Joint analysis of genome-wide cross-trait and multi-omics reveals molecular mechanisms of inflammatory bowel disease and nominates its novel therapeutic genes.

Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome-wide association study (GWAS) cross-trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions.

Microbe-mediated synthesis of defect-rich CeO nanoparticles with oxidase-like activity for colorimetric detection of L-penicillamine and glutathione.

To enhance production efficiency, curtail costs, and minimize environmental impact, developing simple and sustainable nanozyme synthesis methods has been the focus of relevant research. In this report, graphite-coated CeO nanoparticles (CeO NPs) with multiple defects (Ce defects, oxygen vacancies and carbon defects) were synthesized the culture filtrate of the extremely radioresistant bacterium R12 ( R12). The as-prepared CeO NPs exhibit remarkable oxidase (OXD)-like activity, efficiently catalyzing the oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) to form oxTMB, even in the absence of HO.

mTOR Variants Activation Discovers PI3K-like Cryptic Pocket, Expanding Allosteric, Mutant-Selective Inhibitor Designs.

mTOR plays a crucial role in PI3K/AKT/mTOR signaling. We hypothesized that mTOR activation mechanisms driving oncogenesis can advise effective therapeutic designs. To test this, we combined cancer genomic analysis with extensive molecular dynamics simulations of mTOR oncogenic variants.

Fluoride-Induced Autophagy and Apoptosis in the Mouse Ovary: Genomic Insights into IL-17 Signaling and Gut Microbiota Dysbiosis.

Chronic fluoride (F) exposure is linked to gonadotoxicity in females, yet the underlying molecular mechanisms remain unclear. This study investigated fluoride-induced reprotoxicity using advanced genomic profiling. RNA-seq analysis identified significant activation of autophagy, apoptosis, and IL-17 signaling pathways in fluoride-exposed female mice.

Uncovering Antiviral Potential of Cistus ladanifer Extracts Against HSV-1 and SARS-CoV-2 by In Vitro and In Silico Analysis.

Infectious diseases remain a major global health concern. Cistus ladanifer, a plant commonly employed in Moroccan traditional medicine, has been identified as a potential antiviral candidate. This study aimed to evaluate the antiviral activity of C.

Berberine Inhibits the Disruption of the Blood-Brain Barrier and Glial Cell Activation in a Rat Model of Acute Hepatic Encephalopathy.

Background And Aim: Hepatic encephalopathy (HE) is a complex neurological disorder in individuals with liver diseases, necessitating effective neuroprotective interventions to alleviate its adverse outcomes. Berberine (BBR), a natural compound with well-established anti-fibrotic and neuroprotective properties, has not been extensively studied in the context of glial activation under hyperammonaemic conditions. This study evaluates the neuroprotective potential of BBR in a thioacetamide (TAA)-induced HE rat model, focusing on its effects on glial activation and NLRP3 inflammasome signalling.

Computational Analysis of Missense Mutations: Insight into Protein Structure and Interaction Dynamics.

is implicated in a range of conditions, including autism spectrum disorder, intellectual disability, seizures, autosomal recessive nonsyndromic intellectual disability, heterotaxy, and ciliary dysfunction. In order to understand the molecular mechanisms underlying these conditions, we focused on the structural and dynamic activity consequences of mutations within this gene. In this study, whole exome sequencing identified the c.

nematodes influence microbiome and metabolome characteristics of their natural apple substrates over time.

The microbiomes of host organisms and their direct source environments are closely linked and key for shaping microbial community dynamics. The relationship between these linked dynamics is largely unexplored because source substrates are usually unavailable. To address this current knowledge gap, we employed bacteriovorous nematodes as a unique model system, for which source substrates like rotting apples can be easily collected.

Tracking clonal and plasmid transmission in colistin- and carbapenem-resistant .

The surveillance of mobile genetic elements facilitating the spread of antimicrobial resistance genes has been challenging. Here, we tracked both clonal and plasmid transmission in colistin- and carbapenem-resistant using short- and long-read sequencing technologies. We observed three clonal transmissions, all containing Incompatibility group (Inc) L plasmids and New Delhi metallo-beta-lactamase , although not co-located on the same plasmid.

Genomic re-sequencing reveals mutational divergence across genetically engineered strains of model archaea.

Unlabelled: Archaeal molecular biology has been a topic of intense research in recent decades as their role in global ecosystems, nutrient cycles, and eukaryotic evolution comes to light. The hypersaline-adapted archaeal species and serve as important model organisms for understanding archaeal genomics, genetics, and biochemistry, in part because efficient tools enable genetic manipulation. As a result, the number of strains in circulation among the haloarchaeal research community has increased in recent decades.

Influence of Magnesium Ions and Crowding Agents on Structure and Stability of RNA Aptamers.

Aptamers bind to their targets with exceptional affinity and specificity. However, their intracellular application is hampered by the lack of knowledge about the effect of the cellular milieu on the RNA structure/stability. In this study, cellular crowding was mimicked using polyethylene glycol (PEG), and the crucial role of Mg ions in stabilizing the structure of an RNA aptamer was investigated.

Preparation of Zwitterionic Sulfobetaines and Study of Their Thermal Properties and Nanostructured Self-Assembling Features.

Zwitterionic polymers have garnered significant attention for their distinctive properties, such as biocompatibility, antifouling capabilities, and resistance to protein adsorption, making them promising candidates for a wide range of applications, including drug delivery, oil production inhibitors, and water purification membranes. This study reports the synthesis and characterization of zwitterionic monomers and polymers through the modification of linear, vinyl, and aromatic heterocyclic functional groups via reaction with 1,3-propanesultone. Four zwitterionic polymers with varying molecular structures-ranging from linear to five and six membered ring systems-were synthesized: poly(sulfobetaine methacrylamide) (pSBMAm), poly(sulfobetaine-1-vinylimidazole) (pSB1VI), poly(sulfobetaine-2-vinylpyridine) (pSB2VP), and poly(sulfobetaine-4-vinylpyridine) (pSB4VP).

Harnessing the Power of Machine Learning Guided Discovery of NLRP3 Inhibitors Towards the Effective Treatment of Rheumatoid Arthritis.

The NLRP3 inflammasome, plays a critical role in the pathogenesis of rheumatoid arthritis (RA) by activating inflammatory cytokines such as IL1β and IL18. Targeting NLRP3 has emerged as a promising therapeutic strategy for RA. In this study, a multidisciplinary approach combining machine learning, quantitative structure-activity relationship (QSAR) modeling, structure-activity landscape index (SALI), docking, molecular dynamics (MD), and molecular mechanics Poisson-Boltzmann surface area MM/PBSA assays was employed to identify novel NLRP3 inhibitors.

Genetic Characteristics of the Rat Fibroblast Cell Line Rat-1.

The Rat-1 cell line was established as a subclone of the parental rat fibroblastoid line F2408, derived from Fisher 344 rat embryos. Rat-1 cells are widely used in various research fields, especially in cancer biology, to study the effects of oncogenes on cell proliferation. They are also crucial for investigating signal transduction pathways and play a key role in drug testing and pharmacological studies due to their rapid proliferation.

Evolutionarily Developed Alternatively Spliced Exons Containing Translation Initiation Sites.

Alternative splicing is essential for the generation of various protein isoforms that are involved in cell differentiation and tissue development. In addition to internal coding exons, alternative splicing affects the exons with translation initiation codons; however, little is known about these exons. Here, we performed a systematic classification of human alternative exons using coding information.

Metabolomics-Driven Biomarker Discovery for Breast Cancer Prognosis and Diagnosis.

Breast cancer is a cancer with global prevalence and a surge in the number of cases with each passing year. With the advancement in science and technology, significant progress has been achieved in the prevention and treatment of breast cancer to make ends meet. The scientific intradisciplinary subject of "metabolomics" examines every metabolite found in a cell, tissue, system, or organism from different sources of samples.

The Effects of Social Feedback Through the "Like" Feature on Brain Activity: A Systematic Review.

Background: Problematic social media (SM) use is a growing concern, particularly among adolescents who are drawn to these platforms for social interactions important to their age group. SM dependence is characterized by excessive, uncontrolled usage that impairs personal, social, and professional aspects. Despite the ongoing debate over recognizing SM addiction as a distinct diagnostic category, the impact of social feedback, particularly through the "like" button, on brain activity remains under scrutiny.

Towards a Thriving Workplace: A Feasibility Study on Mindfulness and the Mediterranean Lifestyle for Corporate Wellness.

This study explores the potential of integrating mindfulness and the Mediterranean lifestyle into corporate wellness programs to enhance workplace well-being. A survey of 485 employees from Greece and Cyprus examined how mindfulness, resilience, adherence to the Mediterranean lifestyle, and work ability are connected. Pearson correlation analysis showed statistically significant positive relationships between mindfulness, resilience, and work ability ( < 0.

Large Polarization Change Induced by Spin Crossover-Driven Fe(II) Ion Shuttling within a Tripodal Ligand.

The integration of spin crossover (SCO) magnetic switching and electric polarization properties can engender intriguing correlated magnetic and electric phenomena. However, achieving substantial SCO-induced polarization change through rational molecular design remains a formidable challenge. Herein, we present a polar Fe(II) compound that exhibits substantial polarization change in response to a thermally regulated low-spin ↔ high-spin transition.

Ovarian squamous cell carcinoma: clinicopathological features, prognosis and immunotherapy outcomes.

Objective: To explore the characteristics and survival outcomes of ovarian squamous cell carcinoma (SCC) and the treatment effectiveness of immune checkpoint inhibitors (ICIs).

Methods: Patients diagnosed with ovarian SCC at Peking Union Medical College Hospital between January 2000 and September 2023 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method.

Aging of Polystyrene Micro/Nanoplastics Enhances Cephalosporin Phototransformation via Structure-Sensitive Interfacial Hydrogen Bonding.

Beyond their roles in adsorbing and transporting pollutants, microplastics (MPs) and nanoplastics (NPs), particularly polystyrene variants (PS-M/NPs), have emerged as potential accelerators for the transformation of coexisting contaminants. This study uncovered a novel environmental phenomenon induced by aged PS-M/NPs and delved into the underlying mechanisms. Our findings revealed that the aged PS-M/NP particles significantly amplified the photodegradation of common cephalosporin antibiotics, and the extent of enhancement was tightly correlated to the molecular structures of cephalosporin antibiotics.

Molecular and biochemical evolution of casbene-type diterpene and sesquiterpene biosynthesis in rice.

Casbene and neocembrene are casbene-type macrocyclic diterpenes; their derivatives play significant roles in plant defense and have pharmaceutical applications. We had previously characterized a casbene synthase, TERPENE SYNTHASE 28 (OsTPS28), in rice (Oryza sativa). However, the mechanism of neocembrene biosynthesis in rice remained unclear.

Negative linear compressibility of molecular and ionic-molecular crystals.

The compressibility of crystalline tetrabromophthalic anhydride (TBPA) and 1-ethyl-3-methylimidazolium nitrate (EMN) was studied based on density functional theory including dispersion interactions at pressures below 1 GPa. It is found for the first time that EMN demonstrates negative linear compressibility (NLC) up to ∼0.15 GPa, whereas TBPA shows significant NLC at pressures higher than ∼0.

Molecular Weight-Dependent Boron Release Effect in PVA/Chitosan Cryogels and In Vitro Mineralization Evaluations by Osteoblast Cells.

Cryogels were fabricated by combining polyvinyl alcohol (PVA) and chitosan of varying molecular weights (Mw). In this study, the effects of chitosan Mw, types of boron-containing molecules on network formation, and boron release rate in resulted cryogels were investigated. The PVA/chitosan blend maintained a constant 4.