The rapid advances in epigenetic and epitranscriptomic regulatory mechanisms have opened new prospects for precision therapies in various diseases. N-acetyltransferase 10 (NAT10) is currently the only known eukaryotic RNA ac4C acetyltransferase and has also been reported to acetylate multiple protein substrates, regulating diverse physiological processes. In this review, we comprehensively describe the domain organization, structural features and subcellular localization of NAT10. The molecular mechanisms underlying NAT10-mediated RNA ac4C modification and protein acetylation, as well as their biological functions across physiological and pathological contexts, are systematically summarized, with the aim of facilitating its clinical translation. Furthermore, we review the recent advances in NAT10-targeted therapeutic strategies, discuss the potential for combining NAT10-targeted strategies with existing treatment modalities, and propose possible approaches for optimization. By integrating current evidence, this review provides insights into the functions of NAT10 and highlights future research directions for its validation and translational development as a clinical therapeutic target in various diseases. Graphical overview of NAT10 domain organization, RNA ac4C and reported protein-lysine acetylation activities, biological functions across major organ systems, and emerging therapeutic strategies. Since the direct binding between Remodelin and NAT10 remains unconfirmed, relevant effects exerted by this small molecule should be indicated with dashed arrows.

Mouth breathing (MB), a common manifestation of sleep-disordered breathing in children may induce craniofacial developmental abnormalities leading to adenoid facies. Although adenoidectomy and/or tonsillectomy (A T) represents the primary therapeutic intervention, a substantial proportion of pediatric patients exhibit residual mouth breathing postoperatively. Why a substantial subset of children exhibit residual MB remains a critical clinical question. Among the overlooked explanations for this incomplete recovery may be sensitization to airborne allergens—a hidden determinant of postoperative outcomes. This study sought to define the role of this under-investigated risk factor in the failure to resolve MB following A T. A retrospective analysis was conducted on a cohort of children who underwent A T at our hospital from June 2023 to June 2024. Incomplete lip seal during sleep was used as the diagnostic criterion for mouth breathing. Allergic rhinitis and rhinosinusitis symptoms were quantified using the Total Nasal Symptom Score (TNSS). Preoperative serum allergen screening was performed in all cases. Multivariate analyses were employed to assess associations between postoperative mouth breathing resolution and age, gender, BMI, allergen sensitization and TNSS. The study included 502 children. Residual mouth breathing was observed in 39.44

Skin vascular aging is characterized by a specific loss of capillary-associated macrophages (CAMs), driven by impaired local proliferation. This depletion causes microvascular dysfunction. Restoring CAMs via colony-stimulating factor 1 stimulation improves capillary flow, identifying a promising therapeutic target for aging-related and diabetic vascular complications.

The interplay between vaginal and gut microbiota and their collective impact on live birth outcomes remains poorly characterized. This study investigated the association between vaginal and gut microbiota and live birth outcomes in women undergoing frozen-thawed embryo transfer (FET). Vaginal and fecal samples were collected from 137 infertile women (64 controls, 73 with polycystic ovary syndrome (PCOS) undergoing FET and analyzed by 16S rRNA gene sequencing. Machine learning models based on genus-level abundance were used to predict live birth outcomes, and PICRUSt2 was employed to infer functional profiles of microbial communities. Significant differences in microbial composition, β-diversity, and functional profiles were observed between live birth (LB) and non-live birth (NLB) groups (all p < 0.05). NLB cases exhibited synchronized dysbiosis across both niches, with opposing patterns between subgroups: control-NLB showed increased β-diversity, whereas PCOS-NLB showed reduced β-diversity in both vaginal and gut microbiota. Notably, the combined signature of vaginal and gut taxa outperformed single-niche biomarkers for predicting live birth outcomes. In controls, vaginal Ralstonia and gut Escherichia-Shigella achieved an AUC of 0.888. Strikingly, in PCOS patients, we identified a robust, disease-specific interaction: vaginal Streptococcus and gut Bacteroides not only showed high combined predictive performance (AUC = 0.905) but also exhibited a strong positive correlation (r = 0.782, p < 0.001), suggesting a PCOS-associated microbial interaction network. These findings reveal synchronized dysbiosis of vaginal and gut microbiota in NLB outcomes, with vaginal microbiota showing a more direct association with live birth. In PCOS, a specific vaginal Streptococcus-gut Bacteroides axis suggests a disease-specific microbial interaction network associated with reproductive failure in PCOS. Assessing both microbial ecosystems prior to FET may improve risk stratification and guide therapeutic interventions targeting the vaginal-gut axis.

Diabetic wounds are a class of chronic non-healing wounds driven by multiple interacting factors. Conventional therapies remain limited in their ability to actively modulate the wound microenvironment and promote coordinated tissue regeneration. In this context, naturally derived biomaterials with combined biological activity and material functionality have attracted increasing attention. Among them, snail mucus has emerged as a promising source of inspiration because of its multicomponent composition and potential roles in hydration, adhesion, barrier protection, antimicrobial activity, immune regulation, and tissue repair. This review summarizes recent advances in snail mucus and snail mucus-inspired materials for diabetic wound repair, with emphasis on the pathological basis of impaired diabetic wound healing, the biological functions and biomaterial potential of key components, and the engineering strategies derived from these components. We further discuss how snail mucus-derived materials can be reconstructed through hydration and wet-interface control, bioactive component immobilization and presentation, protein-polymer assembly, and spatial or nanoscale integration to regulate material properties and therapeutic functions. Although these materials have shown promising effects in inflammation modulation, antibacterial protection, angiogenesis, re-epithelialization, and tissue reconstruction, current evidence remains largely limited to preclinical studies. Challenges related to raw-material standardization, component definition, biosafety evaluation, and translational validation remain to be addressed. Overall, snail mucus represents not only a natural source of bioactive components for biomaterial construction but also a biomimetic design prototype for developing functional materials for chronic diabetic wound repair.

To explore the relationship between the triglyceride-glucose-waist-to-height ratio (TyG-WHtR) and brachial-ankle pulse wave velocity (baPWV), and to evaluate its utility as an early indicator of arterial stiffness in individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome. Additionally, its performance was compared with the triglyceride-glucose index (TyG), TyG-waist circumference (TyG-WC), and TyG-body mass index (TyG-BMI). This retrospective study included 37,134 adults who underwent health examinations at the Third Xiangya Hospital of Central South University from August 2017 to December 2021. Participants were staged based on CKM diagnostic criteria. Associations between TyG-related indices and baPWV were assessed using correlation and regression analyses. A risk stratification model for arterial stiffness was constructed based on TyG-WHtR quantiles. In addition, a risk stratification model was established by combining quantile analysis, and a comprehensive comparison of the goodness of fit of the model was conducted with TyG, TyG-WC, and TyG-BMI. Progressive arterial stiffness, as measured by baPWV, showed a significant increase from 1226 cm/s (stage 0) to 1441 cm/s (stage 2) (P < 0.001) with advancing CKM stages. Concurrently, the TyG-WHtR index demonstrated a parallel elevation from 3.28 ± 0.51 to 4.85 ± 0.66 (P < 0.001), accompanied by significant worsening of multiple metabolic parameters including BMI, waist circumference, blood pressure, TG, and FBG (all P < 0.001). Notably, the proportion of male patients increased progressively from 36.85

BACKGROUND:Poria cocos is a renowned medicinal and edible macrofungus in China. Alkali-soluble polysaccharide from Poria cocos (PCY) is one of its main active components. However, the biological activity and utilization of PCY are constrained by its poor water solubility. Therefore, we modified PCY with chlorosulfonic acid-pyridine to improve its properties in this study. By comparing the results of solubility, antioxidant and hypoglycemic assays, we chose one derivative for further studies, which was named PCY-S2. We simulated in vitro the digestion and microbial fermentation of PCY-S2 using feces from volunteers and then gavaged it to mice to investigate its impacts on gut microbial modulation. RESULTS:The results showed that PCY-S2 could effectively regulate gut microbiota in fecal fermentation and animal experiments. In in vitro microbial fermentation, PCY-S2 upregulated the abundance of probiotic bacteria such as Streptococcus, Bifidobacterium and Lactococcus. In in vivo microbial studies, PCY-S2 downregulated the ratio of Firmicutes to Bacteroidota at the phylum level, significantly increasing the relative abundance of several beneficial microbiota such as unclassified_f_Muribaculacea, Prevotellaceae_UCG-001 and Alloprevotella at the genus level. Also, it promoted short-chain fatty acid production and reduced the levels of IL-6 and TNF-α. CONCLUSION:Overall, PCY-S2 is beneficial for regulating the composition and structure of gut microbiota, which provides a candidate for developing an effective functional prebiotic. © 2025 Society of Chemical Industry.

Currently, cancer immunotherapy strategies are primarily formulated based on the patient's present condition, representing a ''static'' treatment approach. However, cancer progression is inherently ''dynamic,'' as the immune environment is not fixed but undergoes continuous changes. This dynamism is characterized by the ongoing interactions between tumor cells and immune cells, which ultimately lead to alterations in the tumor immune microenvironment. This process can be effectively elucidated by the concept of cancer immunoediting, which divides tumor development into three phases: ''elimination,'' ''equilibrium,'' and ''escape.'' Consequently, adjusting immunotherapy regimens based on these distinct phases may enhance patient survival and improve prognosis. Targeting ferroptosis is an emerging area in cancer immunotherapy, and our findings reveal that the antioxidant systems associated with ferroptosis possess dual roles, functioning differently across the three phases of cancer immunoediting. Therefore, this review delve into the dual role of the ferroptosis antioxidant system in tumor development and progression. It also propose immunotherapy strategies targeting ferroptosis at different stages, ultimately aiming to illuminate the significant implications of targeting ferroptosis at various phases for cancer immunotherapy.

The immune-responsive gene 1 (IRG1) protein plays a role in various pathological processes by connecting cellular metabolism to a range of cellular activities through the production of itaconate. Recent studies have highlighted the significance of IRG1 and itaconate in bone metabolism and homeostasis. However, the precise role of IRG1 in osteoporosis remains inadequately documented. This study aimed to determine the role of IRG1 in osteoporosis through the utilization of IRG1 knockout (KO) mice and a model of ovariectomy (OVX)-induced osteoporosis. The expression of IRG1 was found to be higher in the bone tissues of postmenopausal osteoporotic mice induced by OVX in comparison to sham control mice. When compared to wild type (WT) mice, OVX-induced bone loss was significantly worse in IRG1 KO mice, and this was accompanied by an increase in osteoclastogenesis and bone resorption. However, the loss of bone and the process of osteoclastogenesis and bone resorption were effectively reversed when the IRG1 KO mice were replenished with itaconate. The osteoclastogenesis induced by receptor activator of nuclear factor kappa-Β ligand (RANKL) in bone marrow-derived macrophages (BMMs) was found to be enhanced by IRG1 deficiency, which could be reversed through the replenishment of itaconate. Further investigation revealed that IRG1 deficiency potentiated the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. The inhibition of NLRP3 inflammasome using a targeted inhibitor significantly ameliorated RANKL-induced osteoclastogenesis in IRG1 KO BMMs. Overall, this study highlights the significance of IRG1 in regulating osteoclastogenesis and proposes it as a potential target for osteoporosis treatment.

Acute lung injury (ALI) is a common critical respiratory disease in clinical practice, especially in the ICU, with a high mortality rate. The pathogenesis of ALI is relatively complex, mainly involving inflammatory response imbalance, oxidative stress, cell apoptosis, and other aspects. However, currently, the treatment measures taken based on the above mechanisms have not had significant effects. Recent research shows that mitochondrial dysfunction and pyroptosis play an important role in ALI, but there is not much analysis on the relationship between mitochondrial dysfunction and pyroptosis at present. This article reviews the situation of mitochondrial dysfunction in ALI, pyroptosis in ALI, whether mitochondrial dysfunction is related to pyroptosis in ALI, and how to do so, and further analyzes the relationship between them in ALI. This review describes how to alleviate mitochondrial dysfunction, and then suppress the associated immunological pyroptosis, providing new ideas for the clinical treatment of ALI.

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect multiple organs throughout the body, predominantly in middle-aged and elderly males, with a male-to-female ratio of 2꞉1 to 3꞉1. IgG4-related retroperitoneal fibrosis (IgG4-RPF), a rare subtype of IgG4-RD, has an unclear etiology, and its comorbidity with type 2 diabetes mellitus is also uncommon. A lack of awareness of this condition in clinical practice can easily lead to misdiagnosis. On July 14, 2016, the Third Xiangya Hospital of Central South University admitted a patient with type 2 diabetes mellitus complicated by IgG4-RPF. Following comprehensive treatment, including blood glucose and blood pressure control, kidney protection, circulation improvement, and the use of prednisone, the patient's condition significantly improved. The retroperitoneal fibrotic mass decreased in size, renal function improved, and serum IgG4 levels decreased. After 8 years of follow-up, the condition did not recur. Analyzing this case in conjunction with a literature review suggests that the development of IgG4-RPF in diabetic patients may be related to chronic inflammation from metabolic syndrome and atherosclerotic plaques associated with long-standing diabetes. This provides valuable clinical ideas for clinicians in diagnosing and treating this rare comorbidity.

Smoking is a serious global health issue. Cigarette smoking contains over 7000 different chemicals. The main harmful components include nicotine, acrolein, aromatic hydrocarbons and heavy metals, which play the key role for cigarette-induced inflammation and carcinogenesis. Growing evidences show that cigarette smoking and its components exert a remarkable impact on regulation of immunity and dysregulated immunity promotes inflammation and cancer. Therefore, this comprehensive and up-to-date review covers four interrelated topics, including cigarette smoking, inflammation, cancer and immune system. The known harmful chemicals from cigarette smoking were summarized. Importantly, we discussed in depth the impact of cigarette smoking on the formation of inflammatory or tumor microenvironment, primarily by affecting immune effector cells, such as macrophages, neutrophils, and T lymphocytes. Furthermore, the main molecular mechanisms by which cigarette smoking induces inflammation and cancer, including changes in epigenetics, DNA damage and others were further summarized. This article will contribute to a better understanding of the impact of cigarette smoking on inducing inflammation and cancer.

Oudemansiella raphanipes is a type of fungus used as both medicine and food. Fungal polysaccharides have demonstrated various bioactivities, involving the adjust and control of gut microbiota, but no such studies on O. raphanipes polysaccharides (OrPs) have been reported. It is by extracting and purifying that OrPs was obtained from O. raphanipes crude polysaccharide and study their effects in mice. The sample contents of total sugar was 97.26%, and the monosaccharide content comprised mannose, rhamnose, glucose, and xylose in a molar ratio of 35.2:2.8:21.2:40.8. The effects of OrPs on body weight (BW), gut microbiota, fecal short-chain fatty acids (SCFAs), and the correlation between fecal SCFAs and gut microbes, in mice were investigated. The results of the experiment found that OrPs significantly (P < 0.01) inhibited the increase in BW, altered the constitution of the gut microbiota, and significantly (P < 0.05) enhanced the content of fecal SCFAs in mice. Moreover, among the top ten bacteria in terms of relative abundance, the Lachnospiraceae and Lachnospiraceae NK4A136 groups were positively associated with the increased production of SCFAs. Other bacteria, such as Atopobiaceae and Bifidobacterium of Actinobacteriota, and Faecalibaculum, Dubosiella, and Clostridium sensu stricto 5 of Firmicutes, were also positively associated with higher content of fecal SCFAs. The results of the experiment suggest that OrPs have a potential prebiotic effect on gut microbiota and may prevent BW gain. Furthermore, the major producers of SCFAs were Firmicutes and Actinobacteriota.

B7 family members act as co-stimulatory or co-inhibitory molecules in the adaptive immune system. Thisstudy aimed to investigate the dysregulation, prognostic value and regulatory network of B7 family members in non-small cell lung cancer (NSCLC). Data for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were extracted from public databases. Patient prognosis was determined by Kaplan–Meier analysis. The downstream signaling pathways of B7 family were identified via GO and KEGG analysis. The key B7 related genes were selected by network, correlation and functional annotation analysis. Most B7 family members were dysregulated in LUAD and LUSC. The expression of B7-1/2/H3 and B7-H5 were significantly associated with overall survival in LUAD and LUSC, respectively. The major pathway affected by B7 family was the EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway. MAPK1, MAPK3 and MAP2K1 were pivotal B7 related genes in both LUAD and LUSC. This study reveals an overall dysregulation of B7 family members in NSCLC and highlights the potential of combination use of tyrosine kinase inhibitors or MEK/ERK inhibitors with B7 member blockade for NSCLC treatment.

Starch from Pueraria lobata (PLS) had polyhedral or spherical granules, displaying a bimodal size distribution within 0.6-30 & mu;m. It showed a trimodal distribution of different molecular weight peaks, with amylose fraction of 18.2 %. PLS had a high crystallinity degree of 37.76 % and consisted of C-type starch, which gelatinized at 64.46-79.61 degrees C, with a high range of gelatinization (15.15 degrees C) and high enthalpy (13.98 J/g). A 21-day supplementation of PLS presented a regulative effect on gut microbiota in normal mice, and alleviated DSS-induced murine colitis through attenuating colonic inflammation, maintaining barrier function, preventing gut dysbiosis, increasing the short-chain fatty acids production and inhibiting NF-& kappa;B/IL-1 & beta; axis. The protective effect of PLS against colitis was in a gut microbiota-dependent manner. Notably, the amylose fraction was responsible for the prebiotic effect of PLS. The results would potentiate new application of PLS and the amylose fraction as functional prebiotics for prevention of colitis.

Grape seeds is a popular health food with various biological activities around the world. Grape seeds polysaccharides (GP) have antioxidant, anti-inflammatory, immunomodulatory and hypolipidemic effects, but little is known about the effects of GP on the gut microbiota. Therefore, we aim to investigate the fermentation properties of polysaccharides isolated from grape seeds and its effect on the mice’s gut microbiota. We obtained polysaccharides from grape seeds by water extraction and alcoholic precipitation. We simulated the digestion and fermentation of GP in human body, and used bioinformation approach to study its effects on the mice’s gut microbiota. In the simulated fermentation experiment of GP, the administration of GP significantly decreased the relative abundance of Fusobacterium and Allisonella , and significantly increased the relative abundance of Bacteroides at genus level. In addition, GP altered the structure and proportion of intestinal microbial community in Kunming mice, especially increased the relative abundance of Lachnospiracea _NK4A136_group (p = 0.008239). In conclusion, the effect of polysaccharides from grape seeds on gut microbiota was investigated in this study, and the results suggested that GP has the potential to become a functional food prebiotic. It provided the basis and insight for further exploration of grape seed polysaccharides, and provided a new idea for the development of functional food prebiotics.

The tumor microenvironment is complicated and continuously evolving. This study was devoted to the identification of potential prognostic biomarkers based on the tumor microenvironment associated with immunotherapy for melanoma. This study integrates a couple of melanoma single cell and transcriptome sequencing datasets and performs a series of silico analyses as nicely as validation of molecular biology techniques. A core set of immune escape related genes was identified through Lawson et al. and the ImmPort portal. The differential proteins were identified through the cBioPortal database. Regression analysis was used to profile independent prognostic factors. Correlation with the level of immune cell infiltration was evaluated by multiple algorithms. The capacity of LCK to predict response was assessed in two independent immunotherapy cohorts. High LCK expression is associated with better prognosis, high levels of TILs and better clinical staging. Pathway analysis showed that high expression of LCK was significantly associated with activation of multiple tumor pathways as well as immune-related pathways. LCK expression tends to be higher in immunotherapy-responsive patients and those with lower IC50s treated with chemotherapeutic agents. RT-qPCR detected that LCK expression was significantly upregulated in melanoma cell lines. Single-cell transcriptome analysis showed that LCK was specifically highly expressed on T cells. CellChat analysis confirmed that LCK in C2 subpopulations and T cell subpopulations exerted immune promotion between cells by binding to CD8 receptors. In conclusion, LCK is a reliable biomarker for melanoma and will contribute to its immunotherapy.

Intestinal stem cells (ISCs) play an important role in maintaining intestinal homeostasis via promoting a healthy gut barrier. Within the stem cell niche, gut microbiota linking the crosstalk of dietary influence and host response has been identified as a key regulator of ISCs. Emerging insights from recent research reveal that ISC and gut microbiota interplay regulates epithelial self-renewal. This article reviews the recent knowledge on the key role of ISC in their local environment (stem cell niche) associating with gut microbiota and their metabolites as well as the signaling pathways. The current progress of intestinal organoid culture is further summarized. Subsequently, the key challenges and future directions are discussed.

Increasing evidence indicated that probiotics can be effective in improving behaviors similar to depression and anxiety disorders. However, the underlying mechanisms remain unclear, as is the effects of single vs. combined probiotics on depression and anxiety. This study aimed to determine whether combined probiotics could attenuate depressive-like and anxiety-like behavior induced by chronic unpredictable mild stress (CUMS) and its potential mechanisms. Rats underwent CUMS treatment and then administered Lactobacillus rhamnosus HN001 (HN001) or Bifidobacterium animalis subsp. lactis HN019 (HN019), alone or in combination. Levels of neurotransmitters, inflammatory factors, and the gut microbiota were measured. HN001 and (or) HN019 treatment improved depressive-like and anxiety-like behavior in rats, including increased moving distance and exploratory behavior (p < 0.05). In addition, altered gut microbiota structure induced by CUMS was amended by HN001 and/or HN019 (p < 0.05). HN001 and/or HN019 intervention also remarkably normalized levels of 5-HT, DA, NE, HVA, DOPAC, HIAA, TNF-α, IL-6, IL-18 and IL-1β in CUMS rats (p < 0.05). Furthermore, the effects of combined probiotics on decreasing inflammation and improved gut microbiota (Chao1 index and ACE index, p < 0.05) were superior to the single probiotics. Moreover, spearman analysis showed a certain correlation between the different microbiota, such as Firmicutes, Bacteroidetes, Verrucomicrobias, Proteobacterias and Actinobacterias, and inflammation and neurotransmitters. These findings suggested that CUMS induced depressive and anxiety-like behaviors can be alleviated by the combination of probiotics, which was possibly associated with the alterations in the gut microbiota composition and increased neurotransmitters and decreased inflammatory factors.

The dried roots of Pueraria lobata (Willd.) Ohwi as an edible medicinal herb are enriched with starch. However, the structure, physiology, and biological bioactivity of P. lobata starch (PLS) has not yet been fully investigated. This study showed that PLS consisted of mixed population of granules with polyhedral or spherical surface. The apparent content of resistant starch was 23.14%, and the molecular weight was 1.93 × 107 Da. PLS showed a branching degree and an average polymerization rate of 2.06% and 20.74%, respectively, with fairly high proportion of B1 short chains. The solubility and swelling power of PLS were 38.51% and 28.10 g/g, respectively, showing high hot stability of the viscosity. In vitro fermentation of PLS resulted in specifically altered composition of gut microbiota and increased production of SCFAs, showing a potential prebiotic effect. Moreover, PLS remarkably alleviated inflammation, hepatic steatosis and dyslipidemia in mice with high-fat high-cholesterol diet induced non-alcoholic fatty liver disease (NAFLD). The protective effect of PLS was associated with amelioration of NAFLD-associated gut dysbiosis through specifically increasing the abundance of Lactobacillus, Bifidobacterium and Turicibacter, and decreasing Desulfovibrio. The results would support the use of PLS as a functional prebiotic for protecting against NAFLD.