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Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. Methods In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. Results To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. Conclusions Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19. A peptide-based magnetic chemiluminescence enzyme immunoassay for the detection of SARS-CoV-2 antibodies was developed; 71.4% (197 of 276) and 57.2% (158 of 276) of the COVID-19 inpatients were positive for IgG and IgM against SARS-CoV-2.

With the high yield of many wells represented by Well JT1 in the Maokou Formation, has catalyzed a surge in exploration activities along the platform margin facies of the Maokou Formation in central Sichuan and further showed the significant exploration potential of the Maokou Formation in the northern slope. However, the fracture cave body of the Maokou Formation exhibits a high degree of development, strong longitudinal and horizontal heterogeneity, large formation pressure differences, and drilling events such as gas kicks and lost circulation occur frequently, which seriously affects the efficient implementation of drilling. Understanding the spatial distribution of the three-pressure in the formation can help better deal with and solve the above problems. Therefore, in order to help the safe, high-quality and rapid drilling of the Maokou Formation in the study area, and enhance the efficiency of oil and gas development, this paper explores the research on the prediction method of the three-pressure of jointing well-seismic data based on the geomechanical experimental data and the actual drilling data. In the process of prediction of pore pressure, this study found that the pore pressure and formation velocity in the study area have an exponential relationship. In order to enhance the applicability of the Filippone’s method in the study area and improve the prediction accuracy of pore pressure, the linear relationship between pore pressure and formation velocity in the Filippone’s method is modified to an exponential relationship, and a pore pressure prediction model suitable for the work area was established. Based on the Mohr–Coulomb criterion and Huang's model, the prediction models of collapse pressure and fracture pressure applicable to the study area were established, respectively. Then, the elastic parameters were obtained through pre-stack inversion, and the three-pressure bodies were calculated based on the elastic parameter bodies. The results indicate that: (1) The three-pressure prediction method of the jointing well-seismic data in this paper can predict the formation's longitudinal and transverse pressure anomaly zones in advance. (2) The Maokou Formation in the study area is characterized by abnormally high pressure, to balance the pressure of the high-ground formation, high-density drilling fluid is necessary. (3) The prediction results of three-pressure in this paper are highly consistent with the actual drilling engineering events, which verifies the reliability of the three-pressure prediction results presented in this study. The results of the study can provide a basis for decision-making in drilling geological design, such as the determination of drilling fluid density, the evaluation of borehole stability and other engineering problems that require support from three-pressure data.

Parkinson’s disease (PD) is a complex neurological disorder characterized by motor and nonmotor features. Although some drugs have been developed for the therapy of PD in a clinical setting, they only alleviate the clinical symptoms and have yet to show a cure. In this study, by employing the C. elegans model of PD, we found that ferulic acid (FA) significantly inhibited α-synuclein accumulation and improved dyskinesia in NL5901 worms. Meanwhile, FA remarkably decreased the degeneration of dopaminergic (DA) neurons, improved the food-sensing behavior, and reduced the level of reactive oxygen species (ROS) in 6-OHDA-induced BZ555 worms. The mechanistic study discovered that FA could activate autophagy in C. elegans, while the knockdown of 3 key autophagy-related genes significantly revoked the neuroprotective effects of FA in α-synuclein- and 6-OHDA-induced C. elegans models of PD, demonstrating that FA exerts an anti-PD effect via autophagy induction in C. elegans. Furthermore, we found that FA could reduce 6-OHDA- or H2O2-induced cell death and apoptosis in PC-12 cells. Moreover, FA was able to induce autophagy in stable GFP-RFP-LC3 U87 cells and PC-12 cells, while bafilomycin A1 (Baf, an autophagy inhibitor) partly eliminated the protective effects of FA against 6-OHDA- and H2O2-induced cell death and ROS production in PC-12 cells, further confirming that FA exerts an anti-PD effect via autophagy induction in vitro. Collectively, our study provides novel insights for FA as a potent autophagy enhancer to effectively prevent neurodegenerative diseases such as PD in the future.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein that mediates SARS-CoV-2 entry into host cells is a major target for vaccines and therapeutics. Thus, insights into its sequence variations are key to understanding the infection and antigenicity of SARS-CoV-2. A dominant mutational variant at position 614 of the S protein (aspartate to glycine, D614G mutation) was observed in the SARS-CoV-2 genome sequence obtained from the Nextstrain database. Using a pseudovirus-based assay, we identified that S-D614 and S-G614 protein pseudotyped viruses share a common receptor, human angiotensin-converting enzyme 2 (ACE2), which could be blocked by recombinant ACE2 with the fused Fc region of human IgG1. However, S-D614 and S-G614 protein demonstrated functional differences. First, S-G614 protein could be cleaved by serine protease elastase-2 more efficiently. Second, S-G614 pseudovirus infected 293T-ACE2 cells significantly more efficiently than did the S-D614 pseudovirus, especially in the presence of elastase-2. Third, an elastase inhibitor approved for clinical use blocked elastase-enhanced S-G614 pseudovirus infection. Moreover, 93% (65/70) convalescent sera from patients with COVID-19 could neutralize both S-D614 and S-G614 pseudoviruses with comparable efficiencies, but about 7% (5/70) convalescent sera showed reduced neutralizing activity against the S-G614 pseudovirus. These findings have important implications for SARS-CoV-2 transmission and immune interventions. Competing Interest Statement The authors have declared no competing interest. Footnotes * Figure 1 updated to give structural implications of the spike D614G change. Figure 3 updated to clarify the role of elastase-2. Figure 4 and 5 revised.

The currently dominant variant of SARS-CoV-2 Omicron, carrying a great number of mutations, has been verified its strong capacity of immune escape in COVID-19 convalescents and vaccinated individuals. An increased risk of SARS-CoV-2 reinfection or breakthrough infection should be concerned. Here we reported higher humoral immune response elicited by Delta and Omicron variants after breaking through previous infection and cross-neutralization against VOCs, compared to the ancestral wild-type (WT) virus infection. To overcome the immune escape of Omicron, Omicron-specific vaccine was considered as a novel and potential strategy. Mouse models were used to verify whether Omicron-specific RBD subunit boost immune response by immunizing Omicron-RBD recombinant proteins. Three doses of Omicron-RBD immunization elicit comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, two doses of WT-RBD with an Omicron-RBD booster increased the NAb geometric mean titers against Omicron by 9 folds. Moreover, an additional boost vaccination with Omicron-RBD protein could increase humoral immune response against both WT and current VOCs. These results suggest that the Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs , and that SARS-CoV-2 vaccines administration using two or more virus lineages as antigens might improve the NAb response. Competing Interest Statement The authors have declared no competing interest. Footnotes * Figure 1-2 revised. Author updated.Supplemental table and figures added.

Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. To screen for antiviral drugs for COVID-19 treatment, we constructed a SARS-CoV-2 spike (S) pseudovirus system using an HIV-1-based lentiviral vector with a luciferase reporter gene to screen 188 small potential antiviral compounds. Using this system, we identified nine compounds, specifically, bis-benzylisoquinoline alkaloids, that potently inhibited SARS-CoV-2 pseudovirus entry, with EC50 values of 0.1–10 μM. Mechanistic studies showed that these compounds, reported as calcium channel blockers (CCBs), inhibited Ca2+-mediated membrane fusion and consequently suppressed coronavirus entry. These candidate drugs showed broad-spectrum efficacy against the entry of several coronavirus pseudotypes (SARS-CoV, MERS-CoV, SARS-CoV-2 [S-D614, S-G614, N501Y.V1 and N501Y.V2]) in different cell lines (293T, Calu-3, and A549). Antiviral tests using native SARS-CoV-2 in Vero E6 cells confirmed that four of the drugs (SC9/cepharanthine, SC161/hernandezine, SC171, and SC185/neferine) reduced cytopathic effect and supernatant viral RNA load. Among them, cepharanthine showed the strongest anti-SARS-CoV-2 activity. Collectively, this study offers new lead compounds for coronavirus antiviral drug discovery. Competing Interest Statement The authors have declared no competing interest. Footnotes * S-pseudotyped coronaviruses including two emerging SARS-CoV-2 variants N501Y.V1 and N501Y.V2, reported in United Kingdom and South Africa, were tested. Figure 1 revised; Figures S1 to S4 revised;Table S1 to S2 updated.

Federated learning is an emerging distributed machine learning framework in the Internet of Vehicles (IoV). In IoV, millions of vehicles are willing to train the model to share their knowledge. Maintaining an active state means the participants must update their state to the FL server in a fixed interval and participate in the next round. However, the cost of maintaining an active state is very large when there are a huge number of participating vehicles. In this paper, we propose a distributed client selection scheme to reduce the cost of maintaining the active state for all participants. The clients with the highest evaluation are elected among the neighbors. In the evaluator, four variables are considered, including the sample quantity, available throughput, computational capability, and the quality of the local dataset. We adopt fuzzy logic as the evaluator since the closed-form solution over four variables does not exist. Extensive simulation results show that our proposal approximates the centralized client selection in terms of accuracy and can significantly reduce the communication overhead.