Cisplatin-induced WWP1-eccDNA expression contributes to ovarian cancer resistance.

Background: Multidrug resistance remains a major obstacle in the treatment of ovarian cancer (OC) patients. Recent research has underscored the critical role of extrachromosomal circular DNA (eccDNA) in tumor initiation and progression. However, there is limited comprehensive understanding of the role eccDNA plays in tumor resistance.

Effect of digital virtual reality simulator on pre-clinical dental surgical skill training: a retrospective study.

Aim: Dental surgical skills training assumes critical importance for aspiring dentists. Our present study aimed to investigate the effectiveness of innovative DVRS approach in assessing competency and improving skill in preclinical dental surgical skill training.

Methods: A total of 142 students participated in this study.

Insights into the role of MSLN-positive circulating tumor cell as an auxiliary diagnostic biomarker in epithelial ovarian cancer.

Background: Epithelial ovarian cancer (EOC) currently lacks highly specific biomarkers for clinical screening. This study aimed to identify and validate novel auxiliary diagnostic markers for EOC.

Methods: Through integrated analysis of transcriptome sequencing data and single-cell RNA sequencing from public databases, we identified mesothelin (MSLN) as an EOC-specific target.

The LSD1/HDAC dual-target inhibitor for cancer therapy: Challenge and opportunity.

In recent years, the epigenetic regulation in tumor development has garnered significant attention. The lysine-specific demethylase 1 (LSD1) and histone deacetylase (HDAC), key enzymes involved in epigenetic modification, are overexpressed in various cancers and promote tumor cell proliferation and differentiation by modulating histone modifications. Although single-target inhibitors for LSD1 or HDAC exhibit efficacy in preclinical models, their clinical utility is hindered by compensatory signaling pathways and the emergence of drug resistance.

Senescent Epithelial Cells Serve as Invasive Growth Drivers in Ameloblastoma.

Cellular senescence and its associated microenvironment play a pivotal role in tumor initiation and progression. Although ameloblastoma (AM) is classified as a benign tumor, it is characterized by local invasiveness and a high recurrence rate. In this study, we identified a distinct population of senescent epithelial cells using senescence-associated β-galactosidase staining and explored the role of this subpopulation in AM progression.

Design, synthesis, and structure-activity relationship study of novel GLP-1/GIP/GCG triple receptor agonists.

In this study, to achieve more effective blood sugar lowering and weight-loss effects, eight glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic peptide (GIP)/glucagon (GCG) triple receptor agonists were designed and synthesized. Their sixteen related conjugates were obtained through Cys alkylation and Lys esterification modifications with two fatty acid side chains, respectively. After chemical structure confirmation using high-resolution mass spectrometry and peptide mapping, in vitro and in vivo biological effects of TRA01-24 were assessed.

The prospects and challenges of small molecule drugs in the treatment of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by mutations in the DMD gene, leading to reduced or absent dystrophin expression. This results in progressive muscle degeneration, cardiomyopathy, respiratory failure, and ultimately death. Conventional glucocorticoid treatments slow disease progression but cause severe side effects with long-term use.

Construction and Application of Traditional Chinese Medicine Knowledge Graph Based on Large Language Model.

Traditional Chinese Medicine (TCM) is a vital component of the Chinese heritage, embodying a wealth of medical knowledge and distinctive therapeutic practices. A critical challenge in TCM modernization lies in extracting essential information from its complex and diverse knowledge system to develop knowledge-based services, which represents a cutting-edge research focus. This study proposes a Large Language Model (LLM)-driven approach for structuring TCM knowledge integrating historical TCM texts with open-source TCM datasets.

Integrated metabolomics and metagenomics reveal plant-microbe interactions driving aroma differentiation in flue-cured tobacco leaves.

Current research on tobacco aroma predominantly focuses on single-omics approaches. In this study, we conducted a comprehensive investigation of the relationships between tobacco metabolite profiles, microbial communities, and aroma characteristics. Untargeted metabolomics and metagenomic analyses were performed on flue-cured upper tobacco leaves to compare light aromatic tobacco (LAT) and strong aromatic tobacco (SAT).

Bioinformatics analysis of hub genes and oxidative stress-related pathways in odontogenic keratocysts.

Objective: The study aimed to examine the hub genes and oxidative stress-related pathways in odontogenic keratocysts (OKCs) and predict transcription factors associated with the hub genes.

Methods: The GSE38494 dataset, which includes 12 OKC tissues and 4 normal oral mucosa tissues, was retrieved from the Gene Expression Omnibus (GEO) database. The limma package in the R programming language was utilized to identify differentially expressed genes (DEGs).

Tissue-Microenvironment-Responsive Self-Assembling Peptide Nanoshells Boost Pirfenidone Efficacy in the Treatment of Liver Fibrosis.

Chronic liver disease culminates in liver fibrosis, responsible for substantial worldwide morbidity and mortality. Traditional chemical drugs that have proven effective at treating other types of tissue fibrosis may be repurposed for treating liver fibrosis but face inefficient outcomes or elicit undesirable side effects. Hepatic-targeted drug nanocarriers offer a potential strategy for achieving localized drug release to effectively alleviate liver fibrosis while mitigating off-target effects.

Comprehensive Integrated Analysis Reveals the Spatiotemporal Microevolution of Cancer Cells in Patients with Bone-Metastatic Prostate Cancer.

Bone metastasis is a frequent and life-threatening event in advanced cancers, affecting up to 70-85% of prostate cancer patients. Understanding the cellular and molecular mechanisms underlying bone metastasis is essential for developing targeted therapies. This study aimed to systematically characterize the heterogeneity and microenvironmental adaptation of prostate cancer bone metastases using single-cell transcriptomics.

Computer aided design of CGA-N9 derived peptides based on oligopeptide transporters and their antifungal evaluations.

CGA-N9 is an antifungal peptide that primarily targets Candida spp. with a mild activity. Our preceding research confirmed that the CGA-N9 crosses cell membrane with the assistance of C.

Programmed death-ligand 1 regulates ameloblastoma growth and recurrence.

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects.

Xanthomonas oryzae Orphan Response Regulator EmvR Is Involved in Virulence, Extracellular Polysaccharide Production and Cell Motility.

Bacteria have evolved a large number of two-component signalling systems (TCSs), which are typically composed of a histidine sensor kinase (HK) and a response regulator (RR), to sense environmental changes and modulate subsequent adaptive responses. Here, we describe the involvement of an orphan single-domain RR named EmvR in the virulence, extracellular polysaccharide (EPS) production and cell motilities of the bacterial leaf streak pathogen Xanthomonas oryzae pv. oryzicola (Xoc), which infects rice leaves mainly via stomata and wounds.

Micro/nanomotors in targeted drug delivery: Advances, challenges, and future directions.

The therapeutic efficacy of drugs is highly dependent on their successful delivery to the target site. However, achieving targeted drug delivery to diseased areas remains a significant challenge. Current drug delivery systems based on nanocarriers often suffer from inefficiencies due to their lack of intrinsic propulsion and active targeting capabilities.

Per- and polyfluoroalkyl substances and type 2 diabetes among older adults: Synthesizing cross-sectional population study and meta-analysis.

The effects of per- and polyfluoroalkyl substances (PFASs) on type 2 diabetes (T2D) remain unclear. We aimed to explore the effects of PFASs exposure on glucose metabolism disorders in older adults. We enrolled 704 elderly individuals aged over 65 years from Wuhan, China.

Mechanism and Selectivity of Iron-Catalyzed [4+2] Cycloadditions of Unactivated Dienes: A Computational Study.

The mechanisms of iron-catalyzed [4 + 2] cycloadditions of unactivated dienes were investigated using density functional theory calculations. The calculation results show that the reaction involves sequential key steps of an initial ligand exchange followed by oxidative coupling, isomerization to form a seven-membered ferracycle intermediate, and C-C reductive elimination to form the cyclohexene product. The C-C reductive elimination step is shown to be the rate-determining step of the catalytic cycle.

Improved sand cat swarm optimization algorithm assisted GraphSAGE-GRU for remaining useful life of engine.

With the development of deep learning, the potential for its use in remaining useful life (RUL) has substantially increased in recent years due to the powerful data processing capabilities. However, the relationships and interdependencies of operation parameters in non-Euclidean space are ignored utilizing the current deep learning-based methods during the degradation process for engine. To address this challenge, an improved sand cat swarm optimization-assisted Graph SAmple and aggregate and gate recurrent unit (ISCSO-GraphSage-GRU) is proposed to achieve RUL prediction in this work.

Type I TR and ROP16 Synergistically Downregulate IL-12 to Inhibit Host Reactive Oxygen Species Production.

is an obligate intracellular opportunistic protozoan parasite. invasion disturbs the balance between reactive oxygen species (ROS) production and antioxidant capacity in the host, triggering the oxidative stress response. Thioredoxin reductase (TR) of helps to escape ROS-induced damage in the host, whereas rhoptry protein 16 (ROP16) downregulates host innate immunity to suppress excessive inflammation and inhibit ROS production.

Causal Association of Primary Biliary Cholangitis with Adverse Pregnancy and Neonatal Outcomes: A Two-Sample Mendelian Randomization Study.

Background: Primary biliary cholangitis (PBC) is associated with multiple adverse pregnancy events and neonatal outcomes. However, the available observational study evidence results are inconsistent, and causality is unclear.

Methods: We used a two-sample Mendelian randomization (MR) analysis to assess the association between PBC and multiple adverse pregnancy events and neonatal outcomes in a European population.

ML-AMPs designed through machine learning show antifungal activity against C. albicans and therapeutic potential on mice model with candidiasis.

Aims: C. albicans resistant strains have led to increasingly severe treatment challenges. Antimicrobial peptides with low resistance-inducing propensity for pathogens have been developed.

Deep Learning Combined with Quantitative Structure‒Activity Relationship Accelerates De Novo Design of Antifungal Peptides.

Novel antifungal drugs that evade resistance are urgently needed for Candida infections. Antifungal peptides (AFPs) are potential candidates due to their specific mechanism of action, which makes them less prone to developing drug resistance. An AFP de novo design method, Deep Learning-Quantitative Structure‒Activity Relationship Empirical Screening (DL-QSARES), is developed by integrating deep learning and quantitative structure‒activity relationship  empirical screening.

DMR040, a potential antifungal compound.

Based on DMR022 [(AEEA-Gly)-AEEA-amphotericin B methyl ester, AEEA is the abbreviation of 8-amino-3,6-dioxaoctanoic acid] and DMR031 [(AEEA)-amphotericin B methyl ester], DMR040 [(AEEA)-amphotericin B methyl ester] was further designed and synthesised. Firstly, DMR040 was assessed for its antifungal activity and haemolytic toxicity with the broth dilution method and sterile defibrinated sheep blood, respectively. The minimal inhibitory concentration (MIC) of DMR040 (2 μg/mL) against Candida albicans ATCC 10231 and ATCC 90028 was reduced by 2 times compared to that of amphotericin B (1 μg/mL).

Metabolic Analysis of Tumor Cells Within Ameloblastoma at the Single-Cell Level.

Background: To meet their high energy needs, tumor cells undergo aberrant metabolic reprogramming. A tumor cell may expertly modify its metabolic pathways and the differential expression of the genes for metabolic enzymes. The physiological requirements of the host tissue and the tumor cell of origin mostly dictate metabolic adaptation.