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Objective: The association between myopia and diabetic retinopathy (DR) is unclear, with inconsistent results reported, and whether the association represents causality remains unknown. This study aimed to investigate the causal associations of genetically determined myopia with DR, and further explore specific mechanisms. Methods: We conducted two-sample mendelian randomization (MR) analyses of any myopia and high myopia on six DR phenotypes, including any DR, background DR, severe background DR, proliferative DR (PDR), diabetic maculopathy and unspecific DR in the primary study. Mechanism exploration of spherical equivalent refraction (SER), corneal curvature (CC) and axial length (AL) on any DR was carried out subsequently. Single-nucleotide polymorphisms (SNPs), used as genetic instruments, were derived from UK Biobank, Genetic Epidemiology Research on Adult Health and Aging cohort (GERA) and FinnGen. The inverse variance weighted (IVW) method was mainly used to assess the causality, and was complemented with sensitivity analyses and causality direction analyses. Results: Using SNPs that have excluded possible confounders, we discovered suggestive and positive causal associations of any myopia with any DR (IVW: odds ratio [OR] ​= ​1.133, 95% confidence interval [95%CI]: 1.070–1.201, P ​= ​1.91×10−5) and PDR (IVW: OR ​= ​1.182, 95% CI: 1.088–1.285, P ​= ​8.31×10−5). Similar but more significant associations were found of high myopia with any DR and PDR (IVW: OR ​= ​1.107, 95%CI: 1.051–1.166, P ​= ​1.39×10−4; OR ​= ​1.163, 95%CI: 1.088–1.244, P ​= ​8.76×10−6, respectively). Further mechanism analyses found only AL, rather than SER or CC, was strongly and significantly associated with any DR. These associations were robust in sensitivity analyses and causality direction analyses. Conclusions: We found significant and positive causal associations of any myopia and high myopia with the risk of DR and PDR, which might be related with AL, indicating the significance of myopia control for preventing DR development and progression.

Abstract Background To analyze the demographic characteristics of retinopathy of prematurity (ROP) in China, attempting to propose optimized screening criteria and hopefully providing valuable information for future updates to the ROP guideline. Methods A multicenter, retrospective-cohort study was conducted. The study included infants born between January 1, 2018, and July 31, 2023, who underwent ROP screening and were diagnosed with ROP at seven screening centers in China. Examinations were carried out in accordance with the ROP guidelines in 2014: infants with a gestational age (GA)

Abstract Posttranslational modifications (PTMs) of tubulin, termed the “tubulin code”, play important roles in regulating microtubule functions within subcellular compartments for specialized cellular activities. While numerous tubulin PTMs have been identified, a comprehensive understanding of the complete repertoire is still underway. In this study, we report that α-tubulin lactylation is catalyzed by HDAC6 by using lactate to increase microtubule dynamics in neurons. We identify lactylation on lysine 40 of α-tubulin in the soluble tubulin dimers. Notably, lactylated α-tubulin enhances microtubule dynamics and facilitates neurite outgrowth and branching in cultured hippocampal neurons. Moreover, we discover an unexpected function of HDAC6, acting as the primary lactyltransferase to catalyze α-tubulin lactylation. HDAC6-catalyzed lactylation is a reversible process, dependent on lactate concentrations. Intracellular lactate concentration triggers HDAC6 to lactylate α-tubulin, a process dependent on its deacetylase activity. Additionally, the lactyltransferase activity may be conserved in HDAC family proteins. Our study reveals the primary role of HDAC6 in regulating α-tubulin lactylation, establishing a link between cell metabolism and cytoskeleton functions.

Abstract PARP1 is crucial in DNA damage repair, chromatin remodeling, and transcriptional regulation. The principle of synthetic lethality has effectively guided the application of PARP inhibitors in treating tumors carrying BRCA1/2 mutations. Meanwhile, PARP inhibitors have exhibited efficacy in BRCA-proficient patients, further highlighting the necessity for a deeper understanding of PARP1 function and its inhibition in cancer therapy. Here, we unveil PIN2/TRF1-interacting telomerase inhibitor 1 (PINX1) as an uncharacterized PARP1-interacting protein that synergizes with PARP inhibitors upon its depletion across various cancer cell lines. Loss of PINX1 compromises DNA damage repair capacity upon etoposide treatment. The vulnerability of PINX1-deficient cells to etoposide and PARP inhibitors could be effectively restored by introducing either a full-length or a mutant form of PINX1 lacking telomerase inhibitory activity. Mechanistically, PINX1 is recruited to DNA lesions through binding to the ZnF3-BRCT domain of PARP1, facilitating the downstream recruitment of the DNA repair factor XRCC1. In the absence of DNA damage, PINX1 constitutively binds to PARP1, promoting PARP1-chromatin association and transcription of specific DNA damage repair proteins, including XRCC1, and transcriptional regulators, including GLIS3. Collectively, our findings identify PINX1 as a multifaceted partner of PARP1, crucial for safeguarding cells against genotoxic stress and emerging as a potential candidate for targeted tumor therapy.

Lupus nephritis (LN) is an autoimmune disease that rapidly progresses as a secondary consequence of systemic lupus erythematosus (SLE) and has a very poor prognosis. Therefore, this study aimed to identify characteristics of immune cell infiltration and investigate potential therapeutic targets using bioinformatics methods and the Murphy Roths Large/lymphoproliferation (MRL/lpr) mouse model. In this study, a total of 2,810 differentially expressed genes (DEGs) were identified, which were primarily enriched in inflammatory and immune regulation pathways. From these DEGs, 226 immune-related genes (IRGs) were also identified. The single-sample gene set enrichment analysis (ssGSEA) revealed that patients with LN had increased infiltration of effector memory CD4+ T cells, effector memory CD8+ T cells, gamma delta T cells, myeloid-derived suppressor cells (MDSC), follicular helper T cells, Th1 cells, and Th2 cells, and this was closely correlated with the DEG-IRGs. Furthermore, the potential therapeutic biomarkers, CD244, S100 calcium binding protein P (S100P), and vascular endothelial growth factor C (VEGFC), were identified by Random Forest Approach (RFA), which were validated in LN mice. These findings provide new evidence and insights for further research on diagnosis and treatment of LN by identifying critical genes and their associations with immune infiltration.

Abstract Purpose This study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab. Experimental design Data from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed. Results The baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07–1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12–1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20–1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model (P = 0.015 and 0.008, respectively). Conclusions A low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.

Abstract Background Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization–frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. Methods/design This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography–mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. Discussion This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. Ethics and dissemination Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. Trial registration ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Abstract Ischemic stroke in rodents is usually induced by intraluminal middle cerebral artery occlusion (MCAO) via the common carotid artery plugging filament invented by Koizumi et al. (MCAO-KM), or the external carotid artery plugging filament created by Zea Longa et al. (MCAO-LG). A systematic review of the distinctions between them is currently lacking. Here, we performed a meta-analysis in terms of model establishment, cerebral blood flow (CBF), and cerebral ischemia–reperfusion injury (CIRI) between them, Weighted Mean Differences and Standardized Mean Difference were used to analyze the combined effects, Cochrane's Q test and the I 2 statistic were applied to determine heterogeneity, sensitivity analysis and subgroup analysis were performed to explore the source of heterogeneity. Literature mining suggests that MCAO-KM brings shorter operation time (p = 0.007), higher probability of plugging filament (p

Abstract The COVID-19 pandemic has raised many issues for higher education institutions, one of which is the continued decline in funding and an increased emphasis on effectiveness and efficiency. Performance-based budgeting is being adopted in organisations to allocate resources more efficiently, and Chinese public universities are no exception. The present study explicitly aimed to examine the relationship among staff capacity, performance-based budgeting, and organisational performance in Chinese public universities. It also investigated the role of top management support as a moderator. A purposive sampling method was used to select a total of 271 participants who agreed to participate in an online survey. A multimethod approach combining partial least squares-structural equation modelling (PLS-SEM), the PROCESS macro and necessary condition analysis (NCA) was adopted. The PLS-SEM results indicated that performance-based budgeting had a positive relationship with university performance and served as a mediator between staff capacity and university performance. The moderated mediation results showed that top management moderated the relationship among the selected variables. The NCA results suggested that both staff capacity and performance-based budgeting are meaningful and significant necessary conditions for university performance. The combined results indicated how researchers and practitioners can identify the factors that are critical for university performance and result in the best possible outcomes. This is possibly the first study to use this multimethod approach in accounting research. Overall, this study offers valuable insights into performance-based budgeting implementation in higher education institutions and may serve as a guideline for public universities to improve the efficiency of funding, reduce costs and increase revenues.

Objective To analyze the clinical and genetic characteristics of zinc finger protein 408 ( ZNF408 )-related familial exudative vitreoretinopathy (FEVR) in a Chinese cohort. Methods Ninety families from Chongqing and 16 families from Xinjiang were selected according to fundus lesion characteristics. Peripheral venous blood was collected from patients and their families; genomic DNA was extracted for whole exome sequencing. Relationships between genotype and phenotype in patients with ZNF408 -related FEVR were analyzed. Results ZNF408 variants were detected in three patients (2.83%, 3/106). ZNF408 variants in these three probands were all missense mutations at novel sites. One proband had a ZNF408 and LRP5 double-gene variant, and two probands had ZNF408 single-gene variants. Patients with double-gene variants did not display more severe clinical manifestations. Conclusions This study expands the spectrum of known ZNF408 variants and confirms that ZNF408 variants can cause FEVR. Most variants detected in this study have not been reported in the literature and are suspected pathogenic variants of FEVR. In patients with FEVR, phenotype and genotype do not necessarily display a direct one-to-one relationship.

Objective: To analyze and compare the reliability of two new three-dimensional classifications of intertrochanteric fractures based on three-dimensional computed tomography (3-D CT) and two traditional classifications based on X-ray. Methods: X-ray and 3-D CT image data of 105 patients with intertrochanteric fractures were collected. Four orthopedic surgeons as observers used Evans-Jensen, AO/OTA-2018, Tang and Japanese new classification systems to classify the classification. Two months later, the original imaging data were renumbered, and the same methods was used for the classification again. κ test was used to evaluate the inter-observer and intra-observer consistency of each classification. Results: The inter-observer κ values of Evans-Jensen, AO/OTA-2018, Tang and Japanese new classifications were 0.91 (range 0.87–0.95), 0.90 (range 0.88–0.92), 0.93 (range 0.89–0.95) and 0.91 (range 0.89–0.93), respectively. There was no significant difference between Evans-Jensen and AO/OTA-2018 classification systems (p > 0.05) but were significant differences between Evans-Jensen and Tang, Evans-Jensen and Japanese new, AO/OTA-2018 and Tang, AO/OTA-2018 and Japanese new, Tang and Japanese new classification systems (p

Pericarpium Citri Reticulatae (PCR) is a natural citrus by-product with beneficial health and nutritive properties that is used widely in food and is an ingredient in traditional Chinese medicine. PCR improves gradually with aging. However, the present research has not yet revealed the reasons for this. Some data prove the important role of microorganisms in the quality of tobacco and fermented tea with the time of the aging of these foods. Our studies further proved that the coexisting Aspergillus niger plays an important role in the change of flavonoids and volatile oil in PCR during this process. Therefore, we put forward that longer storage is better for PCR and is highly correlated with the change of the coexisting microbial population structure caused by environmental factors. Samples of PCR aged in Beijing, Sichuan, Guangdong, and Yunnan were collected at different time points. Using GC/MS and high throughput 16S rDNA and ITS sequencing techniques, massive changes in volatile profile and microbial communities were observed during aging. Spearman correlation analysis indicated that Exobasidium, Xeromyces, Pseudocercospora, Russula, Aspergillus, Herbaspirillum, Sphingomonas, and Streptococcus, which are the dominant microbial genera in Sichuan and Guangdong showed strong connections with volatile components of chemical markers. It was preliminarily verified that the changes of volatile components for PCR are highly correlated with the change of the coexisting microbial population structure caused by environmental factors, providing a new idea for the research on the aging mechanism of PCR and key influencing factors of aging quality.

Abstract Advances in immunotherapy have revolutionized treatments in many types of cancer. Traditional Chinese Medicine (TCM), which has a long history of clinical adjuvant application against cancer, is emerging as an important medical resource for developing innovative cancer treatments, including immunotherapy. In this study, we developed a quantitative and systems pharmacology-based framework to identify TCM-derived natural products for cancer immunotherapy. Specifically, we integrated 381 cancer immune response-related genes and a compound-target interaction network connecting 3273 proteins and 766 natural products from 66 cancer-related herbs based on literature-mining. Via systems pharmacology-based prediction, we uncovered 182 TCM-derived natural products having potential anti-tumor immune responses effect. Importantly, 32 of the 49 most promising natural products (success rate = 65.31%) are validated by multiple evidence, including published experimental data from clinical studies, in vitro and in vivo assays. We further identified the mechanism-of-action of TCM in cancer immunotherapy using network-based functional enrichment analysis. We showcased that three typical natural products (baicalin, wogonin, and oroxylin A) in Huangqin (Scutellaria baicalensis Georgi) potentially overcome resistance of known oncology agents by regulating tumor immunosuppressive microenvironments. In summary, this study offers a novel and effective systems pharmacology infrastructure for potential cancer immunotherapeutic development by exploiting the medical wealth of natural products in TCM.

Objective The high resolution mass spectra database of common alkaloids were established and applied to the automatic screening of poisoning samples. Methods The accurate molecular mass and appropriate collision energy of each alkaloid was obtained by injecting alkaloid standard solutions into the Q exactive mass spectrometry directly or separated by high performance liquid chromatography and mass spectrometry analysis. The chromatographic analysis was performed on a HSS T3 column (2.1 mm×100 mm, 1.8 μm) by gradient elution using methanol and 5 mmol/L ammonium acetate containing 0.1% formic acid solution as mobile phase. The secondary mass information of alkaloid was collected in positive electrospray ionization and targeted-selected ion monitor-ddMS2 mode. The mass spectrometry data were applied to the automatic screening of actual samples. Results The mass spectrometry database of 72 alkaloids were established containing the theoretical accurate molecular mass, retention time collision energy and fragment ions. The multiple alkaloids in actual samples were locked rapidly by automatic screening with the mass spectra database. Conclusion This method is simple, fast, accurate and suitable for the rapid automatic screening of alkaloids in poisoned food sample.

Cordyceps has anti-cancer effects; however, the bioactive substance and its effect are still unclear. Polysaccharides extracted from Cordyceps sinensis, the fugus of Cordyceps, have been reported to have anti-cancer properties. Thus, we speculated that polysaccharides might be the key anti-tumor active ingredients of Cordyceps because of their larger molecular weight than that of polysaccharides in Cordyceps sinensis. In this study, we aimed to investigate the effects of wild Cordyceps polysaccharides on H22 liver cancer and the underlying mechanism. The structural characteristics of the polysaccharides of WCP were analyzed by high-performance liquid chromatography, high-performance gel-permeation chromatography, Fourier transform infrared spectrophotometry, and scanning electron microscopy. Additionally, H22 tumor-bearing BALB/c mice were used to explore the anti-tumor effect of WCP (100 and 300 mg/kg/d). The mechanism by WCP inhibited H22 tumors was uncovered by the TUNEL assay, flow cytometry, hematoxylin–eosin staining, quantitative reverse transcription–polymerase chain reaction, and Western blotting. Here, our results showed that WCP presented high purity with an average molecular weight of 2.1 × 106 Da and 2.19 × 104 Da. WCP was determined to be composed of mannose, glucose, and galactose. Notably, WCP could inhibit the proliferation of H22 tumors not only by improving immune function, but also by promoting the apoptosis of tumor cells, likely through the IL-10/STAT3/Bcl2 and Cyto-c/Caspase8/3 signaling pathways, in H22 tumor-bearing mice. Particularly, WCP had essentially no side effects compared to 5-FU, a common drug used in the treatment of liver cancer. In conclusion, WCP could be a potential anti-tumor product with strong regulatory effects in H22 liver cancer.

Background/Aims: The age-bilirubin-international normalized ratio-creatinine (ABIC) score, which is a predictive model commonly used for alcoholic hepatitis, has not yet been studied in acute-on-chronic hepatitis B liver failure (HBV-ACLF). We aimed to investigate the predictive value of the ABIC score in patients with HBV-ACLF. Methods: This retrospective study involved 398 patients diagnosed with HBV-ACLF, who were divided into a training cohort of 305 patients and a validation cohort of 93 patients. Univariate and multivariate Cox regression models were used to determine risk factors for mortality. Area under the receiver operating characteristic curve (AUC) was calculated to estimate and compare the predictive values of different prognostic scores. Results: The ABIC score was significantly higher in the death group of the training cohort than in its survival group. Independent risk factors for mortality identified by multivariate Cox analysis included blood urea nitrogen, ABIC score, and Chronic Liver Failure Consortium Organ Failure (CLIF-C OF) score. For predicting 1- and 3-month mortality, AUC was higher for the ABIC score than for the Model for End-stage Liver Diseases (MELD) score (0.732 vs. 0.653, P < 0.05, 0.695 vs. 0.619, P < 0.05, respectively), CLIF-C OF score (0.693, P=0.353, 0.656, P=0.341, respectively), and Child-Pugh score (0.675, P=0.189, 0.656, P=0.300, Respectively). Patients with ABIC score > 9.44 had reduced 1- and 3-month survival rates. Conclusion: ABIC score is superior to MELD score in predicting short-term survival in HBV-ACLF patients. ABIC score > 9.44 predicts high short-term mortality risk in HBV-ACLF patients.

Background/Aims: Increasing evidence indicates that the systemic inflammatory response plays a vital role in carcinogenesis. The Glasgow Prognostic Score or modified Glasgow Prognostic Score (GPS/mGPS) is a novel inflammatory indicator which consists of CRP and albumin. Here, we performed a meta-analysis to evaluate the prognostic value of the GPS/ mGPS in patients with colorectal cancer (CRC) and to assess its consistency in different CRC therapies. Methods: The electronic databases PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception through December 2017 for the association between the GPS/mGPS and clinical outcomes. Study characteristics and prognostic data were extracted from each relevant study. Overall survival (OS) and cancer-specific survival (CSS) were considered the primary outcomes, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. The quality of each study was pooled using the random-effects Mantel-Haenszel model. Finally, subgroup analyses were performed to detect the heterogeneity of different CRC treatments. Results: Thirty-four studies, with a combined total of 8834 patients, were eligible for this meta-analysis. Data on OS and CSS were available in 23 and 22 studies, respectively. By comparing the prognostic values of different levels of the GPS in CRC patients, the summary HRs for OS and CSS were 2.18 (95% CI 1.83-2.60) and 1.82 (95% CI 1.57-2.11), respectively. According to the different tumor stages, the subgroup analyses were stratified by different treatments, including curative or palliative therapy. The results robustly confirmed the prognostic role of the GPS/mGPS. Conclusion: Our results suggest that the GPS/mGPS is a novel and effective prognostic indicator for the OS and CSS of patients with CRC.

Background/Aims: Systemic inflammatory response (SIR) is widely considered as a preoperative risk factor for hepatocellular carcinoma (HCC) outcomes. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), two of the prognostic indices, have been investigated in post-therapeutic recurrence and survival of HCC. Here, we quantify the prognostic value of these two biomarkers and evaluate their consistency in different HCC therapies. Methods: A systematic review of electronic database of the Web of Science, Embase, PubMed and the Cochrane Library was conducted to search for associations between the NLR and PLR in the blood and clinical outcomes of HCC. Overall survival (OS) and recurrence-free survival (RFS) were the primary outcomes, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were explored as effect measures. Subgroup analyses were performed to explore the heterogeneity of different therapies. Results: A total of 24 articles comprising 6318 patients were included in the meta-analysis. Overall, the pooled outcomes revealed that a high NLR before treatment predicted a poor OS (HR: 1.54, 95% CI: 1.34 to 1.76, p

The editorial in Frontiers in Immunology discusses the emerging field of immune metabolism in auto- and allo-immunity. The editorial highlights the critical link between metabolic pathways and immune responses, focusing on research articles related to autoimmune diseases like Systemic Lupus Erythematosus and Type 1 Diabetes Mellitus, as well as transplant immunology. The articles explore how metabolic changes in immune cells impact disease pathogenesis and potential therapeutic strategies. Additionally, the editorial discusses the role of proline metabolism in asthma and the potential of immune cell metabolism in transplant tolerance. [Extracted from the article]

Non-alcoholic fatty liver disease (NAFLD) is closely associated with low-grade chronic inflammation which is usually induced by intestinal dysbiosis. As ferulic acid (FA) has been proven effective at improving the intestinal integrity, we aimed to determine the effect of dietary FA on NAFLD development in high-fat dieted (HFD) mice, a well-established model of NAFLD. Male C57BL/6J mice were fed either a normal chow diet (ND) or HFD with or without FA (40 mg/kg) orally for 6 weeks. FA significantly alleviated lipid metabolism disorder and reduced liver inflammation in HFD mice (P < 0.05). As expected, FA improved the ileal intestinal integrity likely via the Nuclear factor E2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway. Importantly, we found that FA also relieved HFD-induced gut microbiota dysbiosis by inhibiting the growth of harmful bacteria such as Helicobacter and increased the abundance of many shortchain fatty acids (SCFAs)-producing bacteria (P 0.05). Our data indicated that FA not only increased the colonic levels of SCFAs, but also maintained the colonic barrier integrity by up-regulating the expression of the epithelial tight junction protein. These data indicated that FA alleviated NAFLD by reducing circulating lipopolysaccharide levels. These effects may be due to improved proximal and distal intestinal barriers, which presumably mediated through the interaction of FA with the gut microbiota. [ABSTRACT FROM AUTHOR]