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Jingjing He, Yifei Guo, Yao Zhang, Jiajia Han, Jingwen Chen, Yidi Jia, Zhenxuan Ma, Jingwen Wu, Shenyan Zhang, Fahong Li, Richeng Mao, Jiming Zhang Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Jiming Zhang; Richeng Mao, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, People’s Republic of China, Email jmzhang@fudan.edu.cn; richengmao@gmail.comPurpose: The study aims to evaluate the effectiveness of a tenofovir alafenamide fumarate (TAF) and pegylated interferon alfa (PegIFN-α) regimen compared to a tenofovir disoproxil fumarate (TDF) and PegIFN-α therapy in patients with chronic hepatitis B (CHB).Patients and Methods: Patients who were treated with PegIFN-α in combination with TAF or TDF were retrospectively enrolled. The primary outcome measured was the HBsAg loss rate. The rates of virological response, serological response for HBeAg, and normalization of alanine aminotransferase (ALT) were also calculated. The cumulative incidences of response rates were compared between the two groups using Kaplan–Meier analysis.Results: A total of 114 patients were retrospectively enrolled in the study, with 33 receiving TAF plus PegIFN-α treatment and 81 receiving TDF plus PegIFN-α treatment. The HBsAg loss rate for the TAF plus PegIFN-α group was 15.2% at 24 weeks and 21.2% at 48 weeks, while the TDF plus PegIFN-α group had rates of 7.4% at 24 weeks and 12.3% at 48 weeks (P=0.204 at 24 weeks, P=0.228 at 48 weeks). In subgroup analysis of HBeAg positive patients, the TAF group had a higher HBsAg loss rate of 25% at week 48, compared to 3.8% in the TDF group (P=0.033). According to Kaplan–Meier analysis, the TAF plus PegIFN-α group achieved virological response more quickly than the TDF plus PegIFN-α group (p=0.013). There was no statistical difference in HBeAg serological rate or ALT normalization rate.Conclusion: There was no significant difference in the HBsAg loss between the two groups. However, subgroup analysis revealed that TAF plus PegIFN-α treatment had a higher HBsAg loss rate than TDF plus PegIFN-α treatment in HBeAg-positive patients. Additionally, TAF plus PegIFN-α treatment demonstrated better virological suppression for CHB patients. Therefore, TAF plus PegIFN-α treatment regimen is recommended for CHB patients who aim to achieve functional cure.Keywords: hepatitis B virus infection, tenofovir alafenamide fumarate, tenofovir disoproxil fumarate, interferon, functional cure, combination therapy

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of enveloped DNA viruses. Recent studies have found that host factors can suppress HBV replication. HBV envelope proteins are reported to be degraded by the endoplasmic reticulum-associated degradation (ERAD) pathway. As a component of the ERAD pathway, suppressor of lin-12-like 1 (SEL1L) was earlier found to be upregulated in the inactive carrier phase of chronic HBV infection relative to that in the immune tolerant phase. However, the role of SEL1L in regulating HBV replication remains largely unknown. In this study, we found the levels of HBV RNA, DNA, and core and envelope proteins to be significantly downregulated by SEL1L overexpression and upregulated by SEL1L silencing in Huh7 cells transiently transfected with an overlength HBV genome. Similar upregulation was observed in HepG2.2.15 cells as well. SEL1L co-localized with HBV surface antigen (HBsAg), which changed its staining pattern. Treatment with an inhibitor of ERAD pathway remarkably increased intracellular S protein. Surprisingly, silencing SEL1L to block the ERAD pathway activated an alternative ER quality control (ERQC)-autophagy pathway, which might account for the increased HBV RNAs and core protein. Together, our results demonstrate that SEL1L is a host restriction factor that exerts anti-HBV effect through ERAD and alternative ERQC-autophagy pathway. OA Förderung 2019

Nitraria tangutorum occupy the largest area among all natural vegetation in the lower reaches of the Shiyang River.The plant is tolerant to high-temperature,drought,salts,wind-erosion and sand burial,so it has been highly regarded as a sand fixation plant.The formation and development of N.tangutorum nebkhas is also the result of interaction between vegetation and environment in the process of community succession.The research on the structure and quantitative characteristics of N.tangutorum communities in different succession stages can provide a scientific basis for its conservation and restoration.Based on growth and habitats,N.tangutorum communities at different succession stages: early development,stable equilibrium,deterioration,and serious deterioration,were selected to look into species composition,life form spectrum,coverage,species diversity and community similarities.The results demonstrated that the species composition of the plant community was relatively simple.There were 29 plant species,belonging to 25 genuses and 11 families.Zygophyllaceae and Chenopodiaceae showed up in all succession processes.Gramineae dominated the early development stage,whereas Chenopodiaceae was predominant in the stable equilibrium.At the deterioration stage,species of Zygophyllaceae were prevailing after N.tangutorum community came to deterioration.Chenopodiaceae was dominant again when the succession was at the serious deterioration phase.The number of species abated significantly from the early development to the stage of stability,whereas that increased gradually from the stable equilibrium to deterioration and serious deterioration.Throughout the succession process,the proportion of annuals was increasing by degrees,from about 26% at the early development to 80% at the serious deterioration stage.So,the degradation succession of desert plants was a course of gradual increase of annual plants.The proportion of phaenerophyte was gradually increasing from the early development to the deterioration stage,and decreasing at the stage of serious deterioration.Chamaephytes had larger quantities at the early development stage,were decreasing at the stable equilibrium stage,and disappeared at the deterioration stage.Hemicryptophyte were prevailing at the early development stage,decreasing at the stable equilibrium phase,and disappeared at the deterioration period,even only 1 species of hemicryptophyte existing at the serious deterioration phase.There was no cryptophytes in all succession processes.The annual variations of community coverage at different succession stages were various and the maximum and minimum values of the community coverage at different succession stages occurred in various months.The mean community covering rates in May to October was in the order stable equilibrium,early development,deterioration,serious deterioration.With respect to community diversity at different stages,the Simpson index,the Shannon-Weiner index,and the Pielou evenness index showed fluctuation.The Simpson and Shannon-Wiener indexes rank the stages in the order of early development,severe decline,decline,and stability.Meanwhile,the pielou index ranked as follows: recession,serious recession,stability,and early development.The species composition of N.tangutorum communities in different succession stages was various with a level of similarities.Coefficients of similarity between communities at the stages of deterioration and serious deterioration were lightly similar,and those between other communities were dissimilar.The closer the successional series,the higher the similarity coefficients.

Motion is an important cue to the intentions of active agents in environments involving collaboration and competition. We demonstrate this in the domain of ice hockey. We develop a framework to represent and reason about hockey behaviors using as input actual player motion trajectory data tracked from game video and supported by knowledge of hockey strategy, game context and specific player profiles. The raw player motion trajectory data consists of space-time point sequences of forward/backward skating registered to rink coordinates. This is augmented with knowledge of possession of the puck and specific player attributes (e.g., shoots left, shoots right). We focus on the analysis of three clearly identifiable situations: 2-on-l offensive attacks, defensive zone breakouts and power play shots from the point. We use a Finite State Machine (FSM) model to represent our total knowledge of a given situation and develop evaluation functions for primitive hockey behaviors (e.g., pass, shot). Based on the augmented trajectory data, the FSMs and the evaluation functions, we describe what happened in each identified situation, assess the outcome, estimate when and where key play choices were made, and attempt to predict whether better alternatives were available to achieve understood goals. A textual natural language description and a simple 2D graphic animation of the analysis are produced as the output. The graphic animation is useful for interactive visualization and debugging. The textual description also provides potentially useful annotation for large databases of player motion trajectories. The framework is flexible to allow the substitution of different analysis modules and extensible to allow the inclusion of additional hockey situations. We expect that the methodology and the framework can be generalized and applied in other domains, such as soccer, basketball, traffic flow control and people surveillance.