Development of Cyclooctyne-Nitrone Based Click Release Chemistry for Bioorthogonal Prodrug Activation both and .

The advancement of bioorthogonal cleavage platforms has emerged as a critical frontier in chemical biology, offering precise molecular liberation through physiologically compatible activation mechanisms. Despite its significant potential, ensuring efficacy typically requires rapid reaction kinetics, high-efficiency payload release, and stable reactants; however, relevant reports remain sparse. Herein, we developed a strain-promoted alkyne-nitrone cycloaddition (SPANC)-based click-release chemistry through installation of a carbamate-linked release moiety at the propargyl position of cyclooctyne, triggering a spontaneous elimination following click cycloaddition to achieve efficient payload liberation.

Burden of Disease Attributable to High Systolic Blood Pressure in Young Adults: An Analysis From the Global Burden of Disease Study 2021.

This study aims to fill this gap by leveraging Global Burden of Disease 2021 (GBD 2021) data to conduct a comprehensive assessment of the disease burden attributable to high systolic blood pressure (SBP) in young adults. Data from the Global Health Data Exchange were utilized to estimate the disease burden attributable to high SBP in young adults, stratified by overall disease, sex, socio-demographic index (SDI) level, GBD region, nation, and specific disease. In 2021, the overall disease attributable to high SBP in young adults was substantial, with approximately 24,626,362 disability-adjusted life years (DALYs) and 477,992 deaths, and the DALYs and mortality rates were 623.

Na-Cl Cotransporter (SLC12A3) Inhibition Exacerbates Age-Related Macular Degeneration Via the Nrf2/HO-1 Ferroptosis Pathway.

Purpose: To explore the causal links between antihypertension drugs usage and age-related macular degeneration (AMD).

Methods: Multiple genetic analyses, including summary data-based Mendelian randomization (SMR), traditional MR, and colocalization analysis, were used to explore the causal associations between antihypertension drugs and AMD. Clinical data from the UK Biobank and the National Health and Nutrition Examination Survey (NHANES) was applied to refined risk assessment of specific antihypertensive medications in the context of AMD development.

Re-Exploration for Dietary Iodine Intake in Chinese Adults using the Obligatory Iodine Loss Hypothesis.

Objective: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis.

Methods: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI).

Analysis of Tongue and Face Image Features of Anemic Women and Construction of Risk-Screening Model.

Objective: To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance.

Methods: A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument.

Serum Lipidomics Profiling to Identify Potential Biomarkers of Ischemic Stroke: A Pilot Study in Chinese Adults.

Objective: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling.

Interferon-induced miR-7705 modulates the anti-virus activity of cholesterol 25-hydroxylase.

Unlabelled: Cholesterol 25-hydroxylase (CH25H), an interferon-stimulated gene (ISG), has been implicated in broad-spectrum antiviral immunity. Here, we identify CH25H as a potent suppressor of hepatitis B virus (HBV) replication that significantly outperforms IFN-α in reducing HBV DNA, pregenomic RNA (pgRNA), HBsAg, and HBeAg, without inducing cytotoxicity. However, CH25H is weakly expressed in hepatocytes and only modestly induced by type I interferon.

Bonding-Guided Anisotropic Growth of Quasi-1D MXSe Thermoelectric Nanowires.

Quasi-1D van der Waals materials have emerged as promising candidates for flexible electronic and thermoelectric applications due to their intrinsic anisotropy, narrow band gaps, and mechanical flexibility. Herein, MXSe (M = Nb, Ta, X = Pd, Pt) nanowires are studied to understand the bonding-directed growth mechanism. Bond valence sums and binding energy analyses reveal that weak X2-Se2 interactions perpendicular to the c-axis facilitate anisotropic growth.

Antifungal Prescribing in European Pediatric Intensive Care Units: Results of a multinational 3-month weekly point-prevalence survey.

Background: Critically ill pediatric patients admitted to the PICU are highly vulnerable to infections, including invasive fungal diseases and antifungal agents are frequently prescribed. Little is known about antifungal usage in PICUs across Europe.

Methods: A multinational 3-month weekly point-prevalence study for measuring antifungal drug use was organized.

Construction of Hollow Structured Covalent Organic Framework with Chiral Internal Catalytic Sites for Asymmetric Hydrogenation.

The functionality of covalent organic frameworks (COFs) is usually highly related to their morphologies. Among various morphologies, the hollow-structured COFs have recently attracted intense attention due to their unique properties. Herein, the synthesis of hollow structured COFs are first reported with the chiral internal sites via combining the chiral templating method with the acid etching approach.

The Age-Associated Long Noncoding RNA lnc81 Regulates Ovarian Granulosa Cell Proliferation and Apoptosis Through TEAD2-CCN1/2 Pathway in Mice.

Ovarian granulosa cells (GCs) are pivotal for follicular homeostasis, and their dysregulated apoptosis drives age-related ovarian aging. The Hippo signaling pathway, modulated by long noncoding RNAs (lncRNAs), is implicated in regulating GCs proliferation and ovarian aging. TEAD2 (Transcriptional Enhanced Associate Domain 2), a key downstream transcription factor of the Hippo signaling pathway, plays a critical role in regulating cell proliferation, apoptosis, and embryonic stem cell self-renewal.

Plasma Proteomic High-Performance Biomarkers for Early Diagnosis of Colorectal Cancer.

Colorectal cancer (CRC) is a major global health challenge due to its high incidence, mortality, and low rate of early detection. Early diagnosis, targeting precancerous lesions (advanced adenomas) and early stage CRC (Tis and T1), is critical for improving patient survival. Given the limitations of current detection methods for advanced adenomas, developing high-performance early diagnostic strategies is essential for effective prevention.

Effects of Combined Exercise Training on Modulating Fine Particulate Matter-Induced Skeletal Muscle Damage in Offspring Gestationally Exposed.

Background: Fine particulate matter has developmental toxicity, and midgestation is an important period for the development of foetal skeletal muscle. The ability of exercise to modulate skeletal muscle damage in mice exposed to PM during gestation remains unclear.

Methods: Pregnant C57BL/6 mice were exposed to 50 μg/m PM for 2 h on five consecutive days starting at embryonic day 12.

2D Active Filler Modified Porous Polymer Network for Stabilizing Zn Anode Under Harsh Conditions.

Artificial porous polymer coatings are promising for alleviating the side reactions and dendrite growth on Zn anodes. Nevertheless, the low ion transport ability constrains their application under harsh conditions such as thin Zn foil, high current density, and high depth of discharge (DOD). Herein, a 2D active filler is introduced to optimize the Zn migration in porous polymer coating.

Epidemiology, pathophysiology, diagnosis and management of atrial functional mitral regurgitation: An expert opinion paper.

Atrial functional mitral regurgitation (AFMR) is an increasingly recognized subtype of mitral regurgitation, characterized by left atrial remodelling and mitral annular dilation in the absence of primary mitral valve disease or left ventricular dysfunction. Closely linked to chronic atrial fibrillation and heart failure with preserved ejection fraction, AFMR is associated with poor clinical outcomes and represents a growing therapeutic challenge. This expert opinion paper summarizes current evidence on the epidemiology, pathophysiology, diagnosis and management strategies, including medical therapy and emerging data supporting surgical and transcatheter interventions in selected patients.

Improved cyclability of high-voltage LiCoO by the coating of medium-entropy nanomaterials.

Although improving the charging cutoff voltage is an effective strategy to increase its capacity, LiCoO ("LCO") undergoes rapid capacity decay due to severe structural and interface degradations at high voltages. Herein, we proposed a multifunctional surface modification by coating nano-sized entropy materials (Li-La-Ti-Zr-Co-O, Nano-MEO). Nano-MEO rivets were constructed on the surface of LCO, which stabilized the fragile surface.

Environmental Stresses Constrain Soil Microbial Community Functions by Regulating Deterministic Assembly and Niche Width.

Increasing evidence indicates that the loss of soil microbial α-diversity triggered by environmental stress negatively impacts microbial functions; however, the effects of microbial α-diversity on community functions under environmental stress are poorly understood. Here, we investigated the changes in bacterial and fungal α- diversity along gradients of five natural stressors (temperature, precipitation, plant diversity, soil organic C and pH) across 45 grasslands in China and evaluated their connection with microbial functional traits. By quantifying the five environmental stresses into an integrated stress index, we found that the bacterial and fungal α-diversity declined under high environmental stress across three soil layers (0-20 cm, 20-40 cm and 40-60 cm).

A myotropic AAV vector combined with skeletal muscle -regulatory elements improve glycogen clearance in mouse models of Pompe disease.

Pompe disease is a glycogen storage disorder caused by mutations in the acid α-glucosidase (GAA) gene, leading to reduced GAA activity and glycogen accumulation in heart and skeletal muscles. Enzyme replacement therapy with recombinant GAA, the standard of care for Pompe disease, is limited by poor skeletal muscle distribution and immune responses after repeated administrations. The expression of GAA in muscle with adeno-associated virus (AAV) vectors has shown limitations, mainly the low targeting efficiency and immune responses to the transgene.

Three-dimensional-printed strontium-incorporated β-TCP bioceramic triply periodic minimal surface scaffolds with enhanced angiogenic and osteogenic properties.

Reconstructing bone defects remains a significant challenge in clinical practice, driving the urgent need for advanced artificial grafts that simultaneously promote vascularization and osteogenesis. Addressing the critical trade-off between achieving high porosity/strength and effective bioactivity at safe ion doses, we incorporated strontium (Sr) into β-tricalcium phosphate (β-TCP) scaffolds with a triply periodic minimal surface (TPMS) structure using digital light processing (DLP)-based three-dimensional (3D) printing. Systematically screening Sr concentrations (0-10 mol%), we identified 10 mol% as optimal, leveraging the synergy between the biomimetic TPMS architecture, providing exceptional mechanical strength (up to 1.

Construction of Silver-Calcium Micro-Galvanic Cell on Titanium for Immunoregulation Osteogenesis.

This work aims to construct a functional titanium surface with spontaneous electrical stimulation for immune osteogenesis and antibacteria. A silver-calcium micro-galvanic cell was engineered on the titanium implant surface to spontaneously generate microcurrents for osteoimmunomodulation and bacteria killing, which provides a promising strategy for the design of a multifunctional electroactive titanium implant. Titanium-based implants are usually bioinert, which often leads to inflammation-induced loosening.

Clinical Outcomes and Complications of Basal, Bolus, and Combination Insulin Regimens in Type 2 Diabetes Mellitus: Evidence from Published Case Reports.

Insulin therapy remains a cornerstone in the management of type 2 diabetes mellitus (T2DM), especially in patients experiencing progressive loss of pancreatic beta-cell function or those with inadequate glycemic control despite oral antidiabetic therapy. This review synthesized clinical outcomes from 44 peer-reviewed case reports published between 2019 and 2024, identified through systematic searches in PubMed and Scopus. The included cases involved 15 males and 29 females, with patient ages ranging from 11 to 91 years (mean 53 ± 20.

Engineered charge adaptive nanoplatform overcomes the drug penetration barriers to potentiate the efficacy of chemotherapy.

Breast cancer continues to present a major clinical hurdle, largely attributable to its aggressive metastatic behavior and the suboptimal efficacy of standard chemotherapeutic regimens. Cisplatin (CDDP) is a representative platinum drug in the treatment of breast cancer, however, its therapeutic application is often constrained by systemic toxicity and the frequent onset of chemoresistance. Here, we introduce a novel charge-adaptive nanoprodrug system, referred to as PP@, engineered to respond to tumor-specific conditions.

Unravelling the molecular network structure of biohybrid hydrogels.

Glycosaminoglycan-based biohybrid hydrogels represent a powerful class of cell-instructive materials with proven potential in tissue engineering and regenerative medicine. Their biomedical functionality relies on a nanoscale polymer network that standard microscopy techniques cannot resolve. Here, we introduce an advanced analytical approach that integrates transmission electron microscopy, X-ray scattering, and computer simulations to directly and quantitatively characterize the nanoscale molecular network structure of these hydrogels.

Mitigative effects of carboxymethyl chitosan on the deterioration of gliadin tractility in frozen rice dough during frozen storage.

Frozen storage deteriorates the texture and digestibility of frozen rice dough by damaging gliadin structure and starch integrity. This study investigated carboxymethyl chitosan (CMCh) and sodium carboxymethyl cellulose (CMCNa) as cry-oprotectants to mitigate these effects. Comprehensive analysis utilizing nuclear magnetic resonance (NMR), texture profile analysis (TPA), dynamic contact angle measurement (DCAT21), reversed-phase high-performance liquid chromatography (RP-HPLC), and circular dichroism (CD) demonstrated that 1.