SARS-CoV-2 membrane protein induces neurodegeneration via affecting Golgi-mitochondria interaction.

Background: Neurological complications are a significant concern of Coronavirus Disease 2019 (COVID-19). However, the pathogenic mechanism of neurological symptoms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is poorly understood.

Methods: We used Drosophila as a model to systematically analyze SARS-CoV-2 genes encoding structural and accessory proteins and identified the membrane protein (M) that disrupted mitochondrial functions in vivo.

Single-Cell WGCNA Combined with Transcriptome Sequencing to Study the Molecular Mechanisms of Inflammation-Related Ferroptosis in Myocardial Ischemia-Reperfusion Injury.

Purpose: Myocardial ischemia-reperfusion injury (MIRI) is characterized by inflammation and ferroptosis, but the precise mechanisms remain unknown. This study used single-cell transcriptomics technology to investigate the changes in various cell subtypes during MIRI and the regulatory network of ferroptosis-related genes and immune infiltration.

Methods: Datasets GSE146285, GSE83472, GSE61592, and GSE160516 were obtained from Gene Expression Omnibus.

Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study.

Background: Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis.

Methods: This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS.

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton, modulating emotional behavior.

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function. Synaptic abnormalities, such as defects in the density and morphology of postsynaptic dendritic spines, underlie the pathology of various neuropsychiatric disorders. Protocadherin 17 (PCDH17) is associated with major mood disorders, including bipolar disorder and depression.

Tissue-specific GlcNAcylation profiling identifies substrates in translational machinery in mushroom body contributing to olfactory learning.

GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an GlcNAc binding activity derived from OGA (OGA) with TurboID proximity labeling in , we developed an GlcNAcylation profiling tool that translates GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment.

Targeting and as a therapeutic strategy for dilated cardiomyopathy: A single-cell sequencing and mendelian randomization analysis.

Background: Dilated cardiomyopathy (DCM) is widely recognized as a significant contributor to heart failure. Nevertheless, the absence of pharmaceutical interventions capable of reversing disease progression and improving prognosis underscores the imperative for additional research in this area.

Methods: First, we identified and evaluated three gene sets, namely "SC-DCM", "EP-DCM" and "Drug", using big data and multiple bioinformatics analysis methods.

Post-translational modification and mitochondrial function in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease with currently no cure. Most PD cases are sporadic, and about 5-10% of PD cases present a monogenic inheritance pattern. Mutations in more than 20 genes are associated with genetic forms of PD.

MLKL deficiency alleviates neuroinflammation and motor deficits in the α-synuclein transgenic mouse model of Parkinson's disease.

Parkinson's disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) is involved in various diseases, including inflammatory bowel disease and neurodegenerative diseases; however, its precise role in PD remains unclear.

GATCF: Graph Attention Collaborative Filtering for Reliable Blockchain Services Selection in BaaS.

Blockchain technology is a decentralized ledger that allows the development of applications without the need for a trusted third party. As service-oriented computing continues to evolve, the concept of Blockchain as a Service (BaaS) has emerged, providing a simplified approach to building blockchain-based applications. The growing demand for blockchain services has resulted in numerous options with overlapping functionalities, making it difficult to select the most reliable ones for users.

Transcriptional pausing induced by ionizing radiation enables the acquisition of radioresistance in nasopharyngeal carcinoma.

Lesions on the DNA template can impact transcription via distinct regulatory pathways. Ionizing radiation (IR) as the mainstay modality for many malignancies elicits most of the cytotoxicity by inducing a variety of DNA damages in the genome. How the IR treatment alters the transcription cycle and whether it contributes to the development of radioresistance remain poorly understood.

Protein O-GlcNAcylation homeostasis regulates facultative heterochromatin to fine-tune sog-Dpp signaling during Drosophila early embryogenesis.

Protein O-GlcNAcylation is a monosaccharide post-translational modification maintained by two evolutionarily conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Mutations in human OGT have recently been associated with neurodevelopmental disorders, although the mechanisms linking O-GlcNAc homeostasis to neurodevelopment are not understood. Here, we investigate the effects of perturbing protein O-GlcNAcylation using transgenic Drosophila lines that overexpress a highly active OGA.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need.

gene frameshift mutations in Alzheimer's disease.

Background: The pathogenic missense mutations of the gelsolin () gene lead to familial amyloidosis of the Finnish type (FAF); however, our previous study identified frameshift mutations existed in patients with Alzheimer's disease (AD). The genotype-phenotype heterogeneity and the role of frameshift mutations in patients with AD are unclear.

Method: In total, 1192 patients with AD and 1403 controls were screened through whole genome sequencing, and 884 patients with AD were enrolled for validation.

Association of variants in the KIF1A gene with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease that affects neurons in the central nervous system and the spinal cord. As in many other neurodegenerative disorders, the genetic risk factors and pathogenesis of ALS involve dysregulation of cytoskeleton and neuronal transport. Notably, sensory and motor neuron diseases such as hereditary sensory and autonomic neuropathy type 2 (HSAN2) and spastic paraplegia 30 (SPG30) share several causative genes with ALS, as well as having common clinical phenotypes.

ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription.

Transposable elements (TEs) through evolutionary exaptation have become an integral part of the human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis have been recognized, their roles in malignancy are only starting to emerge. Here we show that many TEs, especially the pluripotency-related human endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples.

Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction.

Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase β (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs).

PINK1-mediated Drp1 phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission.

Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy. However, the underlying mechanism remains elusive. We show here that Pink1 knockout (KO) mice display defective dendritic spine maturation, reduced axonal synaptic vesicles, abnormal synaptic connection, and attenuated long-term synaptic potentiation (LTP).

Switching Selectivity in Copper-Catalyzed Transfer Hydrogenation of Nitriles to Primary Amine-Boranes and Secondary Amines under Mild Conditions.

A simple and efficient copper-catalyzed selective transfer hydrogenation of nitriles to primary amine-boranes and secondary amines with an oxazaborolidine-BH complex is reported. The selectivity control was achieved under mild conditions by switching the solvent and the copper catalysts. More than 30 primary amine-boranes and 40 secondary amines were synthesized via this strategy in high selectivity and yields of up to 95%.

Revisiting tandem repeats in psychiatric disorders from perspectives of genetics, physiology, and brain evolution.

Genome-wide association studies (GWASs) have revealed substantial genetic components comprised of single nucleotide polymorphisms (SNPs) in the heritable risk of psychiatric disorders. However, genetic risk factors not covered by GWAS also play pivotal roles in these illnesses. Tandem repeats, which are likely functional but frequently overlooked by GWAS, may account for an important proportion in the "missing heritability" of psychiatric disorders.

Glycyrrhizic acid ameliorates myocardial ischemia-reperfusion injury in rats through inhibiting endoplasmic reticulum stress.

The purpose of this study was to investigate the role of glycyrrhizic acid (GA) in regulating myocardial ischemia-reperfusion injury (MIRI) in rats as well as the underlying mechanism. H9c2 cells were subjected to hypoxia/re-oxygenation (H/R) to mimic the MIRI in vitro, while a rat model of ischemia-reperfusion (I/R) was constructed by occlusion of the left anterior descending coronary artery for 0.5 h followed by 2 h of reperfusion.

Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy.

Objective: Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis.

An alternative splicing hypothesis for neuropathology of schizophrenia: evidence from studies on historical candidate genes and multi-omics data.

Alternative splicing of schizophrenia risk genes, such as DRD2, GRM3, and DISC1, has been extensively described. Nevertheless, the alternative splicing characteristics of the growing number of schizophrenia risk genes identified through genetic analyses remain relatively opaque. Recently, transcriptomic analyses in human brains based on short-read RNA-sequencing have discovered many "local splicing" events (e.