Browse Articles

Concise Total Synthesis of (+)-Shearilicine: A Machine Learning-Assisted Strategy for Ligand Optimization of an Enantioselective Palladium-Catalyzed α-Arylation

Vacuolar H ⁺ -ATPase Preserves Cardiolipin Homeostasis Through the Lysosomal-Mitochondrial Axis to Restrain Cardiac Aging

BACKGROUND: Cardiac aging involves progressive mitochondrial dysfunction, contributing to heart failure. Cardiolipin (CL), essential for mitochondrial function, is increasingly depleted in aging cardiomyocytes, promoting mitochondrial decline. Lysosomal degradation relies on v-ATPase (vacuolar-type H+-ATPase)–mediated acidification, and although lysosomes regulate phospholipid metabolism, their roles in CL homeostasis during aging remains unclear. This study examines whether v-ATPase dysfunction drives age-related cardiac changes by disrupting CL metabolism and mitochondrial function. METHODS: To investigate underlying mechanisms and causality, we use RNA sequencing, targeted lipidomics, immunofluorescence microscopy, (co)immunoprecipitation, proximity ligation assays, subcellular fractionation, mitochondrial respiration analysis and echocardiography, a cardiolipin synthase-1 ( Crsl1 ) knockout mouse model, and 2 v-ATPase knockout models. In addition, we assess whether a nutraceutical intervention targeting v-ATPase dysfunction can mitigate heart failure in aging mouse models and elderly people. RESULTS: Our present findings reveal a sequence of events driving age-related cardiomyopathy: declining cardiac nicotinamide adenine dinucleotide levels impair v-ATPase–mediated lysosomal acidification by weakening the interaction between nicotinamide adenine dinucleotide–dependent glycolytic enzyme aldolase and v-ATPase. This disruption increases lysosomal membrane permeability by reducing lysosomal acidification, allowing cathepsin B to leak into mitochondria. There, cathepsin B disrupts mitochondrial CRLS1 (cardiolipin synthase I), impairing CL synthesis and remodeling. The resulting CL deficiency causes mitochondrial oxidative stress and programmed cell death, leading to mitochondrial and cardiac dysfunction. Genetic or chemical inhibition of v-ATPase and of CRLS1 in mouse models reproduce these age-related defects, highlighting their central roles in cardiac aging. Restoring nicotinamide adenine dinucleotide levels rescues lysosomal acidification and CL metabolism, protecting against age-related cardiomyopathy in rodents and humans. CONCLUSIONS: Augmenting v-ATPase–mediated lysosomal acidification offers novel therapeutic strategies to combat age-related cardiomyopathy by rewiring CL homeostasis.

An AI-driven framework for diabetic foot ulcer classification, segmentation, and depth estimation

Universal Base-Catalyzed Aza-Michael Addition: A General Platform for Transforming Polyurethanes into High-Performance Injectable Thermogels

A promising combination strategy: oncolytic adenovirus (ΔE1B-55 K/E3) and arsenic trioxide for potent cancer therapy

Chemical Synthesis of Mirror-Image Proteins Reveals Chirality-Dependent Cellular Uptake Mediated by a Cell-Penetrating Peptide

Unified Organocatalytic Enantioselective Approach to Axially Chiral Spiranes and Alkylidenecycloalkanes

Synthesis and characterization of electrochemically polymerized indole on screen-printed Ag-conductive transparency sheet for enzymatic biofuel cell applications

Inverse Design of Anthraquinone-Mimicking COFs via Electronic Fingerprints for Sacrificial-Agent-Free Photocatalytic H ₂ O ₂ Production under Visible Light

Eyes closed single-leg stance test detects subtle sensorimotor decline in early multiple sclerosis

Site-Specific Raman Probes Reveal Droplet Aging and Residue-Level Fibril Polymorphism in TDP-43 _CTD

Evaluation of our new three-dimensional navigation system in robot-assisted partial nephrectomy

Dynamic Structural Self-Optimization in Mn and Ta Codoped RuO ₂ for Efficient and Long-Term Acidic Water Oxidation

Influence of cooling rates on the fracture properties of asphalt concrete subjected to freeze-thaw cycles

Correction to “An Amino-Acid-Derived Metal–Organic Framework with Large Pores for Unspecific Enantioseparation”

Effects of restricted compared to free arms motion during standing and walking at height in healthy adolescents

Abstract In adults, it is firmly established that height-induced postural threat as well as restriction of arms motion led to detrimental effects on emotional state and standing/walking outcomes. However, little is known about how both factors influence subjective and objective outcomes in adolescents where mechanisms to control standing and walking are still not adult-like. This work investigated emotional state and performance outcomes while standing and walking with free and restricted arms motion at ground level and at height. Twenty-five and 28 adolescents were recruited for study 1 (standing) and study 2 (walking), respectively. Participants stood (tandem stance) or walked (5 m at self-selected speed) with free or restricted arm position at both ground-level (no threat) and 80 cm above ground (threat). Postural sway (i.e., amplitude, frequency, sample entropy) and spatiotemporal gait (i.e., walking speed, time, steps, cadence) parameters were used as objective performance outcomes. Self-reported emotional state responses (i.e., balance confidence, fear of falling, perceived instability, conscious balance processing) were used as subjective indicators. In both studies, height-induced postural threat led to detrimental effects on emotional state and standing/walking outcomes. Further, adolescents in study 1 adopted a postural control strategy that differed from a “stiffening” response reported for young adults. In addition, threat-related deteriorations in spatiotemporal gait outcomes (study 2) were further amplified when arms were restricted. The findings replicate but also expand previous research about the effects of postural threat and restricted arms motion on emotional state and standing/walking outcomes and provide additional knowledge on how young people act under these conditions.

De Novo Design of Near-Infrared Fluorescence-Activating Proteins

Transcriptome analysis across reproductive stages in peripheral blood of female brown bears: a pilot study

Stable Diradical to Pentaradical Cobalt–Dithiolene Complexes: Toward Cobalt-Based Multinuclear–Multiradical Complexes

Gaze and gait dynamics are shaped by terrain type during urban walking

Abstract The structure of the environment fundamentally shapes how humans see and move. Walking through the city requires the continuous coordination of eyes, head, and body movements, revealing the active role of perception in guiding locomotion. Here, we used wearable eye-tracking, foot-mounted inertial sensors, and GPS to examine how terrain type modulates gaze behaviour and locomotor dynamics during naturalistic urban walking. Twenty young adults walked along routes comprising flat pavements, cobblestones, and dirt paths while their gaze, head orientation, and gait were recorded. Gaze behaviour varied systematically with surface irregularity: cobblestones and dirt paths elicited more frequent downward, proximal gaze and larger downward head-pitch deviations. Gait also adapted, with slower pace, shorter strides, and reduced cadence on uneven surfaces. Spatial correlations revealed tightly coupled adjustments between gaze and gait, indicating continuous sensorimotor coordination. These findings show how the physical structure of urban environments shapes predictive visuomotor strategies during real-world locomotion, providing a multimodal foundation for understanding embodied cognition in motion.