简介：Objective:Humanpancreaticcancerisoneofthemostcommonclinicalmalignancies.Theeffectofcomprehensivetreatmentbasedonsurgeryisgeneral.Theeffectsofchemotherapywerenotobviousmainlybecauseoflackoftargetingandchemoresistanceinpancreaticcancer.Thisstudyaimedtoinvestigatetheeffectsoffolatereceptor(FR)-mediatedgemcitabineFA-Chi-Gemnanoparticleswithacore-shellstructurebyelectrostaticsprayonpancreaticcancer.Methods:Inthisstudy,thelevelsofexpressionofFRinsixhumanpancreaticcancercelllineswerestudiedbyimmunohistochemicalanalysis.Theuptakerateofisothiocyanate-labeledFA-ChinanoparticlesinFRhighexpressioncelllineCOLO357wasassessedbyfluorescencemicroscopeandtheinhibitionrateofFAChi-GemnanoparticlesonCOLO357cellswasevaluatedbyMTTassay.Moreover,thebiodistributionofPEG-FA-ICGDER02-Chiintheorthotopicpancreatictumormodelwasobservedusingnear-infraredimagingandthehumanpancreaticcancerorthotopicxenograftsweretreatedwithdifferentnanoparticlesandnormalsalinecontrol.Results:TheexpressionofFRinCOLO357wasthehighestamongthesixpancreaticcancercelllines.TheFRmainlydistributedoncellmembraneandfewerinthecytoplasminpancreaticcancer.Moreover,theabsorptionrateoftheFA-Chi-GemnanoparticleswasmorethantheChinanoparticleswithoutFAmodified.TheproliferationofCOLO357wassignificantlyinhibitedbyFA-Chi-Gemnanoparticles.ThePEG-FAICGDER02-Chinanoparticleswereenrichedintumortissueinhumanpancreaticcancerxenografts,whilenon-targetednanoparticlesweremainlyinnormallivertissue.PEG-FA-Gem-Chisignificantlyinhibitedthegrowthofhumanpancreaticcancerxenografts(PEG-FA-Gem-Chivs.Gem,t=22.950,P=0.000).Conclusions:PEG-FA-FITC-ChinanoparticlesmightbeaneffectivetargeteddrugfortreatinghumanFR-positivepancreaticcancer.

简介：AbstractAfrican swine fever virus (ASFV) is the causative agent of African swine fever, a highly fatal hemorrhagic disease of pigs, which has resulted in great economic losses to the global pork industry, especially in Asia. ASFV particles are comprised of multiple layers encompassing the genomic DNA. Though the capsid structure has been determined, very little is known about the structure of the core shell. The precursor polyprotein pp62 is the structural component of the core shell that gives rise to the p35 and p15 proteins. Herein, we describe the crystal structure of p15 at a resolution of 2.2 Å. The structure of p15 exhibits as a trimeric conformation that is mainly mediated by intermolecular disulfide bonds and supported by multiple hydrogen bond interactions. The button conformation on the surface of adjacent molecules may also play a role in trimeric formation of the ASFV p15. The center of the p15 trimer exhibits opposite electrostatic characteristics on each side. These findings benefit our understanding of ASFV core shell assembly and will aid in the design of antiviral drugs and vaccines.

简介：Glioblastoma(GBM)isoneofthemostlethalhumancancers.GenomicanalysesdefinethemoleculararchitectureofGBMandhighlightacentralfunctionformechanistictargetofrapamycin(mTOR)signaling.mTORkinaseexistsintwomultiproteincomplexes,namely,mTORC1andmTORC2.Thesecomplexesdifferintermsoffunction,regulationandrapamycinsensitivity.mTORC1iswellestablishedasacancerdrugtarget,whereasthefunctionsofmTORC2incancer,includingGBM,remainspoorlyunderstood.ThisstudyreviewstherecentfindingsthatdemonstrateacentralfunctionofmTORC2inregulatingtumorgrowth,metabolicreprogramming,andtargetedtherapyresistanceinGBM,whichmakesmTORC2asacriticalGBMdrugtarget.

简介：AbstractBackground:Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.Methods:One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.Results:HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log10 U/mL P= 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P= 0.025), and Ishak fibrosis score (r= -0.292, P= 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = -0.263, P = 0.014) and HBeAg-negative patients (r= -0.291, P= 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r= 0.366, P= 0.001; r= 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log10 U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).Conclusions:HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.Trial registration:Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1

简介：摘要目的分别用新型复合型层析介质Capto Core 400和传统介质Sepharose 6FF纯化Sabin株脊髓灰质炎病毒(Sabin strain poliovirus，sPV)去除宿主细胞蛋白(hostcell protein，HCP)和DNA，并且比较纯化结果及工艺参数。方法用Capto Core 400与Sepharose 6FF纯化Vero细胞培养的Ⅰ、Ⅱ、Ⅲ型sPV浓缩液。分别检测纯化后sPV的D抗原含量、HCP残留量和DNA残留量，计算D抗原回收率、HCP和DNA去除率，并用t检验分析差异。结果Capto Core 400与Sepharose 6FF纯化Ⅰ、Ⅱ、Ⅲ型sPV的D抗原回收率差异均无统计学意义(t值分别为1.09、1.08、1.02，P值均>0.05)，但前者的Vero细胞HCP(t值分别为3.15、3.23、3.54)和DNA去除率均高于后者(t值分别为3.41、3.25、3.62)，且差异有统计学意义(P值均<0.05)。Capto Core 400与Sepharose 6FF的介质使用体积比值为0.05，上样后纯化时间比值为0.04，工作缓冲液使用量比值为0.25，工艺线性流速比值为10，每升介质上样量比值为20，最大耐压力比值为2。结论对比Sepharose 6FF，Capto Core 400可以更有效地去除Vero细胞HCP与DNA，各个工艺参数得到了优化，提高了sPV层析纯化的工作效率，并节约了时间和成本。