Nobiletin, an activator of the pyruvate kinase isozyme M1/M2 protein, upregulated the glycolytic signalling pathway and alleviated depressive-like behaviour caused by artificial light exposure at night in zebrafish.

We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressive-like behaviour.

Research and application on modeling and landing point prediction technology for water jet trajectory of fire trucks under large-scale scenarios.

To let water jets land at the fire, pitch angle of the fire monitor has to be adjusted manually with successive rounds, which seriously affects the efficiency of fire extinguishing. To improve the efficiency, this paper proposes a technology for water jet trajectory modeling and landing point prediction to help with extinguishing automatically. Considering fragmentation and atomization of water jets, trajectories are analyzed and the predicted trajectory is closer to the real situation.

Hydrochemical insights, water quality, and human health risk assessment of groundwater in a coastal area of southeastern China.

Groundwater is a vital water supply worldwide, but its quality has gradually deteriorated with the development of society. In this study, a total of 40 groundwater samples were collected during the pre- and post-monsoon to analyze the hydrochemical process and assess the groundwater quality and human health risks in a coastal area of southeastern China. The results showed that the concentrations of major ions were in the order of Ca > Mg > Na > K and HCO > SO > Cl > NO > F during the pre- and post-monsoon periods.

Baicalein Inhibits Cerebral Ischemia-Reperfusion Injury through SIRT6-Mediated FOXA2 Deacetylation to Promote SLC7A11 Expression.

Ischemic stroke (IS) poses a serious threat to patient survival. The inhibition of ferroptosis can effectively alleviate ischemia-reperfusion (I/R) injury, suggesting potential targets in the ferroptosis pathway for the treatment of IS. In this study, MCAO/R mice and OGD/R-induced HT22 cell were constructed.

Investigating the causal link between gut microbiota and dry age-related macular degeneration: a bidirectional Mendelian randomization study.

Aim: To assess the causal link between 211 gut microbiota (GM) taxa and dry age-related macular degeneration (dAMD) risk.

Methods: Mendelian randomization using instrumental factors taken from a genome-wide association study (GWAS) were used. Inverse variance weighted (IVW) analysis and sensitivity analysis were performed on the FinnGen project, which included 5095 cases and 222 590 controls.

Hypermethylation and suppression of microRNA219a-2 activates the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis.

Epigenetic regulations, such as DNA methylation and microRNAs, play an important role in renal fibrosis. Here, we report the regulation of microRNA219a-2 by DNA methylation in fibrotic kidneys, unveiling the crosstalk between these epigenetic mechanisms. Through genome-wide DNA methylation analysis and pyrosequencing, we detected the hypermethylation of microRNA219a-2 in renal fibrosis induced by unilateral ureteral obstruction (UUO) or renal ischemia/reperfusion, which was accompanied by a significant decrease in microRNA-219a-5p expression.

Overview of dendritic cells and related pathways in autoimmune uveitis.

Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immune responses. They are widely distributed in various tissues and organs, including the eyes. In the ocular context, permanent DCs are present at the peripheral edge of the retina and the peripapillary area in an immature state.

Eravacycline improves the efficacy of anti-PD1 immunotherapy via AP1/CCL5 mediated M1 macrophage polarization in melanoma.

Screening approved library is a promising and safe strategy to overcome the limitation of low response rate and drug resistance in immunotherapy. Accumulating evidence showed that the application of antibiotics has been considered to reduce the effectiveness of anti-PD1 immunotherapy in tumor treatment, however, in this study, an antibiotic drug (Eravacycline, ERV) was identified to improve the efficacy of anti-PD1 immunotherapy in melanoma through screening approved library. Administration of ERV significantly attenuated melanoma cells growth as well as directly or indirectly benefited M1 macrophage polarization.

PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1.

Background: Spermatogonial stem cells (SSCs) are essential for the maintenance and initiation of male spermatogenesis. Despite the advances in understanding SSC biology in mouse models, the mechanisms underlying human SSC development remain elusive.

Results: Here, we analyzed the signaling pathways involved in SSC regulation by testicular somatic cells using single-cell sequencing data (GEO datasets: GSE149512 and GSE112013) and identified that Leydig cells communicate with SSCs through pleiotrophin (PTN) and its receptor syndecan-2 (SDC2).

Association of coffee consumption with cardiometabolic multimorbidity: A prospective cohort study in the UK biobank.

Background And Aims: Previous observational studies have investigated the association between coffee consumption and single cardiometabolic disease. Yet, the extent to which coffee might confer health advantages to individuals with a singular cardiometabolic disease remains unclear. This study aimed to further investigate the association of coffee consumption and the onset and progression from single cardiometabolic disease to cardiometabolic multimorbidity (CMM).

PCMT1 confirmed as a pan-cancer immune biomarker and a contributor to breast cancer metastasis.

Protein L-isoaspartyl (D-aspartyl) methyltransferase (PIMT, gene name PCMT1) is an enzyme that repairs proteins with altered aspartate residues by methylation, restoring their normal structure and function. This study conducted a comprehensive analysis of PCMT1 in pan-cancer. The Cancer Genome Atlas, Human Protein Atlas website, and the Genotype-Tissue Expression were utilized in analysis of PCMT1 expression.

ERVcancer: a web resource designed for querying activation of human endogenous retroviruses across major cancer types.

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome, co-opted into the dynamic regulatory network of cellular potency in early embryonic development. In recent studies, resurgent HERVs' transcriptional activity has been frequently observed in many types of human cancers, suggesting their potential functions in the occurrence and progression of malignancy. However, a dedicated web resource for querying the relationship between the activation of HERVs and cancer development is lacking.

Linking reproductive tract microbiota to premature ovarian insufficiency: Pathophysiological mechanisms and therapies.

Over the past decade, research on the human microbiota has become a hot topic. Among them, the female reproductive tract (FRT) also has a specific microbiota that maintains the body's health and dynamic balance, especially in the reproductive aspect. When the FRT ecosystem is dysregulated, changes in immune and metabolic signals can lead to pathological and physiological changes such as chronic inflammation, epithelial barrier disruption, changes in cell proliferation and apoptosis, and dysregulation of angiogenesis and metabolism, thereby causing disruption of the female endocrine system.

MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression.

Background: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes.

Methods: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism.

Enhanced Two-Step LAMP-CRISPR Assay with an Engineered Polymerase for Contamination-Free and Ultrasensitive DNA Detection.

Current loop-mediated isothermal amplification (LAMP)-coupled clustered regularly interspaced short palindromic repeats (LAMP-CRISPR) biosensing in two-step or one-step formats has been applied to next-generation accurate molecular diagnosis. However, two-step LAMP-CRISPR assays intrinsically confront aerosol contamination, while one-step assays possess a compromised detection performance. To this end, we propose an enhanced two-step LAMP-CRISPR assay (ETL-CRISPR) with an engineered polymerase to mediate ultrasensitive DNA detection and thoroughly eliminate aerosol contamination.

Identification of a novel 10-hydroxyevodiamine prodrug as a potent topoisomerase inhibitor with improved aqueous solubility for treatment of hepatocellular carcinoma.

Natural product evodiamine (Evo) and its synthetic derivatives represent an attractive dual Topo 1/2 inhibitors with broad-spectrum antitumor efficacy. However, the clinical applications of these compounds have been impeded by their poor aqueous solubility. Herein, a series of water-soluble 10-substituted-N(14)-phenylevodiamine derivatives were designed and synthesized.

Primary neurolymphomatosis with MAG antibody: a case report.

Neurolymphomatosis (NL) is a rare neurologic manifestation of non-Hodgkin lymphoma (NHL) with poor prognosis. Investigations including MRI, PET/CT, nerve biopsy and cerebrospinal fluid (CSF) analysis can aid the diagnosis of NL. In this study, we presented a case of NL with co-existing myelin-associated glycoprotein (MAG) antibody.

A chemical screen identifies PRMT5 as a therapeutic vulnerability for paclitaxel-resistant triple-negative breast cancer.

Paclitaxel-resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Here, using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly.

Dietary sn-2 palmitate influences cognitive behavior by increasing the transport of liver-produced lysophosphatidylcholine VLCPUFAs to the brain.

Investigations indicated that sn-2 palmitate have positive effects on brain development, although its mechanism remains largely unexamined. This research delved into how a diet abundant in sn-2 palmitate influenced the cognitive behavior of mice and elucidated the associated mechanisms using metabolomics and lipidomics. The study demonstrated that dietary sn-2 palmitate led to improved working memory and cognition in mice, as well as an increase in brain BDNF concentration when compared to those fed blend vegetable oil (BVO).