USP10-mediated deubiquitination of NR3C1 regulates bone homeostasis by controlling CST3 expression.

Dysregulated bone homeostasis contributes to multiple diseases including osteoporosis (OP). In this study, osteoporotic mice were successfully generated using ovariectomy to investigate the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in OP. NR3C1, identified as a significantly upregulated gene in OP using bioinformatic tools, was artificially downregulated in osteoporotic mice. NR3C1 expression was significantly elevated in the femoral tissues of osteoporotic patients, and downregulation of NR3C1 alleviated bone loss and restored bone homeostasis in osteoporotic mice, as manifested by increased ALP- and OCN-positive cells and reduced RANKL/OPG ratio. Downregulation of NR3C1 inhibited osteoclastic differentiation of RAW264.7 cells and mouse bone marrow-derived macrophages (BMDM) and promoted osteogenic differentiation of MC3T3-E1 cells. The transcription factor NR3C1 bound to the cystatin-3 (CST3) promoter to repress its transcription in both RAW264.7 and MC3T3-E1 cells. The downregulation of CST3 reversed the protective effect of NR3C1 downregulation against OP. Ubiquitin-specific-processing protease 10 (USP10)-mediated deubiquitination of NR3C1 improved NR3C1 stability. Downregulation of USP10 inhibited osteoclastic differentiation of RAW264.7 cells and BMDM while promoting osteogenic differentiation of MC3T3-E1 cells. Taken together, USP10-mediated deubiquitination of NR3C1 regulates bone homeostasis by controlling CST3 transcription, providing an optical therapeutic strategy to alleviate OP.

SNORA5A regulates tumor-associated macrophage M1/M2 phenotypes via TRAF3IP3 in breast cancer.

Small nucleolar RNAs (snoRNAs) have robust potential functions and therapeutic value in breast cancer. Herein, we investigated the role SNORA5A in breast cancer. Samples from The Cancer Genome Atlas (TCGA) were reviewed. The transcription matrix and clinical information were analyzed using R software and validated in clinical tissue samples. SNORA5A was significantly down-regulated in breast cancer, and high expression of SNORA5A correlated with a favorable prognosis. High expression of SNORA5A induced a high concentration of tumor-associated macrophages M1 and a low concentration of tumor-associated macrophages M2. Moreover, SNORA5A were clustered in terms related to cancer and immune functions. Possible downstream molecules of SNORA5A were identified, among which TRAF3IP3 was positively correlated with M1 and negatively correlated with M2. The function of TRAF3IP3 in tumor inhibition and its relationship with macrophages in clinical tissue samples were in accordance with bioinformatics analysis results. SNORA5A could regulate macrophage phenotypes through TRAF3IP3 and serves as a potential prognostic marker for breast cancer patients.

P T-symmetric photonic lattices with type-II Dirac cones.

The type-II Dirac cone is a special feature of the band structure, whose Fermi level is represented by a pair of crossing lines. It has been demonstrated that such a structure is useful for investigating topological edge solitons and, more specifically, for mimicking the Klein tunneling. However, it is still not clear what the interplay between type-II Dirac cones and the non-Hermiticity mechanism will result in. Here, this question is addressed; in particular, we report the P T-symmetric photonic lattices with type-II Dirac cones for the first time to our knowledge. We identify a slope-exceptional ring and name it the type-II exceptional ring. We display the restoration of the P T symmetry of the lattice by reducing the separation between the sites in the unit cell. Curiously, the amplitude of the beam during propagation in the non-Hermitian lattice with P T symmetry only decays because of diffraction, whereas in the P T symmetry-broken lattice it will be amplified, even though the beam still diffracts. This work establishes the link between the non-Hermiticity mechanism and the violation of Lorentz invariance in these physical systems.

Identification and screening of umami peptides from skipjack tuna (Katsuwonus pelamis) hydrolysates using EAD/CID based micro-UPLC-QTOF-MS and the molecular interaction with T1R1/T1R3 taste receptor.

In this study, the enzymatic hydrolysates of skipjack tuna, Katsuwonus pelamis, were purified by ultrafiltration and further identified through micro-ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (micro-UPLC-QTOF-MS). The potential umami peptides were identified using both conventional collision-induced dissociation (CID) and novel electron-activated dissociation (EAD) fragmentation techniques. Nine novel umami peptides with iUmami-SCM > 588 were screened. Sensory evaluation and electronic tongue analysis were performed to confirm the taste characteristics of the umami peptides, indicating that these umami peptides all exhibited varying degrees of umami taste. Molecular docking and molecular dynamics simulation were utilized to investigate the interaction with T1R1/T1R3 taste receptors. The docking results revealed that Asp234, Ser23, Glu231, and Ile237 appeared most frequently in all docking sites and formed stable complexes through hydrogen bonding and electrostatic interactions. Furthermore, molecular dynamics simulation allowed for a more comprehensive analysis of their interactions within a dynamic environment, providing a deeper understanding of the umami perception mechanism involving umami peptides and receptors.

Driver Situation Awareness for Regaining Control from Conditionally Automated Vehicles: A Systematic Review of Empirical Studies.

OBJECTIVE: An up-to-date and thorough literature review is needed to identify factors that influence driver situation awareness (SA) during control transitions in conditionally automated vehicles (AV). This review also aims to ascertain SA components required for takeovers, aiding in the design and evaluation of human-vehicle interfaces (HVIs) and the selection of SA assessment methodologies. BACKGROUND: Conditionally AVs alleviate the need for continuous road monitoring by drivers yet necessitate their reengagement during control transitions. In these instances, driver SA is crucial for effective takeover decisions and subsequent actions. A comprehensive review of influential SA factors, SA components, and SA assessment methods will facilitate driving safety in conditionally AVs but is still lacking. METHOD: A systematic literature review was conducted. Thirty-four empirical research articles were screened out to meet the criteria for inclusion and exclusion. RESULTS: A conceptual framework was developed, categorizing 23 influential SA factors into four clusters: task/system, situational, individual, and nondriving-related task factors. The analysis also encompasses an examination of pertinent SA components and corresponding HVI designs for specific takeover events, alongside an overview of SA assessment methods for conditionally AV takeovers. CONCLUSION: The development of a conceptual framework outlining influential SA factors, the examination of SA components and their suitable design of presentation, and the review of SA assessment methods collectively contribute to enhancing driving safety in conditionally AVs. APPLICATION: This review serves as a valuable resource, equipping researchers and practitioners with insights to guide their efforts in evaluating and enhancing driver SA during conditionally AV takeovers.

Transmetalation in Surface-Confined Single-Layer Organometallic Networks with Alkynyl-Metal-Alkynyl Linkages.

Transmetalation represents an appealing strategy toward fabricating and tuning functional metal-organic polymers and frameworks for diverse applications. In particular, building two-dimensional metal-organic and organometallic networks affords versatile nanoarchitectures of potential interest for nanodevices and quantum technology. The controlled replacement of embedded metal centers holds promise for exploring versatile material varieties by serial modification and different functionalization. Herein, we introduce a protocol for the modification of a single-layer carbon-metal-based organometallic network via transmetalation. By integrating external Cu atoms into the alkynyl-Ag organometallic network constructed with 1,3,5-triethynylbenzene precursors, we successfully realized in situ its highly regular alkynyl-Cu counterpart on the Ag(111) surface. While maintaining a similar lattice periodicity and pore morphology to the original alkynyl-Ag sheet, the Cu-based network exhibits increased thermal stability, guaranteeing improved robustness for practical implementation.

Exploring the supplementary potential of all-trans retinoic acid with methotrexate in rheumatoid arthritis: modulation of synovial cell apoptosis and autophagy.

OBJECTIVES: The imbalance between apoptosis and proliferation in fibroblast-like synoviocytes (FLSs) plays a key role in the pathogenesis of rheumatoid arthritis (RA). This study aims to investigate the potential of all-trans retinoic acid (ATRA) as a supplementary therapeutic agent alongside methotrexate (MTX) for RA, by examining its ability to inhibit synovial cell proliferation and enhance apoptosis through the ROS-JNK signalling pathway. METHODS: The viability, apoptosis, and autophagy levels of human rheumatoid arthritis fibroblast-like synovial cells (HFLS-RA) were evaluated, while ROS generation was measured through the DCFH-DA fluorescence microplate assay. Western blotting was used to analyse the expression levels of JNK signalling pathway-related proteins. To assess therapeutic potential in vivo, a collagen-induced arthritis (CIA) model was established in Wistar rats. RESULTS: Small doses of MTX did not significantly affect the viability of HFLS-RAs or induce apoptosis. However, when ATRA was added to the treatment, the therapy markedly inhibited cell proliferation and induced apoptosis and excessive autophagy. Mechanistically, ATRA activated the ROS/JNK signalling pathway in HFLS-RAs. ROS scavengers and JNK inhibitors significantly attenuated ATRA-induced apoptosis and autophagy. In vivo, the combination therapy demonstrated a remarkable enhancement of the anti-arthritic efficacy in CIA rats. CONCLUSIONS: The ability of ATRA to inhibit proliferation in RA FLSs through autophagy and apoptosis underscores its potential as a supplementary therapeutic agent alongside MTX for RA, particularly when compared to the limited impact of MTX on these processes. This combined strategy holds promise for enhancing therapeutic outcomes and warrants further investigation in the management of RA.

Unconventional Band Structure via Combined Molecular Orbital and Lattice Symmetries in a Surface-Confined Metallated Graphdiyne Sheet.

Graphyne (GY) and graphdiyne (GDY)-based monolayers represent the next generation 2D carbon-rich materials with tunable structures and properties surpassing those of graphene. However, the detection of band formation in atomically thin GY/GDY analogues has been challenging, as both long-range order and atomic precision have to be fulfilled in the system. The present work reports direct evidence of band formation in on-surface synthesized metallated Ag-GDY sheets with mesoscopic (≈1 µm) regularity. Employing scanning tunneling and angle-resolved photoemission spectroscopies, energy-dependent transitions of real-space electronic states above the Fermi level and formation of the valence band are respectively observed. Furthermore, density functional theory (DFT) calculations corroborate the observations and reveal that doubly degenerate frontier molecular orbitals on a honeycomb lattice give rise to flat, Dirac and Kagome bands close to the Fermi level. DFT modeling also indicates an intrinsic band gap for the pristine sheet material, which is retained for a bilayer with h-BN, whereas adsorption-induced in-gap electronic states evolve at the synthesis platform with Ag-GDY decorating the (111) facet of silver. These results illustrate the tremendous potential for engineering novel band structures via molecular orbital and lattice symmetries in atomically precise 2D carbon materials.

Valorization of Lignocellulose with One-Step Acidified Monophasic Phenoxyethanol Fractionation.

Effective fractionation of lignocelluosic biomass and subsequent valorization of all three major components under mild conditions were achieved. Pretreatment with acidified monophasic phenoxyethanol (EPH) efficiently removed 92.6 % lignin and 80 % xylan from poplar at 110 °C in 60 min, yielding high-value EPH-xyloside, EPH-modified lignin (EPHL), and a solid residue nearly purely composed of carbohydrates. After removing the grafted acetyl groups using 1 % NaOH at 50 °C, the highest enzymatic digestibility reached 92.3 %. EPHL could be recovered in high yield and purity with an uncondensed structure, while xylose was converted to EPH-xyloside, a potential precursor in biomedical industries. Additionally, the acidified monophasic EPH solvent could effectively fractionate biomass from species other than hardwood, achieving over 70 % delignification from recalcitrant pinewood under the same mild conditions, demonstrating the high potential of monophasic EPH pretreatment.

Precise execution of personalized surgical planning using three-dimensional printed guide template in severe and complex adult spinal deformity patients requiring three-column osteotomy: a retrospective, comparative matched-cohort study.

BACKGROUND: The surgical treatment of severe and complex adult spinal deformity (ASD) commonly required three-column osteotomy (3-CO), which was technically demanding with high risk of neurological deficit. Personalized three dimensional (3D)-printed guide template based on preoperative planning has been gradually applied in 3-CO procedure. The purpose of this study was to compare the efficacy, safety, and precision of 3D-printed osteotomy guide template and free-hand technique in the treatment of severe and complex ASD patients requiring 3-CO. METHODS: This was a single-centre retrospective comparative cohort study of patients with severe and complex ASD (Cobb angle of scoliosis > 80° with flexibility < 25% or focal kyphosis > 90°) who underwent posterior spinal fusion and 3-CO between January 2020 to January 2023, with a minimum 12 months follow-up. Personalized computer-assisted three-dimensional osteotomy simulation was performed for all recruited patients, who were further divided into template and non-template groups based on the application of 3D-printed osteotomy guide template according to the surgical planning. Patients in the two groups were age- and gender- propensity-matched. The radiographic parameters, postoperative neurological deficit, and precision of osteotomy execution were compared between groups. RESULTS: A total of 40 patients (age 36.53 ± 11.98 years) were retrospectively recruited, with 20 patients in each group. The preoperative focal kyphosis (FK) was 92.72° ± 36.77° in the template group and 93.47° ± 33.91° in the non-template group, with a main curve Cobb angle of 63.35° (15.00°, 92.25°) and 64.00° (20.25°, 99.20°), respectively. Following the correction surgery, there were no significant differences in postoperative FK, postoperative main curve Cobb angle, correction rate of FK (54.20% vs. 51.94%, P = 0.738), and correction rate of main curve Cobb angle (72.41% vs. 61.33%, P = 0.101) between the groups. However, the match ratio of execution to simulation osteotomy angle was significantly greater in the template group than the non-template group (coronal: 89.90% vs. 74.50%, P < 0.001; sagittal: 90.45% vs. 80.35%, P < 0.001). The operating time (ORT) was significantly shorter (359.25 ± 57.79 min vs. 398.90 ± 59.48 min, P = 0.039) and the incidence of postoperative neurological deficit (5.0% vs. 35.0%, P = 0.018) was significantly lower in the template group than the non-template group. CONCLUSION: Performing 3-CO with the assistance of personalized 3D-printed guide template could increase the precision of execution, decrease the risk of postoperative neurological deficit, and shorten the ORT in the correction surgery for severe and complex ASD. The personalized osteotomy guide had the advantages of 3D insight of the case-specific anatomy, identification of osteotomy location, and translation of the surgical planning or simulation to the real surgical site.

Impact of HER2 status on clinicopathological characteristics and pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: HER2-low triple-negative breast cancer (TNBC) accounted for up to 34%-39% of primary TNBC and 22.2%-32% of metastatic TNBC. Our study aims to explore the relationship between HER2 expression and clinicopathological characteristics, analyze the impact of HER2 expression on the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in TNBC. METHODS: This study involved 191 patients with TNBC who underwent operation after NAC from October 2021 to August 2022. Clinicopathological characteristics and the frequency of pCR were compared between HER2-low and HER2-0 TNBC. RESULTS: 42.2% (81/191) patients in our cohort were HER2-low. They exhibited differences in menopausal status, body mass index (BMI), androgen receptor (AR) expression, and histological grade (P < 0.05). Particularly, in HER2-low TNBC, AR was associated with tumor size, lymph node metastase, histological grade, and the incidence of multifocal disease (P < 0.05). The total pCR rate of entire cohor was 39.8%. Tumor size (P = 0.025), AR status (P = 0.033) and histological grade (P = 0.007) were significantly associated with the pCR rate of them, while the HER2 status did not exert a similar association. The multivariate analysis revealed that BMI (P = 0.004) and histological grade (P < 0.001) were associated with pCR of HER2-low TNBC, while tumor size (P = 0.034) and AR (P = 0.034) were associated with pCR of HER2-0 TNBC, respectively. CONCLUSIONS: In our cohort, HER2-low TNBC patients exhibits specific clinical characteristics and response features to NAC.

U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression.

BACKGROUND: Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated. METHODS: SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted. RESULTS: SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model. CONCLUSION: U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness.

Cellular senescence in chronic lung diseases from newborns to the elderly: An update literature review.

The role of cellular senescence in age-related diseases has been fully recognized. In various age-related-chronic lung diseases, the function of alveolar epithelial cells (AECs) is impaired and alveolar regeneration disorders, especially in bronchopulmonary dysplasia，pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), cancer, etc. Except for age-related-chronic lung diseases, an increasing number of studies are exploring the role of cellular senescence in developmental chronic lung diseases, which typically originate in childhood and even in the neonatal period. This review provides an overview of cellular senescence and lung diseases from newborns to the elderly, attempting to draw attention to the relationship between cellular senescence and developmental lung diseases.

Development and classification of autonomous vehicle's ambiguous driving scenario.

Human drivers are gradually being replaced by highly automated driving systems, and this trend is expected to persist. The response of autonomous vehicles to Ambiguous Driving Scenarios (ADS) is crucial for legal and safety reasons. Our research focuses on establishing a robust framework for developing ADS in autonomous vehicles and classifying them based on AV user perceptions. To achieve this, we conducted extensive literature reviews, in-depth interviews with industry experts, a comprehensive questionnaire survey, and factor analysis. We created 28 diverse ambiguous driving scenarios and examined 548 AV users' perspectives on moral, ethical, legal, utility, and safety aspects. Based on the results, we grouped ADS, with all of them having the highest user perception of safety. We classified these scenarios where autonomous vehicles yield to others as moral, bottleneck scenarios as ethical, cross-over scenarios as legal, and scenarios where vehicles come to a halt as utility-related. Additionally, this study is expected to make a valuable contribution to the field of self-driving cars by presenting new perspectives on policy and algorithm development, aiming to improve the safety and convenience of autonomous driving.

Urban green and blue infrastructure: unveiling the spatiotemporal impact on carbon emissions in China's Yangtze River Delta.

Blue-green infrastructure (BGI) plays a crucial role in regulating urban carbon cycles. Nonetheless, the spatiotemporal effect of BGI on carbon emissions has not received extensive attention. This study used the Yangtze River Delta (YRD) region as the study area and quantified the landscape patterns of BGI. Using a spatiotemporal geographically weighted regression model, we analyzed the impact of evolving spatiotemporal characteristics of BGI on carbon emissions. Additionally, we constructed a spatiotemporal weight matrix using the Moran index ratio to examine the spillover effects of BGI among different regions. Our results show that the aggregation effect of carbon emissions in the YRD region is gradually increasing while BGI has a dynamic impact on carbon emissions. In terms of spatial and temporal spillovers, under the influence of economic connections between regions, patch fragmentation and distance exert a persistent positive influence on carbon emissions, while shape complexity has a negative impact, with area and layout characteristics showing no significant effects. However, area and patch distance have a persistent positive influence on carbon emissions in adjacent areas, while shape complexity exhibits a negative impact. Therefore, optimizing urban BGI through a regional synergistic governance system is important to promote low-carbon urban development.

The small nucleolar RNA SNORA51 enhances breast cancer stem cell-like properties via the RPL3/NPM1/c-MYC pathway.

Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.

SNORA5A regulates tumor-associated macrophage M1/M2 phenotypes via TRAF3IP3 in breast cancer

Small nucleolar RNAs (snoRNAs) have robust potential functions and therapeutic value in breast cancer. Herein, we investigated the role SNORA5A in breast cancer. Samples from The Cancer Genome Atlas (TCGA) were reviewed. The transcription matrix and clinical information were analyzed using R software and validated in clinical tissue samples. SNORA5A was significantly down-regulated in breast cancer, and high expression of SNORA5A correlated with a favorable prognosis. High expression of SNORA5A induced a high concentration of tumor-associated macrophages M1 and a low concentration of tumor-associated macrophages M2. Moreover, SNORA5A were clustered in terms related to cancer and immune functions. Possible downstream molecules of SNORA5A were identified, among which TRAF3IP3 was positively correlated with M1 and negatively correlated with M2. The function of TRAF3IP3 in tumor inhibition and its relationship with macrophages in clinical tissue samples were in accordance with bioinformatics analysis results. SNORA5A could regulate macrophage phenotypes through TRAF3IP3 and serves as a potential prognostic marker for breast cancer patients.

Effects of food-grade iron(III) oxide nanoparticles on cecal digesta- and mucosa-associated microbiota and short-chain fatty acids in rats.

Although iron(III) oxide nanoparticles (IONPs) are widely used in diverse applications ranging from food to biomedicine, the effects of IONPs on different locations of gut microbiota and short-chain fatty acids (SCFAs) are unclear. So, a subacute repeated oral toxicity study on Sprague Dawley (SD) rats was performed, administering low (50 mg/kg·bw), medium (100 mg/kg·bw), and high (200 mg/kg·bw) doses of IONPs. In this study, we found that a high dose of IONPs increased animal weight, and 16S rRNA sequencing revealed that IONPs caused intestinal flora disorders in both the cecal digesta- and mucosa-associated microbiota. However, only high-dose IONP exposure changed the abundance and composition of the mucosa-associated microbiota. IONPs increased the relative abundances of Firmicutes, Ruminococcaceae_UCG-014, Ruminiclostridium_9, Romboutsia, and Bilophila and decreased the relative abundance of Bifidobacterium, and many of these microorganisms are associated with weight gain, obesity, inflammation, diabetes, and mucosal damage. Functional analysis showed that changes in the gut microbiota induced by a high dose of IONPs were mainly related to metabolism, infection, immune, and endocrine disease functions. IONPs significantly elevated the levels of valeric, isobutyric, and isovaleric acid, promoting the absorption of iron. This is the first description of intestinal microbiota dysbiosis in SD rats caused by IONPs, and the effects and mechanisms of action of IONPs on intestinal and host health need to be further studied and confirmed.

All-trans retinoic acid alleviates collagen-induced arthritis and promotes intestinal homeostasis.

All-trans retinoic acid (ATRA) has emerged as a promising adjunctive treatment for rheumatoid arthritis. However, the mechanism by which ATRA mitigates arthritis remains unclear. In this study, we aimed to explore ATRA alleviation of arthritis and the role of ATRA in regulating intestinal homeostasis. Thus, we established a collagen-induced arthritis (CIA) model in Wistar rats. After 6 weeks of ATRA treatment, the arthritis index of CIA rats decreased, synovial inflammation was alleviated, and the disruption of Th17/Treg differentiation in peripheral blood was reversed. Additionally, the Th17/Treg ratio in the mesenteric lymph nodes decreased and the expression of Foxp3 mRNA increased and that of IL-17 mRNA decreased in the colon and ileum. Microscopically, we observed reduced intestinal inflammation. Transmission electron microscopy revealed that ATRA could repair tight junctions, which was accompanied by an increase in the expression of Claudin-1, Occludin and ZO-1. Moreover, ATRA regulated the composition of the gut microbiota, as was characterized based on the reduced abundance of Desulfobacterota and the increased abundance of Lactobacillus. In conclusion, ATRA demonstrates the potential to alleviate arthritis in CIA rats, which might be correlated with modulating the gut microbiota and regulating the intestinal immune response. Our findings provide novel insights into ATRA-mediated alleviation of arthritis.