The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the ...variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.
A Pd(II)-catalyzed enantioselective C–H alkynylation of 2-(arylsulfinyl)pyridines via kinetic resolution using cheap and commercially available l-pGlu-OH as a chiral ligand is reported. A wide ...range of 2-(arylsulfinyl)pyridines were compatible with this protocol, giving the alkynylation products and recovered sulfoxides in high yields with high enantioselectivities (up to 99% ee). Furthermore, the enantioenriched products can be easily transformed to several other types of chiral sulfoxide scaffolds with the retention of enantiopurity.
Wear of polyimide composite cage due to lubrication failure has a significant impact on the lifetime of bearing, but the related mechanisms are still far from understanding due to the complex ...movements of bearing parts, such as rolling, sliding et al. in the real operations. Here, the tribological behaviors of polyimide composite against steel ball were studied under a motion compounded with rolling and sliding in comparison with pure sliding. The rolling-sliding motion has a strong influence on the tribological properties of polyimide composite depending on lubrication conditions. Especially under PAO4 oil lubrication, the rolling-sliding motion can facilitate the degradation of polyimide composite, resulting in severe surface wear and aboundant black products forming. The analysis based on XPS and SEM measurements and the compared results from heating sliding test and thermal treatments indicates that the formation of black products is mainly attributed to the tribochemical reactions accompanying with the rupture of C–O and C = O bonds due to high frictional temperature. This process is further facilitated when the PAO4 oil and the metal from counterface participate in the tribochemical reactions.
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In this paper, we study the problem of achieving the optimal tradeoff between operation risk and expected energy cost for Internet data center (IDC) operators in deregulated electricity markets ...according to the risk preferences of IDC operators. To achieve the target above, we propose a risk-constrained stochastic programming decision framework. Then, we formulate a risk-constrained expected energy cost minimization problem with the uncertainties in spot price and workload. To solve the formulated problem, we use a decomposition-based cutting plane algorithm. Finally, extensive evaluations based on real-life data show the effectiveness of the proposed decision framework.
The flow separation could affect the aerodynamic performance of the wind turbine blades and induce to occur the stall of the wind turbine blades at high angle of attack. The leading edge slat could ...effectively control and delay the flow separation. In this paper, the effects of the leading edge slat on the aerodynamic performance of the S809 airfoil and the Phase VI blade were investigated and the effects of the geometric parameters were considered. The aerodynamic performance of the S809 airfoil and the Phase VI blade was obtained using the RANS approach, and involved the standard transition model SST, k-omega turbulence model. It was shown that the leading edge slat had a great influence on the aerodynamic performance of the S809 airfoil and the Phase VI blade. For Case-1, when the angle of attack was 16.22°, the point of flow separation was shifted from x/c = 0.47 to 0.67, the lift coefficient increased by 52.99%. The torques of the total (included the wind turbine blade and leading edge slat) were increased except the torque of Blade-C1at 10 m/s.
•The effects of the leading edge slat on the airfoil and blade were investigated.•The aerodynamic performance was obtained by the numerical simulation method.•The reasonable arrangement of the leading edge slat had a positive effect.•The leading edge slat can improve the aerodynamic performance of the blade.
In this work, we reported a porous supramolecular framework (A) constructed of a symmetric tetramethylcucurbit6uril (TMeQ6) in aqueous HCl solutions; the driving force was the outer surface ...interaction of cucurbitnurils, as well as hydrogen bonding between latticed water molecules and portal carbonyl oxygens of TMeQ6. Adsorption experimental results revealed that the porous supramolecular framework can absorb certain fluorophore guests (FGs) to form luminescent assemblies (FG@As) by fluorescence enhancement or colour change, and some of them can respond to certain volatile organic compounds. Thus, the TMeQ6-based supramolecular framework could be used as a sensor for certain gas or volatile compounds.
Heavy metal pollution is consistently a critical global issue, and bioremediation is regarded as one of the most promising approaches. In this work, the biosorption characteristics of Cd(II), Pb(II), ...Cu(II) and Zn(II) from aqueous solutions using three phosphorus−accumulating organisms (PAOs) biomasses, Ochrobactrum cicero (PAB−006), Stenotrophomonas maltophilia (PAB−009), and Pseudomonas putida (PAB−0031), as biosorbents were investigated. Results indicated that the equilibrium biosorption capacities of biosorbents to heavy metal ions were sensitive to the solution pH, and increased with increasing pH values. The experimental data of Cd(II), Pb(II), Cu(II) and Zn(II) biosorption were in good agreement with the Pseudo–second–order, Redlich–Peterson and Temkin models, implying that the biosorption was a hybrid chemical reaction–biosorption process. In addition, the theoretical maximum biosorption capacities of Cd(II), Pb(II), Cu(II) and Zn(II) were calculated to be 67.84, 80.23, 50.56 and 63.07 mg/g for PAB−006, 59.99, 87.71, 39.26 and 64.00 mg/g for PAB−009 and 68.31, 85.43, 38.97 and 62.85 mg/g for PAB−031, respectively (pH = 5.0 ± 0.1, T = 25 °C), according to the parameters of the Langmuir model. Moreover, ionic strength had negligible influences or slight promoting effects, while humic acid exhibited positive effects on the removal of heavy metals. Further, PABs were stable and displayed excellent reusability. Characterization techniques of FTIR and XPS revealed that surface complexation, ion exchange, hydrogen bonding and electrostatic interaction were the main mechanisms involved in the biosorption process. In summary, the biosorbent PABs possessed high biosorption performance with excellent reusability, and which hold the great application prospect in the treatment of heavy metal contaminated water.
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•The biosorption potential of PAOs biomasses was reported for the first time.•PAOs biomasses exhibited high biosorption capacity for heavy metals.•The biosorption of PAOs biomasses was a hybrid chemical reaction–adsorption process.•PAOs biomasses can be regarded as efficient biosorbents for heavy metal removal.
Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. The skeletal muscle in MSTN−/– mice is significantly hypertrophied, with muscle fiber type II increasing ...significantly while muscle fiber type I decreasing. However, it is still not clear how the skeletal muscle types change in MSTN−/– pigs, and how the mechanism for MSTN regulates fiber types, especially in large animals like pigs. This study conducted a comprehensive analysis of the composition of skeletal muscle fibers in MSTN−/– pigs produced in our laboratory. It was observed that, compared with wild-type (WT) pigs, both the total mass of skeletal muscle and type IIb muscle fibers increased significantly (P<0.01), while the type I and type IIa muscle fibers decreased significantly (P<0.01), in MSTN−/– Meishan pigs. In addition, to explore the influence of MSTN on muscle fiber type and its regulation mechanism in the embryonic stage, this study selected a few genes (Myf5, Mef2d, MyoD and Six1) associated with muscle fiber type and validated their expression by quantitative RT-PCR. Herein, it was found that Myh7, Myh2, Myh4 and Myh1 can be detected in the skeletal muscle of pigs at 65 days of gestation (dg). Compared with WT pigs, in MSTN−/– Meishan pigs, Myh7 decreased significantly (P<0.01), while Myh4 (P<0.001) and Myh1 (P<0.05) increased significantly. Meanwhile, the increased expression of Myf5 (P<0.05), Mef2d (P<0.01) and Six1 (P<0.05) in MSTN−/– Meishan pigs suggested that MSTN should regulate the directional development of muscle fiber types in the early stage of embryonic development. Thus, at the embryonic stage, the type II muscle fibers began to increase in MSTN−/– pigs. These results can provide valuable information not only for pig meat quality improvement, but also for the study of human skeletal muscle development and disease treatment.
BACKGROUND:Microglia can not only detrimentally augment secondary injury but also potentially promote recovery. However, the mechanism underlying the regulation of microglial phenotypes after stroke ...remains unclear.
METHODS:Mice were subjected to middle cerebral artery occlusion for 60 min. At 3 days after reperfusion, the effects of activation and suppression of triggering receptor expressed on myeloid cells 2 on immunocyte phenotypes (n = 5), neurobehavioral scores (n = 7), infarct volumes (n = 8), and neuronal apoptosis (n = 7) were analyzed. In vitro, cultured microglia were exposed to oxygen–glucose deprivation for 4 h. Inflammatory cytokines, cellular viability (n = 8), neuronal apoptosis (n = 7), and triggering receptor expressed on myeloid cells 2 expression (n = 5) were evaluated in the presence or absence of triggering receptor expressed on myeloid cell-specific small interfering RNA or triggering receptor expressed on myeloid cells 2 overexpression lentivirus.
RESULTS:Triggering receptor expressed on myeloid cells 2 expression in the ischemic penumbra peaked at 3 days after ischemia–reperfusion injury (4.4 ± 0.1-fold, P = 0.0004) and was enhanced in interleukin-4/interleukin-13–treated microglia in vitro (1.7 ± 0.2-fold, P = 0.0119). After oxygen–glucose deprivation, triggering receptor expressed on myeloid cells 2 conferred neuroprotection by regulating the phenotypic conversion of microglia and inflammatory cytokine release. Intraperitoneal administration of triggering receptor expressed on myeloid cells 2 agonist heat shock protein 60 or unilateral delivery of a recombinant triggering receptor expressed on myeloid cells 2 lentivirus into the cerebral ventricle induced a significant neuroprotective effect in mice (apoptotic neurons decreased to 31.3 ± 7.6%; infarct volume decreased to 44.9 ± 5.3%). All values are presented as the mean ± SD.
CONCLUSIONS:Activation or up-regulation of triggering receptor expressed on myeloid cells 2 promoted the phenotypic conversion of microglia and decreased the number of apoptotic neurons. Our study suggests that triggering receptor expressed on myeloid cells 2 is a novel regulator of microglial phenotypes and may be a potential therapeutic target for stroke.
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