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Enteric hyperoxaluria (EH) results from increased oxalate bioavailability in the gastrointestinal (GI) tract, often affecting patients with inflammatory bowel disease (IBD). We investigated the pathophysiology of EH in an ileitis mouse model, hypothesizing that fat malabsorption, increased gut permeability, and microbial shifts collectively contribute to the hyperoxaluric phenotype in the setting of GI tract inflammation. SAMP1/YitFc (SAMP1) mice and their parental AKR controls were fed one of three diets varying in fat content (10%, 45%, or 60% kcal), each supplemented with 1% oxalate, for 6 weeks. Plasma (P), urine (U), oxalate (Ox), and creatinine (Cr) levels were measured, while stool lipid species were analyzed using mass spectrometry. Intestinal permeability was assessed using sucralose and 13C2 oxalate gastric gavage in SAMP1 and AKR mice. Histology, qPCR, and Western blotting were performed on kidney, liver, and GI tissues. Microbial DNA was analyzed at the community, genus, and functional levels. Changes in bacterial metabolic pathways were investigated in the mice fed the highest fat content. The oxalobiome of SAMP1 and AKR mice was characterized using our bioinformatics pipeline. On high-fat diets, SAMP1 mice had higher UOx, POx, and PCr levels than AKR mice. Increased levels of diacylglycerols and free fatty acids in SAMP1 stool samples suggested fat malabsorption. A decrease in ZO1 and occludin intestinal expression, coupled with significantly increased urinary sucralose and oxalate levels, indicated increased intestinal permeability. Microbiome analysis revealed the enrichment of Lactobacilli and Bacteroides in SAMP1 mice, with bacterial pathways favoring lipid synthesis and glyoxylate metabolism. Ileal SLC26A6 protein expression was significantly reduced in SAMP1 mice. SAMP1 mice also developed progressive kidney injury with interstitial inflammation. These findings highlight fat malabsorption as a central pathophysiologic disturbance in EH that reduces luminal calcium availability for oxalate binding, is associated with enhanced intestinal permeability, and accompanies microbiome and enzymatic pathway alterations.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease characterized by hepatic steatosis, inflammation, and fibrosis, which can ultimately lead to cirrhosis and hepatocellular carcinoma. Although recent Food and Drug Administration approvals of resmetirom and semaglutide mark a milestone in MASH therapy, no approved agents directly target hepatic inflammation or fibrosis, underscoring the urgent need for novel therapeutic strategies. Hepatocyte death is a histological hallmark that distinguishes MASH from simple steatosis, yet the mechanisms by which it drives chronic inflammation and fibrosis remain incompletely understood. We identified hepatic crown-like structures (CLSs), aggregates of macrophages surrounding dead hepatocytes, as the histological hub of this process. In steatotic livers, impaired dead cell clearance allows sustained macrophage-dead cell interactions within CLSs, where tissue-resident macrophages acquire profibrotic properties. Cholesterol accumulation in hepatocytes promotes cholesterol crystallization, triggering hepatocyte death and subsequent lysosomal cholesterol overload in CLS-constituting macrophages, thereby accelerating inflammation and fibrosis. Targeting this pathway using a liver-tropic supramolecular β-cyclodextrin polyrotaxane (βCD-PRX), which selectively delivers βCD to lysosomes via endocytosis, ameliorated macrophage lysosomal stress and hepatic fibrosis in murine MASH models without affecting body weight or steatosis. Beyond the liver, CLS-driven chronic inflammation contributes to adipose tissue dysfunction in obesity and the transition from acute kidney injury to chronic kidney disease, suggesting broad therapeutic relevance. Continued investigation of CLSs as a shared pathological microenvironment across metabolic diseases may pave the way for novel diagnostic and therapeutic modalities for MASH and related conditions.

Acute kidney injury (AKI) was a common clinical emergency with serious complications, and its treatment remains challenging. Here, we designed a biocompatible, ultrasound-captured nanomachine (NTMCH) that proactively delivered carbon monoxide (CO) under ultrasound. This system achieved kidney protection and enhanced renal clearance in a mouse model of AKI. The nanomachine was fabricated by coating niobium on one side of amine-functionalized mesoporous TiO2, followed by dimanganese decacarbonyl (Mn2(CO)10) loading and hyaluronic acid modification. Asymmetric CO release both propelled the nanomachine and acted as a therapeutic gas. At the kidney injury site, ultrasound triggers CO release, which stimulates ROS generation from mesoporous titanium dioxide (MTD), cascading Mn2(CO)10 activation. This enhanced CO diffusion and renal clearance in synergy with Nb. This ultrasound-responsive nanomachine offered outstanding potential for kidney protection via CD44 regulation, with findings that could advance future clinical development.

This review starts with the historical background and biological features to classify mainly the liquid biopsy biomarkers, such as circulating tumor DNA, circulating tumor cells, extracellular vesicles, non-coding RNAs, tumor-educated platelets and tumor-associated antigens, and also summarizes the present classification approaches and advanced detection techniques for each biomarker type. On this basis, the potential clinical uses of liquid biopsy in oncology are discussed in detail, including the early cancer detection, the prediction of the responses to chemotherapy, radiotherapy and immunotherapy, the evaluation of the treatment effects, the monitoring of the residual diseases and the investigation into the tumor heterogeneity and the resistance mechanisms. Moreover, the discussion is extended to other non-oncological fields, involving the reproduction medicine, the transplantation medicine, the neurological disorders, the infectious diseases and various chronic diseases such as the metabolic dysfunction-related liver disease and fibrosis, pulmonary fibrosis, lupus nephritis and renal fibrosis as well as rheumatoid arthritis. Finally, based on the comprehensive summary given above, this review summarizes the current status of the research on liquid biopsy, points out the main obstacles which hinder its wide application in clinic, for example, the absence of standard procedures and the necessity of large-scale prospective validation, and suggests possible future trends like the integration of multi-omics, the use of artificial intelligence in the analysis and the approach towards routine clinical practice.

Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease fueled by abnormal immune responses and metabolic dysregulation, often leading to life-threatening lupus nephritis (LN). While Cyclosporine A (CsA) is a potent therapeutic agent, its clinical utility is severely constrained by systemic off-target toxicity and the necessity for frequent, high-dose administration. This study evaluates P2Ns-GA-CsA, a receptor-mediated, targeted nanoparticle formulation designed to modulate the core immune-metabolic axis in LN. Using an NZBWF1/J murine model, the administration of P2Ns-GA-CsA achieves enhanced renal protection compared to conventional oral CsA (Neoral), effectively suppressing serum creatinine, clusterin, and proinflammatory cytokines while preserving renal histoarchitecture. This therapeutic efficacy is realized with less than half the dosing frequency of the clinical standard, requiring 42 doses versus 98 doses over a 14 week period. Mechanistically, P2Ns-GA-CsA treatment is associated with the restoration of gut microbial homeostasis through the enrichment of protective taxa (Lactobacillus and Muribaculaceae), facilitating a metabolic shift. This modulation of the gut-microbial metabolic axis promotes the anti-inflammatory indole pathway while suppressing the pathogenic indoleamine 2,3-dioxygenase 1 (IDO1)-kynurenine pathway. These findings demonstrate that this targeted nanotherapeutic strategy decouples the immunosuppressive benefits of CsA from its systemic toxicity while restoring gut-renal integrity in autoimmune disorders.

Chronic kidney disease (CKD) is increasingly recognized as a model of accelerated biological aging, characterized by premature cardiovascular disease and frailty. Although frailty has become a cornerstone of gero-nephrology, current frailty models primarily emphasize physical performance and functional decline, providing limited insight into the vascular mechanisms underlying biological vulnerability. Conversely, vascular aging is traditionally framed within cardiovascular medicine, with little integration into contemporary frailty research, limiting our understanding of how vascular dysfunction contributes to biological aging in CKD. In this review, we propose vascular frailty as a unifying framework that bridges geroscience, nephrology, and vascular medicine. We summarize the mechanisms through which CKD accelerates vascular aging and discuss vascular reserve and vascular resilience as key biological concepts linking vascular aging to systemic frailty. This underlies our claim that vascular frailty could be a multidimensional phenotype integrating structural vascular remodeling, functional vascular impairment, and conventional frailty assessment. Emerging approaches for operationalizing vascular frailty through vascular imaging, physiological assessment, and biomarker profiling are also highlighted. Rather than representing another frailty subtype, vascular frailty provides a conceptual framework linking vascular aging, loss of vascular reserve, and systemic vulnerability in CKD. Emerging evidence supports the feasibility of integrating structural and functional vascular measures with conventional frailty assessment, although its incremental prognostic and clinical value remain to be established. Further longitudinal and interventional studies are needed to determine whether vascular frailty can contribute to risk stratification, individualized management, and strategies aimed at preserving vascular resilience in CKD and other aging-related conditions.