Liver fibrosis is a progressive condition resulting from chronic liver injury and characterized by excessive extracellular matrix deposition and architectural disruption. Reactive oxygen species (ROS), long considered merely cytotoxic, are now recognized as key modulators of immune responses and fibrogenic pathways. In this context, macrophages play a central role. Traditionally classified into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes, macrophages exhibit greater heterogeneity and plasticity than this binary model suggests. This review critically re-evaluates the role of ROS in liver fibrosis, with emphasis on their dual functions as signaling mediators and inducers of oxidative stress. Particular attention is given to how ROS influence macrophage polarization, activation, and function within the fibrotic liver microenvironment, and how this crosstalk contributes to both fibrogenesis and resolution. By addressing the complexity of redox-immunological interactions, new opportunities emerge for more effective and personalized antifibrotic interventions, including targeted modulation of ROS and immune cell reprogramming. This integrative perspective will help guide the development of more effective and personalized antifibrotic treatments.

Microbiome, representing the collection of commensal microorganisms and the active substances, exert profound influences on environmental biogeochemical cycles and the maintenance of human physiological homeostasis. Their metabolic activities are indispensable for nutrient recycling, climate regulation, and ecosystem resilience. Concurrently, complex microbial communities colonizing human niches are fundamental to digestion, immune responses, and protection against pathogens. Crucially, the functional outcomes of these interactions are largely dictated by microbial diversity and community equilibrium. This review comprehensively summarizes the current understanding of the pivotal roles played by both beneficial and detrimental microbiomes across diverse environmental matrices and human systems. The state-of-the-art technologies enabling comprehensive microbiome analysis are discussed, including high-throughput sequencing and metagenomics, which are revolutionizing microbiome detection and functional characterization. Furthermore, the escalating global crisis of antimicrobial resistance intrinsically linked to microbial ecology and human practices is examined as a critical cross-domain challenge. Finally, the review explores the transformative potential of advanced microbiome bioengineering strategies for targeted environmental remediation, sustainable biotechnology, and biomanufacturing. This comprehensive analysis underscores the intricate interdependence between microbial communities, environmental integrity, and human health, emphasizing the paramount importance of preserving and harnessing microbiome diversity.

In this study, graphdiyne (GDY) was grown in situ on sulfide surfaces derived from polyoxometalate (POM) to construct sp-C–S–M heterointerfaces between metal sulfides (Fe₃S₄ and MoS₂) and GDY, thereby enabling highly efficient bifunctional oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) electrocatalysis. Experimental results reveal that the heterointerface configuration enhances the synergistic interaction between the POM-derived sulfides and GDY, promoting rapid charge transfer and increasing the number of active sites, which collectively boost the intrinsic catalytic activity. At a current density of 10 mA cm^–2, the catalyst demonstrates low overpotentials of 132 mV for the HER and 218 mV for the OER and exhibits excellent catalytic activity. This work systematically clarifies the critical roles of electronic interaction and interfacial architecture between POM-derived components and GDY in enhancing HER and OER activities, offering an effective strategy for the design and construction of high-performance electrocatalysts.

Background: Secondary cardiomyopathies are a major cause of heart failure (HF) with diverse etiologies and high mortality rates. For example, over 50% of patients with end-stage liver disease develop cardiac dysfunction, clinically termed cirrhotic cardiomyopathy (CCM). While serum metabolites mediating cross-organ communication are known to play a critical role in CCM development, the underlying pathogenic mechanisms remain poorly understood due to a lack of optimal experimental models. Methods: We generated Acox2 knockout (KO) mice using CRISPR/Cas9 technology to investigate the role of ACOX2, a rate-limiting peroxisomal enzyme. Cardiac function was assessed via echocardiography. We performed RNA sequencing and quantitative proteomic analyses to evaluate cardiac gene expression. Furthermore, global succinylome profiling was conducted to determine changes in protein succinylation, and global metabolomics analysis was used to identify significantly differentially expressed metabolites (SDMs). Results: Acox2 KO mice successfully recapitulated the hepatic phenotypes observed in patients with ACOX2 homozygous mutations, including liver fibrosis and lymphocytic infiltration. Given that ACOX2 is not expressed in the mouse heart throughout its lifespan, we initially hypothesized that Acox2 deficiency would have no direct impact on cardiac function. However, by 6 months of age, Acox2 KO mice exhibited significantly compromised cardiac parameters via echocardiography, alongside elevated biomarkers of cardiomyopathy and heart failure. While Acox2 deficiency had limited impact on the cardiac proteome, global succinylome profiling revealed a pervasive decrease in protein succinylation in Acox2 KO hearts. Notably, approximately 60% of these hypo-succinylated sites were located on mitochondrial and myofibrillar proteins, including SUCLA2 (K94), CS (K321), FH (K470), MDH1 (K110), OGDH (K999), TNNC1 (K86), VCL (K453), MYH7 (K83), and MYL3 (K9)—a profile tightly associated with cardiomyopathy. Seahorse assays and scanning electron microscopy further indicated impaired mitochondrial function in Acox2 KO mice. Metabolomic analysis revealed a dramatic accumulation of plasma C27 bile acid intermediates and a concomitant decrease in cardiac succinyl-CoA levels. Conclusions: Our findings underscore the critical role of the succinylation landscape in maintaining cardiac function. The cardiac pathology observed in Acox2 KO mice originates from cross-organ metabolic signaling, providing new insights into the pathogenesis of secondary cardiomyopathies, such as cirrhotic cardiomyopathy.