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The associations between obesity and liver diseases are complex and diverse. To explore the causal relationships between obesity and liver diseases, we applied two-sample Mendelian randomisation (MR) and multivariable MR analysis. The data of exposures (BMI and WHRadjBMI) and outcomes (liver diseases and liver function biomarker) were obtained from the open genome-wide association study database. A two-sample MR study revealed that the genetically predicted BMI and WHRadjBMI were associated with non-alcoholic fatty liver disease, liver fibrosis and autoimmune hepatitis. Obesity was not associated with primary biliary cholangitis, liver failure, liver cell carcinoma, viral hepatitis and secondary malignant neoplasm of liver. A higher WHRadjBMI was associated with higher levels of biomarkers of lipid accumulation and metabolic disorders. These findings indicated independent causal roles of obesity in non-alcoholic fatty liver disease, liver fibrosis and impaired liver metabolic function rather than in viral or autoimmune liver disease.

Disasters are more destructive and frequent in the age of climate change, overpopulation, and neoliberal globalisation. While the literature on disaster prevention and management proliferates, the role of for-profit corporations has only recently started to be examined, usually through the lens of corporate social responsibility (CSR)-the expectation that business will consider social and environmental interests in its operations, in addition to profit. There is lately much academic creativity in the CSR space pertaining to why and how large corporations should contribute to disaster recovery, but a conceptual red thread is missing. This paper proposes that the unifying concept is the CSR principle of refraining from exploiting disaster-hit communities. Indeed, CSR principles evolve in time, reflecting contemporary societal priorities. In a contractarian perspective on CSR, a rational community would nowadays have solid reasons to expect, in its social contract with business, the latter's commitment to decency when the former is devastated by earthquakes, pandemics, wars, and the like., (© 2024 ODI.)

Introduction and Objectives: Significant fibrosis is an indicator of clinical intervention for both chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD). There remains a paucity of data regarding the clinical impact of biopsy-defined MASLD on significant fibrosis in CHB patients. The current study aims to elucidate whether patients with concomitant MASLD are at higher risk of significant fibrosis in patients with CHB., Patients and Methods: This retrospective research of two tertiary hospitals comprised 1818 patients between 2009 and 2021 with CHB and hepatic steatosis who had not received antiviral therapy. Pathologic findings by liver biopsy were contrasted between CHB group (n = 844) and CHB + MASLD (n = 974) group. METAVIR values of F≥2 were used to categorize significant fibrosis., Results: Patients with CHB + MASLD had more significant fibrosis (35.5 % vs. 23.5 %, p < 0.001) than CHB group. The presence of MASLD [adjusted odds ratio (aOR) 2.055, 95 % confidence interval (CI) 1.635-2.584; p < 0.001] was strongly associated with significant fibrosis in all CHB patients. There was a trend for patients with more cardiometabolic risk factors (CMRFs) to have a higher prevalence of significant fibrosis: (25.7 % in CMRF1 subgroup v.s. 34.9 % in CMRF2 subgroup v.s. 53.7 % in CMRF≥ 3 subgroup, p < 0.001). Patients with CMRF≥3 had a three-fold higher significant fibrosis than those with just one CMRF., Conclusions: MASLD was associated with higher fibrosis stage in patients with CHB. Early detection and intervention are crucial to patients with three or more cardiometabolic risk factors., Competing Interests: Declaration of interests None., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Aims/Background Bedside ultrasound evaluation of venous excess ultrasound (VExUS) combined with the triglyceride-glucose (TyG) index plays an important role in predicting acute kidney injury (AKI) in patients with acute hyperlipidemic pancreatitis. VExUS can effectively evaluate the degree of venous congestion, while the TyG index is valuable in predicting severe pancreatitis. The combination of these two methods is expected to provide a more accurate AKI risk assessment tool for clinical practice. This study explores the value of combining bedside ultrasound evaluation using the VExUS grading system with the TyG index in predicting acute renal damage in patients with acute hyperlipidemic pancreatitis. Methods From January 2021 to December 2023, 110 patients with acute hyperlipidemic pancreatitis were selected. The patients were divided into two groups based on whether they were complicated with acute kidney injury (AKI): the AKI group (n = 23) and the non-AKI group (n = 87). The general data of the two groups were compared, and the risk factors for AKI in patients with acute hyperlipidemic pancreatitis were analyzed using multivariate logistic regression. The predictive value was assessed using receiver operating characteristic curve (ROC) analysis. Results There were no statistically significant differences in age, gender, outcome, triglyceride (TG), total cholesterol, low-density lipoprotein (LDL) levels at admission, blood nutrition at discharge, creatinine (CREA) at discharge, underlying diseases, start time of enteral nutrition, complications, length of stay, Intensive Care Unit (ICU) days, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, blood glucose level, blood amylase level, CREA, blood urine nitrogen (BUN), blood purification treatment ( p > 0.05). However, there were significant differences ( p < 0.05) between the TyG index and the VExUS score, with variables including the TyG index and the VExUS score (included in the logistic regression analysis as variables), and AKI (AKI = 1, non-AKI = 0) as dependent variables. Multiple logistic regression results showed that the TyG index and VExUS score were independent predictors of AKI in patients with acute hyperlipidemia pancreatitis ( p < 0.05). The standard error, sensitivity and specificity of the TyG index, VExUS score and combined model for predicting AKI in these patients were 0.064, 73.91 and 87.45; 0.036, 78.16 and 95.65; 0.010, 100.00 and 95.65, respectively ( p < 0.05). Conclusion The VExUS score combined with the TyG index is highly valuable in predicting AKI in patients with acute hyperlipidemic pancreatitis.

The hydrochemical characteristics of acid mine drainage (AMD) were investigated in Wuma River Basin, China. AMD was sampled from nine closed coal mine (CCM) sites to study the temporal and spatial evolution of pH, dissolved oxygen (DO), electrical conductivity (ED), total hardness (THR), total dissolved salt (TDS), and trace elements. The surface water (river) and groundwater surrounding mine sites were sampled to evaluate the potential pollution derived from AMDs. The TDS content of AMD was higher than that of surface water and groundwater. The dominant factors influencing TDS were the pH, temperature, and wet or dry season (which played a role in controlling microbial activity), HCO 3 - balance, and REDOX during the evolutionary process. The hydrochemical type of AMD was dependent on the evolutionary stage. From observations, most AMDs were in the form of the SO 4 2- -Ca 2+ •Mg 2+ type that was characterized by a low pH, low [HCO 3 - ], high [SO 4 2- ], and high [Fe]. In addition, the AMD samples were undergoing stage I and II processes, in which SO 4 2- and trace elements were generated. The surface water and groundwater were primarily classified as the HCO 3 - -Ca 2+ •Mg 2+ type, which accounted for their self-cleaning capacity, as indicated by the high [HCO 3 - ]. The surface water and groundwater could be affected by the surrounding AMD depending on the geographical location. The surface water and groundwater sites that were located downstream of subsurface and surface runoff were obviously affected by AMD. After being polluted by AMD, surface water and groundwater contained higher levels of trace elements and emerged as the HCO 3 - •SO 4 2- -Ca 2+ •Mg 2+ type., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The emergence of severe sepsis is contingent upon the occurrence of a cytokine storm (CS), a multifaceted process intricately entwined with the temporal dimension, thereby rendering the infection response remarkably intricate. Consequently, it becomes imperative to discern and accurately identify the optimal timing for interventions, predicated upon the dynamic timeline of inflammatory changes. Moreover, the administration of exogenous low-dose pro-inflammatory agents has exhibited the potential to impede the relentless progression of the inflammatory cascade. Hence, the present study aims to scrutinize the impact of exogenous Local Inflammatory Response (eLIR) on the body surface in the context of the inflammatory cascade during sepsis, within a temporal framework, with a particular emphasis on the point of exacerbation of inflammation., Methods: Rats were induced sterile sepsis by intraperitoneal injection of zymosan (ZY) at an appropriate dosage. The temporal progression of inflammatory changes and eLIR effects were described based on the trend of serum crucial inflammatory cytokines, tring to quest time-point of inflammatory aggravation in sepsis. Then, the varying degrees of surface inflammation caused by eLIR on this time point leading to the final effects on the inflammatory cascade response were explored. In addition, given the authentic pathological progression of sepsis, further observation was conducted on the impact of another intervention timing of eLIR on the inflammatory cascade. The survival rate was measured. Serum and organ related inflammatory cytokines were detected, and organ histopathology was investigated., Results: In present study, a dosage of 600 mg/kg ZY was found to be optimal for the sterile sepsis model. Initiating eLIR 6 h prior to ZY injection, the maximum effect point of eLIR could be precisely align with the inflammatory aggravation point of sterile sepsis. Initiating eLIR at this time, 3 sessions of eLIR were found to be more effective than 1 or 2 sessions in mitigating inflammatory responses during the initial stage of inflammation and the peak of inflammation. Notably, the findings also suggested that this intervention improve survival rate. In addition, the anti-inflammatory efficacy has been substantially diminished by the prompt initiation of 3 sessions of eLIR immediately after ZY injection at the onset of sepsis. Similarly, the current findings did not demonstrate a statistically significant enhancement in survival rates with eLIR at this time point., Conclusions: Compared with the initial stage of inflammation, low-scale inflammation caused by a certain intensity of eLIR (3 sessions) on the body surface can more effectively pry the inflammation aggravation time-point, thereby shifting the pro-inflammatory to anti-inflammatory milieu, impeding the disproportionate cytokines release in inflammatory diseases, slowing down the inflammatory cascade, and improving the survival rate of sepsis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Ectodermal neural cortex 1 (ENC1) is a protein that plays a crucial role in the regulation of various cellular processes such as cell proliferation, differentiation, and apoptosis. Numerous studies have shown that ENC1 is overexpressed in various types of cancers, including breast, lung, pancreatic, and colorectal cancer, and its upregulation is correlated with a poorer prognosis. In addition to its role in cancer growth and spreading, ENC1 has also been linked to neuronal process development and neural crest cell differentiation. In this review, we provide an overview of the current knowledge on the relationship between ENC1 and cancer. We discuss the molecular mechanisms by which ENC1 contributes to tumorigenesis, including its involvement in multiple oncogenic signaling pathways. We also summarize the potential of targeting ENC1 for cancer therapy, as its inhibition has been shown to significantly reduce cancer cell invasion, growth, and metastasis. Finally, we highlight the remaining gaps in our understanding of ENC1's role in cancer and propose potential directions for future research., (© 2024. The Author(s).)

Enzymes are essential catalysts for various chemical reactions in biological systems and often rely on metal ions or cofactors to stabilize their structure or perform functions. Improving enzyme performance has always been an important direction of protein engineering. In recent years, various artificial small molecules have been successfully used in enzyme engineering. The types of enzymatic reactions and metabolic pathways in cells can be expanded by the incorporation of these artificial small molecules either as cofactors or as building blocks of proteins and nucleic acids, which greatly promotes the development and application of biotechnology. In this review, we summarized research on artificial small molecules including biological metal cluster mimics, coenzyme analogs (mNADs), designer cofactors, non-natural nucleotides (XNAs), and non-natural amino acids (nnAAs), focusing on their design, synthesis, and applications as well as the current challenges in synthetic biology.

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Collagen β(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-β1)-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-β1/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., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Hydrogen with high energy content is considered to be a promising alternative clean energy source. Biohydrogen production through microbes provides a renewable and immense hydrogen supply by utilizing raw materials such as inexhaustible natural sunlight, water, and even organic waste, which is supposed to solve the two problems of "energy supply and environment protection" at the same time. Hydrogenases and nitrogenases are two classes of key enzymes involved in biohydrogen production and can be applied under different biological conditions. Both the research on enzymatic catalytic mechanisms and the innovations of enzymatic techniques are important and necessary for the application of biohydrogen production. In this review, we introduce the enzymatic structures related to biohydrogen production, summarize recent enzymatic and genetic engineering works to enhance hydrogen production, and describe the chemical efforts of novel synthetic artificial enzymes inspired by the two biocatalysts. Continual studies on the two types of enzymes in the future will further improve the efficiency of biohydrogen production and contribute to the economic feasibility of biohydrogen as an energy source.

Start temporal landmark is the beginning of a period of time. Previous research has established that individuals have the need for arousal at the start temporal landmarks but less research has focused on individual differences and the relationship between self and others (independent vs. interdependent). This research examines the influence of individuals' self-construal on the relationship between start temporal landmarks and arousal product preference. Three experiments with 1136 participants were recruited from a university, community, and online store in Southern China. The data were analyzed by Cochran-Mantel-Haenszel on SPSS 26.0 software program. The results showed that self-construal influenced the effect of start temporal landmarks on arousal product preference. Specifically, compared with ordinary temporal landmarks, individuals with interdependent self-construal prefer high arousal products under start temporal landmarks, whereas those with independent self-construal show no significantly different preference for high or low arousal products under the start temporal landmarks. Furthermore, psychological resources play a mediating role. This research extends the theoretical research on self-construal in the field of temporal landmarks and arousal. It also has important practical implications for improving the sales of high arousal products.

Introduction: The Omicron variant of the novel coronavirus (COVID-19) has been spreading more rapidly and is more infectious, posing a higher risk of death and treatment difficulty for patients undergoing hemodialysis. This study aims to explore the severity rate and risk factors for hemodialysis patients infected with the Omicron variant and to conduct a preliminary analysis of the clinical efficacy of drugs., Methods: Clinical and biochemical indicators of 219 hemodialysis patients infected with the Omicron variant were statistically analyzed. The patients were divided into two groups based on whether they were severely ill or not, and multiple regression analysis was conducted to determine the risk factors for severe illness. The severely ill patients were then grouped based on discharge or death, and the treatment drugs were included as influencing factors for multiple regression analysis to determine the risk factors and protective factors for death of severely ill patients, and drug efficacy analysis was conducted., Results: Analysis showed that diabetes, low oxygen saturation, and high C-reactive protein (CRP) were independent risk factors for severe illness in hemodialysis patients infected with the Omicron variant. A history of diabetes and high C-reactive significantly increased the risk of severe illness in patients (aOR: 1.450; aOR: 1.011), while a high oxygen saturation level can reduce this risk (aOR: 0.871). In addition, respiratory distress was an independent risk factor for death in severely patients, significantly reducing the probability of discharge for patients (aOR: 0.152). The drugs thymalfasin and Tanreqing significantly increased the probability of discharge for patients (aOR: 1.472; aOR: 3.104), with the latter having a higher correlation, but with a relatively longer effective course., Conclusion: Hemodialysis patients infected with the Omicron variant of COVID-19 should pay special attention to their history of diabetes, CRP, and oxygen saturation levels, as well as respiratory distress symptoms, to reduce the risk of severe illness and death. In addition, thymalfasin and Tanreqing may be considered in treatment., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

A better knowledge of the molecular process behind uterine corpus endometrial carcinoma (UCEC) is important for prognosis prediction and the development of innovative targeted gene therapies. The purpose of this research is to discover critical genes associated with UCEC. We analyzed the gene expression profiles of TCGA-UCEC and GSE17025, respectively, using Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. From four sets of findings, a total of 95 overlapping genes were retrieved. On the 95 overlapping genes, KEGG pathway and GO enrichment analysis were conducted. Then, we mapped the PPI network of 95 overlapping genes using the STRING database. Twenty hub genes were evaluated using the Cytohubba plugin, including NR3C1, ATF3, KLF15, THRA, NR4A1, FOSB, PER3, HLF, NTRK3, EGR3, MAPK13, ARNTL2, PKM2, SCD, EIF5A, ADHFE1, RERGL, TUB, and ENC1. The expression levels of NR3C1, PKM2, and ENC1 were shown to be adversely linked with the survival time of UCEC patients using univariate Cox regression analysis and Kaplan-Meier survival calculation. ENC1 were also overexpressed in UCEC tumor tissues or cell lines, as shown by quantitative real-time PCR and Western blotting. Then we looked into it further and discovered that ENC1 expression was linked to tumor microenvironment and predicted various immunological checkpoints. In conclusion, our data indicate that ENC1 may be required for the development of UCEC and may serve as a future biomarker for diagnosis and therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, He, Luo and Xu.)

Glucocorticoids (GCs) have been widely detected in the aquatic system. However, the hazardous effects of GCs on aquatic organisms were underestimated, and the mechanisms of GCs-induced toxic effects in fish were largely unknown. The zebrafish larvae at 3 dpf were exposed to dexamethasone (DEX) for 48 h, and the toxic effects and the underlying mechanisms were investigated in the current study. The T cells were ablated in zebrafish larvae after being treated with 1, 3, 10, 30 and 100 μM of DEX for 48 h. In addition, osteoporosis was induced and the regeneration of the caudal fin was inhibited, by 48 h-exposure to 10, 30 and 100 μM of DEX. The transcriptomic analysis, biochemical parameters and gene expression profiles revealed that ferroptosis possibly contributed to the DEX-induced toxic effects in zebrafish larvae. Finally, Fer-1 treatment partially attenuated the DEX-induced T cell ablation, but not osteoporosis in zebrafish larvae. Taken together, the current study proved the toxic effects of DEX on zebrafish larvae, and elucidated that ferroptosis was involved in DEX-induced toxicity, providing strong evidence for the toxic effects of GCs on aquatic organisms., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

People pay much attention to food and health issues, more so these days. Organic food brings its own "organic" aura as soon as it is produced. Despite the many studies on organic food packaging at present, they mainly focus on packaging design, materials, and colors and pay less attention to packaging size. In view of this gap in the literature, this study explores the influence of organic food packaging size on consumer purchase intention. This article conducted two experiments with 755 participants to examine the effect of organic food packaging size on purchase intention. The results show that the packaging size of organic food has a significant influence on consumer purchase intention. Specifically, the small size of organic food packaging (vs. large) can improve consumer purchase intention, and the green perceived value plays an intermediary role (Study 1). In addition, the consumers' construal level moderates the influence of organic food packaging size on their purchase intention. For consumers with a high construal level, the small size of organic food packaging (vs. large) can improve their purchase intention. For consumers with a low construal level, large packaging size (vs. small) of organic food can improve their purchase intention (Study 2). This study reveals the psychological mechanism and boundary conditions of organic food packaging size on consumer purchase intention and provides practical enlightenment for enterprises in formulating the size of organic food packaging.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that greatly threatens public health. This study aimed to examine a convenient early-warning biomarker of fatal outcomes in patients with SFTS to reduce mortality., Methods: A retrospective cohort study was performed, and patients with confirmed SFTS were enrolled in the top two hospitals in Anhui Province, China from 1 May 2016 to 31 October 2019. The clinical symptoms, laboratory indicators, and treatment data of patients with SFTS were evaluated. All patients with SFTS were followed up till 28 days from the start of admission. The laboratory indicators that could be used to predict the fatal outcome were identified., Results: A total of 228 patients with SFTS were enrolled, 177 patients were enrolled in the survival group, and 51 patients in the death group. The median age of all 228 patients with SFTS was 63 years. Five laboratory indicators (SFTSV viral load, neutrophil to lymphocyte ratio (NLR), aspartate transaminase (AST)/alanine aminotransferase (ALT), ALT, and blood urea nitrogen (BUN)) were identified as the predicting factors of the fatal outcome of patients with SFTS. The area under the receiver operating characteristic (ROC) curve (AUC) of SFTSV viral load was the highest (0.919), then NLR (0.849), followed by AST/ALT (0.758), AST (0.738), and BUN (0.709). The efficacy of SFTVS viral load and NLR in predicting fatal outcomes was significantly higher than AST/ALT, AST, and BUN. The Kaplan-Meier survival curves show that the case fatality rate was significantly increased in patients whose SFTSV viral load was higher than 500,000 or NLR higher than 2.0. Gamma-globulin treatment showed a significant difference between the survival group and the death group, and the duration of gamma-globulin that had been proposed should not be <3 days., Conclusion: The SFTSV viral load and NLR showed great efficacy in predicting the fatal outcome of patients with SFTS, and NLR is a convenient and efficient early-warning biomarker that helps healthcare workers focus on patients with high risks of fatal outcomes. The efficacy of gamma-globulin provided a new idea for the treatment of SFTS, which needs further analysis in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Wang, Kang, He, Sheng, Qin, Ma, Xu, Hu, Zou, Gao and Li.)

Previous studies on the follow-up effect of serendipity mostly focused on the positive effects and less on the negative effects. Therefore, the purpose of this article is to investigate the negative effect of serendipity on the purchase intention of unexpected products. To verify all hypotheses in this article, we used online and offline survey data in China. Three experimental results showed that serendipity contains a certain degree of uncertainty, which will cause consumers' perceived risk and decrease the purchase intention of unexpected products. Perceived risk plays a mediating role in the effect of serendipity on the purchase intention of unexpected products. Moreover, regulatory focus moderates the effect of serendipity on purchase intention of unexpected products. Specifically, for prevention-focused individuals, the negative effect of serendipity on the purchase intention of unexpected products is strengthened. For promotion-focused individuals, the negative effect of serendipity on the purchase intention of unexpected products is weakened. This article augments the understanding of the negative effects of serendipity and provides theoretical guidance and support for the management practice of marketers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liang, Chu, Zhang, Li, Lan and He.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shu, He, Gao, Xiao, Yang, Wang, Wei, Zhang and Wei.)

Background: Klebsiella pneumoniae ( K. pneumoniae ) causes community-acquired and hospital-acquired pneumonia. The mortality rates of invasive infections caused by hypervirulent K. pneumoniae (HvKP) are extremely high. However, the microbiological characteristics and clinical manifestations of K. pneumoniae in AnHui province still remain unclear., Purpose: To show the high prevalence of HvKP infections regarding clinical characteristics and antimicrobial resistance in Anhui province., Patients and Methods: A retrospective analysis was conducted to study the clinical data of 115 strains of K. pneumoniae from July 2019 to March 2020 in The First Affiliated Hospital of AnHui Medical University. The virulence genes, capsular types, carbapenemase genes, and molecular subtypes of these hypervirulent isolates were detected., Results: Overall, 59.1% (68/115) cases were HvKP infections, mainly from the department of intensive care unit (ICU, n=14, 20.6%) and the department of respiratory and critical care (n=13, 19.1%). K2 was the most prevalent capsular serotype (n=26), followed by K1 (n=21). The results of MLST identification of 68 strains showed that ST23 (n=15, 22.1%) was the most common type of ST, followed by ST11 and ST65 (n=12, 17.6%), ST86 (n=9, 13.2%), and ST412 (n=6, 8.8%). Among 68 hvKP strains, 12 isolates were carbapenem resistant, and all except two harboured KPC ., Conclusion: The high incidence of carbapenemase producing HvKP in the Anhui province, especially the higher mortality of HvKP, should be paid more attention. Meanwhile, epidemiological surveillance and clinical treatment strategies should be continuously determined and implemented., Competing Interests: The authors declare no conflicts of interest in this work., (© 2021 Su et al.)

Acupuncture can significantly ameliorate inflammatory pain in acute visceral hyperalgesia. Hyperalgesia is attenuated by inflammatory mediators that activate transient receptor potential vanilloid 1 (TRPV1), and TRPV1 is regulated by nerve growth factor (NGF)-induced phosphatidylinositol 3-kinase (PI3K)/Akt pathway. However, it is unknown whether NGF-induced PI3K/Akt pathway is associated with manual acupuncture (MA). In this study, the effect and mechanism of MA at Shangjuxu (ST37) and Quchi (LI11) were examined using an acetic acid-induced rat model with visceral hyperalgesia. We demonstrated that MA at ST37 significantly decreased abdominal withdrawal reflex (AWR) scores, proinflammatory cytokine expression (TNF- α , IL-1 β , and IL-6), and TRPV1 protein and mRNA expression in rats with acute visceral hyperalgesia compared with the untreated controls, while MA at LI11 showed no effect. The effects of MA at ST37 were reversed after treatment with the PI3K agonist IGF-1 30 min before MA. In rats with visceral hyperalgesia, the upregulation of NGF, tropomyosin-receptor-kinase A (TrkA), PI3K, and phosphorylation-Akt (p-Akt) was decreased by MA at ST37, indicating that TRPV1 regulation via the NGF-induced PI3K/Akt pathway plays a vital role in the effects of MA-mediated amelioration of acute visceral hyperalgesia., Competing Interests: The authors each declare that there are no conflicts of interest related to the findings presented in this study., (Copyright © 2021 Caiyi Chen et al.)

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., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Enclosed silver nanoloops have unique features in manipulating and controlling light. However, even the conception of their growth mechanism has not been established. The intermediate structure at the growth stage were revealed as the crucial issue for studying their smart growth mechanism of silver nanoloops and nanowires. Early growth stage showed that silver nanorods and nanoparticles were grown in their respective polyvinylpyrrolidone micelles. Then, the silver nanorods and nanoparticles were assembled in a rod-particle-rod pattern via micelle-micelle coupling, forming linear silver nanowires. These silver nanowires were attracted by Van der Waals forces forming the initial nanoloop. Notably, there was a silver nanoparticle between the ends of two adjacent nanowires. This silver nanoparticle acted like solder and played a crucial role in connecting the two adjacent nanowires; consequently, a silver nanoloop was formed. This finding also suggested that similar smart growth patterns might exist for other one-dimensional and looped nanomaterials., (© 2021 IOP Publishing Ltd.)

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 β(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., Competing Interests: Declaration of competing interest Junru Yang, Lingling He, Meixin Gao, Fan Xiao, Fuyang Zhang, Shiwei Wang, Yang Shu, Xiaohui Ye, Wenzheng Qu, Liying Li and Hongshan Wei declare no conficts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In the process of electrolytic aluminium production, a large amount of fluoride is deposited into the surrounding environment. The growth of crops within these areas creates a state of high stress in plants that can easily result in excessive fluorine enrichment in agricultural products, which in turn poses a health threat to humans via the food chain. However, it is not clear what the degree of influence is or how long the impacts of fluorides in soil and agricultural products last for. In this study, 122 vegetable species and 36 surface soil samples were collected within 10 km of an aluminium plant that had been abandoned for five years. The single factor index and the geological accumulation index methods were used to evaluate the degree of fluorine pollution in vegetables and soil within the study area. The hazard index and the hazard quotient were used to assess vegetable and soil health risks, respectively. The results showed that the fluorine content of 89.26% of agricultural products exceeded the Chinese Maximum Levels of Contaminants in Foods and was higher than in other regions, indicating that the emissions of fluoride from the aluminium plant still had a significant effect on fluorine accumulation in vegetables. The total fluorine (F t ) content in the surrounding surface soil (average value 1328.32 mg kg -1 ) was similar to the soil fluorine background in the nearby uncontaminated settlement area, but the soil water-soluble fluorine (F w ) was very high, indicating that the fluorine pollutants emitted from the aluminium plant had gradually been diluted by the high background of the original soil, but the solubility of these pollutants was higher (average 15.00 mg kg -1 ) and would continue to threaten the safety of agricultural products in this region. Within 1 km of the abandoned aluminium plant, the degree of fluorine enrichment in vegetables, and F t and F w in soil were significantly higher than other ranges, indicating that this was the main fluoride deposit area. Based on the HI and HQ evaluation, vegetables and ground dust around the aluminium plant still had high non-carcinogenic risks for children, even though it has been abandoned for more than five years.

Objective: To analyze the difference of immune damage between patients with severe fever with thrombocytopenia syndrome (SFTS) and patients with tsutsugamushi disease., Methods: A prospective case-control study was conducted. Thirty-one patients with SFTS and 16 patients with tsutsugamushi disease admitted to the First Affiliated Hospital of Anhui Medical University from October 2014 to June 2017 were enrolled, and another 10 healthy people were enrolled as control. The counts of CD4 + and CD8 + T lymphocytes, and the proportion of CD3 + T lymphocytes, natural kill cells (NK cells), B lymphocytes and plasma cells were detected by flow cytometry. Thirty-four inflammatory mediators were determined by a multiplex Luminex ® system synchronously. The differences of lymphocytes and cytokines between the two groups were compared., Results: The proportion of CD3 + T lymphocytes, the counts of CD4 + and CD8 + T lymphocytes in SFTS patients were significantly lower than those in patients with tsutsugamushi disease (t values were 4.860, 9.411 and 5.030, respectively, all P < 0.01), and the proportion of NK cells and B lymphocytes were significantly higher than those in patients with tsutsugamushi disease (t values were 2.344 and 5.896, respectively, both P < 0.05). The proportion of plasma cells in peripheral blood of SFTS patients was (7.7±1.2)%, the highest proportion of plasma cells in severe SFTS patients was up to 30%, and all patients showed λ monoclonal cell group in plasma cells. No plasma cells were detected in tsutsugamushi disease patients. The abnormal expressions of interleukin-1 receptor antibody (IL-1RA), interleukin (IL-6, IL-15, IL-10, IL-8), tumor necrosis factor-α (TNF-α), γ-interferon (IFN-γ), granulocyte colony-stimulating factor (G-CSF), eosinophil chemotactic factor (Eotaxin), IFN-γ-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP-1α, MIP-1β), platelet-derived growth factor (PDGF-AA, PDGF-AB/BB), activated regulatory normal T cells and secretion factors (RANTES) were found in patients with SFTS and tsutsugamushi disease. The levels of IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, Eotaxin, IL-8, IP-10, MCP-1 and MIP-1α in SFTS patients were significantly higher than those in patients with tsutsugamushi disease (Z values were 2.312, 2.447, 3.660, 5.444, 1.965, 2.402, 2.402, 2.997, 3.525, 2.481, 3.817, and 2.211, respectively, all P < 0.05), while PDGF-AA, PDGF-AB/BB and RANTES were significantly lower than those in patients with tsutsugamushi disease (Z values were 3.728, 2.514, 2.649, respectively, all P < 0.05). Correlation analysis showed that RANTES, PDGF-AA and PDGF-AB/BB levels were significantly positively correlated with the level of platelet in patients with SFTS and tsutsugamushi disease (SFTS: r values were 0.223, 0.365, 0.330; tsutsugamushi disease: r values were 0.263, 0.632, 0.407, respectively, all P < 0.05). In SFTS patients, compared with the survival group (n = 21), the CD3 + and CD4 + T lymphocytes in the death group (n = 10) significantly decreased, while the plasma cells significantly increased (t values were 3.980, 3.314 and 26.692, respectively, all P < 0.01); IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, Eotaxin, IL-8, IP-10, MCP-1, MIP-1α and MIP-1β significantly increased, while PDGF-AA, PDGF-AB/BB and RANTES significantly decreased (Z values were 3.930, 4.014, 2.832, 3.592, 2.958, 3.508, 2.578, 3.254, 4.270, 3.465, 2.663, 3.085, 3.107, 3.639, 3.043 and 3.825, respectively, all P < 0.05)., Conclusions: The immune function was impaired more seriously in SFTS patients than that in tsutsugamushi disease patients. Excessive humoral immunity and apoptosis of T lymphocytes are closely related to the death in SFTS patients. The detection of CD4 cells, plasma cells and proinflammatory and anti-inflammatory cytokines (e.g. IL-6, IL-10) had great clinical significance for the differentiation and illness evaluation in disease with SFTS or tsutsugamushi disease.

Sepsis is a dangerous disease that is caused by an overreaction of the body's immune system to infection and gradually spreads throughout the body. This experiment was carried out to explore the expression of LncRNA MEG3 in sepsis and its effect on LPS-induced macrophage function. Methods 60 sepsis patients admitted to our hospital from February 2017 to September 2018 were selected as the sepsis group, and 50 non-septic patients diagnosed and treated in our hospital during the same period were selected as the control group. qRT-PCR was used to detect the expression level of MEG3. ROC curve was used to analyze the diagnostic value of serum MEG3 in sepsis. The human macrophage cell line U937 was cultured in vitro and randomly divided into NC group, LPS group, LPS + pcDNA group, and LPS + pcDNA-MEG3 group. Flow cytometry was applied to detect the apoptosis rate. The levels of IL-1β and TNF-α were detected by ELISA. Western blot was used to detect the expression of Bax, Bcl-2 and NF-κB signaling pathway-related proteins p65 and p-p65. Results: The expression level of serum MEG3 in the sepsis group was significantly lower than that in the control group (P &lt;0.05). ROC curve analysis showed that the AUC area was 0.856, the sensitivity was 0.700, and the specificity was 0.883. Compared with the NC group, the macrophage apoptosis rate in the LPS group was increased (P &lt;0.05), the levels of Bax and p-p65 protein were significantly increased (P &lt;0.05), and the level of Bcl-2 protein was decreased (P &lt;0.05), the levels of IL-1β and TNF-α were increased (P &lt;0.05). Compared with the LPS + pcDNA group, the apoptosis rate of the LPS + pcDNA-MEG3 group was significantly reduced (P &lt;0.05), the levels of Bax and p-p65 protein were reduced (P &lt;0.05), and the level of Bcl-2 protein was significantly increased (P &lt;0.05), the levels of IL-1β and TNF-α were reduced (P &lt;0.05). Conclusion: The low expression of LncRNA MEG3 in the serum of patients with sepsis can predict the occurrence of sepsis. Overexpression of MEG3 can inhibit LPS-induced macrophage apoptosis and secretion of inflammatory factors by inhibiting the activation of the NF-κB signaling pathway.

Biochar has recently been fascinating for research in many environment areas due to its potential applications. In this research, graphene, and nano zero-valent iron (nZVI) were integrated with biochar and used for copper immobilization in the soil. Initially, the biomass feedstock was pyrolyzed under N 2 atmosphere from 150 to 650 °C and immersed in an aqueous solution containing graphene, and then impregnated with nZVI. Laboratory characterization with different instruments (eg. SEM, TEM, XRD, UV-Vis, VSM, and XPS) showed that graphene sheets and reactive nZVI were loaded on the biochar surface during the development process. The 450 °C was considered as optimum pyrolysis temperature based on the effective surface properties of the obtain biochar material. Boehm titration and functional group analysis confirmed the presence of carboxylic groups, phenolic groups in the corn stack biochar supported graphene oxide/nZVI (CTBC-GO/nZVI). Thermogravimetric analysis showed that nZVI incorporation to biochar surface could improve thermal stability as compared to graphene oxide incorporated biochar and pristine biochar. The material was utilized for copper (Cu) immobilization in the soil and a comparative evaluation was established on the basis of efficiency. The soil experiment showed that the CTBC-GO/nZVI has a superior immobilization efficiency of copper than pristine biochar and GO@BC. The available Cu content decreased by > 65% in CTBC-GO/nZVI amended soil after 14 days. Sequential extraction procedure (SEP) results suggested that CTBC-GO/nZVI promoted the conversion of more accessible Cu into the less accessible and bioavailable forms to reduce the toxicity of Cu. Therefore, CTBC-GO/nZVI composite is a promising and effective amendment for immobilizing Cu in contaminated soils and improving soil properties. This work can put forward a strategy to develop magnetic biochar composites and an application towards toxic heavy metals immobilization in soil., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Collagen β (1-O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via β (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 CCl 4 . 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 CCl 4 -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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

T helper 17 (Th17) cells and related cytokines are important in multiple sclerosis (MS), which have become the new therapeutic targets of MS. In published studies, the effect of interferon-β (IFN-β) on the proportion of Th17 cells and related cytokines in MS patients remains controversial. We did a meta-analysis to assess the role of IFN-β on Th17 cells and related cytokines in MS patients. Compared with control subjects, MS patients with IFN-β treatment had a lower proportion of Th17 cells in CD4 + T cells of peripheral blood [-1.49 (-2.96 to -0.02)], interleukin (IL)-17 level [-1.08 (-1.77 to -0.40)], and IL-23 level [-1.63 (-2.59 to -0.68)] in serum. The results showed that IFN-β can reduce the proportion of Th17 cells, the levels of IL-17 and IL-23 in serum of MS.

The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC 50 ). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens.

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., Competing Interests: The authors declare no conflicts of interests in this work., (© 2019 Gao et al.)

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., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor (α2-AR) agonist, is widely used as sedative in clinical. Its potential anti-inflammatory properties have been found in recent studies. The current study has investigated the profound effects of DEX on acute liver injury in mice. The mice were intraperitoneally injected lipopolysaccharide (LPS) and D-galactosamine (D-Gal) to induce acute liver injury, and vehicle or DEX were treated 30 min before or 2 h after LPS/D-Gal exposure. The results showed that pre-treatment with DEX inhibited the raising of plasma aminotransferases, reduced the damage of liver tissue, and improved the survival rate in mice exposed to LPS/D-Gal. Pre-treatment with DEX also inhibited the release of TNF-α and suppressed the phosphorylation of c-jun-N-terminal kinase (JNK) in mice exposed to LPS/D-Gal. In addition, pre-treatment with DEX down-regulated the expression of cleavage of caspase-3, decreased the activities of caspase-3, caspase-8, caspase-9, and consequently, reduced hepatocyte apoptosis. Interestingly, post-treatment with DEX also resulted in beneficial outcomes. The current study indicates that administration of DEX might provide protective benefits in inflammatory liver disease., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Background: Warm needle acupuncture (WNA) is a traditional Chinese medicine (TCM) therapy which combines technical advantages of acupuncture and moxibustion. Climacteric insomnia is a common symptom in climacteric women, which can seriously affect the physical and mental health of patients. Relevant studies have been reported that WNA can improve insomnia in climacteric women. In this protocol, the effectiveness and safety of WNA on insomnia in climacteric women will be explored., Methods: Seven electronic databases include 3 English databases [Excerpta Medica database (EMBASE), PubMed, the Cochrane Central Register of Controlled Trials (Cochrane Library)] and 4 Chinese databases [Chinese VIP Information, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang Database] for randomised controlled trials (RCT) of WNA on insomnia in climacteric women will be searched. The changes of the Pittsburgh sleep quality index was used as the main outcome, and the secondary outcome includes the changes of the Kupperman score, serum hormone level, and TCM syndrome score, as well as the adverse events caused by WNA. We will use RevMan software V5.3 to help us to analyze all data and use a Cochrane risk of bias tool to help us to assess the methodological quality for RCTs., Result: This study will provide reliable evidence for WNA on insomnia in climacteric women CONCLUSION:: The findings will be an available reference to evaluate the effectiveness and safety of WNA on insomnia in climacteric women., Registration: PROS-PERO CRD42019125743.

Introduction: In recent years, an increasing number of studies have revealed the possible prognostic significance of Golgi protein 73 (GP73) in hepatocellular carcinoma (HCC), but the results are still controversial. Therefore, we performed a meta-analysis to explore the possible correlation between GP73 and prognostic value in HCC., Material and Methods: Relevant publications were searched for in PubMed, EMBASE, Cochrane Library and the Chinese Biomedical Literature Database up to March 2018. Odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (CI) of eligible studies were assessed by either fixed-effect or random effects models. Publication bias analysis was also performed to assess the reliability of the meta-analysis results., Results: In total, 9 studies including 1292 patients with HCC were included and analysed systematically in the study. The results indicated that GP73 overexpression was significantly associated with later tumour stage, higher tumour grade and poor overall survival (OS). Combined analysis of three studies showed no statistical correlation between high GP73 expression and disease-free survival (DFS). Subgroup analyses were also performed to illustrate the relationship between high GP73 expression and OS., Conclusions: The meta-analysis suggested that overexpression of GP73 may be associated with poor prognosis in HCC and may also have a predictive role for HCC invasion and metastasis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

Post-translational modifications such as glycosylation play an important role in the functions of homeostatic proteins, and are critical driving factors of several diseases; however, the role of glycosylation in autoimmune hepatitis is poorly understood. Here, we established an O-GlcNAc glycosylation-deficient rat model by knocking out the Eogt gene by TALEN-mediated gene targeting. O-GlcNAc glycosylation deficiency overtly aggravated liver injury in concanavalin-A induced autoimmune hepatitis, and delayed self-recovery of the liver. Furthermore, flow cytometry analysis revealed increased CD4 + T cell infiltration in the liver of rats with O-GlcNAc glycosylation deficiency, and normal differentiation of regulatory T cells (Tregs) in the liver to inhibit T cell infiltration could not be activated. Moreover, in vitro experiments showed that O-GlcNAc glycosylation deficiency impaired Treg differentiation to inhibit the Notch signaling pathway in CD4 + T cells. These finding indicate that O-GlcNAc glycosylation plays a critical role in the activation of Notch signaling, which could promote Treg differentiation in the liver to inhibit T cell infiltration and control disease development in autoimmune hepatitis. Therefore, this study reveals a regulatory role for glycosylation in the pathogenesis of autoimmune hepatitis, and highlights glycosylation as a potential treatment target.

Collagen β (1‑O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via β (1‑O) linkages in collagen. The present study investigated the function of the collagen galactosyltransferase activity of GLT25D1 against carbon tetrachloride (CCl4)‑induced acute liver injury in vitro. Glt25d1+/‑ mice and wild‑type (WT) mice were injected intraperitoneally with the same dose of CCl4. The grade of hepatic injury and the extent of hepatocyte necrosis in the acute phase were assessed 48 h following CCl4 injection. Hepatocyte necrosis was evaluated by histological examination and by serum alanine aminotransferase and aspartate aminotransferase levels, which were higher in the Glt25d1+/‑ mice compared with those in the WT mice. Reverse transcription‑quantitative polymerase chain reaction was performed, and the results demonstrated that the mRNA expression levels of inflammatory cytokines, including tumor necrosis factor‑α and interleukin‑6 were significantly increased in the Glt25d1+/‑ mice. Furthermore, western blot analyses were performed, and the results demonstrated that the protein levels of cleaved caspase‑3 and ‑9 were also markedly increased in the Glt25d1+/‑ liver, indicating that hepatocyte apoptosis was induced. Additionally, the expression levels of transforming growth factor (TGF)‑β1 and phosphorylated small mothers against decapentaplegic (Smad)2 were markedly upregulated, indicating activation of the TGF‑β1/Smad2 signaling pathway during CCl4‑induced acute liver injury in Glt25d1+/‑ mice. CCl4 administration also resulted in severe damage to Glt25d1+/‑ primary hepatocytes in vitro. Taken together, the downregulation of Glt25d1 deteriorated CCl4‑induced liver injury in mice, which may involve triggering inflammatory responses, apoptosis and TGF‑β1/Smad2 signaling pathway activation.

Background: Glypican-3 (GPC3) has been widely recognized in the progression of liver tumors for several years. The relationship between overexpression of GPC3 and the poorer prognosis of patients with hepatocellular carcinoma (HCC) was performed by 2 meta-analyses. However, there were also some latest literatures that indicated different conclusions distinctly. It is necessary for us to carry out a meta-analysis by adding the latest data from current studies to explore the correlation between GPC3 and prognostic value in HCC., Methods: We conducted a meta-analysis including a total of 14 studies to assess the potential prognostic significance of GPC3 expression for overall survival (OS) and disease-free survival (DFS). The expression of GPC3 was assessed by immunohistochemistry., Results: Fourteen studies with 2364 patients were incorporated in the meta-analysis. The combined hazard ratios (HRs) revealed that the overexpression of GPC3 could forecast a poor OS [n = 2233 in 12 studies, HR = 1.40, 95% confidence interval (95% CI): 1.07-1.85, Z = 2.42, P = .02] and DFS (n = 1308 in 10 studies, HR = 1.61, 95% CI: 1.13-2.30, Z = 2.63, P = .008) in HCC patients. Subgroup treated by hepatectomy indicated that the pooled HR of OS was 1.43 (95% CI: 1.01-2.01, P = .04) and the combined HR of DFS was 1.59 (95% CI: 1.09-2.31, P = .02). The pooled odds ratios (ORs) showed that high GPC3 expression was also extensively associated with worse tumor differentiation, later tumor stage, presence of vascular invasion, and hepatitis B virus (HBV) infection. Subgroup analyses for GPC3 on HCC OS based on the studies categorized by regions, follow-up period, and sample size were also conducted., Conclusion: The meta-analysis indicated that overexpression of GPC3 was significantly associated with poor prognosis in patients with HCC.

A series of ZnO nanorods were prepared by pyrolysis of zinc acetate at different calcination temperatures and heating rates under ambient atmosphere. The as-prepared ZnO nanorods were characterized by X-ray diffractometer (XRD), scanning electron microscopy (SEM), UV-visible diffuse reflectance spectroscopy (DRS) and X-ray photoelectron spectroscopy (XPS). The photocatalytic performances of the ZnO nanorods were evaluated by the photodegradation of methyl orange (MO) and 4-nitrophenol (4-NP). The morphology, optical property, surface composition, and photocatalytic performance of the ZnO samples were affected by both calcination temperature and heating rate. The photocatalytic activity of the ZnO sample was obviously decreased with increased heating rate, which might be ascribed to the simultaneous decrease of oxygen vacancies and surface adsorption oxygen species. The ZnO nanorods prepared at 300°C with a heating rate of 1°C/min exhibited good photocatalytic activity and photochemical stability, allowing good potential practical application in environmental remediation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We have previously engineered new RNase P-based ribozyme variants with improved in vitro catalytic activity. In this study, we employed a novel engineered variant to target a shared mRNA region of human cytomegalovirus (HCMV) immediate early proteins 1 (IE1) and 2 (IE2), which are essential for the expression of viral early and late genes as well as viral growth. Ribozyme F-R228-IE represents a novel variant that possesses three unique base substitution point mutations at the catalytic domain of RNase P catalytic RNA. Compared to F-M1-IE that is the ribozyme derived from the wild type RNase P catalytic RNA sequence, the functional variant F-R228-IE cleaved the target mRNA sequence in vitro at least 100 times more efficiently. In cultured cells, expression of F-R228-IE resulted in IE1/IE2 expression reduction by 98-99% and in HCMV production reduction by 50,000 folds. In contrast, expression of F-M1-IE resulted in IE1/IE2 expression reduction by less than 80% and in viral production reduction by 200 folds. Studies of the ribozyme-mediated antiviral effects in cultured cells suggest that overall viral early and late gene expression and viral growth were inhibited due to the ribozyme-mediated reduction of HCMV IE1 and IE2 expression. Our results provide direct evidence that engineered RNase P ribozymes, such as F-R228-IE, can serve as a novel class of inhibitors for the treatment and prevention of HCMV infection. Moreover, these results suggest that F-R228-IE, with novel and unique mutations at the catalytic domain to enhance ribozyme activity, can be a candidate for the construction of effective agents for anti-HCMV therapy.

Background and Aims: Hepatic resection (HRN) and microwave ablation (MWA) have significant advantages in treating hepatocellular carcinoma; however, it remains unclear which way produces better outcomes. This meta-analysis of cohort studies compared the treatments in terms of effectiveness and safety., Methods: Six electronic databases (PubMed, Medline, EMBASE, Web of Science, EBSCO, and The Cochrane Library) were retrieved for studies comparing MWA and HRN. The meta-analysis was conducted based on statement of preferred reporting items for systematic reviews and meta-analyses., Results: Nine studies met the inclusion criteria, with a total of 1,480 patients. The overall meta-analysis demonstrated no significant difference in overall survival between the MWA group and the HRN group (HR =0.98, 95% CI =0.76-1.26, P =0.878). There was no difference in disease-free survival between the MWA group and the HRN group (HR =1.16, 95% CI =0.79-1.71, P =0.442). Meanwhile, the meta-analysis demonstrated that MWA was associated with shorter operation time (standardized mean difference [SMD] =-1.37, 95% CI =-1.92 to -0.81, P =0.000), less amount of blood loss in operation (SWD =-1.19, 95% CI =-1.76 to -0.61, P =0.000), and less complications (OR =0.22, 95% CI =0.12-0.40, P =0.000) than HRN., Conclusion: In conclusion, our meta-analysis suggests that MWA may be superior to HRN as it is as effective as HRN in terms of overall survival, disease-free survival, tumor recurrence, and is associated with shorter operation time, less amount of blood loss, and fewer complications., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The preparation of highly efficient visible-light-driven photocatalyst for the photodegradation of organic pollutants has received much attention due to the increasing global energy crises and environmental pollution. In this study, carnation-like ZnO@AgI hierarchical nanostructures assembled by AgI nanoparticles-decorated ZnO nanosheets were successfully prepared via a room-temperature route. The as-prepared ZnO@AgI nanostructures exhibited highly efficient photocatalytic activity under visible light irradiation (λ>400nm). Under optimized AgI content, the ZnO@AgI-5% sample showed high photocatalytic activity, which was 25.7 and 1.5 times the activity of pure ZnO and pure AgI, respectively. Mechanism studies indicated that superoxide anion radicals (O 2 - ) was the main reactive species in the photocatalytic process. The high photocatalytic activity of the ZnO@AgI nanostructures is attributed to the highly active AgI nanoparticles and the heterojunction between AgI nanoparticles and ZnO nanosheets. The heterojunction structure reduced the recombination of the photogenerated electron-hole pairs in the conduction band (CB) and valence band (VB) of AgI nanoparticles by transferring the electrons from the CB of AgI nanoparticles to the CB of ZnO nanosheets. The composite of ZnO and AgI not only improves photocatalytic efficiency but also reduces photocatalyst cost, which is beneficial for practical application., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The neutrophil-lymphocyte ratio (NLR) is a new prognostic predictor for patients with liver cancer. The association of NLR and T lymphocytes with the pathogenesis and progression of liver cancer is poorly understood., Methods: Seventy-three patients with hepatitis B virus (HBV)-associated primary liver cancer (HBV-PLC), 50 patients with HBV-associated liver cirrhosis (HBV-LC) and 37 patients with chronic HBV infection (CHB) were prospectively enrolled from July 1, 2013 to February 28, 2014 in Beijing Ditan Hospital, Capital Medical University (Beijing, China). The NLR, proportions and concentrations of neutrophils and lymphocytes, concentration of subpopulations of lymphocytes, and the expression of CD31 (index for recent thymic output) and HLA-DR (index for activation of T lymphocytes) of T cells in the peripheral blood samples of the patients were assessed and statistically compared between different groups., Results: The NLR was significantly increased from patients with CHB, those with HBV-LC to those with HBV-PLC (P<0.05), along with significant increase of neutrophils and decrease of lymphocytes in the same way (P<0.05). The concentrations of T lymphocytes, natural killer cells, B cells, CD4+ T cells and CD8+ T cells were decreased from patients with CHB, those with HBV-LC to those with HBV-PLC, and were significantly reduced in patients with HBV-PLC compared with those in patients with CHB (P<0.05). The CD31 and HLA-DR expression of naive CD4+ and CD8+ T cells was significantly decreased and increased, respectively in patients with HBV-PLC compared with that in patients with CHB., Conclusions: Elevated NLR, resulted from the increase of neutrophils and decrease of lymphocytes, is positively associated with the pathogenesis and progression of HBV-PLC. The reduced thymic output and hyperactivation of T lymphocytes may contribute to the decrease of T lymphocytes, which could be also related to the pathogenesis of HBV-PLC.

Aim . To determine whether nucleot(s)ide analogs therapy has survival benefit for patients with HBV-related HCC after unresectable treatment. Method . A systematic search was conducted through seven electronic databases including PubMed, OVID, EMBASE, Cochrane Databases, Elsevier, Wiley Online Library, and BMJ Best Practice. All studies comparing NA combined with unresectable treatment versus unresectable treatment alone were considered for inclusion. The primary outcome was the overall survival (OS) after unresectable treatment for patients with HBV-related HCC. The secondary outcome was the progression-free survival (PFS). Results were expressed as hazard ratio (HR) for survival with 95% confidence intervals. Results . We included six studies with 994 patients: 409 patients in nucleot(s)ide analogs therapy group and 585 patients without antiviral therapy in control group. There were significant improvements for the overall survival (HR = 0.57; 95% CI = 0.47-0.70; p < 0.001) and progression-free survival (HR = 0.84; 95% CI = 0.71-0.99; p = 0.034) in the NA-treated group compared with the control group. Funnel plot showed that there was no significant publication bias in these studies. When it comes to antiviral drugs and operation method, it also showed benefit in NA-treated group. At the same time, overall mortality as well as mortality secondary to liver failure in NA-treated group was obviously lesser. Sensitivity analyses confirmed the robustness of the results. Conclusions . Nucleot(s)ide analogs therapy after unresectable treatment has potential beneficial effects in terms of overall survival and progression-free survival. NA therapy should be considered in clinical practice., Competing Interests: The authors deny any conflict of interests.

Aim . To establish a new score model to predict risk of death in patients with hepatocellular carcinoma and type 2 diabetes mellitus. Methods . This was a retrospective study of 147 patients with hepatocellular carcinoma and type 2 diabetes mellitus who came to Beijing Ditan Hospital between October 2008 and June 2013. Univariate and multivariate logistic regression analysis was performed to obtain the independent factors associated with death risk. A new score model was devised according to these factors. Results . A prediction score model composed of HbA1c, NLR, age, and CTP class was devised, which ranged from 0 to 7. AUROC of the score was 0.853 ( P < 0.001, 95% CI: 0.791-0.915). Scores 0-2, 3-4, and 5-7 identified patients as low-, medium-, and high-risk categories. The cumulative survival rate was 93.6%, 83.0%, and 74.5% in the low-risk group in 1, 2, and 3 years, while it was 64.0%, 46.0%, and 26.0% in the medium-risk group, whereas it was 24.0%, 12.0%, and 6.0% in the high-risk group, respectively. The cumulative survival rate was significantly higher in the low-risk group than that in the medium-risk group and high-risk group ( P < 0.001). Conclusion . The HbA1c-based score model can be used to predict death risk in patients with hepatocellular carcinoma and type 2 diabetes mellitus., Competing Interests: The authors declare that they have no competing interests.

The findings regarding the effects of thiazolidinediones (TZDs) in nonalcoholic steatohepatitis (NASH) patients have been inconsistent, and the assessment of different clinical variables for evaluating the effects of TZDs confound a direct comparison of the results of different randomized clinical trials (RCTs), especially with regard to lifestyle changes. In this paper, we performed a meta-analysis of randomized controlled trials to clarify the effects of TZD treatment with and without lifestyle changes on histological markers of NASH and clinical variables related to insulin resistance (IR), hyperlipidemia, and obesity. We searched the literature using the following MeSH terms: "nonalcoholic steatohepatitis," "non-alcoholic steatohepatitis," "thiazolidinedione," "pioglitazone," "rosiglitazone," "randomized," and "clinical trial." Five eligible RCTs were selected, in which patients were treated with either pioglitazone or rosiglitazone, with or without lifestyle changes. We compared the effects of TZD treatment on hepatic fibrosis, lobular inflammation, IR improvement, fasting serum insulin, adiposity, and dyslipidemia between the various studies using fixed and random effects models, and heterogeneity in clinical outcomes was assessed. Significant improvement in hepatic fibrosis did not occur among the patients treated with TZDs alone or in those who underwent both lifestyle changes and TZD therapy. Lobular inflammation decreased in NASH patients who received TZD treatment and in those who underwent both TZD therapy and lifestyle changes. Although TZD treatment resulted in no significant improvement in IR, NASH patients who underwent both lifestyle changes and TZD therapy experienced a significantly greater reduction in their fasting insulin level than that observed in the control patients, whereas patients treated with TZDs alone did not. Although TZD-treated patients experienced significantly greater weight gain than the control patients, TZD treatment had no significant impact on body-mass index, percentage of body fat, or serum levels of cholesterol and triglyceride. Our findings indicate that additional variables should be assessed to obtain a more comprehensive evaluation of the effects of TZD treatment on IR and comorbidity risk factors in NASH patients, and suggest that including lifestyle changes and additional insulin-sensitizing agents in TZD regimens might improve the benefits of TZD therapy for NASH., Competing Interests: All listed authors declare that there are no conflicts of interest.

Objective: It is well known that high lipid and high energy diet is harmful to health. But the different effects of high lipid diet composed of either saturated fatty acids or unsaturated fatty acids have not been distinguished., Method: Eighteen pregnant C57BL/6j (22-25g) mice were randomly divided into three groups of six each and fed with chow or high lipid diet composed of either flaxseed oil (chow diet 84%, cholesterol 0.2%, flaxseed oil 15.8%) or lard fat (chow diet 84%, cholesterol 0.2%, lard fat 15.8%). After weaning, the offspring were fed the same diet as their mothers were fed during the experiment, and their spatial memory and learning ability were evaluated by Morris water maze when they were 8 weeks old. Next, the blood and tissues were sampled when they were 9 weeks old. Serum lipids were determined using kits, and brain fatty acids were measured using a gas chromatograph., Results: Compared to chow diet (control), high flaxseed oil diet (HFO) increased high density lipoprotein cholesterol level (HDL-C) in the mothers but not in offspring; high lard fat diet (HLF) increased serum total cholesterol level (TC) and low density lipoprotein cholesterol level (LDL-C) both in mothers and offspring. Brain fatty acids profile was altered by HLF compared with chow diet. Polyunsaturated fatty acids and long-chain polyunsaturated fatty acids content were significantly lower in the HLF group than in the control group, but saturated fatty acids content were significantly higher in HLF group than those in control group. The changed fatty acids composition affected the spatial memory and learning ability of adult offspring., Conclusions: A long-term high lard diet increased offspring serum TC and LDL-C levels and affected the brain's fatty acid composition, and memory and learning ability. The polyunsaturated fatty acid content of the brain may be correlated with serum cholesterol levels.