Capsid destabilization and epitope alterations of human papillomavirus 18 in the presence of thimerosal

Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic exponential decay model.The potential effect of thimerosal on protein function,particularly for thiolcontaining proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.

折合频率对三维跨声速压气机颤振稳定性的影响

It is well known that fan/compressor blade flutter stability increases with the increase of reduced frequency.Less well-known is that the least stable inter blade phase angle(IBPA)increases with the drop of reduced frequency.However,it is quite striking that little can be found in the open literature about the mechanism to the observations.In this paper,a numerical investigation is carried out to uncover the mechanism of the effect of reduced frequency on flutter stability and the least stable IBPA.The NASA rotor 67 has been used as the test vehicle with its first bending and torsion modes being considered.The time domain harmonic balance method together with the influence coefficient method is used to obtain the worksum-IBPA curves for all cases.It is found that:1)the deterioration of flutter stability with the decrease of reduced frequency is dictated by the dominant decrease of aerodamping due to a blade own vibration;2)the increase of the least stable IBPA with the decrease of reduced frequency arises largely from the increase of the least stable IBPA of the aerodamping from the nearest blade on a blade pressure side.

Baseline Characteristics and Treatment Patterns of the Patients Recruited to the China Registry of Hepatitis B

Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis B.Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data.Exclusion criteria were patients with hepatocellular car-cinoma.The baseline clinical,laboratory and treatment pro-files were analyzed.Results: Finally,40,431 patients were included.The median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,respectively.The propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in 2016.Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study.About half of the patients were HBeAg-positive.NAs were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.

HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog:New Switch Study

Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Influence of soil texture on the process of subsurface drainage in saturated-unsaturated zones

This study addressed the problem of low drainage efficiency or even no drainage in subsurface drainage systems buried in saturated-unsaturated zones above the water table.An indoor experiment on infiltration under ponded conditions in a homogeneous soil column was performed to study the effects of soil texture on the soil wetting front morphology,soil infiltration rate,drainage efficiency of the subsurface drainage pipe,vertical distribution of soil water content and salinity along the soil column.The results showed that the drainage process of subsurface drainage pipes above the water table was quite different from that of subsurface drainage pipes below the water table.When a subsurface drainage pipe was located in sandy soil,the migration of soil water toward the bottom of the drainage pipe was significant,and the water could not be discharged into the pipe.When the drainage pipe was located in loamy clay,the movement of soil water towards the bottom of the pipe was retarded,and the water could be discharged into the pipe.During the drainage process,the drainage of the pipe can produce nonequilibrium flow in the soil,and the continuity of the nonequilibrium flow can be affected by the hydraulic conductivity of the soil above the pipe,which can result in discontinuous drainage and low drainage efficiency.The water holding capacity,permeability and aeration of soil are important factors that affect the drainage under unsaturated conditions.Eliminating the hysteresis effect and capillary barrier around the drainage pipe and adjusting water holding capacity,the permeability and aeration of soil structure through a new subsurface drainage structure may enhance the drainage efficiency of subsurface drainage pipes in saturated-unsaturated zones.