Blue light pollution induces dry eye by damaging conjunctival stem cells through cAMP-PKA-Pax6 signaling pathway.

Purpose: Blue light exposure constitutes a risk factor for dry eye. The research explores the influence of conjunctival stem cells (CjSCs) by blue light, elucidating the pathogenesis of blue light-induced dry eye.

Materials And Methods: Primary SD rat CjSCs and rats were irradiated with blue light at 460 nm.

Multifaceted Determinants of Varicella Vaccination Uptake Among Children Aged 1-10 Years in China: Findings of a Population-Based Survey Among 996 Parents.

Background/objectives: Chickenpox is an ongoing health threat for young children. This study aimed to investigate varicella vaccination uptake among children and its determinants at both the individual and interpersonal levels.

Methods: A cross-sectional survey of parents of children aged 0-15 years and with administrative health records was conducted between September and October 2024 in Shenzhen, China.

TNG260 is a Small-Molecule CoREST Inhibitor that Sensitizes STK11-Mutant Tumors to Anti-PD-1 Immunotherapy.

Non-small cell lung cancer (NSCLC) patients with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti-PD-1. Here, we conducted an in vivo CRISPR screen that identified HDAC1 as a target to reverse anti-PD-1 resistance driven by loss of STK11 and developed TNG260, a potent small-molecule inhibitor of the CoREST complex with selectivity exceeding previously generated inhibitors in this class in preclinical studies. Treatment with TNG260 led to increased expression of immunomodulatory genes in STK11-deficient cancer cells.

Non-coding RNA mediates the defense-associated reverse transcriptase (DRT) anti-phage oligomerization transition.

Defense-associated reverse transcriptase (DRT) systems are implicated in prokaryotic resistance to viral infections, yet the molecular mechanisms underlying their functionality remain largely unknown. Here, we characterize a two-component DRT9 system, composed of a reverse transcriptase (RT) and a non-coding RNA (ncRNA), which exhibits a protein-primed DNA synthesis activity upon phage infection. We also determine its cryo-electron microscopy (cryo-EM) structures in different functional states.

Exosome-mediated microglia-astrocyte interactions drive neuroinflammation in Parkinson's disease with Peli1 as a potential therapeutic target.

Neuroinflammation is a key feature of Parkinson's disease (PD), characterized by activated microglia and the conversion of astrocytes into the neurotoxic phenotype, exacerbating the neuroinflammation. In PD, microglia critically drive neurotoxic reactive astrocytes (A1, A1-like, or neuroinflammatory reactive astrocytes)-though the underlying mechanisms remain elusive. Given the established role of exosomes as critical intercellular messengers, we investigated whether microglia-derived exosomes contribute to neurotoxic astrocyte transformation.

Clinical Significance of CD109 Expression and Methylation Patterns in Acute Myeloid Leukemia.

Introduction: The altered expression of CD109 has been observed in solid tumors of various types, and evidence suggests a correlation between CD109 expression and development and prognosis of tumors. However, the expression and methylation patterns of CD109 in acute myeloid leukemia (AML) and their clinical significance remain unclear.

Methods: CD109 mRNA expression and promoter methylation were determined in AML patients and leukemia cells.

ABIDA: An Automated Brain Imaging Data Processing and Analysis Platform.

Addressing RS-fMRI toolkit limitations-notably operational complexity and expertise barriers-this study introduces ABIDA toolbox. Integrating cross-toolkit functions with intelligent algorithms and quantitative metrics enhances workflow through intuitive design and automation.

Targeting KRAS in colorectal cancer (Review).

RAS genes play crucial roles in regulating important biological processes such as cell growth, differentiation, and apoptosis in normal cells. When RAS genes undergo mutations or abnormal expression, they can become oncogenic drivers, and the oncogenic mechanism of KRAS mutations which drive cancer progression is highly complex. Colorectal cancer carrying KRAS mutation genes often exhibits poor prognosis.

Report of a rare case of childhood adrenocortical carcinoma and literature review.

Adrenocortical carcinoma (ACC)in children is rare, and its nonspecific clinical presentation renders early diagnosis challenging. Surgery remains the primary therapeutic approach. A multidisciplinary, multimodal treatment strategy and long-term follow-up are essential to improve prognosis.

CRIS: A Centralized Resource for High-Quality RNA Structure and Interaction Data in the AI Era.

The Crosslinking-based RNA Interactomes and Structurome (CRIS) database is a unified platform for RNA structure and interaction data, combining rigorously curated datasets, standardized workflows, and user-friendly tools. While advancements in experimental and computational methods expand our understanding of RNA structure and function, challenges in reproducibility, quality control, and data accessibility remain prevalent due to inconsistencies in data processing. As a result, many existing databases lack breadth in their data sources, are inconsistent in their processing pipelines, and limit accessibilities for end users.

MTA-Cooperative PRMT5 Inhibitors are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models.

Purpose: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with poor prognosis. The enzyme methylthioadenosine phosphorylase (MTAP) is lost in ~25-50% of MPNST, which is associated with loss of the tumor suppressor gene, CDKN2A. Inhibition of PRMT5 was found to be synthetically lethal in cells with MTAP loss due to accumulation of the substrate methylthioadenosine (MTA), an endogenous PRMT5 inhibitor.

Research Progress of Senolytic Drugs in the Treatment of Orthopedic Diseases.

Background: Orthopedic diseases, including osteoarthritis, osteoporosis, and age-related musculoskeletal disorders, significantly impact quality of life and are becoming increasingly prevalent with aging populations. A growing body of evidence highlights the role of cellular senescence in the pathogenesis of these conditions. Senescent cells (SCs), characterized by irreversible cell cycle arrest, accumulate in tissues over time, contributing to inflammation, tissue degeneration, and impaired regeneration.

Ferroptosis-related lncRNAs as prognostic biomarkers in renal cell carcinoma: a systematic review and meta-analysis.

Background: Abundant evidences have indicated that long non-coding RNAs (lncRNAs) can be used to evaluate the prognosis of patients with renal cell carcinoma (RCC), and the purpose of this study was to evaluate the association between ferroptosis-related lncRNAs (FRLs) and the prognosis of patients with RCC by means of a meta-analysis.

Materials And Methods: All studies assessing the prognosis of patients with FRLs and RCC were collected up to 31 October 2024 by searching databases such as PubMed, Web of Science, Embase, Scopus and Cochrane Library. Pooled analyses were performed on the collected data, including metrics such as gender, age, risk score, tumor stage, and tumor grade.

Multi-Omics-Based Characterization of DNA Methylation Episignatures for Papillary Thyroid Cancer in a Chinese Population.

Thyroid cancer is the most common endocrine malignancy, with papillary thyroid cancer (PTC) accounting for ∼80% of all cases. DNA methylation alterations and gene expression changes in cancer, offer valuable insights into tumor biology and serve as potential clinical biomarkers. However, the functional implications of DNA methylation changes in PTC patients, particularly based on multiomics analysis in the Chinese population, remain insufficiently explored.

A promising approach to diabetic osteoporosis: oxymatrine's effects on gut microbiota and osteoblasts.

Objectives: Oxymatrine (OMT), a quinolizidine alkaloid derived from Sophora flavescens Ait., has demonstrated therapeutic potential in type 2 diabetes mellitus (T2DM). This study aimed to investigate its effects on diabetic osteoporosis (DOP) and explore the underlying mechanisms involving gut microbiota and osteogenic regulation.

Discovery of TNG-6132, a potent, selective, and orally bioavailable USP1 inhibitor.

USP1 (ubiquitin-specific peptidase 1) is a deubiquitinating enzyme that has been identified as essential in BRCA1/2 mutant cells and implicated in the DNA damage response. Inhibition of USP1 by small molecule inhibitors disrupts DNA repair and replication and is being pursued as a potential anticancer therapeutic in BRCA1/2 mutant cancers. We report the discovery of an in vitro and in vivo USP1 inhibitor tool compound TNG-6132 (18), a reversible, allosteric inhibitor of USP1, which strongly inhibits USP1 enzymatic activity.

Curcuminoids WM03 inhibits ovarian cancer cisplatin-resistant cells proliferation and reverses cisplatin resistance by targeting DYRK2.

Purpose: Cisplatin is a common chemotherapy agent used to treat ovarian cancer and cisplatin resistance is the most common consequence after its treatment. Curcumin has been shown to effectively inhibit the proliferation and invasion of ovarian cancer cells but its bioavailability restricts its application. The objective of this study was to develop the novel curcumin derivatives with high efficacy and synergic effects with cisplatin to inhibit cisplatin resistant ovarian cancers.

Cochlear Cell Atlas of Two Laryngeal Echolocating Bats-New Evidence for the Adaptive Nervous Physiology in Constant Frequency Bat.

Bats have evolved highly adapted auditory mechanisms associated with ecological specialisation. However, there is scattered knowledge about the neurophysiological and cellular basis underlying high-frequency hearing in echolocating bats. Herein, the total cochlear cell atlas of Rhinolophus ferrumequinum (constant frequency (CF) bat) and Myotis pilosus (frequency modulated (FM) bat) was conducted using the 10x Genomics single-nucleus RNA sequencing method.

MiR-218 Exhibits Anti-Leukemia Effects by Targeting CTNND2 in Primary Acute Erythroid Leukemia HEL Cells.

Acute erythroid leukemia (AEL) is a rare acute myeloid leukemia (AML) subtype that is highly aggressive and is associated with a poor prognosis. Notably, the blockage of erythroid differentiation represents a significant factor in the pathogenesis of erythroleukemia. Prior studies indicated that miR-218 inhibited the erythroid differentiation in a chronic myeloid leukemia (CML)-derived erythroleukemia cell line K562.

Insights into the compact CRISPR-Cas9d system.

Cas9d, the smallest known member of the Cas9 family, employs a compact domain architecture for effective target cleavage. However, the underlying mechanism remains unclear. Here, we present the cryo-EM structures of the Cas9d-sgRNA complex in both target-free and target-bound states.

Discovery of TNG462: A Highly Potent and Selective MTA-Cooperative PRMT5 Inhibitor to Target Cancers with Deletion.

The gene encoding for MTAP is one of the most commonly deleted genes in cancer, occurring in approximately 10-15% of all human cancer. We have previously described the discovery of TNG908, a brain-penetrant clinical-stage compound that selectively targets -deleted cancer cells by binding to and inhibiting PRMT5 cooperatively with MTA, which is present in elevated concentrations in -deleted cells. Herein we describe the discovery of TNG462, a more potent and selective MTA-cooperative PRMT5 inhibitor with improved DMPK properties that is selective for -deleted cancers and is currently in Phase I/II clinical trials.

Paranodal instability driven by axonal mitochondrial accumulation in ischemic demyelination and cognitive decline.

Background: Subcortical ischemic demyelination is the primary cause of vascular cognitive impairment in the elderly. However, its underlying mechanisms remain elusive.

Methods: Using a bilateral common carotid artery stenosis (BACS) mouse model and an in vitro cerebellar slice model treated with low glucose-low oxygen (LGLO), we investigated a novel mechanism of vascular demyelination.

Ocular Surface Involvements in the Development of Sjögren's Syndrome-Associated Dry Eye in the IL14α Transgenic Mouse.

Purpose: To investigate the ocular surface changes during progress of the Sjögren's Syndrome (SS), using a previously described IL14α transgenic mice (IL14α TG) SS model.

Methods: The ocular surface of IL14α TG and C57BL/6 wild-type (WT) female mice were evaluated at the age of six, nine, 12, 15, and 18 months. Slit lamp microscopy observation, Oregon green dextran staining, Schirmer test, and periodic-acid-Schiff staining were assessed.

Bioinformatic characterization of STING expression in hematological malignancies reveals association with prognosis and anti-tumor immunity.

Introduction: Stimulator of interferon response cGAMP interactor (STING) is essential for both innate and adaptive immunity. However, a comprehensive molecular characterization of STING expression across hematological malignancies is lacking.

Methods: In this study, the pan-blood-cancer landscape related to STING expression was identified using the GTEx, CCLE, Hemap, and TCGA databases, and the potential value for predicting prognosis was investigated.