The prevalence of chronic kidney disease (CKD) in Asia was determined by comparing differences in age, sex, area, and analytical methods. This meta-analysis comprised 42 studies with 2,271,169 participants from five databases that were searched until February 30, 2025. The total prevalence of CKD 1-5 was 17.0%, whereas that of stages 3-5 was 7.7% in Asia. Individuals aged >60 years had a higher prevalence rate of CKD 1-5 compared to those aged <60 years. Compared with Asia (as the comparator), the age-standardized prevalence of CKD (aCKD) 1-5 was the highest in Nepal and South Asia, whereas it was the lowest in Vietnam. Compared with the comparator, Vietnam and Malaysia had the highest aCKD 3-5; while, South Korea and India had lower aCKD 3-5. The sex-standardized prevalence of CKD (sCKD) 1-5 was lower in Nepal, Taiwan, Korea, and South Asia and was higher in Bangladesh than in the comparator. The sCKD 3-5 was lowest in Korea and Taiwan and was highest in Iran and Sri Lanka compared with the comparator. Iranian women and men had the highest prevalence of CKD 3-5. South Asia has a higher prevalence of CKD among men and women than East Asia. The prevalence of CKD was greater in the Chronic Kidney Disease Epidemiology Collaboration-based studies than in the Modification of Diet in Renal Disease (MDRD)-based research. The findings indicate that evaluating populations without considering sex and age is difficult, especially when the sex and age of the groups differ greatly.

Lyotropic liquid crystalline nanoparticles (LCNPs), including cubosomes, are increasingly investigated as antimicrobial nanomaterials because non-lamellar lipid nanoparticles can fuse with biological membranes, exchange lipids, and improve antimicrobial delivery or antibiotic combination treatment. However, prior studies have mainly addressed fusion, uptake, encapsulation, or payload stabilization, rather than testing whether retained internal curvature can be isolated as a design variable for antibacterial potentiation in a matched LCNP series. Herein, we generated lamellar vesicles, primitive cubosomes (P-cubosomes, Im3m), and diamond cubosomes (D-cubosomes, Pn3m) from the same phytantriol/DPPS lipid system. When combined with free daptomycin, rather than being used as drug-loaded carriers, these LCNPs exhibited curvature-dependent potentiation hierarchy against methicillin-resistant Staphylococcus aureus (MRSA), vesicles < P-cubosomes < D-cubosomes. Fluorescence imaging, electron microscopy, and neutron reflectometry showed progressively stronger membrane association, lipid extraction, and bilayer disruption with increasingly negative curvature. In a murine bacteremia model using a sub-optimal daptomycin regimen, the same curvature-dependent efficacy trend was retained in vivo, providing proof-of-concept support rather than therapeutic validation. This study provides direct experimental evidence, in a matched antibacterial LCNP system, that retained internal curvature modulates membrane remodeling and potentiates daptomycin against MRSA.

Delayed graft function (DGF) remains a significant complication following deceased donor kidney transplantation. This study aimed to develop and validate a multidimensional machine learning model for predicting DGF by integrating clinical data, machine perfusion parameters, donor scores, and histopathological scores. A retrospective analysis was conducted on 961 deceased donor kidney transplant recipients from January 2019 to December 2021. The dataset was stratified by the target variable and randomly divided into training (80

INTRODUCTION:Intestinal ischemia/reperfusion (I/R)-induced acute lung injury (ALI) is a key contributing factor to mortality and disability following surgery for acute abdominal emergencies. Panax notoginseng (PN) exerts a significant alleviating effect on intestinal I/R-induced ALI. The objective of this study is to use Ultra-high performance liquid chromatography-Mass spectrometry (UHPLC-MS/MS), network pharmacology, and molecular docking methods to investigate the main active components of PN in alleviating intestinal I/R-induced ALI and their molecular mechanisms. METHODS:The chemical compositions of PN were identified using UHPLC-MS/MS, and potential targets for these compounds were predicted using the Swiss Target Prediction database. Subsequently, Cytoscape 3.7.2 was utilized to design a network that demonstrates the interactions of drugs, components, and targets. Targets associated with intestinal I/R-induced ALI were detected using the GeneCards and OMIM databases. Cross-- targets between the drug and the disease were analyzed, and a PPI network was established via the STRING database. The targets that overlap were subjected to GO and KEGG enrichment analyses. The interactions between core bioactive substances and key proteins were validated through molecular docking. RESULTS:UHPLC-MS/MS analysis identified 71 major chemical constituents in PN. Protein- protein interactions (PPI) network analysis revealed that TNF, IL-6, AKT1, and IL-1β were the most highly interconnected hub targets. The GO analysis revealed a notable enrichment in biological processes such as response to xenobiotic stimulus, positive regulation of gene expression, and inflammatory response. According to the KEGG pathway analysis, significant signaling pathways include PI3K-Akt, TNF, and HIF-1. The stable binding conformations of L-Tryptophan, Quercetin, Adenosine, Linolenic acid ethyl ester, and Bryodulcosigenin with core targets TNF, IL-6, AKT1, IL-1β, and GAPDH were confirmed through molecular docking. DISCUSSION:This computational study provides a systematic framework for deciphering the complex mechanisms of traditional medicines. Our analysis proposes that PN alleviates intestinal I/R-induced ALI through a "multi-component, multi-target, multi-pathway" mechanism. The findings serve as a robust hypothesis-generating resource, offering precise candidates and pathways for future experimental validation. CONCLUSION:This research predicts the effective components of PN and their potential molecular mechanisms in treating intestinal I/R-induced ALI, laying a theoretical groundwork for future experimental confirmation and clinical application.

The oral delivery of drugs for treating intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), is hindered by four primary intestinal barriers: chemical, microbial, mechanical, and immunological barriers. Micro- and nanoparticles have garnered significant attention as platforms for intestinal-targeted delivery due to their small size and unique structural composition, which enhance drug accumulation and prolong residence time at the site of action, thereby facilitating localized therapy. Oral micro/nanomedicines have emerged as a promising strategy to overcome these barriers and enable the selective targeting of drugs to pathological sites within the intestine. This review systematically examines the chemical, microbial, mechanical, and immune barriers of the intestinal mucosa encountered in intestinal diseases, introduces oral micro/nanomedicines designed to target these barriers, discusses their latest advancements in the context of intestinal diseases, and ultimately provides insights into the challenges faced by oral micro/nanomedicine.

Acute kidney injury (AKI) remains a major clinical challenge driven by oxidative stress and inflammation, particularly in ischemia-reperfusion and cisplatin-induced injury. Here, we synthesized aminophenol-ethylenediamine-based carbon dots functionalized with polyethylene glycol (AE-CDs@PEG), exhibiting excellent biocompatibility and strong antioxidant capacity with SOD-like activity exceeding 10,000 U/mg. In vitro, AE-CDs@PEG effectively alleviated oxidative damage, mitochondrial dysfunction, and inflammation in human renal tubular epithelial (HK-2) cells under LPS, H2O2, and hypoxia/reoxygenation stress. In vivo, AE-CDs@PEG significantly improved renal function, reduced histological damage, and mitigated oxidative stress in both ischemia-reperfusion injury (IRI)-and cisplatin-induced AKI models. Transcriptomic and 16S rRNA analyses revealed that AE-CDs@PEG modulated key inflammatory pathways and restored gut microbiota homeostasis by enriching Akkermansia and elevating short-chain fatty acids, particularly acetic and butyric acids. These findings highlight AE-CDs@PEG as a promising multi-target antioxidant nanozyme for AKI therapy.

Renal ischemia-reperfusion injury (RIRI) mainly comes from inflammation and oxidative stress. Treating with inflammation monotherapy or oxidative stress monotherapy can't reduce RIRI. This study involved the synthesis of Panax notoginseng-derived carbon dots (PN-CDs) herbzymes, nanozymes from Chinese herbal medicines, exhibiting inherent antioxidant enzymatic activity. The diverse surface functional groups facilitate the effective scavenging of reactive oxygen species (ROS) and suppress the expression of inflammatory factors. In the RIRI model, PN-CDs demonstrated extended systemic circulation and improved renal targeting, effectively decreasing renal tissue concentrations of neutrophil gelatinase-associated lipocalin (NGAL), creatinine, blood urea nitrogen, and kidney injury molecule-1 (KIM-1). They also decreased inflammatory factors and lipid peroxidation markers, thereby mitigating renal damage. Multi-omics analysis showed that PN-CD protects kidney function mainly via gut microbiota, shrinking nephrotoxins such as indoxyl sulfate and enhancing beneficial metabolisms such as β-indol-3-acetamide and stimulating pathways like aryl hydrocarbon receptor (AHR), ERK to reduce inflammation and oxidative stress. In conclusion, PN-CDs herbzyme was a potential treatment for RIRI and provided the theoretical basis for the herbzyme therapy of kidney disease, as well as the proof-of-concept for the gut-kidney axis.

INTRODUCTION:Kidney dysfunction (KD) is a major metabolic risk factor for cardiovascular disease (CVD) and has been playing an increasingly significant role in the global burden of disease. However, there is still a lack of comprehensive, long-term, and systematic research assessing the global burden of CVD attributable to KD. METHODS:Using data from the Global Burden of Disease (GBD) 2021 database, we extracted burden indicators related to KD-associated CVD, including the number of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and their corresponding age-standardized rates, and evaluated annual trends using estimated annual percentage change. We performed decomposition analysis to identify three main drivers of burden changes-population, aging, and epidemiological change; and applied an autoregressive integrated moving average model to project future trends from 2022 to 2050. RESULTS:From 1990 to 2021, the global absolute numbers of deaths, DALYs, YLLs, and YLDs caused by KD-related CVD increased, while the corresponding age-standardized rates generally declined. Males exhibited a higher disease burden compared to females, and the elderly population, particularly those aged 75-84 years, represented the primary burden group. Middle-SDI countries experienced the highest burden, while inequality remained pronounced in low-SDI countries. Decomposition analysis revealed that, however, the increase in burden was primarily driven by population and aging, epidemiological change showed improvement. Forecasting results indicated that by 2050, the total number of cases will continue to rise, age-standardized rates will keep declining, but the YLD among females is expected to increase. CONCLUSION:The burden of CVD attributable to KD is expected to continue rising in the future, characterized by increasing absolute numbers and declining age-standardized rates. This trend suggests that stratified prevention strategies may be needed across countries with varying SDI levels, with particular attention to older populations and integrated heart-kidney disease management to reduce the global burden of the disease.

BACKGROUND:Lung ischemia-reperfusion injury (LIRI) is a complex pathophysiological process with few existing therapeutic options. New drugs are needed to target both oxidative stress and enhanced sterile inflammation during ischemia-reperfusion. RESULTS:In this study, we developed a metal-phenolic nanozyme (CurFe) that possesses significant enzyme-like activities, including superoxide dismutase (SOD)-like activity and hydroxyl radical (•OH) scavenging ability, and can effectively modulate inflammatory cytokines and maintain cellular homeostasis in vitro. In the mouse LIRI model, nebulized inhalation of Cur-Fe nanozyme significantly reduced lung inflammation and oxidative stress, improved lung tissue function, and restored alveolar structure. It is important to note that transcriptomics and metabolomics analyses demonstrated that Cur-Fe nanozyme modulated key metabolic pathways, including the cGMP-PKG signaling pathway and amino acid metabolism, thereby promoting its protective effects on lung tissue. CONCLUSION:In this study, we present a Cur-Fe nanozyme that shows great potential in mitigating LIRI-associated lung injury by targeting oxidative stress and inflammation as well as regulating key transcriptional and metabolic pathways. This innovative approach provides a new avenue for the development of nanomedicines for the treatment of ischemia-reperfusion-related diseases with promising clinical applications.

Nanozymes are a distinct category of nanomaterials that exhibit catalytic properties resembling those of enzymes such as peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Nanozymes derived from Chinese herbal medicines exhibit the catalytic functions of their enzyme mimics, while retaining the specific medicinal properties of the herb (termed "herbzymes" ). These nanozymes can be categorized into three main groups based on their method of synthesis: herb carbon dot nanozymes, polyphenol–metal nanozymes, and herb extract nanozymes. The reported catalytic activities of herbzymes include POD, SOD, CAT, and GPx. This review presents an overview of the catalytic activities and potential applications of nanozymes, introduces the novel concept of herbzymes, provides a comprehensive review of their classification and synthesis, and discusses recent advances in their biomedical applications. Furthermore, we also discuss the significance of research into herbzymes, including the primary challenges faced and future development directions.

Renal ischemia-reperfusion injury (IRI) is a prevalent cause of acute kidney injury, however, the regulatory mechanisms of miR-374b-5p in renal IRI remain poorly understood. We established hypoxia/reoxidation (H/R)-induced renal injury models using HK-2 and TCMK-1 cells, as well as an ischemia-reperfusion (I/R)-induced mouse model. Renal tubular epithelial cells (RTECs) viability and apoptosis were assessed using CCK-8, flow cytometry, and TUNEL assays. The targeting relationship between miR-374b-5p and SRSF7 was analyzed using dual luciferase reporter assays. The interaction between METTL3 and miR-374b-5p was confirmed through methylated RNA immunoprecipitation (MeRIP) and co-immunoprecipitation (Co-IP) assays. We found that miR-374b-5p levels were significantly upregulated in H/R-induced HK-2 and TCMK-1 cells. Furthermore, miR-374b-5p promoted H/R-induced RTEC injury by suppressing cell viability and exacerbating apoptosis. SRSF7 was identified as a downstream target of miR-374b-5p, inhibition of SRSF7 reversed the inhibitory effects of miR-374b-5p inhibitors on RTEC injury. Additionally, METTL3 interacted with the microprocessor protein DGCR8 and modulated the processing of pri-miR-374b-5p in an m6A-dependent manner. In the renal IRI model, METTL3 and miR-374b-5p levels were upregulated, and knockdown of METTL3 inhibited apoptosis in H/R-induced HK-2 and TCMK-1 cells. Conversely, miR-374b-5p reversed the protective effects of METTL3 knockdown on renal IRI. Our findings provide novel insights into the role of m6A methylation in the development of renal IRI, demonstrating that METTL3 promotes renal IRI by modulating the miR-374b-5p/SRSF7 axis.

The tumor suppressor BRCA1-associated protein 1 (BAP1) encodes a nuclear deubiquitinase that specifically removes H2A monoubiquitination at Lys119 (H2Aub) and plays a crucial role in the epigenetic regulation of gene expression through cooperating with several transcriptional factors and chromatin-modifying enzymes. Our previous studies have confirmed that BAP1 represses SLC7A11-mediated cystine metabolism and promotes ferroptosis-dependent tumor suppression. However, how BAP1 regulates gene expression at the genome level and whether additional mechanisms are involved in the BAP1 regulation of ferroptosis remain unclear. Here, we integrate multi-omics analyses to explore the effects of BAP1-mediated H2Aub deubiquitination on the regulation of chromatin accessibility and gene transcription. Notably, we identified a novel target gene, ACSL4, which is positively regulated by BAP1 and contributes to BAP1-mediated ferroptosis. Importantly, genetic knockout or pharmacological inhibition of ACSL4 prevents the upregulation of lipid biosynthesis and ferroptotic cell death caused by BAP1. In addition, we demonstrated that BAP1-mediated regulation of gene expression and ferroptosis is dependent on ASXL family members instead of other BAP1-associated factors like FOXK1/2, HCFC1, and OGT. Together, our findings uncover a previously unappreciated epigenetic mechanism underlying the regulation of ACSL4 by H2A monoubiquitination, which connects ACSL4-mediated lipid metabolism to ferroptosis driven by BAP1, providing new insights into the understanding of metabolic regulation of BAP1-related diseases such as cancers.

The rapid emergence of antimicrobial resistant Gram-negative bacteria compromises current antibiotic efficacy, including the last-resort antibiotic polymyxins, emphasizing the urgent need for novel therapeutic strategies. Nanoscale-based antimicrobials exhibit potential as an alternative treatment strategy. In this study, four furoxan-based nitric oxide (NO)-releasing nanoparticles (NPs) were prepared and their antimicrobial efficacy was tested against different Gram-negative bacteria, including: Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli via minimum inhibitory testing, where NPs exhibited selective activity against lipopolysaccharide (LPS)-deficient A. baumannii strains and LPS-truncated strains tested. Advanced microscopic techniques and mechanistic investigations using model membranes mimicking the LPS-deficient A. baumannii membrane and LPS-containing membrane, via neutron reflectometry and small-angle neutron scattering, indicated that the NPs specifically destabilize the LPS-deficient A. baumannii membrane, leading to the release of cellular content. This work provides mechanistic insight into the selective activity of the NPs against LPS-deficient A. baumannii and their lack of efficacy in strains with LPS, highlighting membrane-level determinants that may inform future antimicrobials development.

Lyotropic liquid crystalline nanoparticles (LCNPs) have shown significant potential as nanocarriers for antibiotic delivery and as an alternative polytherapy strategy with antibiotics. Mechanistic studies indicate that these nanoparticles can fuse with bacterial membranes, causing destabilization and lipid extraction. While current research on LCNPs has primarily focused on surface functionality to enhance antibiotic delivery based on their known membrane fusion properties, the role of LCNP curvature in enhancing fusion and penetration remains unexplored. Specifically, understanding how structural design, such as the optimization of lamellar and bicontinuous cubic phases, affects membrane fusion capabilities could unlock new opportunities for more effective therapeutic-loaded LCNPs and polytherapy approaches. Herein, we have synthesized lamellar vesicles with zero curvature and then structurally modulated into non-lamellar primitive (P-cubosomes) and diamond (D-cubosomes) cubic phases with increasingly negative curvatures. The tested polytherapy of three distinct LCNPs with daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) strains, demonstrating that manipulating LCNP curvature enhances their synergy with daptomycin. Fluorescent and electron microscopy analyses demonstrated that increased negative curvature enhances membrane interactions, establishing a clear link between LCNP’s nanostructures and antimicrobial effectiveness, following the order of vesicles < P-cubosomes < D-cubosomes, with D-cubosomes showing the strongest effects. Neutron reflectometry using model membranes provided Ångström-level details, confirming that curvature positively impacts membrane interaction. This study presents the first experimental evidence linking LCNP curvature to enhanced interaction with bacterial membranes and marks the first application of LCNPs against MRSA, suggesting that curvature manipulation could serve as a novel strategy for designing more potent antimicrobial agents.

Renal ischemia-reperfusion injury (IRI) is a significant condition that leads to acute kidney injury, exacerbating the progression of renal failure clinically and affecting the patient's prognosis. Following the identification of miR-182-5p as a significant molecule in IRI, we conducted a detailed analysis of its potential downstream genes and assessed its involvement in the SIRT1/Nrf2/ferroptosis pathway. To validate these findings in vivo, we implemented an exosome-mediated drug delivery protocol and assessed its therapeutic efficacy in C57BL/6. miR-182-5p exhibited a notable upregulation in renal IRI. Utilizing bioinformatics approaches, the study further investigated and validated its downstream SIRT1/Nrf2 pathway, establishing its role in ferroptosis. By employing LTHVVWL(LTH)-anchored exosomes, the delivery of miR-182-5p to the kidney was significantly improved, thereby illustrating its potential efficacy in mitigating renal IRI. The findings of our study demonstrated that miR-182-5p suppressed SIRT1/Nrf2 activity and facilitated ferroptosis, suggesting its potential as a therapeutic target for clinical IRI treatment. The inhibition of miR-182-5p via LTH-anchored exosomes was shown to significantly mitigate renal IRI, providing a novel approach for the development of miRNA-based therapeutic drug delivery systems.