RNA-Targeting CRISPR/CasRx system relieves disease symptoms in Huntington's disease models.

Background: HD is a devastating neurodegenerative disorder caused by the expansion of CAG repeats in the HTT. Silencing the expression of mutated proteins is a therapeutic direction to rescue HD patients, and recent advances in gene editing technology such as CRISPR/CasRx have opened up new avenues for therapeutic intervention.

Methods: The CRISPR/CasRx system was employed to target human HTT exon 1, resulting in an efficient knockdown of HTT mRNA.

Potential drug targets for asthma identified through mendelian randomization analysis.

Background: The emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options for moderate-to-severe asthma treatment remain limited, highlighting the urgent need for novel therapeutic drug targets. In this study, we aimed to identify new treatment targets for asthma using the Mendelian randomization method and large-scale genome-wide association data (GWAS).

Targeting deubiquitinase USP7-mediated stabilization of XPO1 contributes to the anti-myeloma effects of selinexor.

Background: Targeting exportin1 (XPO1) with Selinexor (SEL) is a promising therapeutic strategy for patients with multiple myeloma (MM). However, intrinsic and acquired drug resistance constitute great challenges. SEL has been reported to promote the degradation of XPO1 protein in tumor cells.

Specific plasma metabolite profile in intestinal Behçet's syndrome.

Background: Intestinal Behçet's syndrome (IBS) has high morbidity and mortality rates with serious complications. However, there are few specific biomarkers for IBS. The purposes of this study were to investigate the distinctive metabolic changes in plasma samples between IBS patients and healthy people, active IBS and inactive IBS patients, and to identify candidate metabolic biomarkers which would be useful for diagnosing and predicting IBS.

Bacillus subtilis HGCC-1 improves growth performance and liver health via regulating gut microbiota in golden pompano.

Probiotics as green inputs have been reported to regulate metabolism and immunity of fish. However, the mechanisms by which probiotics improve growth and health of fish are unclear. Therefore, the aim of this study was to investigate the effect of Bacillus subtilis HGCC-1, an indigenous probiotic isolated from fish, on growth performance, host lipid metabolism, liver inflammation and gut microbiota of golden pompano.

Amantadine modulates novel macrophage phenotypes to enhance neural repair following spinal cord injury.

Background: Spinal cord injury (SCI) triggers a complex inflammatory response that impedes neural repair and functional recovery. The modulation of macrophage phenotypes is thus considered a promising therapeutic strategy to mitigate inflammation and promote regeneration.

Methods: We employed microarray and single-cell RNA sequencing (scRNA-seq) to investigate gene expression changes and immune cell dynamics in mice following crush injury at 3 and 7 days post-injury (dpi).

Histone demethylases in autophagy and inflammation.

Autophagy dysfunction is associated with changes in autophagy-related genes. Various factors are connected to autophagy, and the mechanism regulating autophagy is highly complicated. Epigenetic changes, such as aberrant expression of histone demethylase, are actively associated not only with oncogenesis but also with inflammatory responses.

Identification and validation of the important role of KIF11 in the development and progression of endometrial cancer.

Background: Human kinesin family member 11 (KIF11) plays a vital role in regulating the cell cycle and is implicated in the tumorigenesis and progression of various cancers, but its role in endometrial cancer (EC) is still unclear. Our current research explored the prognostic value, biological function and targeting strategy of KIF11 in EC through approaches including bioinformatics, machine learning and experimental studies.

Methods: The GSE17025 dataset from the GEO database was analyzed via the limma package to identify differentially expressed genes (DEGs) in EC.

Upregulated astrocyte HDAC7 induces Alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis.

Background: Astrocytes, the most abundant glial cell type in the brain, will convert into the reactive state in response to proteotoxic stress such as tau accumulation, a characteristic feature of Alzheimer's disease (AD) and other tauopathies. The formation of reactive astrocytes is partially attributed to the disruption of autophagy lysosomal signaling, and inhibiting of some histone deacetylases (HDACs) has been demonstrated to reduce the molecular and functional characteristics of reactive astrocytes. However, the precise role of autophagy lysosomal signaling in astrocytes that regulates tau pathology remains unclear.

Socioeconomic status moderate the relationship between mental health literacy, social participation, and active aging among Chinese older adults: evidence from a moderated network analysis.

Objective: The aging population represents a formidable global challenge, with China experiencing an accelerated demographic shift. While previous research has established a directional link between mental health literacy, social participation, and active aging, the moderating effect of socioeconomic status (SES) on these associations remains underexplored. This study sought to address this gap by employing moderated network analysis, in contrast to the total score approaches commonly used in prior literature.

The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy.

KRAS is one of the most mutated genes, driving alternations in metabolic pathways that include enhanced nutrient uptaking, increased glycolysis, elevated glutaminolysis, and heightened synthesis of fatty acids and nucleotides. However, the beyond mechanisms of KRAS-modulated cancer metabolisms remain incompletely understood. In this review, we aim to summarize current knowledge on KRAS-related metabolic alterations in cancer cells and explore the prevalence and significance of KRAS mutation in shaping the tumor microenvironment and influencing epigenetic modification via various molecular activities.

tRNA-derived small RNAs: their role in the mechanisms, biomarkers, and therapeutic strategies of colorectal cancer.

Colorectal cancer (CRC) is the third most prevalent malignancy and the second leading cause of cancer-related mortality worldwide, with an increasing shift towards younger age of onset. In recent years, there has been increasing recognition of the significance of tRNA-derived small RNAs (tsRNAs), encompassing tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Their involvement in regulating translation, gene expression, reverse transcription, and epigenetics has gradually come to light.

Global burden and attributable risk factors of inflammatory cardiomyopathy and myocarditis from 1990 to 2019.

Background: Our understanding of the global burden distribution of inflammatory cardiomyopathy and myocarditis is very limited.

Objective: To comprehensively assess the global burden distribution and attributable risk factors of inflammatory cardiomyopathy and myocarditis from 1990 to 2019.

Methods: We extracted the data on death, disability-adjusted life years (DALY), and age-standardized rate (ASR) of inflammatory cardiomyopathy and myocarditis from the 2019 Global Burden of Disease (GBD) study, including the comprehensive data and the data classified by age/sex.

Gut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation.

Background: The conversion of primary bile acids to secondary bile acids by the gut microbiota has been implicated in colonic inflammation. This study investigated the role of gut microbiota related bile acid metabolism in colonic inflammation in both patients with inflammatory bowel disease (IBD) and a murine model of dextran sulfate sodium (DSS)-induced colitis.

Methods: Bile acids in fecal samples from patients with IBD and DSS-induced colitis mice, with and without antibiotic treatment, were analyzed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS).

AGD1/USP10/METTL13 complexes enhance cancer stem cells proliferation and diminish the therapeutic effect of docetaxel via CD44 m6A modification in castration resistant prostate cancer.

Background: Most patients with prostate cancer inevitably progress to castration-resistant prostate cancer (CRPC), at which stage chemotherapeutics like docetaxel become the first-line treatment. However, chemotherapy resistance typically develops after an initial period of therapeutic efficacy. Increasing evidence indicates that cancer stem cells confer chemotherapy resistance via exosomes.

Establishment and validation of predictive model of ARDS in critically ill patients.

Background: Acute respiratory distress syndrome (ARDS) is a prevalent complication among critically ill patients, constituting around 10% of intensive care unit (ICU) admissions and mortality rates ranging from 35 to 46%. Hence, early recognition and prediction of ARDS are crucial for the timely administration of targeted treatment. However, ARDS is frequently underdiagnosed or delayed, and its heterogeneity diminishes the clinical utility of ARDS biomarkers.

Degenerated vision, altered lipid metabolism, and expanded chemoreceptor repertoires enable Lindaspio polybranchiata to thrive in deep-sea cold seeps.

Background: Lindaspio polybranchiata, a member of the Spionidae family, has been reported at the Lingshui Cold Seep, where it formed a dense population around this nascent methane vent. We sequenced and assembled the genome of L. polybranchiata and performed comparative genomic analyses to investigate the genetic basis of adaptation to the deep sea.

Improving prognostic evaluations in patients with stage IIIb light chain cardiac amyloidosis: role of haemodynamic parameters.

Background: There is no unified prognostic scoring system for light chain cardiac amyloidosis (AL-CA), particularly stage IIIb AL-CA. This study aimed to use invasive haemodynamic information to investigate markers that can more accurately evaluate the prognosis of patients with stage IIIb AL-CA.

Methods: In this retrospective cohort study, we conducted invasive haemodynamic measurements concurrently with myocardial biopsies to diagnose AL-CA.

YTHDF1-mediated m6A modification of GBP4 promotes M1 macrophage polarization in acute lung injury.

Background: Acute lung injury (ALI) is a severe condition with multifaceted causes, including inflammation and oxidative stress. This research investigates the influence of m6A (N6-methyladenosine) modification on GBP4, a protein pivotal for macrophage polarization, a critical immune response in ALI.

Methods: Utilizing a mouse model to induce ALI, the study analyzed GBP4 expression in alveolar macrophages.

Combined 25-hydroxyvitamin D concentrations and physical activity on mortality in US stroke survivors: findings from the NHANES.

Background: 25-hydroxyvitamin D [25(OH)D] concentrations and physical activity (PA) are linked and both are associated with changes in mortality. We examined the association of 25(OH)D and PA with all-cause or cause-specific mortality risk in stroke survivors.

Methods: The analysis included 677 stroke survivors from National Health and Nutrition Examination Survey (NHANES) 2007-2008 to 2017-2018.

Drug-target binding affinity prediction based on power graph and word2vec.

Background: Drug and protein targets affect the physiological functions and metabolic effects of the body through bonding reactions, and accurate prediction of drug-protein target interactions is crucial for drug development. In order to shorten the drug development cycle and reduce costs, machine learning methods are gradually playing an important role in the field of drug-target interactions.

Results: Compared with other methods, regression-based drug target affinity is more representative of the binding ability.

Association between triglyceride-glucose (TyG) related indices and cardiovascular diseases and mortality among individuals with metabolic dysfunction-associated steatotic liver disease: a cohort study of UK Biobank.

Background: Triglyceride-glucose (TyG) related indices, which serve as simple markers for insulin resistance, have been closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular disease (CVD), and mortality. However, the prognostic utility of TyG-related indices in predicting the risk of CVD and mortality among patients with MASLD remains unclear.

Methods: Data of 97,331 MASLD patients, with a median age of 58.

Association between estimated glucose disposal rate and cardiovascular diseases in patients with diabetes or prediabetes: a cross-sectional study.

Background: Insulin resistance proxy indicators are significantly associated with cardiovascular disease (CVD) and diabetes. However, the correlations between the estimated glucose disposal rate (eGDR) index and CVD and its subtypes have yet to be thoroughly researched.

Methods: 10,690 respondents with diabetes and prediabetes from the NHANES 1999-2016 were enrolled in the study.

Signal integrator function of CXXC5 in Cancer.

CXXC type zinc finger protein 5 (CXXC5) is a member of the ZF-CXXC family and plays a pivotal role in signal integration and information transfer within cell signaling network. CXXC5 acts as a regulator in various physiological processes, and abnormalities in its protein structure or function have been linked to multiple pathological processes. In this article, we correspondingly describe the composition of the ZF-CXXC family, emphatically introducing the features of the CXXC5 gene and protein, review the role of CXXC5 in cellular signaling networks, the physiological and pathological processes associated with CXXC5 dysregulation, and particularly focus on the correlation between CXXC5 and cancers.