α-Lipoic acid mitigates age-related macular degeneration via ferroptosis: integrative multi-omics and network pharmacology.

Background: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly. α-Lipoic acid (ALA), a naturally occurring antioxidant and iron-chelator, has shown potential in modulating ferroptosis, but its mechanism in AMD remains unclear.

Methods: Network pharmacology, transcriptomic profiling, and machine learning were used to identify potential molecular targets of ALA in AMD.

Retinal transduction profiling of diverse AAV serotypes via intravitreal injection.

Unlabelled: Optimizing adeno-associated virus (AAV) capsid and dosing selection is critical for the clinical translation of retinal gene therapy. This study aims to provide a comprehensive reference by comparing the transduction efficiency, cellular tropisms, and temporal retinal expression patterns of various AAV serotypes for intravitreal retinal gene therapy. A series of AAV vectors were intravitreally injected into C57BL/6J mice.

Development and validation of a nomogram model for predicting one-year unplanned readmission in patients with chronic obstructive pulmonary disease.

Objective: The aim of this study was to investigate the influencing factors of unplanned readmission in patients with chronic obstructive pulmonary disease (COPD) within 1 year after discharge, construct a risk prediction model and evaluate its effect.

Methods: In this prospective study, we included 719 individuals diagnosed with COPD, identify optimal predictors of unplanned readmission and developed a nomogram prediction model. The model's performance was assessed through receiver operator characteristic curves, calibration plots, and decision curve analysis.

Single-cell polygenic risk scores dissect cellular and molecular heterogeneity of complex human diseases.

Polygenic risk scores (PRSs) predict an individual's genetic risk for complex diseases, yet their utility in elucidating disease biology remains limited. We introduce scPRS, a graph neural network-based framework that computes single-cell-resolved PRSs by integrating reference single-cell chromatin accessibility profiles. scPRS outperforms traditional PRS approaches in genetic risk prediction, as demonstrated across multiple diseases including type 2 diabetes, hypertrophic cardiomyopathy, Alzheimer disease and severe COVID-19.

Clinical characteristics and economic burden of Alzheimer's disease inpatients in Hubei Province, China: a retrospective analysis of hospitalization costs and length of stay.

Background: The rapid aging of the population in China has led to a significant increase in the incidence of Alzheimer's disease (AD). This escalating trend has resulted in a substantial economic burden, posing a formidable challenge to society.

Methods: The study population comprised inpatients with AD in Hubei Province from January 2019 to December 2021.

Double-Weak Coordination Electrolyte Enables 5 V and High Temperature Lithium Metal Batteries.

Layered oxide cathodes offer high specific capacity and operating voltage, whereas constructing a stable interface to maintain the stable operation of high-voltage cathodes under high charge state and elevated temperature remains challenging. Herein, a double-weak coordination strategy which triggers by single solvent and dilute is designed. The solvent tris(2,2,2-trifluoroethyl) phosphate (TFEP) exhibits weak lithium coordination due to the partial fluorination of the alkyl chain, while the dilute ethoxy(pentafluoro)cyclo triphosphazene (PFPN) is involved in the inner solvation structure by weak lithium-TFEP coordination and its mild lithium affinity.

Systematic Identification of Mitochondrial Signatures in Alzheimer's Disease and Inflammatory Bowel Disease.

Mitochondrial dysfunction is increasingly recognized as a shared feature of Alzheimer's disease (AD) and inflammatory bowel disease (IBD), linked through overlapping pathways of hypoxia and immune dysregulation. Our study integrated transcriptomic and genetic analyses to uncover mitochondria-related mechanisms underlying these diseases. By analyzing multiple AD and IBD datasets through differential expression gene (DEG) analyses, biological pathway enrichment, and co-expression module construction, we identified hypoxia-induced mitochondrial dysfunction as a central risk factor for both conditions.

Deciphering novel mitochondrial signatures: multi-omics analysis uncovers cross-disease markers and oligodendrocyte pathways in Alzheimer's disease and glioblastoma.

Introduction: Alzheimer's disease (AD) and glioblastoma (GBM) are severe neurological disorders that pose significant global healthcare challenges. Despite extensive research, the molecular mechanisms, particularly those involving mitochondrial dysfunction, remain poorly understood. A major limitation in current studies is the lack of cell-specific markers that effectively represent mitochondrial dynamics in AD and GBM.

Comparative characterization of human accelerated regions in neurons.

Human accelerated regions (HARs) are conserved genomic loci that have experienced rapid nucleotide substitutions following the divergence from chimpanzees. HARs are enriched in candidate regulatory regions near neurodevelopmental genes, suggesting their roles in gene regulation. However, their target genes and functional contributions to human brain development remain largely uncharacterized.

ELAV/Hu RNA-binding protein family: key regulators in neurological disorders, cancer, and other diseases.

The ELAV/Hu family represents a crucial group of RNA-binding proteins predominantly expressed in neurons, playing significant roles in mRNA transcription and translation. These proteins bind to AU-rich elements in transcripts to regulate the expression of cytokines, growth factors, and the development and maintenance of neurons. Elav-like RNA-binding proteins exhibit remarkable molecular weight conservation across different species, highlighting their evolutionary conservation.

CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes.

Background: During oocyte maturation, DNA double-strand breaks (DSBs) can decrease oocyte quality or cause mutations. How DSBs are repaired in dividing oocytes and which factors influence DSB repair are not well understood.

Results: By analyzing DSB repair pathways in oocytes at different stages, we found that break-induced replication (BIR) and RAD51-mediated homology-directed repair (HDR) were highly active in germinal vesicle breakdown (GVBD) oocytes but suppressed in metaphase II (MII) oocytes and the BIR in oocytes was promoted by CDK1 activity.

The PRC2.1 subcomplex opposes G1 progression through regulation of CCND1 and CCND2.

Progression through the G1 phase of the cell cycle is the most highly regulated step in cellular division. We employed a chemogenetic approach to discover novel cellular networks that regulate cell cycle progression. This approach uncovered functional clusters of genes that altered sensitivity of cells to inhibitors of the G1/S transition.

Progress in photoreceptor replacement therapy for retinal degenerative diseases.

Retinal degenerative diseases encompass a diverse range of eye conditions that result in blindness, many due to photoreceptor dysfunction and loss. Regrettably, current clinical treatments are frequently not overly effective. However, photoreceptor transplantation shows promise as a potential therapy for late-stage retinal degenerative diseases.

Downstream transcription promotes human recurrent CNV associated AT-rich sequence mediated genome rearrangements in yeast.

AT-rich sequence can cause structure variants such as translocations and its instability can be accelerated by replication stresses. When human 16p11.2 or 22q11.

Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2.

Gestational diabetes mellitus (GDM), a common pregnancy disease, has long-term negative effects on offspring health. Epigenetic changes may have important contributions to that, but the underlying mechanisms are not well understood. Here, we report the influence of GDM on DNA methylation of offspring (GDF1) oocytes and the possible mechanisms.

Maternal obesity may disrupt offspring metabolism by inducing oocyte genome hyper-methylation via increased DNMTs.

Maternal obesity has deleterious effects on the process of establishing oocyte DNA methylation; yet the underlying mechanisms remain unclear. Here, we found that maternal obesity disrupted the genomic methylation of oocytes using a high-fat diet (HFD) induced mouse model, at least a part of which was transmitted to the F2 oocytes and livers via females. We further examined the metabolome of serum and found that the serum concentration of melatonin was reduced.

Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery.

Over the past decade, single-cell genomics technologies have allowed scalable profiling of cell-type-specific features, which has substantially increased our ability to study cellular diversity and transcriptional programs in heterogeneous tissues. Yet our understanding of mechanisms of gene regulation or the rules that govern interactions between cell types is still limited. The advent of new computational pipelines and technologies, such as single-cell epigenomics and spatially resolved transcriptomics, has created opportunities to explore two new axes of biological variation: cell-intrinsic regulation of cell states and expression programs and interactions between cells.

Discrimination of wheat gluten quality utilizing terahertz time-domain spectroscopy (THz-TDS).

Wheat is an important food crop in the world, and wheat gluten quality is one of the important standards for judging the use of wheat. In this study, a combination of chemometric and machine learning methods based on THz-TDS were used to identify three different gluten wheats (high gluten, medium gluten, and low gluten). After collecting the time-domain spectral information of the samples, the frequency-domain spectra, refractive index spectra and absorption coefficient spectra of the samples were obtained by calculating the optical parameters.

De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.

Three-dimensional genome organization plays a critical role in gene regulation, and disruptions can lead to developmental disorders by altering the contact between genes and their distal regulatory elements. Structural variants (SVs) can disturb local genome organization, such as the merging of topologically associating domains upon boundary deletion. Testing large numbers of SVs experimentally for their effects on chromatin structure and gene expression is time and cost prohibitive.

Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas.

Mosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)-modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown. We addressed these questions using clinical data and blood samples from patients previously treated with CAR-T and subsequently treated on a phase 1/2 study of mosunetuzumab.

Flavopiridol induces cell cycle arrest and apoptosis by interfering with CDK1 signaling pathway in human ovarian granulosa cells.

Several clinical trials have been conducted to evaluate the use of flavopiridol (FP) to treat a variety of cancers, and almost all cancer drugs were found to be associated with toxicity and side effects. It is not clear whether the use of FP will affect the female reproductive system. Granulosa cells, as the important cells that constitute the follicle, play a crucial role in determining the reproductive ability of females.

Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.

Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays.

Enhancing Sensitivity and Selectivity: Current Trends in Electrochemical Immunosensors for Organophosphate Analysis.

This review examines recent advancements in electrochemical immunosensors for the detection of organophosphate pesticides, focusing on strategies to enhance sensitivity and selectivity. The widespread use of these pesticides has necessitated the development of rapid, accurate, and field-deployable detection methods. We discuss the fundamental principles of electrochemical immunosensors and explore innovative approaches to improve their performance.