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Recent studies found that Omicron variant escapes vaccine-elicited immunity. Interestingly, potent cross-clade pan-sarbecovirus neutralizing antibodies were found in survivors of the infection by SARS-CoV-1 after BNT162b2 mRNA vaccination (N Engl J Med. 2021 Oct 7;385(15):1401-1406). These pan-sarbecovirus neutralizing antibodies were observed to efficiently neutralize the infection driven by the S protein from both SARS-CoV and multiple SARS-CoV-2 variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta). However, whether these cross-reactive antibodies could neutralize the Omicron variant is still unknown. Based on the data collected from a cohort of SARS-CoV-1 survivors received 3-dose of immunization, our studies reported herein showed that a high level of neutralizing antibodies against both SARS-CoV-1 and SARS-CoV-2 were elicited by a 3rd-dose of booster vaccination of protein subunit vaccine ZF2001. However, a dramatically reduced neutralization of SARS-CoV-2 Omicron Variant (B.1.1.529) is observed in sera from these SARS-CoV-1 survivors received 3-dose of Vaccination. Our results indicates that the rapid development of pan-variant adapted vaccines is warranted.
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The COVID-19 pandemic has caused an unprecedented global public health and economy crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, comparing to the SARS-CoV-2-like CoVs identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human ACE2 as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2 from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activity, respectively. Among the remaining species, ACE2 from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models. ImportanceSARS-CoV-2 uses human ACE2 as primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologues and found that wild type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models and molecular basis of receptor binding for SARS-CoV-2.
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C3A is a sub-clone of human hepatoblastoma HepG2 cell line with the strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ADAP2, GILT and LY6E, three cellular proteins with known activity of interfering virus entry, expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-OC43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFITM3 restriction of human coronavirus entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a distinct mechanism. ImportanceVirus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control by host innate and adaptive immune responses. In the last decade, several interferon inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as host factors to facilitate the entry of several human pathogenic viruses, including human immunodeficiency virus, influenza A virus and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection.
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Objective@#To investigate the effect of early-stage training combined with the ultrashort wave therapy on the functional recovery of rats after a spinal cord injury, and to observe the expression of aquaporin protein-4 (AQP-4) and glial fibrillary acidic protein (GFAP).@*Methods@#Fifty female Sprague-Dawley rats had spinal cord injury (SCI) induced using the modified Allen′s method. After successful modeling, 40 were randomly divided into a sham operation group, a control group, an ultrashort wave group, a treadmill group and a combined group, each of 8. Motor function in their hind limbs was evaluated 4 weeks after the operation using BBB scoring. GFAP and AQP-4 immunohistochemical staining were used to determine the integral optical density (IOD) of the protein expression.@*Results@#The average BBB score of the sham operation group was 21, while the other four groups averages were all less than 1 on the 1st day after the operation. They gradually increased with time, and by 4 weeks the increases were significant. Compared with the control group at the same time point, the average BBB scores of the treadmill and the combined groups were significantly higher. Compared with the ultrashort wave group, the average BBB score of the treadmill group was higher after 4 weeks, and the combined group′s average was significantly higher at 2, 3 and 4 weeks after the operation. Four weeks after the SCI modeling, the average AQP-4 IOD and GFAP IOD levels of the ultrashort wave group, the treadmill group and the combined group were lower than that of the control group, while the average AQP-4 and GFAP IOD levels of the combined group were significantly lower than those of the ultrashort wave group. Compared with the treadmill group, the combined group had a significantly lower average GFAP level.@*Conclusions@#Both treadmill training and ultrashort wave treatment promote motor function recovery after a spinal cord injury. The mechanism may be related to downregulation of AQP-4 and GFAP expression at the injured site. Combining the two treatments gives better effects.
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Objective To investigate the effect of early-stage training combined with the ultrashort wave therapy on the functional recovery of rats after a spinal cord injury, and to observe the expression of aquaporin pro-tein-4 ( AQP-4) and glial fibrillary acidic protein ( GFAP ) . Methods Fifty female Sprague-Dawley rats had spinal cord injury ( SCI) induced using the modified Allen's method. After successful modeling, 40 were randomly divided into a sham operation group, a control group, an ultrashort wave group, a treadmill group and a combined group, each of 8. Motor function in their hind limbs was evaluated 4 weeks after the operation using BBB scoring. GFAP and AQP-4 immunohistochemical staining were used to determine the integral optical density ( IOD) of the protein expres-sion. Results The average BBB score of the sham operation group was 21, while the other four groups averages were all less than 1 on the 1st day after the operation. They gradually increased with time, and by 4 weeks the increa-ses were significant. Compared with the control group at the same time point, the average BBB scores of the treadmill and the combined groups were significantly higher. Compared with the ultrashort wave group, the average BBB score of the treadmill group was higher after 4 weeks, and the combined group's average was significantly higher at 2, 3 and 4 weeks after the operation. Four weeks after the SCI modeling, the average AQP-4 IOD and GFAP IOD levels of the ultrashort wave group, the treadmill group and the combined group were lower than that of the control group, while the average AQP-4 and GFAP IOD levels of the combined group were significantly lower than those of the ultrashort wave group. Compared with the treadmill group, the combined group had a significantly lower average GFAP level. Conclusions Both treadmill training and ultrashort wave treatment promote motor function recovery after a spinal cord injury. The mechanism may be related to downregulation of AQP-4 and GFAP expression at the injured site. Combining the two treatments gives better effects.
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BACKGROUND:Implant related problems such as loosening,dislocation and infection often come along with joint replacement.Nanotechnology provides a new insight into the preparation of joint replacement implants.OBJECTIVE:To elaborate the research progress of nanotechnology in improving joint replacement implants.METHODS:The first author used the computer to retrieve PubMed databases using the key words of joint replacement,artificial implant,nanotechnology,nano-materials,nanoscales,biocompatibility in English,to find relevant literature on nanotechnology and joint replacement implants.All data were primarily screened to exclude repeated and irrelevant articles,and finally 51 articles related to the study were retained.RESULTS AND CONCLUSION:Through reviewing these 51 articles,we make a detailed introduction about some of the biological responses that occur with nano-materials,and some of the biocompatibility problems that have been raised in relation to materials,as well as the ways that have been employed to improve biocompatibility of nano structured materials.But the long-term effect of nanotechnology on the human body is still worthy of further research in medicine or related fields.
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Therapeutic HIV vaccine was considered as a hopeful curative method for AIDS patients. However, there is still no suitable HIV animal model for vaccine study since the difference in the immune system between human and animals. To evaluate the therapeutic effect of combined immunization strategy with multiple vector vaccines in macaque models. Plasmid DNA, recombinant Ad5 and MVA vaccines which expressing SIV gag and env genes were constructed. Sequential and repeated immune strategy were applied to immunize mice with these three vaccines. Cellular immune responses in mice immunized with these three vaccines were measured by ELISPOT test in vitro and CTL assay in vivo. The results were analyzed and compared with different antigen combination, order of vaccines and intervals to choose a suitable immunization strategy for macaque immunization in future. It indicated that strong SIV-Gag/Env-specific cellular immune responses were induced by these three vector vaccines. It laid a foundation for evaluating the therapeutic effect of combined immunization strategy with multiple vector vaccines in SIV infected macaque models.
