Publications by authors named "Qin Ning"

347 Publications

Immunomodulatory function of the active ingredients in traditional Chinese prescriptions on early stage esophageal cancer with dysplasia.

Am J Transl Res 2021 15;13(3):1667-1675. Epub 2021 Mar 15.

Department of TCM, Affiliated Hospital of Nantong University Nantong 226001, Jiangsu Province, China.

Objective: To explore the effects of the ingredients in a traditional Chinese prescription on the immune regulation of esophageal cancer in patients with early atypical hyperplasia.

Methods: A total of 60 C57BL mice were randomly selected as the positive control group; another 240 C57BL mice were randomly divided into a blank control group (n=30), a 4NQO group (n=60) and an experimental group (n=120). The experimental group was divided into the prevention group which received carcinogens and the prescription composition simultaneously, and the treatment group which received carcinogens first and the prescription composition second. The lymphocyte proliferation responses in peripheral blood and spleen cells were determined, and the changes of CD4, CD8, B7H4, CD4CD25 before and after administration were measured.

Results: The CD4 cell concentration in the 4NQO group was significantly higher than that in the other four groups (<0.05). No significant difference was found in the CD4B7H4 cell concentration among the five groups (>0.05); the CD8 concentration in the 4NQO and the prevention groups was significantly higher than that in the other three groups (<0.05).

Conclusion: The composition of traditional Chinese prescriptions can improve antitumor immunity and slow down the development of esophageal precancerous lesions by inhibiting the expression of T cells on lymphocytes and the positive expression of B7H4 and CD4 in esophageal cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014365PMC
March 2021

Discovery of a Novel Respiratory Syncytial Virus Replication Inhibitor.

Antimicrob Agents Chemother 2021 Mar 29. Epub 2021 Mar 29.

Infectious Disease Discovery, Medicinal Chemistry, and Lead Discovery Roche Pharmaceutical Research and Early Development, Roche Innovation Center Shanghai, Add: Building 5, Lane 371, Li Shizhen Road, Shanghai 201203, China

A high-throughput screen of a Roche internal chemical library based on inhibition of the respiratory syncytial virus (RSV)-induced cytopathic effect (CPE) on HEp-2 cells was performed to identify RSV inhibitors. Over 2000 hits were identified and confirmed to be efficacious against RSV infection Herein, we report the discovery of a Triazole-oxadiazole derivative, designated Triazole-1, as an RSV replication inhibitor and the characterization of its mechanism of action. Triazole-1 inhibited the replication of both RSV A and B subtypes with IC values of approximately 1 μM but was not effective against other viruses, including influenza virus A, human enterovirus 71, and vaccinia virus. Triazole-1 was shown to inhibit RSV replication when added at up to 8 hrs after viral entry, suggesting it inhibits RSV after the viral entry. In a minigenome reporter assay in which RSV transcription regulatory sequences flanking a luciferase gene was co-transfected with RSV N/P/L/M2-1 genes into HEp-2 cells, Triazole-1 demonstrated specific and dose-dependent RSV transcription inhibitory effects. Consistent with these findings, deep sequencing of the genomes of Triazole-1-resistant mutants revealed a single point mutation (A to G) at nucleotide 13546 of the RSV genome, leading to a T to A change at amino acid position 1684 of the L protein, which is the RSV RNA polymerase for both viral transcription and replication. The effect of Triazole-1 on minigenome transcription, which was mediated by the L protein containing the T1684A mutation, was significantly reduced, suggesting that the T1684A mutation alone conferred viral resistance to Triazole-1.
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http://dx.doi.org/10.1128/AAC.02576-20DOI Listing
March 2021

Transcriptome Analysis of Ovarian Follicles Reveals Potential Pivotal Genes Associated With Increased and Decreased Rates of Chicken Egg Production.

Front Genet 2021 10;12:622751. Epub 2021 Mar 10.

College of Agricultural & Environmental Sciences, University of Georgia, Athens, GA, United States.

Egg production is an important economic trait in the commercial poultry industry. Ovarian follicle development plays a pivotal role in regulation of laying hen performance and reproductive physiology. However, the key genes and signaling pathways involved in the various-stages of laying hen follicular development remain poorly understood. In this study, transcriptomes of ovarian follicles at three developmental stages, the large white follicle (LWF), small yellow follicle (SYF), and large yellow follicle (LYF), were comparatively analyzed in hens with high (HR) and low (LR) egg-laying rates by RNA-sequencing. Eighteen cDNA libraries were constructed and a total of 236, 544, and 386 unigenes were significantly differentially expressed in the LWF, SYF, and LYF follicles of HR and LR hens, respectively. Among them, 47 co-transcribed differentially expressed genes (DEGs) in LWF and SYF, 68 co-expressed DEGs in SYF and LYF, and 54 co-expressed DEGs in LWF and LYF were mined. Thirteen co-expressed DEGs were found in LWF, SYF, and LYF follicles. Eighteen candidate genes, including , , , , , , , , , , , , , , , , , and were identified to be potentially related to egg production. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis indicated neuroactive ligand-receptor interaction, cell adhesion molecules, peroxisome proliferator-activated receptor pathway, and cAMP signaling pathway might elicit an important role in formation of egg-laying traits by influencing ovarian follicle development. This study represents the first transcriptome analysis of various-sized follicles between HR and LR hens. These results provide useful molecular evidence for elucidating the genetic mechanism underlying ovarian follicle development associated with egg production in chicken.
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http://dx.doi.org/10.3389/fgene.2021.622751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987945PMC
March 2021

Immunological Characteristics in Type 2 Diabetes Mellitus Among COVID-19 Patients.

Front Endocrinol (Lausanne) 2021 11;12:596518. Epub 2021 Mar 11.

Department of Pediatrics, Center for the Diagnosis of Genetic Metabolic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634.

Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear.

Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients.

Design And Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups.

Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4 T cells, CD8 T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8 T cells and NK cells than survivors.

Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8 T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.
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http://dx.doi.org/10.3389/fendo.2021.596518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992040PMC
April 2021

Compound heterozygous UGT1A1*28 and UGT1A1*6 or single homozygous UGT1A1*28 are major genotypes associated with Gilbert's syndrome in Chinese Han people.

Gene 2021 May 23;781:145526. Epub 2021 Feb 23.

Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. Electronic address:

Gilbert's syndrome (GS) is a mild condition characterized by periods of hyperbilirubinemia, which results in variations in the UDP-glucuronosyltransferase 1 (UGT1A1) gene. Variant genotypes of UGT1A1 vary in different populations in the world. The present study aimed to determine the genotype of the UGT1A1 promoter and exon that are related to the serum total bilirubin (STB) level in the Chinese Han population. A total of 120 individuals diagnosed with GS (GS group) and 120 healthy individuals (non-GS group) were enrolled. Routine blood, liver function tests, and antibodies associated with autoimmune liver diseases were assessed. Blood samples were collected for DNA purification. Sequencing of the UGT1A1 promoter and exons was conducted for post segment amplification by PCR. Compound heterozygous UGT1A1*28 and UGT1A1*6 (25/120, 20.83%), single homozygous UGT1A1*28 (24/120, 20.00%) and single heterozygous UGT1A1*6 (18/120, 15.00%) were the most frequent genotypes in the GS group. However, single heterozygous UGT1A1*6 (30/120, 25.00%) and single heterozygous UGT1A1*28 (19/120, 15.83%) were the most frequent genotypes in the non-GS group. Further, the frequencies of single homozygous UGT1A1*28, compound heterozygous UGT1A1*28 and UGT1A1*6, and compound heterozygous UGT1A1*28, UGT1A1*6 and UGT1A1*27 were significantly higher in the GS group than those in the non-GS group. The STB levels of GS patients with the homozygous UGT1A1*28 genotype were remarkably higher than those of patients with other genotypes. Homozygous UGT1A1*28 and heterozygous UGT1A1*6 variants were associated with the highest and lowest risks of hyperbilirubinemia, respectively. Our study revealed that compound heterozygous UGT1A1*28 and UGT1A1*6, or single homozygous UGT1A1*28 are major genotypes associated with GS in Chinese Han people. These findings might facilitate the precise genomic diagnosis of Gilbert's syndrome.
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http://dx.doi.org/10.1016/j.gene.2021.145526DOI Listing
May 2021

Long-term micro-structure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations.

J Clin Invest 2021 Feb 25. Epub 2021 Feb 25.

Department of Radiology, Tongi Medical College, Huazhong University of Science and Technology, Wuhan, China.

The coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although patients totally recover from COVID-19 pneumonia, long-term effects on the brain still need to be explored. Here, two subtypes (mild type-MG and severe type-SG) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI three months after discharge were recruited. Changes in gray matter morphometry, cerebral blood flow (CBF) and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers were further analyzed. Compared with healthy controls, the decrease in cortical thickness/CBF, and the changes in WM microstructure were observed to be more severe in the SG than MG, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF and tracts parameters were significantly correlated with inflammatory markers. The indirect injury related to inflammatory storm may damage the brain, that led to these interesting observations. There are also other likely potential causes, such as hypoxemia and dysfunction of vascular endothelium, et al. The abnormalities in these brain areas need to be monitored in the process of complete recovery, which could help clinicians to understand the potential neurological sequelae of COVID-19.
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http://dx.doi.org/10.1172/JCI147329DOI Listing
February 2021

Therapeutic plasma-exchange improves systemic inflammation and survival in acute-on-chronic liver failure: A propensity-score matched study from AARC.

Liver Int 2021 Feb 2. Epub 2021 Feb 2.

Départment of Hepatology Institute of Liver and Biliary Science, New Delhi, India.

Background And Aim: Plasma-exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients.

Methods: Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE.

Results: ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); [PE (n = 131), FPSA (n = 31)] or were continued on standard medical therapy (SMT) (n = 1704). In the PRS-matched cohort (n = 208, [ALS-119; PE-94, FPSA-25)], SMT-89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42-24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5-11.1), and lower liver-failure-related deaths as compared to FPSA and SMT (P < .05). PE cleared inflammatory cytokines, damage-associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA) compared to non-responders. PE was associated with lesser adverse effects as compared to FPSA.

Conclusions: PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma-exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients.
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http://dx.doi.org/10.1111/liv.14806DOI Listing
February 2021

Single copper sites dispersed on defective TiO as a synergistic oxygen reduction reaction catalyst.

J Chem Phys 2021 Jan;154(3):034705

Department of Materials Science and Engineering, Guangdong-Hong Kong-Macao Joint Laboratory for Photonic-Thermal-Electrical Energy Materials and Devices, Southern University of Science and Technology, Shenzhen 518055, China.

Catalysts containing isolated single atoms have attracted much interest due to their good catalytic behavior, bridging the gap between homogeneous and heterogeneous catalysts. Here, we report an efficient oxygen reduction reaction (ORR) catalyst that consists of atomically dispersed single copper sites confined by defective mixed-phased TiO. This synergistic catalyst was produced by introducing Cu to a metal organic framework (MOF) using the Mannich reaction, occurring between the carbonyl group in Cu(acac) and the amino group on the skeleton of the MOF. The embedding of single copper atoms was confirmed by atomic-resolution high-angle annular dark-field scanning transmission electron microscopy and x-ray absorption fine structure spectroscopy. Electronic structure modulation of the single copper sites coupling with oxygen vacancies was further established by electron paramagnetic resonance spectroscopy and first-principles calculations. Significantly enhanced ORR activity and stability were achieved on this special Cu single site. The promising application of this novel electrocatalyst was demonstrated in a prototype Zn-air battery. This strategy of the stabilization of single-atom active sites by optimization of the atomic and electronic structure on a mixed matrix support sheds light on the development of highly efficient electrocatalysts.
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http://dx.doi.org/10.1063/5.0030559DOI Listing
January 2021

Transcriptomic characterization reveals prognostic molecular signatures of sorafenib resistance in hepatocellular carcinoma.

Aging (Albany NY) 2021 01 20;13(3):3969-3993. Epub 2021 Jan 20.

Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Sorafenib is the first-line treatment for patients with advanced unresectable hepatocellular carcinoma (HCC); however, only a small number of patients benefit from sorafenib, and many develop sorafenib resistance (SR) and severe side effects. To identify biomarkers for SR, we systematically analyzed the molecular alterations in both sorafenib-resistant HCC specimens and cultured cells. By combining bioinformatics tools and experimental validation, four genes (, insulin-like growth factor 2 receptor, complement factor B, and paraoxonase 1) were identified as key genes related to SR in HCC and as independent prognostic factors significantly associated with clinical cancer stages and pathological tumor grades of liver cancer. These genes can affect the cytotoxicity of sorafenib to regulate the proliferation and invasion of Huh7 cells . Additionally, immune-cell infiltration according to tumor immune dysfunction and exclusion, a biomarker integrating the mechanisms of dysfunction and exclusion of T cells showed good predictive power for SR, with an AUC of 0.869. These findings suggest that immunotherapy may be a potential strategy for treating sorafenib-resistant HCC. Furthermore, the results enhance the understanding of the underlying molecular mechanisms of SR in HCC and will facilitate the development of precision therapy for patients with liver cancer.
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http://dx.doi.org/10.18632/aging.202365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906139PMC
January 2021

Seraprevir and sofosbuvir for treatment of chronic hepatitis C virus infection: A single-arm, open-label, phase 3 trial.

J Gastroenterol Hepatol 2021 Jan 24. Epub 2021 Jan 24.

Department of Hepatology, The First Hospital of Jilin University, Changchun, China.

Background And Aim: This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis.

Methods: Treatment-naive or interferon-experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12).

Results: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post-treatment course and 3 discontinued follow-up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention.

Conclusions: The all-oral, ribavirin-free regimen of seraprevir and sofosbuvir is an effective and well-tolerated treatment option for Chinese patients mono-infected with HCV, including those with a history of interferon treatment.
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http://dx.doi.org/10.1111/jgh.15412DOI Listing
January 2021

Defective STING expression potentiates IL-13 signaling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps.

J Allergy Clin Immunol 2020 Dec 17. Epub 2020 Dec 17.

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown.

Objective: Our aim was to explore the expression, regulation, and function of STING in CRSwNP.

Methods: STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B in vitro.

Results: STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13-induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP.

Conclusions: Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP.
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http://dx.doi.org/10.1016/j.jaci.2020.12.623DOI Listing
December 2020

Microfluidic Technology for Antibacterial Resistance Study and Antibiotic Susceptibility Testing: Review and Perspective.

ACS Sens 2021 01 18;6(1):3-21. Epub 2020 Dec 18.

Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

A review on microfluidic technology for antibacterial resistance study and antibiotic susceptibility testing (AST) is presented here. Antibiotic resistance has become a global health crisis in recent decades, severely threatening public health, patient care, economic growth, and even national security. It is extremely urgent that antibiotic resistance be well looked into and aggressively combated in order for us to survive this crisis. AST has been routinely utilized in determining bacterial susceptibility to antibiotics and identifying potential resistance. Yet conventional methods for AST are increasingly incompetent due to unsatisfactory test speed, high cost, and deficient reliability. Microfluidics has emerged as a powerful and very promising platform technology that has proven capable of addressing the limitation of conventional methods and advancing AST to a new level. Besides, potential technical challenges that are likely to hinder the development of microfluidic technology aimed at AST are observed and discussed. To conclude, it is noted that (1) the translation of microfluidic innovations from laboratories to be ready AST platforms remains a lengthy journey and (2) ensuring all relevant parties engaged in a collaborative and unified mode is foundational to the successful incubation of commercial microfluidic platforms for AST.
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http://dx.doi.org/10.1021/acssensors.0c02175DOI Listing
January 2021

Decoupled Redox Catalytic Hydrogen Production with a Robust Electrolyte-Borne Electron and Proton Carrier.

J Am Chem Soc 2021 Jan 17;143(1):223-231. Epub 2020 Dec 17.

Department of Materials Science and Engineering, Faculty of Engineering, National University of Singapore 117576, Singapore.

Electrolytic water splitting is an effective approach for H mass production. A conventional water electrolyzer concurrently generates H and O in neighboring electrode compartments separated by a membrane, which brings about compromised purity, energy efficiency, and system durability. On the basis of distinct redox electrochemistry, here, we report a system that enables the decoupling of both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) from the electrodes to two spatially separated catalyst bed reactors in alkaline solutions. Through a pair of close-loop electrochemical-chemical cycles, the system operates upon 7,8-dihydroxy-2-phenazinesulfonic acid (DHPS) and ferricyanide-mediated HER and OER, respectively, on Pt/Ni(OH) and NiFe(OH) catalysts. Near unity faradaic efficiency and sustained production of hydrogen has been demonstrated at a current density up to 100 mA/cm. The superior reaction kinetics, particularly the HER reaction mechanism of DHPS as a robust electrolyte-borne electron and proton carriers, were scrutinized both computationally and experimentally. We anticipate the system demonstrated here would provide an intriguing alternative to the conventional water electrolytic hydrogen production.
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http://dx.doi.org/10.1021/jacs.0c09510DOI Listing
January 2021

Redox of Dual-Radical Intermediates in a Methylene-Linked Covalent Triazine Framework for High-Performance Lithium-Ion Batteries.

ACS Appl Mater Interfaces 2021 Jan 16;13(1):514-521. Epub 2020 Dec 16.

Department of Materials Science and Engineering, Guangdong-Hong Kong-Macao Joint Laboratory for Photonic-Thermal-Electrical Energy Materials and Devices, Southern University of Science and Technology, Shenzhen, 518055 Guangdong, P. R. China.

Covalent triazine frameworks (CTFs) are promising electrodes for rechargeable batteries due to their adjustable structures, rich redox sites, and tunable porosity. However, the CTFs usually exhibit inferior electrochemical stability because of the inactivation of the unstable radical intermediates. Here, a methylene-linked CTF has been synthesized and evaluated as a cathode for rechargeable lithium-ion batteries. Electron paramagnetic resonance (EPR) and in situ Raman characterizations demonstrated that the redox activity and reversibility of α-C and triazine radical intermediates are essentially important for the charging/discharging process, which have been efficiently stabilized by the synergetic π conjugation and hindrance effect caused by the adjacent rigid triazine rings and benzene rings in the unique CTF-p framework. Additionally, the methylene groups provided extra redox-active sites. As a result, high capacity and cycling stability were achieved. This work inspires the rational modulation of the radical intermediates to enhance the electrochemical performance of organic electrode materials for the next-generation energy storage devices.
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http://dx.doi.org/10.1021/acsami.0c17692DOI Listing
January 2021

Expressing a cytosolic pyruvate dehydrogenase complex to increase free fatty acid production in Saccharomyces cerevisiae.

Microb Cell Fact 2020 Dec 10;19(1):226. Epub 2020 Dec 10.

Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, No.15 North Third Ring Road East, Chaoyang District, Beijing, 100029, People's Republic of China.

Background: Saccharomyces cerevisiae is being exploited as a cell factory to produce fatty acids and their derivatives as biofuels. Previous studies found that both precursor supply and fatty acid metabolism deregulation are essential for enhanced fatty acid synthesis. A bacterial pyruvate dehydrogenase (PDH) complex expressed in the yeast cytosol was reported to enable production of cytosolic acetyl-CoA with lower energy cost and no toxic intermediate.

Results: Overexpression of the PDH complex significantly increased cell growth, ethanol consumption and reduced glycerol accumulation. Furthermore, to optimize the redox imbalance in production of fatty acids from glucose, two endogenous NAD-dependent glycerol-3-phosphate dehydrogenases were deleted, and a heterologous NADP-dependent glyceraldehyde-3-phosphate dehydrogenase was introduced. The best fatty acid producing strain PDH7 with engineering of precursor and co-factor metabolism could produce 840.5 mg/L free fatty acids (FFAs) in shake flask, which was 83.2% higher than the control strain YJZ08. Profile analysis of free fatty acid suggested the cytosolic PDH complex mainly resulted in the increases of unsaturated fatty acids (C16:1 and C18:1).

Conclusions: We demonstrated that cytosolic PDH pathway enabled more efficient acetyl-CoA provision with the lower ATP cost, and improved FFA production. Together with engineering of the redox factor rebalance, the cytosolic PDH pathway could achieve high level of FFA production at similar levels of other best acetyl-CoA producing pathways.
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http://dx.doi.org/10.1186/s12934-020-01493-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730738PMC
December 2020

Efficient photocatalytic removal of phthalates easily implemented over a bi-functional {001}TiO surface.

Chemosphere 2021 Jan 4;263:128257. Epub 2020 Sep 4.

School of Chemical Science and Engineering, Shanghai Key Lab of Chemical Assessment and Sustainability, Key Laboratory of Yangtze River Water Environment, Tongji University, Shanghai, 200092, People's Republic of China. Electronic address:

It is stubborn to remove the lowly concentrated phthalic acid esters (PAEs) that usually coexist with other highly concentrated but low-toxic pollutants in municipal sewage. Herein, we report a novel strategy for completely removing the PAEs over a bi-functional {001}TiO surface (with highly exposed {001} facet), which not only serve as functional sites to specifically adsorb the target PAEs pollutants, but also contribute to an enhanced oxidation ability. The adsorption behavior of PAEs on {001}TiO is analyzed deeply through kinetic experiments combining with in situ ATR-FTIR spectroscopy and theoretical calculations. The results reveal that the adsorption capacities of PAEs on {001}TiO are about 4-5 times higher than that on TiO, both of which follow the pseudo-second-order and Langmuir model. This is mainly attributed to the interfacial Lewis Acid-Base Pair between {001} facet Ti sites and CO of PAEs. Benefitting from the specific adsorption capability toward target pollutant and enhanced oxidation ability of {001} facets, nearly 100% of DMP or DEP in simulated wastewater can be eliminated by {001}TiO within 2 h illumination, and the relevant degradation rate constants (k) (3.67 h for DMP and 2.19 h for DEP) are 5.73 and 3.08 folds higher than that of pure TiO, respectively. In the application of municipal wastewater, nearly 76% of DMP and 85% DEP can be eliminated by {001}TiO within 2 h illumination, which are nearly 3-6 fold higher than that of pure TiO.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128257DOI Listing
January 2021

WGO Guidance for the Care of Patients With COVID-19 and Liver Disease.

J Clin Gastroenterol 2021 01;55(1):1-11

Department of Gastroenterology & Hepatology, Koç University Medical School, Istanbul, Turkey.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the least deadly but most infectious coronavirus strain transmitted from wild animals. It may affect many organ systems. Aim of the current guideline is to delineate the effects of SARS-CoV-2 on the liver. Asymptomatic aminotransferase elevations are common in coronavirus disease 2019 (COVID-19) disease. Its pathogenesis may be multifactorial. It may involve primary liver injury and indirect effects such as "bystander hepatitis," myositis, toxic liver injury, hypoxia, and preexisting liver disease. Higher aminotransferase elevations, lower albumin, and platelets have been reported in severe compared with mild COVID-19. Despite the dominance of respiratory disease, acute on chronic liver disease/acute hepatic decompensation have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a higher risk of respiratory disease progression than those without MAFLD. Alcohol-associated liver disease may be severely affected by COVID-19-such patients frequently have comorbidities including metabolic syndrome and smoking-induced chronic lung disease. World Gastroenterology Organization (WGO) recommends that interventional procedures such as endoscopy and endoscopic retrograde cholangiopancreatography should be performed in emergency cases or when they are considered strictly necessary such as high risk varices or cholangitis. Hepatocellular cancer surveillance may be postponed by 2 to 3 months. A short delay in treatment initiation and non-surgical approaches should be considered. Liver transplantation should be restricted to patients with high MELD scores, acute liver failure and hepatocellular cancer within Milan criteria. Donors and recipients should be tested for SARS-CoV-2 and if found positive donors should be excluded and liver transplantation postponed until recovery from infection.
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http://dx.doi.org/10.1097/MCG.0000000000001459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713641PMC
January 2021

Recommendations for the Diagnosis, Prevention, and Control of Coronavirus Disease-19 in Children-The Chinese Perspectives.

Front Pediatr 2020 5;8:553394. Epub 2020 Nov 5.

Department of Pediatrics, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Ever since SARS-CoV-2 began infecting people by the end of 2019, of whom some developed severe pneumonia (about 5%), which could be fatal (case fatality ~3.5%), the extent and speed of the COVID-19 outbreak has been phenomenal. Within 2.5 months (by March 18, 2020) over 191,127 COVID-19 patients have been identified in 161 countries. By then, over 700 pediatric patients were confirmed to have COVID-19 in China, with only about 58 diagnosed elsewhere. By now, there are thousands of children and adolescents infected. Chinese pediatricians would like to share their experience on how these patients were managed in China and the key recommendations that had guided them in meeting the evolving challenges. A group of experts were summoned by the Chinese Pediatric Society and Editorial Board of Chinese Journal of Pediatrics to extract informative data from a survey on confirmed COVID-19 pediatric patients in China. Consensus on diagnosis, management, and prevention of pediatric COVID-19 were drawn up based on the analysis of such data plus insights gained from the past SARS and MERS coronavirus outbreaks. Relevant cumulating experiences from physicians managing adult patients, expedited reports on clinical and scientific COVID-19 and SARS-CoV-2 data, and the National Health Committee guidelines on COVID-19 management were integrated into this proposal.
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http://dx.doi.org/10.3389/fped.2020.553394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674551PMC
November 2020

Changes in children's asthma prevalence over two decades in Lanzhou: effects of socioeconomic, parental and household factors.

J Thorac Dis 2020 Oct;12(10):6365-6378

Beijing Innovation Center for Engineering Science and Advanced Technology, State Key Joint Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, And Center for Environment and Health, Peking University, Beijing, China.

Background: The prevalence of childhood asthma may have changed with rapid economic development. This study aims to ascertain potential changes in asthma prevalence in relation to changes in socioeconomic, parental and household factors, based on a comparison between two periods spanning over 20 years in Lanzhou, a large northwestern city of China.

Methods: Cross-sectional studies using the same protocols were performed in Lanzhou, China in 1994-1995 (Period I) and in 2017 (Period II). Children of 6-12 years old from elementary schools were selected by a multistage sampling method. Information on the presence of asthma and asthma-related symptoms of children, socioeconomic status, feeding methods, parental illness and behavior patterns, as well as household characteristics, were collected through a questionnaire survey. Logistic regression models were used to estimate odds ratios of asthma prevalence with regard to socioeconomic, parental and household factors, respectively.

Results: Significant prevalence reductions were observed for paternal smoking, household coal use, and parental asthma, while the prevalence increased significantly for children sleeping in their own rooms or own beds, ventilation use during cooking, and parental occupation and education level after 22 years. In children, the prevalence of ever-diagnosed asthma decreased from 3.2% in period I to 1.5% in Period II (P<0.001); the prevalence of wheeze also decreased from 15.4% to 9.3% (P<0.001). Passive smoking (OR =1.531, 95% CI: 1.032-2.270) and poor household ventilation (OR =1.709, 95% CI: 1.208-2.416) were significantly associated with an increased prevalence of wheeze in Period I, whereas household mold (OR =2.112, 95% CI: 1.203-3.811) was significantly associated with prevalence of wheeze. Parental asthma history was associated with increased prevalence of asthma and asthma-related symptoms. Breastfeeding was significantly associated with reduced risk of asthma in period II children.

Conclusions: The prevalence of asthma and that of asthma-related symptoms were lower in 2017 than in 1994-1995 in school children living in Lanzhou. In 2017 with increased urbanization and industrialization, breastfeeding became a significant protective factor and household mold was a significant risk factor for asthma diagnosis and asthma-related symptoms. Promoting breastfeeding and household mold control is recommended to reduce the risk of childhood asthma in contemporary Lanzhou.
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http://dx.doi.org/10.21037/jtd-19-crh-aq-008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656413PMC
October 2020

The impacts of algae biological pump effect on the occurrence, source apportionment and toxicity of SPM-bound PAHs in lake environment.

Sci Total Environ 2021 Jan 25;753:141980. Epub 2020 Aug 25.

MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. Electronic address:

The algae biological pump (ABP) effect for hydrophobic organic contaminants in deep oligotrophic lakes and oceans has been well studied. Suspended particulate matter (SPM) plays a connective role in ABP processes. However, little is known about the impacts of ABP effect on the occurrence, source apportionment and toxicity of SPM-bound polycyclic aromatic hydrocarbons (PAHs) in a typically shallow eutrophic lake under strong anthropogenic emissions of PAHs. In this study, we study this gap knowledge on the eutrophic Lake Chaohu, China. SPM-bound PAHs in Lake Chaohu were controlled by anthropogenic emissions in all seasons. Apparent ABP effect only occurred in spring and summer in lake area. Algae blooms in spring and summer significantly increased 46.5% ± 7.9% (mean ± standard deviation) and 19.8% ± 2.4% of Σ SPM-bound PAHs, and greatly enhanced their toxicity (1.98 ± 0.46 times in spring and 32.9% ± 4.2% in summer). Therefore, there need more attentions focusing on the coupling effect of persistent toxic substances such as PAHs and harmful algae blooms in aquatic environment for sustainable development. The apparent ABP effect had little influence on their source apportionment. However, it may cause a regime shift for the source apportionment on a short-term scale. Further study could pay more attentions on in-depth and short-term studies on ABP effect.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141980DOI Listing
January 2021

Rewiring Central Carbon Metabolism Ensures Increased Provision of Acetyl-CoA and NADPH Required for 3-OH-Propionic Acid Production.

ACS Synth Biol 2020 12 13;9(12):3236-3244. Epub 2020 Nov 13.

Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, 100029 Beijing, China.

The central carbon metabolite acetyl-CoA and the cofactor NADPH are important for the synthesis of a wide array of biobased products. Here, we constructed a platform yeast strain for improved provision of acetyl-CoA and NADPH, and used the production of 3-hydroxypropionic acid (3-HP) as a case study. We first demonstrated that the integration of phosphoketolase and phosphotransacetylase improved 3-HP production by 41.9% and decreased glycerol production by 48.1% compared with that of the control strain. Then, to direct more carbon flux toward the pentose phosphate pathway, we reduced the expression of phosphoglucose isomerase by replacing its native promoter with a weaker promoter, and increased the expression of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by replacing their native promoters with stronger promoters. This further improved 3-HP production by 26.4%. Furthermore, to increase the NADPH supply we overexpressed cytosolic aldehyde dehydrogenase, and improved 3-HP production by another 10.5%. Together with optimizing enzyme expression of acetyl-CoA carboxylase and malonyl-CoA reductase, the final strain is able to produce 3-HP with a final titer of 864.5 mg/L, which is a more than 24-fold improvement compared with that of the starting strain. Our strategy combines the PK pathway with the oxidative pentose phosphate pathway for the efficient provision of acetyl-CoA and NADPH, which provides both a higher theoretical yield and overall yield than the reported yeast-based 3-HP production strategies the malonyl-CoA reductase-dependent pathway and sheds light on the construction of efficient platform cell factories for other products.
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http://dx.doi.org/10.1021/acssynbio.0c00264DOI Listing
December 2020

Potential for developing independent daytime/nighttime LUR models based on short-term mobile monitoring to improve model performance.

Environ Pollut 2021 Jan 29;268(Pt B):115951. Epub 2020 Oct 29.

School of Energy and Environmental Engineering, University of Science and Technology of Beijing, Beijing, 100083, China. Electronic address:

Land use regression model (LUR) is a widespread method for predicting air pollution exposure. Few studies have explored the performance of independently developed daytime/nighttime LUR models. In this study, fine particulate matter (PM), inhalable particulate matter (PM), and nitrogen dioxide (NO) concentrations were measured by mobile monitoring during non-heating and heating seasons in Taiyuan. Pollutant concentrations were higher in the nighttime than the daytime, and higher in the heating season than the non-heating season. Daytime/nighttime and full-day LUR models were developed and validated for each pollutant to examine variations in model performance. Adjusted coefficients of determination (adjusted R) for the LUR models ranged from 0.53-0.87 (PM), 0.53-0.85 (PM), and 0.33-0.67 (NO). The performance of the daytime/nighttime LUR models for PM and PM was better than that of the full-day models according to the results of model adjusted R and validation R. Consistent results were confirmed in the non-heating and heating seasons. Effectiveness of developing independent daytime/nighttime models for NO to improve performance was limited. Surfaces based on the daytime/nighttime models revealed variations in concentrations and spatial distribution. In conclusion, the independent development of daytime/nighttime LUR models for PM/PM has the potential to replace full-day models for better model performance. The modeling strategy is consistent with the residential activity patterns and contributes to achieving reliable exposure predictions for PM and PM. Nighttime could be a critical exposure period, due to high pollutant concentrations.
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http://dx.doi.org/10.1016/j.envpol.2020.115951DOI Listing
January 2021

Long-term outcomes in Chinese patients with chronic hepatitis B receiving nucleoside/nucleotide analogue therapy in real-world clinical practice: 5-year results from the EVOLVE study.

Antivir Ther 2020 Oct 22. Epub 2020 Oct 22.

Bristol-Myers Squibb, Shanghai, China.

Background: In China, the optimal management of individuals living with chronic HBV infection remains an unmet need. The EVOLVE was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naïve CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies.

Methods: Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or HBeAg status were enrolled from Tier 2 city hospitals (between 2012-2014). The choice of initial therapy and subsequent treatment modifications was at the discretion of treating physicians. Key outcomes included treatment modifications, virologic response (HBV DNA <300copies/mL), and HBV disease progression.

Results: Of the 3408 patients enrolled, 1807 and 628 received ETV and LAM-based therapy, respectively. The mean age was 39.5 years, 74% were male, and 22.9% had cirrhosis. The rate of treatment modification was higher in the LAM-based vs ETV group (25.9% vs 13.7%); viral breakthrough was the most common reason in LAM-based group vs financial reasons in ETV group. At week 240, the virologic response rate was 73% in both treatment groups. Compared with LAM-based therapy, ETV was associated with a significantly lower incidence of viral breakthrough (12.6% vs 2.1%) and genotypic resistance (10.1% vs 1.2%; p<0.0001 for both); significantly lower risk of HBV disease progression (14.0% vs 10.7%; p=0.0113); and lower rates of progression to decompensated cirrhosis (9.6% vs 6.4%) and hepatocellular carcinoma (1.9% vs 0.8%).

Conclusions: This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough, and resistance with ETV vs LAM-based therapy.
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http://dx.doi.org/10.3851/IMP3372DOI Listing
October 2020

Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis.

J Clin Transl Hepatol 2020 Sep 11;8(3):255-261. Epub 2020 Sep 11.

Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.

Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment. Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy. The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.
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http://dx.doi.org/10.14218/JCTH.2020.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562795PMC
September 2020

Intrauterine inflammation induced white matter injury protection by fibrinogen-like protein 2 deficiency in perinatal mice.

Pediatr Res 2020 Oct 19. Epub 2020 Oct 19.

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: White matter injury (WMI) induced by intrauterine inflammation can cause adverse neurological outcomes. Fibrinogen-like protein 2 (FGL2)/fibroleukin is an important trigger of inflammatory responses and is involved in some cerebral diseases. However, the role of FGL2 in intrauterine inflammation-induced WMI remains unclear.

Methods: Lipopolysaccharide (LPS) was intraperitoneally injected into wild-type and FGL2 knockout mice to induce intrauterine inflammation. Body weight and brain weight of offspring were monitored. Major basic protein (MBP) expression was evaluated to demonstrate the myelination of offspring. To investigate the regulatory mechanism of FGL2, cytokine expression, microglial polarization, and the activation of mitogen-activated protein kinase (MAPK) signaling pathway in the offspring were analyzed.

Results: Upon LPS exposure, FGL2 knockout offspring showed a significant increase in body weight loss. MBP reduction induced by LPS was prevented in FGL2 knockout offspring. Expression levels of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α, and M1 marker CD86 were suppressed, while the expression levels of anti-inflammatory cytokines IL-10 and M2 marker CD206 were increased. FGL2 deficiency significantly inhibited the phosphorylation of p38MAPK and c-Jun N-terminal kinase (JNK) protein.

Conclusions: FGL2 deficiency can ameliorate WMI induced by intrauterine inflammation, reducing inflammatory cascade and improving hypomyelination, through the regulation of microglial polarization and MAPK signaling pathways.

Impact: Intrauterine inflammation induces WMI leading to severe neurological sequelae. FGL2 plays an important role in the progression of WMI induced by intrauterine inflammation. FGL2 deficiency can protect against WMI by inhibiting p38 MAPK and JNK phosphorylation, regulating microglia polarization, and reducing inflammation response. FGL2 could be a novel molecular target for protecting against WMI induced by intrauterine inflammation.
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http://dx.doi.org/10.1038/s41390-020-01211-wDOI Listing
October 2020

Endothelin receptors promote schistosomiasis-induced hepatic fibrosis via splenic B cells.

PLoS Pathog 2020 10 19;16(10):e1008947. Epub 2020 Oct 19.

Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Endothelin receptors (ETRs) are activated by vasoactive peptide endothelins and involved in the pathogenesis of hepatic fibrosis. However, less is known about the role of ETRs in Schistosoma (S.) japonicum-induced hepatic fibrosis. Here, we show that the expression of ETRs is markedly enhanced in the liver and spleen tissues of patients with schistosome-induced fibrosis, as well as in murine models. Additional analyses have indicated that the expression levels of ETRs in schistosomiasis patients are highly correlated with the portal vein and spleen thickness diameter, both of which represent the severity of fibrosis. Splenomegaly is a characteristic symptom of schistosome infection, and splenic abnormality may promote the progression of hepatic fibrosis. We further demonstrate that elevated levels of ETRs are predominantly expressed on splenic B cells in spleen tissues during infection. Importantly, using a well-studied model of human schistosomiasis, we demonstrate that endothelin receptor antagonists can partially reverse schistosome-induced hepatic fibrosis by suppressing the activation of splenic B cells characterized by interleukin-10 (IL-10) secretion and regulatory T (Treg) cell-inducing capacity. Our study provides insights into the mechanisms by which ETRs regulate schistosomiasis hepatic fibrosis and highlights the potential of endothelin receptor antagonist as a therapeutic intervention for fibrotic diseases.
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http://dx.doi.org/10.1371/journal.ppat.1008947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595619PMC
October 2020

Coblopasvir and sofosbuvir for treatment of chronic hepatitis C virus infection in China: A single-arm, open-label, phase 3 trial.

Liver Int 2020 11 13;40(11):2685-2693. Epub 2020 Oct 13.

Department of Hepatology, the First Hospital of Jilin University, Changchun, China.

Background & Aim: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) infection.

Methods: Treatment-naïve and interferon-experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12).

Results: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty-one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow-up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention.

Conclusions: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis.

Lay Summary: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population.
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http://dx.doi.org/10.1111/liv.14633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702130PMC
November 2020

Clinical characteristics and risk factors of liver injury in COVID-19: a retrospective cohort study from Wuhan, China.

Hepatol Int 2020 Sep 7;14(5):723-732. Epub 2020 Oct 7.

Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury.

Methods: A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury.

Results: Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)].

Conclusion: Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.
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http://dx.doi.org/10.1007/s12072-020-10075-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539280PMC
September 2020

Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

Liver Int 2021 01;41(1):150-157

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Background: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF).

Methodology: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively.

Results: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores.

Conclusion: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.
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http://dx.doi.org/10.1111/liv.14671DOI Listing
January 2021