YTHDF2 in peritumoral hepatocytes mediates chemotherapy-induced antitumor immune responses through CX3CL1-mediated CD8+ T cell recruitment.

Peritumoral hepatocytes are critical components of the liver cancer microenvironment, However, the role of peritumoral hepatocytes in the local tumor immune interface and the underlying molecular mechanisms have not been elucidated. YTHDF2, an RNA N6-methyladenosine (m6A) reader, is critical for liver tumor progression. The function and regulatory roles of YTHDF2 in peritumoral hepatocytes are unknown. This study demonstrated that oxaliplatin (OXA) upregulated m6A modification and YTHDF2 expression in hepatocytes. Studies using tumor-bearing liver-specific Ythdf2 knockout mice revealed that hepatocyte YTHDF2 suppresses liver tumor growth through CD8+ T cell recruitment and activation. Additionally, YTHDF2 mediated the response to immunotherapy. Mechanistically, OXA upregulated YTHDF2 expression by activating the cGAS-STING signaling pathway and consequently enhanced the therapeutic outcomes of immunotherapeutic interventions. Ythdf2 stabilized Cx3cl1 transcripts in an m6A-dependent manner, regulating the interplay between CD8+ T cells and the progression of liver malignancies. Thus, this study elucidated the novel role of hepatocyte YTHDF2, which promotes therapy-induced antitumor immune responses in the liver. The findings of this study provide valuable insights into the mechanism underlying the therapeutic benefits of targeting YTHDF2.

Quantification and visual inspection of adipic dihydrazide in textile using a xanthylium-based ratiometric fluorescent probe.

Residual adipic dihydrazide (ADH) in textiles may react with formaldehyde to form hydrazone, which is a source of the formaldehyde pollutant indoors. In this paper, a xanthylium-based ratiometric fluorescent probe SH-Py was developed for ADH detection. The emission of SH-Py at 680 nm decreased, whereas that at 463 nm increased upon the addition of ADH in pure DMSO. The LOD was as low as 24.5 nM, and the possible sensing mechanism is presented. Good recoveries were observed in the standard recovery experiments of SH-Py for ADH detection in textiles. Moreover, the visualization of ADH in textiles was successfully achieved by spraying the probe solution and then inspecting it under a UV lamp. Additionally, SH-Py has the potential to quantify other aliphatic hydrazides in various samples.

Impurity Level-Induced Broadband Photoelectric Response in Wide-Bandgap Semiconductor SrSnO3.

Broadband spectrum detectors exhibit great promise in fields such as multispectral imaging and optical communications. Despite significant progress, challenges like materials instability in such devices, complex manufacturing process, and high cost still hinder their further application. Here, we present a method that achieves broadband spectral detection by impurity-level in SrSnO3. We report over 500 mA/W photoresponsivity at 275 nm (ultraviolet C solar-bind) and 367 nm (ultraviolet A) and ∼60 mA/W photoresponsivity at 532 and 700 nm (visible) with a voltage bias of -5 V. Further transport and photoluminescence results reveal a new phase transition at 88 K, which would significantly affect the impurity level of the La-doped SrSnO3 film, indicating that the broadband response attributes to the impurity levels and mutual interactions. Additionally, the photodetector demonstrates excellent robustness and stability under repeated tests and prolonged exposure in air. These findings show the potential of SrSnO3 as a material for photodetectors and propose a method to achieve broadband spectrum detection, creating new possibility for the development of single-phase, low-cost, simple structure, and high-efficiency photodetectors.

The gut microbiota-aromatic hydrocarbon receptor (AhR) axis mediates the anticolitic effect of polyphenol-rich extracts from Sanghuangporus.

Inflammatory bowel disease (IBD) is a significant global health concern. The gut microbiota plays an essential role in the onset and development of IBD. Sanghuangporus (SH), a traditional Chinese medicinal mushroom, has excellent anti-inflammatory effects and is effective at modulating the gut microbiota. Despite these attributes, the specific anticolitic effects of SH and the mechanisms through which the gut microbiota mediates its benefits remain unclear. Herein, we demonstrated that polyphenol-rich extract from SH effectively alleviated the pathological symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by modulating the gut microbiota. Treatment with SH distinctly enriched Alistipes, especially Alistipes onderdonkii, and its metabolite 5-hydroxyindole-3-acetic acid (5HIAA). Oral gavage of live A. onderdonkii or 5HIAA potently mitigated DSS-induced colitis in mice. Moreover, both 5HIAA and SH significantly activated the aromatic hydrocarbon receptor (AhR), and the administration of an AhR antagonist abrogated their protective effects against colitis. These results underscore the potent efficacy of SH in diminishing DSS-induced colitis through the promotion of A. onderdonkii and 5HIAA, ultimately activating AhR signaling. This study unveils potential avenues for developing therapeutic strategies for colitis based on the interplay between SH and the gut microbiota.

Effectiveness and safety of Governor vessel acupuncture therapy for post-stroke cognitive impairment: A meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of Governor vessel acupuncture (GV Ac) in treating post-stroke cognitive impairment (PSCI). METHODS: There was a total of seven databases examined. Four English databases (Cochrane Library, PubMed, Embase, and Medline) and three Chinese databases (Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Databases (VIP), and Wan Fang Database) contain all randomized controlled trials (RCTs) comparing Governor vessel acupuncture to other treatments or none acupuncture for PSCI. The exact dates for the search period are from January 1, 2000, to January 1, 2023.Two researchers independently reviewed the literature, gathered RCT data, and performed statistical analysis. All data were analyzed using Review Manager software (Rev Man) 5.3. RESULTS: This meta-analysis includes a total of 39 trials with 2044 patients. There were 1022 participants in each of the test and control groups. Following 12-120 days of acupuncture treatment, a meta-analysis revealed that the treatment groups (GV Ac combined with conventional treatment groups) significantly increased their scores on the Curative ratio (OR = 3.00, 95 %CI = 2.37-3.79, P = 0.98, I² = 0 %), Montreal Cognitive Assessment (MoCA)(MD = 1.82, 95 %CI = 1.60-2.03, P = 0.11, I² = 25 %), Mini-Mental State Examination (MMSE)(MD = 2.18, 95 %CI = 1.64-2.72, P<0.005, I² = 92 %), and Activity of Daily Living (ADL)(MD = 5.99, 95 %CI = 5.33-6.64, P = 0.19, I² = 26 %). CONCLUSION: The results suggested that acupuncture on points of the Governor vessel enhanced cognitive function in stroke survivors.

IGF2BP2 regulates the inflammation of fibroblast-like synoviocytes via GSTM5 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with an unknown etiology. RA cannot be fully cured and requires lengthy treatment, imposing a significant burden on both individuals and society. Due to the lack of specific drugs available for treating RA, exploring a key new therapeutic target for RA is currently an important task. Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the progression of RA, which release interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α resulting in abnormal inflammatory reaction in the synovium. A previous study has highlighted the correlation of m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) with inflammation-related diseases in human. However, the role of IGF2BP2 in the inflammatory reaction of FLSs during RA progression has not been assessed. In this study, IGF2BP2 expression was decreased in the synovial tissues of RA patients and collagen-induced arthritis (CIA) rats. Intra-articular injection of an adeno-associated virus (AAV) vector overexpressing IGF2BP2 relieved paw swelling, synovial hyperplasia and cartilage destruction in CIA rats. IGF2BP2 overexpression also inhibited lipopolysaccharide (LPS)-mediated RA fibroblast-like synoviocytes (RA-FLSs) migration and invasion accompanied by a decreased level of inflammatory factors in vitro. Conversely, IGF2BP2 suppression promoted RA-FLSs migration and invasion with an elevated level of inflammatory factors in vitro. The sequencing result showed that glutathione S-transferase Mu 5 (GSTM5), a key antioxidant gene, was the target mRNA of IGF2BP2. Further experiments demonstrated that IGF2BP2 strengthened the stability of GSTM5 mRNA, leading to weakened inflammatory reaction and reduced expression of matrix metalloproteinase 9 and 13 (MMP9, MMP13). Therefore, IGF2BP2-GSTM5 axis may represent a potential therapeutic target for RA treatment.

Black raspberry-mediated metabolic changes in patients with familial adenomatous polyposis associated with rectal polyp regression.

Familial adenomatous polyposis (FAP) patients face an almost certain 100% risk of developing colorectal cancer, necessitating prophylactic colectomy to prevent disease progression. A crucial goal is to hinder this progression. In a recent clinical trial involving 14 FAP patients, half received 60 g of black raspberry (BRB) powder orally and BRB suppositories at bedtime, while the other half received only BRB suppositories at bedtime over 9 months. This intervention led to a notable reduction in rectal polyps for 11 patients, although 3 showed no response. In this study, we delved into the metabolic changes induced by BRBs in the same patient cohort. Employing mass spectrometry-based non-targeted metabolomics, we analyzed pre- and post-BRB urinary and plasma samples from the 11 responders. The results showed significant alterations in 23 urinary and 6 plasma metabolites, influencing various pathways including polyamine, glutathione metabolism, the tricarboxylic acid cycle, inositol metabolism, and benzoate production. BRBs notably elevated levels of several metabolites associated with these pathways, suggesting a potential mechanism through which BRBs facilitate rectal polyp regression in FAP patients by modulating multiple metabolic pathways. Notably, metabolites derived from BRB polyphenols were significantly increased post-BRB intervention, emphasizing the potential therapeutic value of BRBs in FAP management.

Analysis of lncRNA-related studies of ivermectin-sensitive and -resistant strains of Haemonchus contortus.

In this study, 858 novel long non-coding RNAs (lncRNAs) were predicted as sensitive and resistant strains of Haemonchus contortus to ivermectin. These lncRNAs underwent bioinformatic analysis. In total, 205 lncRNAs significantly differed using log2 (difference multiplicity) > 1 or log2 (difference multiplicity) < - 1 and FDR < 0.05 as the threshold for significant difference analysis. We selected five lncRNAs based on significant differences in expression, cis-regulation, and their association with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. These expressions of lncRNAs, namely MSTRG.12610.1, MSTRG.8169.1, MSTRG.6355.1, MSTRG.980.1, and MSTRG.9045.1, were significantly downregulated. These findings were consistent with the results of transcriptomic sequencing. We further investigated the relative expression of target gene mRNAs and the regulation of mRNA and miRNA, starting with lncRNA cis-regulation of mRNA, and constructed a lncRNA-mRNA-miRNA network regulation. After a series of statistical analyses, we finally screened out UGT8, Unc-116, Fer-related kinase-1, GGPP synthase 1, and sart3, which may be involved in developing drug resistance under the regulation of their corresponding lncRNAs. The findings of this study provide a novel direction for future studies on drug resistance targets.

Examining starch metabolism in lotus roots (Nelumbo nucifera Gaertn.) during post-harvest storage at different temperatures.

This study explores the impact of postharvest storage temperatures (4 °C and 25 °C) on starch metabolism and textural attributes of glutinous lotus root. While starch metabolism is a well-known factor influencing texture, changes in powdery and sticky qualities have remained unexplored. Our research reveals that storing lotus roots at 4 °C delays water dissipation, amylopectin reduction, and the decline in textural elements such as hardness, adhesiveness, springiness, gumminess, and resilience. Lower temperatures postpone amylopectin reduction and sugar interconversion, thereby preserving the sticky texture. Additionally, they suppress starch formation, delay starch metabolism, and elevate the expression of genes involved in starch metabolism. The correlation between gene expression and root texture indicates the critical role of gene regulation in enzyme activity during storage. Overall, low-temperature storage extends lotus root preservation by regulating metabolite content, enzyme activities, and the corresponding genes involved in starch metabolism, preserving both intrinsic and external root quality.

Fast detection of sodium dithionite in sugar using a xanthylium-based fluorescent probe.

Dithionite remained in the foodstuff may pose a great threat to the health of consumers. Three xanthylium-based probes were synthesized and their responses to dithionite were explored. Probe SH-1 could respond to dithionite selectively in PBS buffer (15% DMSO, 10 mM, pH = 7.4). Upon the addition of dithionite, the fluorescent emission of SH-1 at 684 nm dropped quickly (within 10 s) and the fluorescence decline was proportional to the concentration of dithionite (0-7.0 µM). The limit of detection was determined to be 0.139 µM. Then, the sensing mechanism was tentatively presented and the structure of resulted adduct (SH-1-SO3-) which was the reaction product of SH-1 and dithionite via a Micheal addition reaction followed by an oxidation reaction was verified. Moreover, white granulated sugar was subjected to the standard spike experiments and the results demonstrated a great potential of SH-1 for the quantitative monitoring of dithionite in foodstuffs.

Preparation and characterization of water vapor-responsive methylcellulose-polyethylene glycol-400 composite membranes and an indication of freshness of shiitake mushrooms.

Intelligent packaging with freshness indication capability can help consumers purchase fresh food. However, current research primarily focuses on carbon dioxide-sensitive intelligent packaging, with limited research on water vapor-sensitive indication packaging. In this study, the water vapor-sensitive indicator membrane was prepared and used to determine the freshness of mushrooms. The results of this study showed that the water permeability of the indicator membrane decreased from 33.17 % to 21.59 % with the increase of Polyethylene glycol-400(PEG-400) content in methylcellulose(MC) membrane, and the contact angle of the indicator membrane increased from 87 % to 98 % with the addition of PEG-400. The addition of plasticizer PEG-400 increased the hydrophobicity of the indicator film, which could be attributed to the improvement of the molecular arrangement and crystallinity of the indicator film by the addition of PEG-400. After encountering water, the transparency of the indicator membrane changes from completely opaque (white) to transparent. Addition of PEG-400 reduces the rate of change in the transparency of the indicator membrane. The indicator membrane was successfully used to indicate the freshness of mushrooms and effectively reflected the freshness of mushrooms during storage. This technology could be applied to measure the freshness of other foods.

Acupuncture for cognitive impairment after stroke: A systematic review and meta-analysis.

Objective: Acupuncture as an alternative therapy for post-stroke cognitive impairment (PSCI) has emerged as a research focus. The inclusion of additional external treatments in many previous studies prevents a clear, direct assessment of acupuncture's impact on PSCI. In order to prevent patients from developing hypersensitivity to other treatments and misinterpreting acupuncture's true therapeutic value, this study establish stricter intervention criteria and exclude therapies beyond acupuncture. The review aimed to offering a clearer evaluation of acupuncture's efficacy and safety in PSCI treatment. Methods: This research involved a comprehensive search for randomized controlled trials (RCTs) across eight databases, adhering to the Cochrane Systematic Reviewer's Handbook 5.1.0 for risk-of-bias and quality assessments. A meta-analysis was conducted using RevMan 5.3 software. Results: The inclusion of 18 publications, totaling 1361 patients, was achieved. The meta-analysis demonstrated a significantly higher overall efficacy of acupuncture for PSCI compared to controls (OR = 4.06, 95 % CI 2.86-5.76, Z = 7.82). Notable statistical differences were observed in the Montreal Cognitive Assessment scores (MD = 2.32, 95 % CI 1.68-2.97, Z = 7.10) and the Mini-Mental State Examination scores (MD = 2.02, 95 % CI 1.06-2.98, Z = 4.13) between the groups. Improvements in the Barthel Index scores were noted for the experimental group (MD = 5.70, 95 % CI 4.68-6.72, Z = 10.92). Conclusion: Integrating acupuncture with Western medications offers significant benefits for treating PSCI over Western medications alone. However, the long-term efficacy of acupuncture in PSCI treatment and its potential in reducing recurrence rates remain undetermined. Further high-standard RCTs are essential to explore acupuncture's effectiveness in PSCI treatment more thoroughly.

Machine-learning-based models to predict cardiovascular risk using oculomics and clinic variables in KNHANES.

BACKGROUND: Recent researches have found a strong correlation between the triglyceride-glucose (TyG) index or the atherogenic index of plasma (AIP) and cardiovascular disease (CVD) risk. However, there is a lack of research on non-invasive and rapid prediction of cardiovascular risk. We aimed to develop and validate a machine-learning model for predicting cardiovascular risk based on variables encompassing clinical questionnaires and oculomics. METHODS: We collected data from the Korean National Health and Nutrition Examination Survey (KNHANES). The training dataset (80% from the year 2008 to 2011 KNHANES) was used for machine learning model development, with internal validation using the remaining 20%. An external validation dataset from the year 2012 assessed the model's predictive capacity for TyG-index or AIP in new cases. We included 32122 participants in the final dataset. Machine learning models used 25 algorithms were trained on oculomics measurements and clinical questionnaires to predict the range of TyG-index and AIP. The area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score were used to evaluate the performance of our machine learning models. RESULTS: Based on large-scale cohort studies, we determined TyG-index cut-off points at 8.0, 8.75 (upper one-third values), 8.93 (upper one-fourth values), and AIP cut-offs at 0.318, 0.34. Values surpassing these thresholds indicated elevated cardiovascular risk. The best-performing algorithm revealed TyG-index cut-offs at 8.0, 8.75, and 8.93 with internal validation AUCs of 0.812, 0.873, and 0.911, respectively. External validation AUCs were 0.809, 0.863, and 0.901. For AIP at 0.34, internal and external validation achieved similar AUCs of 0.849 and 0.842. Slightly lower performance was seen for the 0.318 cut-off, with AUCs of 0.844 and 0.836. Significant gender-based variations were noted for TyG-index at 8 (male AUC=0.832, female AUC=0.790) and 8.75 (male AUC=0.874, female AUC=0.862) and AIP at 0.318 (male AUC=0.853, female AUC=0.825) and 0.34 (male AUC=0.858, female AUC=0.831). Gender similarity in AUC (male AUC=0.907 versus female AUC=0.906) was observed only when the TyG-index cut-off point equals 8.93. CONCLUSION: We have established a simple and effective non-invasive machine learning model that has good clinical value for predicting cardiovascular risk in the general population.

The mediation mechanism of calcium ions on black bean type 3 resistant starch: Metabolomics, structure characteristics and digestibility.

The type 3 resistant starch (RS3) is beneficial for blood glucose management. A high quality RS3 was provided and its formation mechanism after calcium ion (Ca2+) treatment was investigated in this study. The metabolomics, structure and digestion properties were evaluated. Metabolomics was performed by untargeted UHPLC-Q-TOF/MS, and a total of 11 significantly different metabolites was found. The NMR, ATR-FTIR, and XRD results showed that the degree of double helix decreased from 5.34 to 1.07, crystallinity decreased from 33.58 % to 19.88 %, and the amorphous region increased from 69.76 % to 78.33 %. Large particle polymers were observed by SEM on the granule surface of starch with Ca2+ treatment. Digestion test showed that Ca2+ increased the RS3 from 9.70 % to 22.26 %. The result indicated that Ca2+ induced the formation of chelates between Ca2+ and -OH, promoted the RS3 content and regulated carbohydrate metabolism. The study provided theoretical basis for producing low-glycemic black bean foods.

The dual function of calcium ion in fruit edible coating: Regulating polymer internal crosslinking state and improving fruit postharvest quality.

The edible coating is proved to be a convenient approach for fruit preservation. Among these published explorations, naturally sourced macromolecules and green crosslinking strategies gain attention. This work centers on edible coatings containing Ca2+ as crosslinker for the first time, delving into crosslinking mechanisms, include alginate, chitosan, Aloe vera gel, gums, etc. Additionally, the crucial functions of Ca2+ in fruit's quality control are also elaborated in-depth, involving cell wall, calmodulin, antioxidant, etc. Through a comprehensive review, it becomes evident that Ca2+ plays a dual role in fruit edible coating. Specifically, Ca2+ constructs a three-dimensional dense network structure with polymers through ionic bonding. Moreover, Ca2+ acts directly with cell wall to maintain fruit firmness and serve as a second messenger to participate secondary physiological metabolism. In brief, coatings containing Ca2+ present remarkable effects in preserving fruit and this work may provide guidance for Ca2+ related fruit preservation coatings.

Surface modifications towards superhydrophobic wood-based composites: Construction strategies, functionalization, and perspectives.

Amidst the burgeoning interest in multifunctional superhydrophobic wood-based composites (SWBCs) for their varied applications and the need for improved environmental resilience, recent efforts focus on enhancing their utility by integrating features such as mechanical and chemical stability, self-healing capabilities, flame resistance, and antimicrobial properties. Research indicates that various external conditions can influence the wettability and additional characteristics of SWBCs. This comprehensive review outlines three critical factors affecting SWBCs' performance: synthesis methods, wood taxonomy, and chemical agents. It further provides a detailed overview of SWBCs' specific attributes, including essential qualities for diverse applications and the limitations posed by different contexts. Additionally, it elaborates on performance evaluation techniques, offering a foundational framework for SWBCs' practical application. This work aims to serve as an important resource for future research and development in SWBC engineering.

TPR is a prognostic biomarker and potential therapeutic target associated with immune infiltration in hepatocellular carcinoma.

Liver cancer is the fourth leading cause of cancer-related mortality worldwide and hepatocellular carcinoma (HCC) is the most common primary liver cancer. In the present study, it was demonstrated that translocated promoter region (TPR) was upregulated in tumor tissues and associated with prognosis and immune infiltration in HCC. The clinical outcome of patients with HCC with aberrant expression of TPR was examined using multiple databases, including Gene Expression Omnibus, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression, Kaplan-Meier (KM) Plotter and Xiantao tool. The clinicopathologic characteristics of patients from TCGA database that were associated with overall survival were assessed using Cox regression and KM analysis. The potential hallmarks associated with TPR expression were further predicted by Metascape and Gene Set Enrichment Analysis, and the relationship between TPR and immune infiltration was explored using the Tumor-Immune System Interactions Database and the Tumor Immune Estimation Resource. The results demonstrated that TPR expression was higher in HCC and its overexpression was associated with a worse prognosis, alongside a correlation with several clinical features. Furthermore, cell differentiation, a prospective new hallmark of cancer, was differentially enriched in the high TPR expression phenotype pathway. Moreover, TPR may also modulate the tumor immune microenvironment as it was significantly associated with immunoregulators and chemokines, as well as different tumor infiltration immune cells. According to the in vitro experiments, TPR silencing inhibited the phosphorylation of AKT and the proliferation of HCC cells. In summary, TPR may be a new marker and target for HCC therapy.

ALOX5 drives the pyroptosis of CD4+ T cells and tissue inflammation in rheumatoid arthritis.

Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A4 (LTA4), were increased in CD4+ T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission. Knockdown or pharmacological inhibition of ALOX5 suppressed CD4+ T cell pyroptosis and improved symptoms in two rodent models of RA. Mechanistically, the increase in ALOX5 activity in RA CD4+ T cells enhanced the production of the LTA4 derivative LTB4, which stimulated Ca2+ influx through ORAI3 channels, leading to the activation of NLRP3 inflammasomes and pyroptosis. Our findings reveal a role for ALOX5 in RA and provide a molecular basis for further exploring the clinical utility of ALOX5 inhibition in RA and for using ALOX5 as a biomarker to distinguish active disease and remission in RA.

Simulated gastrointestinal digestion of walnut protein yields anti-inflammatory peptides.

The impact of the simulated gastrointestinal digestion process on walnut protein and the potential anti-inflammatory properties of its metabolites was studied. Structural changes induced by digestion, notably in α-Helix, ß-Turn, and Random Coil configurations, were unveiled. Proteins over 10,000 Da significantly decreased by 35.6 %. Antioxidant activity in these metabolites paralleled increased amino acid content. Molecular docking identified three walnut polypeptides-IPAGTPVYLINR, FQGQLPR, and VVYVLR-with potent anti-inflammatory properties. RMSD and RMSF analysis demonstrated the stable and flexible interaction of these polypeptides with their target proteins. In lipopolysaccharide (LPS)-induced inflammation in normal human colon mucosal epithelial NCM460 cells, these peptides decreased 5-hydroxytryptamine (5-HT), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) expression, while mitigating cell apoptosis and inflammation. Our study offers valuable insights into walnut protein physiology, shedding light on its potential health benefits.

Endoplasmic reticulum aminopeptidase 2 regulates CD4+ T cells pyroptosis in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease with a complex pathogenesis that has not yet been fully elucidated, and T-cell pyroptosis is an important pathogenetic factor in RA. This study aimed to investigate the role of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the pyroptosis of CD4+ T cells in RA and the specific molecular mechanism. METHODS: Peripheral venous blood was collected from human subjects, and CD4+ T cells were isolated and activated to measure the level of pyroptosis and ERAP2 expression. Pyroptosis levels were assessed using immunofluorescence, flow cytometry, qRT-PCR, and Western blotting. Changes in pyroptosis levels were observed upon knockdown or overexpression of ERAP2. To detect activated Caspase-1 in tissues, chimeric mice were engrafted with human synovial tissue and reconstituted with human CD4+ T cells. CD4 + T cells were treated with GLI1 antagonists and SMO receptor agonists to detect changes in pyroptosis levels. RESULTS: CD4+ T cell levels undergoing pyroptosis were found to be elevated in the blood and synovium of RA patients. The gene and protein expression of ERAP2 were significantly higher in CD4+ T cells from RA patients. Deletion of ERAP2 suppressed pyroptosis of these cells, attenuated the activation of Caspase-1 in tissue T cells, and reduced tissue inflammatory responses. Reciprocally, overexpression of ERAP2 triggered inflammasome assembly, activated Caspase-1, and induced pyroptosis in CD4+ T cells. Mechanistically, ERAP2 inhibits the Hedgehog signaling pathway and upregulates the expression of nucleotide-binding oligomerization segment-like receptor family 3(NLRP3), cleaved Caspase-1, and Gasdermin D to promote pyroptosis in CD4+ T cells. CONCLUSIONS: Taken together, our results identify a novel mechanism by which ERAP2 regulates RA development and document the effect of the ERAP2/Hedgehog signaling axis on pyroptosis of CD4+ T cells from RA patients.