Enhanced Single-Particle Collision Electrochemistry at Polysulfide-Functionalized Microelectrodes for SARS-CoV-2 Detection.

Single-particle collision electrochemistry (SPCE) has shown great promise in biosensing applications due to its high sensitivity, high flux, and fast response. However, a low effective collision frequency and a large number of interfering substances in complex matrices limit its broad application in clinical samples. Herein, a novel and universal SPCE biosensor was proposed to realize sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on the collision and oxidation of single silver nanoparticles (Ag NPs) on polysulfide-functionalized gold ultramicroelectrodes (Ps-Au UMEs). Taking advantage of the strong interaction of the Ag-S bond, collision and oxidation of Ag NPs on the Ps-Au UME surface could be greatly promoted to generate enhanced Faraday currents. Compared with bare Au UMEs, the collision frequency of Ps-Au UMEs was increased by 15-fold, which vastly improved the detection sensitivity and practicability of SPCE in biosensing. By combining magnetic separation, liposome encapsulation release, and DNAzyme-assisted signal amplification, the SPCE biosensor provided a dynamic range of 5 orders of magnitude for spike proteins with a detection limit of 6.78 fg/mL and a detection limit of 21 TCID50/mL for SARS-CoV-2. Furthermore, SARS-CoV-2 detection in nasopharyngeal swab samples of infected patients was successfully conducted, indicating the potential of the SPCE biosensor for use in clinically relevant diagnosis.

Influencing Factors and Symbiotic Mechanism of the Integration of Medical Care and Disease Prevention during the COVID-19 Pandemic: A Cross-Sectional Survey of Public Hospital Employees.

Background: The COVID-19 outbreak has accelerated the huge difference between medical care and disease prevention in Chinese medical institutions. This study aimed to investigate the relationship between the symbiotic units, environments, models, and effects of the integration of medical care and disease prevention. Methods: This cross-sectional study involved 762 employees of public hospitals in 11 cities in Zhejiang Province by random stratified sampling. We analyzed the influence paths of elements in the mechanism of integration of medical care and disease prevention and the mediating effect of symbiotic models among symbiotic units, symbiotic environments, and effects on this integration. Results: The path coefficient of the symbiotic unit on the symbiosis model was 0.46 (p < 0.001), the path coefficient of the symbiotic environment on the symbiosis model was 0.52 (p < 0.001). The path coefficient of the symbiotic unit and the environment was 0.91 (p < 0.001). The symbiotic models exhibited a partial mediation effect between symbiotic units and the effect of this integration. Sobel test = 3.27, ß = 0.152, and the mediating effect accounted for 34.6%. Conclusions: It is suggested that health policymakers and public hospital managers should provide sufficient symbiotic units, establish collaborative symbiotic models, and improve the effects of integration of medical care and disease prevention in public hospitals.

AI-Aided Design of Novel Targeted Covalent Inhibitors against SARS-CoV-2.

The drug repurposing of known approved drugs (e.g., lopinavir/ritonavir) has failed to treat SARS-CoV-2-infected patients. Therefore, it is important to generate new chemical entities against this virus. As a critical enzyme in the lifecycle of the coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive target for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with a fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from the lead compounds based on our structure-based optimization policy (SBOP). All of the 47 lead compounds obtained directly with our AI model and related derivatives based on the SBOP are accessible in our molecular library. These compounds can be used as potential candidates by researchers to develop drugs against SARS-CoV-2.

[Spatiotemporal Distribution and Risk Assessment of Pharmaceuticals in Typical Drinking Water Sources in the Middle Reaches of the Yangtze River].

The seasonal variation and spatial distribution of pharmaceuticals in typical drinking water sources in the middle reaches of the Yangtze River were analyzed using the solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry methods. Combined with the risk entropy method, the corresponding ecological risks for aquatic organisms were evaluated. The results showed that 80% of the target pharmaceuticals were detected in the drinking water sources, with average concentrations of 0.07-13.00 ng·L-1. The concentrations of the target pharmaceuticals were lower than or comparable with those in other drinking water sources reported in China. The spatiotemporal distribution of different pharmaceuticals varied. Generally, the detection level in winter was higher than that in summer, and there was no significant difference between that upstream and that downstream. This might be mainly attributed to seasonal/regional use and emissions of the pharmaceuticals, the impact of flow rate on dilution, and the impact of temperature on biodegradation. Compared with those before the COVID-19 epidemic, the detection concentrations of the target pharmaceuticals were relatively low. The reason for this might be that the prevention and control of the epidemic reduced the use and emission of the pharmaceuticals to a certain extent, and the high rainfall and runoff strengthened the dilution of water flow. The target pharmaceuticals, especially antibiotics, posed medium or low risks to aquatic organisms (especially algae). Considering the ecological risks and genotoxicity of pharmaceuticals and the potential risks of antibiotic-resistant genes, it is suggested to strengthen the investigation, evaluation, treatment, and control of pharmaceuticals in the water environment.

AI-Aided Design of Novel Targeted Covalent Inhibitors against SARS-CoV-2

The drug repurposing of known approved drugs (e.g., lopinavir/ritonavir) has failed to treat SARS-CoV-2-infected patients. Therefore, it is important to generate new chemical entities against this virus. As a critical enzyme in the lifecycle of the coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive target for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with a fragment-based drug design (ADQN–FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from the lead compounds based on our structure-based optimization policy (SBOP). All of the 47 lead compounds obtained directly with our AI model and related derivatives based on the SBOP are accessible in our molecular library. These compounds can be used as potential candidates by researchers to develop drugs against SARS-CoV-2.

A general controllable release amplification strategy of liposomes for single-particle collision electrochemical biosensing.

As an important component of the COVID-19 mRNA vaccines, liposomes play a key role in the efficient protection and delivery of mRNA to cells. Herein, due to the controllable release amplification strategy of liposomes, a reliable and robust single-particle collision electrochemical (SPCE) biosensor was constructed for H9N2 avian influenza virus (H9N2 AIV) detection by combining liposome encapsulation-release strategy with immunomagnetic separation. The liposomes modified with biotin and loaded with platinum nanoparticles (Pt NPs) were used as signal probes for the first time. Biotin facilitated the coupling of biomolecules (DNA or antibodies) through the specific reaction of biotin-streptavidin. Each liposome can encapsulate multiple Pt NPs, which were ruptured under the presence of 1 × PBST (phosphate buffer saline with 0.05% Tween-20) within 2 min, and the encapsulated Pt NPs were released for SPCE experiment. The combination of immunomagnetic separation not only improved the anti-interference capabilities but also avoided the agglomeration of Pt NPs, enabling the SPCE biosensor to realize ultrasensitive detection of 18.1 fg/mL H9N2 AIV. Furthermore, the reliable SPCE biosensor was successfully applied in specific detection of H9N2 AIV in complex samples (chicken serum, chicken liver and chicken lung), which promoted the universality of SPCE biosensor and its application prospect in early diagnosis of diseases.

Traditional Uses, Pharmacological Effects, and Molecular Mechanisms of Licorice in Potential Therapy of COVID-19.

The current Coronavirus disease 2019 (COVID-19) pandemic has become a global challenge, and although vaccines have been developed, it is expected that mild to moderate patients will control their symptoms, especially in developing countries. Licorice, not only a food additive, but also a common traditional Chinese herbal medicine, which has several pharmacological effects, such as anti-inflammation, detoxification, antibacterial, antitussive, and immunomodulatory effects, especially in respiratory diseases. Since the outbreak of COVID-19, glycyrrhizin, glycyrrhizin diamine and glycyrrhizin extract have been widely studied and used in COVID-19 clinical trials. Therefore, it is a very interesting topic to explore the material basis, pharmacological characteristics and molecular mechanism of licorice in adjuvant treatment of COVID-19. In this paper, the material basis of licorice for the prevention and treatment of COVID-19 is deeply analyzed, and there are significant differences among different components in different pharmacological mechanisms. Glycyrrhizin and glycyrrhetinic acid inhibit the synthesis of inflammatory factors and inflammatory mediators by blocking the binding of ACE 2 to virus spike protein, and exert antiviral and antibacterial effects. Immune cells are stimulated by multiple targets and pathways to interfere with the pathogenesis of COVID-19. Liquiritin can prevent and cure COVID-19 by simulating type I interferon. It is suggested that licorice can exert its therapeutic advantage through multi-components and multi-targets. To sum up, licorice has the potential to adjuvant prevent and treat COVID-19. It not only plays a significant role in anti-inflammation and anti-ACE-2, but also significantly improves the clinical symptoms of fever, dry cough and shortness of breath, suggesting that licorice is expected to be a candidate drug for adjuvant treatment of patients with early / mild COVID-19.

Impact of Expressing Cells on Glycosylation and Glycan of the SARS-CoV-2 Spike Glycoprotein.

The spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the first point of contact for the virus to recognize and bind to host receptors, is the focus of biomedical research seeking to effectively prevent and treat coronavirus disease (COVID-19). The mass production of spike glycoproteins is usually carried out in different cell systems. Studies have been shown that different expression cell systems alter protein glycosylation of hemagglutinin and neuraminidase in the influenza virus. However, it is not clear whether the cellular system affects the spike protein glycosylation. In this work, we investigated the effect of an expression system on the glycosylation of the spike glycoprotein and its receptor-binding domain. We found that there are significant differences in the glycosylation and glycans attached at each glycosite of the spike glycoprotein obtained from different expression cells. Since glycosylation at the binding site and adjacent amino acids affects the interaction between the spike glycoprotein and the host cell receptor, we recognize that caution should be taken when selecting an expression system to develop inhibitors, antibodies, and vaccines.

The effect of remote peer support on stigma in patients after breast cancer surgery during the COVID-19 pandemic: A protocol for systematic review and meta-analysis.

BACKGROUND: Patients after breast cancer surgery have a high sense of stigma due to the formation of surgical scars, loss of breast shape or other reasons, leading to anxiety, depression, and other adverse mental health problems, thus reducing their quality of life. Remote peer support intervention based on telephone, internet or email is low-cost and easy to spread, and protects patients' privacy, solves the barriers to access that many patients face when attending face-to-face programs. Therefore, remote peer support may be an effective way to reduce stigma and improve mental health in patients after breast cancer surgery during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Eight databases (PubMed, Embase, Cochrane Library, CNKI, PsycNET, MEDLINE, Psychology & Behavioral Sciences Collection and Web of Science) will be used to select eligible studies that were published from inception to May, 2021. The eligible studies will be screened, extracted and then the methodological quality will be evaluated independently by 2 reviewers. Review manager software version 5.3 software and Stata version 14.0 software will be used for meta-analysis. RESULTS: The results of this study will show the effect of remote peer support on stigma, depression and anxiety in patients after breast cancer surgery during the COVID-19 pandemic and will be submitted to a peer-reviewed journal for publication. CONCLUSION: The results of this study will provide evidence for the effectiveness of remote peer support in patients after breast cancer surgery during the COVID-19 pandemic. PROSPERO REGISTRATION NUMBER: CRD42021255971.

A study on clinical effect of Arbidol combined with adjuvant therapy on COVID-19.

This study aims to explore the clinical effect of Arbidol (ARB) combined with adjuvant therapy on patients with coronavirus disease 2019 (COVID-19). The study included 62 patients with COVID-19 admitted to the First Hospital of Jiaxing from January to March 2020, and all patients were divided into the test group and the control group according to whether they received ARB during hospitalization. Various indexes in the two groups before and after treatment were observed and recorded, including fever, cough, hypodynamia, nasal obstruction, nasal discharge, diarrhea, C-reactive protein (CRP), procalcitonin (PCT), blood routine indexes, blood biochemical indexes, time to achieve negative virus nucleic acid, and so on. The fever and cough in the test group were relieved markedly faster than those in the control group (P < .05); there was no obvious difference between the two groups concerning the percentage of patients with abnormal CRP, PCT, blood routine indexes, aspartate aminotransferase, and alanine aminotransferase (P > .05); the time for two consecutive negative nucleic acid tests in the test group were shorter than that in the control group; the hospitalization period of the patients in the test group and control group were (16.5 ± 7.14) days and (18.55 ± 7.52) days, respectively. ARB combined with adjuvant therapy might be able to relieve the fever of COVID-19 sufferers faster and accelerate the cure time to some degree, hence it's recommended for further research clinically.