The N-terminal domain of gasdermin D induces liver fibrosis by reprogrammed lipid metabolism.

Background: The emerging incidence of pathogenic liver conditions is turning into a major concern for global health. Induction of pyroptosis in hepatocytes instigates cellular disintegration, which in turn liberates substantial quantities of pro-inflammatory intracellular substances, thereby accelerating the advancement of liver fibrosis. Consequently, directing therapeutic efforts towards inhibiting pyroptosis could potentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.

Mirvetuximab Soravtansine in solid tumors: A systematic review and meta-analysis.

Background: Mirvetuximab Soravtansine (MIRV) is a promising antibody‒drug conjugate (ADC) that targets folate receptor alpha (FRα), which is overexpressed in several types of solid tumors. In November 2022, MIRV was approved in the USA for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received 1-3 prior systemic treatment regimens. Therefore, high-quality evidence for its efficacy and safety in different cancers is urgently needed.

Regulation of catechins with different structure characteristics on the physicochemical properties of casein and the structure-activity relationship.

Regulation of catechins with different structure characteristics on the physicochemical properties of casein were investigated, and the structure-activity relationship was further explored. All testing catechins effectively modulated the physicochemical properties of casein, and esterified catechins showed the stronger binding affinity to casein than non-esterified catechins. Catechins significantly altered the secondary and tertiary structures of casein.

Data mining in FAERS: association of newer-generation H1-antihistamines with nervous system disorders.

Background: H1-antihistamines are widely used to treat symptoms depending on histamine release in a variety of conditions. However, neurological adverse events have been reported in post-marketing surveillance studies and there are limited literatures comparing the neurological disorders associated with newer-generation H1-antihistamines from real-world datasets.

Aims: We performed a comparative analysis of nervous system disorders and several newer-generation H1-antihistamines including: cetirizine, loratadine, levocetirizine, desloratadine and fexofenadine.

Glutamine-αKG axis affects dentin regeneration and regulates osteo/odontogenic differentiation of mesenchymal adult stem cells via IGF2 m6A modification.

Background: Multi-lineage differentiation of mesenchymal adult stem cells (m-ASCs) is crucial for tissue regeneration and accompanied with metabolism reprogramming, among which dental-pulp-derived m-ASCs has obvious advantage of easy accessibility. Stem cell fate determination and differentiation are closely related to metabolism status in cell microenvironment, which could actively interact with epigenetic modification. In recent years, glutamine-α-ketoglutarate (αKG) axis was proved to be related to aging, tumorigenesis, osteogenesis etc.

Testing cognitive normal for Alzheimer's disease prediction.

One standing challenge for Alzheimer's disease (AD) research is early diagnosis, which provides a time window for early intervention. Sharmin et al recently reported a positive association between plasma ptau181 and plasma metabolites, medium- and long-chain acylcarnitines (ACs) in both cognitively normal (CN) Aβ- and CN Aβ+ older adults, suggesting a link between initial Aβ pathology and acylcarnitine-mediated energy metabolism pathways. Consistently, ACs could classify PET-Aβ status in elderly individuals.

Addition of SHR-1701 to first-line capecitabine and oxaliplatin (XELOX) plus bevacizumab for unresectable metastatic colorectal cancer.

This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.

YTHDF2 promotes arsenic-induced malignant phenotypes by degrading PIDD1 mRNA in human keratinocytes.

Arsenic is a widespread environmental carcinogen, and its carcinogenic mechanism has been the focus of toxicology. N-methyladenosine (mA) binding protein YTH domain family protein 2 (YTHDF2) performs various biological functions by degrading mA-modified mRNAs. However, the mA-modified target mRNA of YTHDF2 in regulating arsenic carcinogenesis remains largely unknown.

Multifunctional hyaluronic acid-based coating to direct vascular cell fate for enhanced vascular tissue healing.

Ensuring excellent anticoagulant, anti-inflammatory, and endothelialization properties in vascular stents through coating construction is crucial for their satisfactory performance post-implantation. In this study, we propose a cell-membrane mimetic multifunctional hyaluronic acid (HA)-based coating by combining the aminolyzed methacryloyloxyethyl phosphorylcholine (MPC) copolymer with oxidized hyaluronic acid (Ox-HA) through Schiff base reaction. Compared with traditional anti-fouling design, the composite coating present a stage-specific ability, which can resist the adhesion of blood components, while mediating vascular cell fate with the incorporation of HA.

Self-Assembled EGCG Nanoparticles with Enhanced Intracellular ROS Scavenging for Skin Radioprotection.

Purpose: Skin radiation damage is a prevalent form of tissue injury encountered during radiotherapy, radiation accidents, and occupational exposure. The only clinically approved radioprotective agent, amifostine, is associated with numerous side effects, underscoring the urgent need for the development of safe and effective radioprotective agents. Natural products with reductive properties possess high antioxidant activity and biocompatibility, but their low bioavailability limits their radioprotective efficacy and clinical application.

Shared and disorder-specific large-scale intrinsic and effective functional network connectivities in postpartum depression with and without anxiety.

Postpartum depression and postpartum depression with anxiety, which are highly prevalent and debilitating disorders, become a growing public concern. The high overlap on the symptomatic and neurobiological levels led to ongoing debates about their diagnostic and neurobiological uniqueness. Delineating the shared and disorder-specific intrinsic functional connectivities and their causal interactions is fundamental to precision diagnosis and treatment.

Associations between ethylene oxide exposure and biological age acceleration: evidence from NHANES 2013-2016.

Introduction: Population aging is a global concern, with the World Health Organization predicting that by 2030, one in six individuals worldwide will be 60 years or older. Ethylene oxide (EO) is a widely used industrial chemical with potential health risks, including associations with age-related diseases. This study investigates the relationship between EO exposure and biological age acceleration.

Single-cell transcriptome profiling of mA regulator-mediated methylation modification patterns in elderly acute myeloid leukemia patients.

Millions of people worldwide die of acute myeloid leukaemia (AML) each year. Although N6-methyladenosine (mA) modification has been reported to regulate the pathogenicity of AML, the mechanisms by which mA induces dysfunctional hematopoietic differentiation in elderly AML patients remain elusive. This study elucidates the mechanisms of the mA landscape and the specific roles of mA regulators in hematopoietic cells of elderly AML patients.

Reinforced enzyme mineralized chitosan hydrogels with superior mechanical and osteogenic properties.

As a natural cationic polymer material, the application of chitosan hydrogel for bone tissue engineering has been greatly limited due to its poor mechanical strength. Enzymatic mineralization has drawn increased attention to effectively improve the mechanical properties of hydrogels. In this study, carboxymethyl chitosan (CMCS) hydrogels cross-linked with different concentrations of genipin (2.

Delayed Magnetic Resonance Imaging of Alzheimer's Disease by Using Poly(2-(methacryloyloxy)ethyl phosphorylcholine)-Functionalized Nanoprobes.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, commonly affecting the aged, with pathophysiological changes presenting 15 to 20 years before clinical symptoms. Early diagnosis and intervention are crucial in effectively slowing the progression of AD. In the current study, poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC)-functionalized NaGdF nanoparticles (NaGdF-PMPC) were developed as magnetic resonance imaging (MRI) contrast agents for targeting alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) in AD mice.

The roles of lactate and the interplay with mA modification in diseases.

Lactate exhibits various biological functions, including the mediation of histone and non-histone lactylation to regulate gene transcription, influencing the activity of T lymphocytes, NK cells, and macrophages in immune suppression, activating G protein-coupled receptor 81 for signal transduction, and serving as an energy substrate. The mA modification represents the most prevalent post-transcriptional epigenetic alteration. It is regulated by mA-related regulatory enzymes (including methyltransferases, demethylases, and recognition proteins) that control the transcription, splicing, stability, and translation of downstream target RNAs.

A Chemically Defined Culture for Tooth Reconstitution.

It is known for decades that dental epithelium and mesenchyme can reconstitute and regenerate a functional tooth. However, the mechanism of tooth reconstitution remains largely unknown due to the lack of an efficient in vitro model. Here, a chemically defined culture system is established that supports tooth reconstitution, further development with normal anatomy, and prompt response to chemical interference in key developmental signaling pathways, termed as toothoids.

A novel optical strategy for ALP detection and development of matched smartphone app.

Alkaline phosphatase (ALP) is a reliable biomarker for various diseases, making the development of new detection methods highly significant. Herein, we report a simple and accurate dual-signal optical detection strategy for measuring ALP activity across the entire clinical range in adults. Based on this, we designed a smartphone app to eliminate the limitations of large instruments, enabling real-time field detection.

The primary studies of epigallocatechin-3-gallate in improving brain injury induced by chronic high-altitude natural environment in rats by 7.0T high-field MR imaging.

Background: Epigallocatechin-3-gallate (EGCG) is one of the most abundant and important bioactive polyphenolic compounds in green tea. However, despite its potent antioxidant effects, its neuroprotective effects on chronic high altitude (HA)-induced nerve damage have not been reported. The purpose of this study is to use quantitative susceptibility mapping (QSM) with pathology to dynamically evaluate the status of brain damage and the effect of EGCG.

Discovery and structure-activity relationship study of nicotinamide derivatives as DNA demethylase ALKBH2 inhibitors.

AlkB homolog 2 (ALKBH2) is a Fe (II) and 2-oxoglutarate (2OG)-dependent DNA demethylase. It has been reported to be highly expressed in many cancers including glioblastoma (GBM) and affected disease progression by regulating gene expression. Small molecule inhibitors of ALKBH2 might be used as disease intervention reagents or chemical tools for bio-functional studies of ALKBH2, but currently no potent and selective ALKBH2 inhibitors are reported.

METTL3 and IGF2BP2 coordinately regulate FOSL1 mRNA via m6A modification, suppressing trophoblast invasion and contributing to fetal growth restriction.

Fetal growth restriction (FGR) increases the risk of short-term and long-term complications. Widespread N6-methyladenosine (m6A) modifications on mRNAs have been found to be involved in various biological processes. However, the role of m6A modification in the pathogenesis of FGR remains elusive.