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

This article reported a typical case of paroxysmal kinesigenic dyskinesia(PKD).The patient was a 26-year-old female with a medical history of 10 years.The patient manifested as paroxysmal choreoathetosis of the limb and head triggered by sudden movement in a quiet state,without sensory aura.The symptoms resolved spontaneously after tens of seconds.She was conscious during and between attacks,had a clear family history and a normal neurological examination.No abnormalities were found in brain magnetic resonance image and electroencephalogram.Genetic test showed a frame-shift mutation of c.776del in PRRT2 gene of the proband and her father with similar phenotype.The patient was diagnosed with PKD according to the diagnostic criteria for PKD.The symptoms were significantly relieved after one month of oxcarbazepine treatment with good prognosis.PKD is a rare movement disorder.The patient has typical symptoms,and the mutation site has not been reported in the Human Gene Mutation Database.Therefore,this article enriched the pathogenic gene mutation spectrum of PKD,provided a basis for genetic counseling of PKD and increased the awareness of this rare disease among physicians.

Objective To understand the health-related quality of life (HRQOL) of migrant workers with pneumoconiosis who received basic medical treatment in Hunan Province. Methods A total of 613 migrant workers with pneumoconiosis who received basic medical treatment and assistance in Hunan Province was selected as the study subjects using stratified random sampling method. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to assess their HRQOL. Results The abnormality of the five dimensions of the EQ-5D health description system, from high to low, were as follows： daily activities, mobility, pain/discomfort, anxiety/depression, and self-care, with the abnormal rates of 50.9%, 46.8%, 41.1%, 21.0%, and 14.5%, respectively. The visual analogue scale (VAS) score of EQ-5D was (63.5±18.6) points. Patients with stage Ⅲ pneumoconiosis had high abnormality in mobility, daily activities, and pain/discomfort compared with those with stage Ⅰ and Ⅱ disease (all P<0.02). Patients in stage Ⅱ and Ⅲ of pneumoconiosis had higher incidence of anxiety/depression compared with those with stage I disease (all P<0.02). Patients with complications in addition to pneumoconiosis had higher abnormality in mobility, self-care, and pain/discomfort compared to those with simple pneumoconiosis or those eligible for lung lavage treatment (all P<0.02). Patients with simple pneumoconiosis had a higher incidence of anxiety/depression compared with those eligible for lung lavage treatment (P<0.02). Patients with stage Ⅲ pneumoconiosis had lower average VAS scores compared with stage Ⅰ and Ⅱ patients (all P<0.02). Patients with simple pneumoconiosis or those with complications had lower average VAS scores compared with those eligible for lung lavage treatment (all P<0.05). Conclusion The HRQOL of pneumoconiosis patients among migrant workers needs improvement, especially for patients with stage Ⅲ disease and those with complications. This study indicates the need of optimizing policies, raising the hospitalization expense limit for critically ill patients with stage Ⅲ pneumoconiosis or with complications, and improving their HRQOL.

ObjectiveTo investigate the effect of Qiling Baitouweng Tang （QLBTWT） on proliferation and apoptosis， Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway and interleukin-10 （IL-10） in diffuse large B-cell lymphoma （DLBCL）. MethodWith human DLBCL cells OCI-LY10 and U2932 as research objects， cell proliferation was detected by cell counting kit-8 （CCK-8） assay. After treatment with 0， 4.6， 9.3， 18.7， 37.5， 75， 150 mg·L^-1 QLBTWT for 24 h， the half-inhibitory concentration （IC₅₀） of OCL-LY10 and U2932 cells was calculated to be 9.33， 16.13 mg·L^-1， respectively， based on which， 9.5， 19， 38 mg·L^-1 QLBTWT were selected for subsequent experiments. After 0， 9.5， 19， 38 mg·L^-1 QLBTWT treatment for 24 h， the zymogen activities of Caspase-3， Caspase-8 and Caspase-9 in OCI-LY10 and U2932 cells were detected using corresponding activity assay kits （colorimetric）， and the IL-10 expression was detected by enzyme-linked immuno sorbent assay （ELISA）. The apoptosis rate and cell cycle of OCI-LY10 and U2932 cells treated with different concentrations of QLBTWT for 24 h were detected by flow cytometry. The expressions of apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved poly adenosine diphosphate ribose polymerase （cleaved PARP）， cleaved Caspase-3］， JAK2， STAT3， phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3） pathway proteins， and c-Myc protein in OCL-LY10 and U2932 cells after 24 h treatment with 0， 9.5， 19， 38 mg·L^-1 QLBTWT were all tested by Western blot. ResultAfter QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， cell proliferation was inhibited in each QLBTWT group compared with that in the control group （P<0.05， P<0.01）. The zymogens of Caspase-3， Caspase-8 and Caspase-9 were activated （P<0.01）， and there was an increase in cell apoptosis （P<0.05， P<0.01） and cell cycle arrest at Gap phase1 （G₁） phase in 9.5， 19 and 38 mg·L^-1 QLBTWT group （P<0.05， P<0.01）. After 9.5， 19 and 38 mg·L^-1 QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， the expressions of Bcl-2， p-JAK2 and p-STAT3 proteins were decreased （P<0.01）， and the expressions of Bax， cleaved PARP and cleaved Caspase-3 proteins were increased （P<0.01）， but no significant change was observed in the expressions of JAK2 and STAT3 proteins. Compared with the conditions in the control group， the expressions of c-Myc， p-JAK2， and p-STAT3 proteins were down-regulated in 19 mg·L^-1 QLBTWT group and 19 mg·L^-1 QLBTWT+10 μg·L^-1 IL-10 group （P<0.05， P<0.01）， and up-regulated in 10 μg·L^-1 IL-10 group （P<0.05， P<0.01）， while there was no difference in JAK2/STAT3 proteins. ConclusionQLBTWT can inhibit proliferation and induce apoptosis of human DLBCL cells OCI-LY10 and U2932， and the potential mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.

By reviewing the materia medica， medical books and scripture history， combining modern and contemporary literature and field investigation， this paper systematically reviewed the name， origin， scientific name， producing area， quality， harvesting and processing of Scorpio in famous classical formulas to clarify the relationship between ancient and modern times and provide a reference basis for the development of related famous classical formulas. After the textual research， it can be seen that there are many names of Scorpio， and most of the materia medica use Xie or Quanxie as the official name. The origin of Scorpio used in the past dynasties is Buthus martensii， which is the same in ancient and modern times. B. martensii is mainly distributed in the central and eastern parts of China， as well as Mongolia， Korea and other places， located in East Asia. Therefore， pharmaceutical workers in China mostly continue to use the early Chinese name， that is， Dongya Qianxie， while modern Scorpiones taxonomists set its Chinese name as Mashi Zhengqianxie. In order to maintain the stability and continuity of the origin of Scorpio， the previous editions of Chinese Pharmacopoeia have always used the name of B. martensii. The geo-authentic producing area of Scorpio， which has been respected in the past dynasties， was Qingzhou， Shandong. Until the Republic of China， due to the different processing methods in the production area， the geo-authentic producing area expanded to Yu county， Henan， with Yu county as the distribution center， the best quality of Scorpio is produced by boiling in clear water and drying after boiling. The origin processing of Scorpio is mainly divided into clean water and salt water boiling and then drying， where the method of boiling with salt water was first described in Bencao Yuanshi， the purpose is antiseptic and suitable for storage， and the salt should be washed away when used clinically. There are few processing methods of Scorpio， in ancient times， it was used for roasting or frying after removing the feet， in modern times， it is mostly to remove impurities， wash and dry. Scorpio is not only used for medicinal purposes， but also has the habit of eating in many areas， so the consumption of resources is relatively large， and it is still mainly harvested from the wild， resulting in the decrease of wild resources year by year. Based on the research conclusion， it is recommended that B. martensii， which is produced in Qingzhou， Luyi or Yuzhou， should be used in the the development of famous classical formulas containing Scorpio， and the origin processing is preferable to be dried after boiling with water， and the processing specification should be selected as raw products. And B. martensii in geo-authentic producing areas was used as the seed source to establish a standardized breeding base to ensure the sustainable development of the resources of Scorpio.

Objective:To evaluate the application value of three-dimensional shear wave elastography(3D-SWE) with quantitative parameters and qualitative analysis of stiff rim sign in differentiating benign and malignant breast masses.Methods:One hundred and seventeen female patients (121 breast masses) admitted to the First Affiliated Hospital of Soochow University from January 2020 to February 2021 were examined by conventional ultrasound, two-dimensional shear wave elastography (2D-SWE) and 3D-SWE. Surgical or puncture pathology were used as the gold standard, the ROC curves of 2D-SWE and 3D-SWE were drawn to obtain the optimal qualitative and quantitative indicators. Afterwards, BI-RADS category was adjusted according to the optimal indicators, which could be used to evaluate the diagnostic value in differentiating benign and malignant breast masses.Results:The area under ROC curve (AUC) of BI-RADS category was 0.846, the sensitivity and specificity were 89.6% and 79.6%, respectively. The AUC value of mass-to-fat elasticity ratio(Eratio) of coronal plane was 0.869, which was the highest among all quantitative parameters and was significantly higher than that of 2D-SWE ( P<0.05). In addition, the AUC value of stiff rim sign of coronal plane was significantly higher than those of 2D-SWE, sagittal plane and transverse plane (All P<0.05). The AUC of combination of stiff rim sign of coronal plane and conventional US was 0.901, which was significantly higher than that using conventional ultrasound alone( P<0.05). Conclusions:Compared with 2D-SWE, Eratio and stiff rim sign of coronal plane of 3D-SWE yield better diagnostic efficiency.Adjusting stiff rim sign coronal plane to BI-RADS category can effectively improve the diagnostic efficiency.

Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb. Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain, very few studies have been carried out on the use of karacoline due to its potential toxicity. In this study, we selected key matrix metalloproteinases (MMPs), collagen II, and aggrecan as targets due to their association with intervertebral disc degeneration (IDD). Using these targets, we then used network pharmacology to predict a series of molecules that might exert therapeutic effects on IDD. Of these molecules, karacoline was predicted to have the best effect. Tumor necrosis factor (TNF)-αis known to promote the degeneration of the extracellular matrix in IDD. We therefore applied different concentrations of karacoline (0, 1.25, or 12.88μM) along with 100 ng/mL TNF-αto rat nucleus pulposus cells and found that karacoline reduced the expression of MMP-14 in IDD by inhibiting the nuclear factor (NF)-κB pathway, while collagen II and aggrecan expression was increased. This suggested that extracellular matrix degradation was inhibited by karacoline (P<0.05). Our data therefore reveal a new clinical application of karacoline and provide support for the use of network pharmacology in predicting novel drugs.

Objective To investigate the effects of PM2.5 exposure on the quality of IVF eggs and the quality of embryos. Methods 40 healthy female Kunming mice and 10 male mice were used in this study. 40 female mice were randomly divided into 4 groups:low dose of PM2.5 group (1.5 mg/kg),middle dose of PM2.5 group (7.5 mg/kg),high dose of PM2.5 group (15 mg/kg) and the control group (to give the same volume of saline),with 10 mice in each group. PM2.5 was administered via tracheal instillation. The number of oocytes ,fertilization rate ,abnormal fertilization rate ,2PN cleavage rate ,2PN blastocyst rate and blastocyst formation rate were determined ,as well as levels of TNF-α and IFN-γ. Results The number of oocytes , fertilization rate and cleavage rate of 2PN were significantly higher in PM2.5 high dose of PM2.5 group than those in PM2.5 group. The rate of high quality embryos and blastocyviast formation were decreased ,but abnormal fertilization rate were decreased (P < 0.05). The expressions of TNF-α and IFN-γ in the high-dose of PM2.5 group were significantly higher than those in the middle-dose of PM2.5 group and in the low-dose of PM2.5 group(P < 0.05),while the expressions of TNF-α and IFN-γ in the middle dose group was significantly higher than those in the low dose group(P<0.05). Conclusions PM2.5 exposure can decrease the number of oocytes , fertilization rate ,2PN cleavage rate ,2PN blastocyst rate and blastocyst formation rate of in vitro fertilization in mice.

Objective To observe the protective effect of epigallocatechin gallate(EGCG)on homocysteine-induced proliferation of human aortic smooth muscle cells(HASMCs).Methods HASMCs were served as objects,which were cultured in various media,including Hcy(100,200,500,1 000 μmol/L),EGCG(EGCG 5,10,20 μmol/L),Hcy+EGCG(Hcy 500 μmol/L+EGCG 5 μmol/L,Hcy 500 μmol/L+EGCG 10 μmol/L,Hcy 500 μmol/L+EGCG 20 μmol/L)for 24 h.The proliferation of HASMCs was determined by cell counting kit-8(CCK-8)and bromodeoxyuridine(BrdU)labeling.The level of angiotensin Ⅱ(AngII)was determined by enzyme-linked immunosorbent assay(ELISA),and the level of angiotensin Ⅱ type 1 receptor(AT-1R)was determined by Western blot.Results After treatment for 24 h,compared with the control group,the proliferation of cells in different Hcy groups significantly increased(P<0.05),while the proliferation of cells in EGCG 10 and 20 μmol/L group significantly reduced(P<0.05).Compared with the Hcy 500 μmol/L group,cell proliferation significantly reduced after adding EGCG 10 and 20 μmol/L(P<0.01),while the expression levels of AngII and AT-1R decreased significantly(P<0.01).Conclusion EGCG can inhibit Hcy-induced proliferation of VSMCs.