A novel fibroblast growth factor 15-dependent and bile acid-independent promotion of liver regeneration in mice

Objective:The role of intestine-derived factors in promoting liver regeneration after partial hepatectomy(PHx)are not entirely known,but bile acids(BAs)and fibroblast growth factor 15(Fgf15)that are highly expressed in the mouse ileum could promote hepatocyte proliferation.Fgf15 strongly suppresses the synthesis of BAs,and emerging evidence indicates that Fgf15 is important for liver regeneration.

Thermal Stability and Decomposition Kinetics of Polysuccinimide

The thermal stability and decomposition kinetics of polysuccinimide (PSI) were investigated using analyzer DTG-60 under high purity nitrogen atmosphere at different heating rates (3, 6, 9, 12 K/min). The thermal decomposition mechanism of PSI was determined by Coats-Redfern method. The kinetic parameters such as activation energy (E), pre-exponential factor (A) and reaction order (n) were calculated by Flynn-Wall-Ozawa and Kissinger methods. The results show that the thermal decomposition of PSI under nitrogen atmosphere mainly occurs in the temperature range of 619.15-693.15 K, the reaction order (n) was , the activation energy (E) and pre-exponential factor (A) were obtained to be 106.585 kJ/mol and 4.644 × 109 min-1, the integral and differential forms of the thermal decomposition mechanism of PSI were found to be and , respectively. The results play an important role in understanding the thermodynamic properties of polysuccinimide.

Treating COVID-19 with Chloroquine

A novel coronavirus disease 2019(COVID-19)emerged around December 2019 in Wuhan,China and has spread rapidly worldwide(Lu et al.,2020).Until March 27,2020,the Chinese health authorities had reported 82082 confirmed COVID-19 cases in China with 3298 deaths and 381443 confirmed cases with 20787 deaths outside China.The World Health Organization(WHO)named the virus SARS-CoV-2,which belongs to a distinct clade from the human severe acute respiratory syndrome CoV(SARS-CoV)and Middle East respiratory syndrome CoV(MERSCoV)(Zhu et al.,2020).

Risk factors for very low-level viremia in patients with chronic hepatitis B virus infection: A single-center retrospective study

Background and aim:Several effective antiviral drugs are now available;however,the risk of liver-related complications is still present.Low-level viremia(LLV),defined as a hepatitis B virus(HBV)deoxy-ribonucleic acid(DNA)load lower than 2000 IU/mL,is one of the major factors responsible for these complications.It has been reported that 22.7e43.1%of patients with HBV experience LLV.Herein,we aimed to explore the risk factors for very LLV(VLLV)during antiviral treatment.Methods:We collected data of patients with chronic hepatitis B(CHB)who received nucleos(t)ide analog treatment from October 2016 to April 2021.VLLV was defined as an HBV DNA load of 9e20 IU/mL.A total of 139 patients with LLV were matched with 139 patients with a sustained virological response at a 1:1 ratio according to age and gender.Results:Seropositivity rates for hepatitis B e antigen(HBeAg)(45.3%vs.17.3%,P<0.001)and hepatitis B surface antigen(HBsAg,3.11±0.68 lg IU/mL vs.2.54±1.04 lg IU/mL,P<0.001)and alanine amino-transferase levels(30.34±15.08 U/L vs.26.15±16.66 U/L,P¼0.040)in the two groups were significantly different.The multivariate analysis showed that both HBeAg seropositivity(adjusted odd ratio(aOR),3.63;95% confidence interval(CI):1.98±6.64;P<0.001)and HBsAg levels(aOR,2.21;95% CI:1.53±3.20;P<0.001)are independent risk factors for VLLV.During the multivariate analysis in the subgroup of HBeAg-positive patients,male gender(aOR,3.68;95% CI:1.23±10.76;P=0.017)and high HBsAg(aOR,4.86;95%CI:1.73e13.64;P¼0.003)levels were significantly correlated with VLLV.However,this was not the case in HBeAg-negative patients(P>0.050).HBeAg seropositivity(aOR,5.08;95% CI:2.15±12.02;P<0.001 vs.aOR,2.78;95% CI:1.16±7.00;P=0.022)and HBsAg levels(aOR,2.75;95% CI:1.41e5.37;P=0.003 vs.aOR,2.10;95% CI:1.27±3.46;P=0.004)significantly increased the risk of VLLV,irrespective of the age group.Both HBsAg(area under the receiver operating characteristic curve(AUC),0.681;95% CI:0.623±0.736;P<0.001)and HBeAg(AUC,0.640;95% CI:0.581±0.697;P<0.001)had certain pre-dictive value for VLLV.Conclusion:HBeAg seropositivity and higher HBsAg levels were not only risk factors for VLLV but also predicted its occurrence.When a patient with CHB remains HBeAg seropositive with high HBsAg levels after antiviral treatment for 48 weeks,emphasis should be placed on the potential occurrence of VLLV,warranting the use of highly sensitive HBV DNA detection methods.

Effects of intestine-specific deletion of fibroblast growth factor 15 on alcoholic liver disease development in mice

Background and aims:Alcoholic liver disease(ALD)is an important and growing cause for the development of chronic liver diseases in the world.Bile acid(BA)levels are increased in patients with ALD anddysregulation of BA homeostasis worsens ALD.BA synthesis is critically regulated by fibroblast growthfactor(FGF)15 in mice and FGF19 in humans.FGF15/19 are mainly produced in the ileum and their mainfunction is to suppress BA synthesis in the liver through the activation of fibroblast growth factor receptor 4(FGFR4)on hepatocytes.The effects of intestine-specific Fgf15 deficiency on the development ofALD were determined in the current study.Methods:Enterocyte-specific Fgf15 knockout mice(Fgf15intint^(-/-))and the established mouse model bychronic and binge ethanol feeding(NIAAA model)were adapted in this study.Results:The Fgf15intint^(-/-)mice had increased BA pool size,consistent with negative effects of FGF15-FGFR4signaling on BA synthesis.There were not obviously physical and hepatic histological abnormalitiespresented in Fgf15intint^(-/-)mice compared to wild-type mice.Following alcohol treatment,the Fgf15intint^(-/-)mice exhibited a higher degree of liver injury,increased hepatic expression of Cd14,a receptor forlipopolysaccharide expressed in the liver,and increased hepatic lipid levels.We did not observe alterations in the levels of fibrosis in the liver or expression of genes involved in hepatic fibrosis,regardless ofgenotypes or following the alcohol treatment.Conclusions:FGF15 may prevent hepatic steatosis in the development of ALD in mice,and maintainingFGF19/FGFR4 signaling may be critical in the prevention and/or treatment of ALD in humans in thefuture.

Prevalence, diagnosis, treatment, and associated factors of hepatitis C in the United States from 1999 to 2018: A population-based cross- sectional study

Background and aim:Hepatitis C virus(HCV)infection is one of the major global health challenges,leading to a significant increase in rates of hepatic fibrosis,cirrhosis and hepatocellular carcinoma.A comprehensive nationwide survey of trends in prevalence and associated factors could facilitate pre-ventive behavioral interventions.Herein,we sought to determine prevalence,diagnosis,treatment,and risk factors for HCV infection in the general United States(US)population.Methods:This was a secondary analysis of the publicly available data from the US National Health and Nutrition Examination Survey(NHANES).The prevalence of HCV-RNA-positive(HCV-RNAþ)was weighted using patient serum sample data collected from 1999 to 2018.A propensity score matching model was used due to the imbalance in the number of HCV-RNAþand HCV-RNA-negative(HCV-RNA?)patients.Matched variables included gender,age,educational level,marital status,language,household size,alcohol consumption,smoking,number of family members and family income to poverty ratio.Results:The weighted prevalence of HCV-RNAþwas 1.11%(95%confidence interval(CI):1.02e1.20),1.58%(95%CI:1.42e1.74)for men and 0.67%(95%CI:0.57e0.77)for women aged 20 years or older in the US from 1999 to 2018.The weighted prevalence of HCV-RNAþincreased from 0.87%(95%CI:0.62e1.12)in 2013e2014,0.95%(95%CI:0.68e1.22)in 2015e2016 to 1.00%(95%CI:0.72e1.28)in 2017e2018,respectively.In propensity-matched analysis,patients with HCV-RNAþwere more likely to be non-Hispanic black,and have had drug use and blood transfusions.Meanwhile,the weighted diagnostic and treatment rates were 56.27%(95%CI:50.90e61.64)and 35.40%(95%CI:27.64e43.16)from 1999 to 2018,respectively.Conclusions:Active HCV infection rate increased between 2013 and 2018,varied by demographic and risk variables.In the direct-acting antiviral era,affordable treatment and universal screening have the potential to improve overall national health.

Analysis and Verification of Aerodynamic Characteristics of Tianwen-1 Mars Parachute

The Mars parachute flight environment is supersonic,low-density,and low dynamic pressures.To ensure the operating performance and reliability,the design optimization and verification of the Tianwen-1 Mars parachute have been carried out.Firstly,through supersonic and subsonic wind tunnel tests,the design optimization of the parachute structure is realized.Subsequently,the high-altitude flight tests of four parachutes were conducted,the drag coefficient and the oscillation angle of the parachute from supersonic to subsonic speed were gained,and the aerodynamic characteristics and reliable opening of the parachutes were thoroughly tested and verified.This article presents the design,development,and qualification of the Tianwen-1 Mars parachute,which can provide a reference for the creation of future Mars exploration parachutes.