Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Lack of sufficient technical supports for sharing and management of current curriculum resource, which leads to inefficiency in searching curriculum information, has become a common issue in current higher medical education. The key to best use of increasing digital medical teaching resource lies in coping with the problems of sharing and integration. A cloud based storage platform is built to manage the teaching resource of obstetrics, which enables the efficiently sharing and integration of obstetrics related courses. The achievements gained from the platform have demonstrated to improve the work efficacy of teachers and provide students with the opportunity of systematically learning, both of which ultimately con-tribute to the improvement of the quality of theoretical and clinic teaching on obstetrics and gynecology.

Regulatory T cells are a subset of T cells, and can inhibit the body′s immune response and induce immune tolerance, which has become one of the hot topics in the field of immunological research in recent years. Regulatory T cell dysfunction and the change in the number of regulatory T cells are closely associated with the progression and treatment of autoimmune diseases, infectious diseases, tumor immune tolerance, transplant rejection, and allergic diseases. This article summarizes the surface markers and immunological mechanism of regulatory T cells, as well as the association of regulatory T cells with the pathogenesis of hepatitis B and antiviral therapy.

Objective To study the pathological alterations,such as oxidative stress,cell proliferation and insulin resistance,especially autophagy,in Alzheimer' s disease (AD) complicated with type 2 diabetes (AD + T2DM).Methods The mouse models of T2DM,AD and AD + T2DM were used in the study,and totally 80 mice were divided into four groups:control group,T2DM group,AD group and AD + T2DM group.Morris water maze was applied to test the ability of learning and memory among the above mentioned groups.In the meantime,insulin resistance index,the expression of insulin receptor substrate 2,oxidative stress,cell proliferation and autophagy were observed with chemical analysis,immunofluorescent labeling,transmission electron microscopy and Western blotting.Results On day 4,the difference of time to find Morris water maze in control group,T2DM group,AD group and AD + T2DM group ((26.08 ±4.93) s,(38.46 ± 4.07) s,(47.32 ± 5.86) s,(53.01 ± 6.12) s,F =2.454,P =0.025) was statistically significant,and the time in AD + T2DM group was longer than that in AD group (t =-3.624,P =0.033).Compared with control group,insulin resistance occurred in T2DM group,AD group and AD + T2DM group (4.35 ± 0.48,16.12 ± 3.57,7.03 ± 3.11,18.78 ± 5.06,F =5.602,P =0.009),and the reduction of insulin receptor substrate 2 expression,the oxidative stress reaction,neural proliferative suppression and autophagy (F =418.344,222.514,436.250,113.934,23.772,35.469,all P ＜ 0.05) were induced in T2DM group,AD group and AD + T2DM group,which were more serious in AD + T2DM group than in AD group (t =-2.796,21.723,-8.041,9.037,-4.403,-32.011,-26.593,all P ＜0.05).Conclusion AD + T2DM mice suffered more serious cognitive impairment than AD and T2DM mice.The oxidative stress levels of AD + T2DM mice were upregulated,and thus led to the inhibition of cell proliferation,eventually leading to promotion of autophagy.

Objective To evaluate the effects of the short-term intervention lifestyle intervention on metabolic measurements of community patients with impaired glucose regulation (IGR). Methods A total of 90 IGR participants were randomly assigned to the control group (n=45) or the intervention group (n= 45). The subjects in the control group received routine diet and physical exercise advice once a month. The subjects in the intervention group received additional individualized diet counseling and circuit-type resistance training. Metabolic parameters were compared before or after the intervention between the two groups. Results In oral glucose tolerance test (OGTT),2-h plasma glucose (PG) and homeostasis model of insulin resistance index (HOMA-IR) were significantly decreased in the intervention group at 3 months(F= 13.47 or 82.25 ,both P < 0.05). Body mass index (t=-2.44, P<0.05), systolic blood pressure (t= -3.39, P<0.05), diastolic blood pressure (t=-3.97, P<0.05), fasting plasma glucose (t=-3.89, P<0.05),2-h PG (t=-7.22,P <0.05) ,total cholesterol (t=-2.72,P<0.05),low-density lipoprotein cholesterol (t=-2.74, P<0.05), and glycosylated hemoglobin A1 C (t=-3.73, P<0.05) were significantly declined in the intervention group compared to the control group (all P<0.05). Conclusions Intensive lifestyle intervention can significantly improve the metabolic markers of IGR subjects and should be used to prevent type 2 diabetes.