Innate immune targets of hepatitis B virus infection

Approximately 400 million people are chronically infected with hepatitis B virus(HBV) globally despitethe widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.

Crosstalk between innate and adaptive immunity in hepatitis B virus infection

Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is res-ponsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.

Preparation of crystalline rare earth carbonates with large particle size from the lixivium of weathered crust elution-deposited rare earth ores

Crystalline rare-earth(RE)carbonates having large particle size were prepared from the lixivium of weathered crust elution-deposited rare-earth ores using the precipitation method with ammonium bicarbonate as the precipitant.Their chemical composition was studied using elemental and thermogravimetric analyses(TGA),and their structure and morphology were characterized using Fourier transform infrared(FTIR)spectroscopy,X-ray diffraction(XRD),and scanning electron microscopy(SEM).The results demonstrate that the crystalline rareearth carbonate is a hydrated basic carbonate or oxycarbonate and not astable intermediate carbonate in the process of thermal decomposition.The particle size of crystalline rare-earth carbonates with large particle size is in the range of 50–200μm.With an RE2O3 content of up to 95wt%,the quality of crystalline rare-earth carbonates is higher compared to the Chinese National Standard(GB/T 28882–2012).The quality of the product is superior to the Chinese National Standard.

A versatile framework for analyzing galaxy image data by incorporating Human-in-the-loop in a large vision model

The exponential growth of astronomical datasets provides an unprecedented opportunity for humans to gain insight into the Universe.However,effectively analyzing this vast amount of data poses a significant challenge.In response,astronomers are turning to deep learning techniques,but these methods are limited by their specific training sets,leading to considerable duplicate workloads.To overcome this issue,we built a framework for the general analysis of galaxy images based on a large vision model(LVM)plus downstream tasks(DST),including galaxy morphological classification,image restoration object detection,parameter extraction,and more.Considering the low signal-to-noise ratios of galaxy images and the imbalanced distribution of galaxy categories,we designed our LVM to incorporate a Human-in-the-loop(HITL)module,which leverages human knowledge to enhance the reliability and interpretability of processing galaxy images interactively.The proposed framework exhibits notable fewshot learning capabilities and versatile adaptability for all the abovementioned tasks on galaxy images in the DESI Legacy Imaging Surveys.In particular,for the object detection task,which was trained using 1000 data points,our DST in the LVM achieved an accuracy of 96.7%,while ResNet50 plus Mask R-CNN reached an accuracy of 93.1%.For morphological classification,to obtain an area under the curve(AUC)of~0.9,LVM plus DST and HITL only requested 1/50 of the training sets that ResNet18 requested.In addition,multimodal data can be integrated,which creates possibilities for conducting joint analyses with datasets spanning diverse domains in the era of multi-messenger astronomy.

Tribology of rotating band and gun barrel during engraving process under quasi-static and dynamic loading

The engraving process of a projectile rotating band is one of the most basic research aspects in interior ballistics,which has not been thoroughly understood thus far.An understanding of this process is of great importance from the viewpoints of optimal design,manufacturing,use,and maintenance of gun and projectile.In this paper,the interaction of copper and nylon rotating bands with a CrNiMo gun barrel during engraving was studied under quasi‐static and dynamic loading conditions.The quasi‐static engraving tests were performed on a CSS‐88500 electronic universal testing machine(EUTM)and a special gas‐gun‐based test rig was designed for dynamic impact engraving of the rotating bands.The mechanical behaviors of copper and nylon were investigated under strain rates of 10^(−3) s^(−1) and 2×10^(3) s^(−1) using an MTS 810 and a split Hopkinson pressure bar(SHPB),respectively.Morphologies of the worn surfaces and cross‐sectional microstructures were observed with scanning electron microscope(SEM)and optical microscope(OM).It was found that large deformation and severe friction occur during engraving.The surface layer is condensed and correlated with a hardness gradient along the depth from the top worn surface.The structure of the rotating band and gun bore,band material,and loading rate have great effects on band engraving.The flow stress‐strain of the copper strongly depends on the applied strain rate.It is suggested that strain rate and temperature play significant roles in the deformation mechanism of rotating bands.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir

Background and Aims:Chronic hepatitis B(CHB)can cause liver fibrosis and lead to cirrhosis and cancer.As the effectiveness of antiviral therapy to reverse liver fibrosis is limited,We aimed to evaluate the effect of An-Luo-Hua-Xian pill(ALHX)on fibrosis regression in CHB patients treated with entecavir(ETV).Methods:Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX(ETV+ALHX)between October 1,2013 and December 31,2020.Demographic,laboratory,and liver histology data before and after 78 weeks of treatment were collected.The Ishak fibrosis score(F)was used and fibrosis regression required a decrease in F of≥1 after treatment.Results:A total of 780 patients were enrolled,and 394 with a second liver biopsy after treatment were included in the per-protocol population,132 in ETV group and 262 in ETV+ALHX group.After 78 weeks of treatment,the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients:124/211(58.8%)vs.45/98(45.9%),p=0.035.The percentage of patients with a decreased liver stiffness measurement(LSM)was higher in the ETV+ALHX group:156/211(73.9%)vs.62/98(63.%),p=0.056.Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression[odds ratio(OR)=1.94,p=0.018],and a family history of hepatocellular carcinoma was on the contrary.(OR=0.41,p=0.031).Conclusions:ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Unsatisfying antiviral therapeutic effect in patients with mother-tochild transmissed chronic hepatitis B virus infection: a prospective multi-center clinical study

Background:Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B(HBV)carriers infected by mother-to-child transmission(MTCT).This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group.Methods:The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016.Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected.Results:Patients infected by MTCT were more likely to have e antigen positive(68.6%vs.58.2%,x^2=-2.491,P=0.012)than those with horizontal transmission.However,in patients with MTCT,levels of alkaline phosphatase(ALP)(P=0.031),Fibroscan(P=0.013),N-terminal propeptide of Type III procollagen(PIIINP)(P=0.014),and Laminin(LN)(P=0.006)were high,in contrast to the patients with horizontal transmission for whom the levels of albumin(ALB)(P=0.041),matrix metalloproteinase-3(MMP-3)(P=0.001)were high.The 47.2% of patients with MTCT and 36.8%of those with horizontal transmission had significant liver fibrosis(P=0.013).Following antiviral therapy for 78 weeks,21.2%and 38.0%patients with MTCT and horizontal transmission acquired hepatitis B e antigen(HBeAg)clearance,respectively(P=0.043),and the virological response rates were 54.7%and 74.1%in the MTCT and horizontal groups,respectively(P=0.005).MTCT was a risk factor for HBeAg clearance and virological response.Conclusion:Adult patients with MTCT were more prone to severe liver diseases,and the therapeutic efficacy was relatively poor,which underlined the importance of earlier,long-term treatment and interrupting perinatal transmission.

Analysis of platelet parameters and activation markers in hematologic metastases of lung cancer

To the Editor: Although the causes and mechanisms of lung cancer (LC) are still not clear, with the advances in science and technology and the progress in research methods, it has been shown that tumor cells aggregate with platelets (PLTs) and escape being recognized by the immune system. They adhere to distant vascular endothelial cells and continue to metastasize, invade and grow through the blood circulation.[1] Therefore, the hypercoagulable state and enhancement of PLT functions promote tumor growth, invasion, and metastasis.[2,3] Therefore, the effective reduction in PLT counts and their activities can help reduce the progression and prognosis of LC. We conducted this research to explore the effect of the tumor on circulating platelets in patients with LC.