A general strategy for recycling polyester wastes into carboxylic acids and hydrocarbons.

Chemical recycling of plastic wastes is of great significance for sustainable development, which also represents a largely untapped opportunity for the synthesis of value-added chemicals. Herein, we report a novel and general strategy to degrade polyesters via directly breaking the Calkoxy-O bond by nucleophilic substitution of halide anion of ionic liquids under mild conditions. Combined with hydrogenation over Pd/C, 1-butyl-2,3-dimethylimidazolium bromide can realize the deconstruction of various polyesters including aromatic and aliphatic ones, copolyesters and polyester mixtures into corresponding carboxylic acids and alkanes; meanwhile, tetrabutylphosphonium bromide can also achieve direct decomposition of the polyesters with ß-H into carboxylic acids and alkenes under hydrogen- and metal-free conditions. It is found that the hydrogen-bonding interaction between ionic liquid and ester group in polyester enhances the nucleophilicity of halide anion and activates the Calkoxy-O bond. The findings demonstrate how polyester wastes can be a viable feedstock for the production of carboxylic acids and hydrocarbons.

Upcycling poly(succinates) with amines to N-substituted succinimides over succinimide anion-based ionic liquids.

The chemical transformation of waste polymers into value-added chemicals is of significance for circular economy and sustainable development. Herein, we report upcycling poly(succinates) (PSS) with amines into N-substituted succinimides over succinimide anion-based ionic liquids (ILs, e.g, 1,8-diazabicyclo[5.4.0]undec-7-ene succinimide, [HDBU][Suc]). Assisted with H2O, [HDBU][Suc]) showed the best performance, which could achieve complete transformation of a series of PSS into succinimide derivatives and corresponding diols under mild and metal-free conditions. Mechanism investigation indicates that the cation-anion confined hydrogen-bonding interactions among IL, H2O, ester group, and amino/amide groups, strengthens nucleophilicity of the N atoms in amino/amide groups, and improves electrophilicity of carbonyl C atom in ester group. The attack of the amino/amide N atom on carbonyl C of ester group results in cleavage of carbonyl C-O bond in polyester and formation of amide group. This strategy is also effective for aminolysis of poly(trimethylene glutarate) to glutarimides, and poly(1,4-butylene adipate) to caprolactone diimides.

Lactate anion catalyzes aminolysis of polyesters with anilines.

Chemical transformation of spent polyesters into value-added chemicals is substantial for sustainable development but still challenging. Here, we report a simple, metal-free, and efficient aminolysis strategy to upcycle polylactic acid by anilines over lactate-based ionic liquids (e.g., tetrabutylammonium lactate), accessing a series of N-aryl lactamides under mild conditions. This strategy is also effective for degradation of poly(bisphenol A carbonate), affording bisphenol A and corresponding diphenylurea derivatives. It is found that, with the assistance of water, lactate anion as hydrogen-bond donor can efficiently activate carbonyl C atom of polyesters via hydrogen bonding with carbonyl O atom; meanwhile, as hydrogen-bond acceptor, it can enhance nucleophilicity of the N atom of anilines via hydrogen bonding with amino H atom. The nucleophilic attack of N atom of anilines on carbonyl C atom of polyesters results in cleavage of C─O bond of polymers and formation of the target products.

A Green Route to Benzyl Phenyl Sulfide from Thioanisole and Benzyl Alcohol over Dual Functional Ionic Liquids.

Benzyl phenyl sulfide is a kind of important chemicals with wide usage, which is mainly prepared through a nucleophilic reaction of thiophenol with benzyl chlorides or benzyl alcohols, suffering from inherent drawbacks, such as low efficiency, requirements for equivalent acid or base catalysts and formation of harmful byproducts and waste. Herein, we report a green route to access various benzyl phenyl sulfide derivatives in good to excellent yields under mild conditions via the reaction of thioanisoles with benzyl alcohols over ionic liquid 1-propylsulfonate-3-methylimidazolium trifluoromethanesulfonate ([SO3 HPrMIm][OTf]). Mechanism investigation indicates that the synergic effect of cation and anion of [SO3 HPrMIm][OTf] activates thioanisoles and benzyl alcohols via hydrogen bonding, thus catalyzes the dehydration of benzyl alcohol to dibenzyl ether and the subsequent metathesis reaction between dibenzyl ether and benzyl phenyl sulfide, finally generating benzyl phenyl sulfide derivatives. This is a simple, highly efficient, and green approach to produce benzyl phenyl sulfide derivatives, which has promising application potentials.

IgG response to spike protein of SARS-CoV-2 in healthy individuals and potential of intravenous IgG as treatment for COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which is currently a worldwide pandemic. There are limited available treatments for severe COVID-19 patients. However, some evidence suggests that intravenous immunoglobulin (IVIg) provides clinical benefits for these patients. METHODS: We administered IVIg to 23 severe COVID-19 patients, and all of them survived. Four related coronaviruses can cause the common cold. We speculated that cross-reactivity of SARS-CoV-2 and other common coronaviruses might partially explain the clinical efficacy of IVIg therapy. Thus, we performed multiple alignment analysis of the spike (S), membrane (M), and nucleotide (N) proteins from SARS-CoV-2 and the common coronaviruses to identify conserved regions. Next, we synthesized 25 peptides that were conserved regions and tested their IVIg seropositivity. RESULTS: The results indicated four peptides had significant or nearly significant seropositivity, and all of them were associated with the S and M proteins. Examination of the immune responses of healthy volunteers to each synthetic peptide indicated high seropositivity to the two peptides from S protein. Blood samples from healthy individuals may have pre-existing anti-SARS-CoV-2 IgGs, and IVIg is a potentially effective therapy for severe COVID-19. CONCLUSION: In conclusion, blood samples from many healthy individuals have pre-existing anti-SARS-CoV-2 IgGs, and IVIg may be an effective therapy for severe COVID-19.

Lactobacillus reuteri improves function of the intestinal barrier in rats with acute liver failure through Nrf-2/HO-1 pathway.

OBJECTIVES: We aimed to explore whether Lactobacillus reuteri could have a positive role in reducing inflammation and bacterial translocation in rats with acute liver failure. METHODS: Lactobacillus reuteri were gavaged to Sprague-Dawley (SD) rats at a dose of 1 × 109 CFU/mL once a day for 14 d. D-galactosamine was injected intraperitoneally to induce acute liver failure for 24 h on the 15th day. Liver function, liver and ileum histology, intestinal cytokines, intestinal tight junction proteins, lipopolysaccharide binding protein, apoptosis molecules, and nuclear factor erythroid-derived 2 (Nrf-2) / heme oxygenase (HO-1) molecules were assessed. RESULTS: The results showed that L. reuteri alleviated liver injury and intestinal inflammation induced by D-galactosamine. L. reuteri also improved the expression of intestinal tight junction proteins and maintained the integrity of the intestinal barrier by inhibiting apoptosis of intestinal epithelial cells. L reuteri induced an increase in Nrf-2 nuclear translocation and elevated induction of HO-1. L. reuteri treatment significantly enhanced the expression of phosphoinositide 3-kinase/protein kinase B (PI3 K/Akt), protein kinase C (PKC), and their phosphorylated forms but not mitogen-activated protein kinase. The nuclear factor kappa B (NF-κB) pathway was inhibited after L. reuteri treatment. Interleukin (IL)-17A produced by Th17 cells and γδT17 cells may not contribute to an improved function of the intestinal barrier in L. reuteri-treated SD rats. CONCLUSIONS: Overall, our study indicated that L. reuteri-induced expression of intestinal tight junction proteins is mediated by the PI3 K/Akt-Nrf-2/HO-1-NF-κB and PKC-Nrf-2/HO-1-NF-κB pathways, which leads to inhibition of the apoptosis of intestinal epithelial cells, thus maintaining the integrity of the damaged intestinal barrier.

Development of a Bile Acid-Related Gene Signature for Predicting Survival in Patients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common diseases that threaten millions of lives annually. Evidence supports that bile acid (BA) affects HCC through inflammation, DNA damage, or other mechanisms. Methods: A total of 127 BA-associated genes were analyzed in HCC tumor and nontumor samples using The Cancer Genome Atlas data. Genes correlated to the prognosis of patients with HCC were identified using univariate and multivariate Cox regression analyses. Furthermore, a prediction model with identified genes was constructed to evaluate the risk of patients with HCC for prognosis. Results: Out of 26 genes with differential expressions between the HCC and nontumor samples, 19 and 7 genes showed upregulated and downregulated expressions, respectively. Three genes, NPC1, ABCC1, and SLC51B, were extrapolated to construct a prediction model for the prognosis of patients with HCC. Conclusion: The three-gene prediction model was more reliable than the pathological staging characters of the tumor for the prognosis and survival of patients with HCC. In addition, the upregulated genes facilitating the transport of BAs are associated with poor prognosis of patients with HCC, and genes of de novo synthesis of BAs benefit patients with HCC.

Soluble urokinase plasminogen activator receptor is associated with short-term mortality and enhanced reactive oxygen species production in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a comprehensive syndrome characterized by an acute deterioration of liver function and high short-term mortality rates in patients with chronic liver disease. Whether plasma soluble urokinase plasminogen activator receptor (suPAR) is a suitable biomarker for the prognosis of patients with ACLF remains unknown. METHOD: A prospective cohort of 282 patients with ACLF from three hospitals in China was included. 88.4% of the group was hepatitis B virus-related ACLF (HBV-related ACLF). Cox regression was used to assess the impact of plasma suPAR and other factors on 30- and 90-day mortality. Reactive oxygen species (ROS) production were detected to explore the role of suPAR in regulating neutrophil function in HBV-related ACLF. RESULT: There was no difference in plasma suPAR levels between HBV-related and non-HBV-related ACLF. Patients with clinical complications had higher suPAR levels than those without these complications. A significant correlation was also found between suPAR and prognostic scores, infection indicators and inflammatory cytokines. Cox's regression multivariate analysis identified suPAR ≥ 14.7 ng/mL as a predictor for both day 30 and 90 mortality (Area under the ROC curve: 0.751 and 0.742 respectively), independent of the MELD and SOFA scores in patients with ACLF. Moreover, we firstly discovered suPAR enhanced neutrophil ROS production under E.coli stimulation in patients with HBV-related ACLF. CONCLUSIONS: suPAR was a useful independent biomarker of short-term outcomes in patients with ACLF and might play a key role in the pathogenesis. Trial registration CNT, NCT02965560.

Effect of ORF7 of SARS-CoV-2 on the Chemotaxis of Monocytes and Neutrophils In Vitro.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most significant public health threat worldwide. Patients with severe COVID-19 usually have pneumonia concomitant with local inflammation and sometimes a cytokine storm. Specific components of the SARS-CoV-2 virus trigger lung inflammation, and recruitment of immune cells to the lungs exacerbates this process, although much remains unknown about the pathogenesis of COVID-19. Our study of lung type II pneumocyte cells (A549) demonstrated that ORF7, an open reading frame (ORF) in the genome of SARS-CoV-2, induced the production of CCL2, a chemokine that promotes the chemotaxis of monocytes, and decreased the expression of IL-8, a chemokine that recruits neutrophils. A549 cells also had an increased level of IL-6. The results of our chemotaxis Transwell assay suggested that ORF7 augmented monocyte infiltration and reduced the number of neutrophils. We conclude that the ORF7 of SARS-CoV-2 may have specific effects on the immunological changes in tissues after infection. These results suggest that the functions of other ORFs of SARS-CoV-2 should also be comprehensively examined.

Cryptococcosis in patients with liver cirrhosis: Death risk factors and predictive value of prognostic models.

BACKGROUND: Liver cirrhosis is associated with immune deficiency, which causes these patients to be susceptible to various infections, including cryptococcus infection. Mortality in cirrhotic patients with cryptococcosis has increased. The present study was to explore the risk factors of mortality and the predictive ability of different prognostic models. METHODS: Forty-seven cirrhotic patients with cryptococcosis at a tertiary care hospital were included in this retrospective study. Data on demographics, clinical parameters, laboratory exams, diagnostic methods, medication during hospitalization, severity scores and prognosis were collected and analyzed. Student's t test and Mann-Whitney test were used to compare characteristics of survivors and non-survivors at a 90-day follow-up and cerebrospinal fluid (CSF) manifestations of cryptococcal meningitis. Multivariate Cox regression analysis was used to identify the independent risk factors for mortality. Kaplan-Meier curves were used to analyze patient survival. Receiver operating characteristic (ROC) curves were used to evaluate the different prognostic factors. RESULTS: The 30- and 90-day survival rates were 93.6% and 80.9%, respectively, in cirrhotic patients with cryptococcosis. Cryptogenic liver diseases [hazard ratio (HR) = 7.567, 95% confidence interval (CI): 1.616-35.428, P = 0.010], activated partial thromboplastin time (APTT) (HR = 1.117, 95% CI: 1.016-1.229, P = 0.022) and Child-Pugh score (HR = 2.146, 95% CI: 1.314-3.504, P = 0.002) were risk factors for 90-day mortality in cirrhotic patients with cryptococcosis. Platelet count (HR = 0.965, 95% CI: 0.940-0.991, P = 0.008) was a protective factor. APTT (HR = 1.120, 95% CI: 1.044-1.202, P = 0.002) and Child-Pugh score (HR = 1.637, 95% CI: 1.086-2.469, P = 0.019) were risk factors for 90-day mortality in cirrhotic patients with cryptococcal meningitis. There was significant difference in the percentage of lymphocytes in CSF between survivors and non-survivors [60.0 (35.0-75.0) vs. 95.0 (83.8-97.2), P < 0.001]. The model of end-stage liver disease-sodium (MELD-Na) score was more accurate for predicting 30-day mortality both in patients with cryptococcosis [area under curve (AUC): 0.826, 95% CI: 0.618-1.000] and those with cryptococcal meningitis (AUC: 0.742, 95% CI: 0.560-0.924); Child-Pugh score was more useful for predicting 90-day mortality in patients with cryptococcosis (AUC: 0.823, 95% CI: 0.646-1.000) and those with cryptococcal meningitis (AUC: 0.815, 95% CI: 0.670-0.960). CONCLUSIONS: These results showed that cryptogenic liver diseases, APTT and Child-Pugh score were associated with mortality in cirrhotic patients with cryptococcosis and cryptococcal meningitis. MELD-Na score was important for predicting 30-day mortality, and Child-Pugh score was critical for predicting 90-day mortality.

Reduced Energy Metabolism Impairs T Cell-Dependent B Cell Responses in Patients With Advanced HBV-Related Cirrhosis.

Background and Aims: Patients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism. Methods: Changes in phenotypes and subsets of peripheral B cells between HBV D-LC patients and healthy controls (HCs) were compared by flow cytometry. Isolated B cells were activated by coculture with circulating T follicular (cTfh) cells. After coculture, the frequencies of plasmablasts and plasma cells and immunoglobin levels were analyzed. Oxidative phosphorylation (OXPHOS) and glycolysis were analyzed by a Seahorse analyzer. Mitochondrial function and the AKT/mTOR pathway were analyzed by flow cytometry. Results: The proliferation and differentiation capacities of B cells after T cell stimulation were impaired in D-LC. Furthermore, we found that B cells from D-LC patients showed reductions in OXPHOS and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway. Conclusions: B cells from HBV D-LC patients showed dysfunctional energy metabolism after T cell-dependent activation. Understanding the regulations of B cell metabolic pathway and their changes may provide a new direction to rescue B cell hyporesponsiveness in patients with HBV D-LC, preventing these patients be infected and improving sensitivity to vaccines.

A narrative review of the roles of indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in liver diseases.

Indoleamine 2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are induced by several immune factors, such as interferon-γ, and act as intracellular enzymes that catabolize essential amino acid tryptophan into kynurenine and other downstream metabolites, including kynurenic acid (KYNA), xanthurenic acid (XA) and so on. IDO and TDO work as a double-edge sword. On one hand, they exert the immunomodulatory effects, especially immunosuppressive effects on the microenvironment including infections, pregnancy, tumor cells escape and transplantation. TDO plays the major role under basal conditions, while IDO comes into play under different circumstances of immune activation, thus IDO has a wider spectrum of immune regulation. On the other hand, these enzymes also inhibit pathogens such as Chlamydia pneumoniae, Staphylococcus aureus, Toxoplasma gondii and so on. Moreover, IDO regulates metabolic health through shaping intestinal microbiota. Recently, these enzymes have attracted more and more attention in liver diseases. Several studies have indicated that IDO and TDO can modulate viral hepatitis, autoimmune liver diseases, non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, liver cancer even liver transplantation. Targeting them or their antagonists may provide novel therapeutic treatments for liver diseases. In this review, we will discuss the exact roles that IDO and TDO play in diverse hepatic diseases.

Construction of a convolutional neural network classifier developed by computed tomography images for pancreatic cancer diagnosis.

BACKGROUND: Efforts should be made to develop a deep-learning diagnosis system to distinguish pancreatic cancer from benign tissue due to the high morbidity of pancreatic cancer. AIM: To identify pancreatic cancer in computed tomography (CT) images automatically by constructing a convolutional neural network (CNN) classifier. METHODS: A CNN model was constructed using a dataset of 3494 CT images obtained from 222 patients with pathologically confirmed pancreatic cancer and 3751 CT images from 190 patients with normal pancreas from June 2017 to June 2018. We established three datasets from these images according to the image phases, evaluated the approach in terms of binary classification (i.e., cancer or not) and ternary classification (i.e., no cancer, cancer at tail/body, cancer at head/neck of the pancreas) using 10-fold cross validation, and measured the effectiveness of the model with regard to the accuracy, sensitivity, and specificity. RESULTS: The overall diagnostic accuracy of the trained binary classifier was 95.47%, 95.76%, 95.15% on the plain scan, arterial phase, and venous phase, respectively. The sensitivity was 91.58%, 94.08%, 92.28% on three phases, with no significant differences (χ 2 = 0.914, P = 0.633). Considering that the plain phase had same sensitivity, easier access, and lower radiation compared with arterial phase and venous phase , it is more sufficient for the binary classifier. Its accuracy on plain scans was 95.47%, sensitivity was 91.58%, and specificity was 98.27%. The CNN and board-certified gastroenterologists achieved higher accuracies than trainees on plain scan diagnosis (χ 2 = 21.534, P < 0.001; χ 2 = 9.524, P < 0.05; respectively). However, the difference between CNN and gastroenterologists was not significant (χ 2 = 0.759, P = 0.384). In the trained ternary classifier, the overall diagnostic accuracy of the ternary classifier CNN was 82.06%, 79.06%, and 78.80% on plain phase, arterial phase, and venous phase, respectively. The sensitivity scores for detecting cancers in the tail were 52.51%, 41.10% and, 36.03%, while sensitivity for cancers in the head was 46.21%, 85.24% and 72.87% on three phases, respectively. Difference in sensitivity for cancers in the head among the three phases was significant (χ 2 = 16.651, P < 0.001), with arterial phase having the highest sensitivity. CONCLUSION: We proposed a deep learning-based pancreatic cancer classifier trained on medium-sized datasets of CT images. It was suitable for screening purposes in pancreatic cancer detection.

A self-powered bidirectional partition microfluidic chip with embedded microwells for highly sensitive detection of EGFR mutations in plasma of non-small cell lung cancer patients.

Circulating tumor DNA (ctDNA) is a promising biomarker for tumor genotyping and therapy monitoring. Herein, we developed a digital PCR chip with embedded microwell and bidirectional partition network for highly sensitive ctDNA analysis. The embedded microwell contributes to increasing microreaction density (up to 7000 microwells/cm2) and reducing evaporation during amplification. The bidirectional partition network can achieve fast and random distribution of targets, ensuring the precise quantification of nucleic acid. We used plasmids, artificial samples and 32 clinical blood samples from non-small cell lung cancer patients to test the performance of this platform. The results demonstrated that our chip has not only comparable quantification performance to commercial counterpart but also the ability to detect EGFR mutations with as low as 0.01% mutation rate and 20 alter molecules in 27 ng genomic DNA. The identification of EGFR mutations in plasma using developed chip exhibited 85.71% sensitivity and 94.44% specificity for L858R mutation and 100% sensitivity and 86.96% specificity for T790 M mutation. Moreover, the monitoring of mutant allele in plasma was accomplished in this work. In conclusion, the developed chip has a potential in lung tumor genotyping and therapy monitoring for precision medicine, even other tumors.

Immune checkpoint targeting TIGIT in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has an extremely poor prognosis and is one of the most common malignancies worldwide. Immune checkpoint suppression has become the most effective treatment option for liver cancer. The strategies used for immune checkpoint inhibitor targeting cancer therapies have been affected by some significant successes, including blocking the advanced-stage malignant tumor by death protein 1 (PD-1)/programmed cell death ligand (PDL-1), and cytotoxic T-lymphocyte antigen-4 (CTLA4) pathways. T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) is an immune checkpoint that participates in tumor immune surveillance. Mainly expressed on T cells, natural killer (NK) cells, and other antigen-presenting cells (APCs), it diminishes cytokine production and exhibits strong suppressive properties. TIGIT achieves a more active antitumor immune response and highlights a pivotal role for cancer immunotherapy. Preclinical studies have found inhibitory effects using a targeted approach. Monotherapy targeting TIGIT or in combination with anti-PD-1/PD-L1 monoclonal antibodies for the treatment of patients with advanced solid malignancies have demonstrated improved antitumor immune responses. Due to the high tumor heterogeneity of liver cancer, immune checkpoint suppression therapy still needs further exploration. Therefore, we provide insights into the characteristics of TIGIT and the immune system in HCC.

In vitro inhibition effects of hepatitis B virus by dandelion and taraxasterol.

Hepatitis B virus (HBV) causes hepatitis, which progresses to fatal liver diseases and remains a global health problem. Current treatments for chronic hepatitis B are unable to cure hepatitis. Thus, new antiviral drugs must be developed. In this study, the viral inhibition effects of dandelion and taraxasterol were assessed in HepG2.2.15 cell line. Taraxacum officinale F.H.Wigg. (compositae) with English name dandelion is used as a traditional herb for liver disorders and as a common antiviral agent. Taraxasterol is one of the active compounds of dandelion. The secretion of HBV DNA and HBV surface antigen (HBsAg) and HBeAg was detected using fluorescence quantitative PCR (qPCR) and ELISA, respectively. Intracellular HBsAg was detected by immunofluorescence. In order to demonstrate the potential mechanism of anti-viral activity, the expression levels of host factors polypyrimidine tract binding protein 1 (PTBP1) and sirtuin 1 (SIRT1) were detected with Western blotting and qPCR. Dandelion and taraxasterol effectively reduced the secretion of HBsAg, HBeAg and the HBV DNA in cell supernatants, and significantly reduced the intracellular HBsAg as indicated by immunofluorescence results. Taraxasterol may be one of the main effective components of dandelion. It significantly decreased the protein expression levels of PTBP1 and SIRT1. The present study revealed that dandelion and its component taraxasterol could inhibit HBV and may be a potential anti-HBV drug, whose potential targets were the host factors PTBP1 and SIRT1.

sTim-3 alleviates liver injury via regulation of the immunity microenvironment and autophagy.

Liver failure (LF) is a monocyte/macrophage-mediated liver injury that has been associated with inflammatory mediators. However, the mechanism through which monocytes/macrophages regulate LF has not been fully elucidated. In this study, we investigated the role of soluble T-cell immunoglobulin domain and mucin domain-containing molecule-3 (sTim-3) in inhibition of release of inflammatory mediators. We further assess this role in protection against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver failure (ALF), via monocyte/macrophage regulation and autophagy induction in mice. Our findings indicate significantly higher plasma sTim-3 in acute-on-chronic liver failure (ACLF) group relative to other groups, with this trend associated with disease progression. Furthermore, infiltrated recombinant sTim-3 inhibited release of various inflammatory mediators, including cytokines and human high-mobility group box-1 (HMGB1), potentially via autophagy induction. Furthermore, H&E staining and the low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ALF mice, supported that recombinant sTim-3 effectively alleviated liver injury. Moreover, sTim-3 induced changes in monocyte/macrophage population in mice's liver or blood, which consequently caused a reduction in proinflammatory CD11bhiF4/80lo monocyte-derived macrophages and Ly-6C(+)CD11b(+) monocytes. Conversely, sTim-3 increased autophagy levels of hepatic CD11b(+) monocyte-derived macrophages and decreased apoptosis rate of CD11b (+) monocytes in the blood. Collectively, our findings demonstrated that sTim-3 alleviated inflammatory response and liver injury by promoting autophagy and regulating monocyte/macrophage function. This indicates its potential for future development of novel therapeutic strategies against LF.

Role of γδT cells in liver diseases and its relationship with intestinal microbiota.

γδT cells are unconventional T lymphocytes that bridge innate and adaptive immunity. Based on the composition of T cell receptor and the cytokines produced, γδT cells can be divided into diverse subsets that may be present at different locations, including the liver, epithelial layer of the gut, the dermis and so on. Many of these cells perform specific functions in liver diseases, such as viral hepatitis, autoimmune liver diseases, non-alcoholic fatty liver disease, liver cirrhosis and liver cancers. In this review, we discuss the distribution, subsets, functions of γδT cells and the relationship between the microbiota and γδT cells in common hepatic diseases. As γδT cells have been used to cure hematological and solid tumors, we are interested in γδT cell-based immunotherapies to treat liver diseases.

Epstein-Barr virus associated hepatic smooth muscle tumor in a patient with acquired immunodeficiency syndrome: A case report.

INTRODUCTION: Epstein-Barr virus (EBV) associated smooth muscle tumors (SMTs) usually present under the condition of immunosuppression, including congenital immunodeficiency syndrome-SMT, post-transplantation-SMT and HIV-SMT. HIV-SMTs are most likely to invade the central nervous system, followed by the liver, lungs, and other locations. Many laboratory techniques, including serological techniques, polymerase chain reaction and immunohistochemistry (IHC), are employed to determine the aetiologies of these tumours. With respect to therapy, surgical resection is the main treatment. In patients with immunodeficiency, improving immune status is significant for defending against other viruses. We describe a case of the primary focus of SMT in the liver of HIV-positive patient without any metastasis. PATIENT CONCERNS: A young male HIV-positive patient complained of fever and abdominal pain for 2 months. DIAGNOSIS: IHC of liver tissue confirmed the finding: EBV-related smooth muscle tumor. INTERVENTIONS: Given the patient's general condition, he was not a suitable candidate for surgical resection. He was given antibiotics, antifungal agents and EBV-directed agents to control infection as well as highly active antiretroviral therapy to enhance the immunity. OUTCOMES: The patient's symptoms improved. He was discharged. CONCLUSIONS: In conclusion, EBV-related HIV-SMTs is a rare neoplasm found in the liver among immunodeficient patients. This case highlights that a variety of examinations such as IHC for smooth muscle markers (smooth muscle actin and desmin) and EBER, as well as polymerase chain reaction for EBV DNA should be done when diagnoses are ambiguous.

Factors associated with a SARS-CoV-2 recurrence after hospital discharge among patients with COVID-19: systematic review and meta-analysis.

BACKGROUND: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. METHODS: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. RESULTS: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4+ T counts were at risk of COVID-19 recurrence (OR=1.71, range between 1.07 and 2.75; WMD=-1.06, range between -1.55 and -0.57, WMD=-40.39, range between -80.20 and -0.48, and WMD=-55.26, range between -105.92 and -4.60, respectively). CONCLUSIONS: The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4+ T counts, and clinical symptoms including cough, sputum production, headache, and dizziness. These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.