Cisplatin-induced acute kidney injury (AKI) remains a serious clinical complication, with excessive reactive oxygen species (ROS) recognized as key contributors. The natural antioxidant epigallocatechin-3-gallate (EGCG) shows promise in mitigating oxidative stress-related damage. However, its clinical application is limited by poor stability and low renal bioavailability. To address this, we developed a biocompatible nanoplatform by encapsulating EGCG within mesoporous polydopamine nanoparticles (EGCG-MPDA). Ultrasmall nanoparticles (<10 nm or <20 kDa) undergo rapid glomerular filtration and renal clearance, limiting therapeutic retention. While uncoated MPDA nanoparticles (∼200 nm) are large enough to avoid renal filtration, their size renders them highly susceptible to opsonization and MPS sequestration. To address this MPS-mediated clearance, we coated MPDA with a preclinically used BSA shell to create EGCG-MPDA@BSA. The biocompatible BSA corona acts as a "stealth" layer to attenuate opsonization, reduce early hepatic sequestration, and enhance interactions with peritubular endothelial cells, promoting nanoparticle passage into injured tubular epithelial cells. In a murine cisplatin-induced AKI model, EGCG-MPDA@BSA exhibited significantly enhanced therapeutic efficacy compared to uncoated nanoparticles and free EGCG. Transcriptomic and biochemical analyses revealed that its superior therapeutic efficacy arises from the activation of the Nrf2/HO-1/GPX4 antioxidant pathway, thereby alleviating oxidative stress, inflammation, and tubular damage. Collectively, this work presents an albumin corona strategy that enables effective renal retention of large nanoparticles, offering a safe, translatable approach for localized AKI therapy.

This study elucidates the antiobesity mechanism of the Fu brick tea extract-millet complex (FTE-M). FTE-M exhibited a dense and smooth microstructure, resulting in improved digestive properties compared with millet alone, including a reduced glycemic index and increased slowly digestible starch and resistant starch contents. In a 10-week high-fat diet mouse model, dietary supplementation with FTE-M inhibited small intestinal α-amylase activity, delayed starch digestion, and improved glucose and lipid metabolism while alleviating inflammation. FTE-M also modulated gut microbiota composition, normalized bile acid profiles, and enriched short-chain fatty acids (SCFAs)-producing bacteria, including Akkermansia, leading to a 2.49-fold increase in total SCFAs. Mechanistically, elevated SCFAs were associated with the activation of free fatty acid receptor 2 (Ffar2) and increased expression of glucagon (Gcg) and peptide YY (Pyy), contributing to enhanced satiety. These findings highlight the potential of combining traditional millet with bioactive components to enhance metabolic functionality, providing a theoretical basis for developing starch-based antiobesity foods.

Mitochondrial function plays a critical role in skin aging. Chlorogenic acid (CGA), a botanical compound, has demonstrated regulatory effects on mitochondrial function and senescence inhibition. However, whether the anti-aging effects of CGA are attributable to its regulation of mitochondrial function remains unclear. There is a need to investigate the anti-aging effect and mechanism of CGA by modulating mitochondrial function, particularly its mode of action on mitochondrial function. Normal human dermal fibroblasts and human epidermal keratinocytes were used to detect the regulation of collagen I production, mitochondrial functions, and anti-aging properties of CGA and confirmed by mitochondrial transplantation. The photo-aging mouse model was established by ultraviolet (UV) radiation, followed by the treatment of CGA-gel (1 mmol/kg/d) for 14 days. The skin tissues were collected and tested. CGA promotes collagen I (Col1) production by activating the TGF-β/Smad signaling pathway, while concurrently inhibiting cellular senescence. CGA administration significantly reduced the expression of p21, senescence-associated secretory phenotype (SASP) production, and SA-β-Gal activity in skin cells. Additionally, CGA treatment notably enhanced mitochondrial function, improving disrupted mitochondrial cristae in senescent cells and boosting the oxidative phosphorylation (OXPHOS) process. ATP levels increased by approximately 40–80

Mitochondrial targeting represents a promising antitumor strategy by modulating cell differentiation, metabolic reprogramming, and immune responses. While chlorogenic acid (CGA) has demonstrated the ability to induce tumor cell differentiation and enhance antitumor immunity, the involvement of mitochondrial regulation in these effects remains unclear. This study investigated whether CGA mediates antitumor immune effects through mitochondrial regulation, thereby providing a theoretical framework for natural product-based, mitochondria-targeted therapies. Our findings reveal that CGA inhibits the translocation of mitochondrial transcription factor A (TFAM) into the mitochondria and promotes mtDNA leakage by disrupting the ATF5-mtHSP70 signaling axis. The cytosolic leakage of mtDNA activates the cGAS/STING pathway, triggering the activation of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), which ultimately facilitates antitumor immunity. In a mouse model, ATF5 knockout enhances cGAS/STING signaling and subsequent immune responses, leading to tumor growth inhibition. These results highlight a novel role of CGA in regulating mitochondrial-associated proteins, positioning it as a potential therapeutic strategy for cancer via the mtDNA-cGAS-STING pathway.

Artemisia argyi (A. argyi) is a Chinese herbal medicine with reported anti-inflammatory effects. In this study, the A. argyi was extracted with water and ethanol, and the concentrations of 35 flavonoids in A. argyi water extract (WE) and ethanol extract (EE) were measured via targeted metabolomics. The antioxidant and anti-inflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment, respectively. Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), & centerdot;OH, and O2 & centerdot; radical scavenging ability in a dose-dependent manner, and reduced the levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-22 (IL-22) in lipopolysaccharide (LPS) induced RAW264.7 cell model. In addition, the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium (DSS)-induced colitis mice, and the underlying mechanisms were elucidated by 16S rDNA sequencing and targeted metabolomics. We found that both WE and EE relieved colitis in mice, characterized by decreased disease activity index, increased colon length, improved pathological changes in colon tissue, while EE showed better anti-colitis activity. In addition, both 16S rDNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid (LCA), which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor (FXR). In summary, this study identified the anti-colitis mechanism of A. argyi EE by modulating gut microbiota, facilitating the production of LCA, activating FXR and improving intestinal barrier function.

Fat deposition significantly influences both carcass composition and meat quality; however its molecular regulation is highly complex and displays pronounced variation across tissues and genetic backgrounds. Integrating transcriptomic data from multiple tissues and populations can help identify conserved regulatory programs that distinguish lean-type commercial pigs from fat-type indigenous pigs. This study aimed to combine transcriptomic datasets across multiple studies and tissues with differential expression analysis and gene co-expression network analysis to identify candidate regulators associated with fat deposition. We integrated 814 publicly available RNA sequencing samples from 32 pig populations, including muscle (n = 626), adipose tissue (n = 117) and liver (n = 71). All datasets were reprocessed with a unified workflow for read quality control, alignment and gene quantification, followed by batch-effect adjustment using surrogate variable analysis. Differentially expressed genes (DEGs) between lean-type commercial pigs and fat-type indigenous pigs were identified within each tissue using linear models with empirical Bayes moderation. Multiple testing was controlled by the false discovery rate (0.05), together with an absolute log2-transformed fold change threshold of ≥ 1. Functional enrichment of DEG sets and modules was evaluated using hypergeometric tests based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations. Weighted gene co-expression networks were constructed using Pearson correlations under a scale-free topology criterion, and module–trait associations were assessed by Pearson correlation; hub genes were prioritized by network connectivity and protein interaction information. We identified 1,614 differentially expressed genes in muscle tissue, 4,647 in adipose tissue and 573 in liver between lean-type commercial pigs and fat-type indigenous pigs, respectively. Thirty-six genes were consistently differentially expressed across all three tissues and were enriched for mitochondrial energy metabolism, including oxidative phosphorylation and respiratory chain processes. Co-expression network analysis clustered 19,760 genes into 29 modules and revealed distinct tissue–group associated modules, including Cyan (liver tissue of lean-type commercial pigs), Orange (adipose tissue of fat-type indigenous pigs) and Tan (muscle tissue of lean-type commercial pigs). Integration of shared differentially expressed genes and trait-associated modules prioritized five candidate regulatory genes: ND6, UQCRC1, UQCRFS1, TBXA2R and LIFR. Integrative multi-tissue transcriptomic data with differential expression analysis and co-expression network analysis identified mitochondrial energy metabolism as a central program underlying fat deposition The prioritized candidate genes provide a basis for understanding the molecular regulatory mechanisms underlying fat deposition and may support molecular breeding strategies to optimize carcass traits and meat quality.

Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose-lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR's capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub-axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling.

Importance:Berberine is a potential therapy for metabolic disorders, yet its effects on visceral adipose tissue (VAT) and liver fat remain uncertain. Objectives:To evaluate the efficacy and safety of berberine in reducing VAT area and liver fat content in diabetes-free individuals with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Design, Setting, and Participants:In this multicenter, double-blind randomized clinical trial, diabetes-free individuals with obesity and MASLD were enrolled at 11 hospitals in China between July 6 and December 29, 2023, with a follow-up duration of 6 months. Interventions:Participants were randomly assigned to receive either oral berberine, 1 g/d, or a matching placebo. Main Outcomes and Measures:The primary outcomes were relative percentage change in VAT area and absolute change in liver fat content assessed by computed tomography. Other outcomes included changes in parameters of glucose, lipids, and inflammation. Analyses were conducted according to the intention-to-treat principle. Results:Among 337 randomized participants (mean [SD] age, 41.8 [10.6] years; 221 [65.6%] male), 169 received berberine and 168 placebo. The mean (SD) medication adherence rates were 90.3% (14.7%) for berberine and 90.7% (17.4%) for placebo. No significant differences were observed between study arms for VAT area (1.4% [97.5% CI, -2.4% to 5.2%]) or liver fat content (0.9% [97.5% CI, -0.4% to 2.1%). Berberine was associated with larger reductions in low-density lipoprotein cholesterol (-7.72 [95% CI, -13.13 to -1.93] mg/dL), apolipoprotein B (-3.42 [95% CI, -6.33 to -0.51] mg/dL) and high-sensitivity C-reactive protein (hs-CRP) (-0.072 [95% CI, -0.140 to -0.004] mg/dL) vs placebo, but not other secondary outcomes. The incidence of adverse events was similar between study arms. Post hoc analyses suggested consistent patterns of larger reductions in low-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP levels in participants with higher baseline hs-CRP levels. Conclusions and Relevance:In this randomized clinical trial of diabetes-free individuals with obesity and MASLD, a 6-month berberine treatment at a daily dose of 1 g had an excellent safety profile but did not reduce VAT area or liver fat content. Trial Registration:ClinicalTrials.gov Identifier: NCT05647915.

Objective: This study presented a systematic bibliometric analysis of global treatment research on phenylketonuria (PKU) from 2000 to 2025. The aim is to qualify publication trends, collaboration patterns, thematic evolution, and research gaps, thereby informing future scientific and clinical directions. Methods: This study used the Web of Science Core Collection and searched on September 13, 2025, yielding 1,877 English-language articles and reviews published between 2000 and 2025. Publication trends were analyzed using Microsoft Excel (version 16.101), while VOSviewer 1.6.20 and CiteSpace 6.4 R1 were used to visualize country- and institutional-level collaborations, journal networks, keyword co-occurrence, citation bursts, and thematic clusters. Statistical charts were generated with GraphPad Prism 10.2.1. Results: Annual publication output demonstrated an overall upward trend, peaking in 2022 with 111 publications. The United States led in both publication volume (375 studies) and total citations (11,142 citations), maintaining strong collaborative ties with several European countries, particularly the Netherlands and the United Kingdom. China ranked seventh globally in publication volume, although its citation impact remains comparatively limited. Key institutions, including the University of Birmingham and the University of Copenhagen, as well as prominent scholars such as Francjan J. van Spronsen and Anita MacDonald occupied central positions in global collaboration networks. High-frequency and high-centrality keywords, such as "phenylalanine," "dietary treatment," and "tetrahydrobiopterin," highlighted continued emphasis on metabolic control and targeted therapies. Keyword burst analysis revealed a gradual shift from conventional dietary management toward enzyme replacement therapies, investigations of neurocognitive outcomes, and precision medicine-oriented approaches. Conclusion: Over the past 25 years, PKU treatment research has progressed from foundational dietary interventions to molecular mechanistic studies and individualized therapeutic strategies. Future research should prioritize longitudinal multi-omics investigations, targeted metabolic correction technologies, and enhanced international collaboration, particularly to strengthen diagnosis and management capacities in low- and middle-income regions. Such efforts will be critical to advancing global standards of PKU care. This study presented a systematic bibliometric analysis of global treatment research on phenylketonuria (PKU) from 2000 to 2025. The aim is to qualify publication trends, collaboration patterns, thematic evolution, and research gaps, thereby informing future scientific and clinical directions. This study used the Web of Science Core Collection and searched on September 13, 2025, yielding 1,877 English-language articles and reviews published between 2000 and 2025. Publication trends were analyzed using Microsoft Excel (version 16.101), while VOSviewer 1.6.20 and CiteSpace 6.4 R1 were used to visualize country- and institutional-level collaborations, journal networks, keyword co-occurrence, citation bursts, and thematic clusters. Statistical charts were generated with GraphPad Prism 10.2.1. Annual publication output demonstrated an overall upward trend, peaking in 2022 with 111 publications. The United States led in both publication volume (375 studies) and total citations (11,142 citations), maintaining strong collaborative ties with several European countries, particularly the Netherlands and the United Kingdom. China ranked seventh globally in publication volume, although its citation impact remains comparatively limited. Key institutions, including the University of Birmingham and the University of Copenhagen, as well as prominent scholars such as Francjan J. van Spronsen and Anita MacDonald occupied central positions in global collaboration networks. High-frequency and high-centrality keywords, such as "phenylalanine," "dietary treatment," and "tetrahydrobiopterin," highlighted continued emphasis on metabolic control and targeted therapies. Keyword burst analysis revealed a gradual shift from conventional dietary management toward enzyme replacement therapies, investigations of neurocognitive outcomes, and precision medicine-oriented approaches. Over the past 25 years, PKU treatment research has progressed from foundational dietary interventions to molecular mechanistic studies and individualized therapeutic strategies. Future research should prioritize longitudinal multi-omics investigations, targeted metabolic correction technologies, and enhanced international collaboration, particularly to strengthen diagnosis and management capacities in low- and middle-income regions. Such efforts will be critical to advancing global standards of PKU care.

In triple-negative breast cancer (TNBC), chemotherapy-induced immunogenic cell death (ICD) often fails to trigger truly effective antitumor immunity. This failure primarily stems from the simultaneous release of damage-associated molecular patterns (DAMPs) and immunosuppressive prostaglandin E2 (PGE2), creating an intrinsic NOT-AND signaling conflict. This barrier hinders efficient immune priming, a response rarely induced by conventional chemotherapy. To address this conflict while minimizing toxicity, R-Gem@Cel-PV, a spatiotemporally programmed nanovesicle, was designed to impose both spatial localization and sequential signal control within the tumor microenvironment. Following preferential accumulation in tumor tissue, enzymatic disassembly of the nanomedicine triggers the rapid release of celecoxib to suppress local PGE2 signaling and alleviate immune suppression. Subsequently, the delayed activation of a phospholipid-gemcitabine prodrug induces DAMP-releasing cell death. This temporal decoupling—unachievable with free drug combinations—converts gemcitabine from a weak ICD inducer into a potent one. In TNBC models, R-Gem@Cel-PV boosted dendritic cell maturation, orchestrated a robust antitumor immune response, and significantly inhibited both primary tumor growth and metastasis. These findings demonstrate that resolving the immunosignal conflict through precise spatiotemporal control is essential for effective immune engagement in TNBC and offer a generalizable strategy for reprogramming the immune response to chemotherapy in immune-refractory tumors.

Asthma is a chronic inflammatory disease with limited therapeutic options, highlighting the urgent need to explore alternative mechanisms and agents. Chlorogenic acid (CGA), a dietary polyphenol, exhibits anti-asthmatic properties, but its precise molecular mechanisms remain poorly understood. This study aimed to elucidate the mechanistic basis of CGA's anti-asthmatic effects, hypothesizing a central role in regulating polyunsaturated fatty acid metabolism and ferroptosis. An ovalbumin-induced murine asthma model was established in female BALB/c mice to evaluate the therapeutic efficacy of CGA through inflammatory cell counts, cytokine levels (ELISA), and lung histopathology. Integrated lung lipidomics (LC-MS/MS) was employed to profile lipid mediators and phospholipids. The underlying mechanism was investigated in erastin-induced ferroptosis in BEAS-2B cells and validated in mouse lung tissue using qPCR, immunofluorescence, and assays for reactive oxygen species (ROS) and Fe2+. CGA treatment significantly attenuated airway inflammation, reduced Th2 cytokine (IL-4, IL-5) and IgE levels, and ameliorated lung pathology in a dose-dependent manner. Lipidomics revealed that asthma was associated with dysregulated docosahexaenoic acid (DHA) metabolism, characterized by elevated pro-inflammatory lipid peroxidation products (e.g., 11-HDoHE, 14-HDoHE), a profile reversed by CGA intervention. Mechanistically, molecular docking and subsequent validation identified CGA as an activator of the Nrf2 antioxidant pathway, leading to upregulation of the key ferroptosis defense genes SLC7A11 and GPX4 both in vitro and in vivo. Consequently, CGA treatment suppressed erastin-induced ROS production and Fe2+ accumulation in BEAS-2B cells. In conclusion, this study demonstrates that CGA exerts anti-asthmatic effects by reprogramming DHA metabolism to suppress ferroptosis while enhancing antioxidant pathways. These findings reveal a novel mechanistic axis for CGA and establish that targeting lipid peroxidation-driven ferroptosis represents a promising therapeutic strategy for asthma.

Sorghum 3-deoxyanthocyanidins (3-DAs) exhibit notable bioactivity but are limited by low extraction efficiency. Nine natural deep eutectic solvents (NADESs) were prepared using choline chloride with various organic acids. Their structures and physicochemical properties were characterized. Extraction efficiency was influenced by viscosity and HBD structure, with malate-based NADES (ChCl-Ma) showing the highest yield under optimized conditions (25% water, 40 °C, 1:20, 30 min). Compared with methanol extraction, 3-DAs obtained by ChCl-Ma exhibited superior antioxidant and glycoside hydrolase inhibitory activities. Overall, this work not only provides a greener and efficient method for extracting 3-DAs from sorghum but also offers a theoretical basis for the high-value utilization of sorghum and highlights the potential of 3-DAs in food and pharmaceutical applications.

Background:Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism, and if untreated, leads to severe neurocognitive impairment. Over the past 2 decades, treatment strategies have evolved from strict dietary phenylalanine restriction to include pharmacological therapies such as tetrahydrobiopterin and, more recently, enzyme substitution with pegvaliase. Despite these advances, significant heterogeneity exists in global research priorities, collaboration patterns, and the translation of emerging therapies into clinical practice. A systematic overview of the field's development, thematic shifts, and remaining knowledge gaps is currently lacking. Objective:This study aimed to provide a systematic bibliometric analysis of global treatment research on PKU from 2000 to 2025. The aim was to quantify publication trends, collaboration patterns, thematic evolution, and research gaps, thereby informing future scientific and clinical directions. Methods:A search of the Web of Science Core Collection was performed on September 13, 2025. The search initially identified 1877 records. After screening, 1462 English-language articles and reviews were included. Publication trends were analyzed using Microsoft Excel (version 16.101), while VOSviewer 1.6.20 and CiteSpace 6.4R1 were used to visualize country- and institutional-level collaborations, journal networks, keyword co-occurrence, citation bursts, and thematic clusters. Statistical charts were generated with GraphPad Prism 10.2.1. Results:Annual publication output demonstrated an overall upward trend, peaking in 2022 with 111 publications. The United States led in both publication volume (375 studies) and total citations (11,142 citations), maintaining strong collaborative ties with several European countries, particularly the Netherlands and the United Kingdom. China ranked seventh globally in publication volume, although its citation impact remains comparatively limited. Key institutions, including the University of Groningen and Birmingham Children's Hospital, as well as prominent scholars such as Francjan J van Spronsen and Anita MacDonald, have occupied central positions in the global PKU treatment research collaboration network over the study period. High-frequency and high-centrality keywords, such as "phenylalanine," "dietary treatment," and "tetrahydrobiopterin," highlighted continued emphasis on metabolic control and targeted therapies. Keyword burst analysis revealed a gradual shift from conventional dietary management toward enzyme replacement therapies, investigations of neurocognitive outcomes, and precision medicine-oriented approaches. Conclusions:Over the past 25 years, PKU treatment research has progressed from foundational dietary interventions to molecular mechanistic studies and individualized therapeutic strategies. Future research should prioritize longitudinal multiomics investigations, targeted metabolic correction technologies, gene-based therapeutic approaches, and enhanced international collaboration, particularly to strengthen diagnosis and management capacities in low- and middle-income regions. Such efforts will be critical to advancing global standards of PKU care.

Melanoma is aggressive with limited treatment options. Paclitaxel (PTX) is effective but limited by poor solubility, systemic toxicity, and insufficient intratumoral retention. Here, we report an in situ needle-free platform that amplifies local PTX exposure via multiretention nanoscale mixed polymeric micelles composed of Soluplus and a dipotassium glycyrrhizinate-PEG-folic acid conjugate (DG-pp-FA). Needle-free intratumoral jet injection at the tumor site reduces needle-related barriers and discomfort. The micelles integrate thermoenabled local deposition and physical retention, pH-responsive stabilization and release in acidic tumor microenvironments, and folate-receptor targeting for enhanced uptake and selectivity. Central composite design optimization yielded stable micelles with a hydrodynamic size of 68 ± 3.8 nm, PDI of 0.08 ± 0.01, and 98 ± 0.11% PTX encapsulation efficiency, showing sustained release. Compared with free PTX, NF#PTX@Soluplus/DG-pp-FA improved tumor retention, increased cellular uptake, and more strongly inhibited melanoma proliferation, migration, and invasion. Single-cell sequencing, spatial transcriptomics, and proteomics revealed dual actions of direct tumor suppression and immune microenvironment remodeling, including increased leukocyte infiltration, extracellular matrix (ECM) reprogramming to improve penetration, enhanced immune activation, and reduced fibrosis. In vivo studies confirmed improved tumor localization, prolonged retention, lower toxicity, and good biocompatibility.

Melanoma, the most lethal form of skin cancer, remains a significant therapeutic challenge despite advances in immunotherapy. Although PD-1/PD-L1 blockade improves clinical outcomes, its effectiveness is frequently limited by suboptimal response rates and treatment resistance. Here, we developed a novel strategy targeting iron-dependent PD-L1 regulation. Since elevated iron activates phosphoinositide-3-kinase (PI3K)/AKT signaling and upregulates PD-L1, we employed the iron chelator deferasirox (DFX) to disrupt this pathway. To overcome DFX's poor solubility and bioavailability, we engineered tumor-targeting, glutathione-responsive albumin nanoparticles modified with cRGD peptides (RGDAB@DFX NPs). These NPs selectively accumulated in B16F1 melanoma tumors and released DFX in response to intracellular glutathione, effectively downregulating PD-L1. These findings suggest that iron modulation represents a promising approach to enhance immunotherapy efficacy, with RGDAB@DFX NPs serving as an optimized delivery platform for clinical application.

This study systematically analyzed the literature on tumor antigen-based cancer immunotherapy by integrating quantitative bibliometric analysis with knowledge network visualization. It aimed to provide an overview of the developmental trajectory of this field, identify major research hotspots and key scientific challenges, and explore the underlying drivers of its evolution, thereby providing references for future antigen-targeted immunotherapy strategies and clinical translation. Literature related to tumor antigen-based cancer immunotherapy was retrieved from the Web of Science Core Collection, covering the period from September 15, 2005, to September 15, 2025. A total of 2,801 research articles were included. Bibliometric data were statistically analyzed using CiteSpace, VOSviewer, Charticulator, Scimago Graphica, and Bibliometrix, and visual scientific network maps were generated. Bibliometric analysis showed that annual publication output in this field has remained relatively stable over the past six years, with approximately 170 publications per year and a peak of 188 publications in 2021. Regarding national contributions, the United States ranked first in publication output (1,282 publications), total citations (83,431 citations), and network centrality (0.46). Although China showed rapid growth in publication output and ranked second globally, its overall citation impact remained lower than that of several Western countries. In terms of academic influence, researchers such as Jeffrey Schlom from the National Cancer Institute and Chien-Fu Hung from Johns Hopkins University have maintained important positions through long-term research on tumor antigen recognition, immune regulation, and vaccine development. Temporal keyword analysis revealed an evolutionary transition from early adoptive immunotherapy-related studies, represented by terms such as “transfer therapy” and “adoptive immunotherapy”, to immune checkpoint regulatory strategies involving “nivolumab” and “immune checkpoint blockade”, and subsequently to emerging tumor antigen vaccine approaches characterized by “nanovaccine” and “mRNA vaccine”. Co-citation analysis further supported this evolutionary trajectory, indicating a gradual shift from broadly enhancing immune activation toward precise tumor antigen identification and optimization of antigen-driven immune responses. Over the past two decades, tumor antigen-based cancer immunotherapy has evolved from adoptive immune cell therapy and immune checkpoint regulation to personalized neoantigen vaccine strategies, forming a multi-level therapeutic framework involving antigen recognition, immune activation, and targeted delivery. Future advances in antigen prediction, sequencing technologies, mRNA vaccine platforms, and immune regulatory strategies may further promote the development of more precise, effective, and personalized cancer immunotherapies.

To systematically examine global research trends in the association between ferroptosis and autoimmune diseases from 2018 to 2025, thereby informing future mechanistic and translational investigations in this field. On March 17, 2026, relevant publications were obtained from the Web of Science Core Collection and PubMed databases. This included articles and reviews written in English and published between 2018 and 2025. Bibliometric visualization was conducted using CiteSpace 6.4.R1, VOSviewer 1.6.20, and Scimago Graphica to map countries, authors, institutions, keywords, journals, and references. Data processing and descriptive statistical analysis were performed using Microsoft Excel 2019. Seven hundred and nineteen publications from 27 countries were included in the analysis. The annual number of publications showed a consistent upward trend, with China contributing the largest share (487 publications). High-frequency keywords included rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, oxidative stress, and lipid peroxidation, indicating research hotspots in this field. Research on the association between ferroptosis and autoimmune diseases has expanded substantially over the past 8 years. However, the field remains in a relatively early stage of development. These findings suggest that the field is receiving increasing scholarly attention and may provide useful references for future biomarker discovery and novel therapeutic strategy development.

Pulmonary arterial hypertension is a progressive pulmonary vascular disease with a poor prognosis.The RhoA/ROCK pathway orchestrates multiple cellular functions such as contraction,proliferation,and endothelial function,which are closely related to the development of pulmonary arterial hypertension.Inhibition of the RhoA/ROCK pathway provides a new therapeutic option to alleviate pulmonary arterial hypertension.In addition,the search for new medicines from traditional Chinese herbs or the use of herbs as complementary medicines has been practiced among physicians.Many traditional Chinese herbs have the potential to inhibit the RhoA/ROCK pathway and alleviate experimental pulmonary arterial hypertension.In summary,this review will focus on the unique contribution of traditional Chinese herbs in this field based on an in-depth understanding of the relationship between the RhoA/ROCK pathway and pulmonary arterial hypertension.

ObjectiveAccumulating evidence highlights the important role of B vitamins in maintaining the balance of gut microbial ecology and metabolism, however, few studies have focused on changes in B vitamins homeostasis in the gut and their associations with disease. This study aims to investigate the potential interplay between B vitamins, gut microbiota, and obesity.MethodsWe conducted an integrated analysis of fecal shotgun metagenomics, fecal metabolome concerning B vitamins and short chain fatty acids (SCFAs), and obese phenotypes in a cohort of 63 participants, including 31 healthy controls and 32 individuals with obesity.ResultsMetabolomic analysis identified significantly lower levels of fecal thiamine in individuals with obesity (PWilcoxon < 0.001). Fecal thiamine levels exhibited a positive correlation with HDL-C and a negative correlation with BMI, DBP, fasting serum insulin, HOMA-IR, triglycerides, and propionic acid. Binary logistics regression suggested that fecal thiamine deficiency may be a potential contributor to the onset of obesity (Odds ratio: 0.295). Metagenomic analysis indicated that the microbial composition in individuals with obesity was characterized by a predominance of potential opportunistic pathogens, a loss of complexity, and a decrease in thiamine-producing bacteria. Integrated analysis indicated that thiamine deficiency was positively associated with the depletion of thiamine auxotrophic bacteria in the obese microbiome. Functional analysis revealed that KOs content for enzymes involved in the microbial production of thiamine were significantly lower in obesity, including tRNA uracil 4-sulfurtransferase (ThiI, PWilcoxon = 0.001) and nucleoside-triphosphatase (NTPCR, PWilcoxon = 0.006), both of which were positively associated with fecal thiamine.ConclusionOur study highlights the impairment of microbial thiamine production and its broad associations with gut microbiota dysbiosis and obesity-related phenotypes. Our findings provide a rationale for developing treatments that utilize thiamine to prevent obesity by modulating gut microbiota.

Background and Objectives Considerable evidence has shown that alterations in gut microbiota composition are associated with atrial fibrillation (AF). However, the causal associations remain largely unresolved. This study aims to reveal the causality between gut microbiota and AF. Methods We incorporated data from the largest genome-wide association studies (GWASs) of gut microbiota composition (involving 18,304 individuals) and GWASs of AF (comprising 60,620 cases and 970,216 controls) in European individuals. A two-sample Mendelian randomization framework was designed to investigate the role of gut microbiota in the development of AF. The inverse variance weighted method was applied for the main causal estimate. Complementary sensitivity analyses were utilized to confirm the robustness of the results. Finally, gene ontology enrichment analyses and Kyoto Encyclopedia of genes and genomes pathway analysis are used to investigate the bio-function. Results Among all gut microbiota, five microbial taxa, namely Lachnospiraceae FCS020 , Rikenellaceae RC9 gut group , Catenibacterium , Victivallis , and Erysipelatoclostridium were identified to be causally associated with the higher risk of AF. Besides, genetically predicted eight microbial taxa, namely Lachnospiraceae NK4A136 group , Howardella , Intestinibacter bartlettii , Alloprevotella , Anaerostipes , Odoribacter , Ruminococcus (gnavus group) , and Ruminiclostridium 5 can prevent AF. Conclusion Our study provides evidence of the causal effect of the gut microbiota on AF, highlighting causal microbial taxa. Our results may offer novel insights into gut microbiota-mediated mechanisms and interventions of AF.