Enzyme-Responsive Metallopeptide Hydrogel Enables Cancer Cell-Selective Prodrug Activation via Bioorthogonal Catalysis.

Chemotherapy is often hindered by systemic toxicity and poor selectivity. To address these issues, we develop an enzyme-responsive metallopeptide hydrogel (HY-Pd) that integrates enzyme-instructed self-assembly (EISA) and bioorthogonal catalysis for selective tumor-targeted prodrug activation. Upon exposure to alkaline phosphatase (ALP), which is overexpressed in osteosarcoma cells (Saos-2), HY-Pd selectively accumulates and self-assembles into catalytic nanofibers.

A multi-module enhanced YOLOv8 framework for accurate AO classification of distal radius fractures: SCFAST-YOLO.

Introduction: CT-based classification of distal ulnar-radius fractures requires precise detection of subtle features for surgical planning, yet existing methods struggle to balance accuracy with clinical efficiency. This study aims to develop a lightweight architecture that achieves accurate AO (Arbeitsgemeinschaft für Osteosynthesefragen) typing[an internationally recognized fracture classification system based on fracture location, degree of joint surface involvement, and comminution, divided into three major categories: A (extra-articular), B (partially intra-articular), and C (completely intra-articular)] while maintaining real-time performance. In this task, the major challenges are capturing complex fracture morphologies without compromising detection speed and ensuring precise identification of small articular fragments critical for surgical decision-making.

An enhanced double carbon layer-coated silicon-based anode for lithium-ion batteries.

Silicon (Si)-based anodes are widely recognized as one of the most promising anode materials in next-generation lithium-ion batteries (LIBs) due to their high specific capacities. However, the commercialization of Si-based materials is still constrained by their poor cycle life and rate performance. Herein, a Si@rGO@PNC/C composite with a double-layer carbon structure is synthesized through a secondary coating process followed by high-temperature calcination, in which graphene-coated Si nanoparticles (NPs) are combined with needle coke (NC) and pitch.

Enzyme-instructed disassembly of phosphorylated temporin supramolecules enhances doxorubicin synergy for targeted cancer inhibition.

Enzyme-instructed self-assembly has emerged as a powerful tool to engineer selective functional materials. However, its reverse process, enzyme-instructed disassembly, has been largely overlooked despite its critical implications in pharmaceutical research. This study introduces a new approach employing enzyme-instructed peptide disassembly to selectively inhibit cancer cells.

Comorbidity of common psychiatric disorders and attention-deficit/hyperactivity disorder in Chinese adults.

Objective: We aimed to investigate the comorbidity and influencing factors of attention-deficit/hyperactivity disorder (ADHD) with other psychiatric disorders in Chinese adults.

Methods: Adult patients (n = 3772) diagnosed with schizophrenia (SCZ), major depressive disorder (MDD), bipolar disorder (BD), and general anxiety disorder (GAD) were enrolled in 29 sites from Oct 2022 to Jan 2024. A custom questionnaire including demographics, the Adult ADHD Symptoms Rating Scale v1.

Histone deacetylases in myocardial infarction: Orchestrating programmed cell death pathways and emerging therapeutic opportunities.

Myocardial infarction (MI) remains a major global health challenge, characterized by irreversible cardiomyocyte loss primarily mediated by multiple programmed cell death (PCD) pathways - including apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Histone deacetylases (HDACs) have emerged as pivotal epigenetic regulators orchestrating these diverse PCD processes by modulating the acetylation status of histone and non-histone proteins, thereby significantly influencing myocardial injury, inflammation, oxidative stress, and cardiac remodeling. Individual HDAC isoforms exhibit complex, dual, and context-dependent roles, acting either as promoters or suppressors of cardiomyocyte death depending on cellular stress conditions.

Enhanced Intracellular Delivery by Twisted CC-Loop Conformation in Cyclic Cell-Penetrating Peptides.

Biological drugs hold great promise for treating various diseases, but their efficacy is often limited by poor cellular uptake. Herein, we introduce cyclic cell-penetrating peptides (CPPs) to enhance the delivery efficiency. Three cyclic peptides with varying ring sizes were designed from a classic amphiphilic CPP disulfide bond formation.

Lipid Metabolism in Gastrointestinal Malignancies: Exploring Dysregulation, Biomarkers, and Treatment Strategies.

Background: Gastrointestinal malignancies are a major public health concern worldwide, characterized by high incidence and mortality rates. Despite continuous advancements in existing treatment methods, overall survival rates remain low. Lipid metabolism plays a crucial role in the occurrence, progression, and treatment of gastrointestinal malignancies.

Mesenchymal stem cells and their extracellular vesicles: new therapies for cartilage repair.

Cartilage is crucial for joints, and its damage can lead to pain and functional impairment, causing financial burden to patients. Due to its weak self-repair, cartilage injury control is a research focus. Cartilage injury naturally with age, but mechanical trauma, lifestyle factors and certain genetic abnormalities can increase the likelihood of symptomatic disease progression.

Atomic Insights Into Self-Assembly of Zingibroside R1 and its Therapeutic Action Against Fungal Diseases.

Natural products are a crucial resource for drug discovery, but poor understanding of the molecular-scale mechanisms of their self-assembly into soluble, bioavailable hydrogels limits their applications and therapeutic potential. It is demonstrated that Zingibroside R1 (ZR1), derived from Panax notoginseng, undergoes spontaneous self-assemble into a hydrogel comprising helical nanofibrils with potent antifungal activity lacking in its monomeric state. Cryogenic electron microscopy (cryo-EM) revealed an intricate hydrogen-bonding network that facilitates ZR1 nanofibril formation, characterized by a hydrophobic core and hydrophilic exterior architecture, which underpin its binding activity with cell wall in the vulvovaginal candidiasis (VVC) pathogen, C.

HMAMP: Designing Highly Potent Antimicrobial Peptides Using a Hypervolume-Driven Multiobjective Deep Generative Model.

Antimicrobial peptides (AMPs) have exhibited unprecedented potential as biomaterials in combating multidrug-resistant bacteria, prompting the proposal of many excellent generative models. However, the multiobjective nature of AMP discovery is often overlooked, contributing to the high attrition rate of drug candidates. Here, we propose a novel approach termed hypervolume-driven multiobjective AMP design (HMAMP), which prioritizes the simultaneous optimization of multiattribute AMPs.

Single-Cell Transcriptomic Landscape Deciphers Intratumoral Heterogeneity and Subtypes of Acral and Mucosal Melanomas.

Purpose: To identify the specific intratumoral and microenvironmental heterogeneity of acral melanoma (AM) and mucosal melanoma (MM), we aimed to delineate their distinct cellular compositions, evolutionary trajectories, and subtype-specific therapeutic strategies.

Experimental Design: Single-cell transcriptomic and genomic landscapes were analyzed across 42 melanoma (28 AM, 11 MM, and 3 nonacral cutaneous melanoma) samples, supplemented by in vitro and in vivo validation. Tumor and stromal cells were profiled using single-cell RNA sequencing, whole-exome sequencing, and functional assays, including transwell migration, co-culture systems, and xenograft models.

SR-B1 deficiency suppresses progression in acute myeloid leukemia via ferroptosis and reverses resistance to venetoclax.

Increase of immature myeloid cells in the bone marrow drives the development of acute myeloid leukemia (AML). The study aimed to clarify the biological function and regulatory mechanism of scavenger receptor class B type 1 (SR-B1) in AML, mainly its effect on ferroptosis and the influences on leukemogenesis and resistance to venetoclax. In this study, we found that the SR-B1 deficiency directly reduced the invasion and promoted death of malignant cells in AML.

Androgen receptor-induced lncRNA SOX2-OT promotes triple-negative breast cancer tumorigenesis via targeting miR-320a-5p-CCR5 axis.

Our previous study showed that androgen receptor (AR) promotes triple-negative breast cancer (TNBC) cell tumorigenesis, but the underlying mechanisms remain unclear. Herein, using microarray analysis of long noncoding RNA expression profiles, we identified an AR-related long noncoding RNA SOX2-OT in TNBC. We found that AR could promote TNBC tumorigenesis by acting as a transcription factor to activate the expression of SOX2-OT.

FGF21, a modulator of astrocyte reactivity, protects against ischemic brain injury through anti-inflammatory and neurotrophic pathways.

Ischemic stroke is a frequent cause of mortality and disability, and astrocyte reactivity is closely associated with injury outcomes. Fibroblast growth factor 21 (FGF21), an endogenous regulator, has been shown to perform pleiotropic functions in central nervous system (CNS) disorders. However, studies on neurological diseases have paid little attention to the effects and detailed mechanisms of FGF21 in astrocytes.

Normobaric hyperoxia combined with endovascular treatment for acute ischaemic stroke in China (OPENS-2 trial): a multicentre, randomised, single-blind, sham-controlled trial.

Background: Endovascular treatment improves the recanalisation rate for patients with acute ischaemic stroke; however, even with endovascular treatment, approximately half of patients do not have a favourable functional outcome. We aimed to evaluate the effect of normobaric hyperoxia combined with endovascular treatment on functional outcomes up to 90 days after treatment in patients who had an acute ischaemic stroke with large-vessel occlusion.

Methods: In this multicentre, randomised, single-blind, sham-controlled trial, patients aged 18-80 years presenting within 6 h of acute ischaemic stroke attributed to large-vessel occlusion in anterior circulation, who were candidates for endovascular treatment, were recruited from 26 comprehensive stroke centres in China.

Revolutionizing public health through digital health technology.

The aging population and increasing chronic diseases strain public health systems. Advancements in digital health promise to tackle these challenges and enhance public health outcomes. Digital health integrates digital health technology (DHT) across healthcare, including smart consumer devices.

Extracellular vesicle-mediated VEGF-A mRNA delivery rescues ischaemic injury with low immunogenicity.

Background And Aims: Lackluster results from recently completed gene therapy clinical trials of VEGF-A delivered by viral vectors have heightened the need to develop alternative delivery strategies. This study aims to demonstrate the pre-clinical efficacy and safety of extracellular vesicles (EVs) loaded with VEGF-A mRNA for the treatment of ischaemic vascular disease.

Methods: After encapsulation of full-length VEGF-A mRNA into fibroblast-derived EVs via cellular nanoporation (CNP), collected VEGF-A EVs were delivered into mouse models of ischaemic injury.

Indications of a benthic foraminifer Cribrononion gnythosuturatum to salinities revealed by eDNA metabarcoding and morphological methods.

Cribrononion gnythosuturatum is a widely distributed benthic foraminifer. However, its adaptability to salinity changes is still poorly understood. To investigate the response of C.

Serum Glucose-Phosphate Ratio on Admission as a Potential Biomarker for Severity, Functional Outcome, and Recurrence in Acute Ischemic Stroke.

Background And Objective: Raised serum glucose-phosphate ratio on admission is associated with severity and poor outcome of aneurysmal subarachnoid hemorrhage and severe traumatic brain injury. However, its role in acute ischemic stroke (AIS) remains still unknown. Therefore, this prospective study aimed to investigate the association between admission serum glucose-phosphate ratio and the severity and 1-year clinical outcome of AIS.

Peptides for Liquid-Liquid Phase Separation: An Emerging Biomaterial.

Liquid-liquid phase separation (LLPS) refers to a spontaneous separation behavior of biomacromolecules under specific physiological conditions, playing a crucial role in regulating various biological processes. Recent advances in synthetic peptides have greatly improved our understanding of peptide-based coacervate droplets and expanded their applications in biomedicine. Numerous peptide sequences have been reported that undergo phase separation, enabling the concentration and sequestration of different guest molecules for purposes such as drug delivery, catalytic performance, and bioanalytical techniques.

Exploring heparin's protective mechanism against AGEs induced endothelial injury.

Advanced glycation end products (AGEs) in diabetes can cause endothelial damage. Heparin, widely known as a recognized anticoagulant, is also a multifunctional therapeutic drug. This study investigated whether heparin could ameliorate AGEs-induced endothelial injury.

Injectable self-assembling peptide hydrogel as a promising vitreous substitute.

Vitreoretinal diseases pose significant threats to vision, often requiring vitrectomy and substitution of vitreous humor to restore ocular structure and visual function. However, existing substitutes have limitations that compromise patient outcomes. Supramolecular hydrogels, particularly peptide-based formulations, have emerged as promising alternatives due to their superior optical clarity, biocompatibility, and viscoelasticity.