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.

Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery. METHODS: This prospective, single-center, double-blind, randomized controlled trial involved 509 patients at high risk for AKI who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Patients were randomized to receive RIPC (4 cycles of 5-minute inflation and 5-minute deflation on 1 upper arm with a blood pressure cuff) 24 hours before surgery or a sham condition (control group) that was induced by 4 cycles of 5-minute inflation to a pressure of 20 mm Hg followed by 5-minute cuff deflation. The primary end point was the incidence of AKI within the prior 7 days after cardiac surgery. The secondary end points included renal replacement therapy during hospitalization, change in urinary biomarkers of AKI and markers of myocardial injury, duration of intensive care unit stay and mechanical ventilation, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. RESULTS: A total of 509 patients (mean age, 65.2±8.2 years; 348 men [68.4%]) were randomly assigned to the RIPC group (n=254) or control group (n=255). AKI was significantly reduced in the RIPC group compared with the control group (69/254 [27.2%] versus 90/255 [35.3%]; odds ratio, 0.68 [95% CI, 0.47-1.00]; P=0.048). There were no significant between-group differences in the secondary end points of perioperative myocardial injury (assessed by the concentrations of cardiac troponin T, creatine kinase myocardial isoenzyme, and NT-proBNP [N-terminal pro-brain natriuretic peptide]), duration of stay in the intensive care unit and hospital, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. CONCLUSIONS: Among high-risk patients undergoing cardiac surgery, delayed RIPC significantly reduced the occurrence of AKI. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000035568.

The efficacy of neoadjuvant immunotherapy and lymphocyte subset predictors in locally advanced esophageal squamous cell carcinoma: A retrospective study.

BACKGROUND: Despite the recognized therapeutic potential of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in advanced esophageal squamous cell carcinoma (ESCC), their role in neoadjuvant therapy and reliable efficacy biomarkers remain elusive. MATERIALS AND METHODS: We retrospectively analyzed locally advanced ESCC patients who underwent surgery following a 2-cycle platinum and paclitaxel-based treatment, with or without PD-1 inhibitors (January 2020-March 2023). We assessed peripheral blood indexes and tertiary lymphoid structures (TLS) density to evaluate their impact on pathological response and prognosis, leading to a clinical prediction model for treatment efficacy and survival. RESULTS: Of the 157 patients recruited, 106 received immunochemotherapy (ICT) and 51 received chemotherapy (CT) alone. The ICT group demonstrated a superior pathological response rate (PRR) (47.2% vs. 29.4%, p = 0.034) with comparable adverse events and postoperative complications. The ICT group also showed a median disease-free survival (DFS) of 39.8 months, unattained by the CT group. The 1-year DFS and overall survival (OS) rates were 73% and 91% for the ICT group, and 68% and 81% for the CT group, respectively. We found higher baseline activated T cells, lower baseline Treg cells, and a decreased posttreatment total lymphocyte and CD4+/CD8+ ratio predicted an enhanced PRR. Reduced posttreatment CD4+/CD8+ ratio and increased NK cells were associated with prolonged survival, while higher TLS density indicated poorer prognosis. Among ICT group, a lower posttreatment CD4+/CD8+ ratio indicated longer DFS and reduced posttreatment B cells indicated longer OS. A nomogram integrating these predictors was developed to forecast treatment efficacy and survival. CONCLUSION: The combination of PD-1 inhibitors and chemotherapy appears promising for locally advanced ESCC. Evaluating the differentiation status and dynamic changes of peripheral blood immune cells may provide valuable predictive insights into treatment efficacy and prognosis.

Effect of omicron infection on maternal and neonatal delivery outcomes: A retrospective cohort study.

BACKGROUND: People are very concerned about the adverse effects of Omicron infection on delivery modes, duration of labor, and the postpartum status of pregnant women and neonates. METHODS: 382 pregnant women (Omicron group: 136 cases; non-Omicron group: 246 cases) giving birth in our hospital were collected, demographic characteristics, vaccination, clinical manifestation and medication, delivery outcomes of pregnant women and neonates were recorded. Delivery outcomes were compared between the Omicron and non-Omicron groups, acute infection and non-acute infection groups to explore the relationship between adverse delivery outcomes and Omicron infection. RESULTS: Pregnant women in the Omicron group had a longer hospitalization time (6.3 ± 3.6 days vs.5.5 ± 2.3 days), more 2-hour postpartum hemorrhage (291.7 ± 104.9 mL vs.262.7 ± 91.2 mL) and higher neonatal-pediatric transfer rate (20.6 % vs. 2.8 %), which might be associated with fetal distress, prenatal fever and pneumonia/respiratory distress. Neonates transferred to pediatrics due to jaundice were unique in the Omicron group. Fever-pregnant women have a more prolonged second stage of labor and hospital stay while coughing or expectoration ones have a shorter third stage of labor. Delivery outcomes did not differ whether the infected pregnant women were in the acute phase and whether to use antipyretics. CONCLUSION: Omicron infection can increase the 2-hour postpartum hemorrhage volume and the neonatal-pediatric transfer rate. The symptoms can affect the duration of labor and hospital stay. However, whether the infected pregnant women are in the acute phase or use antipyretics do not affect the delivery outcome.

PdPtCu mesoporous nanocube-based electrochemical sandwich immunosensor for detection of HIV-p24.

The construction of simple, stable, low-cost and reproducible enzyme-free electrochemical biosensors can effectively avoid the problem of signal attenuation caused by enzyme inactivation. Hererin, we prepared a novel nanoenzymes PdPtCu mesoporous nanocubes (MNCs) to construct a label-free sandwich electrochemical immunosensor for the highly sensitivity detection of HIV-p24. PdPtCu MNCs have excellent peroxidase activity against hydrogen peroxide (H2O2) due to their synergistic ternary composition, large surface area and ability to penetrate mesoporous channels. Moreover, highly conductive and biocompatible gold nanoparticles@graphene oxide (AuNPs@GO) was introduced as a substrate to modify a glassy carbon electrode (GCE). Owing to the excellent electrochemical performance of the PdPtCu MNCs and AuNPs@GO, the developed immunosensors exhibited a good linear response from 0.04 pg/mL to 100 ng/mL with a low detection limit of 20 fg/mL. In addition, the established method exhibited excellent practical performance in human serum. This novel strategy provides a promising platform for ultrasensitive detection of the HIV-p24 in the field of clinical diagnostics.

Efficacy and Safety of Risankizumab in the Treatment of Crohn's Disease of the Pouch.

Risankizumab has shown efficacy in the treatment of moderate-to-severe Crohn's disease (CD). The use of risankizumab in the treatment of CD of the pouch has not been previously reported. Here, we have 10 patients with biologics exposed CD of the pouch treated with risankizumab. Some patients showed endoscopic improvement regarding inflammation with minimal clinical improvement. Our findings warrant further study to validate the efficacy and safety of risankizumab in the treatment of CD of the pouch.

Insights from meta-analysis on carbon to nitrogen ratios in aerobic composting of agricultural residues.

Given the heterogeneity of raw materials, the diversity of composting processes, and the complexity of biological transformations, systematically exploring the critical role of the initial carbon-to-nitrogen (C/N) ratio in the aerobic composting of agricultural residues is challenging within a single experimental study. This study employs meta-analysis to investigate this role. Statistical analysis of 192 scholarly articles confirmed that most studies adhere to the recommended optimal initial C/N range of 25 and 30, where enhanced compost maturity and nutrient accumulation are observed. The findings indicate that optimal initial C/N ratios vary by agricultural residue type. A C/N ratio of 20 to 30 facilitates controlling the composting duration within 45 days, while a C/N ratio of 30 to 35 necessitates extending the duration beyond 45 days. The study highlights the effectiveness of adjusting the C/N ratio and applying microbial inoculants and physical amendments to optimize composting outcomes and control the composting duration.

FN-1501 Inhibits Diffuse Large B-Cell Lymphoma Tumor Growth by Inducing Cell Cycle Arrest And Apoptosis.

BACKGROUND: Due to its high degree of aggressiveness, diffuse large B-cell lymphoma (DLBCL) presents a treatment challenge because 30% to 50% of patients experience resistance or relapse following standard chemotherapy. FN-1501 is an effective inhibitor of cyclin-dependent kinases and Fms-like receptor tyrosine kinase 3. OBJECTIVE: This study aimed to examine the anti-tumor impact of FN-1501 on DLBCL and clarify its molecular mechanism. METHODS: This study used the cell counting kit-8 assay to evaluate cell proliferation, along with western blotting and flow cytometry to analyze cell cycle progression and apoptosis influenced by FN-1501 in vitro. Afterward, the effectiveness of FN-1501 was evaluated in vivo utilizing the xenograft tumor model. In addition, we identified the potential signaling pathways and performed rescue studies using western blotting and flow cytometry. RESULTS: We found that FN-1501 inhibited cell proliferation and induced cell cycle arrest and apoptosis in DLBCL cells in vitro. Its anti-proliferative effects were shown to be time- and dose-dependent. The effect on cell cycle progression resulted in G1/S phase arrest, and the apoptosis induction was found to be caspase-dependent. FN-1501 treatment also reduced tumor volumes and weights and was associated with a prolonged progressionfree survival in vivo. Mechanistically, the MAPK and PI3K/AKT/mTOR pathways were significantly inhibited by FN-1501. Additional pathway inhibitors examination reinforced that FN-1501 may regulate cell cycle arrest and apoptosis through these pathways. CONCLUSION: FN-1501 shows promising anti-tumor activity against DLBCL in vivo and in vitro, suggesting its potential as a new therapeutic option for patients with refractory or relapsed DLBCL.

Dynamic cerebellar and sensorimotor network compensation in tremor-dominated Parkinson's disease.

AIM: Parkinson's disease (PD) tremor is associated with dysfunction in the basal ganglia (BG), cerebellum (CB), and sensorimotor networks (SMN). We investigated tremor-related static functional network connectivity (SFNC) and dynamic functional network connectivity (DFNC) in PD patients. METHODS: We analyzed the resting-state functional MRI data of 21 tremor-dominant Parkinson's disease (TDPD) patients and 29 healthy controls. We compared DFNC and SFNC between the three networks and assessed their associations with tremor severity. RESULTS: TDPD patients exhibited increased SFNC between the SMN and BG networks. In addition, they spent more mean dwell time (MDT) in state 2, characterized by sparse connections, and less MDT in state 4, indicating stronger connections. Furthermore, enhanced DFNC between the CB and SMN was observed in state 2. Notably, the MDT of state 2 was positively associated with tremor scores. CONCLUSION: The enhanced dynamic connectivity between the CB and SMN in TDPD patients suggests a potential compensatory mechanism. However, the tendency to remain in a state of sparse connectivity may contribute to the severity of tremor symptoms.

Early goal-directed renal replacement therapy in severe pneumonia associated acute kidney injury.

INTRODUCTION: Severe pneumonia is a crucial issue in the development of acute kidney injury (AKI). This study evaluated the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of severe pneumonia-associated AKI. METHODS: In this real-world retrospective cohort study, we recruited 180 patients with severe pneumonia who were hospitalized and received GDRRT in a third-class general hospital in East China between January 1, 2017, and December 31, 2021. Clinical data on baseline characteristics, biochemical indicators, and renal replacement therapy were collected. Patients were divided into Early and Late RRT groups according to fluid status, inflammation progression, and pulmonary radiology. We investigated in-hospital all-cause mortality (primary endpoint) and renal recovery (secondary endpoint) between the two groups. RESULTS: Among the 154 recruited patients, 80 and 74 were in the early and late RRT groups, respectively. There were no significant differences in the demographic characteristics between the two groups. The duration of admission to RRT initiation was significantly shorter in Early RRT group [2.5(1.0, 8.7) d vs. 5.0(1.5,13.5) d, p = 0.027]. At RRT initiation, the patients in the Early RRT group displayed a lower percentage of fluid overload, lower doses of vasoactive agents, higher CRP levels, and higher rates of radiographic progression than those in the Late RRT group. The all-cause in-hospital mortality was significantly lower in the Early RRT group than in Late group (52.5% vs. 86.5%, p < 0.001). Patients in the Early RRT group displayed a significantly higher proportion of complete renal recovery at discharge (40.0% vs. 8.1%, p < 0.001). CONCLUSION: This study clarified that early GDRRT for the treatment of severe pneumonia-associated AKI based on fluid status and inflammation progression, was associated with reduced hospital mortality and better recovery of renal function. Our preliminary study suggests that early initiation of RRT may be an effective approach for severe pneumonia-associated AKI.

Identification of a novel immune infiltration-related gene signature, MCEMP1, for coronary artery disease.

Background: This study aims to identify a novel gene signature for coronary artery disease (CAD), explore the role of immune cell infiltration in CAD pathogenesis, and assess the cell function of mast cell-expressed membrane protein 1 (MCEMP1) in human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL). Methods: To identify differentially expressed genes (DEGs) of CAD, datasets GSE24519 and GSE61145 were downloaded from the Gene Expression Omnibus (GEO) database using the R "limma" package with p < 0.05 and |log2 FC| > 1. Gene ontology (GO) and pathway analyses were conducted to determine the biological functions of DEGs. Hub genes were identified using support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO). The expression levels of these hub genes in CAD were validated using the GSE113079 dataset. CIBERSORT program was used to quantify the proportion of immune cell infiltration. Western blot assay and qRT-PCR were used to detect the expression of hub genes in ox-LDL-treated HUVECs to validate the bioinformatics results. Knockdown interference sequences for MCEMP1 were synthesized, and cell proliferation and apoptosis were examined using a CCK8 kit and Muse® Cell Analyzer, respectively. The concentrations of IL-1ß, IL-6, and TNF-α were measured with respective enzyme-linked immunosorbent assay (ELISA) kits. Results: A total of 73 DEGs (four down-regulated genes and 69 up-regulated genes) were identified in the metadata (GSE24519 and GSE61145) cohort. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that these DEGs might be associated with the regulation of platelet aggregation, defense response or response to bacterium, NF-kappa B signaling pathway, and lipid and atherosclerosis. Using SVM-RFE and LASSO, seven hub genes were obtained from the metadata. The upregulated expression of DIRC2 and MCEMP1 in CAD was confirmed in the GSE113079 dataset and in ox-LDL-treated HUVECs. The associations between the two hub genes (DIRC2 and MCEMP1) and the 22 types of immune cell infiltrates in CAD were found. MCEMP1 knockdown accelerated cell proliferation and suppressed cell apoptosis for ox-LDL-treated HUVECs. Additionally, MCEMP1 knockdown appeared to decrease the expression of inflammatory factors IL-1ß, IL-6, and TNF-α. Conclusions: The results of this study indicate that MCEMP1 may play an important role in CAD pathophysiology.

Pelvic Radiation Therapy Increases Risk of Pouch Failure in Patients with Inflammatory Bowel Disease and Ileal Pouch.

BACKGROUND: The effect of radiation on the ileal pouch is less well studied in patients with inflammatory bowel disease (IBD) and ileal pouch-anal anastomosis. AIMS: This retrospective study investigates the impact of external radiation therapy on the outcomes of ileal pouches. METHODS: The study included 82 patients with IBD and ileal pouches, of whom 12 received pelvic radiation, 16 abdominal radiation, 14 radiation in other fields, and 40 served as controls with no radiation. Pouch-related outcomes, including pouch failure, worsening of symptoms, pouchitis, and development of strictures, along with changes in Pouch Disease Activity Index (PDAI) scores pre- and post-radiation were assessed. RESULTS: The pelvic radiation group exhibited a significantly higher rate of pouch failure (25%, p < 0.004) and worsening pouch-related symptoms (75%, p = 0.012) compared to other groups. Although not statistically significant, a higher incidence of pouchitis was observed in the pelvic radiation group (45.5%, p = 0.071). Strictures were more common in the pelvic radiation group (25%, p = 0.043). Logistic regression analysis revealed that pelvic radiation significantly increased the odds of pouch-related adverse outcomes (OR 5.66; 95% confidence interval: 1.61-21.5). CONCLUSION: Pelvic radiation significantly impacts the outcomes of ileal pouches in patients with IBD, increasing the risk of pouch failure, symptom exacerbation, and structural complications. These findings underscore the need for careful consideration of radiation therapy in this patient population and highlight the importance of closely monitoring and managing radiation-induced pouch dysfunction.

Inhibition of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptors Ameliorates Atrial Inflammation and Vulnerability to Atrial Fibrillation in Rats with Anxiety Disorders.

ABSTRACT: Previous studies have found that anxiety disorders may increase the incidence of atrial fibrillation (AF). More and more studies have shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are involved in the occurrence and development of cardiovascular diseases. However, the role of AMPARs in AF associated with anxiety disorder remains unclear. The aim of this study was to investigate the effect of AMPARs on AF susceptibility in rats with anxiety disorder and its possible mechanism. The anxiety disorder rat model was established by unpredictable empty bottle stimulation and was treated with AMPARs agonist and antagonist. Our results showed that AMPARs antagonist treatment significantly reduced sympathetic activity, improved heart rate variability, shortened action potential duration, prolonged effective refractory period, reduced AF induction rate, and improved cardiac electrical remodeling and the expression of inflammatory factors. In addition, inhibition of AMPARs reduced the phosphorylation of IκBα and p65. Our experimental results suggest that inhibition of AMPARs can reduce autonomic remodeling, improve atrial electrical remodeling, and suppress myocardial inflammation, which provides a potential therapeutic strategy for the treatment of AF associated with anxiety disorder.

Direct antiglobulin test type, red blood cell distribution width, and estimated glomerular filtration rate for early prediction of in-hospital mortality of patients with COVID-19.

Objective: This study aimed to investigate the correlation between COVID-19 and the direct antiglobulin test (DAT) and establish an in-hospital mortality risk predictive model based on the DAT type, which can be used for the early prediction of inpatients with COVID-19. Methods: In this study, 502 patients admitted to our hospital who underwent DAT testing from January 29 to February 8, 2023, were included (252 DAT-positive and 250 DAT-negative). Among them, 241 cases of COVID-19 were screened(171 DAT-positive and 70 DAT-negative), clinical and laboratory indicators were compared between DAT-positive and DAT-negative groups. Univariate and multivariate logistic regression analysis, the Kaplan-Meier survival curve and receiver operating curves were used to explore the relation between the DAT type and in-hospital mortality of patients with COVID-19. Results: The proportion of confirmed COVID-19 cases was higher in the DAT-positive group than in the DAT-negative group (67.9 % vs. 28.0 %, P < 0.05). Patients with COVID-19 in the DAT-positive group had higher age-adjusted Charlson comorbidity index scores, red blood cell distribution width (RDW), lactate dehydrogenase, prothrombin time, D-dimer, creatinine, and high-sensitive cardiac troponin T levels than the negative group (P < 0.05), In contrast, hemoglobin and estimated glomerular filtration rate (eGFR) levels were lower in the DAT-positive group. The DAT-positive group also had a higher red blood cell usage volume and in-hospital mortality rate than the DAT-negative group. The mortality rate of patients with COVID-19 with both IgG and C3d positive was higher than that of the other groups. Multivariate logistic regression analysis showed that RDW and eGFR were associated with mortality in patients with COVID-19. The combined predictive model of DAT type, RDW, and eGFR showed an area under the curve of 0.782, sensitivity of 0.769, and specificity of 0.712 in predicting in-hospital mortality risk in patients with COVID-19. Conclusion: The established predictive model for in-hospital mortality risk of patients with COVID-19 based on DAT type, RDW, and eGFR can provide a basis for timely intervention to reduce the mortality rates of patients with COVID-19. This model is accessible at https://jijijiduola.shinyapps.io/0531// for research purposes.

Dissection and Fine-Mapping of Two QTL Controlling Grain Size Linked in a 515.6-kb Region on Chromosome 10 of Rice.

Grain size is a primary determinant of grain weight, which is one of the three essential components of rice grain yield. Mining the genes that control grain size plays an important role in analyzing the regulation mechanism of grain size and improving grain appearance quality. In this study, two closely linked quantitative trait loci (QTL) controlling grain size, were dissected and fine-mapped in a 515.6-kb region on the long arm of chromosome 10 by using six near isogenic line populations. One of them, qGS10.2, which controlled 1000 grain weight (TGW) and grain width (GW), was delimited into a 68.1-kb region containing 14 annotated genes. The Teqing allele increased TGW and GW by 0.17 g and 0.011 mm with the R2 of 12.7% and 11.8%, respectively. The other one, qGL10.2, which controlled grain length (GL), was delimited into a 137.3-kb region containing 22 annotated genes. The IRBB52 allele increased GL by 0.018 mm with the R2 of 6.8%. Identification of these two QTL provides candidate regions for cloning of grain size genes.

Novel Susceptibility Genes and Biomarkers for Obstructive Sleep Apnea: Insights from Genetic and Inflammatory Proteins.

STUDY OBJECTIVES: Numerous observational studies link obstructive sleep apnea (OSA) to inflammatory proteins, yet the directionality of these associations remains ambiguous. Therefore, we aimed to clarify the potential associations of gene-predicted inflammatory proteins with OSA. METHODS: Based on genome-wide association study data, we applied Mendelian randomization (MR) to explore potential connections between circulating inflammatory proteins and OSA, primarily using the inverse variance weighting method for robustness. Cochran's Q test, MR‒Egger intercept test, MR-PRESSO, and leave-one-out method were used to perform sensitivity tests for pleiotropy and heterogeneity. Replication analyses and meta-analyses were performed using other independent data. Steiger tests and multivariate MR assessed the independent effects of exposure factors, and the functional mapping and annotation (FUMA) platform was used to identify key genes to enhance the understanding of genetics. RESULTS: Our investigation revealed 21 circulating inflammatory proteins significantly associated with OSA-related phenotypes. Notably, IL-10RA, IL-18R1, TNFSF14, CCL23, ADA, and SLAMF1 had significant effects on multiple phenotypes. After FDR correction, IL-18R1, SLAMF1, IL-10RA, and IL-17C were identified as important candidates for OSA, and multivariate MR analysis strengthened the independent heritability of 20 inflammatory factors. The FUMA platform revealed seven overlapping genes: ROBO1, PRIM1, NACA, SHBG, HSD17B6, RBMS2, and WWOX. All reverse MR analyses and sensitivity analyses confirmed the robustness of these associations. CONCLUSIONS: Our results underscore crucial associations between inflammatory proteins and OSA pathogenesis, revealing new correlates and susceptibility genes. These findings advance biomarker identification for OSA risk and highlight the importance of genetic and inflammatory profiles in OSA management.

Hybrid van der Waals Epitaxy.

The successful growth of non-van der Waals (vdW) group-III nitride epilayers on vdW substrates not only opens an unprecedented opportunity to obtain high-quality semiconductor thinfilm but also raises a strong debate for its growth mechanism. Here, combining multiscale computational approaches and experimental characterization, we propose that the growth of a nitride epilayer on a vdW substrate, e.g., AlN on graphene, may belong to a previously unknown model, named hybrid vdW epitaxy (HVE). Atomic-scale simulations demonstrate that a unique interfacial hybrid-vdW interaction can be created between AlN and graphene, and, consequently, a first-principles-based continuum growth model is developed to capture the unusual features of HVE. Surprisingly, it is revealed that the in-plane and out-of-plane growth are strongly correlated in HVE, which is absent in existing growth models. The concept of HVE is confirmed by our experimental measurements, presenting a new growth mechanism beyond the current category of material growth.