Browse Articles

A Synergistically Engineered Protein Hydrogel Integrating Topological Reinforcement and Metal‐Ion Coordination for Diabetic Wound Repair

ABSTRACT The clinical translation of extracellular matrix (ECM)‐mimetic protein hydrogels is often hampered by their inadequate mechanical strength and structural disorder. Innovative strategies that integrate structural control with bioactive cues are urgently needed for diabetic wound repair. We present a synergistic “topological engineering/metal‐coordination” strategy to design a new class of collagen‐like protein hydrogels. Via genetic encoding, metal‐binding domains (Zn 2 + , Ag + , Cu 2 + ), together with a cell‐adhesive RGD motif and stabilizing Vα/Vβ domains, were incorporated into collagen scaffolds (CLP3/CLP1). We further engineered hydrogels with precisely defined point‐, cyclic‐, and bis‐cyclic‐crosslinked topologies. The Zn 2 + ‐coordinated, bis‐cyclic‐crosslinked hydrogel based on CLP3 (BZnCα3) exhibited optimal integrated performance. It demonstrated skin‐like stress‐strain curves, superior toughness, and excellent fatigue resistance. In vitro, BZnCα3 promoted cell adhesion, proliferation, migration, and exhibited potent antibacterial and anti‐inflammatory effects. In a diabetic mouse model, BZnCα3 significantly accelerated wound closure, enhanced re‐epithelialization and collagen deposition, and orchestrated a pro‐healing microenvironment by polarizing macrophages to the M2 phenotype, upregulating regenerative factors, and alleviating oxidative stress. This work establishes a genetically encoded platform for creating protein hydrogels with tunable topology and dynamic mechanics, emerging as a multifaceted biomaterial that effectively addresses mechanical and biological barriers, holding great promise as a therapeutic dressing for refractory diabetic wounds.

A Multitask Deep Learning Model for Pediatric Echocardiography Analysis

BACKGROUND: Congenital heart defects afflict ≈1% of all births worldwide. Although deep learning has shown significant promise in automating and improving adult echocardiography analysis, existing pediatric-based models are often limited to single tasks and specific echocardiographic views. To address this, we introduce EchoAI-Peds, a multitask deep learning model for pediatric echocardiography. Our model was developed using the most comprehensive set of pediatric labels to date and is designed to integrate information from multiple views simultaneously. METHODS: We trained a video-based vision transformer to simultaneously detect 28 congenital heart defects, structural and functional abnormalities, repairs, and interventions directly from complete pediatric echocardiography studies with multiple videos. Our model was developed using >700 000 videos derived from >12 000 studies performed at Stanford Medicine between 2014 and 2021. Specifically, our model was trained on 10 815 studies (median age, 8 [IQR 2–14] years; 45% girls) and validated on 1294 studies (median age, 9 [IQR 2–15] years; 46% girls). Model efficacy was tested on an internal held-out data set of 1336 studies from that same period. In addition, model generalizability was tested on a spatially and temporally distinct patient cohort at the Children’s Hospital of Philadelphia using 2121 studies performed between 2024 and 2025. RESULTS: Our model achieved macroaveraged (area under the receiver operating characteristic curve (AUROC) values of 0.91 (95% CI, 0.90–0.92) on the internal test set (median age, 8 [IQR 2–14] years; 47% girls) and AUROC values of 0.89 (95% CI, 0.88–0.90) on the external test set (median age 6 [IQR 0.92–13] years; 44.4% girls). Moreover, EchoAI-Peds significantly outperformed adult-based echocardiography foundation models trained on substantially larger data sets, including EchoCLIP (internal AUROC=0.58, 95% CI, 0.56–0.60; external AUROC=0.61, 95% CI, 0.59–0.62) and EchoPrime (internal AUROC=0.58, 95% CI, 0.57–0.61; external AUROC=0.60, 95% CI, 0.59–0.62). Finally, our model demonstrated robust performance across patient age, patient sex, and studies with varying number of videos. CONCLUSIONS: Our findings demonstrate the remarkable potential for multitask deep learning models to aid the interpretation of pediatric echocardiograms. In addition, our results underscore the need for models that are specifically tailored to pediatric populations.

2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

AIM The “2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome” retires, replaces, and expands upon the “2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults.” The primary intended audience for this guideline is clinicians who care for patients across the spectrum of cardiovascular-kidney-metabolic syndrome, an interrelated condition characterized by the interconnections among metabolic risk factors (including obesity and type 2 diabetes), chronic kidney disease, and cardiovascular disease. METHODS A comprehensive literature search was conducted from October 29, 2024, to April 14, 2025, to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human subjects that were published since 2015 in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE The focus of this clinical practice guideline is to create a living, working document that provides current knowledge in the field of cardiovascular-kidney-metabolic syndrome aimed at all practicing cardiologists, endocrinologists, nephrologists, and primary care and specialty clinicians who manage these patients.

Strong Coupling Hybrid Modes for Narrow‐band, Directional and Polarized OLEDs

ABSTRACT Linearly polarized organic light‐emitting diodes (LP‐OLEDs) featuring high color purity and directional emission have become essential light sources for near‐eye displays, holographic projection, and high‐precision optical sensing. However, a strategy capable of simultaneously controlling multiple parameters including color purity, directionality, polarization, and optoelectronic efficiency has remained an unmet challenge in OLED development. Herein, we demonstrate a blue‐emitting OLED that combines high color purity with highly directional transverse‐electric (TE)‐polarized emission, realized through a strongly photon‐photon mode‐coupled microcavity architecture. By hybridizing the second‐order Fabry‐Perot mode with the first‐order grating microcavity mode, the system achieves strong coupling with a mode splitting energy of 321 me. Consequently, the resulting polarized OLED exhibits outstanding performance including a transverse‐electric/transverse‐magnetic polarization extinction ratio of 17.3 dB, an external quantum efficiency of 3.4%, and a narrow full width at half maximum of 17.0 nm with an angular distribution of 10°. These findings validate the practical viability of microcavity coupling for advancing optoelectronic devices, particularly in display technologies and photonic integration.

Targeting E3 Ubiquitin Ligase Hrd1 Prevents Myocardial Ischemia-Reperfusion Injury Through Enhancing ALDH2 Enzymatic Activity

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury presents a significant clinical challenge characterized by a complex pathological mechanism. The role of protein ubiquitination in I/R injury has not been systematically investigated. Global ubiquitinome profiling was conducted to identify the potential key players in myocardial I/R injury. METHODS: The ubiquitination levels of proteins in mouse hearts subjected to either sham surgery or I/R injury were analyzed using ubiquitinome. A combined analysis of ubiquitinome, single-cell RNA sequencing (RNA-seq), and proteomics data was employed to predict potential E3 ubiquitin ligases associated with myocardial I/R injury. Global heterozygous 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase degradation 1 (Hrd1) knockout, endothelial cell (EC)–specific Hrd1 deficiency (Hrd1 f/f ; Cdh5 Cre ), and EC-specific Hrd1 overexpression (AAV-EC-Hrd1) mice were used to assess the role of Hrd1 in myocardial I/R injury. Mass spectrometry and immunoprecipitation were used to elucidate the interaction between Hrd1 and aldehyde dehydrogenase 2 (ALDH2). Additionally, we assessed ubiquitination and vasomotor reactivity to clarify the mechanisms by which Hrd1 regulates ALDH2 activity and EC dysfunction during I/R injury. RESULTS: Ubiquitinome analysis revealed that protein ubiquitination exacerbates endothelial dysfunction after myocardial I/R injury. Integrative analysis of the ubiquitinome, proteomics, and single-cell RNA-seq revealed a significant upregulation of the E3 ubiquitin-protein ligase Hrd1 in CD45 + ECs. In both humans and mice, the level of endothelial Hrd1 protein was found to increase in response to I/R in vivo. Genetic ablation of Hrd1 significantly alleviated myocardial infarction, endothelial dysfunction, and infiltration of inflammatory cells after I/R injury. Mechanistically, Hrd1 promoted the K33-linked polyubiquitination of ALDH2 and then inhibited the formation of its active tetramers, which reduced the apoptosis of CD45 + ECs and exacerbated endothelial dysfunction through the NO/cGMP/PKG (nitric oxide–cyclic guanosine monophosphate–protein kinase G) signaling pathway. Furthermore, our findings demonstrated that pharmacological inhibition of Hrd1 robustly ameliorated myocardial I/R injury and endothelial dysfunction. CONCLUSIONS: Our findings demonstrated a previously unidentified crucial role of cardiac EC Hrd1 in myocardial I/R injury. Hrd1 may serve as a therapeutic target for preventing myocardial I/R injury.

Neodymium Single‐Atom Regulator via Electronic State Nonlinear Change for Piezoelectric Sonodynamic Therapy

ABSTRACT In recent years, using ultrasound‐sensitive characteristics of piezoelectric materials for antitumor therapy has become a rapidly developing therapeutic method. However, the limited piezoelectric catalytic efficiency severely constrains the efficacy of piezoelectric sonodynamic therapy (SDT). It is still urgent to propose effective strategies to improve the efficiency of piezoelectric catalysis. In this study, we construct a neodymium (Nd) single‐atoms electronic regulator by loading Nd single‐atoms on vacancy‐enriched Bi 2 O 3 support (Nd SABs). The introduction of Nd single‐atoms provides electrons that modulate electron transfer and enhance the activation of adsorbed oxygen, promoting the production of toxic reactive oxygen species (ROS) under ultrasound (US) irradiation to inhibit tumor cells. Both in vitro and in vivo experiments show that Nd SABs efficiently generate ROS and exhibit excellent antitumor effects under US irradiation. In addition, Nd single‐atoms on Nd SABs can emit the desired second near‐infrared window (NIR‐II) emission under 808 nm laser irradiation to achieve NIR‐II fluorescence imaging. This work not only proposes a strategy of using rare earth single‐atom electronic regulators to improve piezoelectric catalytic efficiency, but also reports NIR‐II emission of Nd single‐atoms, which expands the application of rare earth single‐atoms systems in the field of tumor diagnosis and therapy.

Letter by Zhang and Zhang Regarding Article, “Short-Term Anticoagulation Versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure: The ANDES Randomized Clinical Trial”

Photoresponsive Granular Hydrogels Enable Spatiotemporal Control of Matrix Mechanics and MSC Behavior

ABSTRACT Granular hydrogels offer a powerful platform for engineering porous, cell‐instructive scaffolds with tunable mechanical, structural, and biochemical properties, yet introducing spatial and functional heterogeneity typically requires multiple microgel populations or complex fabrication strategies. Here, we present a programmable, photoresponsive granular hydrogel platform that enables post‐assembly spatiotemporal control of scaffold mechanics and cell microenvironments from a single microgel formulation. Poly(ethylene glycol) microgels containing photolabile allyl sulfide moieties were synthesized via strain‐promoted azide‐alkyne cycloaddition and assembled into granular scaffolds capable of light‐mediated remodeling through radical addition‐fragmentation chain transfer. This chemistry afforded dynamic, on‐demand, and spatially defined tuning of mechanical properties (G′ = 0.7–3.7 kPa) while maintaining scaffold porosity (∼20%). High‐resolution photopatterning across multiple length (6 µm‐1 mm) and timescales enabled precise modulation of local microenvironments. Human mesenchymal stem/stromal cells embedded in these scaffolds responded to spatiotemporal modulation of matrix mechanics as observed by changes in morphology, yes‐associated protein 1 (YAP) nuclear localization, and secretory profiles. Together, these results establish a versatile and broadly applicable strategy for programming mechanical heterogeneity and regulating cell behavior in granular hydrogels through photolabile moieties.

2026 Cardiovascular-Kidney-Metabolic Guidelines: Practical Implementation Strategies

Host–Guest Synergy of COF and CoO Enables In Situ Oxygen Vacancies and Regulated Li ⁺ Behavior for High‐Performance Anode‑Free/Less Li Metal Batteries

ABSTRACT Anode‐free Li metal batteries (AFLMBs) are excellent candidates for electric vehicles and low‐altitude aircrafts because of their high energy density. However, the industrialization of AFLMBs remains limited by the poor reversibility of Li + deposition and stripping on Cu current collectors (CCs). In this study, a composite CC (TCMS@Cu) integrating a covalent organic framework (COF) membrane and CoO nanoparticles is constructed to address these challenges. The TCMS@Cu forms a dense COF crystalline membrane on Cu foil via epitaxial growth and incorporates lithiophilic CoO nanoparticles. The host–guest synergistic effect between the COF and CoO effectively guides Li + migration into COF cavities, effectively suppressing dendrite formation and the accumulation of inactive Li. During the initial deposition process, CoO reacts with Li + to generate oxygen vacancies, further enhancing the performance of the TCMS membrane. The anode‐less Li metal batteries (ALLMBs) assembled with LiFePO 4 cathode achieve an exceptional cycle life of 850 cycles and a high‐rate capacity retention of 94.4% at 5C. The assembled AFLMB pouch cells deliver energy densities of 288 Wh kg −1 (LFP|CC) and 452 Wh kg −1 (NCM811|CC) (calculated without cell can and tabs). This work provides an effective strategy for designing high performance AFLMBs and promotes the development of next‐generation energy storage devices.

Response by Xu et al to Letter Regarding Article, “Geometric Features of Ventricular Tachycardia Corridors in Patients with Ischemic Cardiomyopathy”

Sulfonated MOF‑Enhanced Nafion Membranes for High‑Temperature, Durable Proton Exchange Membrane Water Electrolysis

ABSTRACT High‐temperature proton exchange membrane water electrolysis (HT‐PEMWE) is a promising strategy for low‐energy, high‐efficiency hydrogen production. However, practical implementation relies critically on the development of novel PEMs that simultaneously offer high proton conductivity and long‐term stability at high temperatures. While metal–organic frameworks (MOFs) have been widely investigated as high‐performance proton‐conducting materials, their specific incorporation into Nafion matrices for HT‐PEMWE remains largely unexplored. In this work, we designed and fabricated a sulfonated MOF‐reinforced Nafion (S/N‐Nafion) composite membrane. The S/N‐Nafion membrane achieved a proton conductivity of 154.7 mS cm −1 at 100 °C, which is twice that of recast Nafion (75.6 mS cm −1 ), while also possessing excellent mechanical strength and dimensional stability at elevated temperatures. When used as the solid electrolyte, an electrolyzer with S/N‐Nafion reached only 1.59 V at 120 °C and 3.0 A cm −2 , which is 120 mV lower than recast Nafion (1.71 V) under the identical conditions. Moreover, during a 300‐h durability test at 120 °C and 1.0 A cm −2 , the S/N‐Nafion‐PEMWE exhibited an extremely low voltage decay rate of 6.0 µV h −1 . These results underscore the immense potential of the S/N‐Nafion membrane for enabling highly efficient and stable high‐temperature electrolytic hydrogen production.

Contrastive Machine Learning to Quantify Hypertensive Multiorgan Damage and Identify New Disease Phenotypes: A Multinational Multimodal Study

BACKGROUND: Hypertension induces structural and functional damage in multiple organs. Evidence of subclinical damage increases risk of vascular events and death but can be difficult to identify in the clinic. We developed a novel machine learning approach that quantifies current hypertension-associated multiorgan damage, mapping progression from health to advanced disease, in a pseudotemporal manner and predicts organ-specific disease progression trajectories. METHODS: We analyzed 566 multimodal imaging and nonimaging variables from 27 099 participants in the UK Biobank imaging substudy to develop a semisupervised contrastive trajectory inference (cTI) framework that models multiorgan alterations associated with hypertension exposure, including heart, brain, kidneys, vasculature, lungs, liver, and metabolic information. Model stability was validated through multiple internal validation steps, and external validity was tested on 5507 participants from the Atherosclerosis Risk in Communities study (ARIC). Clinical relevance was evaluated against existing risk scores and through ability to predict survival and incident multiorgan disease for up to 7 years, across both UK Biobank and ARIC. RESULTS: In the UK Biobank (mean age 63.27±7.48 years; 53.4% women) our global organ damage score (HyperScore) achieved an area under the curve of 0.964 (0.941–0.987) for identification of individuals with severe end-organ disease and robust stability in cross-validation with a mean root mean square error of 0.104±0.084. Survival odds differed significantly across HyperScore stages ( P <0.001), whereas stratification by blood pressure was nonsignificant. We further revealed 6 hypertensive disease phenotypes (HyperTrajectory), characterized by predominant cardiac, lipoprotein, atherothrombosis, brain, cardiorenal, and liver features, respectively. External testing in ARIC confirmed stability of the model, with Jensen-Shannon distances as low as 0.10 for HyperScore distributions, without significant deviation in organ damage progression patterns ( P >0.05) and consistent end-organ and outcome characteristics between ARIC and UK Biobank across HyperTrajectories. CONCLUSIONS: Machine learning–derived global organ damage scores are feasible in hypertension and enable identification of distinct hypertension-associated organ-disease phenotypes. New frameworks for hypertension assessment and monitoring using imaging to derive personalized risk assessment and phenotype-specific intervention may be achievable.

Cellulosic Composites in Lithium Metal Batteries

ABSTRACT Lithium metal batteries (LMBs) hold great promise for next‐generation high‐energy‐density energy storage, yet their practical deployment is severely hindered by lithium dendrite growth, unstable solid electrolyte interphase (SEI), infinite volume expansion of lithium anodes, and poor thermal safety. As an abundant, renewable, biodegradable, and low‐cost biomass polymer, cellulose and its derivatives feature outstanding mechanical robustness, tunable flexibility, rich surface hydroxyl groups, and designable hierarchical micro/nanostructures, which endow them with unique advantages in addressing critical bottlenecks of LMBs. This review focuses on the multifunctional roles and underlying mechanisms of cellulose‐based composites in boosting the electrochemical and safety performance of LMBs. By virtue of polar functional groups and rigid‐flexible integrated structures, cellulose can effectively homogenize Li + flux, guide uniform lithium deposition, suppress dendrite nucleation and propagation, and alleviate volume fluctuation during cycling. Meanwhile, cellulose‐based matrices significantly enhance the mechanical strength, thermal stability, flame retardancy, and ionic conductivity of polymer electrolytes and separators. Seven types of functional cellulose composites are highlighted regarding their applications in electrolytes, separators, 3D anode hosts, artificial interphase layers, and interface regulators. Finally, the future development of cellulose materials toward high‐performance LMBs is prospected from the aspects of precise molecular modification, biomimetic ordered ion transport, and scalable green fabrication. This review provides systematic insights into the performance enhancement mechanisms and application strategies of cellulose for high‐safety and long‐lifespan lithium metal batteries.

Medial Arterial Calcification in a 4500-Year-Old Egyptian King: A Deep-Time View of a Vascular Calcification Continuum

Experimental and simulation study of preformed particle gel-assisted conformance control in dual sandpack systems for enhanced oil recovery

Slimmed Solvation Structure With Dual‐Interface Regulation for High‐Performance and Safe Lithium‐Sulfur Batteries

ABSTRACT A crucial step toward widespread electrochemical energy storage is the design of lithium–sulfur batteries (LSBs) that integrate high energy density with robust safety. Realizing practical LSBs demands an electrolyte that possesses high interfacial stability, excellent ion‐environment regulation capability, and high electrocatalytic activity. Although current electrolyte technologies have improved the cycling performance of LSBs, preparing electrolytes that simultaneously deliver high energy density, high cycling stability, and high safety remains a significant challenge. Here, we report an electrolyte design strategy aimed at achieving high‐performance and high‐safety LSBs. This is primarily accomplished by incorporating symmetric ionic plastic crystals into the electrolyte to construct a slimmed solvation structure (Li + ) regulated by suppression of anion aggregation (S n 2− and TFSI − ) during discharge. The electrolyte exhibits high ionic conductivity, low desolvation energy barrier, high electrocatalytic activity, and interfacial stability. This design acts simultaneously on the cathode and anode interfaces, enabling stable and rapid cycling of LSBs, with high energy density (pouch cell: 704 Wh kg −1 ) and high stability (average capacity decay rate per cycle of 0.018% over 600 cycles). Our solvation structure model design provides a feasible approach for realizing high‐performance and high‐safety LSBs.

Predictive Value of Coronary Artery Calcium Score From Nongated Chest CT Scans Compared With Gated Scans and Incidence of Cardiovascular Events

BACKGROUND: Data on the prognostic value of incidental coronary artery calcium (CAC) from nongated chest computed tomography scans are limited. Using paired computed tomography scans from the MESA (Multi-Ethnic Study of Atherosclerosis) exam 5, we evaluated the relationship between nongated CAC, gated CAC, and future cardiovascular events. METHODS: Between April 2010 and December 2011, a total of 2601 participants underwent same-day gated and nongated chest computed tomography scans. After excluding 106 with previous coronary heart disease or cardiovascular disease and 23 for missing covariates, 2472 participants formed the study population. Gated and nongated scans were interpreted at a core laboratory, blinded to acquisition methodology. Cox regression examined associations between CAC (gated and nongated) and incident coronary heart disease/cardiovascular disease events. Correlation was assessed with Pearson coefficients, model performance with receiver operating characteristic curves and C-statistic, and overall accuracy with Brier scores. RESULTS: Among the 2472 participants, 53% were female, 38% white, 13% Chinese, 26% Black, and 23% Hispanic/Latino. Compared with participants with zero CAC, those with moderate (101–299) and severe (≥300) nongated CAC had higher coronary heart disease risk (hazard ratio, 2.67 [95% CI, 1.14–6.27]; hazard ratio, 5.22 [95% CI, 2.37–11.5]) and cardiovascular disease risk (hazard ratio, 1.32 [95% CI, 1.32–4.04]; hazard ratio, 2.89 [95% CI, 1.68–4.96]). Gated and nongated log-standardized CAC highly correlated ( r =0.961; P <0.001). The area under the receiver operating characteristic curves, C-statistic, and Brier scores were statistically similar for gated and nongated CAC. CONCLUSIONS: Nongated CAC predicts cardiovascular events with performance comparable to gated CAC. Given the large number of nongated scans performed annually, incorporating their quantification into clinical practice offers a scalable approach to personalized preventive care. Our findings are particularly relevant in light of the recent 2026 American College of Cardiology/American Heart Association dyslipidemia guidelines, which endorse the use of incidental CAC from nongated computed tomography scans for atherosclerotic cardiovascular disease risk stratification and guiding lipid-lowering therapy.

The UnderwaterVLA dual-brain vision-language-action architecture enables robust autonomous underwater navigation

Rapid Hematological Profiling of the GPNMB/GRN Ratio via Bioelectronic Platform for Early Diagnosis of Parkinson's Disease

ABSTRACT Early blood‐based diagnosis of Parkinson's disease (PD) remains challenging owing to the lack of reliable composite biomarkers and rapid, sensitive, and cost‐effective detection platforms. Here, we report a bioelectronic sensor based on an organic electrochemical transistor (OECT) driven by a laser‐induced graphene (LIG) array. By integrating an alternating‐current (AC)‐mediated LIG rapid incubation system (LRIS), the platform enables multiplexed protein profiling directly from clinical samples within approximately 6 min, with attomolar‐level detection limits. We identify the glycoprotein non‐metastatic melanoma protein B (GPNMB)/granulin (GRN) ratio as a sensitive composite biomarker of neuroinflammatory dysregulation, showing pronounced alterations at early disease stages and complementing α‐synuclein for PD assessment. In PD mouse models spanning mild to severe stages ( n = 32), this ratio correlated with disease progression and enabled the detection of mild neuronal loss. Clinical validation in healthy individuals and patients with PD or prodromal PD ( n = 54) showed that the GPNMB/GRN ratio distinguished patients with PD from healthy controls with 80% sensitivity, 90% specificity, and 85% accuracy. Incorporating α‐synuclein further improved diagnostic accuracy. This biomarker–platform strategy provides a rapid, ultrasensitive, and scalable framework for blood‐based PD screening and early risk assessment.