In situ architecture and membrane fusion of SARS-CoV-2 Delta variant

Among the current five Variants of Concern, infections caused by the SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, architecture of intact Delta virions remains veiled. Moreover, molecular evidences for the detailed mechanism of S-mediated membrane fusion are missing. Here we reported the in situ structure and distribution of S on the authentic Delta variant, and discovered invagination in the distinctive Delta architecture. We also captured fusion snapshots from the virus-virus fusion events, provided structural evidences for Deltas attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S over that of the Wuhan-Hu-1 S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant. In BriefCryo-ET of intact SARS-CoV-2 Delta variant revealed its distinctive architecture and captured snapshots of its membrane fusion in action.

Molecular architecture of the SARS-CoV-2 virus

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins and the complexes of the spike (S) proteins with the cellular receptor ACE2 or neutralizing antibodies, detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in both pre- and postfusion conformations were determined to average resolutions of 8.7-11 [A]. Compositions of the N-linked glycans from the native spikes were analyzed by mass-spectrometry, which revealed highly similar overall processing states of the native glycans to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNP) and its higher-order assemblies were revealed. Overall, these characterizations have revealed the architecture of the SARS-CoV-2 virus in unprecedented detail, and shed lights on how the virus packs its [~]30 kb long single-segmented RNA in the [~]80 nm diameter lumen.

Hysterosalpingographyand MRIfeaturesofintrauterineadhesion / 实用放射学杂志

Objective Toevaluatehysterosalpingography(HSG)and MRImanifestationsofintrauterineadhesion(IUA).Methods 40patientswithIUAconfirmedbyhysteroscopyunderwentHSGand MRIexamination.Wefoundoutthefeaturesofthoseimages, andworkedoutthedetectablerateofeachexamination.Results Inall40patients,19patientsweremildIUAprovedbyhysteroscopy,in which10patientswerediscoveredbyHSG,10patientsby MRIT2WI,16patientsby MRICUBE.16patientsweremiddleIUA,in which9patientswerediscoveredbyHSG,10patientsbyMRIT2WI,16patientsbyMRICUBE.5patientsweresevereIUA,allpatients werediscoveredbyHSG,MRIT2WIand MRICUBE.Andinallcases,therewere12casesofmembraneadhesions,inwhich5cases wereshowninHSG,8casesinMRIT2WIand10casesinMRICUBE.23caseswerefibrousadhesions,inwhich12caseswereshown in HSG,17casesinMRIT2WIand22casesinMRICUBE.5patientsweremuscularadhesions,allpatientswerediscoveredbyHSG, MRIT2WIandMRICUBE.Conclusion ComparingtoHSG,MRIexaminationshowshigherdetectablerateofIUA.MRICUBEsequences playsanimportantpartinthediagnosisofIUA.

Relationship between gH genotyping and clinical characteristics of children with congenital cytomegalovirus infection / 中华儿科杂志

Objective@#To study the relationship between human cytomegalovirus (HCMV) envelope glycoprotein gene H and clinical features of children with congenital cytomegalovirus infection.@*Methods@#A cohort study was conducted. Newborns diagnosed with congenital cytomegalovirus infection, hospitalized in the Department of Neonatology and Neonatal Intensive Care Unit (NICU) of the Children′s Hospital, Zhejiang University School of Medicine, were included from July 2013 to December 2015.HCMV-DNA gH typing in urine, sputum or blood was conducted. Patients then were divided into gH1 group and gH2 group according to gH genotypes. Patients′ data during hospitalization in newborn and 3-5 years of follow-up were collected.The relationships between gH genotype and clinical manifestations, laboratory examinations, hearing loss and neurological prognosis were analyzed by chi-square test, t test and non-parametric test.@*Results@#A total of 21 cases were enrolled as congenital HCMV infection and followed-up for 3-5 years. Among them, 14 (67%) were gH1 type and 7 (33%) were gH2 type. No mixed infection was found. In the two groups, there were no significant differences in the ratio of males (9/14 vs. 3/7,P=0.397), or birth weight ((2 609±686) vs. (3 021±451) g, t=-1.436, P=0.167). Gestational age of gH1 group was younger than that of gH2 group (38 (29-40) vs. 39(38-40) weeks, Z=-2.18, P=0.029). Moderate to severe hearing loss detected by neonatal auditory brainstem response were found in 40 ears (20 cases). It was higher in gH1 group than that in gH2 group (4/22 vs.0/18, χ2=5.145, P=0.023). In the imaging examination of the nervous system, the Alarcon score of gH1 group was lower than that of gH2 group (0.4±0.3 vs. 1.3±1.1, t=-2.459,P=0.024).No significant statistical difference was found in the probability of motor or language development lag in gH2 group and gH1 group (4/7 vs.4/14, P=0.346).@*Conclusions@#Compared with gH2 infection, gH1 infection in children has a younger gestational age. The major type of hearing loss in neonatal period is gH1 infection. Children with gH2 congenital infections are more likely to suffer from nervous systems damage.

Clinical Investigation and Analysis of the Combination Use of Western Medicines and Chinese Patent Drugs Containing Salvia Miltiorrhiza or Its Active Ingredients / 中国药师

Objective: To understand the combination use and rationality of Chinese patent drugs containing Salvia Miltiorrhiza or its active ingredients and western medicines to provide reference for regulating prescriptions and improving rational drug use level. Methods: The prescriptions of outpatients in our hospital during January 2016 and December 2016 were collected by a retrospective study method, and the ones with the combination use of Chinese patent drugs containing Salvia Miltiorrhiza or its active ingredients and western medicines were analyzed. The rationality of the combination use was analyzed in aspects of physicochemical properties, phar-macological effects, pharmacodynamics and pharmacokinetics. Results: Totally 257 730 prescriptions were examined selectively, and among them, 8 894 were with the combination use of western medicines and Chinese patent medicines containing Salvia Miltiorrhiza or its active ingredients including 1 213 irrational prescriptions (13. 64% ). The irrational prescriptions showed such problems as antago-nism in pharmacologic action causing decreased efficacy (510, 42. 04% ), overlaying in pharmacological effects causing increased effi-cacy (492, 40. 56% ), precipitation because of physical and chemical reactions and chemical taboos (299, 24. 65% ) and reduced bioavailability and affected efficacy due to complex reactions (174, 14. 34% ). Conclusion: The combination use of western medicines and Chinese patent medicines containing Salvia Miltiorrhiza or its active ingredients should be careful to avoid irrational problems. When they are auditing prescriptions and monitoring medication, clinical pharmacists should strengthen intervention of the combination use of Chinese patent medicines and western medicines reasonably combining with physical and chemical properties of medicines, phar-macological effects, pharmacodynamics and other characteristics.

Somatic KRAS mutation in an infant with linear nevus sebaceous syndrome associated with lymphatic malformations: A case report and literature review.

RATIONALE: Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome, characterized by nevus sebaceous,central nervous system (CNS), ocular and skeletal abnormalities. The present study describes KRAS somatic mosaic mutation in a case of LNSS with lymphatic malformations (LMs). PATIENT CONCERNS: A 4-month-old female with a clinical diagnosis of LNSS presented with infantile spasms, mental retardation, skull dysplasia, ocular abnormalities, congenital atrial septal defect, and LMs. DIAGNOSIS: Cervical ultrasonography revealed a 4.6 × 4.6 × 2.2cm no echo packet with clear boundary in the subcutaneous tissues of the right neck. The neck MRI indicated a cyst in the subcutaneous tissues of the right neck. Whole-exome sequencing revealed a low-level heterozygous mutation of the KRAS gene (c.35C > T; p.G12D, 19%) in the skin lesion sample. This mutation was not present in the blood samples of the patient and her parents. INTERVENTIONS: The patient received sclerotherapy with paicibanil (OK-432) injection for the cyst. OUTCOMES: Following 1 year of treatment, the patient exhibited fewer seizures. The mental and motor development was significantly improved. The patient can currently walk with assistance and speak simple words. LESSONS: LNSS is a rare, congenital neurocutaneous syndrome consisting of a spectrum of abnormalities involving the skin, central nervous system, eyes, LMs and other systems. LNSS can be caused by postzygotic somatic mutation in the RAS family of genes. Multidisciplinary evaluation and treatment is needed.

Removal of protein extract from moringa oleifera seed presscake on turbidity water / 中国生化药物杂志

Objective To study the removal effect of Moringa seedprotein on turbidity water. Methods The protein of Moringaoleifera seed was extracted by salting out and salting out methodand the protein concentration of Moringa oleifera seed wasdetermined by Coomassie blue staining;The removal effect of Moringa seed protein on turbidity water was determined by coagulation test.The contents of COD, ammonia nitrogen and nitrate nitrogen in the water were determined to determine the effect of Moringa seed protein on water quality. Results The experimental results showed that Moringa oleifera seed protein has good removal effect on high and medium turbidity water, and its removal effect is in a dose - dependent manner.The removal rate of 7 mg/L of Moringa seed protein to high and medium turbidity water reached 92.25 ％ and 64.71 ％ respectively. But the removal efficiency of low turbidity water was less than 7 mg/L, the removal rate of low turbidity water was only 31.91％.The results of determination of COD, ammonia nitrogen and nitrate nitrogen showed that the Moringa seed protein did not increase the content of organic matter in the water while removing turbidity effectively. Conclusion Moringa oleifera seed protein has a certain removal effect on turbidity water, among which the removal effect of high and medium turbidity water is strong, and the removal effect of low turbidity water is poor.Moringa oleifera seed protein had little effect on water quality.