A high potent synthetic nanobody with broad-spectrum activity neutralizes SARS-Cov-2 virus and Omicron variant through a unique binding mode

The major challenge to control COVID pandemic is the rapid mutation rate of the SARS-Cov-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-Cov-2 variants. Here, we reported a synthetic nanobody (named C5G2) obtianed by phage display and subsequent antibody engineering. C5G2 has a single digit nanomolar binding affinity to RBD domain and inhibits its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assay indicated that the monovalent C5G2 could protect the cells from the infection of SARS-Cov-2 wild type virus and most of the virus of concern, i.e. Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron among all the variants with the IC50 of 4.9ng/mL. The Cryo-EM structure of C5G2 in complex with the Spike trimer showed that C5G2 bind to RBD mainly through its CDR3 at a conserved region that not overlapping with the ACE2 binding surface. Additionally, C5G2 bind simultaneously to the neighboring NTD domain of spike trimer through the same CDR3 loop, which may further increase its potency against the virus infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may be served as an effective drug for the prophylaxis and therapy against Omicron as well as future variants.

Influences on morphology and biomechanics in rabbit's femur cortex of ovariectomy / 中华骨科杂志

Objective To investigate the influences on the femur cortex of the rabbit after ovariectomy and its mechanism.Methods Eighty 6 months-old female pure New Zealand rabbits were divided into two groups:40 rabbits in ovariectomy group and 40 in sham-operation group.The weight averaged 2.2±0.28 kg.Four weeks and 8 weeks after operation,a series of tests were performed in both groups concerning the number,the volume,the rate and the maximal load of cortical bone porosity.The number,the length and the density of linear crack in rabbit femur cortex were documented after repetitive application of minor trauma.Results Micro-CT demonstrated that both on week 4 and 8 after operation,the number,the volume and the rate of cortical bone porosity were all significantly higher in ovariectomy group than that of the control group.Four weeks after operation,the biomechanical test showed the significantly lower average maximal load of rabbit femur in ovariectomy group (1 892.60±59.09) than that of in control group (1 949.25±53.12) (P=0.003).Eight weeks after operation,the average load of both groups decreased to some extent,which was 1 944.55±41.76 in control group and 1 692.40±85.08 in ovariectomy group respectively (P=0.000).However,the average maximal load of ovariectomy group decreased more significantly.Having application of repetitive minor trauma to the bone,the number,the length and the density of linear crack of cortical bone were 3.40± 1.67,216.80± 17.60 μm and 0.40±0.08/mm2 in ovariectomy group,and 2.00± 1.17,160.45± 16.89 μm and 0.29±0.13/mm2 in control group 4 weeks later.And after 8 weeks,they were 5.15±1.18,334.60±13.94 μm and 0.35±0.10/mm2 in ovariectomy group,and 3.10±1.37,182.10±9.80 μm and 0.24±0.09/mm2 in control group.The number,the length and the density of linear crack of cortical bone were all significantly higher in ovariectomy group than that of in control group both on week 4 and on week 8 after operation.Conclusion Ovariectomy increases the porosity of cortical bone of rabbit,destroys its biological property,accelerates the fatigued damage and delays the healing process.These changes may be attributed to fracture and delayed union after fracture.

Efficacy and safety of mixture of dexmedetomidine and low-concentration ropivacaine in lumbar plexus block for elderly patients / 实用医学杂志

Objective To observe the clinical efficacy and safety of 2 differentdoses of dexmedetomidine combined with low-concentration ropivacaine during lumbar plexus block for elderly patients. Methods Ninety elderly patients were randomly divided into group A,B and C with 30 cases in each group. All patients were performed lumbar plexus block guided by ultrasound and nerve stimulator.35 mL of 0.25% ropivacaine was injected in group A,35ml of 0.25% ropivacaine plus dexmedetomidine 0.5 μg/kg in group B,and 35 mL of 0.25% ropiva-caine plus dexmedetomidine 1 ug·kg-1in group C. Onset time,duration,blocking extent and the occurrence of adverse events wererecordedafter lumbar plexus block.Ramssay sedation score,blood pressure,heart rate and res-piration were monitored intraoperatively,and the dosage of analgesic within 24 hours after operation was measured. Results Group C witnessed the shortest onset time of sensory and motor block and the longest duration,followed by group B and A(P<0.01).The Ramssay sedation score of group C was higher than that of group A and B(P<0.05),but no significant difference was found between group A and B. Group C witnessed the lowest blood pres-sure and heart rate(P < 0.05),followed by group A and B(P < 0.05). The dosage of analgesics in group C was less than thatof group A and B(P<0.05),withthe lest in group B(P<0.05).All patients in group B and C com-pleted the surgery only under nerve blockade.However,there were6 patients in group Arequiring additional intrave-nous anesthesia to complete the surgery for poor outcome of nerve blockade. Conclusions The mixture of 0.5~1 μg·kg-1dexmedetomidine and 0.25% ropivacaine in lumbar plexus block can achieve good anesthetic outcome for elderly patients,with moderate sedation,stable respiration and circulation,and less adverse events.

Numerical simulation of supersonic gap flow.

Various gaps in the surface of the supersonic aircraft have a significant effect on airflows. In order to predict the effects of attack angle, Mach number and width-to-depth ratio of gap on the local aerodynamic heating environment of supersonic flow, two-dimensional compressible Navier-Stokes equations are solved by the finite volume method, where convective flux of space term adopts the Roe format, and discretization of time term is achieved by 5-step Runge-Kutta algorithm. The numerical results reveal that the heat flux ratio is U-shaped distribution on the gap wall and maximum at the windward corner of the gap. The heat flux ratio decreases as the gap depth and Mach number increase, however, it increases as the attack angle increases. In addition, it is important to find that chamfer in the windward corner can effectively reduce gap effect coefficient. The study will be helpful for the design of the thermal protection system in reentry vehicles.

Construction of a non-redundant human SH2 domain database / 基因组蛋白质组与生物信息学报·英文版

Domain database is essential for domain property research. Eliminating redundant information in database query is very important for database quality. Here we report the manual construction of a non-redundant human SH2 domain database. There are 119 human SH2 domains in 110 SH2-containing proteins. Human SH2s were aligned with ClustalX, and a homologous tree was generated. In this tree, proteins with similar known function were classified into the same group. Some proteins in the same group have been reported to have similar binding motifs experimentally. The tree might provide clues about possible functions of hypothetical proteins for further experimental verification.