Loss of FAM172A gene prompts cell proliferation in liver regeneration.

The present study was designed to explore the function of FAM172A in liver regeneration and HCC. Mice were sacrificed after 70% partial hepatectomy (PH). RNA sequencing was performed on primary hepatocytes of WT and FAM172A-/- mice. We used HepG2 cells to construct cell lines with stably knockdown and overexpression of FAM172A. The expression of FAM172A in liver tissues was investigated by immunohistochemical staining, and we also used public database to perform survival analysis and prognostic model in HCC. Compared with WT mice after PH, normalized liver weight/body weight (LW/BW) ratio and the proliferating cell nuclear antigen (PCNA) protein level of FAM172A-/- mice elevated. The DEGs were mainly enriched in inflammatory response, tumor necrosis factor production, and wound healing. FAM172A knockdown enhanced the NFκB-TNFα and pERK-YAP1-Cyclin D1 axis. FAM172A peptide inhibited proliferation of primary hepatocytes. Moreover, the low expression of FAM172A in human HCC tissues implies a lower likelihood of survival and a valid diagnostic marker for HCC. Loss of FAM172A gene promotes cell proliferation by pERK-YAP1-Cyclin D1 and pNFκB-TNFα pathways during liver regeneration after PH. FAM172A may be a favorable diagnosis marker of HCC.

From NAFLD to MASLD: When metabolic comorbidity matters.

INTRODUCTION AND OBJECTIVES: In a recent development, a cohort of hepatologists has proposed altering the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated steatotic liver disease (MASLD), accompanied by modified diagnostic criteria. Our objective was to investigate the effect of the revised definition on identifying significant hepatic fibrosis. PATIENTS AND METHODS: From Jan 2009 to Dec 2022, a total of 428 patients with biopsy-proven hepatic steatosis were diagnosed with NAFLD. Patients were classified into subgroups according to MASLD and Cryptogenic-SLD diagnostic criteria. The clinical pathological features were compared between these two groups. Risk factors for significant fibrosis were analysed in the MASLD group. In total, 329 (76.9 %) patients were diagnosed with MASLD, and 99 (23.1 %) were diagnosed with Cryptogenic-SLD. RESULTS: Those with MASLD exhibited a higher degree of disease severity regarding histology features than Cryptogenic-SLD. The prevalence of significant fibrosis increased from 13 % to 26.6 % for one and two criteria present to 42.5 % for meeting three or more cardiometabolic risk factor (CMRF) criteria (p = 0.001). ALB (aOR:0.94,95 %CI:0.90-1.00; p = 0.030), lower levels of PLT (aOR:0.99, 95 %CI:0.99-1.00; p < 0.001), and more metabolic comorbidities (aOR:1.42,95 %CI:1.14-1.78; p = 0.012) were independent risk factors of significant fibrosis in MASLD. CONCLUSIONS: The new nomenclature of MASLD and SLD is more applicable to identifying significant fibrosis than NAFLD. Patients with three or more cardiometabolic risk factors are at higher risk of fibrosis.

GLUT5: structure, functions, diseases and potential applications.

Glucose transporter 5 (GLUT5) is a membrane transporter that specifically transports fructose and plays a key role in dietary fructose uptake and metabolism. In recent years, a high fructose diet has occupied an important position in the daily intake of human beings, resulting in a significant increase in the incidence of obesity and metabolic diseases worldwide. Over the past few decades, GLUT5 has been well understood to play a significant role in the pathogenesis of human digestive diseases. Recently, the role of GLUT5 in human cancer has received widespread attention, and a large number of studies have focused on exploring the effects of changes in GLUT5 expression levels on cancer cell survival, metabolism and metastasis. However, due to various difficulties and shortcomings, the molecular structure and mechanism of GLUT5 have not been fully elucidated, which to some extent prevents us from revealing the relationship between GLUT5 expression and cell carcinogenesis at the protein molecular level. In this review, we summarize the current understanding of the structure and function of mammalian GLUT5 and its relationship to intestinal diseases and cancer and suggest that GLUT5 may be an important target for cancer therapy.

FAM172A Deletion May Enhance Hepatic Steatosis by Promoting ER Stress.

BACKGROUND: Endoplasmic reticulum (ER) stress is one of the major causes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Our previous study showed that maintains the homeostasis of ER could effectively alleviate NAFLD. In this study, we found that the loss of FAM172A increased ER stress. AIMS: The aims of this study were to explore whether FAM172A could improve NAFLD by inhibiting ER stress. METHODS: The expression levels of FAM172A and ER stress were detected by western blot. The method of immunofluorescence was used to determine FAM172A location. The interacted proteins of FAM172A were identified by immunocoprecipitation. The methods of MTS and caspase-3/7 activity were taken to confirm the effect of FAM172A on cell viability and proliferation. The expression levels of inflammation were detected by qPCR. RESULTS: We confirmed that FAM172A might alleviate NAFLD through inhibiting ER stress. Loss of FAM172A increased the expressions of ATF6, peIF2α, but decreased the expression of IRE1α. Then, it was shown that FAM172A located in ER and FAM172A directly interacted with ATF6 and peIF2α and IRE1α. More importantly, the binding of FAM172A and eIF2a in tunicamycin-treated group increased significantly compared with the control group. However, the binding of FAM172A and ATF6 or IRE1α did not change. Next, we found that the lack of FAM172A could produce more apoptosis and inflammation. CONCLUSIONS: Our results suggest that FAM172A improve steatosis by alleviating ER stress.

Prognosis of endotherapy versus splenectomy and devascularization for variceal bleeding in patients with hepatitis B-related cirrhosis.

OBJECTIVE: This study aimed to compare the long-term outcome of endotherapy versus a combination of splenectomy and devascularization for variceal bleeding in patients with hepatitis B-related cirrhosis (HBRC). MATERIALS AND METHODS: A total of 1074 patients with HBRC and acute variceal bleeding (AVB) treated with endotherapy and 248 patients with HBRC treated with a combination of splenectomy and devascularization surgery were included in the analysis. After one-to-one propensity score matching, 151 paired patients were selected. The primary end-point was death. The secondary outcomes were 3-year survival, 5-year survival, and rebleeding. Complications were recorded. RESULTS: The median follow-up time was 1165 days in the endoscopic group and 1709 days in the surgical group. Before matching, the 1-year, 3-year, and 5-year survival rates were significantly lower in the endoscopic group than in the surgical group (91.1 vs 96.3%, P = 0.017; 79.6 vs 91.6%, P = 0.001; 65.2 vs 81.3%, P = 0.001). After matching, no significant differences were found between groups (94.5 vs 95.2%, P = 0.767; 87.0 vs 88.9%, P = 0.635; 77.9 vs 77.9%, P = 0.905). The rebleeding rate was lower in the surgical group than in the endoscopic group; the rebleeding-free survival rate was similar in the two groups. No patient died of complications. No statistically significant difference was observed in complications between groups. CONCLUSIONS: Both endotherapy and a combination of splenectomy and devascularization are good choices for patients with AVB. The rebleeding rate was lower after the surgical procedure, but the long-term prognosis was similar.

New model predicting gastroesophageal varices and variceal hemorrhage in patients with chronic liver disease.

INTRODUCTION AND OBJECTIVES: The predictors for gastroesophageal varices (GOV) and hemorrhage development have not been well studied in different liver diseases or different population. This study aimed to evaluate whether a new algorithm focusing on chronic hepatitis B (CHB) patients is also applicable to other chronic liver diseases (CLDs) in Chinese population. PATIENTS OR MATERIALS AND METHODS: We retrospectively analyzed 659 CHB patients and 386 patients with other CLDs. A total of 439 CHB patients were included in training set, the other 220 CHB patients and other patients with CLDs were included in validation set. A new algorithm for diagnosing GOV was established and its sensitivity and specificity for predicting the varices was verified. RESULTS: Multivariable logistic regression revealed that the rough surface of the liver (p<0.001), splenic thickness (p<0.001), and liver stiffness (p=0.006) were independent predictors of GOV. The new algorithm was considered to be a reliable diagnostic model to evaluate the presence of varices. The AUROC was 0.94 (p<0.001) in CHB validation set and 0.90 (<0.001) in non-CHB validation set. When the cut-off value was chosen as -1.048, the sensitivity and specificity in diagnosing GOV in CHB population were 89.1% and 82.5%, respectively. Importantly, the new algorithm accurately predicted the variceal hemorrhage not only in CHB patients, but also in patients with other CLDs. CONCLUSION: The new algorithm is regarded as a reliable model to prognosticate varices and variceal hemorrhage, and stratified not only the high-risk CHB patients, but also in patients with other CLDs for developing GOV and variceal bleeding.

Antiviral therapy reduces rebleeding rate in patients with hepatitis B-related cirrhosis with acute variceal bleeding after endotherapy.

BACKGROUND: The preventive effects of antiviral therapy to reduce rebleeding rate in patients with hepatitis B-related cirrhosis undergoing endoscopic treatment have not yet been reported. METHODS: In this retrospective cohort study, 1139 patients with chronic hepatitis B with first acute variceal bleeding after endoscopic therapy from September 2008 to December 2017 were included. Among them, 923 who received and 216 who did not receive antiviral therapy were followed up for rebleeding. Cumulative rebleeding rate was calculated using the Kaplan-Meier method. Univariate and multivariate logistic regression analyses were performed to estimate the effects of antiviral therapy on rebleeding risk. The propensity score matched method and inverse probability of treatment weighting analysis were used to calculate the rebleeding rate between the antiviral and non-antiviral groups. RESULTS: The rebleeding rates were 40.5, 60.7, 72.6, and 89.2% in antiviral group at 1, 2, 3, and 5 years, respectively. The corresponding rebleeding rates in the non-antiviral group were 54.2, 72.4, 84.4, and 93.3%, respectively. The multivariate logistic regression analysis revealed that antiviral therapy was an independent protective factor associated with rebleeding. CONCLUSION: Antiviral treatment significantly reduced rebleeding rate in patients with HBV-related cirrhosis who received endoscopic treatment after the first variceal bleeding.

Glt25d2 Knockout Directly Increases CD25+CD69- but Decreases CD25-CD69+ Subset Proliferation and is Involved in Concanavalin-Induced Hepatitis.

BACKGROUND/AIMS: The elaborate structure of the extracellular matrix (ECM) and the appropriate surface glycoforms upon it are indispensable to CD4+ T cell regulation. METHODS: To explore the effects of Glcα1,2Galß1 glycosylation mediated by GLT25D2 (Colgalt2) for CD4+ T cell regulation, we prepared C57BL/6J Glt25d2-/- mice. In the induction of hepatitis, after concanavalin A (Con A) challenge for 6, 12, and 24 h, more extensive parenchymal injury was noted in Glt25d2-/- mice than in wild-type (WT) mice at 12 h. Immunohistochemistry and laser scanning confocal microscopy were used to detect GLT25D2 expression, and subsets of CD4+T cells was analyzed by flow cytometry. A total of 26 cytokines in serum samples were determined using Luminex technology. RESULTS: The trend in liver injury score variation was consistent with serum alanine aminotransferase and aspartate aminotransferase levels. The levels of interleukin 4 (IL-4), IL-1ß, IL-9, and several chemokines such as macrophage inflammatory protein-2, eotaxin, and growth-related oncogene α were significantly increased in Glt25d2-/- mice compared with WT mice after Con A challenge. A further phenotype analysis of primary Glt25d2-/- CD4+ T cells showed that Glt25d2 knockout increased the frequency of the CD25+CD69- subset but decreased the frequency of the CD25-CD69+ subset after Con A challenge for 6, 12, and 24 h compared with those of WT CD4+ T cells. Activation-induced apoptosis was also significantly increased in Glt25d2-/- CD4+ T cells after Con A challenge compared with WT CD4+ T cells. Lectin microarray hybridization showed that Glt25d2 knockout increased the binding activity of Narcissus pseudonarcissus lectin to CD4+ T cells but Amaranthus caudatus lectin-binding activity was lost during Con A challenge. CONCLUSION: The present results suggest that collagen glycosylation mediated by GLT25D2 may regulate a subset of CD4+ T cells and be involved in the pathogenesis of Con A-induced hepatitis.

Deletion of the C6orf120 gene with unknown function ameliorates autoimmune hepatitis induced by concanavalin A.

The present study was conducted to characterize the C6orf120 gene, by using C6orf120 gene-deleted rats (C6orf120-/-), to determine its role in the development and severity of autoimmune hepatitis induced by concanavalin A (Con A), as well as the underlying mechanisms. We found that following Con A injection, C6orf120-/- rats were less susceptible to developing autoimmune hepatitis with low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) post challenge. Additionally, C6orf120 deficiency increased the frequency of cluster of differentiation (CD)4+ CD25+ Forkhead box P3+ regulatory T cells (Tregs) among intrahepatic lymphocytes, splenocytes, peripheral blood mononuclear cells, and CD4+ T in vitro. Moreover, C6orf120 deficiency downregulated interleukin (IL)-1ß, IL-6, tumor necrosis factor alpha-α, interferon-γ and IL-17a secretion in the plasma and liver tissues. Our results indicated that the C6orf120 gene-deleted rats were less susceptible to Con A-induced autoimmune hepatitis, which may be partly related to the increased frequency of Tregs and inhibited secretion of inflammatory cytokines.

Mechanism of the effect of glycosyltransferase GLT8D2 on fatty liver.

BACKGROUND: Recent studies have shown that some glycosyltransferases are involved in the development of nonalcoholic fatty liver disease (NAFLD). The objective of this study was to explore the effect and mechanism of glycosyltransferase GLT8D2 on fatty liver. METHODS: Rat model of NAFLD was established by induction with high-fat-diet. The GLT8D2 expression in rat liver was examined using immunohistochemistry. Oil Red O staining and triglyceride assay were used to measure the effect of abnormal GLT8D2 expression on lipid accumulation in HepG2 cells. The expression levels of lipid metabolism-related key molecules, namely sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-coA desaturase (SCD), carnitine palmitoyltransferase-1 (CPT1) and microsomal triglyceride transfer protein (MTP), in HepG2 cells with abnormal GLT8D2 expression were determined by western blot analyses. RESULTS: The expression of GLT8D2 was higher in the liver of rats with NAFLD than in the control rats, and GLT8D2 was mainly located around lipid droplets in hepatocytes. GLT8D2 expression increased in steatosis HepG2 cells compared with that in normal HepG2 cells. GLT8D2 positively regulated lipid droplet accumulation and triglyceride content in HepG2 cells. Upregulation or knockdown of GLT8D2 had no effect on the expressions of SREBP-1c, SCD or CPT-1 proteins in HepG2 cells. However, GLT8D2 expression negatively regulated the expression of MTP protein in HepG2 cells. CONCLUSION: GLT8D2 participated in NAFLD pathogenesis possibly by negatively regulating MTP expression. Specific inhibition of GLT8D2 via an antagonistic strategy could provide a potential candidate approach for treatment of NAFLD.

Novel insights into post-marketing adverse events associated with lenvatinib: A comprehensive analysis utilizing the FAERS database.

Purpose: The primary aim of this study was to closely monitor and identify adverse events (AEs) linked to lenvatinib, a pharmacotherapeutic agent employed for the management of renal cell carcinoma, thyroid cancer, and hepatocellular carcinoma. The ultimate goal was to optimize patient safety and provide evidence-based guidance for the appropriate utilization of this medication. Methods: A comprehensive collection and analysis of reports from the FDA Adverse Event Reporting System (FAERS) database was conducted, encompassing the period from the first quarter of 2015 to the first quarter of 2023. Disproportionality analysis, employing robust algorithms including ROR, PRR, BCPNN, and EBGM was employed for effective data mining to quantify signals associated with lenvatinib-related AEs. Results: Among the collected reports, a total of 15,193 cases were identified where lenvatinib was the "primary suspected (PS)" drug, resulting in 50,508 lenvatinib-induced AEs. An analysis was conducted to examine the occurrence of lenvatinib-induced adverse drug reactions (ADRs) across 26 organ systems. The findings revealed the presence of expected ADRs, including diarrhea, vomiting, stomatitis, hepatic encephalopathy, decreased appetite, dehydration, decreased weight, and electrolyte imbalances, which were consistent with the information provided in the drug labels. Furthermore, unexpected significant ADRs were observed at the preferred terms (PT) level, such as interstitial lung disease, pneumothorax, hypophysitis, failure to thrive, polycythemia, hypopituitarism, spontaneous pneumothorax, pulmonary cavitation, and limbic encephalitis. These findings indicated the potential occurrence of adverse effects that are currently not documented in the drug instructions. Conclusions: This study has successfully detected novel and unforeseen signals pertaining to ADRs associated with the administration of lenvatinib, thereby contributing significant insights into the intricate correlation between ADRs and the utilization of lenvatinib. The outcomes of this investigation underscore the utmost significance of continuous monitoring and vigilant surveillance in order to promptly identify and effectively manage AEs, consequently enhancing overall patient safety and well-being in the context of lenvatinib therapy.

GP73 is a potential marker for evaluating AIDS progression and antiretroviral therapy efficacy.

Golgi protein-73 (GP73) is upregulated in cancers and viral infections; however, its role in human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) remains undetermined. GP73 was evaluated as a biomarker of HIV progression and AIDS treatment efficacy. Forty-eight HIV patients (≤ 350 CD4 + T cells/µL) undergoing highly active antiretroviral therapy (HAART group) and 18 HIV patients expected to undergo HAART within 9 months (>350 CD4 + T cells/µL) (control group) were enrolled in a prospective, single center, cohort study from May 2009 to Jun 2012. Blood aspartate aminotransferase, alanine aminotransferase (ALT), cholesterol, triglycerides, and total bilirubin were assessed at baseline, 2 weeks, and 1, 3, 6, 9, and 12 months (HAART group) or 3 month intervals (control group). Serum HIV RNA level (viral load) was determined by reverse-transcriptase polymerase chain reaction (RT-PCR), and serum and peripheral blood mononuclear cell (PBMC) GP73 concentration were determined by chemiluminescent immunoassay kit and western blot, respectively. Significant positive and negative correlations in baseline serum GP73 concentration and HIV viral load (r = 0.39, P < 0.001) and CD4 + T cell count (r = -0.501, P < 0.001) were observed, respectively. In receiver operator characteristic (ROC) analysis, area under the curve (AUC) was 0.79 (95 % CI 0.66-0.92). The sensitivity and specificity of GP73 for correct identification of patients with ≤350 CD4 + T cells/µL were 76.09 and 75.0 %, respectively, with an ROC-derived cut-off of 100.6 ng/mL. For HIV patients undergoing antiretroviral therapy, GP73 may be a potential biomarker treatment efficacy useful in AIDS management.

Γ-aminobutyric acid B receptor improves carbon tetrachloride-induced liver fibrosis in rats.

BACKGROUND: It was well known that angiotension II can inhibit hepatic stellate cell activation. The GABAB receptor was upregulated when the hepatic stellate cell line was stimulated by angiotension II in our previous study. But the role of the GABAB receptor in liver fibrosis has never been reported. AIM: In the present study, we investigated the effects of this receptor on carbon tetrachloride-induced liver fibrosis in rats. METHODS: The rats were divided into four groups including GABAB receptor agonist, antangonist, model and control group. α-smooth muscle actin (α-SMA) and GABAB receptor expression levels were detected by immunohistochemistry and real-time polymerase chain reaction. Liver function tests were performed once blood samples was taken; Western blot analysis was used to detect protein expression level of α-SMA and TGF-ß1. RESULTS: We found baclofen ameliorated the CCl4-induced rats's liver fibrosis. The highest liver enzymes and α-SMA protein levels were found in the CGP35348 group. CONCLUSION: The GABAB receptor may have a protective role in the liver.

Glycosyltransferase GLT8D2 positively regulates ApoB100 protein expression in hepatocytes.

Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation in hepatocytes. Very low density lipoprotein (VLDL) is a major secretory product of the liver that transports endogenously synthesized TG. Disrupted VLDL secretion may contribute to the accumulation of TG in hepatocytes. ApoB100 (apolipoprotein B100) is a glycoprotein and an essential protein component of VLDL. Its glycosylation may affect VLDL assembly and secretion. However, which glycosyltransferase catalyzes apoB100 glycosylation is unknown. In this study, we cloned the GLT8D2 (glycosyltransferase 8 domain containing 2) gene from HepG2 cells and generated a series of plasmids for in vitro studies of its molecular functions. We discovered that GLT8D2 was localized in the ER, interacted with apoB100, and positively regulated the levels of apoB100 protein in HepG2 cells. Based on these results, we propose that GLT8D2 is a glycosyltransferase of apoB100 that regulates apoB100 levels in hepatocytes.

Development of a prognostic signature based on anoikis-related genes in hepatocellular carcinoma with the utilization of LASSO-cox method.

To develop a signature based on anoikis-related genes (ARGs) for predicting the prognosis of patients with hepatocellular carcinoma (HCC), and to elucidate the molecular mechanisms involved. In this study, bioinformatic algorithms were applied to integrate and analyze 777 HCC RNA-seq samples from the cancer genome atlas and international cancer genome consortium repositories. A prognostic signature was developed via the least absolute shrinkage and selection operator-cox regression method. To evaluate the accuracy of the signature in predicting events, multi-type technical means, such as Kaplan-Meier plots, receiver operating characteristic curve analysis, nomogram construction, and univariate and multivariate Cox regression studies were performed. We investigated the underlying molecular biological mechanisms and immune mechanisms of the signature using gene set enrichment analysis and the CIBERSORT R package, respectively. Meanwhile, immunohistochemical staining acquired from the human protein atlas was used to confirm the differential expression levels of hub genes involved in the prognostic signature. We developed an HCC prognostic signature with a collection of 5 ARGs, and the prognostic value was successfully assessed and verified in both the test and validation cohorts. The risk scores calculated by the prognostic signature were proved to be an independent negative prognostic factor for overall survival. A set of nomograms based on risk scores was established and found to be effective in predicting OS. Further investigation of the underlying molecular biological mechanisms and immune mechanisms indicated that the signature may be relevant to metabolic dysregulation and infiltration of gamma delta T cells in the tumor. The survival prognosis of HCC patients can be predicted by the anoikis-related prognostic signature, and it serves as a valuable reference for individualized HCC therapy.

Prognostic risk factors for patients with hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloids.

Pyrrolizidine alkaloids induced hepatic sinusoidal obstruction syndrome (PA-HSOS) often occurs after consuming herbs or a dietary supplement containing the plant Tu-San-Qi. Limited data exists to identify patients with fatal outcomes for early interventions. We aimed to analyze the predictors for 3-month survival. We retrospectively enrolled PA-HSOS patients in 5 hospitals and extracted data from the onset of PA-HSOS to 36 months. Outcome measurements were 3-month and 36-month survival rates, baseline prognostic predictors for survival, and the effects of anticoagulant therapy. Among 49 enrollees, the median age was 60 and 49% male. At the onset of PA-HSOS, patients with Child-Turcotte-Pugh (CTP) class of A, B, or C were 8.2% (4/49), 42.8% (21/49) and 49.0% (24/49), respectively. None of them received a transjugular intrahepatic portosystemic shunt or a liver transplant. The 3-month and 36-month survival rates were 86% and 76%, respectively. Compared to the CTP class A or B, class C at baseline independently predicted lower survival rates at both 3 and 36 months. However, anticoagulation therapy treatment within the first 3 months independently predicted significantly higher survival rates at both time points. CTP class C and anticoagulant therapy were the independent predictors for short-term and long-term survival. Anticoagulant therapy could decrease mortality rate of CTP class C patients. The greatest benefit of anticoagulant evaluated by 3-month survival rate was in patients with CTP class C compared with those without treatment (93% vs 40%, P = .009). There were no bleeding complications reported in patients treated with the anticoagulant.

Upregulation of GLT25D1 in Hepatic Stellate Cells Promotes Liver Fibrosis via the TGF-ß1/SMAD3 Pathway In Vivo and In vitro.

Background and Aims: Collagen ß(1-O) galactosyltransferase 25 domain 1 (GLT25D1) is associated with collagen production and glycosylation, and its knockout in mice results in embryonic death. However, its role in liver fibrosis remains elusive, particularly in hepatic stellate cells (HSCs), the primary collagen-producing cells associated with liver fibrogenesis. Herein, we aimed to elucidate the role of GLT25D1 in HSCs. Methods: Bile duct ligation (BDL)-induced mouse liver fibrosis models, primary mouse HSCs (mHSCs), and transforming growth factor beta 1 (TGF-ß1)-stimulated LX-2 human hepatic stellate cells were used in in vivo and in vitro studies. Stable LX-2 cell lines with either GLT25D1 overexpression or knockdown were established using lentiviral transfection. RNA-seq was performed to investigate the genomic differences. HPLC-MS/MS were used to identify glycosylation sites. Scanning electronic microscopy (SEM) and second-harmonic generation/two-photon excited fluorescence (SHG/TPEF) were used to image collagen fibril morphology. Results: GLT25D1 expression was upregulated in nonparenchymal cells in human cirrhotic liver tissues. Meanwhile, its knockdown attenuated collagen deposition in BDL-induced mouse liver fibrosis and inhibited mHSC activation. GLT25D1 was overexpressed in activated versus quiescence LX-2 cells and regulated in vitro LX-2 cell activation, including proliferation, contraction, and migration. GLT25D1 also significantly increased liver fibrogenic gene and protein expression. GLT25D1 upregulation promoted HSC activation and enhanced collagen expression through the TGF-ß1/SMAD signaling pathway. Mass spectrometry showed that GLT25D1 regulated the glycosylation of collagen in HSCs, affecting the diameter of collagen fibers. Conclusions: Collectively, the upregulation of GLT25D1 in HSCs promoted the progression of liver fibrosis by affecting HSCs activation and collagen stability.

Dual carbon and void space confined SiOx/C@void@Si/C yolk-shell nanospheres with high-rate performances and outstanding cyclability for lithium-ion batteries anodes.

Silicon-based anode materials with high theoretical capacity have great challenges of enormous volume expansion and poor electronic conductivity. Herein, a novel dual carbon confined SiOx/C@void@Si/C yolk-shell monodisperse nanosphere with void space have been fabricated through hydrothermal reaction, carbonization, and in-situ low-temperature aluminothermic reduction. Furthermore, the O/Si ratio and void space between SiOx/C core and Si/C shell can be effectively tuned by the length of aluminothermic reduction time. The SiOx/C core plays a role of maintaining the spherical structure and the void space can accommodate the volume expansion of Si. Moreover, the inner and outer carbons not only alleviate volume variation of SiOx and Si but also enhance the electrical conductivity of composites. Benefiting from the synergy of the double carbon and void space, the optimized VSC-14 anode affords prominent cycle stability with reversible capacity of 1094 mAh g-1 after 550 cycles at 200 mA g-1. By pre-lithiation treatment, the VSC-14 achieves an initial Coulombic efficiency of 93.27% at 200 mA g-1 and a reversible capacity of 348 mAh g-1 at 5 A g-1 after 4000 cycles. Furthermore, the pouch cell using VSC-14 anode and LiFePO4 cathode delivers a reversible capacity of 138 mAh g-1 at 0.2C. We hope this strategy can provide a scientific method to synthesis yolk-shell Si-based materials.

Comparison of hepatitis B X gene mutation between patients with hepatocellular carcinoma and patients with chronic hepatitis B.

Hepatitis B virus (HBV), a major causative agent of hepatocellular carcinoma (HCC), encodes an oncogenic X protein (HBx) that transcriptionally activates multiple viral and cellular promoters. The present study aimed to identify the specific gene mutation related to the clinical outcome of HCC. Seventy-two HBV-infected patients (38 with chronic HBV infection and 34 with HCC) with well-characterized clinical profiles were enrolled. The HBx region was amplified from patient serum samples and analyzed by sequencing. Genotypes were determined using the National Center for Biotechnology Information genotype tool. All isolates were genotype B or C. Enhancer II nucleotide substitutions in the HCC group were significantly different from those in the chronic hepatitis B (CHB) group (Ρ < 0.05). HCC patients with genotype C had a higher risk of harboring the 1762/1764 double mutation than those with genotype B. The incidence of the 1762/1764 double mutation was higher in the high viral load group (>10(6) copies/ml) than in the low viral load group (≤10(6) copies/ml) (P = 0.03). The 1762/1764 double mutations may be related to the genotype and viral load. We found significantly more direct repeat sequence 1 (DR1) nucleotide substitutions in the HCC group (32.4%, 11/34) than in the CHB group (10.5%, 4/38) (Ρ < 0.05). Patients with higher viral load and genotype C had a higher incidence of 1762/1764 double mutations, which may not be related with development of HCC. Enhancer II and DR1 may play an important role in HCC development via nucleotide substitution.