Renal ischemia-reperfusion injury (IRI), a cause of acute kidney injury (AKI), involves mitochondrial dysfunction. Under metabolic stress, the ketone body β-hydroxybutyrate functions as an alternative substrate for mitochondrial energy production, the underlying mechanisms remain incompletely understood. Here, we identify FK506 binding protein 4 (FKBP4) as a critical regulator of mitochondrial energy metabolism in AKI. A bilateral renal IRI mouse model was established with pretreatment of ketogenic diet (KD) or sodium β-hydroxybutyrate (BHBNa). Metabolomics and bulk RNA-seq were performed to assess mitochondrial oxidative stress and energy metabolism. In vitro, human renal tubular epithelial cells (HK-2) underwent hypoxia/reoxygenation (H/R) to mimic ischemia/hypoxia injury, with mitochondrial energy metabolism evaluated via the seahorse assay. Chromatin immunoprecipitation (ChIP) was used to identify downstream targets of β-hydroxybutyrylation of histone H3K4 (H3K4bhb). Administration of KD or BHBNa ameliorated renal dysfunction at 24 h post-ischemia. The renoprotective effect of BHBNa was mediated by FKBP4. In HK-2 cells, both overexpression and knockdown of FKBP4 significantly altered mitochondrial energy metabolism. Mechanistically, β-hydroxybutyrate-induced autophagy was dependent on FKBP4, and its knockdown suppressed both autophagy and mitochondrial oxidative phosphorylation (OXPHOS). FKBP4 functions as a co-chaperone that binds β-hydroxybutyryllysine (Kbhb) and facilitates nuclear receptor trafficking to mediate conjugation of H3K4bhb. This ketone body-induced epigenetic modification enhances mitochondrial OXPHOS in renal tubules, providing critical energy support during renal IRI. Our findings indicate that supplemental ketone bodies mitigate IRI-induced AKI, and identify FKBP4 as a central coordinator of mitochondrial energy metabolism through upregulation of autophagy and mediation of H3K4bhb.

Immunoglobulin A nephropathy (IgAN) is a leading cause of end-stage renal disease (ESRD). There is a critical need for sensitive biomarkers to predict disease progression, as traditional indicators like serum creatinine (Scr) have limitations. This study investigates the association of routine metabolic indicators with renal function, pathology, and hospitalization expenses in IgAN patients. In this cross-sectional study, lactate dehydrogenase (LDH) levels were significantly correlated with mesangial hypercellularity (M) and tubular atrophy/interstitial fibrosis (T) in the MEST-C score in the Oxford classification. Furthermore, LDH levels showed a consistent association with estimated glomerular filtration rate (eGFR) and total hospitalization expenses in unadjusted and multivariable-adjusted analyses. Serum uric acid (SUA) levels also demonstrated a strong relationship with renal function. In lipid metabolism, high-density lipoprotein cholesterol was significantly associated with eGFR after multivariable adjustment, whereas triglycerides (TGs) showed correlations with eGFR only in the unadjusted analysis. Serum total protein (TP) levels exhibited a linear positive correlation with eGFR in the unadjusted analysis and emerged as a robust predictor of M, segmental glomerulosclerosis (S), and T lesions in the Oxford Classification. After false discovery rate correction for multiple comparisons, TP was found to be significantly associated with T lesions, which was the most crucial finding of our study, whereas associations involving LDH and other markers were exploratory. Importantly, S and T lesions were strongly associated with a decline in renal function and M1 lesions were found to respond favorably to corticosteroid therapy, whereas T2 lesions signaled an increased risk of progression to ESRD. These hypothesis-generating findings suggest that the strict control of lipid and SUA levels is essential for patients with IgAN in clinical practice. Elevated LDH and decreased TP levels may alert clinicians to the risks of renal function deterioration and ESRD. Moreover, such patients may respond favorably to corticosteroid therapy, which should be considered within the framework of KDIGO 2025 guidelines based on comprehensive risk assessment.

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and remains a major cause of chronic kidney disease and kidney failure. Conventional monitoring still depends largely on proteinuria, estimated glomerular filtration rate (eGFR), hematuria, blood pressure and biopsy-based pathological classification. These measures are clinically indispensable, but they mainly capture downstream kidney injury and may lag behind the mucosal and systemic immune events that drive active disease. In the targeted-therapy era, this limitation has become more consequential. Targeted-release budesonide, BAFF/APRIL dual inhibitors, APRIL inhibitors and complement-directed therapies act at different levels of the IgAN immunopathogenic cascade. Galactose-deficient IgA1 (Gd-IgA1) remains central to disease biology, yet its standalone value as a marker of disease activity or prognosis is limited by assay heterogeneity, ethnic and clinical variability, treatment exposure and differences in histopathological context. Increasing evidence suggests that the pathogenicity of IgA depends not only on Gd-IgA1 concentration, but also on mucosal origin, polymeric state, autoantibody binding, immune-complex formation, mesangial retention and complement activation. This Review synthesizes recent advances in immune biomarker monitoring in IgAN, with emphasis on mucosal immune activity, Gd-IgA1, polymeric IgA, IgA-containing immune complexes, complement activation and kidney injury biomarkers. Its contribution is not another undifferentiated catalog of candidate markers. Instead, biomarkers are organized according to their position in the disease cascade and their relationship to treatment mechanism: upstream mucosal immune activation, pathogenic IgA immune-complex burden, complement-mediated intrarenal amplification and tissue injury, and conventional clinical outcomes. The framework is intended to support mechanistic research, trial enrichment and longitudinal pharmacodynamic assessment, while distinguishing established clinical measures from biomarkers that remain investigational. Its use for treatment selection or routine precision monitoring requires prospective validation and assay standardization.

Background: Sleep-related problems are common among patients receiving dialysis for end-stage renal disease (ESRD), while pharmacological management may be complicated by comorbidities, polypharmacy, and altered drug clearance. This systematic review and meta-analysis evaluated the effects of non-pharmacological interventions on sleep-related outcomes, anxiety symptoms, depressive symptoms, and fatigue symptoms in this population. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to February 2026. The prespecified eligibility criterion was restricted to randomized controlled trials (RCTs) involving adults with ESRD receiving hemodialysis or peritoneal dialysis and reporting an eligible sleep-related outcome. One quasi-cluster randomized trial was retained as a documented protocol deviation. Standardized mean differences (SMDs) calculated using Hedges’ g and 95% confidence intervals (CIs) were pooled using random-effects models with restricted maximum-likelihood estimation and the Hartung–Knapp–Sidik–Jonkman adjustment (REML–HKSJ). Risk of bias was assessed using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2), and evidence certainty was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. PROSPERO: CRD420251123449. Results: The 19 RCTs and one quasi-cluster randomized trial contributed an effective sample size of 1294 participants. The pooled estimate favored non-pharmacological interventions for sleep-related outcomes (Hedges’ g = −0.820, 95% CI −1.188 to −0.451; p = 0.0002), with substantial heterogeneity (I2 = 83.1%; τ2 = 0.4879). The 95% prediction interval (PI) ranged from −2.325 to 0.685. The pooled effects on anxiety symptoms (Hedges’ g = −0.29, 95% CI −0.99 to 0.41; p = 0.219), depressive symptoms (Hedges’ g = −0.64, 95% CI −2.32 to 1.04; p = 0.313), and fatigue symptoms (Hedges’ g = −0.41, 95% CI −0.93 to 0.11; p = 0.087) were not statistically significant. Effect estimates differed significantly by comparator type (Q-between = 11.28, df = 2; p = 0.0036). Conclusions: Non-pharmacological interventions may improve sleep-related outcomes in patients receiving dialysis for ESRD. However, substantial heterogeneity and a prediction interval crossing the null value limit confidence in the pooled estimate. Current evidence does not demonstrate clear benefits for anxiety symptoms, depressive symptoms, or fatigue symptoms.

Maladaptive repair following acute kidney injury (AKI) is an independent risk factor for the progression to chronic kidney disease (CKD). We hypothesize that renal tubular cell senescence and subsequent epithelial-mesenchymal transition drive maladaptive repair after AKI, ultimately leading to chronic renal fibrosis. We re-analyzed single-cell RNA sequencing data (ScRNA-seq, GSE212273) from kidney tissues post-IRI. In vivo, we employed unilateral IRI and folic acid models to simulate the AKI to CKD transition. Senolytics or verteporfin were given from Day 3 post-modeling. In vitro, human renal tubular epithelial (HK-2) cells were exposed to hydrogen peroxide or TGF-β. Sustained YAP1 overexpression promoted fibroblast activation and a profibrotic phenotypic shift. AKI induced a sustained increase in YAP1 expression, which was associated with tubular cell senescence and renal interstitial fibrosis. Senolytics effectively suppressed YAP1 activity, renal senescence, and alleviated kidney fibrosis. In vitro, persistent oxidative stress upregulated YAP1 expression and induced cell senescence. Knockdown of YAP1 downregulated Hippo signaling pathway, extracellular matrix reorganization, and reduced cell senescence. Conversely, YAP1 overexpression reversed the anti-senescence effect of senolytics. Finally, pharmacological inhibition of YAP1/TEAD1 attenuated cell senescence and post-ischemic renal fibrosis. Our findings indicate that sustained YAP1 overexpression mediates tubular cell senescence, which drives maladaptive kidney repair and facilitates the AKI to CKD transition. Senolytics or verteporfin therapy initiated after the peak of AKI offers a dual benefit: it protects the regenerative capacity of tubular cells and concurrently inhibits YAP1-driven epithelial-mesenchymal transition, thereby mitigating the progression of renal fibrosis.

Lipid accumulation and chronic inflammation are key drivers of chronic kidney disease (CKD) progression to renal fibrosis, but the underlying mechanisms remain incompletely understood. The stimulator of interferon genes (STING), a central regulator of innate immunity and inflammatory responses, has recently garnered significant attention in the context of kidney disease. In this study, we demonstrate that STING expression is markedly upregulated in fibrotic kidneys from both CKD patients and mice subjected to ischemia-reperfusion injury (IRI). Genetic ablation or pharmacological inhibition of STING alleviated renal fibrosis, inflammation, and lipid accumulation in IRI mice, effects that were closely associated with hexokinase 3 (HK3)-mediated lipid metabolism. Moreover, inhibition of STING suppressed NF-κB activation and subsequently reduced HK3 upregulation, thereby attenuating hypoxia/reoxygenation-induced fibrosis, inflammation, and lipid accumulation in primary mouse renal tubular cells (RTECs) and HK-2 cells. Mechanistically, activation of the cGAS-STING signaling pathway promotes the binding of its downstream effector NF-κB p65 to the HK3 promoter, which initiates transcriptional upregulation of HK3, leading to dysregulated lipid metabolism, enhanced inflammation, and ultimately renal fibrosis. Taken together, our findings indicate that the cGAS-STING-NF-κB-HK3 signaling axis may represent a novel therapeutic target for early-stage renal fibrosis.

Objectives:Cordycepin (COR) is a natural bioactive compound derived from Cordyceps militaris. Relevant studies have shown that COR can alleviate kidney damage, but the underlying mechanism of its action in the treatment of acute kidney injury (AKI) remains to be further clarified. Materials and Methods:The GSE148420 dataset and GeneCards were used to identify AKI-related targets. GeneCards was used to obtain ischemia/reperfusion (I/R)-related targets. BATMAN 1.0 and GeneCards were used to identify potential drug targets of COR. Renal function, tissue damage, and molecular markers were assessed to explore the effects of COR on apoptosis and necroptosis in the treatment of AKI. Results:Network pharmacological analysis showed that AKI and COR shared 28 drug targets. Enrichment analysis showed that the targets were involved in signaling pathways, including apoptosis and necroptosis. In vitro experiments revealed that COR alleviated hypoxia/re-oxygenation(H/R)-induced HK-2 cells injury by reducing the expression of Bax and cleaved-Caspase3 while increasing the expression of Bcl-2. Necroptosis was lessened under COR treatment in vitro and in H/R-induced HK-2 cells by reducing the expression of RIPK1, RIPK3, MLKL, and p-MLKL. COR and Nec-1 (a RIPK1 inhibitor) had the same inhibitory effect, confirming the role of COR in alleviating AKI by inhibiting RIPK1-driven necroptosis. COR alleviated AKI by ameliorating renal morphology injury and pathological injury in vivo, manifested as a decrease in Scr and BUN levels, a significant reduction in the mRNA expression levels of KIM-1 and NGAL, and a decrease in p-MLKL at the immunohistochemical level. Conclusion:COR may ameliorate I/R-induced AKI by inhibiting apoptosis and RIPK1/RIPK3/p-MLKL-mediated necroptosis.

This retrospective study analyzed 10,934 hyperkalemia episodes to compare outcomes between the hyperkalemia routine group and the hyperkalemia standardized group, the latter managed with a strategy supported by the 'Serum Potassium Management Center System' in a real-world implementation setting. The study compared process and outcome metrics between this system-level intervention cohort and the routine care cohort. The hyperkalemia standardized group exhibited significantly higher rates of diagnosis (19.00% vs. 15.43%), treatment (85.23% vs. 58.29%), and review (89.41% vs. 60.86%) (all p < 0.05). With respect to disease burden, the hyperkalemia standardized group was associated with lower hospitalization costs in the chronic kidney disease-heart failure (CKD-HF) and chronic kidney disease-diabtes mellitus-heart failure comorbid subgroups, as well as shorter hospital stays in the CKD-HF comorbid subgroup (all p < 0.05). A non-significant trend toward reduced hospitalization costs and shorter hospital stays was also observed in the CKD subgroup. In conclusion, implementation of the 'Serum Potassium Management Center System' was associated with improved quality of hyperkalemia care, as reflected by more favorable process indicators and disease burden-related outcomes. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR) ChiCTR2600116550 on January 12, 2026.

The recent study provides compelling evidence for the neuroprotective effects of a polyherbal extract (PHE) in a rat model of diabetic neuropathy (DN). While the authors demonstrate significant improvements in metabolic, oxidative, and inflammatory parameters, this review posits that these downstream effects are likely orchestrated by a crucial upstream mechanism: The modulation of the gut microbiota. We argue that DN is intrinsically linked to gut dysbiosis, which promotes a “leaky gut”, systemic inflammation, and a deficit in neuroprotective microbial metabolites like short-chain fatty acids. The complex, poorly absorbed components of the PHE likely act as prebiotics, restoring microbial homeostasis. This single action can mechanistically explain the observed systemic benefits from reduced inflammation to improved neurotrophic support. Recognizing the gut microbiota as the central mediator bridges the multi-component nature of traditional herbal medicine with the complex, multi-system pathology of DN, paving the way for novel, microbiome-targeted therapeutic strategies.

Hemodialysis vascular access is the lifeline of patients receiving maintenance hemodialysis, yet access dysfunction remains a major cause of inadequate dialysis, repeated intervention, unplanned catheter use, hospitalization, and eventual access loss. Current vascular access care relies on physical examination, auscultation, dialysis-machine parameters, access-flow surveillance, duplex ultrasound, and angiography. Although these approaches remain clinically indispensable, they are episodic, operator-dependent, and poorly suited for continuous home-based warning. Recent advances in artificial intelligence, digital auscultation, photoplethysmography, pulse radar sensing, soft thermal sensors, wireless thrill sensors, ultrasound video analysis, and artificial intelligence of things systems have created new opportunities to transform vascular access surveillance from intermittent clinical assessment to continuous digital phenotyping. In this review, we propose a framework for artificial intelligence–enabled vascular access monitoring organized around four linked domains: pathophysiological signal generation, sensor-based digital phenotyping, artificial intelligence–based risk inference, and clinically actionable home-based warning. We summarize recent evidence from acoustic artificial intelligence, photoplethysmography-based classification, pulse radar sensing, wearable thermal and vibration sensors, artificial intelligence–assisted ultrasound, and multimodal clinical risk prediction models across the vascular access life cycle. We further discuss key barriers to clinical translation, including inconsistent definitions of access dysfunction, heterogeneous reference standards, small single-center datasets, limited external validation, device usability, alert fatigue, workflow integration, regulatory requirements, and the need for prospective outcome-based trials. Future studies should move beyond offline diagnostic accuracy toward standardized external validation, longitudinal patient-specific baselines, workflow-integrated monitoring systems, and prospective trials demonstrating reductions in thrombosis, unplanned catheter placement, delayed intervention, access loss, and patient burden. Hemodialysis vascular access is the lifeline of patients receiving maintenance hemodialysis, yet access dysfunction remains a major cause of inadequate dialysis, repeated intervention, unplanned catheter use, hospitalization, and eventual access loss. Current vascular access care relies on physical examination, auscultation, dialysis-machine parameters, access-flow surveillance, duplex ultrasound, and angiography. Although these approaches remain clinically indispensable, they are episodic, operator-dependent, and poorly suited for continuous home-based warning. Recent advances in artificial intelligence, digital auscultation, photoplethysmography, pulse radar sensing, soft thermal sensors, wireless thrill sensors, ultrasound video analysis, and artificial intelligence of things systems have created new opportunities to transform vascular access surveillance from intermittent clinical assessment to continuous digital phenotyping. In this review, we propose a framework for artificial intelligence–enabled vascular access monitoring organized around four linked domains: pathophysiological signal generation, sensor-based digital phenotyping, artificial intelligence–based risk inference, and clinically actionable home-based warning. We summarize recent evidence from acoustic artificial intelligence, photoplethysmography-based classification, pulse radar sensing, wearable thermal and vibration sensors, artificial intelligence–assisted ultrasound, and multimodal clinical risk prediction models across the vascular access life cycle. We further discuss key barriers to clinical translation, including inconsistent definitions of access dysfunction, heterogeneous reference standards, small single-center datasets, limited external validation, device usability, alert fatigue, workflow integration, regulatory requirements, and the need for prospective outcome-based trials. Future studies should move beyond offline diagnostic accuracy toward standardized external validation, longitudinal patient-specific baselines, workflow-integrated monitoring systems, and prospective trials demonstrating reductions in thrombosis, unplanned catheter placement, delayed intervention, access loss, and patient burden. Hemodialysis vascular access is the lifeline of patients receiving maintenance hemodialysis, yet access dysfunction remains a major cause of inadequate dialysis, repeated intervention, unplanned catheter use, hospitalization, and eventual access loss. Current vascular access care relies on physical examination, auscultation, dialysis-machine parameters, access-flow surveillance, duplex ultrasound, and angiography. Although these approaches remain clinically indispensable, they are episodic, operator-dependent, and poorly suited for continuous home-based warning. Recent advances in artificial intelligence, digital auscultation, photoplethysmography, pulse radar sensing, soft thermal sensors, wireless thrill sensors, ultrasound video analysis, and artificial intelligence of things systems have created new opportunities to transform vascular access surveillance from intermittent clinical assessment to continuous digital phenotyping. In this review, we propose a framework for artificial intelligence–enabled vascular access monitoring organized around four linked domains: pathophysiological signal generation, sensor-based digital phenotyping, artificial intelligence–based risk inference, and clinically actionable home-based warning. We summarize recent evidence from acoustic artificial intelligence, photoplethysmography-based classification, pulse radar sensing, wearable thermal and vibration sensors, artificial intelligence–assisted ultrasound, and multimodal clinical risk prediction models across the vascular access life cycle. We further discuss key barriers to clinical translation, including inconsistent definitions of access dysfunction, heterogeneous reference standards, small single-center datasets, limited external validation, device usability, alert fatigue, workflow integration, regulatory requirements, and the need for prospective outcome-based trials. Future studies should move beyond offline diagnostic accuracy toward standardized external validation, longitudinal patient-specific baselines, workflow-integrated monitoring systems, and prospective trials demonstrating reductions in thrombosis, unplanned catheter placement, delayed intervention, access loss, and patient burden. Hemodialysis vascular access is the lifeline of patients receiving maintenance hemodialysis, yet access dysfunction remains a major cause of inadequate dialysis, repeated intervention, unplanned catheter use, hospitalization, and eventual access loss. Current vascular access care relies on physical examination, auscultation, dialysis-machine parameters, access-flow surveillance, duplex ultrasound, and angiography. Although these approaches remain clinically indispensable, they are episodic, operator-dependent, and poorly suited for continuous home-based warning. Recent advances in artificial intelligence, digital auscultation, photoplethysmography, pulse radar sensing, soft thermal sensors, wireless thrill sensors, ultrasound video analysis, and artificial intelligence of things systems have created new opportunities to transform vascular access surveillance from intermittent clinical assessment to continuous digital phenotyping. In this review, we propose a framework for artificial intelligence–enabled vascular access monitoring organized around four linked domains: pathophysiological signal generation, sensor-based digital phenotyping, artificial intelligence–based risk inference, and clinically actionable home-based warning. We summarize recent evidence from acoustic artificial intelligence, photoplethysmography-based classification, pulse radar sensing, wearable thermal and vibration sensors, artificial intelligence–assisted ultrasound, and multimodal clinical risk prediction models across the vascular access life cycle. We further discuss key barriers to clinical translation, including inconsistent definitions of access dysfunction, heterogeneous reference standards, small single-center datasets, limited external validation, device usability, alert fatigue, workflow integration, regulatory requirements, and the need for prospective outcome-based trials. Future studies should move beyond offline diagnostic accuracy toward standardized external validation, longitudinal patient-specific baselines, workflow-integrated monitoring systems, and prospective trials demonstrating reductions in thrombosis, unplanned catheter placement, delayed intervention, access loss, and patient burden. Hemodialysis vascular access is the lifeline of patients receiving maintenance hemodialysis, yet access dysfunction remains a major cause of inadequate dialysis, repeated intervention, unplanned catheter use, hospitalization, and eventual access loss. Current vascular access care relies on physical examination, auscultation, dialysis-machine parameters, access-flow surveillance, duplex ultrasound, and angiography. Although these approaches remain clinically indispensable, they are episodic, operator-dependent, and poorly suited for continuous home-based warning. Recent advances in artificial intelligence, digital auscultation, photoplethysmography, pulse radar sensing, soft thermal sensors, wireless thrill sensors, ultrasound video analysis, and artificial intelligence of things systems have created new opportunities to transform vascular access surveillance from intermittent clinical assessment to continuous digital phenotyping. In this review, we propose a framework for artificial intelligence–enabled vascular access monitoring organized around four linked domains: pathophysiological signal generation, sensor-based digital phenotyping, artificial intelligence–based risk inference, and clinically actionable home-based warning. We summarize recent evidence from acoustic artificial intelligence, photoplethysmography-based classification, pulse radar sensing, wearable thermal and vibration sensors, artificial intelligence–assisted ultrasound, and multimodal clinical risk prediction models across the vascular access life cycle. We further discuss key barriers to clinical translation, including inconsistent definitions of access dysfunction, heterogeneous reference standards, small single-center datasets, limited external validation, device usability, alert fatigue, workflow integration, regulatory requirements, and the need for prospective outcome-based trials. Future studies should move beyond offline diagnostic accuracy toward standardized external validation, longitudinal patient-specific baselines, workflow-integrated monitoring systems, and prospective trials demonstrating reductions in thrombosis, unplanned catheter placement, delayed intervention, access loss, and patient burden. Hemodialysis vascular access is the lifeline of patients receiving maintenance hemodialysis, yet access dysfunction remains a major cause of inadequate dialysis, repeated intervention, unplanned catheter use, hospitalization, and eventual access loss. Current vascular access care relies on physical examination, auscultation, dialysis-machine parameters, access-flow surveillance, duplex ultrasound, and angiography. Although these approaches remain clinically indispensable, they are episodic, operator-dependent, and poorly suited for continuous home-based warning. Recent advances in artificial intelligence, digital auscultation, photoplethysmography, pulse radar sensing, soft thermal sensors, wireless thrill sensors, ultrasound video analysis, and artificial intelligence of things systems have created new opportunities to transform vascular access surveillance from intermittent clinical assessment to continuous digital phenotyping. In this review, we propose a framework for artificial intelligence–enabled vascular access monitoring organized around four linked domains: pathophysiological signal generation, sensor-based digital phenotyping, artificial intelligence–based risk inference, and clinically actionable home-based warning. We summarize recent evidence from acoustic artificial intelligence, photoplethysmography-based classification, pulse radar sensing, wearable thermal and vibration sensors, artificial intelligence–assisted ultrasound, and multimodal clinical risk prediction models across the vascular access life cycle. We further discuss key barriers to clinical translation, including inconsistent definitions of access dysfunction, heterogeneous reference standards, small single-center datasets, limited external validation, device usability, alert fatigue, workflow integration, regulatory requirements, and the need for prospective outcome-based trials. Future studies should move beyond offline diagnostic accuracy toward standardized external validation, longitudinal patient-specific baselines, workflow-integrated monitoring systems, and prospective trials demonstrating reductions in thrombosis, unplanned catheter placement, delayed intervention, access loss, and patient burden.

The genus Sanghuangporus, renowned in China for its traditional use due to its antitumor, antioxidant, and hypoglycemic properties, includes medicinal species with therapeutic potential. However, the metabolic profile of Sanghuangporus quercicola under different cultivation strategies remains poorly understood. Here, we present the first metabolomic comparison of S. quercicola fruiting bodies and mycelia obtained via substitute cultivation, solid-state fermentation, and submerged fermentation. (I) UHPLC-QTOF-MS-based untargeted metabolomics identified 164 metabolites, including phenolics, terpenoids, steroids, and nitrogen-containing compounds, with 57 showing significant differential accumulation. (II) Multivariate analyses (PCA, PLS-DA) and KEGG pathway enrichment revealed that solid-state fermentation enhanced bioactive metabolite accumulation, especially phenolics and terpenoids, whereas substitute cultivation yielded greater chemical diversity in fruiting bodies, suggesting potential for targeted therapeutic development. (III) In vitro assays showed that the solid-state fermentation extract exhibited the strongest α-glucosidase inhibition (95.35

Phosphorus is one of essential nutrients for the human body that plays an indispensable role in various physiological processes. The balance of blood phosphorus is crucial in all living organisms. Chronic kidney disease （CKD） patients often develop hyperphosphatemia due to the imbalance of the key hormone regulating blood phosphorus in the body. Phosphate is indispensable for basic cellular functions， but hyperphosphatemia is toxic that impairs organ function. Cardiovascular disease is an important cause of death in CKD patients. Hyperphosphatemia can drive the occurrence of vascular calcification （VC） and increase the incidence and mortality of cardiovascular disease. This paper reviewed the current research progress between vascular calcification and hyperphosphatemia， aiming to improve the clinicians’ understanding of the role of hyperphosphatemia in the diagnosis and treatment of CKD combined with cardiovascular disease.

ObjectiveTo investigate the features of gut microbiota in cirrhotic patients with myosteatosis and identify specific bacterial species that may be involved in the pathogenesis of myosteatosis.Methods80 patients with liver cirrhosis were categorized into the myosteatosis group (n = 44) and the non-myosteatosis group (n = 36). Metagenomic sequencing was used to analyze the differences in gut microbiota composition between the two groups. Subsequently, the value of meaningful gut microbiota in the diagnosis of myosteatosis in patients with liver cirrhosis was analyzed.ResultsAt the species level, however, 15 bacterial species exhibited significant differences in relative abundance between these two groups. The relative abundance of Roseburia hominis and Subdoligranulum unclassified was inversely associated with mean muscle attenuation density at the L3 level (p < 0.05). Assessement of the diagnostic potential of Roseburia hominis and Subdoligranulum unclassified for the development of myosteatosis showed that the areas under the ROC curves (AUCs) was 0.869 [95% confidence interval (CI): 0.709–1.029; p < 0.05] for Roseburia hominis and 0.828 (95% CI: 0.6472–1.009; p < 0.05) for Subdoligranulum unclassified.ConclusionOur study establishes compositional alterations of gut microbiota in patients with liver cirrhosis combined with myosteatosis and suggests the diagnostic potential for using gut microbiota as noninvasive biomarkers.

The kidney possesses a highly complex reabsorption function, with tubular epithelial cells (TECs) being the primary functional units. The TECs mainly rely on fatty acid oxidation (FAO) for energy supply. FAO is hindered during ischemia-reperfusion (I/R)-induced acute kidney injury (AKI), leading to impairments in oxidative phosphorylation. The energy supply to renal TECs then shifts from FAO to glycolysis. Impaired fatty acid uptake and oxidation, coupled with sustained increases in glycolysis, can lead to irreversible damage or failure of TEC regeneration. This causes TEC atrophy, inadequate adaptive repair, progression to chronic kidney disease (CKD), and fibrosis. Irisin, a protein secreted by skeletal muscle, is a factor in regulating energy homeostasis. The beneficial effects of exercise on diabetic kidney disease are primarily mediated through its actions. In vitro and in vivo models of our experiments show that irisin can correct the energy metabolic disorders of renal TECs following I/R, increase FAO, reduce glycolysis, and improve I/R-induced AKI. Target points of irisin were explored to elucidate the specific mechanisms of action. We found that the integrin αVβ5 receptor, a target of irisin, is also expressed in TECs and is upregulated following hypoxia/reoxygenation (H/R). Bioinformatics showed significant differences in the AMPK (PRKAA2) and mTOR genes between AKI and normal mice and identified protein interaction among FNDC5/irisin, AMPK, and mTOR. Examination of the effects of irisin on AMPK, mTOR, and the mTOR downstream target HIF-1α showed that pre-treatment with irisin increased the phosphorylation of AMPK in H/R-treated HK-2 cells while simultaneously suppressing mTOR phosphorylation and reducing HIF-1α expression. However, pretreatment with an anti-integrin αVβ5 antibody inhibited the regulatory effects of irisin on AMPK/mTOR phosphorylation and HIF-1α protein levels in H/R-treated HK-2 cells. Given their recognized regulatory roles in energy metabolism, particularly in FAO and glycolysis, our experiments investigating the effects of AMPK and mTOR modulation demonstrated that suppression of AMPK or stimulation of mTOR impeded Irisin's ability to modulate these processes in response to I/R, as well as its ameliorative impact on AKI. Therefore, we concluded that irisin exerts its beneficial effects by binding to the integrin αVβ5 receptor on the membrane of renal TECs, thereby modulating the AMPK/mTOR pathway to improve FAO and reduce glycolysis, ultimately ameliorating I/R-induced AKI, with HIF-1α also participating in this regulatory process. (Graphical Abstract).

ObjectiveTo determine whether mesenchymal stem cells （MSCs） pretreated with cordycepin can protect human renal tubular epithelial cells （HK-2） from apoptosis induced by hypoxia/reoxygenation （H/R）.MethodsTargets related to stem cell therapy for acute kidney injury （AKI） were obtained from the Gene Expression Omnibus （GEO） database. Cordycepin-associated targets were retrieved from BATMAN-TCM （Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine）. Intersection of these target sets identified common candidate genes. In vitro experiments included four groups： Control （HK-2）， hypoxia/reoxygenation （H/R）， H/R co-cultured with MSCs （MSCs+H/R）， and H/R co-cultured with cordycepin-pretreated MSCs （COR-MSCs+H/R）.ResultsThe results of the Cell Counting Kit-8 （CCK-8） showed that the cordycepin treatment significantly increased MSC viability in a dose-dependent manner； 40 μmol/L produced a notable enhancement （P<0.001）. Cordycepin also improved MSC migration in scratch assays. Western blot and immunofluorescence showed that cordycepin preserved MSC stemness， with significant upregulation of octamer-binding transcription factor 4 （OCT4） and homeobox protein Nanog versus untreated controls （P<0.05）. In HK-2 cells subjected to H/R， co-culture with MSCs significantly increased anti-apoptotic B cell lymphoma-2 （Bcl-2） and decreased pro-apoptotic Bcl-2 associated x protein （Bax） and cleaved caspase-3 （P<0.05 or P<0.01）， indicating an anti-apoptotic effect. Co-culture with cordycepin-pretreated MSCs （COR-MSCs+H/R） further increased Bcl-2 （P<0.05） and further reduced Bax and cleaved caspase-3 （P<0.01）， enhancing apoptosis inhibition. Integrative network pharmacology and bioinformatics analysis identified six common target genes between MSC-based AKI therapy and cordycepin， with chemokine （C-C motif） ligand 2 （CCL2） as a representative candidate. Enzyme linked immunosorbent assay （ELISA） showed that CCL2 levels were significantly reduced in MSCs+H/R versus H/R alone （P<0.0001） and were further reduced in COR-MSCs+H/R versus MSCs+H/R （P<0.0001）.ConclusionMesenchymal stem cells pretreated with cordycepin may protect H/R-injured renal tubular cells from apoptosis by reducing the release of CCL2， providing a theoretical basis for stem cell therapy in acute kidney injury.

Mitochondrial biogenesis (MB) is involved in the regulation of cellular energy metabolism, stress response, and survival. This review examines therapeutic approaches to acute kidney injury (AKI) that target MB, emphasizing clinical research findings and translational strategies in this field. AKI is a severe condition with high mortality and often leads to chronic kidney disease. AKI suppresses MB, resulting in mitochondrial dysfunction, oxidative stress, and further renal damage. Furthermore, studies have shown that ischemia-reperfusion-, sepsis-, and drug-induced AKI inhibit MB and subsequent kidney injury. Studies have shown that targeting MB through genetic and pharmacological interventions can alleviate AKI by restoring mitochondrial function and improving renal outcomes. Small molecule compounds, such as pyrroloquinoline quinone, ZLN005, and resveratrol, can enhance MB, offering potential therapeutic benefits. Nonetheless, further studies are needed to ensure efficacy across different models and mitigate related side effects. Future research should focus on optimizing drug design, understanding MB regulation, and conducting clinical trials to establish effective treatments for AKI.

Wound oxidative stress, resulting from excessive reactive oxygen species (ROS), is a significant obstacle to wound recovery. The application of exogenous antioxidants to the wound site can effectively mitigate ROS. In this study, a straightforward covalent cross-linking method was used to incorporate Cordyceps militaris polysaccharides (CmPs) into bacterial nanocellulose (BNC) via aminosilane modification, resulting in the formation of an S-mBNC/CmPs hydrogel material. CmPs, a homogeneous polysaccharide, was extracted from the fruiting body of C. militaris and had an average molecular weight of 1.0615 x 103 kDa. Experimental analysis and characterization confirmed the successfully incorporating of CmPs into BNC. Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) confirmed the covalent bonding between CmPs and BNC. Furthermore, compared to pure BNC, S-m-BNC/CmPs exhibited improved swelling properties (769 %), fracture stress (0.24 MPa), and decreased crystallinity (61.90 %). Moreover, the incorporation of CmPs endowed S-mBNC/CmPs hydrogels with potent antioxidant properties, enabling them to scavenge free radicals effectively. The scavenging rates of DPPH center dot and center dot OH radicals were 55.33 % and 57.35 %, respectively. These results suggest that Sm-BNC/CmPs offers a promoting approach for broad application in the biomedical field, attributed to its effective preparation process and outstanding dressing properties.

Fabry disease is an X-linked inherited disorder that belongs to the category of lysosomal storage diseases （LSDs）. Due to mutations in the GLA gene associated with Fabry disease， α-galactosidase A （α-GalA） encoded by it results in an impaired activity.α-GalA is a lysosomal-related metabolic enzyme， and the impairment of this enzyme activity causes the accumulation of cellular metabolic substrate. As the metabolic substrates accumulate in the cells， they eventually lead to cellular dysfunction. Currently， the treatments for Fabry disease include enzyme replacement therapy （ERT）， substrate reduction therapy， molecular chaperone therapy， and gene therapy. ERT treatment involves the intravenous injection of exogenous recombinant α-GalA to replace the enzymes with reduced activity or complete deficiency in the patient's body， promoting the degradation of GL3， reducing the accumulation of related metabolic substrates in the organs and tissues， and improving the corresponding symptoms. It also aims to prevent or delay the progression of multi-systemic disorders. Currently， ERT drugs include agalsidase beta and agalsidase alpha， and their efficacy has been proven by numerous studies. The national health insurance system has included ERT drugs in the insurance system， and ERT is currently the main treatment method for Fabry disease patients in China. However， ERT also has obvious limitations. This article briefly introduced the mechanism of action， usage， and research progress of ERT therapy， focusing on the challenges it faces and its future direction.