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.

Curative effect of pelvic floor muscle exercise on urinary incontinence after radical prostatectomy-Comparisons of different approaches at different time point.

Pelvic floor muscle exercise (PFME) is widely applied for urinary incontinence (UI) after radical prostatectomy (RP). This research aimed to explore the relationship between PFME and UI after RP. We searched databases for studies that met our requirements until 17/4/2021. The UI symptoms of the PFME group and the control group were compared at 1, 3, 6 and 12 months after the operation. Subgroup analysis based on surgical approach (open radical prostatectomy vs laparoscopy & robotics radical prostatectomy) and UI definition (questionnaire vs. pad weight) were also conducted. The UI rate in PFME group is significantly lower when compared with control group at each time point. According to subgroup analysis, PFME is more effective to alleviate UI after laparoscopy & robotics radical prostatectomy when compared with open RP at mid-term (3s and 6 months) whereas no significant difference was detected between two groups at short (1 month) or long (12 months) term. According to this meta-analysis, post-operation PFME treatment can effectively alleviate the symptoms of UI after RP at any time point; pre-operation PFME alone was not sufficient to relieve UI. Compared with open prostatectomy, PFME is more effective for the UI after laparoscopy & robotics radical prostatectomy.

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

Effects of body mass index, appendicular skeletal muscle mass index and serum lipid levels on the risk of tumor progression in patients with high-risk renal clear cell carcinoma / 中华临床营养杂志

Objective:To evaluate the potential effects of serum lipid levels, appendicular skeletal muscle mass index (ASMI) and body mass index (BMI), together with its dynamic changes, on tumor progression in renal clear cell carcinoma patients, so as to inform body weight management.Methods:This prospective cohort study included a total of 100 patients with high-risk clear cell renal cell carcinoma. Serum lipid levels were detected, ASMI and BMI were measured using bioelectrical impedance analysis and the dynamic changes of BMI were tracked. The effects of BMI, ASMI and serum lipid levels on tumor progression within 2 years were explored.Results:Patients with normal BMI and low ASMI had 5.248 (95% CI: 1.946 to 14.153, P = 0.001) times higher risk of tumor progression than those who were overweight or obese. For every 0.1-unit increase in pre-operative HDL-C, the risk of tumor progression decreased by 0.771 (95% CI: 0.631 to 0.942, P = 0.011) times. Patients who experienced more than 5% decrease in BMI compared with baseline had 5.165 (95% CI: 1.735 to 15.370, P = 0.003) times the progression risk of patients whose BMI changed within ±5% from baseline. Conclusions:The advantage of obese clear cell carcinoma patients over normal-weight patients in tumor progression-free survival may be influenced by ASMI, pre-onset involuntary weight loss and lipid levels. Therefore, patient weight management should not merely focus on absolute BMI but tailor to individual characteristics, including cancer stage, body composition and metabolic status.

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.

Patient-derived mutations impact pathogenicity of SARS-CoV-2

The sudden outbreak of the severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has spread globally with more than 1,300,000 patients diagnosed and a death toll of 70,000. Current genomic survey data suggest that single nucleotide variants (SNVs) are abundant. However, no mutation has been directly linked with functional changes in viral pathogenicity. We report functional characterizations of 11 patient-derived viral isolates. We observed diverse mutations in these viral isolates, including 6 different mutations in the spike glycoprotein (S protein), and 2 of which are different SNVs that led to the same missense mutation. Importantly, these viral isolates show significant variation in cytopathic effects and viral load, up to 270-fold differences, when infecting Vero-E6 cells. Therefore, we provide direct evidence that the SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity.

Therapeutic effect of music therapy and speech language therapy on post-stroke patients with non-fluent aphasia / 中华神经科杂志

Objective Estimating the therapeutic effect of music therapy and speech language therapy on post-stroke patients with non-fluent aphasia.Methods Eighty-four post-stroke patients diagnosed with non-fluent aphasia who came from the First Affiliated Hospital of Medical College of Shihezi University were collected between June 2012 and May 2014,then they were randomly divided into music therapy group (n =42) and speech language therapy group (n =42;including chronic (n =46) and acute groups (n =38)) based on table of random numbers.On the basis of conventionally using neurological drugs,music therapy and speech language therapy were given to the patients for one month,respectively.And language function was assessed by partial items of Chinese Version-Western Aphasia Battery before and after therapy.Results No significant changes were found in spontaneous speech,comprehension,repetition,naming and aphasia quotient in chronic and acute group patients through the music therapy and speech language therapy.Significant improvements were revealed in repetition (32.00 (15.00,53.75) vs 48.50(24.50,72.00),Z =2.147,P =0.032;33.00(14.50,49.25) vs 48.50(18.50,63.75),Z =2.018,P=0.038),naming (20.00 (8.50,34.75) vs 37.5(12.50,64.75),Z =2.298,P =0.022;19.50 (7.00,31.25) vs 34.50 (15.00,52.75),Z =2.039,P =0.041) and aphasia quotient (24.50 (10.50,37.50) vs 43.00 (18.00,64.75),Z =2.432,P =0.015;22.50 (10.00,34.50) vs 36.00 (14.00,54.00),Z =2.027,P =0.043) through music therapy and speech language therapy in chronic group patients.Comprehension was significantly improved through music therapy in chronic group patients.Repetition (24.50 (11.00,38.75) vs 46.50 (24.50,67.75),Z =2.038,P =0.043;26.50 (9.50,36.25) vs 42.50(19.00,64.25),Z =1.972,P =0.048) was significantly improved through music therapy and speech language therapy in acute group patients.And spontaneous speech (2.00 (1.00,3.75) vs 8.00 (4.00,12.75),Z =2.012,P =0.036),comprehension (51.00 (17.50,73.75) vs 85.00 (48.00,101.00),Z =2.298,P =0.022),naming (17.50(6.00,29.00) vs 37.50(16.00,58.75),Z =2.161,P =0.031) and aphasia quotient (18.00 (7.50,31.25) vs 42.50 (20.50,63.75),Z =2.256,P =0.024) were significantly improved through music therapy in acute group patients.However,no significant improvements were found in the speech language therapy group of acute patients.Conclusion The two therapies are effective in the chronic patients with non-fluent aphasia,and music therapy is also effective in acute patients with non-fluent aphasia.