The high prevalence and substantial burden of kidney diseases necessitate advanced approaches to elucidate molecular mechanisms and promote precision medicine. Mass spectrometry (MS)-based proteomics has evolved into a widely used analytical platform, delivering high-sensitivity, high-throughput protein profiling capabilities that have contributed substantially to biomarker discovery, mechanistic dissection, and therapeutic target identification across a broad range of kidney diseases. This review provides a comprehensive overview of MS-based proteomics applications in kidney disease research, covering progress in biomarker identification, pathogenic mechanism interrogation, and clinical translation. It highlights methodological advances, emerging trends, and persistent challenges that shape the field. Existing literature has uncovered abundant disease-specific biomarkers and revealed key pathogenic pathways, including podocyte injury-associated protein interaction networks, dysregulated complement activation, and metabolic reprogramming, and have critically assessed their translational potential. Additionally, investigations into posttranslational modifications such as phosphorylation and glycosylation have provided valuable insights for targeted therapies. Collectively, these findings illustrate the contributions of MS-based proteomics to the characterization of disease molecular heterogeneity, the identification of key pathogenic drivers, and the development of precision medicine approaches. This review further addresses current challenges in clinical applications, including sample heterogeneity, data complexity, and standardization issues. We additionally emphasize the critical need for minimum reporting standards and multicenter harmonization to accelerate the clinical translation of renal proteomics. Future research should focus on integrating multiomics and artificial intelligence-driven data mining to enhance precise disease subtyping, dynamic monitoring, and personalized treatment strategies.

Kidney diseases present substantial clinical challenges, with aberrant glycoproteins emerging as key pathogenic drivers. Minor glomerular abnormalities (MGAs), a category of unclassified glomerular lesions defined by subtle structural changes, are commonly detected in patients with persistent, asymptomatic, isolated proteinuria or microhematuria. Still their site-specific N-glycosylation patterns remain unexplored. To address this gap, a laboratory-developed pressure cycling technology-based quantitative glycoproteomics workflow was applied to compare intact N-glycopeptides (IGPs) among distant non-neoplastic tissues (DNTs; n = 24) and trace renal biopsy samples from MGA patients (n = 27). Integrated with high-resolution mass spectrometry, 672 upregulated IGPs (FC > 1.5, p < 0.05) and 573 downregulated IGPs (FC < 0.67, p < 0.05) in MGA tissues were quantified. Compared with DNTs, 24 glycoproteins associated with the PI3K-Akt signaling pathway exhibited broadly elevated IGP abundances in MGA samples. Site-specific N-glycosylation analysis further revealed distinct patterns among IgG subclasses and complement-related markers that distinguish MGA from DNT, offering new mechanistic insights into MGA pathogenesis. These novel glyco-signatures clarify the role of N-glycosylation in renal disease and validate this workflow as a powerful tool for trace-tissue analysis. This study lays the groundwork for translating N-glycosylation findings into clinical applications to improve MGA diagnosis and management.

The discovery of glycoRNAs—RNAs covalently conjugated to complex glycans—is a transformative development that establishes a new class of epitranscriptomic modifications, challenging the longstanding perception that glycosylation is restricted to proteins and lipids. This rapidly advancing field has seen methodological evolution from early-stage metabolic labeling and click chemistry to highly selective enrichment techniques, such as SPCgRNA (for N-glycoRNAs) and TnORNA (for O-glycoRNAs), and now leverages breakthroughs in spatial and single-cell analysis—such as ARPLA for single cells, drFRET for small extracellular vesicles (sEVs), and SUGAR-seq for multi-omics integration—to allow for high-resolution profiling alongside the transcriptome and proteome. Structurally, the covalent attachment of N-glycans to the modified uridine acp3U on tRNAs has been confirmed, while O-glycans constitute a major and heterogeneous component of the glycoRNA landscape; functionally, glycoRNAs are emerging as critical regulators in immunology and disease, mediating processes like neutrophil recruitment via surface display and acting as ligands for receptors like P-selectin (SELP) and Siglec-5. They also exhibit a dual role in innate immunity, both triggering immune responses and providing N-glycan "shielding" to prevent the aberrant activation of innate immune sensors like TLR3 and TLR7. Despite these foundational discoveries, challenges persist, including resolving interference from glycoprotein signals and developing a universal O-glycan endoglycosidase; however, given their extracellular location, strong correlation with disease, and promising clinical performance, glycoRNAs hold significant potential as highly accurate diagnostic biomarkers and macromolecular therapeutic targets in oncology, cardiovascular disease, and inflammation.

Sonodynamic therapy (SDT), which involves the use of sonosensitizing agents under ultrasound (US) irradiation, is an effective treatment modality for enhancing immune responses in cancer therapy and is also known as sonoimmunotherapy. This study developed a US-responsive biocatalytic system based on a single-atom copper polyphthalocyanine network (poly(CuPc)), leveraging its it-conjugated structure for efficient treatment of breast cancer. Poly(CuPc) exhibits peroxidase-like activity in the tumor microenvironment (TME), catalyzing the production of cytotoxic center dot OH and center dot O2- from endogenous H2O2. Its narrow band gap also enhances sonosensitivity, promoting the generation of 1O2 under US irradiation. The platform operates through three main mechanisms: (1) ROS production induces tumor cell death via immunogenic cell death (ICD), leading to dendritic cell activation. (2) It promotes macrophage polarization, increases T cell infiltration, and upregulates pro-inflammatory cytokines, thereby strengthening antitumor immunity and fostering immune memory. (3) In combination with anti-PD-L1 (aPD-L1), it enhances ICD and reprograms the TME, effectively eliminating primary tumors, suppressing metastasis, and inducing robust antitumor immunity along with long-term immune memory. This work provides a conceptual framework for designing high-performance, biocompatible platforms aimed at remodeling the immunosuppressive TME and overcoming PD-L1-mediated immune evasion, offering a viable strategy for clinical translation in breast cancer treatment.

Glycosylation is one of the most common protein post-translational modifications (PTMs) and plays a critical role in regulating various biological functions by influencing protein folding, trafficking, and subcellular localization. Aberrant glycosylation patterns are closely associated with the onset and progression of numerous health conditions, including cancer, inflammation, autoimmune disorders, and other diseases. Glycoproteomics, as a key field dedicated to studying protein glycosylation, has demonstrated increasingly significant value in the discovery of disease biomarkers and the investigation of underlying pathogenic mechanisms. Human body fluids serve as a crucial “window” into disease information, with their glycoproteomes harboring rich pathophysiological insights. Mass spectrometry (MS) is a powerful tool for deciphering the glycoproteome of body fluids. In this review, a concise overview of the types and biological processes of glycosylation was provided, followed by an introduction to MS-based glycoproteomic workflows. Recent advances in MS-based glycoproteomic studies involving various human body fluids, such as blood, urine, cerebrospinal fluid, tears, seminal plasma, milk, and saliva, were summarized with emphasis on current research regarding the types, abundance, and structural features of glycoproteins and glycans identified in these fluids. Furthermore, trends in glycosylation alterations under disease conditions and potential glycoprotein-or glycan-based biomarkers and therapeutic targets that have been discovered were highlighted. This review aims to offer a comprehensive perspective and reference for understanding the role of fluid-based glycoproteomics in disease and facilitating its clinical translation.

Biocatalytic generation of reactive oxygen species (ROS) by artificial enzymes offers a promising strategy for treating diverse diseases, including pathogenic infections and malignancies. However, the sluggish ROS biocatalytic efficiency and unstable active sites have hindered their potential clinical translation. Here, inspired by natural vanadium haloperoxidases and NADPH oxidase-based ROS-catalytic systems, we report the de novo design of a sono-activated artificial vanadium enzyme (Vx+-SonoAE) for efficient and renewable ROS nanobiocatalytic therapies. By mimicking the electron transport chains and active VO4 centers in natural enzymes, our innovative bionic approach not only yields efficient, robust, and precise vanadium active sites on TiO2 but also enables continuous regeneration of redox centers during ROS biocatalysis via efficient electron transfer from sono-activated TiO2 to the Vx+ site. Consequently, the Vx+-SonoAE achieves remarkable ROS-catalytic performance with a superior turnover number (TON = 54 × 10-3 s-1) that far surpasses the reported state-of-the-art metal oxides-based nanobiocatalysts. Moreover, this new artificial enzyme system demonstrates exceptional therapeutic efficiency in infection control and tumor regression with sustained and sono-activated treatment properties. This work establishes a new paradigm for designing efficient and renewable nanobiocatalysts, combining fundamental insights from natural enzymatic systems with advanced materials engineering to create robust therapeutic platforms with long-term efficacy.

BackgroundAmyloidosis is a group of heterogeneous diseases characterized by the deposition of amyloid fibrils in various organs and tissues. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults.Case presentationWe report three cases of early-stage MN occurring concurrently with distinct types of renal amyloidosis: apolipoprotein A-I (AApoA-I) amyloidosis, leukocyte chemotactic factor 2 (ALECT2) amyloidosis, and monoclonal immunoglobulin light-chain (AL) amyloidosis. Each case represents a different pathogenic mechanism, therapeutic approach, and clinical prognosis.ConclusionsThese cases underscore the pivotal role of renal pathology in the accurate diagnosis of patients with coexisting amyloidosis and MN. Correct classification of renal amyloidosis is essential for guiding therapy and predicting outcomes. When amyloidosis coexists with MN or other potentially treatable renal diseases, therapeutic decisions should prioritize the condition with the greater potential for organ damage or the one most responsive to available treatment.

Background Minor glomerular abnormalities (MGAs) are histopathologically heterogeneous renal lesions with subtle structural changes and latent clinical manifestations, yet their molecular mechanisms remain poorly characterized and underexplored. Methods In this study, we employed pressure cycling technology-assisted sample preparation combined with data-independent acquisition mass spectrometry to systematically compare the proteomic profiles of distant non-neoplastic tissues (n = 24) and MGA tissues (n = 27). Results A total of 9 529 protein groups were quantified with a false discovery rate < 1%, and 1 338 differentially expressed protein groups were identified (fold-change > 2 or < 0.5, P < 0.05), including 190 downregulated and 1 148 upregulated protein groups in MGA tissues. Gene ontology analysis revealed that the downregulated proteins were enriched in cell adhesion, ion binding, and molecular transport, whereas the upregulated proteins were enriched in transcriptional regulation, DNA replication/repair, and nucleic acid binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated inhibition of metabolic pathways and the peroxisome proliferator-activated receptor signaling pathway, as well as the activation of basal transcription factors and nucleotide excision repair in MGAs. Further screening revealed 13 core upregulated nuclear proteins (e.g. YY1, TAF9, RFC1, and POLR1D) with a >90% detection rate in MGA tissues; these proteins are functionally associated with renal inflammation, cell proliferation, and the DNA damage response. Conclusion Our study establishes a high-resolution proteomic landscape of MGAs, provides novel insights into their molecular pathogenesis, and identifies potential tissue biomarkers and therapeutic targets. The pressure cycling technology-assisted data-independent acquisition workflow also offers a robust technical framework for proteomic analysis of microscale renal biopsy samples.

Self-assembly of fenugreek polysaccharides FS60 (a natural macromolecular material) with curcuminoid has been proved to improve curcumin (Cur) water dispersion in preliminary studies. This study further explored the effect of FS60 on Cur bioavailability in vivo to assess the significance of this delivery method. In this study, we optimized the formulation parameters of FS60-curcuminoid aggregates (FC) and studied their effects on Cur pharmacokinetics in rats. Results showed that the optimized aggregates had an encapsulation efficiency (EE) of 88.22 % and hydrodynamic diameter (DH) of 231.48 nm. Additionally, administering FC significantly increased curcumin glucuronide (Cur-O-Glu) levels. The C max was 51 times higher and AUC 0-12h was 19 times higher than curcuminoid alone. Moreover, FS60 intervention for seven days increased the absorption speed of Cur-O-Glu into the bloodstream. Further mechanistic studies indicated that FS60 promoted Cur ingestion, increased UGT expression, and inhibited enterocyte transporters, allowing large amounts of Cur-O-Glu to enter the bloodstream. Moreover, the gut microbiota modulated by FS60 accelerated the mutual conversion of pentose and gluconate to provide sufficient glucuronic acid for the glucuronidation of Cur in enterocytes. Consequently, the nano delivery system composed by FS60 and curcuminoid facilitated gastrointestinal Cur glucuronidation and Cur-O-Glu absorption.

Wound healing is a dynamic and continuous process. Hydrogels, as three-dimensional polymeric networks, have emerged as versatile platforms for tissue repair due to their tunable mechanical properties, environmental responsiveness, and diverse application forms. Despite extensive research, the mechanisms by which hydrogel properties regulate cellular interactions and tissue regeneration remain poorly understood. While hydrogels have demonstrated good biocompatibility in animal models, further research is needed to translate these findings to human chronic wound healing. Existing reviews largely focus on material characteristics or single bioactive agents, with limited discussion of integrated multifunctional design strategies. Recent studies demonstrate that diversified hydrogel designs and functionalities can effectively enhance wound healing, including accelerated healing and disease-specific applications. This review systematically summarizes these advances, emphasizing the relationships between hydrogel properties, their functional roles in tissue repair, and their application across pathological contexts, providing insights to guide the rational design and clinical translation of next-generation hydrogel-based wound dressings.

In recent years, mRNA vaccine has achieved increasing interest owing to its high potency, safety, ease of production, and low-cost manufacturing. Currently approved mRNA vaccines are administered intramuscularly to transfect local antigen-presenting cells (APCs) to initiate low to moderate immune responses. Spleen, the largest secondary lymphoid organ in the body which contains a large number of APCs close to B and T lymphocytes, could be the ideal site for effective initiation of an enhanced immune response. Here, we provide an overview of the recent advances in the development of synthetic materials for spleen-specific mRNA delivery, and lipid nanoparticle-based approaches will be highlighted. We further discuss the main challenges for spleen-specific mRNA delivery to provide a reference for the development of next-generation synthetic nanomaterials with optimal properties.

The impact of drying temperature on peanut quality and flavor is established, but specific effects require further exploration. This study investigated the influence of drying at 35 f 1 degrees C and 65 f 1 degrees C on the flavor and quality of Shuhua 9 peanuts using HC-GC-IMS, untargeted metabolomics, and TMT-based proteomics. Results showed that drying at 65 f 1 degrees C accelerated lipid oxidation compared to 35 f 1 degrees C, causing greater fatty acid degradation and increased flavor compounds production. Moreover, higher ethanol and ethyl acetate levels, potentially contributing to off-odors, were also observed. Metabolomics identified fatty acid degradation as a key pathway affected by drying temperature. Separately, proteomic analysis revealed significant upregulation of proteins involved in stress responses and antioxidant defense, particularly those related to arginine and proline metabolism. Integrated analysis further highlighted the crucial roles of these pathways in shaping peanut flavor and quality under different drying conditions. These findings provide valuable insights for optimizing peanut drying processes in the industry.

Purpose To assess the impact of prolonged and intense exposure to video display terminals (VDTs) on ocular surface homeostasis. Methods 30 subjects limited daily VDT usage to less than 3 h for one week, then extended usage to more than 8 h/day for the next three weeks. Ocular symptoms and signs were evaluated weekly using the Ocular Surface Disease Index (OSDI) questionnaire and clinical examinations. Eyelid margins and meibomian glands were examined, and ocular surface samples were collected for transcriptomic analysis. Results Average daily VDT time increased from 2.55 ± 0.46 h initially to 11.17 ± 2.45, 11.75 ± 2.63, and 10.89 ± 2.41 h over three weeks. The dry eye diagnosis rate rose from 6.67 % to 51.67 %. Total OSDI score (P = 0.008), symptoms score (P = 0.014), and visual function score (P = 0.002) significantly increased. Mean fluorescein break-up time (FBUT) decreased from 6.46s to 3.08s. Corneal fluorescein staining (CFS) score (P < 0.001) and lissamine green conjunctival staining (LCjs) score (P = 0.036) worsened. Ocular redness index (RI) increased at 1 week and 3 weeks (P = 0.007, P = 0.001). Telangiectasia scores of both upper and lower eyelid margins increased at 3 weeks (P = 0.002, P < 0.001). Meibomian gland orifice blockage worsened (P = 0.014, P = 0.002). Transcriptomic analysis revealed dynamic alterations in ocular surface gene expression, including inflammatory and hormonal responses. MUC5AC and TFF1 genes showed negative correlations with OSDI and conjunctival staining score, respectively. Conclusion Prolonged VDT exposure deteriorates ocular surface symptoms and signs, with significant inflammatory responses and hormonal activity indicating an imbalance in ocular surface homeostasis.

During cancer peritoneal metastasis (PM), conventional antigen-presenting cells (dendritic cells, macrophages) promote tumorigenesis and immunosuppression in peritoneal cavity. While intraperitoneal immunotherapy (IPIT) has been used in clinical investigations to relieve PM, the limited knowledge of peritoneal immunocytes has hindered the development of therapeutic IPIT. Here, a dendritic cell-independent, next-generation IPIT is described that activates peritoneal cavity B (PerC B) cell subsets for intraperitoneal anti-tumor immunity via exogenous antigen presentation. The PerC B-cell-involved IPIT framework consists of an isotropic-porous, cell-fitting, thermogenetics-based CXCL12 generator. Such nanoscale thermal-confined generator can programmatically fine-tune the expression of CXCL12 to recruit disseminated tumor cells (DTCs) through CXCL12-CXCR4 axis while avoiding cytokine storm, subsequently release DTC-derived antigen to trigger PerC B-cell-involved immunity. Notably, antigen-presenting B-cell cluster, expressing the regulatory signaling molecules Ptpn6, Ms4a1, and Cd52, is identified playing the key role in the IPIT via single-cell RNA sequencing. Moreover, such IPIT availably assuages peritoneal effusion and PM in an orthotopic gastric cancer and metastatic model. Overall, this work offers a perspective on PerC B-cell-involved antigen-presenting in intraperitoneal immunity and provides a configurable strategy for activating anti-DTC immunity for next-generation IPIT.

Central venous catheters are commonly used for hemodialysis, but prolonged use can lead to complications such as central venous occlusion, resulting in catheter-dependent dialysis patients being unable to undergo dialysis. Herein, we present the case of a 57-year-old female patient who had been dependent on catheter-based hemodialysis for 8 years. Her tunneled central venous catheter (TCC) had been replaced three times and she had developed severe central venous occlusion. For this patient, a procedure was performed involving a percutaneous puncture through the site of superior vena cava occlusion to gain access to the right atrium. The intervention utilized multiple surgical instruments, including a transseptal needle in combination with the stiffening cannula from the RUPS-100 Suite, to facilitate re-catheterization for maintenance hemodialysis. We discuss the feasibility of such procedures as a last-resort option while emphasizing the associated risks.

Cisplatin resistance is a major cause of poor prognosis in patients with cervical cancer. Dysregulation of long noncoding RNAs (lncRNAs) plays a key role in chemoresistance. Our results reveal that the lncRNA UCA1 is upregulated in cisplatin (DDP)-resistant cervical cancer tissues and HeLa cells. Mechanistically, the lncRNA UCA1 acts as a sponge for miR-195-5p, targeting IKBKB. UCA1 enhances proliferation, migration, and invasion while reducing apoptosis in DDP-resistant HeLa cells via the miR-195-5p/IKBKB axis. Additionally, UCA1 upregulates BNIP3Δex2 and p-p65 expressions and downregulates BNIP3 expression in DDP-resistant HeLa cells. Abnormal expressions of BNIP3Δex2 and BNIP3 significantly alter the malignant progression of HeLa/DPP cells. In vivo, UCA1 silencing inhibits growth, enhances apoptosis, and upregulates IKBKB, BNIP3Δex2, and p-p65 expressions while downregulating BNIP3 expression in subcutaneous xenografts in nude mice by targeting miR-195-5p. Overall, this study highlights a novel promising target for the treatment of DDP-resistant cervical cancer.

Paocai is valued for its palatable taste and potential health benefits, but faces challenges such as prolonged fermentation periods and inconsistent quality. This study addressed these issues by investigating the effects of Lactiplantibacillus plantarum CBPC, a strain isolated from high-quality fermented paocai, on radish paocai fermentation and comparing its performance to a control group. The aim was to enhance fermentation efficiency, improve flavor, and ensure product safety. Physicochemical properties, flavor characteristics, and safety indicators were systematically analyzed, and shelf-life extension was evaluated using electron beam (e-beam) irradiation. Results revealed that inoculation with Lactiplantibacillus plantarum CBPC significantly accelerated fermentation, achieving full fermentation two days earlier than the control, reduced yellowing (Delta E > 5), and decreased nitrite levels. Inoculated fermentation also enriched the flavor profile by increasing concentrations of lactic acid, oxalic acid, glutamic acid, proline, arginine, rhodinol, and camphene hydrate, resulting in enhanced taste and aroma. Furthermore, e-beam irradiation effectively controlled microbial load and maintained stable pH and nitrite levels over 60 days of storage, ensuring long-term safety and quality. This study highlights the practical potential of combining inoculated fermentation and e-beam irradiation to produce high-quality, safe radish paocai.

ETHNOPHARMACOLOGICAL RELEVANCE:Wuwei Leze Powder (WLP, སླྱེ་ཏྱེསལྔ་ཐང།) is a classic Traditional Tibetan medicine formula, which has certain clinical efficacy for rheumatoid arthritis (RA). Nevertheless, the pharmacological effects and potential therapeutic mechanisms of WLP on RA remain unclear. AIM OF THE STUDY:The present study aimed to investigate the potential pharmacological mechanisms of anti- RA effect of WLP. MATERIALS AND METHODS:The chemical constituents of WLP were analyzed by UPLC-Q-TOF-MS. A collagen-induced arthritis (CIA) rat model was established to evaluate the swelling, arthritis index. Pathohistological staining and micro-CT were employed to evaluate the therapeutic effects of WLP. Subsequently, serum metabolomic analysis was conducted to elucidate the potential biomarkers and pathways. Finally, an enzyme-linked immunosorbent assay, along with immunofluorescence, RT-qPCR and western blotting, were utilized to verify the anti-RA mechanism of WLP. RESULTS:A total of 109 chemical constituents from WLP were identified by UPLC-Q-TOF-MS. WLP reduced paw swelling, arthritis scores and organ index in the CIA rat model. Histopathological staining and micro-CT observed WLP possesses both anti-inflammatory and bone-protective properties. Subsequently, serum metabolomics identified 12 potential biomarkers, mainly related to amino acid metabolism and the mTOR signaling pathway. ELISA showed that WLP can regulate abnormal levels of inflammatory cytokines (IL-4, IL-10, TNF-α, IL-6, INF-γ and IL-17). Immunofluorescence demonstrated that WLP could regulate the expression of MMP-1, MMP-9, MMP-13 and RANKL. The effect of WLP on the expression of Wnt3a, Wnt10b, β-catenin, RANKL, OPG, p65 and MMP-9 were verified using RT-qPCR and WB, thereby elucidating the anti-arthritis mechanism of WLP. CONCLUSION:The possible mechanism underlying the anti-RA of WLP involves the downregulation of the Wnt/RANKL/NF-κB axis, the restoration of abnormal host metabolite levels, the suppression of synovitis responses, and the attenuation of bone erosion. Considering the high variability of plant materials, the present study takes a batch of WLP as an example, which inevitably has limitations.

A bidirectional nucleus-mitochondria communication is essential for homeostasis and stress. By acting as critical molecules, the nuclear-encoded lncRNAs (nulncRNAs) have been implicated in the nucleus-to-mitochondria anterograde regulation. However, role of mitochondrial-derived lncRNAs (mtlncRNAs) in the mitochondria-to-nucleus retrograde regulation remains elusive. Here, we identify functional implication of the mtlncRNAs MDL1AS, lncND5 and lncCyt b in retrograde regulation. Mediated by HuR and PNPT1 proteins, the mtlncRNAs undergo a mitochondria-to-nucleus traveling and then regulate a network of nuclear genes. Moreover, as an example of the functional consequence, we showed that the nuclear-translocated lncCyt b cooperates with the splicing factor hnRNPA2B1 to influence several aspects of cell metabolism including glycolysis, possibly through their regulatory effect on the post-transcriptional processing of related nuclear genes. This study advances our knowledge in mitochondrial biology and provides new insights into the role of mtlncRNAs in mitochondria-nucleus communications.