. Scutellarin is isolated from Erigeron breviscapus. Its vascular relaxative, myocardial protective, and anti-inflammatory effects have been well established. This study was designed to detect the biological roles of scutellarin in asthma and its related mechanisms. The asthma-like conditions were induced by ovalbumin challenges. The airway resistance and dynamic compliance were recorded as the results of AHR. Bronchoalveolar lavage fluid (BALF) was collected and processed for differential cell counting. Hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson staining were conducted to examine histopathological changes. The levels of asthma-related cytokines were measured by enzyme-linked immunosorbent assay. For in vitro analysis, the 16HBE cells were stimulated with 10 ng/mL transforming growth beta-1 (TGF-ß1). Cell migration was estimated by Transwell assays and wound healing assays. E-cadherin, N-cadherin, and α-smooth muscle actin (α-SMA) were analyzed by western blotting, real-time quantitative polymerase chain reaction, immunofluorescence staining, and immunohistochemistry staining. The underlying mechanisms of the mitogen-activated protein kinase (MAPK) and Smad pathways were investigated by western blotting. In an ovalbumin-induced asthmatic mouse model, scutellarin suppressed inflammation and inflammatory cell infiltration into the lungs and attenuated AHR and airway remodeling. Additionally, scutellarin inhibited airway EMT (upregulated E-cadherin level and downregulated N-cadherin and α-SMA) in ovalbumin-challenged asthmatic mice. For in vitro analysis, scutellarin prevented the TGF-ß1-induced migration and EMT in 16HBE cells. Mechanistically, scutellarin inhibits the phosphorylation of Smad2, Smad3, ERK, JNK, and p38 in vitro and in vivo. In conclusion, scutellarin can inactivate the Smad/MAPK pathways to suppress the TGF-ß1-stimulated epithelial fibrosis and EMT and relieve airway inflammation and remodeling in asthma. This study provides a potential therapeutic strategy for asthma.

Study on the burden of digestive diseases among Chinese residents in the 21st century.

Background: The global burden of digestive diseases has increased in recent years. The study aims to comprehend the trend of incidence and death rates related to digestive diseases in China from 2000 to 2020. Methods: The study collected data on digestive diseases and their causes, such as incidence rates, death rates, Years of Life Lost, Years Lived with Disability, Disability-Adjusted Life Years and estimated annual percentage change from the 2019 Global Burden of Disease website and the Chinese Health and Wellness Statistical Yearbook spanning. And we employed the age-period-cohort model to analyze the influence of age, period, and birth cohort on the trend of death rates associated with digestive diseases. Results: In contrast to the global burden of digestive disease, China experienced increases in the age-standardized incidence for inflammatory bowel disease, gallbladder and biliary diseases, as well as appendicitis from 2000 to 2019. The corresponding estimated annual percentage change for these diseases were 2.06, 1.74, and 0.99. Females showed a significantly higher incidence of digestive diseases, while males experienced a higher death rate. Moreover, individuals in the age groups under 5 years and over 60 years exhibited higher death rates than those in other age groups. Conclusion: The findings underscore the ongoing importance of digestive diseases as a substantial public health issue in China. Reducing the disease burden of IBD in China necessitates healthcare systems to enhance their infrastructure and personnel readiness, ensuring an equitable, affordable, and accessible distribution of care for IBD patients. To reduce the occurrence and mortality rates of digestive diseases in China, the government should promote the adoption of early screening policies for individuals under the 5 year and those above the 60 year. These policies should be accompanied by customized preventive measures.

Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case-control study based on the China Neonatal Genomes Project.

Objective: We aimed to investigate the clinical and genetic risk factors associated with neonatal severe unconjugated hyperbilirubinemia. Methods: This was a retrospective, 1:1 matched, case-control study. We included 614 neonates diagnosed with severe unconjugated hyperbilirubinemia (serum total bilirubin level ≥425 µmol/L or serum total bilirubin concentration that met exchange transfusion criteria) from the China Neonatal Genomes Project in Children's Hospital of Fudan University. Clinical exome sequencing data were analyzed using a data analysis pipeline of Children's Hospital of Fudan University. The factors associated with severe unconjugated hyperbilirubinemia were assessed using univariable and multivariable logistic regression analyses. Interaction analyses were examined between clinical and genetic risk factors. Results: ABO/Rh incompatibility hemolysis (odds ratio [OR] 3.36, 95% confidence interval [CI] 2.32-4.86), extravascular hemorrhage (OR 2.95, 95% CI 2.24-3.89), weight loss (OR 5.46, 95% CI 2.88-10.36), exclusive breastmilk feeding (OR 3.56, 95% CI 2.71-4.68), and the homozygous mutant of UGT1A1 211G>A (OR 2.35, 95% CI 1.54-3.59) were all identified as factors significantly associated with severe unconjugated hyperbilirubinemia. The presence of UGT1A1 211G>A mildly increased the risk of severe unconjugated hyperbilirubinemia caused by ABO/Rh incompatibility hemolysis (OR 3.98, 95% CI 2.19-7.23), although the effect is not statistically significant. Conclusion: ABO/Rh incompatibility hemolysis, extravascular hemorrhage, weight loss, exclusive breastmilk feeding, and the homozygous mutant of UGT1A1 211G>A were found to be risk factors for severe unconjugated hyperbilirubinemia. Clinical factors remain the most crucial and preventable determinants in managing severe unconjugated hyperbilirubinemia, with a minimal genetic contribution. The establishment of preconception care practices and the reinforcement of screening for the aforementioned risk factors are essential steps for preventing severe unconjugated hyperbilirubinemia.

Application of Metabolomics and Traditional Chinese Medicine for Type 2 Diabetes Mellitus Treatment.

Diabetes is a major global public health problem with high incidence and case fatality rates. Traditional Chinese medicine (TCM) is used to help manage Type 2 Diabetes Mellitus (T2DM) and has steadily gained international acceptance. Despite being generally accepted in daily practice, the TCM methods and hypotheses for understanding diseases lack applicability in the current scientific characterization systems. To date, there is no systematic evaluation system for TCM in preventing and treating T2DM. Metabonomics is a powerful tool to predict the level of metabolites in vivo, reveal the potential mechanism, and diagnose the physiological state of patients in time to guide the follow-up intervention of T2DM. Notably, metabolomics is also effective in promoting TCM modernization and advancement in personalized medicine. This review provides updated knowledge on applying metabolomics to TCM syndrome differentiation, diagnosis, biomarker discovery, and treatment of T2DM by TCM. Its application in diabetic complications is discussed. The combination of multi-omics and microbiome to fully elucidate the use of TCM to treat T2DM is further envisioned.

Management of Cardiovascular Diseases in Chronic Hemodialysis Patients.

Hemodialysis (HD) is the main treatment modality for patients with end-stage kidney disease. Cardiovascular diseases (CVD) are highly prevalent in HD patients and are the leading cause of death in this population, with the mortality from CVD approximately 20 times higher than that of the general population. Traditional and non-traditional cardiovascular risk factors accelerate progression of CVD and exacerbate the prognosis in HD patients. This review provides a brief overview of the characteristics of CVD in HD patients, and a description of advances in its management.