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Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summaryA sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.
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The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3g or 6 g per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans. One Sentence SummaryA purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology
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Objective@#To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth.@*Methods@#HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student’s t-test was used to test means of two groups and chi-square test was used for multiple samples.@*Results@#The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm3), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ2 = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96).@*Conclusion@#AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.
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Muscle strength training plays an important role in improving limb movement function, preventing muscle atrophy and promoting muscle function recovery in patients with various bone and joint diseases. The sports function of elbow joint is closely related to people's daily life activity ability. At present, Chinese muscle strength training devices are depended on import. Therefore, it is of great significance to develop muscle strength training devices. Based on the concepts and characteristics of isometric training, isotonic training, passive training and isokinetic training, in the upper computer, the servo driver and servo motor are controlled through the LabView interface, and the real-time torque is detected by the torque sensor, realizing four training modes. The main parameters of the multi-mode elbow joint muscle strength training device meet the requirements, and the trainers have a good experience.
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Humans , Elbow Joint , Physiology , Muscle Strength , Muscle, Skeletal , Resistance Training , TorqueABSTRACT
A mathematical model of competition-type lateral flow immunoassay (LFIA) was developed to describe the dynamic process of LFIA.The competition-type LFIA was divided into two categories: TwA-competition-type LFIA and TnA-competition-type LFIA.On the basis of the developed model, the COMSOL software was exploited to simulate the dynamic process of LFIA.The simulation result demonstrated the relationships between the concentrations of substances on the test and control lines and the influence factors.In particular, the influence factors in the TwA-competition-type LFIA included the concentrations of target analyte A (0-20 mol/L) and reporter particle P (0.01-100 mol/L), and the position of the test line (5-20 mm).On the other hand, the influence factors in the TnA-competition-type LFIA included the concentrations of target analyte A (0-20 mol/L) and reporter particle P (0.01-100 mol/L), and the porosity.Experiment result showed that the developed model could be used to explore the influence of the parameters on the test results, and optimize the performance of LFIA.
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Objective To study the homology and clinical characteristics of healthcare-associated infection(HAI) due to Pseudomonas aeruginosa (P.aeruginosa)in medical intensive care unit (MICU),so as to guide the clinical prevention of P.aeruginosa transmission and improve therapeutic effect.Methods 55 P.aeruginosa strains isola-ted from 25 patients with HAI in the MICU of a hospital in January-December 2014 were performed pulsed-field gel electrophoresis (PFGE)homology analysis and clustering analysis,clinical characteristics,antimicrobial resistance, and transmission characteristics were analyzed.Results A total of 25 patients were investigated,with an average age of (69.62±2.13)years,mean hospital stay (49.34±3.18)days;prior to the isolation of P.aeruginosa, 84.00% of patients were treated with broad-spectrum antimicrobial agents for >2 weeks,76.00% of patients had been admitted to MICU,and 52.00% had a ventilator-assisted ventilation.55 strains of P.aeruginosa were mainly A,F,H,K,N,V,and W,which were the main epidemic strains;patients infected with A,F,H and K strains all had cross in their hospital stay;PFGE profiles of isolates from 4 patients during different periods showed different strain patterns;resistance rates of P.aeruginosa to ceftazidime (72.73%), piperacillin/tazobactam (70.91%),and imipenem(70.91%)were all high,resistance rate to amikacin was the lowest(25.45%).Conclusion Management of antimicrobial agents should be strengthened in medical institutions,HAI control meas-ures should be strengthened,so as to prevent the transmission of multidrug-resistant and extensively drug-resistant bacteria in hospitals.
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Prion diseases are infectious and fatal neurodegenerative diseases. The pathogenic agent is an abnormal prion protein aggregate. Microglial activation in the centre nervous system is a characteristic feature of prion disease. In this study, we examined the effect of PrP 106-126 on PrP mRNA gene expression in Mouse microglia cells BV-2 by real-time quantitative PCR. PrP mRNA expression level was found to be significantly increased after 18 h exposure of BV-2 cells to PrP 106-126, with 3-fold increase after 18 h and 4.5-fold increase after 24 h and BV-2 cells proliferating occurred correspondingly. Our results provide the first in vitro evidence of the increase of PrP mRNA levels in microglial cells exposed to PrP 106-126, and indicate that microglial cells might play a critical role in prion pathogenesis.
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ObjectiveTo investigate the protection of extract form earthworm a traditional Chinese medicine in auricle microcirculation disturbance in mice. MethodThe microcirculation disturbance in mice was brought by rapid injection of high molecule dextran. Observe the microvascular diameter,the blood flow speed,the blood fluid state and crossing net patency quantity of micrangium in mice before injection and after injection 10min,20min,30min with WX-9 microcirculation microscope and analytical system. ResultHigh and low dose of extract form earthworm could expend the diameter of the vein and artery of micrangium, quicken the blood flow speed,improve the blood fluid state,increase micrangium crossing net patefaction numbers. To compare with the control group, threr’s significant difference (P
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Objective To investigate the effect of intracerebroventricular injection of morphine and orphanin FQ (OFQ) on somatosensory evoked potential (SEP) and Na+-K+ATPase activity in cerebral cortex of rat. MethodsTo study the SEP with the BL-420 biological signal collecting system. The cerebral cortex tissues were extracted, homogenized and centrifuged. Na+-K+ATPase activity was measured with ATPase analytical kit. Results After intracerebroventricular injection with OFQ 0.9 ?g, the amplitude of P1-N1 and N1-P2 increased significantly(P
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The mathematical models for simulation of cardiac sodium, potassium and calcium channel kinetics courses and currents were developed to simulate the properties of ionic currents and channel dynamic courses. With modifications of these models, it is possible to make them integrated for simulating the whole process of action potential, thus additional discussion on ionic mechanism could provide a theoretical foundation for further animal experiments and clinical applications.