Basic Science and Pathogenesis.

Background: The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic determinant for Alzheimer's disease and cognitive function in nearly all human populations, yet inconsistent effects have been reported in South Asians. The population of India has admixed genetic ancestry with most people falling on a North/South cline and having varying proportions of Ancestral North Indian (ANI) and Ancestral South Indian (ASI) ancestries, and those in east of India fall off the cline due to ancestry from additional ancestral populations. This study examined the ε4 association with cognitive function across 18 states/union territories of India and investigated whether ancestral background modulates ε4 association with cognitive function in 2,590 participants from the Longitudinal Aging Study in India - Diagnostic Assessment of Dementia (LASI-DAD).

Basic Science and Pathogenesis.

Background: The prevalence of dementia in India is approximately 7.4% among those aged 60 years and older, yet little is known about genetic risk factors for dementia in this population. Examining genetic variants at higher frequency in India than other ancestries (i.

Gate-Controlled Superconducting Switch in GaSe/NbSe van der Waals Heterostructure.

The demand for low-power devices is on the rise as semiconductor engineering approaches the quantum limit, and quantum computing continues to advance. Two-dimensional (2D) superconductors, thanks to their rich physical properties, hold significant promise for both fundamental physics and potential applications in superconducting integrated circuits and quantum computation. Here, we report a gate-controlled superconducting switch in GaSe/NbSe van der Waals (vdW) heterostructure.

The effect of calf muscular vein thrombosis on the prognosis within one year postoperatively of geriatric hip fracture patients: a propensity score-matched analysis.

Introduction: Calf muscular vein thrombosis (CMVT) is a type of distal deep vein thrombosis, which is common in geriatric hip fracture patients. However, studies focusing on whether the orthopedic operation has an impact on the prognosis of geriatric hip fracture patients with CMVT are very limited. Therefore, the aim of this study was to explore whether geriatric hip fractures with CMVT affect the mortality of patients within one year postoperatively.

Identification of key genes and variants associated with boar sperm freezability using whole genome resequencing.

Cryopreservation induces various cryodamages to the structural or functional aspects of boar sperm, resulting in the deterioration of sperm quality. The extent of cryodamages varies significantly among different individual boars. In our study, 50 boars with either good sperm freezability (GSF) or poor sperm freezability (PSF) were selected from a population of 402 boars.

Epigenome-wide mediation analysis of the relationship between psychosocial stress and cardiometabolic risk factors in the Health and Retirement Study (HRS).

Background: Exposure to psychosocial stress is linked to a variety of negative health outcomes, including cardiovascular disease and its cardiometabolic risk factors. DNA methylation has been associated with both psychosocial stress and cardiometabolic disease; however, little is known about the mediating role of DNA methylation on the association between stress and cardiometabolic risk. Thus, using the high-dimensional mediation testing method, we conducted an epigenome-wide mediation analysis of the relationship between psychosocial stress and ten cardiometabolic risk factors in a multi-racial/ethnic population of older adults (n = 2668) from the Health and Retirement Study (mean age = 70.

Exploration oxidative stress underlying gastroesophageal reflux disease and therapeutic targets identification: a multi-omics Mendelian randomization study.

Introduction: Gastroesophageal reflux disease (GERD) is a chronic inflammatory gastrointestinal disease, which has no thoroughly effective or safe treatment. Elevated oxidative stress is a common consequence of chronic inflammatory conditions.

Methods: We employed Summary-data based MR (SMR) analysis to assess the associations between gene molecular characteristics and GERD.

Bispecific antibody and chimeric antigen receptor (CAR) modified T-cell in the treatment of multiple myeloma: Where do we stand today?

Although the prognosis of patients with multiple myeloma (MM) has been significantly improved by the introduction of proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies, MM is still considered an incurable disease in the vast majority of the patients. In recent years, T-cell based immunotherapy represents a novel treatment strategy for relapsed/refractory (RR) MM. So far, chimeric antigen receptor (CAR) modified T-cells and bispecific T-cell engaging antibodies (bsAb) have shown promising anti-MM efficacy and manageable safety profile within clinical trials, and B-cell maturation antigen (BCMA) is the most commonly used immune target for T-cell based immunotherapies in MM.

Unraveling the Cleavage Reaction of Hydroxylamines with Cyclopropenones Considering Biocompatibility.

We develop a latent biocompatible cleavage reaction involving the hitherto unexplored interaction between hydroxylamines and cyclopropenones. Our study addresses the regioselectivity challenges commonly observed in asymmetric cyclopropenone transformations, substantiated by variations in substrate, Density Functional Theory calculations, and NMR analysis. This reaction is characterized by high efficiency, broad substrate scope, stability, latent biocompatibility, and mild reaction conditions.

Relationship between EZH2 expression and prognosis of patients with hepatocellular carcinoma using a pathomics predictive model.

Background: Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is overexpressed in hepatocellular carcinoma, promoting tumorigenesis and correlating with poor prognosis. Traditional histopathological examinations are insufficient to accurately predict hepatocellular carcinoma (HCC) survival; however, pathomics models can predict EZH2 expression and HCC prognosis. This study aimed to investigate the relationship between pathomics features and EZH2 expression for predicting overall survival of patients with HCC.

p53 induces circFRMD4A to suppress cancer development through glycolytic reprogramming and cuproptosis.

Cuproptosis is a type of copper-induced cell death that mainly impacts cells relying on mitochondrial metabolism. Although p53 regulates glycolytic metabolism, its role in cuproptosis remains unclear. Here, we report that the circular RNA, circFRMD4A, is crucial for p53-mediated metabolic reprogramming and cuproptosis.

Construction of rhodamine-based fluorescent sensor for fast, on-site quantitative detection of hazardous salicylic acid in practical sample analysis.

Salicylic acid (SA) is widely used in food storage, preservatives, additives, healthcare, and the pharmaceutical industry. However, various poisoning symptoms are frequently reported upon ingestion of a large amount of SA. Therefore, discovering new tools for sensing SA with fast, simple, and portable performance is imperative.

FABIO: TWAS fine-mapping to prioritize causal genes for binary traits.

Transcriptome-wide association studies (TWAS) have emerged as a powerful tool for identifying gene-trait associations by integrating gene expression mapping studies with genome-wide association studies (GWAS). While most existing TWAS approaches focus on marginal analyses through examining one gene at a time, recent developments in TWAS fine-mapping methods enable the joint modeling of multiple genes to refine the identification of potentially causal ones. However, these fine-mapping methods have primarily focused on modeling quantitative traits and examining local genomic regions, leading to potentially suboptimal performance.

Approximation of functionals on Korobov spaces with Fourier Functional Networks.

Learning from functional data with deep neural networks has become increasingly useful, and numerous neural network architectures have been developed to tackle high-dimensional problems raised in practical domains. Despite the impressive practical achievements, theoretical foundations underpinning the ability of neural networks to learn from functional data largely remain unexplored. In this paper, we investigate the approximation capacity of a functional neural network, called Fourier Functional Network, consisting of Fourier neural operators and deep convolutional neural networks with a great reduction in parameters.

Targeting RACGAP1 suppresses growth hormone pituitary adenoma growth.

Purpose: Growth hormone pituitary adenoma (GHPA) is a major subtype of pituitary adenoma (PA), with tumor enlargement and abnormal secretion of growth hormone (GH) often causing complications. Rac GTPase-activating protein 1 (RACGAP1), a member of the guanine triphosphatase-activating protein family, is highly overexpressed in multiple tumors and promotes tumor growth. However, the role of RACGAP1 in GHPA remains unelucidated.

Visible Light-Mediated [4+2] Annulation of Silylimines with Olefins to 1-Aminotetralins Enabled by Diradical Hydrogen Atom Transfer of C-H Bonds.

A facile photochemical, one-pot synthesis of highly functionalized 1-aminotetralins derivatives (>70 examples) from readily accessible o-alkyl and o-formyl aryl silylimines with olefins is described. A diradical-mediated hydrogen atom transfer (DHAT) of primary, secondary, and tertiary C(sp)-H bonds of o-alkyl arylsilylimines and C(sp)-H bonds of o-formyl arylsilylimines enabled a [4+2] annulation with olefins in excellent diastereoselectivity. This was accomplished upon irradiation at λ = 420 nm in the presence of thioxanthen-9-one (10 mol %) as the sensitizer via energy transfer.

Injectable Photocrosslinked Hydrogel Dressing Encapsulating Quercetin-Loaded Zeolitic Imidazolate Framework-8 for Skin Wound Healing.

: Wound management is a critical component of clinical practice. Promoting timely healing of wounds is essential for patient recovery. Traditional treatments have limited efficacy due to prolonged healing times, excessive inflammatory responses, and susceptibility to infection.

Outcome prediction comparison of ischaemic areas' radiomics in acute anterior circulation non-lacunar infarction.

The outcome prediction of acute anterior circulation non-lacunar infarction (AACNLI) is important for the precise clinical treatment of this disease. However, the accuracy of prognosis prediction is still limited. This study aims to develop and compare machine learning models based on MRI radiomics of multiple ischaemic-related areas for prognostic prediction in AACNLI.

Engineering Saccharomyces cerevisiae for continuous secretory production of hEGF in biofilm.

Human epidermal growth factor (hEGF) plays a crucial role in promoting cell growth and has various clinical applications. Due to limited natural sources and the high cost of chemical synthesis, researchers are now exploring genetic engineering as a potential method for hEGF production. In this particular study, a novel hEGF expression system was developed using Saccharomyces cerevisiae.

Proteome-wide association studies for blood lipids and comparison with transcriptome-wide association studies.

Blood lipid traits are treatable and heritable risk factors for heart disease, a leading cause of mortality worldwide. Although genome-wide association studies (GWASs) have discovered hundreds of variants associated with lipids in humans, most of the causal mechanisms of lipids remain unknown. To better understand the biological processes underlying lipid metabolism, we investigated the associations of plasma protein levels with total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol in blood.