Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomization.

The escalating threat of widespread exposure to environmental pollutants on human health has drawn increasing attention, particularly regarding mycotoxin contaminants with potent carcinogenic properties. As a prototypical environmental toxin, the molecular mechanisms underlying aflatoxin B1-induced gastric carcinogenesis remain poorly defined. This study systematically elucidates the molecular network through which aflatoxin B1 (AFB1) synergistically drives the malignant progression of gastric cancer by specifically targeting five core regulatory genes, exemplified by its upregulation of cyclin genes CCNE1 and CCNE2.

Effect of finerenone on urinary protein and inflammatory factor levels in type 2 diabetes mellitus patients with diabetic kidney disease.

Aims: This study aimed to investigate the efficacy and safety of finerenone in the treatment of diabetic kidney disease (DKD) in the real-world medical setting and explore the underlying mechanism of its kidney-protecting effects from the perspective of the inflammatory response.

Materials And Methods: Forty-eight DKD patients were selected and completed a 6-month finerenone treatment. Renal parameters, inflammatory cytokines, other related indicators and adverse effects were collected at every visit.

Blood plasma proteome-wide association study implicates new proteins in type 2 diabetes mellitus pathogenesis.

The pathophysiological mechanisms underlying type 2 diabetes mellitus (T2DM) remain incompletely understood, and the disease continues to impose a substantial burden on global health. In this study, we integrated the data from the largest genome-wide association study (GWAS; N = 898,130) of T2DM with human plasma protein quantitative trait locus (pQTL; N = 53,022) data to conduct the first proteome-wide association study (PWAS) of T2DM. Following Mendelian randomization and colocalization analyses, we identified nine independent putatively causal proteins.

Blood plasma proteome-wide association study implicates novel proteins in the pathogenesis of multiple cardiovascular diseases.

Background: Cardiovascular diseases (CVD) are the leading cause of global mortality, yet current treatments benefit only a subset of patients. To identify new potential treatment targets, we conducted the first proteome wide association study (PWAS) for 26 CVDs using plasma proteomics data from the largest cohort to date (53,022 individuals in the UK Biobank Pharma Proteomics Project (UKB-PPP)).

Methods And Results: We calculated single nucleotide polymorphism (SNP)-protein weights using the UKB-PPP dataset and integrated these weights with genome-wide association study (GWAS) summary statistics for 26 CVDs across three categories (16 cardiac, 5 venous, and 5 cerebrovascular diseases) in up to 1,308,460 individuals.

Application and challenges of artificial intelligence in predicting perioperative complications of colorectal cancer.

Colorectal cancer (CRC) is a prevalent malignancy, with surgery playing a key role in its treatment. However, perioperative complications, such as anastomotic leaks, infections, and mortality, can significantly affect surgical outcomes, extend hospital stays, and increase healthcare costs. Traditional risk prediction models often lack precision, leading to increased interest in artificial intelligence (AI) for improving risk stratification.

Long noncoding RNA LINC00339 promotes osteoporosis development via modulating of regulator CDC42 by binding PARP1.

Background: Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and microarchitectural deterioration of bone tissue. Our previous investigation provided preliminary evidence that single nucleotide polymorphisms (SNPs) may functionally interact with the LINC00339, potentially contributing to the pathogenesis and progression of osteoporosis through undefined molecular pathways. However, the exact mechanistic basis of LINC00339's involvement in osteoporotic bone remodeling remains incompletely characterized and warrants systematic exploration.

Yttrium-90 microsphere therapy for hepatocellular carcinoma: Clinical efficacy, mechanistic insights, and comparative therapeutic perspectives.

Yttrium-90 (Y-90) microsphere therapy, known as radioembolization, has emerged as a pivotal treatment modality for hepatocellular carcinoma (HCC), delivering targeted radiation with minimal collateral damage to healthy liver tissues. This review meticulously synthesizes current evidence regarding the clinical efficacy, underlying therapeutic mechanisms, patient selection criteria, and comparative advantages of Y-90 therapy. Clinical studies consistently demonstrate significant improvements in overall survival and progression-free survival, coupled with robust tumor response rates and manageable adverse events.

Genetic transcriptional regulation profiling of cartilage reveals pathogenesis of osteoarthritis.

Background: Genome-wide association studies (GWAS) have identified more than one hundred risk loci for osteoarthritis (OA). Identifying the effector genes and deciphering the underlying regulatory mechanisms are of great importance but remains challenging due to limited availability of OA-related tissue data. This study aims to address this issue by generating a cartilage expression quantitative trait loci (eQTLs) and a functional fine-mapping resource.

Long noncoding HOXD-AS1: a crucial regulator of malignancy.

Long non-coding RNAs (lncRNAs) play a crucial role in the occurrence and progression of various cancers. HOXD-AS1, an antisense RNA 1 of the lncRNA HOXD cluster, (also known as HAGLR, MIR7704HG, Mdgt, and STEEL), is located at human chromosome 2q31.1.

Exploring the research hotspots and trends in genetic education reform.

Genetics, as a core discipline of life sciences, has broad applications in medicine, agriculture, and environmental protection. With the rapid development in biotechnology, genetic education is facing new challenges and demands. Traditional teaching models have gradually revealed limitations in cultivating students' innovative abilities, practical skills, and comprehensive qualities.

Temporal Dynamics of Genetic Diversity in Protected and Unprotected Wild Rice (Oryza rufipogon) Populations: Implications for Conservation.

Genetic diversity is vital for population survival, yet there is a paucity of studies focusing on the effectiveness of establishing protected areas for maintaining the population genetic diversity of threatened plant species. To evaluate the effectiveness of in situ conservation measures, we used simple sequence repeats (SSR) and single nucleotide polymorphisms (SNP) markers to monitor temporal dynamics in genetic diversity of the threatened wild rice Oryza rufipogon in both protected and unprotected populations in China between 2001 and 2020. Unprotected populations tended to have decreased census population sizes (Nc) compared to protected populations, although they both showed a reduction in effective population size (Ne).

Incidence trends and a nomogram for predicting overall survival in children with hepatoblastoma: A population-based analysis.

Background: In recent years, the incidence of pediatric hepatoblastoma has increased significantly. The aims of our study were to analyze the incidence trends, identify independent risk factors affecting the prognosis, and create a nomogram based on these risk factors to guide clinical treatment.

Methods: The Clinicopathological data from children diagnosed with hepatoblastoma between 2000 and 2018 were extracted from the SEER database to analyze the incidence trends.

Systematic functional characterization of non-coding regulatory SNPs associated with central obesity.

Central obesity is associated with higher risk of developing a wide range of diseases independent of overall obesity. Genome-wide association studies (GWASs) have identified more than 300 susceptibility loci associated with central obesity. However, the functional understanding of these loci is limited by the fact that most loci are in non-coding regions.

RUNX2 Phase Separation Mediates Long-Range Regulation Between Osteoporosis-Susceptibility Variant and XCR1 to Promote Osteoblast Differentiation.

GWASs have identified many loci associated with osteoporosis, but the underlying genetic regulatory mechanisms and the potential drug target need to be explored. Here, a new regulatory mechanism is found that a GWAS intergenic SNP (rs4683184) functions as an enhancer to influence the binding affinity of transcription factor RUNX2, whose phase separation can mediate the long-range chromatin interaction between enhancer and target gene XCR1 (a member of the GPCR family), leading to changes of XCR1 expression and osteoblast differentiation. Bone-targeting AAV of Xcr1 can improve bone formation in osteoporosis mice, suggesting that XCR1 can be a new susceptibility gene for osteoporosis.

Baihui-Penetrating-Qubin Acupuncture Attenuates Neurological Deficits Through SIRT1/FOXO1 Reducing Oxidative Stress and Neuronal Apoptosis in Intracerebral Hemorrhage Rats.

Background: Intracerebral hemorrhage (ICH) is a significant global disease with high mortality and disability. As of now, there is no effective therapy available. Oxidative stress and neuronal apoptosis play essential roles in ICH, determining neuronal survival.

Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.

Background: Neurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear.

Idiopathic nodular glomerulosclerosis: A case report and literature review.

This paper reports a 49-year-old male patient with a long-term smoking history who developed renal insufficiency and proteinuria in the range of nephropathy without diabetes. Renal biopsy showed nodular glomerulosclerosis with vitreous degeneration of arterioles and moderate and severe proliferation of glomerular mesangial cells and matrix. The patient was diagnosed with idiopathic nodular glomerulosclerosis.

Revealing brain cell-stratified causality through dissecting causal variants according to their cell-type-specific effects on gene expression.

The human brain has been implicated in the pathogenesis of several complex diseases. Taking advantage of single-cell techniques, genome-wide association studies (GWAS) have taken it a step further and revealed brain cell-type-specific functions for disease loci. However, genetic causal associations inferred by Mendelian randomization (MR) studies usually include all instrumental variables from GWAS, which hampers the understanding of cell-specific causality.

Proto-oncogene c-Myb potentiates cisplatin resistance of ovarian cancer cells by downregulating lncRNA NKILA and modulating cancer stemness and LIN28A-let7 axis.

Ovarian cancer is a major gynecological cancer that has poor prognosis associated mainly to its late diagnosis. Cisplatin is an FDA approved ovarian cancer therapy and even though the therapy is initially promising, the patients mostly progress to resistance against cisplatin. The underlying mechanisms are complex and not very clearly understood.

Unveiling Promising Neuroimaging Biomarkers for Schizophrenia Through Clinical and Genetic Perspectives.

Schizophrenia is a complex and serious brain disorder. Neuroscientists have become increasingly interested in using magnetic resonance-based brain imaging-derived phenotypes (IDPs) to investigate the etiology of psychiatric disorders. IDPs capture valuable clinical advantages and hold biological significance in identifying brain abnormalities.

The Causal Relationships Between Gut Microbiota, Brain Volume, and Intelligence: A Two-Step Mendelian Randomization Analysis.

Background: Growing evidence indicates that dynamic changes in gut microbiome can affect intelligence; however, whether these relationships are causal remains elusive. We aimed to disentangle the poorly understood causal relationship between gut microbiota and intelligence.

Methods: We performed a 2-sample Mendelian randomization (MR) analysis using genetic variants from the largest available genome-wide association studies of gut microbiota (N = 18,340) and intelligence (N = 269,867).

Mechanism of Efferocytosis in Determining Ischaemic Stroke Resolution-Diving into Microglia/Macrophage Functions and Therapeutic Modality.

After ischaemic cerebral vascular injury, efferocytosis-a process known as the efficient clearance of apoptotic cells (ACs) by various phagocytes in both physiological and pathological states-is crucial for maintaining central nervous system (CNS) homeostasis and regaining prognosis. The mechanisms of efferocytosis in ischaemic stroke and its influence on preventing inflammation progression from secondary injury were still not fully understood, despite the fact that the fundamental process of efferocytosis has been described in a series of phases, including AC recognition, phagocyte engulfment, and subsequent degradation. The genetic reprogramming of macrophages and brain-resident microglia after an ischaemic stroke has been equated by some researchers to that of the peripheral blood and brain.

A landscape of gene expression regulation for synovium in arthritis.

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition.