Endocytosis is essential for cysteine-deprivation-induced ferroptosis.

Ferroptosis is a form of cell death caused by iron-dependent phospholipid peroxidation and subsequent membrane rupture. Autophagic degradation of the iron-storage protein ferritin promotes ferroptosis by increasing cytosolic bioactive iron, presumably explaining how lysosomal inhibitors suppress ferroptosis. Surprisingly, we found that lysosomal inhibitors suppress cysteine-deprivation-induced (CDI) ferroptosis, even in autophagy-defective cells, and subsequently discovered that clathrin-mediated endocytosis (CME) of transferrin is essential for CDI ferroptosis.

Dual positivity for Anti-Ro52 and Anti-Ro60 antibodies is linked to greater organ involvement and disease progression in systemic sclerosis.

Objectives: To investigate the distinct and combined effects of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies on the clinical features and prognosis of patients with systemic sclerosis (SSc).

Methods: A single-center observational study was conducted using data from the Renji Scleroderma Longitudinal Cohort (Renji-SLOC), including 379 SSc patients with at least 1 year of follow-up. The patients were categorized into four groups based on serological status: double-negative (Ro52/Ro60), isolated anti-Ro52/TRIM21 positive (Ro52), isolated anti-Ro60/SSA positive (Ro60), double-positive (Ro52/Ro60).

Biodiversity Patterns and Community Construction in Subtropical Forests Driven by Species Phylogenetic Environments.

To explore the characteristics of species diversity and phylogenetic diversity, as well as the dominant processes of community construction, in different forest types (deciduous broad-leaved forest, mixed coniferous and broad-leaved forest, and Chinese fir plantation) in subtropical regions, analyze the specific driving patterns of soil nutrients and other environmental factors on the formation of forest diversity in different forest types, and clarify the differences in response to environmental heterogeneity between natural forests and plantation forests. Based on 48 fixed monitoring plots of 50 m × 50 m in Shouchang Forest Farm, Jiande City, Zhejiang Province, woody plants with a diameter at breast height ≥5 cm were investigated. Species diversity indices (Margalef index, Shannon-Wiener index, Simpson index, and Pielou index), phylogenetic structure index (PD), and environmental factors were used to analyze the relationship between diversity characteristics and environmental factors through variance analysis, correlation analysis, and generalized linear models.

Efficacy and safety of TACE-HAIC combined with tyrosine kinase inhibitors and immune checkpoint inhibitors for the patients with BCLC-defined stage B-C HCC.

Background: To evaluate the therapeutic efficacy and safety profile of combining transarterial chemoembolization (TACE) with hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in patients with hepatocellular carcinoma (HCC) classified as Barcelona Clinic Liver Cancer (BCLC) stage B or C.

Methods: This single-center retrospective analysis included patients with intermediate-to-advanced HCC diagnosed and treated between January 2020 and December 2023. Of 197 eligible patients meeting inclusion criteria, 103 were allocated to the TACE+HAIC+TKI+ICI (T+H+T+I) group and 94 to the HAIC+TKI+ICI (H+T+I) group.

Harnessing tyrosine kinase 2: Breakthroughs in autoimmune disease and cancer therapy.

TYK2 (Tyrosine Kinase 2), a crucial member of the JAK (Janus Kinase) family, plays a pivotal role in mediating the signaling of various immune-related cytokines. Traditional JAK inhibitors, due to their low selectivity, are often associated with risks of adverse effects and may lead to reduced therapeutic efficacy over time with prolonged use. Selectively targeting TYK2 provides a promising therapeutic strategy to address these challenges by minimizing off-target effects and preserving the function of other JAK family members.

Androgen receptor as a potential therapeutic target in castration-resistant prostate cancer: a bibliometric analysis (2005-2024).

Introduction: The androgen receptor (AR) remains a focal target in castration-resistant prostate cancer (CRPC) research, with recent studies providing valuable insights for advancing AR-targeted therapies. This study employs bibliometric methods to comprehensively analyze research trends in the CRPC and AR fields, identifying emerging hotspots and future directions.

Methods: Publications from 2005 to 2024 were extracted from the Web of Science Core Collection (WoSCC).

Stable and highly selective Co-CeF@NiN sheet-on-sheet heterostructures for PET electro-upgrading and hydrogen production.

The electro-upgrading of polyethylene terephthalate (PET) alkaline hydrolysate provides an energy-saving strategy towards green hydrogen and value-added anodic products, but the selectivity and stability at industrial-scale current densities (>200 mA cm) remain challenging. Herein, hierarchical Co-CeF@NiN sheet-on-sheet nanostructures supported on nickel foam (Co-CeF@NiN/NF) were fabricated for PET hydrolysate electro-upgrading coupled with H generation. The hierarchical nanostructures can enlarge the accessible active area, while the introduction of Co species can modulate the electronic configuration, which can reduce the active species formation potential and optimize the adsorption behaviors of key reactants and reactive intermediates.

Precise metabolic dependencies of cancer through deep learning and validations.

Cancer cells exhibit metabolic reprogramming to sustain proliferation, creating metabolic vulnerabilities absent in normal cells. While prior studies identified specific metabolic dependencies, systematic insights remain limited. Here, we build a graph deep learning-based metabolic vulnerability prediction model, "DeepMeta," which can accurately predict the dependent metabolic genes for cancer samples based on transcriptome and metabolic network information.

IL-6R blockade combined with immunosuppressants alleviates adult-onset Still's disease through immune remodeling: a mass cytometry study.

Background: Early administration of IL-6R blockade is effective in adult-onset Still's disease (AOSD), but the underlying immune alterations during combined immunotherapy remain unclear.

Methods: We employed high-dimensional single-cell mass cytometry and an unbiased bioinformatics pipeline to characterize the immune landscape in treatment-naïve AOSD patients, stable AOSD patients after 24 weeks of IL-6R blockade plus methotrexate and prednisone, and matched healthy controls. Cytokine profiling was conducted using a high-throughput cytometric bead array, and potential regulatory networks were identified using the PerformanceAnalytics package.

Proteomics based discovery of Salvia miltiorrhiza Bunge treating Parkinson's disease through the PINK1/Parkin pathway.

Ethnopharmacological Relevance: Salvia miltiorrhiza Bunge, a traditional Chinese medicine, has been utilized in the treatment of Parkinson's disease (PD) for thousands of years, as evidenced by its inclusion in ancient formulas such as YangXue XingNao Tang and XingGan ZhenFeng Tang. However, the underlying mechanisms of its therapeutic effects on PD remain unclear.

Aim Of The Study: This study aims to evaluate the therapeutic effects of Salvia miltiorrhiza Bunge on a rotenone-induced PD rat model and elucidate its mechanism of action.

Pharmacokinetics/pharmacodynamics of gamithromycin for treating Pasteurella multocida infection in cattle using a tissue cage model.

In this study, gamithromycin, a long-acting azalide antibiotic recently introduced for bovine respiratory disease (BRD) treatment, was evaluated for its effectiveness against Pasteurella multocida using a cattle tissue cage model. Gamithromycin (6 mg/kg) was administered via both intravenous and subcutaneous routes and the gamithromycin contents in sera, transudates, and exudates were measured using HPLC/MS-MS. Non-compartmental methods were utilized for assessing pharmacokinetic parameters and an inhibitory sigmoid Emax model determined associations between the pharmacokinetic/pharmacodynamic (PK/PD) indices and antibacterial activity.

Discovery of quinazoline derivatives as RIPK3 inhibitors that switch cell death from necroptosis to apoptosis for psoriasis treatment.

In this study, we employed a structure-based approach and step-by-step structural optimization to identify a series of quinazoline derivatives as potent receptor interacting protein kinase 3 (RIPK3) inhibitors. Among these, compound 32 emerged as the most effective inhibitor, with strong inhibition of RIPK3 (IC = 27 nM) and necroptosis (EC = 0.45 μM).

Controlled release of ionic carrier hydrogels for sequential immunomodulation to facilitate stage-specific treatment of infectious wound.

Infected wounds present a significant clinical challenge, exacerbated by antibiotic resistance, which complicates effective treatment. This study introduces a hydrogel (CC/AP@CM) embedded with core-shell bioactive glass nanoparticles designed for the controlled, sequential release of copper (Cu) and magnesium (Mg) ions. The hydrogel is crosslinked via a Schiff base reaction, endowing it with injectable, self-healing, and adhesive properties.

FLT4 activation promotes acute lymphoid leukemia survival through stabilization of MDM2/MDMX and inactivation of p53.

Aberrant Receptor Tyrosine Kinase (RTK) signaling allows cancer cells to modulate survival, proliferation, and death, leading to tumorigenesis and chemoresistance. In leukemia, the RTK FMS-Related Tyrosine Kinase 4 (FLT4) (also known as VEGFR3, Vascular Endothelial Growth Factor Receptor- 3) is deregulated and correlates with cancer progression. However, the underlying consequences of its deregulation remain to be determined.

Ex Vivo Pharmacokinetic/Pharmacodynamic Integration Model of Cefquinome Against in Foals.

Cefquinome is used to treat septicemia caused by () and respiratory infections caused by subsp. in foals. However, studies reporting the use of cefquinome to target as pathogens of sepsis are lacking.

Engineered Stem Cell Clusters for Extracellular Vesicles-Mediated Gene Delivery to Rejuvenate Chondrocytes and Facilitate Chondrogenesis in Osteoarthritis Therapy.

Gene therapy offers an ideal potential treatment strategy for osteoarthritis (OA). However, the safe and efficient delivery of therapeutic genes remains highly challenging because of the inactivation in direct delivery of miRNA, low transfection efficiency, and a short half-life. This study introduced a gene therapy strategy using mesenchymal stem cells (MSCs) as a gene delivery platform and achieved the sustained delivery of therapeutic genes via engineered MSCs-derived extracellular vesicles (EVs).

Specific Activation of the STING Pathway by Engineering Piezoelectric Hydrogel Microspheres for Boosting Implant Infection Immunotherapy.

Implant-associated infections (IAIs) represent the primary cause of prosthetic implant failure. Bacterial biofilms hinder the host's immune response, creating ″immune cold zones.″ ″Immune activation therapy″ presents a viable strategy for addressing IAIs.

Improved antibacterial activity of a sustained-release biocompatible nanofilm for treating wound infection and .

Objectives: The primary goal of this research was to design a useful and biocompatible nanofilm system (CNF) encapsulating chlorhexidine acetate (CHX) for wounds that is endowed with antibacterial and anti-inflammatory activities and promotes wound healing.

Methods: The nanofilm system was developed on the basis of the successful preparation of its nanoemulsion and PVA-CS film system and then important properties of the nanofilm system, including its morphological and physicochemical characteristics, stability and safety, its antimicrobial efficacy against was also evaluated and . The antibacterial effect, wound healing effect and inflammatory factor change were evaluated.

Anomaly detection in cropland monitoring using multiple view vision transformer.

In recent times, the importance of low-altitude security, especially in agricultural surveillance, has seen a remarkable upswing. This paper puts forward a novel Internet of Drones framework tailored for low-altitude operations. Anomaly detection, which is pivotal for ensuring the integrity of the entire system, poses a substantial challenge.

Water Quality Criteria of Dieldrin for the Protection of Aquatic Organisms and Wildlife Using a Tissue Residue Approach.

Dieldrin is legacy organochlorine insecticide, which was listed in the Stockholm Convention because of its persistence, bioaccumulation and toxicity. However, it is still present in the environment and in organisms two decades after its ban. The current criteria used for risk assessment in China are based on acute toxicity data in water columns without considering the bioavailability and bioaccumulation, which accordingly lead to the under-protection of aquatic organisms and wildlife.

Discovery of Potent and Balanced Dual RIPK2 and 3 Inhibitors as a New Strategy for the Treatment of Inflammatory Bowel Diseases.

Receptor-interacting serine/threonine protein kinase 2 (RIPK2) and RIPK3 have been demonstrated to be promising targets for treating multiple inflammatory diseases, including inflammatory bowel diseases (IBDs). Due to the complexity of IBD pathogenesis, on the basis of synergy strategies, we herein describe the discovery and optimization of a series of ,7-diaryl-quinazolin-4-amine derivatives as dual RIPK2 and RIPK3 inhibitors. Based on a step-by-step process involving three rounds of structural modifications, compound was identified as the most one, exhibiting balanced potency against RIPK2 (IC = 12 nM) and RIPK3 (IC = 18 nM), as well as demonstrating good selectivity over other kinase targets.

Prevalence of bacteria, fungi, and virus coinfections with SARS-CoV-2 Omicron variant among patients with severe COVID-19 in Guangzhou, China, winter 2022.

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5.2 or BF.