Analyses of GWAS and Sub-Threshold Loci Lead to the Discovery of Dendrite Development and Morphology Dysfunction Underlying Schizophrenia Genetic Risk.

Schizophrenia (SCZ) is highly polygenic, and its biological underpinnings remain unclear. In this study, a cost-effective strategy of including sub-threshold GWAS (subGWAS) loci (i.e.

UPLC fingerprinting combined with quantitative analysis of multicomponents by a single marker for quality evaluation of YiQing granules.

Research Background: YiQing granules (YQGs) are a patented drug commonly used in clinics in China. However, the quality control index of this preparation is relatively limited, which does not effectively ensure the quality of the product. Thus, a comprehensive quality evaluation of YQGs is lacking.

Bifidobacterium boosts anti-PD-1 effectiveness through JAK pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and deadly cancer. Gut microbiota affect tumor immunity and immunotherapy efficacy, but the exact mechanisms are unclear. A study compared gut microbiota in HCC patients and healthy controls (HC) using 16S rDNA analysis and metabolomics.

Tensor decomposition of multi-dimensional splicing events across multiple tissues to identify splicing-mediated risk genes associated with complex traits.

Identifying risk genes associated with complex traits remains challenging. Integrating gene expression data with Genome-Wide Association Study (GWAS) through Transcriptome-Wide Association Study (TWAS) methods has discovered candidate risk genes for various complex traits. Splicing, which explains a comparable heritability of complex traits as gene expression, is under-explored due to its multidimensionality.

A Deep Learning Model for Preoperative Prediction of Lymph Node Metastasis in cT1-Stage Lung Adenocarcinoma: A Multicenter External Validation Study.

Purpose: To develop and validate a deep learning (DL) model for preoperative prediction of lymph node metastasis (LNM) in clinical T1-stage lung adenocarcinoma (LUAD), and to compare its performance with conventional semantic and radiomics signatures.

Methods: This multicenter retrospective study enrolled 2503 patients with 2568 pathologically confirmed cT1-stage LUAD nodules from eight institutions. Data from six centers (1994 patients/2059 nodules) were randomly divided into training (1600 patients/1664 nodules) and internal test (394 patients/395 nodules) cohorts.

IL31 identified as a key genetic risk factor for prurigo nodularis.

Background: Although previous studies have suggested that genetic risk factors can contribute to the development of prurigo nodularis (PN), little is known about the specific variants involved.

Objective: We aimed to test which genetic variants increase predisposition to PN by conducting a large genome-wide association study.

Methods: Five separate cohorts (4239 case patients with PN and 583,544 controls) were combined through genome-wide association study meta-analysis, and the results were validated by using the Michigan Genomics Initiative.

Childhood emotional neglect and depression in emerging adults: Exploring the roles of rumination and resilience.

Background: Childhood Emotional Neglect (CEN) is a highly prevalent subtype of child maltreatment and a significant factor contributing to psychiatric distress in emerging adulthood, particularly depression. Understanding how caregiver neglect raises psychiatric risk is critical. The purpose of this study is to examine the roles of resilience and rumination in the relationship between CEN and depression among Chinese emerging adults.

Molecular mechanisms of aberrant fatty acids metabolism in driving cardiovascular diseases: key regulatory targets and dietary interventions.

In recent years, cardiovascular diseases (CVDs) have emerged as one of the leading global risk factors for mortality. As the primary energy source for myocardial metabolism, alterations in fatty acid (FAs) metabolism play a crucial role in myocardial energy imbalance in patients with CVDs. These metabolic disruptions can affect vascular and myocardial cell function through various mechanisms, thereby contributing to the onset and progression of CVDs.

Impact of Molecular Tumor Board on Clinical Outcomes in Patients with Refractory Solid Tumor: a Real-World Study.

Introduction: Providing precise oncologic treatment for patients with refractory solid tumor is still an unmet need in clinical practice. This study aimed to assess whether treatments recommended by a molecular tumor board (MTB) can improve clinical outcomes in patients with refractory solid tumors.

Methods: We screened all patients with refractory solid tumor during the period from 2017 to 2022 at the authors' center.

Parameter design and experiment of rotary plate pineapple fruit picker.

Research on pineapple harvesting machinery remains in its early stages, and the design and development of such machinery play a crucial role in advancing mechanization and automation within the pineapple industry. This study designs the rotary plate pineapple fruit harvester's cutting table structure based on the physical and mechanical properties of pineapple plants. The design process includes simulating manual harvesting techniques.

Novel compound heterozygous DOCK6 variants expand the mutational spectrum in prenatal diagnosis of Adams-Oliver syndrome 2.

Background: Adams-Oliver syndrome (AOS) is a rare developmental disorder, and the DOCK6 gene is an identified AOS gene. This report highlights the prenatal diagnosis of AOS-2 by ultrasonography and genetic testing.

Methods: A growth-restricted fetus with bilateral ventriculomegaly, paraventricular calcifications, and ventricular septal defect underwent trio-whole-exome sequencing (trio-WES).

Anlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial.

Evidence-guided regimens for advanced gastric cancer (AGC) in patients with performance status 2 (PS 2) are limited. Here, we proposed a structured therapeutic framework termed "performance status-matched strategy", and further conducted the APICAL-GC trial (NCT04278222). This open-label, single-arm phase II study evaluated the efficacy and safety of anlotinib combined with toripalimab among 24 treatment-naïve AGC patients with PS 2.

Mammography-based artificial intelligence for breast cancer detection, diagnosis, and BI-RADS categorization using multi-view and multi-level convolutional neural networks.

Purpose: We developed an artificial intelligence system (AIS) using multi-view multi-level convolutional neural networks for breast cancer detection, diagnosis, and BI-RADS categorization support in mammography.

Methods: Twenty-four thousand eight hundred sixty-six breasts from 12,433 Asian women between August 2012 and December 2018 were enrolled. The study consisted of three parts: (1) evaluation of AIS performance in malignancy diagnosis; (2) stratified analysis of BI-RADS 3-4 subgroups with AIS; and (3) reassessment of BI-RADS 0 breasts with AIS assistance.

Structural insights into the ubiquitin-independent midnolin-proteasome pathway.

The protein midnolin (MIDN) augments proteasome activity in lymphocytes and dramatically facilitates the survival and proliferation of B-lymphoid malignancies. MIDN binds both to proteasomes and to substrates, but the mode of interaction with the proteasome is unknown, and the mechanism by which MIDN facilitates substrate degradation in a ubiquitin-independent manner is incompletely understood. Here, we present cryoelectron microscopy (cryo-EM) structures of the substrate-engaged, MIDN-bound human proteasome in two conformational states.

The exploration and analysis of the superfluous lithium storage capacity of a BiSe-based composite.

The development of advanced anode materials is of great significance to improve the operating efficiency of lithium-ion batteries. The BiSe-based composites (BiSe-CDs-Ni) prepared in this paper exhibit abnormal cyclic behavior: the capacity increases and exceeds the initial capacity. The change of lithium storage mechanism leads to an increase in capacity.

A Protocol for Conformity and Risk Assessment of Pharmaceutical Product by High Performance Liquid Chromatography Based on Measurement Uncertainty.

Conformity assessment plays a critical role in the process of drug manufacturing, significantly influencing product outcomes of acceptance or rejection. Measurement uncertainty is an important parameter inherent to the analysis method itself. The introduction of uncertainty can effectively control and assess the risk of making wrong decisions in the conformity assessment process.

Multi-omics analysis reveals aspirin is associated with reduced risk of Alzheimer's disease.

The urgent need for safe and effective therapies for Alzheimer's disease (AD) has spurred a growing interest in repurposing existing drugs to treat or prevent AD. In this study, we combined multi-omics and clinical data to investigate possible repurposing opportunities for AD. We performed transcriptome-wide association studies (TWAS) to construct gene expression signatures of AD from publicly available GWAS summary statistics, using both transcriptome prediction models for 49 tissues from the Genotype-Tissue Expression (GTEx) project and microglia-specific models trained on eQTL data from the Microglia Genomic Atlas (MiGA).

A Novel De Novo KAT6B Mutation Causes Hypospadias in a Chinese Fetus at 29 Weeks Gestation.

KAT6B mutations are responsible for Say-Barber-Biesecker-Young-Simpson syndrome or Genitopatellar syndrome, with most mutations occurring in its exon 18. A pregnancy with normal early antenatal examination revealed the presence of hypospadias in the fetus but with no abnormal amniotic fluid volume in ultrasonography at 29th weeks' gestation. After amniocentesis, the trios' whole exome sequencing was performed and a novel frameshift mutation (KAT6B: exon10: c.

Longitudinal Analysis of Electronic Health Records Reveals Medical Conditions Associated with Subsequent Alzheimer's Disease Development.

Background: Several health conditions are known to increase the risk of Alzheimer's disease (AD). We aim to systematically identify medical conditions that are associated with subsequent development of AD by leveraging the growing resources of electronic health records (EHRs).

Methods: This retrospective cohort study used de-identified EHRs from two independent databases (MarketScan and VUMC) with 153 million individuals to identify AD cases and age- and gender-matched controls.

Low level of lactate and trophoblast dysfunction mediated by SNAI1/PDK1 contributes to miscarriage.

Introduction: Although the significance of metabolic remodelling in maintaining homeostasis at the maternal-foetal interface has been established, research on its implications in miscarriage remains limited.

Methods: Immunofluorescence, qRT-PCR, and western blotting were used to detect the expression of SNAI1 in miscarriage and normal villi. The function of the zinc-finger transcription factor SNAI1 was evaluated in three-dimensional (3D) trophoblast spheroids.

A Genetics-guided Integrative Framework for Drug Repurposing: Identifying Anti-hypertensive Drug Telmisartan for Type 2 Diabetes.

Drug development is a long and costly process, and repurposing existing drugs for use toward a different disease or condition may serve as a cost-effective alternative. As drug targets with genetic support have a doubled success rate, genetics-informed drug repurposing holds promise in translating genetic findings into therapeutics. In this study, we developed a Genetics Informed Network-based Drug Repurposing via in silico Perturbation (GIN-DRIP) framework and applied the framework to repurpose drugs for type-2 diabetes (T2D).

Biomass-derived carbon dots: synthesis, modification and application in batteries.

Biomass-derived carbon dots (BCDs) have attracted considerable attention for their promising attributes, including low toxicity, excellent solubility, biocompatibility, and eco-friendliness. Their rich surface chemistry and impressive photoluminescent properties have sparked widespread research interest, particularly in areas such as sensing and biomedicine. However, the potential applications of BCDs in the energy sector, especially in electrochemical energy storage batteries, have received scant review focus.

Multi-parametric MRI Habitat Radiomics Based on Interpretable Machine Learning for Preoperative Assessment of Microsatellite Instability in Rectal Cancer.

Rationale And Objectives: This study constructed an interpretable machine learning model based on multi-parameter MRI sub-region habitat radiomics and clinicopathological features, aiming to preoperatively evaluate the microsatellite instability (MSI) status of rectal cancer (RC) patients.

Materials And Methods: This retrospective study recruited 291 rectal cancer patients with pathologically confirmed MSI status and randomly divided them into a training cohort and a testing cohort at a ratio of 8:2. First, the K-means method was used for cluster analysis of tumor voxels, and sub-region radiomics features and classical radiomics features were respectively extracted from multi-parameter MRI sequences.

Alterations in gut microbiota in Rheumatoid arthritis patients with interstitial lung Disease: A Comparative study.

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is considered one of the most severe complications of rheumatoid arthritis. The etiology of RA-ILD is complex, involving genetic and environmental factors. Recent studies suggest that the gut microbiota, a critical component of the immune system, may influence the pathogenesis of RA and other autoimmune disorders.

Protective effect of serum carotenoids on mortality among metabolic syndrome patients: attenuated by lipid-lowering drugs.

Background: Limited evidence exists about the relationship between serum carotenoid and mortality in metabolic syndrome (MetS) patients, and the effects of medication use on this association remains unclear.

Methods: The study encompassed 2,521 MetS patients from the National Health and Nutrition Examination Survey (NHANES) 2001-2006 and 2017-2018. A total of 7 serum carotenoids were evaluated.