Targeting S100A12 to Improve Angiogenesis and Accelerate Diabetic Wound Healing.

Long-term inflammation and impaired angiogenesis are thought to be the causes of delayed healing or nonhealing of diabetic wounds. S100A12 is an essential pro-inflammatory factor involved in inflammatory reactions and serves as a biomarker for various inflammatory diseases. However, whether high level of S100A12 exists in and affects the healing of diabetic wounds, as well as the underlying molecular mechanisms, remain unclear. In this study, we found that the serum concentration of S100A12 is significantly elevated in patients with type 2 diabetes. Exposure of stratified epidermal cells to high glucose environment led to increased expression and secretion of S100A12, resulting in impaired endothelial function by binding to the advanced glycation endproducts (RAGE) or Toll-like receptor 4 (TLR4) on endothelial cell. The transcription factor Krüpple-like Factor 5 (KLF5) is highly expressed in the epidermis under high glucose conditions, activating the transcriptional activity of the S100A12 and boost its expression. By establishing diabetic wounds model in alloxan-induced diabetic rabbit, we found that local inhibition of S100A12 significantly accelerated diabetic wound healing by promoting angiogenesis. Our results illustrated the novel endothelial-specific injury function of S100A12 in diabetic wounds and suggest that S100A12 is a potential target for the treatment of diabetic wounds.

Reoperation for ipsilateral local recurrence following prior nephron-sparing surgery: innovative surgical insights from a high-volume urological center with cross-sectional study.

BACKGROUND: The main aim of this study was to examine the perioperative results of reoperations and suggest novel surgical approaches. Based on a substantial number of robotic and laparoscopic nephron-sparing surgery (NSS), we aim to propose novel surgical strategies that offer practical recommendations to surgeons. METHODS: Renal cell carcinoma patients with ipsilateral recurrent tumors, without evidence of metastasis, and who underwent primary NSS at our center between 2013 and 2023 were enrolled in this study, and all received the second time surgery. We conducted an analysis to evaluate perioperative outcomes and observed trends over a decade. Additionally, based on the findings from this study, we developed our surgical strategies. RESULTS: In the past decade, our center has successfully conducted a total of 2546 surgeries for renal cell carcinoma, out of which this study includes 15 patients who met the specified criteria. For reoperation, robotic-assisted surgery was applied in 5 cases (33.3%), laparoscopic surgery in 6 cases (40%), and open surgeries in 4 cases (26.7%). While 4 (26.7%) patients underwent NSS while radical nephrectomy was performed on 11 patients (73.3%). The median operative time was 215 minutes (IQR: 135-300), and the median estimated blood loss was 50 ml (IQR: 50-100). The median length of postoperative hospitalization was 6 days (IQR: 5-9). Furthermore, there has been a yearly increase in the application of robotic-assisted NSS at our institution. CONCLUSION: Reoperation following the pNSS is a secure and effective surgical approach. We introduce novel surgical strategies for primary surgery and reoperation, which offer valuable insights to surgeons in current study.

Optimizing anterior urethral stricture assessment: leveraging AI-assisted three-dimensional sonourethrography in clinical practice.

PURPOSE: This investigation sought to validate the clinical precision and practical applicability of AI-enhanced three-dimensional sonographic imaging for the identification of anterior urethral stricture. METHODS: The study enrolled 63 male patients with diagnosed anterior urethral strictures alongside 10 healthy volunteers to serve as controls. The imaging protocol utilized a high-frequency 3D ultrasound system combined with a linear stepper motor, which enabled precise and rapid image acquisition. For image analysis, an advanced AI-based segmentation process using a modified U-net algorithm was implemented to perform real-time, high-resolution segmentation and three-dimensional reconstruction of the urethra. A comparative analysis was performed against the surgically measured stricture lengths. Spearman's correlation analysis was executed to assess the findings. RESULTS: The AI model completed the entire processing sequence, encompassing recognition, segmentation, and reconstruction, within approximately 5 min. The mean intraoperative length of urethral stricture was determined to be 14.4 ± 8.4 mm. Notably, the mean lengths of the urethral strictures reconstructed by manual and AI models were 13.1 ± 7.5 mm and 13.4 ± 7.2 mm, respectively. Interestingly, no statistically significant disparity in urethral stricture length between manually reconstructed and AI-reconstructed images was observed. Spearman's correlation analysis underscored a more robust association of AI-reconstructed images with intraoperative urethral stricture length than manually reconstructed 3D images (0.870 vs. 0.820). Furthermore, AI-reconstructed images provided detailed views of the corpus spongiosum fibrosis from multiple perspectives. CONCLUSIONS: The research heralds the inception of an innovative, efficient AI-driven sonographic approach for three-dimensional visualization of urethral strictures, substantiating its viability and superiority in clinical application.

Altered leptin level in autism spectrum disorder and meta-analysis of adipokines.

BACKGROUND: Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis. METHODS: Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies. RESULTS: Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis. CONCLUSIONS: These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.

Adsorption mechanism of hexavalent chromium on electron beam-irradiated aged microplastics: Novel aging processes and environmental factors.

Microplastics are widely present in the natural environment and exhibit a strong affinity for heavy metals in water, resulting in the formation of microplastics composite heavy metal pollutants. This study investigated the adsorption of heavy metals by electron beam-aged microplastics. For the first time, electron beam irradiation was employed to degrade polypropylene, demonstrating its ability to rapidly age microplastics and generate a substantial number of oxygen-containing functional groups on aged microplastics surface. Adsorption experiments revealed that the maximum adsorption equilibrium capacity of hexavalent chromium by aged microplastics reached 9.3 mg g-1. The adsorption process followed second-order kinetic model and Freundlich model, indicating that the main processes of heavy metal adsorption by aged microplastics are chemical adsorption and multilayer adsorption. The adsorption of heavy metals on aged microplastics primarily relies on the electrostatic and chelation effects of oxygen-containing functional groups. The study results demonstrate that environmental factors, such as pH, salinity, coexisting metal ions, humic acid, and water matrix, exert inhibitory effects on the adsorption of heavy metals by microplastics. Theoretical calculations confirm that the aging process of microplastics primarily relies on hydroxyl radicals breaking carbon chains and forming oxygen-containing functional groups on the surface. The results indicate that electron beam irradiation can simultaneously oxidize and degrade microplastics while reducing hexavalent chromium levels by approximately 90%, proposing a novel method for treating microplastics composite pollutants. Gas chromatography-mass spectrometry analysis reveals that electron beam irradiation can oxidatively degrade microplastics into esters, alcohols, and other small molecules. This study proposes an innovative and efficient approach to treat both microplastics composite heavy metal pollutants while elucidating the impact of environmental factors on the adsorption of heavy metals by electron beam-aged microplastics. The aim is to provide a theoretical basis and guidance for controlling microplastics composite pollution.

Investigating the molecular mechanisms of Pseudalteromonas sp. LD-B1's algicidal effects on the harmful alga Heterosigma akashiwo.

Heterosigma akashiwo is a harmful algal bloom species that causes significant detrimental effects on marine ecosystems worldwide. The algicidal bacterium Pseudalteromonas sp. LD-B1 has demonstrated potential effectiveness in mitigating these blooms. However, the molecular mechanisms underlying LD-B1's inhibitory effects on H. akashiwo remain poorly understood. In this study, we employed the comprehensive methodology, including morphological observation, assessment of photosynthetic efficiency (Fv/Fm), and transcriptomic analysis, to investigate the response of H. akashiwo to LD-B1. Exposure to LD-B1 resulted in a rapid decline of H. akashiwo's Fv/Fm ratio, with cells transitioning to a rounded shape within 2 hours, subsequently undergoing structural collapse and cytoplasmic leakage. Transcriptomic data revealed sustained downregulation of photosynthetic genes, indicating impaired functionality of the photosynthetic system. Additionally, genes related to the respiratory electron transfer chain and antioxidant defenses were consistently downregulated, suggesting prolonged oxidative stress beyond the cellular antioxidative capacity. Notably, upregulation of autophagy-related genes was observed, indicating autophagic responses in the algal cells. This study elucidates the molecular basis of LD-B1's algicidal effects on H. akashiwo, advancing our understanding of algicidal mechanisms and contributing to the development of effective strategies for controlling harmful algal blooms.

Left atrial and ventricular longitudinal strain by cardiac magnetic resonance feature tracking improves prognostic stratification of patients with ST-segment elevation myocardial infarction.

We aimed to investigate the predictive value of left atrium (LA) and left ventricle (LV) longitudinal strain derived by CMR-FT early after ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Patients with STEMI who received pPCI and completed CMR within the following week were enrolled. LA and LV longitudinal strain parameters were derived from cine CMR by FT; conventional CMR indexes were also performed. The primary endpoint was the occurrence of major cardiovascular adverse events (MACE), defined as a composite of death, reinfarction, and congestive heart failure (HF). 276 participants (median age, 57 years, IQR, 48-66 years; 85% men) were included in this study. CMR was usually completed on the 5 (IQR,4-7) days after pPCI. During a median follow-up of 16 months, MACE occurred in 35 (12.7%) participants. Multivariable Cox regression analysis showed that LA conduit strain (HR 0.91, 95%CI: 0.84, 0.98, p = 0.013) and LV global longitudinal strain (HR 1.17, 95%CI: 1.03, 1.34, p = 0.016) remained independently associated with MACE. Participants with impaired LA conduit strain (≤ 12.8%) and LV global longitudinal strain (> -13.1%) had a higher risk of MACE than those with preserved. Longitudinal strain of LA and LV could provide independent prognostic information in STEMI patients, and comprehensive assessment of Left atrial and ventricular longitudinal strain significantly improved the prognosis.

Impact and migration behavior of triclosan on waste-activated sludge anaerobic digestion.

Triclosan (TCS), a hydrophobic antibacterial agent, is extensive application in daily life. Despite a low biodegradability rate, its hydrophobicity results in its accumulation in waste-activated sludge (WAS) during domestic and industrial wastewater treatment. While anaerobic digestion is the foremost strategy for WAS treatment, limited research has explored the interphase migration behavior and impacts of TCS on WAS degradation during anaerobic digestion. This study revealed TCS migration between solid- and liquid-phase in WAS digestion. The solid-liquid distribution coefficients of TCS were negative for proteins and polysaccharides and positive for ammonium. High TCS levels promoted volatile-fatty-acid accumulation and reduced methane production. Enzyme activity tests and functional prediction indicated that TCS increased enzyme activity associated with acid production, in contrast to the inhibition of key methanogenic enzymes. The findings of the TCS migration behavior and its impacts on WAS anaerobic digestion provide an in-depth understanding of the evolution of enhanced TCS-removing technology.

SEC61 translocon gamma subunit is correlated with glycolytic activity, epithelial mesenchymal transition and the immune suppressive phenotype of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) remains a predominant cause of cancer-related mortality globally, underscoring the urgency for targeted therapeutic strategies. The specific role and impact of the SEC61 translocon gamma subunit (SEC61G) in LUAD progression and metastasis remain largely unexplored. In this study, we use a multifaceted approach, combining bioinformatics analysis with experimental validation, to elucidate the pivotal role of SEC61G and its associated molecular mechanisms in LUAD. Our integrated analyses reveal a significant positive correlation between SEC61G expression and the glycolytic activity of LUAD, as evidenced by increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT scans. Further investigations show the potential influence of SEC61G on metabolic reprogramming, which contributes to the immunosuppressive tumor microenvironment (TME). Remarkably, we identify a negative association between SEC61G expression levels and the infiltration of critical immune cell populations within the TME, along with correlations with immune checkpoint gene expression and tumor heterogeneity scores in LUAD. Functional studies demonstrate that SEC61G knockdown markedly inhibits the migration of A549 and H2030 LUAD cells. This inhibitory effect is accompanied by a significant downregulation of key regulators of tumor progression, including hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A, and genes involved in the epithelial-mesenchymal transition pathway. In conclusion, our comprehensive analyses position SEC61G as a potential prognostic biomarker intricately linked to glycolytic metabolism, the EMT pathway, and the establishment of an immune-suppressive phenotype in LUAD. These findings underscore the potential of SEC61G as a therapeutic target and predictive marker for immunotherapeutic responses in LUAD patients.

Monitoring levetiracetam concentration in saliva during pregnancy is stable and feasible.

AIMS: This multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy. METHODS: The slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC-MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose-normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy. RESULTS: In total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 µg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915-0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 µg/mL (upper limit) with an AUC of 0.952 (0.914-0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007. CONCLUSION: The saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non-pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.

Enhanced resilience in urban stormwater management through model predictive control and optimal layout schemes under extreme rainfall events.

Optimizing the layout of urban stormwater management systems is an effective method for mitigating the risk of urban flooding under extreme storms. However, traditional approaches that consider only economic costs or annual runoff control rates cannot dynamically respond to the uncertainties of extreme weather, making it difficult to completely avoid large accumulations of water and flooding in a short period. This study proposes an integrated method combining system layout optimization and Model Predictive Control(MPC)to enhance the system's resilience and effectiveness in flood control. An optimization framework was initially built to identify optimal system layouts, balancing annual average life cycle cost (AALCC) and resilience index. The MPC was then applied to the optimal layout selected using the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method, aiming to alleviate inundation cost-effectively. The adaptability of MPC to varying sets of control horizons and its efficacy in managing the hydrograph and flood dynamics of urban drainage system were examined. Conducted in Yubei, Chongqing, this study revealed patterns in optimal layout fronts among various extreme design rainfalls, showing that peak position rate and return period significantly influence system resilience. The contribution of MPC to the optimal system layout was particularly notable, resulting in improved instantaneous and overall flood mitigation. The application of MPC increased the resilience index by an average of 0.0485 and offered cost savings of 0.0514 million yuan in AALCC. Besides, our findings highlighted the importance of selecting an optimal set of control horizons for MPC, which could reduce maximum flood depth from 0.43m to 0.19m and decrease conduit peak flow by up to 14% at a flood-prone downstream location.

Dysregulated Wnt/ß-catenin signaling confers resistance to cuproptosis in cancer cells.

Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/ß-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/ß-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/ß-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the ß-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. Knockdown of TCF4 or pharmacological Wnt/ß-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/ß-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.

Chassis engineering for high light tolerance in microalgae and cyanobacteria.

Oxygenic photosynthesis in microalgae and cyanobacteria is considered an important chassis to accelerate energy transition and mitigate global warming. Currently, cultivation systems for photosynthetic microbes for large-scale applications encountered excessive light exposure stress. High light stress can: affect photosynthetic efficiency, reduce productivity, limit cell growth, and even cause cell death. Deciphering photoprotection mechanisms and constructing high-light tolerant chassis have been recent research focuses. In this review, we first briefly introduce the self-protection mechanisms of common microalgae and cyanobacteria in response to high light stress. These mechanisms mainly include: avoiding excess light absorption, dissipating excess excitation energy, quenching excessive high-energy electrons, ROS detoxification, and PSII repair. We focus on the species-specific differences in these mechanisms as well as recent advancements. Then, we review engineering strategies for creating high-light tolerant chassis, such as: reducing the size of the light-harvesting antenna, optimizing non-photochemical quenching, optimizing photosynthetic electron transport, and enhancing PSII repair. Finally, we propose a comprehensive exploration of mechanisms: underlying identified high light tolerant chassis, identification of new genes pertinent to high light tolerance using innovative methodologies, harnessing CRISPR systems and artificial intelligence for chassis engineering modification, and introducing plant photoprotection mechanisms as future research directions.

An unusual cecal submucosal mass in an elderly gentleman.

A 60-years-old man with previous hypertension was hospitalized because of colonoscopy revealed a cecal submucosal mass for community health examination 1 month ago. The patient has no symptoms such as poor appetite, fatigue, abdominal pain, diarrhea, nausea and vomiting. Laboratory tests and physical examination was unremarkable. A protrusion with multiple superficial small ulcers on the smooth surface measuring 1.5 × 2.0-cm was found beside the appendiceal orifice by colonoscopy. Abdominal computed tomography demonstrated a high-density mass without enhancement protruding towards the ileocecal cavity at the appendiceal orifice measured 1.5 × 1.8 cm. Laparoscopic ileocecal resection was performed because of appendiceal tumor couldn't be excluded and the patient's strong request. Pathology examination of the postoperative specimen revealed dilated appendix cavity with fecalith inside in the submucosal layer of the ileocecal region. The patient was diagnosed as appendiceal orifice submucosal fecalith. He was discharged home uneventfully and no symptoms was observed in 3 months follow-up.

Dynamics of Long-Term Quality of Life After Treatment for Esophageal Cancer: A Community-Based Patient Study.

PURPOSE: To characterize the pattern of post-treatment quality of life (QoL) for esophageal cancer (EC) survivors and construct models predicting their long-term QoL. METHODS: On the basis of a randomized trial in an EC high-risk region in China, we interviewed 363 EC survivors and 25,245 permanent residents matched with the survivors on age, sex, and township as the baseline. QoL was measured using three-level version of European Quality of Life 5-Dimensions instrument. We constructed piecewise mixed models estimating the QoL of EC survivors that varied by age, sex, patient type, hospital level, and therapy to ascertain QoL determinants. RESULTS: The post-treatment QoL of EC survivors dropped by 15.7% within the first year and recovered by 9.3% between 1 and 9 years compared with the baseline. Therapy was found to be a determinant of QoL, and a series of therapy-specific models were fitted accordingly, which all showed the pattern of decreasing rapidly and recovering gradually. Endoscopic treatment had the least impact on post-treatment QoL (7.5% drop within 5 years) compared with esophagectomy (12.2% drop within 1 year) and chemoradiotherapy (37.8% drop within 2 years). The usual activities dimension showed the greatest impairment among those patients (34.4% drop within 1 year). CONCLUSION: This community-based study described the long-term QoL trajectory for EC survivors after different therapeutic modalities and constructed models to predict therapy-specific QoL at different time points after treatment. It provided new insights into decision making in treatment for EC from the perspective of QoL protection, offering a convenient tool for estimating quality-adjusted life-years.

[Retracted] Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head: Systematic review.

[This retracts the article DOI: 10.3892/br.2015.527.].

Efferent pathways from the suprachiasmatic nucleus to the horizontal limbs of diagonal band promote NREM sleep during the dark phase in mice.

The regulation of circadian rhythms and the sleep-wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep-wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN-HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non-rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN-HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep-wake states regulation.

FGF21-dependent alleviation of cholestasis-induced liver fibrosis by sodium butyrate.

Background: The beneficial effects of fibroblast growth factor 21 (FGF21) and sodium butyrate (NaB) on protection against cholestasis-induced liver fibrosis are not well known. This study aimed to explore the effects of FGF21 and NaB on bile duct ligation (BDL)-induced liver fibrosis. Methods: Wild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson's staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing. Results: BDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice. Conclusion: FGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.