In vivo self-assembled siRNAs ameliorate neurological pathology in TDP-43-associated neurodegenerative disease.

Abnormal accumulation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Small interfering RNAs (siRNAs) targeting TDP-43 offer potential therapeutic strategies for these diseases. However, efficient and safe delivery of siRNAs to the central nervous system (CNS) remains a critical challenge.

Integration of humanized ROBO1 CAR in PD-1 locus in natural killer cells delivers synergistic tumor-killing effect against non-small cell lung cancer.

Lung cancer is the most common cancer and one of the leading causes of cancer-related deaths in the world, however, the treatment of non-small cell lung cancer (NSCLC) is still limited, and it is a clinically urgent problem. ROBO1 is an important surface receptor on tumor cells, but the role of humanized chimeric antigen receptor (CAR) modified natural killer (NK) cells targeting ROBO1 in NSCLC is rarely explored. Furthermore, the role of PD-1 in NK cell killing tumor cells remains controversial.

Malachite green in environmental samples: Updates on sources, fates, distribution and removal techniques.

Malachite green (MG) is a synthetic triphenylmethane dye originally employed as an industrial colorant in textile, paper, and leather industries. Its subsequent application in aquaculture was driven by its demonstrated antibacterial and antiparasitic properties. However, substantial evidence has revealed its high toxicity, including carcinogenic, teratogenic, and mutagenic effects, posing severe threats to both ecological systems and human health, leading to strict regulations or outright bans in numerous countries.

3D printable phase change information storage label films for dynamic and multi-level anti-counterfeiting.

Anti-counterfeiting technology demands continuous innovation to address escalating global counterfeiting challenges. This study introduces 3D printable phase change information storage label films for dynamic, multi-level anti-counterfeiting applications. Utilizing extrusion-based 3D printing, customizable anti-counterfeiting labels with complex encrypted information such as barcodes and QR codes were fabricated.

Landscape of extracellular small RNA and identification of biomarkers in multiple human cancers.

Extracellular RNAs (exRNAs) in biofluids, sourced from diverse tissues, exhibit various biological functions and diagnostic potential. Small non-coding RNAs, such as rsRNAs and tsRNAs, are abundant in tissues and likely secreted into biofluids, contributing to exRNA profiles. To comprehensively evaluate exRNAs, we employed traditional and enzymatic treatment RNA sequencing to systematically profile exRNAs across six human biofluids including serum, ascites, urine, milk, seminal plasma and saliva as well as sera from mice, rats, rabbits, and bovines.

Preparation of glycine-pectin complex and its application in drug delivery system.

The side chain modification of apple pectin was carried out to enhance its usablitity as a drug carrier. During the sequential drug release, indomethacin released with very low rate in the early two hours in artificial gastric juice, and then it released with much higher rate in the next six hours in artificial intestinal juice. Among all the tested samples, glycine-pectin complex showed the highest difference between the amount of cumulative drug release in artificial gastric juice and artificial intestinal juice.

In vivo self-assembled SOD1-siRNAs mitigate muscle atrophy and denervation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the death of both upper and lower motor neurons. Approximately 20% of familial ALS cases are associated with mutations in the superoxide dismutase type 1 (SOD1) gene. Developing a specific strategy to characteristically silence the pathogenic SOD1 gene remains a crucial goal amidst significant challenges.

Effects of second-generation antipsychotics and long-term atherogenic indices trajectories on metabolic syndrome in patients with schizophrenia.

Background: Atherogenic indices (AIs) predict metabolic abnormalities, yet their longitudinal patterns and interaction with antipsychotics in schizophrenia-related metabolic syndrome (MetS) remain unclear.

Methods: This longitudinal study composed of 469 MetS-free participants identified AIs trajectories from three follow-up assessments (2019-2021). Group-based trajectory modeling characterized atherogenic index of plasma (AIP), atherogenic coefficient (AC), and Castelli risk index II (CRI-II).

Impact of baseline and trajectory of the cardiometabolic indices on incident microvascular complications in patients with type 2 diabetes.

Background: For patients with type 2 diabetes (T2D), the triglyceride-glucose (TyG) index, the atherogenic index of plasma (AIP) and the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) are recognized as reliable predictors of cardiovascular diseases. However, the association of these predictors with microvascular complications (MVCs) in T2D remains controversial and warrants further investigation.

Methods: Using data from the Action to Control Cardiovascular Risk in Diabetes study, we examined the association of cardiometabolic indices with the risk of incident microvascular outcomes, including diabetic kidney disease (DKD), diabetic neuropathy (DN) and diabetic retinopathy (DR).

Atheroprotective roles of exercise-regulated microRNAs.

Cardiovascular disease remains the leading cause of death worldwide, with atherosclerosis (AS) serving as a critical underlying pathological process and major risk factor. Regular physical exercise is widely recognized as an effective strategy to reduce the risks and severity of AS, yet the precise molecular mechanisms through which exercise exerts its protective effects are still not fully understood. MicroRNAs (miRNAs), key regulators of gene expression, play integral roles in the progression of AS by influencing vascular function, lipid metabolism, and inflammation.

Protecting and rejuvenating ageing skin by regulating endogenous hyaluronan metabolism using adipose-derived stem cell-secreted siRNAs.

Background: Loss of moisture is the primary cause of skin ageing and dysfunction. The skin's hydration largely depends on hyaluronan (HA) and its ability to retain water. Ultraviolet (UV) irradiation, which accounts for 80% of skin ageing (commonly referred to as photoaging), gradually disrupts the balance of HA metabolism, leading to a reduction in HA levels, dehydration, and, ultimately, the formation of wrinkles.

Comparing Artificial Intelligence-Generated and Clinician-Created Personalized Self-Management Guidance for Patients With Knee Osteoarthritis: Blinded Observational Study.

Background: Knee osteoarthritis is a prevalent, chronic musculoskeletal disorder that impairs mobility and quality of life. Personalized patient education aims to improve self-management and adherence; yet, its delivery is often limited by time constraints, clinician workload, and the heterogeneity of patient needs. Recent advances in large language models offer potential solutions.

Oxytocin Improves Autistic Behaviors by Positively Shifting GABA Reversal Potential via NKCC1 in Early-Postnatal-Stage.

Accumulating evidence has identified disrupted oxytocin signaling in both autistic patients and animal models of autism. Nevertheless, the specific timing of the impact of oxytocin on social behavior has remained unclear. Using mouse strains from oxytocin-Cre mice crossed with Cre-dependent chemogenetic mice, oxytocinergic neuronal activity is selectivity manipulated during the early or late postnatal stages and revealed, for the first time, that the suppression of oxytocinergic neurons in the early rather than late postnatal stage led to the emergence of autistic-like behaviors.

Unraveling new therapeutic targets in ankylosing spondylitis: Multi-omics Mendelian randomization on immune cells, metabolites, and inflammation proteins.

This study aims to identify novel immunological, metabolic, and inflammatory determinants of ankylosing spondylitis (AS) using Mendelian randomization (MR), offering new insights into its pathogenesis and potential therapeutic interventions. Employing a bidirectional, secondary validation two-sample MR, this study investigated causal associations among 1400 serum metabolites, 731 immune cell traits, and 91 circulating inflammatory proteins with AS. Instrumental variables were identified using PLINK for minimal linkage disequilibrium, applying strict significance thresholds.

Blocking triggering receptors expressed on myeloid cell-1 alleviates alveolar epithelial cell senescence by inhibiting oxidative stress in pulmonary fibrosis.

Pulmonary fibrosis (PF) is an insidious, progressive, and fatal age-associated disease that occurs primarily in older adults and has a poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. The accumulation of oxygen radicals, commonly referred to as reactive oxygen species (ROS), strongly contributes to cellular senescence.

The role of the hippocampus and SLC39A8 in chronic musculoskeletal pain-induced dementia: a Mendelian randomization study.

Despite observational studies suggesting a link between chronic musculoskeletal pain (CMP) and increased risk of cognitive decline and dementia, the causal nature of this relationship remains uncertain due to potential confounding factors and reverse causality. We employed two-sample Mendelian Randomization (TSMR), bidirectional MR, mediation MR, drug-target MR, and colocalization analysis, along with gene set enrichment and protein-protein interaction (PPI) analyses. TSMR assessed the causal associations between CMP and the risk of dementia and its subtypes, including Alzheimer's disease (AD), vascular dementia (VaD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and Parkinson's disease (PD).

Association between serum bilirubin and type 2 diabetes mellitus risk: Findings from a schizophrenia cohort.

Background: The relationship between serum bilirubin levels and type 2 diabetes mellitus (T2DM) in individuals with schizophrenia (SCZ) remains poorly understood. This study investigated associations between total, conjugated, and unconjugated bilirubin (TB, CB, and UCB) and T2DM risk, while exploring the potential role of inflammatory pathways.

Methods: The study included 862 SCZ patients from Baiyun Jingkang Hospital, Guangzhou, the People's Republic of China.

Disentangling Multiple pH-Dependent Factors on the Hydrogen Evolution Reaction at Au(111).

Understanding how the electrolyte pH affects electrocatalytic activity is a topic of crucial importance in a large variety of systems. However, unraveling the origin of the pH effects is complicated often by the fact that both the reaction driving forces and reactant concentrations in the electric double layer (EDL) change simultaneously with the pH value. Herein, we employ the hydrogen evolution reaction (HER) at Au(111)-aqueous solution interfaces as a model system to disentangle different pH-dependent factors.

Exploring the multifaceted roles of histone deacetylase inhibitor vorinostat in the cell growth, mycelial morphology, pigments, and citrinin biosynthesis of Monascus purpureus.

Acetylation is an important modification type of histones, which is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, the histone acetylation level of Monascus was enhanced through the exogenous addition of the HDACs inhibitor vorinostat, and the regulation effects of histone acetylation on cell growth and secondary metabolism were evaluated. The results demonstrated that the augmentation of histone acetylation level could slightly facilitate sugar consumption, increase biomass weight, and significantly induce noticeable morphological alterations.

siRNA-AGO2 complex inhibits bacterial gene translation: A promising therapeutic strategy for superbug infection.

Silencing resistance genes of pathogenic bacteria by RNA interference (RNAi) is a potential strategy to fight antibiotic-resistant bacterial infections. Currently, RNAi cannot be achieved in bacteria due to the lack of RNA-induced silencing complex machinery and the difficulty of small interfering RNA (siRNA) delivery. Here, we show that exosomal siRNAs can be efficiently delivered into bacterial cells and can silence target genes primarily through translational repression without mRNA degradation.

N-homocysteinylation of β-arrestins biases GPCR signaling and promotes platelet activation.

Hyperhomocysteinemia (HHcy) is strongly associated with cardiovascular diseases (CVDs), and it has been identified as a risk factor for thrombotic diseases. Most patients with HHcy die from various complications closely related to thrombotic diseases. However, the underlying mechanisms have not been fully elucidated.

L1CAM extracellular vesicles derived from the serum of adolescents with major depressive disorder induce depression-like phenotypes in adolescent mice.

Background: It has been reported that L1 cell adhesion molecule (L1CAM) antibody can capture neuron-derived extracellular vesicles (NDEVs) derived from peripheral blood. This antibody is significantly associated with occurrence of adult psychiatric disorders. However, the role and mechanism of L1CAM EVs (L1 EVs) in adolescent with major depressive disorder (AMDD) is not well understood.

Computed tomography enterography-based radiomics for assessing mucosal healing in patients with small bowel Crohn's disease.

Background: Mucosal healing (MH) is the major therapeutic target for Crohn's disease (CD). As the most commonly involved intestinal segment, small bowel (SB) assessment is crucial for CD patients. Yet, it poses a significant challenge due to its limited accessibility through conventional endoscopic methods.