Application of Python-Based Abaqus Secondary Development in Laser Shock Forming of Aluminum Alloy 6082-T6.

Aluminum alloy 6082-T6 is an important material for manufacturing the outer skin of high-speed trains, and laser shock forming can realize the rapid forming of complex-shaped plates. In order to improve the efficiency of the simulation modeling of laser shock forming for aluminum alloy 6082-T6, Python scripting language was used for the secondary development of Abaqus. A plugin was utilized to simulate and analyze the laser shock forming process of aluminum alloy 6082-T6. The coordinates of the plate after laser impact molding were measured using a coordinate measuring machine to calculate the arc bow height of the plate. The accuracy of the simulation model was verified by comparing with the simulation results. The deformation characteristics of plastic strain and arc height of aluminum alloy 6082-T6 under different laser process parameters were analyzed. The simulation plugin has a concise interface, high operability, and accurate results with the other parameters unchanged. When the laser energy is 5 J, 6 J, and 7 J, the corresponding arc heights are 5.9 mm, 6.6 mm, and 7.2 mm, respectively. As the thickness of the sheet increases, the deformation changes from concave at 1 mm to convex at 2 mm, 3 mm, 4 mm, and 5 mm. As the spot size increases from 1 mm to 5 mm, the transmission mode of the shock wave gradually changes from spherical wave to planar wave, and the arc height of the sheet increases from 4.6 mm to 8.2 mm. With the increase in the spot overlap rate, the impact area accumulates residual stress, and the arc height of the sheet is 5.7 mm, 6.6 mm, 7.3 mm, and 8.5 mm, respectively. The secondary development of ABAQUS 2021 using Python 3.6 scripting language has improved the efficiency of simulation modeling and provided reference for rapidly predicting the deformation characteristics of aluminum alloy 6082-T6 under different laser process parameters.

Effect of Adding Intermediate Layers on the Interface Bonding Performance of WC-Co Diamond-Coated Cemented Carbide Tool Materials.

The interface models of diamond-coated WC-Co cemented carbide (DCCC) were constructed without intermediate layers and with different interface terminals, such as intermediate layers of TiC, TiN, CrN, and SiC. The adhesion work of the interface model was calculated based on the first principle. The results show that the adhesion work of the interface was increased after adding four intermediate layers. Their effect on improving the interface adhesion performance of cemented carbide coated with diamond was ranked in descending order as follows: SiC > CrN > TiC > TiN. The charge density difference and the density of states were further analyzed. After adding the intermediate layer, the charge distribution at the interface junction was changed, and the electron cloud at the interface junction overlapped to form a more stable chemical bond. Additionally, after adding the intermediate layer, the density of states of the atoms at the interface increased in the energy overlapping area. The formant formed between the electronic orbitals enhances the bond strength. Thus, the interface bonding performance of DCCC was enhanced. Among them, the most obvious was the interatomic electron cloud overlapping at the diamond/SiCC-Si/WC-Co interface, its bond length was the shortest (1.62 Å), the energy region forming the resonance peak was the largest (-5-20 eV), and the bonding was the strongest. The interatomic bond length at the diamond/TiNTi/WC-Co interface was the longest (4.11 Å), the energy region forming the resonance peak was the smallest (-5-16 eV), and the bonding was the weakest. Comprehensively considering four kinds of intermediate layers, the best intermediate layer for improving the interface bonding performance of DCCC was SiC, and the worst was TiN.

Effect of the Coil Excitation Method on the Performance of a Dual-Coil Inductive Displacement Transducer.

A dual-coil inductive displacement transducer is a non-contact type measuring element for measuring displacement and is widely used in large power equipment systems such as construction machinery and agricultural equipment. However, the effect of the coil excitation method on the performance of dual-coil inductive displacement sensors has not been studied. This paper investigates the impact of different coil excitation methods on the operating performance of displacement transducers. The working principle, electromagnetic characteristics, and electrical characteristics were analyzed by building a mathematical model. A transducer measurement device was used to determine the relationship between core displacement and coil inductance. Three coil excitation methods were proposed, and the effects of the three coil excitation methods on the amplitude variation, phase shift, linearity, and sensitivity of the output signal were studied by simulation based on the AD630 chip as the core of the conditioning circuit. Finally, the study's feasibility was demonstrated by comparing the experiment to the simulation. The results show that, under the uniform magnetic field strength distribution in the coil, the coil voltage variation is proportional to the inductive core displacement. The amplitude variation is the largest for the dual-coil series three-wire (DCSTW) and is the same for the dual-coil series four-wire (DCSFW) and dual-coil parallel differential (DCPD). DCSFW has an enormous phase shift. DCSTW has the best linearity. The research in this paper provides a theoretical basis for selecting a suitable coil excitation, which is conducive to further improving the operating performance of dual-coil inductive displacement transducers.

Effect of Excitation Signal on Double-Coil Inductive Displacement Transducer.

A double-coil inductive displacement transducer is a non-contact element for measuring displacement and is widely used in large power equipment systems such as construction machinery and agricultural machinery equipment. The type of coil excitation signal has an impact on the performance of the transducer, but there is little research on this. Therefore, the influence of the coil excitation signal on transducer performance is investigated. The working principle and characteristics of the double-coil inductive displacement transducer are analyzed, and the circuit simulation model of the transducer is established. From the aspects of phase shift, linearity, and sensitivity, the effects of a sine signal, a triangle signal, and a pulse signal on the transducer are compared and analyzed. The results show that the average phase shift, linearity, and sensitivity of the sine signal were 11.53°, 1.61%, and 0.372 V/mm, respectively; the average phase shift, linearity and sensitivity of the triangular signal were 1.38°, 1.56%, and 0.300 V/mm, respectively; and the average phase shift, linearity, and sensitivity of the pulse signal were 0.73°, 1.95%, and 0.621 V/mm, respectively. It can be seen that the phase shift of a triangle signal and a pulse signal is smaller than that of a sine signal, which can result in better signal phase-locked processing. The linearity of the triangle signal is better than the sine signal, and the sensitivity of the pulse signal is better than that of the sine signal.

Interface Bonding Properties of CrAlSiN-Coated Cemented Carbides Doped with CeO2 and Y2O3 Rare Earth Oxides.

This study performed first-principle-based calculations of the interface adhesion work in interface models of three terminal systems: CrAlSiNSi/WC-Co, CrAlSiNN/WC-Co, and CrAlSiNAl/WC-Co. The results proved that the CrAlSiNSi/WC-Co and CrAlSiNAl/WC-Co interface models had the highest and lowest interface adhesion work values (4.312 and 2.536 J·m-2), respectively. Thus, the latter model had the weakest interface bonding property. On this basis, rare earth oxides CeO2 and Y2O3 were doped into the Al terminal model (CrAlSiNAl/WC-Co). Then, doping models of CeO2 and Y2O3 doped on the WC/WC, WC/Co, and CrAlSiNAl/WC-Co interfaces were established. The adhesion work value was calculated for the interfaces in each doping model. When CeO2 and Y2O3 were doped in the WC/WC and CrAlSiNAl/WC-Co interfaces, four doping models were constructed, each model contains interfaces withreduced adhesion work values, indicating deteriorated interface bonding properties. When the WC/Co interface was doped with CeO2 and Y2O3, the interface adhesion work values of the two doping models are both increased, and Y2O3 doping improved the bonding properties of the Al terminal model (CrAlSiNAl/WC-Co) more significantly than CeO2 doping. Next, the charge density difference and the average Mulliken bond population were estimated. The WC/WC and CrAlSiNAl/WC-Co interfaces doped with CeO2 or Y2O3, with decreased adhesion work, exhibited low electron cloud superposition and reduced values of charge transfer, average bond population, and interatomic interaction. When the WC/Co interface was doped with CeO2 or Y2O3, superposition of the atomic charge densities of electron clouds was consistently observed at the CrAlSiNAl/WC-Co interface in the CrAlSiNAl/WC/CeO2/Co and CrAlSiNAl/WC/Y2O3/Co models; the atomic interactions were strong, and the interface bonding strength increased. When the WC/Co interface was doped with Y2O3, the superposition of atomic charge densities and the atomic interactions were stronger than for CeO2 doping. In addition, the average Mulliken bond population and the atomic stability were also higher, and the doping effect was better.

Research on Interface Bonding Properties of TiAlSiN/WC-Co Doped with Graphene.

Based on the first-principles method, TiAlSiN/WC-Co interface models with graphene doped into the matrix, coating, and the coating/matrix are constructed. The interface adhesion work is calculated and modeled to study the interface bonding properties from the atomic microscopic point of view. The results show that the interface bonding properties of TiAlSiN/WC-Co can be improved when the matrix is doped with the main surface of intrinsic graphene, and the interface bonding property of TiAlSiNN/WC-Co can be improved when the coating and coating/matrix are doped separately with the main surface of intrinsic graphene or single vacancy defective graphene. Furthermore, the model electronic structures are analyzed. The results show that there exist strong Si/Co and N/Co covalent bonds in the interfaces when the matrix is doped with the main surface of intrinsic graphene, which causes the adhesion work of TiAlSiN/WC/msGR/Co to be greater than that of TiAlSiN/WC-Co. Additionally, when the graphene is doped into the coating, in the interface of TiAlSiN/msGR/TiAlSiNN/WC-Co, there exist strong N/Co covalent bonds that increase the interface adhesion work. Additionally, more charge transfer and orbital hybridization exist in the coating/matrix interface doped with the main surface of intrinsic graphene or single vacancy defective graphene, which explains the essential mechanism that the adhesion work of TiAlSiNN/msGR/WC-Co is greater than that of TiAlSiNN/WC-Co, and the adhesion work of TiAlSiNN/svGR/WC-Co is greater than that of TiAlSiNN/WC-Co.

Design and Organocatalytic Asymmetric Synthesis of Indolyl-Pyrroloindoles Bearing Both Axial and Central Chirality.

An axially chiral indolyl-pyrroloindole scaffold, a new member of axially chiral indole-based scaffolds, has been designed, and the catalytic asymmetric construction of this scaffold has been established by the strategy of organocatalytic asymmetric (2 + 3) cycloaddition of 3,3'-bisindoles with isoindolinone-based propargylic alcohols. By this approach, a series of indolyl-pyrroloindole derivatives bearing both axial chirality and central chirality were synthesized in high yields with excellent diastereo- and enantioselectivities (up to 95% yield, 91:9 dr, 99% ee). This reaction not only realizes the first catalytic asymmetric (2 + n) cycloaddition of 3,3'-bisindoles as 1,2-dinucleophiles but also provides a new strategy for atroposelective construction of axially chiral indole-based scaffolds bearing five-five-membered rings, thus solving the challenges in constructing this class of axially chiral indole-based scaffolds.

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.

Influence of Milling-Electrochemical Polishing on Corrosion Resistance of NiTi Shape Memory Alloy.

As an important artificial implant material, the corrosion resistance of NiTi shape memory alloy is closely related to the machined surface quality. In this paper, the multiple analysis methods concerning potentiodynamic polarization, impedance spectrum and corrosion morphology are used to analyze the corrosion resistance of the alloy. The potentiodynamic polarization and impedance spectrum test results show that the conductivity and corrosion current density of electrochemical polishing surface decrease, and the polarization resistance and corrosion potential increase compared with milling. After electrochemical polishing, the surface roughness of the milling sample is decreased, and the NiTi alloy of austenite phase is transformed into TiO2, which improves the corrosion resistance of the alloy. In addition, there are pitting corrosion, hole corrosion and crevice corrosion morphology on the milling surface, while the pitting corrosion and hole corrosion exist on the electrochemical polishing surface. The corrosion morphology verified the analysis of potentiodynamic polarization and impedance spectrum. The multiple analysis method proposed in this paper can be used as a more accurate evaluation method for the corrosion resistance of alloy surface, avoiding the error of analysis results caused by the impedance spectrum equivalent circuit and potentiodynamic polarization following Tafel relationship.

Adolescent Empathy Influences Bystander Defending in School Bullying: A Three-Level Meta-Analysis.

Even though numerous studies have shown that adolescent empathy is positively related to bystander defending in school bullying, others have failed to detect a significant association between these two variables. To address this discrepancy, a three-level meta-analysis of 27 papers (35 independent studies, N = 25,012 adolescents) was conducted. The results showed that empathy was positively correlated with bystander defending. Furthermore, the strength of the relationship between empathy and bystander defending was moderated by the type of empathy and the evaluators of defending. Specifically, the correlation coefficient between affective empathy and bystander defending (r = 0.27, 95% CI [0.22, 0.32]) was significantly stronger than that between cognitive empathy and bystander defending (r = 0.22, 95% CI [0.17, 0.28]). Finally, the strength of the relationship between empathy and bystander defending was moderated by the evaluator of defending behavior. That is, the correlation coefficient of bystander defending measured by self-evaluation was significantly stronger than that measured by peer-evaluation. The results showed that empathy was closely related to bystander defending. Thus, school bullying can be prevented from the perspective of enhancing empathy among adolescents.

Collagen ß(1-O) galactosyltransferase 2 deficiency contributes to lipodystrophy and aggravates NAFLD related to HMW adiponectin in mice.

AIM: Our previous results showed that Colgalt1 knock-out resulted in fetal death on day E11.5, and collagen secretion was retarded. This study aimed to elucidate the role of Collagen ß(1-O) galactosyltransferase 2 (Colgalt2) in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). METHODS: Colgalt2-/- mice were fed a high-fat diet (HFD) or methionine-and choline-deficient diet (MCD). Nanopore long-read RNA-Seq analysis of liver tissues was used to profile genomic variation. In vitro, hepatocyte steatosis and differentiation of primary pre-adipocytes were induced. RESULTS: Colgalt2-/- mice exhibited lipodystrophy, increased body weight, and hepatic lipid accumulation at 6 weeks of age. Colgalt2 deficiency aggravated hepatic steatosis in mice fed an HFD or a standard laboratory chow diet. Colgalt2 deficiency promotes steatohepatitis in MCD-fed mice. In HFD mice, Colgalt2 deficiency caused lipodystrophy and decreased plasma HMW, total adiponectin, and leptin levels. Colgalt2 deficiency also reduced circulating HMW/Total adiponectin in mice fed a HFD diet without differences of adiponectin mRNA and protein level in WT and Colgalt2-/- mice. The nanopore long-read RNA-Seq analysis results revealed transcriptional changes in the adiponectin receptor downstream signaling pathway and lipogenic genes, including the AMPK signaling pathway, adipocytokine signaling pathway, and lipid metabolism (Cidea, Cidec, CD36, and PPARγ). Colgalt2 deficiency did not promote lipid accumulation in OA-induced HepG2 cells or primary hepatocytes. However, Colgalt2 deficiency inhibited adipogenesis and reduced PPARγ, adipogenesis-related transcription factors, and expression during adipocyte differentiation. CONCLUSIONS: In mice, Colgalt2 deficiency contributes to lipodystrophy and promotes NAFLD related to HMW adiponectin. These results suggest that Colgalt2 could be a novel and promising therapeutic strategy for the treatment of NAFLD.

EOGT Correlated With Immune Infiltration: A Candidate Prognostic Biomarker for Hepatocellular Carcinoma.

Background: A preliminary study by our group revealed that the deficiency of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) impaired regulatory T-cell differentiation in autoimmune hepatitis. Nevertheless, the prognostic value of EOGT in advanced hepatocellular carcinoma (HCC) and its relationship with immune infiltration remain obscured. Methods: Initially, EOGT expression was evaluated by Oncomine, TIMER, GEO, and UALCAN databases. Besides, the prognostic potential of EOGT expression was analyzed using GEPIA, Kaplan-Meier plotter, CPTAC, Cox regression, and nomogram in HCC samples. Furthermore, we investigated the association between EOGT expression and tumor mutation burden, DNA methylation, and immune infiltration in addition to its possible mechanism via cBioPortal, TIMER, GEPIA, ESTIMATE, CIBERSORT, GSEA, STRING, and Cytoscape. Results: The expression of EOGT in HCC was significantly higher than that in normal tissues. Additionally, elevated EOGT expression was correlated with advanced tumor staging and linked to poor overall survival and relapse-free survival, serving as a significant unfavorable prognostic indicator in HCC patients. Remarkably, our results revealed that high-EOGT expression subgroups with elevated TP53 or low CTNNB1 mutations have worse clinical outcomes than the others. Regarding immune infiltration, immunofluorescent staining showed that immune cells in HCC were positive for EOGT. Besides, elevated EOGT expression was linked to exhausted T cells and immune suppressor cells in HCC samples. More importantly, the proportion of CD8+ T cells was reduced in HCC samples with a high level of EOGT expression, but EOGT did not exhibit prognostic potential in HCC samples with increased CD8+ T cells. Conclusions: EOGT may hold great potential as a novel biomarker to distinguish prognosis and immune profiles of HCC patients.

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.

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.

Deficiency of O-linked-glycosylation regulates activation of T cells and aggravates Concanavalin A-induced liver injury.

OBJECTIVE: Protein glycosylation is involved in immunological recognition and immune cell activation. The role of O-glycosylation in Concanavalin A (Con A)-induced autoimmune hepatitis (AIH) was elucidated in the present study. METHODS: Mice were intravenously injected with Con A (10 mg/kg) to establish an AIH mouse model. Here, 24 h prior to administration of Con A, experimental mice were intragastrically administrated with O-glycosylation inhibitor (benzyl-α-GalNAc) at doses of 1 and 5 mg/kg, respectively, while control mice were administrated with the same volume of saline. Before and after administration of Con A for 6 and 12 h, mice were sacrificed and their plasma and livers were collected to score liver injury. Peripheral blood, spleen, and thymus were collected for flow cytometry analysis. The expression levels of neutrophilic alkaline phosphatase-3 (NALP3) and NALP6 in liver were evaluated as well. RESULTS: Pre-treatment with benzyl-α-GalNAc increased the serum transaminase levels and induced more infiltration and necrosis in livers of Con A administrated mice. The levels of some pro-inflammation cytokines also increased in administrated mice. In addition, pretreatment with benzyl-α-GalNAc up-regulated the expression levels of NALP3 and NALP6. And benzyl-α-GalNAc inhibited the levels of apoptosis of thymus cells and influenced activation of T cells in peripheral blood and spleen of Con A administrated mice, especially that accelerated the physiological progression of CD4+CD25-CD69+ subset. CONCLUSION: The present research demonstrated that benzyl-α-GalNAc aggravated Con A-induced AIH, and the role of the O-glycosylation inhibitor as the aggravation may be related to regulation of the levels of cytokines, as well as influencing proliferation of T cells.

Down-regulation of GLT25D1 inhibited collagen secretion and involved in liver fibrogenesis.

Collagen ß (1-O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via ß (1-O) linkages in collagen. However, the role of Glt25d1 in liver fibrogenesis is still unknow. Recently, we generated a Glt25d1 knockout mouse to elucidate the role of Glt25d1 in vivo. However, we found that complete deletion of the Glt25d1 gene resulted in embryonic lethality at E11.5. Histopathological analysis revealed that dysplasia in Glt25d1-/- labyrinth with defects of the vascular network. Immunohistochemical showed that the decrease in proliferation of Glt25d1-/- liver and the developing central nervous system (CNS). The role of Glt25d1 in liver fibrogenesis was explored by Glt25d1+/- mice. Glt25d1+/- mice and wild-type (WT) mice were injected intraperitoneally with the same dose of CCl4. The higher level of serum alanine aminotransferase was observed in Glt25d1+/- mice. Reverse transcription-quantitative polymerase chainreaction demonstrated that the mRNA expression levels of the inflammatory cytokines such as, Tnf-α, Cxcl-1 and Mcp-1, showed a significantly increase in CCl4-treated Glt25d1+/- mice. Collagen-I, collagen-III and α-SMA transcripts accumulation was markedly increased in the Glt25d1+/- mice. However, Masson's trichrome staining revealed a trend to decrease in the ECM proteins deposition of Glt25d1+/- liver. Immunohistochemistry and Western blots revealed that the protein expression of Collagen-III was reduced and a trend to a decrease in collagen-I was observed in the Glt25d1+/- liver compared with those of WT mice. Our results demonstrate that Glt25d1 knockout results in embryonic lethality and down-regulation of Glt25d1 may inhibit collagen secretion during liver fibrogenesis.

Diammonium Glycyrrhizinate Mitigates Liver Injury Via Inhibiting Proliferation Of NKT Cells And Promoting Proliferation Of Tregs.

PURPOSE: Diammonium glycyrrhizinate (DG) is a replacement for glycyrrhizic acid, which is used as a hepatic protector in clinical practice for most liver diseases. The potential role of immune response during autoimmune hepatitis-induced by concanavalin A (Con A)-remains to be elucidated. METHODS: C57BL/6J mice were treated with two different doses of DG (75 and 200 mg/kg) 2 hrs before administering Con A. The mice were sacrificed after administering Con A for 0, 6, and 24 hrs. Liver damage grade and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin levels were evaluated. The expression level of cleaved-caspase 3 in liver was detected by Western blotting. Inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interferon γ (IFN-γ) in liver were detected by RT-PCR. Thymus, peripheral blood, spleen, and liver tissues were collected to analyze the percentages of NKT cells, subsets of CD4+CD25-CD69+ and CD8+CD69+ T cells, and subsets of regulatory T cells (Tregs). RESULTS: Our results revealed that DG pre-treatment significantly decreased the serum ALT and AST levels and improved the histological damage in Con A-induced autoimmune liver injury. Pre-treatment with DG down-regulated the inflammatory cytokines upon challenge with Con A. The DG pre-treatment inhibited the apoptosis of T lymphocytes in the thymus. Further, it effectively suppressed the proliferation of CD4+CD25-CD69+ and CD8+CD69+ subsets in the peripheral blood and spleen. In addition, the DG pretreatment significantly downregulated the frequency of NKT cells, while upregulating the frequency of Tregs in the liver. CONCLUSION: We believe that the potential protective effect of DG against Con A-induced hepatitis may be partially attributed to its inhibitory activities on inflammatory cytokines in the livers, lymphocyte apoptosis in the thymus, NKT cells proliferation, and activation of CD8+T cells; further, there may also be a possibility of DC promoting Tregs proliferation.

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.

A new algorithm for predicting long-term survival in chronic hepatitis B patients with variceal bleeding after endoscopic therapy.

BACKGROUND AND AIMS: A predictive algorithm for survival is urgently needed in clinical practice. This study aimed to establish an algorithm to predict long-term survival in chronic hepatitis B (CHB) patients with hepatic cirrhosis and variceal bleeding after endoscopic therapy. METHODS: This was a retrospective study in which 603 patients who followed-up for three years were randomly assigned into a training cohort and a validation cohort in a 2:1 ratio. A new score model was devised based on the result of Cox regression analysis in the training cohort, and was verified in the validation cohort. RESULTS: A prediction score model composed of age, neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase and MELD score was established. The score ranged from 0 to 11. Areas under the ROC curve of the score were 0.821 (p < 0.001, 95% CI: 0.769-0.873) and 0.827 (p < 0.001, 95% CI: 0.753-0.900) in the training cohort and validation cohort, respectively. Scores 0-4 and 5-11 identified patients as low-risk and high-risk categories, respectively. The cumulative 3-year survival rate was significantly higher in the low-risk group than in the high-risk group (p < 0.001). CONCLUSION: The new score model can be used to predict long-term survival in CHB patients with hepatic cirrhosis and variceal bleeding after endoscopic therapy.