Flavonoids from the roots and rhizomes of Sophoratonkinensis and their in vitro anti-SARS-CoV-2 activity.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 µmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 µmol·L-1, respectively.

COVID-19 vaccination boosts the potency and breadth of the immune response against SARS-CoV-2 among recovered patients in Wuhan.

The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed. Nevertheless, the antibody response decreased over time, and the Omicron variant exhibited more pronounced resistance to neutralization than the prototype and Delta strains. Moreover, the intensity of the SARS-CoV-2-specific CD4+ T cell response was also increased in recovered patients who received COVID-19 vaccines. Overall, the repeated antigen exposure provided by inactivated COVID-19 vaccination greatly boosted both the potency and breadth of the humoral and cellular immune responses against SARS-CoV-2, effectively protecting recovered individuals from reinfection by circulating SARS-CoV-2 and its variants.

Macroeconomic attention and stock market return predictability

Our investigation evaluates the novel macroeconomic attention indices (MAI) of Fisher et al. (2021) in terms of their ability to predict stock market returns based on dimension reduction methods and shrinkage methods. Our results demonstrate that macroeconomic attention indices can predict stock market returns with a significant degree of accuracy. In addition, the components of MAI indices based on partial least squares (PLS) and the least absolute shrinkage and selection operator (LASSO) methods have a greater capacity to improve the accuracy of the prediction of stock market returns than the components of the traditional macroeconomic variables. Moreover, we find that shrinkage methods can generate performances superior to those of the other models for forecasting stock market returns. We further demonstrate that macroeconomic attention indices embody superior predictive ability during the COVID-19 pandemic and over longer periods of time. Our study sheds new light on stock market returns’ prediction from the perspective of macroeconomic fundamentals.

Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

Hybrid Cryptography with a One–Time Stamp to Secure Contact Tracing for COVID–19 Infection

The COVID-19 pandemic changed the lives of millions of citizens worldwide in the manner they live and work to the so-called new norm in social standards. In addition to the extraordinary effects on society, the pandemic created a range of unique circumstances associated with cybercrime that also affected society and business. The anxiety due to the pandemic increased the probability of successful cyberattacks and as well as their number and range. For public health officials and communities, location tracking is an essential component in the efforts to combat the disease. The governments provide a lot of mobile apps to help health officials to trace the infected persons and contact them to aid and follow up on the health status, which requires an exchange of data in different forms. This paper presents the one-time stamp model as a new cryptography technique to secure different contact forms and protect the privacy of the infected person. The one-time stamp hybrid model consists of a combination of symmetric, asymmetric, and hashing cryptography in an entirely new way that is different from conventional and similar existing algorithms. Several experiments have been carried out to analyze and examine the proposed technique. Also, a comparison study has been made between our proposed technique and other state-of-the-art alternatives. Results show that the proposed one-time stamp model provides a high level of security for the encryption of sensitive data relative to other similar techniques with no extra computational cost besides faster processing time.

Structural basis for replicase polyprotein cleavage and substrate specificity of main protease from SARS-CoV-2.

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key enzyme, which extensively digests CoV replicase polyproteins essential for viral replication and transcription, making it an attractive target for antiviral drug development. However, the molecular mechanism of how Mpro of SARS-CoV-2 digests replicase polyproteins, releasing the nonstructural proteins (nsps), and its substrate specificity remain largely unknown. Here, we determine the high-resolution structures of SARS-CoV-2 Mpro in its resting state, precleavage state, and postcleavage state, constituting a full cycle of substrate cleavage. The structures show the delicate conformational changes that occur during polyprotein processing. Further, we solve the structures of the SARS-CoV-2 Mpro mutant (H41A) in complex with six native cleavage substrates from replicase polyproteins, and demonstrate that SARS-CoV-2 Mpro can recognize sequences as long as 10 residues but only have special selectivity for four subsites. These structural data provide a basis to develop potent new inhibitors against SARS-CoV-2.

Policy uncertainty and carbon neutrality: Evidence from China

This paper examines the effects of China's economic policy uncertainty (CEPU) index and climate policy uncertainty (CPU) index on the Wind carbon neutral concept (CNCI) index volatility. We find that both CEPU and CPU indices have significant effects on the CNCI volatility. In addition, when the market suffers more volatile risks, the CPU index has relatively better performance than the CEPU index for forecasting CNCI index volatility. This paper can provide new insights to realize China's goal of achieving peak emissions by 2030 and carbon neutrality by 2060.

Effect of Spatial-Temporal Light Competition on Cotton Yield and Yield Distribution

The photosynthetically active radiation (PAR) of crop canopy is highly related to yield formation, but how it relates to yield and yield distribution is not well understood. The focus of this study was to explore the relationship between light competition under different densities and yield distributions of cotton. The experiment was conducted in 2019 and 2020 at the Cotton Research Institute of the Chinese Academy of Agricultural Sciences in Anyang city, Henan Province, China. A randomized block design was employed, with a total of three repeats. Each repeat had six density treatments: D1: 15,000;D2: 33,000;D3: 51,000;D4: 69,000;D5: 87,000;and D6: 105,000 plants·ha−1. As predicted, the results showed that the canopy light interception, leaf area index, plant height, and biomass of high-density cotton were higher than those of low-density cotton. The aboveground biomass produced by D6 was the highest, and was 12.9, 19.5, 25.4, 46.3, and 69.2% higher in 2019 and 14.3, 19.9, 32.5, 53.7, and 109.9% higher in 2020 than D5, D4, D3, D2, and D1, respectively. Leaf area, plant height, biomass, boll number, and boll weight were significantly correlated with the light interception rate. D5 (87,000 plants·ha−1) had a higher light interception rate and the highest yield. The highest lint yields produced by D5 were 1673.5 and 1375.4 kg·ha−1 in two years, and was 3.2, 4.3, 5.6, 9.7, and 24.7% higher in 2019, and 6.8, 10.6, 13.5, 21.5, and 34.4% higher in 2020 than D6, D4, D3, D2, and D1, respectively. The boll retention of the lower fruit branch under D5 reached 0.51 and 0.57 in two years, respectively. The shedding rate of the upper fruit branch decreased with the increase in cotton density in two years. The boll retention rate and shedding rate in the lower part of cotton plants were most closely related to light interception, with R2 values of 0.91 and 0.96, respectively. Our study shows cotton yield could be improved through higher light interception by optimizing planting density and canopy structure. [ FROM AUTHOR] Copyright of Agronomy is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Etiological and epidemiological features of acute respiratory infections in China.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.

China’s Wildlife Management Policy Framework: Preferences, Coordination and Optimization

The coronavirus disease 2019 pandemic led to global concerns about the delicate relationship between humans and wildlife. However, quantitative research on the elements of a wildlife management policy framework in a certain country is lacking. In this study, we try to close this research gap by analyzing the formulation preferences of key elements in the wildlife management policy framework, as well as the coordination between them, in China, which is generally regarded as a main wildlife consumption country. Based on the content analysis of China’s wildlife management policy documents, with a three-dimensional analytical framework, we find that: China’s wildlife management policy framework prefers the use of compulsory tools, while voluntary and mixed tools are not fully used;adequate attention is paid to the biodiversity conservation objectives and attention is paid to the objectives of public health protection and wildlife welfare, while the utilization objective is restricted to some extent;government sectors, industry, citizens, and non-governmental organizations are involved in wildlife management policies and the degrees of participation of citizens and non-governmental organizations are relatively low. In conclusion, we draw wider implications for China’s wildlife management policy formulation, arguing for a more coordinated and participatory policy framework.

Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan.

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.

Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) urgently needs an effective cure. 3CL protease (3CLpro) is a highly conserved cysteine proteinase that is indispensable for coronavirus replication, providing an attractive target for developing broad-spectrum antiviral drugs. Here we describe the discovery of myricetin, a flavonoid found in many food sources, as a non-peptidomimetic and covalent inhibitor of the SARS-CoV-2 3CLpro. Crystal structures of the protease bound with myricetin and its derivatives unexpectedly revealed that the pyrogallol group worked as an electrophile to covalently modify the catalytic cysteine. Kinetic and selectivity characterization together with theoretical calculations comprehensively illustrated the covalent binding mechanism of myricetin with the protease and demonstrated that the pyrogallol can serve as an electrophile warhead. Structure-based optimization of myricetin led to the discovery of derivatives with good antiviral activity and the potential of oral administration. These results provide detailed mechanistic insights into the covalent mode of action by pyrogallol-containing natural products and a template for design of non-peptidomimetic covalent inhibitors against 3CLpros, highlighting the potential of pyrogallol as an alternative warhead in design of targeted covalent ligands.

Mindfulness-based online intervention on mental health and quality of life among COVID-19 patients in China: an intervention design.

BACKGROUND: COVID-19 can lead to increased psychological symptoms such as post-traumatic stress disorder (PTSD), depression, and anxiety among patients with COVID-19. Based on the previous mindfulness-based interventions proved to be effective, this protocol reports a design of a randomized controlled trial aiming to explore the efficacy and possible mechanism of a mindful living with challenge (MLWC) intervention developed for COVID-19 survivors in alleviating their psychological problems caused by both the disease and the pandemic. METHODS: In April 2021, more than 1600 eligible participants from Hubei Province of China will be assigned 1:1 to an online MLWC intervention group or a waitlist control group. All participants will be asked to complete online questionnaires at baseline, post-program, and 3-month follow-up. The differences of mental health status (e.g. PTSD) and physical symptoms including fatigue and sleeplessness between the COVID-19 survivors who receiving the online MLWC intervention and the control group will be assessed. In addition, the possible mediators and moderators of the link between the MLWC intervention and target outcomes will be evaluated by related verified scales, such as the Five Facets Mindfulness Questionnaire. Data will be analyzed based on an intention-to-treat approach, and SPSS software will be used to perform statistical analysis. DISCUSSION: The efficacy and potential mechanism of MLWC intervention in improving the quality of life and psychological status of COVID-19 survivors in China are expected to be reported. Findings from this study will shed light on a novel and feasible model in improving the psychological well-being of people during such public health emergencies. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000037524; Registered on August 29, 2020, http://www.chictr.org.cn/showproj.aspx?proj=60034 .

Application of SARS-CoV-2 antibody sample panel in quality evaluation of test cassettes for colloidal gold lateral flow assay

Objective: To establish a SARS-CoV-2 antibody sample panel and apply to the quality evaluation of test cassettes for colloidal gold lateral flow assay.