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Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19. HighlightsO_LISARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusion C_LIO_LIHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice models C_LIO_LIRhesus macaques showed no adverse side effects when administered with HB27 C_LIO_LICryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor C_LI
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The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. One sentence summaryA potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.
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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 study the effect and mechanism of endoplamic reticulum stress on the auditory cortex injury after focal cerebral ischemia-reperfusion injury in rats.Methods 30 healthy male adult SD rats were chosen and randomly divided into 2 groups,ischemia-reperfusion(I/R) group and sham operated control,with each group 15 rats.The rats in I/R group were operated for suture-occluded method to establish middle cerebral artery occlusionmodel(MCAO),with ischemia for 60 mins followed by reperfusion for 24 h.And the control group was only to be isolated cervical vessels,with no thread embolism inserted.The auditory brainstem response (ABR) was tested before operation and at 24 h post-operation respectively.The neurological deficits,ratio of infarct volume were evaluated.The pathological changes were observed by HE.Neurocyte apoptosis were observed by Tunel,and the AI were determined.The expression of GRP78,Caspase-12 were detected by immunohistochemistry and Western blotting.Results Compared with the sham group,the neurological function scores,the infarct volume of brain of I/R group increased significantly.The threshold of ABR elevated significantly and AI rised in I/R group.HE staining showed that the neurons in the sham group were arranged in order,the shape was normal,but in the I/R group the normal structure disappeared,the nuclei were condensed.The expression of GRP78,Caspase-12 protein were significantly up-regulated.All of the differences above have statistical significance(P＜0.05).Conclusion The mechanism of hearing loss after focal cerebral ischemia-reperfusion injury in rats is perhaps related to endoplamic reticulum stress,and GRP78,Caspase-12 participate in the process of neuron apoptosis on auditory cortex caused by ERS.
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Through indoor and field comparative experiments, the properties of membrane type leaf evaporation inhibitors and its effects on photosynthesis of and compatibility and synergistic of pesticide were studied. The evaporation inhibitors and were chosen to investigate the suppression of water evaporation and the compatibility with pesticides. The effect of evaporation inhibitors on photosynthesis of leaves was determined by the chlorophyll fluorescence imaging system. The results showed that water evaporation of leaves of different leaf age were evidently suppressed after treated with evaporation inhibitor. The inhibitor was well compatible with pesticide and effectively improved the pesticide efficacy，and had no significant effect on chlorophyll fluorescence parameters. It is concluded that the evaporation inhibitor has good compatibility with the pesticide, and has remarkable effect of restraining moisture evaporation, which make it can be used for reducing the dosage and improving the efficacy of the pesticide in the field of
Subject(s)
Chlorophyll , Lycium , Physiology , Pesticides , Chemistry , Photosynthesis , Plant Leaves , Physiology , Plant TranspirationABSTRACT
Objective To study the mechanism of endoplamic reticulum stress(ERS)pretreatment induced by 2-DG on the auditory cortex injury after focal cerebral ischemia-reperfusion injury in rats. Methods The SD rats were randomly divided into 3 groups,sham group,I/R group,and ERS pretreatment group. Tread occlusion was used to prepare the model of MCAO in the mice for 60 min followed by reperfusion for 24 h. Neurological assessment was exercised and brain infarction volume was evaluated. The auditory brainstem response was tested. The pathological changes were observed by HE staining. Neurocyte apoptosis was observed by Tunel ,and the apop-tosis index(AI)was determined. Expression of GRP78 and Caspase-12 were detected by immunohistochemistry. Results Compared with the sham group,the neurological scores,ratio of infarct volume and the hearing thresh-olds in I/R group increased significantly. HE staining showed the normal structure disappeared ,and apoptotic index increased significantly. Expression of GRP78 and Caspase-12 protein significantly up-regulated. Compared with I/R group,the indicators above showed improvement to some degrees. Conclusions The ERS pretreatment can alleviate the ischemia-reperfusion injury and neuron apoptosis in auditory cortex ,and reduce the possibility of hearing loss.
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Objective To investigate the expression of GRP78 and caspase-12 on the auditory cortex and to study the effects of endoplasmic reticulum stress in the auditory cortex neuron apoptosis after the brain ischemia reperfusion injury in guinea pig.Methods Fifty healthy male guinea pigs were selected and randomly divided into 5 groups which were hormal group group A(reperfusion for 6 hours),group B(reperfusion for 12 hours),group C (reperfusion for 24 hours),group D(reperfusion for 72 hours).The cerebral ischemia reperfusion injury model was produced by the occlusion of bilateral common carotid arteries.The guinea pigs were sacrificed at reperfusion of 6, 12,24,and 72 hours respectively after they received ABR tests.The pathological changes were observed by HE and the levels of GRP78 and caspase-12 protein were detected by immunohistochemistry and Western blot.Results The hearing thresholds increased gradually from the normal group to group B,and decreased gradually from group C to group D,but the thresholds of group D were still higher than that of the normal group.HE staining showed that the neurons in the normal control group were arranged in order,the cytoplasm was abundant,large and round.The cells were stained clearly.After reperfusion,the number of neurons in each time point was decreased,the nucleus presented atrophic,fragmented,the disappeared.The expression of GRP78 and caspase-12 protein in normal con-trol group was only a trace or a small amount by immunohistochemistry and Western blot.The expression of GRP78 and caspase-12 began to inerease.The expression of GRP78 reached the peak at reperfusion of 12 hours and de-creased gradually.There were significant statistic differences between each group comparison.The expression of caspase-12 reached the peak at reperfusion of 24 hours,then decreased gradually.There was no statistic difference between group A and group B.There were significant statistic differences anong other groups.Conclusion Endo-plasmic reticulum stress(ERS)may be induced by brain ischemia reperfusion injury,and can increase the expression of GRP78 and caspase-12.GRP78 and caspase-12 participate in the process of neuron apoptosis on auditory cor-tex caused by ERS.
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Objective To assess pertinent indicators of elderly-friendly city, so as to provide the basis for carrying out the related work. Methods There were 1 500 elderly people aged at and above 60 years old that were surveyed via questionnaires and structured interviews. Results The core indicators:79.8%reported that their neighborhood was convenient for walking;90.3% reported that bus, under-ground and taxi in Shanghai were suitable for all types of people ( including the physically handicapped, the blind, and the deaf);94.8%reported that there was no difficulty in the payment of housing;96.0%reported that the community had good atmosphere of respecting for the elderly; 56 .8% participated in community volunteer activities;6.7%participated in paid work;53.5%participated in social and cultural activities;99 .7% reported that they could obtain information on health and social services from the community;71.2%reported that they could obtain services for free or below market price when necessary at home.Some core indicators had obvious differences among different genders, age groups, culture, marital status, household types, income sources and income levels.Supplementary and optional indicators:98.6%thought there should be at least one item of house facilities for home-based care for the aged, while 75.6%thought there should be at least four items.26.3% reported to have participated in community team activities.55.2%reported to have participated at least one education or training project during the past one year.90.5% self-reported of good health conditions. Conclusion There is high coverage of barrier-free facility construction, good atmosphere of respecting for the elderly in the community, wide coverage of home-based care for the aged.The elderly people, to some extent, are involved in community activities and various types of training.However, there are still improvements of participation of the elderly in decision-making of local policies, and of senile transformation of the houses the elderly.At the same time, economic, social, demographical, cultural and other factors should be paid close attention to.
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Pharmaceutical preparations, particularly as a "secret recipe" of traditional Chinese medicine in medical institutions, are the product of China's medical and health industry, and they are also an important means of competing of different medical institutions. Although pharmaceutical preparations have advantages and characteristics than institutes for drug and pharmaceutical companies, the quality standards of pharmaceutical preparations in medical institutions has not reached the desired level over the years. As we all know, the quality of pharmaceutical preparations is important to ensure the efficacy, especially under the environment of people pay more sttention on drug safety and effectiveness and contry increase emphasis on the stste of pharmaceutical preparations. In view of this, we will improve the grade, stability, and clinical efficacy of pharmaceutical preparations by the advanced equipment, testing instruments and the process dynamic quality control technology. Finally, we hope we can provide new ideas for the quality control of pharmaceutical preparations.
