Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT

The cytoskeletal proteins tubulin and actin are the obligate substrates of TCP-1 ring complex/Chaperonin containing TCP-1 (TRiC/CCT), and their folding involves co-chaperone. Through cryo-electron microscopy analysis, we present a more complete picture of TRiC-assisted tubulin/actin folding along TRiC adenosine triphosphatase cycle, under the coordination of co-chaperone plp2. In the open S1/S2 states, plp2 and tubulin/actin engaged within opposite TRiC chambers. Notably, we captured an unprecedented TRiC-plp2-tubulin complex in the closed S3 state, engaged with a folded full-length β-tubulin and loaded with a guanosine triphosphate, and a plp2 occupying opposite rings. Another closed S4 state revealed an actin in the intermediate folding state and a plp2. Accompanying TRiC ring closure, plp2 translocation could coordinate substrate translocation on the CCT6 hemisphere, facilitating substrate stabilization and folding. Our findings reveal the folding mechanism of the major cytoskeletal proteins tubulin/actin under the coordination of the biogenesis machinery TRiC and plp2 and extend our understanding of the links between cytoskeletal proteostasis and related human diseases

Influence of Nickel Doping on Ultrahigh Toluene Sensing Performance of Core-Shell ZnO Microsphere Gas Sensor

As a volatile organic compound, toluene is extremely harmful to the environment and human health. In this work, through a simple one-step solvothermal method, Ni-doped ZnO sensitive materials (0.5, 1, and 2 at% Ni-doped ZnO) with a core-shell morphology were synthesized for the first time for toluene gas detection. The sensing test results showed that the sensor based on 1 at% Ni-doped ZnO exhibited the best toluene sensing performance. The response was up to 210 to 100 ppm toluene at 325 °C. The sensor exhibited high selectivity, fast response/recovery characteristics (2/77 s), and low detection limit (500 ppb, 3.5). Furthermore, we carried out molecular-level research on the sensitive material prepared in this experiment by various characterization methods. The SEM characterization results showed that ZnO and Ni-doped ZnO possessed the core-shell morphology, and the average grain size decreased with the increase in the Ni doping content. The UV–Vis test showed that the band gap of ZnO became smaller with the increase in the Ni doping amount. The enhanced toluene sensing performance of 1 at% Ni-doped ZnO could be ascribed to the structural sensitization and Ni doping sensitization, which are discussed in detail in the sensing mechanism section

Influence of Nickel Doping on Ultrahigh Toluene Sensing Performance of Core-Shell ZnO Microsphere Gas Sensor

As a volatile organic compound, toluene is extremely harmful to the environment and human health. In this work, through a simple one-step solvothermal method, Ni-doped ZnO sensitive materials (0.5, 1, and 2 at% Ni-doped ZnO) with a core-shell morphology were synthesized for the first time for toluene gas detection. The sensing test results showed that the sensor based on 1 at% Ni-doped ZnO exhibited the best toluene sensing performance. The response was up to 210 to 100 ppm toluene at 325 °C. The sensor exhibited high selectivity, fast response/recovery characteristics (2/77 s), and low detection limit (500 ppb, 3.5). Furthermore, we carried out molecular-level research on the sensitive material prepared in this experiment by various characterization methods. The SEM characterization results showed that ZnO and Ni-doped ZnO possessed the core-shell morphology, and the average grain size decreased with the increase in the Ni doping content. The UV–Vis test showed that the band gap of ZnO became smaller with the increase in the Ni doping amount. The enhanced toluene sensing performance of 1 at% Ni-doped ZnO could be ascribed to the structural sensitization and Ni doping sensitization, which are discussed in detail in the sensing mechanism section

A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection

SARS-CoV-2, the causative agent of COVID-19$^{1}$, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein$^{1-6}$. Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics$^{7-17}$. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic nanobodies (sybodies) against RBD by in vitro selection using three libraries. The best sybody, MR3 binds to RBD with high affinity (K$_{D}$ = 1.0 nM) and displays high neutralization activity against SARS-CoV-2 pseudoviruses (IC$_{50}$ = 0.42 μg mL$^{-1}$). Structural, biochemical, and biological characterization suggests a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency have been generated by structure-based design, biparatopic construction, and divalent engineering. Two divalent forms of MR3 protect hamsters from clinical signs after live virus challenge and a single dose of the Fc-fusion construct of MR3 reduces viral RNA load by 6 Log$_{10}$. Our results pave the way for the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid development of targeted medical interventions during an outbreak

A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection

SARS-CoV-2, the causative agent of COVID-191, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein1–6. Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics7–17. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic nanobodies (sybodies) against RBD by in vitro selection using three libraries. The best sybody, MR3 binds to RBD with high affinity (KD = 1.0 nM) and displays high neutralization activity against SARS-CoV-2 pseudoviruses (IC50 = 0.42 μg mL−1). Structural, biochemical, and biological characterization suggests a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency have been generated by structure-based design, biparatopic construction, and divalent engineering. Two divalent forms of MR3 protect hamsters from clinical signs after live virus challenge and a single dose of the Fc-fusion construct of MR3 reduces viral RNA load by 6 Log10. Our results pave the way for the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid development of targeted medical interventions during an outbreak

Incidence and prediction of ankle injury risk

Objectives This study examines the incidence of ankle injuries and identifies ankle injury risk among contemporary preprofessional dancers. Methods A total of 91 first-year contemporary preprofessional dancers were prospectively followed during one academic year. Self-reported ankle injuries, assessed with the Oslo Sports Trauma Research Centre questionnaire, were categorised as all complaint ankle injuries, substantial ankle injuries or time-loss ankle injuries. In addition, ankle injuries leading to medical attention were included. Regression analyses were used to determine the association between potential risk factors (dancer characteristics, history of ankle injury in the previous year, ankle range of motion and dorsiflexion) and ankle injuries. Results The 1-year ankle injury incidence prop