Optimizing the Cleaning and Disinfection Scheme for Dockless Shared Bikes

Shared bikes can help cities achieve carbon neutrality goals. Cleaning and disinfection are vital procedures of the maintenance of shared bikes, especially during the COVID-19 pandemic because shared bikes could be a transmission intermediary of viruses. This study proposes an optimization model of the cleaning and disinfection scheme of the dockless shared bikes. The disinfection is assumed to be performed at night, when the usage is lowest. By regarding the disinfection staff as traveling salesmen, the model is formulated as an extension of the Multidepot Multiple Traveling Salesman Problem (MDMTSP). The objective function is to minimize the total cost;which consists of the cost associated with the working time and per-capita cost of the disinfection staff. A heuristic algorithm combining k -means clustering and genetic algorithm (K-GA) is adopted to find the lower bound solution. Then, the K-GA-adjustment algorithm has been adopted to find the solutions that satisfy the constraints. To reduce the computing time needed, an approximate function for the lower bound of the optimal number of disinfection staff is obtained by constructing a Continuous Approximation (CA) model. A case study based on real location data of shared bikes in Chengdu, China, is performed to show how the maintenance department could adopt the optimization framework to design an efficient scheme to clean and disinfect the shared bikes. [ABSTRACT FROM AUTHOR] Copyright of Journal of Advanced Transportation is the property of Hindawi Limited 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Feasibility, Usability, and Acceptability of Online Mind-Body Exercise Programs for Older Adults: A Scoping Review.

Objectives: Engaging in mind-body exercises (MBEs: e.g., Tai Chi and yoga) can have physical and mental health benefits particularly for older adults. Many MBEs require precise timing and coordination of complex body postures posing challenges for online instruction. Such challenges include difficulty viewing instructors as they demonstrate different movements and lack of feedback to participants. With the shift of exercise programs to online platforms during the COVID-19 pandemic, we conducted a scoping review to examine the feasibility, usability, and acceptability of online MBE classes for older adults. Materials and Methods: We followed the scoping review methodology and adhered to the PRISMA reporting checklist. We searched five databases: Medline, Embase, CINHAL, Web of Science, and ACM digital library. Screening of articles and data extraction was conducted independently by two reviewers. Settings/Location: Online/virtual. Subjects: Older adults ≥55 years of age. Outcome Measures: Feasibility measures. Results: Of 6711 studies retrieved, 18 studies were included (715 participants, mean age 66.9 years). Studies reported moderate to high retention and adherence rates (mean >75%). Older adults reported online MBE classes were easy to use and reported high satisfaction with the online format. We also identified barriers (e.g., lack of space and privacy and unstable internet connection) and facilitators (e.g., convenience and technical support) to the online format. Opinions related to social connectedness were mixed. Conclusion: Online MBE programs for older adults appear to be a feasible and acceptable alternative to in-person programs. It is important to consider the type of exercise (e.g., MBE), diverse teaching styles, and learner needs when designing online exercise classes.

Structure and Function of Cationic and Ionizable Lipids for Nucleic Acid Delivery.

Hereditary genetic diseases, cancer, and infectious diseases are affecting global health and become major health issues, but the treatment development remains challenging. Gene therapies using DNA plasmid, RNAi, miRNA, mRNA, and gene editing hold great promise. Lipid nanoparticle (LNP) delivery technology has been a revolutionary development, which has been granted for clinical applications, including mRNA vaccines against SARS-CoV-2 infections. Due to the success of LNP systems, understanding the structure, formulation, and function relationship of the lipid components in LNP systems is crucial for design more effective LNP. Here, we highlight the key considerations for developing an LNP system. The evolution of structure and function of lipids as well as their LNP formulation from the early-stage simple formulations to multi-components LNP and multifunctional ionizable lipids have been discussed. The flexibility and platform nature of LNP enable efficient intracellular delivery of a variety of therapeutic nucleic acids and provide many novel treatment options for the diseases that are previously untreatable.

UBR5 Acts as an Antiviral Host Factor against MERS-CoV via Promoting Ubiquitination and Degradation of ORF4b.

Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome encoded fewer accessory proteins, among which the ORF4b protein had anti-immunity ability in both the cytoplasm and nucleus. Our work for the first time revealed that ORF4b protein was unstable in the host cells and could be degraded by the ubiquitin proteasome system. After extensive screenings, it was found that UBR5 (ubiquitin protein ligase E3 component N-recognin 5), a member of the HECT E3 ubiquitin ligases, specifically regulated the ubiquitination and degradation of ORF4b. Similar to ORF4b, UBR5 can also translocate into the nucleus through its nuclear localization signal, enabling it to regulate ORF4b stability in both the cytoplasm and nucleus. Through further experiments, lysine 36 was identified as the ubiquitination site on the ORF4b protein, and this residue was highly conserved in various MERS-CoV strains isolated from different regions. When UBR5 was knocked down, the ability of ORF4b to suppress innate immunity was enhanced and MERS-CoV replication was stronger. As an anti-MERS-CoV host protein, UBR5 targets and degrades ORF4b protein through the ubiquitin proteasome system, thereby attenuating the anti-immunity ability of ORF4b and ultimately inhibiting MERS-CoV immune escape, which is a novel antagonistic mechanism of the host against MERS-CoV infection. IMPORTANCE ORF4b was an accessory protein unique to MERS-CoV and was not present in SARS-CoV and SARS-CoV-2 which can also cause severe respiratory disease. Moreover, ORF4b inhibited the production of antiviral cytokines in both the cytoplasm and the nucleus, which was likely to be associated with the high lethality of MERS-CoV. However, whether the host proteins regulate the function of ORF4b is unknown. Our study first determined that UBR5, a host E3 ligase, was a potential host anti-MERS-CoV protein that could reduce the protein level of ORF4b and diminish its anti-immunity ability by inducing ubiquitination and degradation. Based on the discovery of ORF4b-UBR5, a critical molecular target, further increasing the degradation of ORF4b caused by UBR5 could provide a new strategy for the clinical development of drugs for MERS-CoV.

Host E3 ligase HUWE1 attenuates the proapoptotic activity of the MERS-CoV accessory protein ORF3 by promoting its ubiquitin-dependent degradation.

With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins. While the number of each of these proteins varies greatly among different coronaviruses, accessory proteins are most closely related to the pathogenicity of the virus. We found for the first time that the ORF3 accessory protein of MERS-CoV, which closely resembles the ORF3a proteins of severe acute respiratory syndrome coronavirus and SARS-CoV-2, has the ability to induce apoptosis in cells in a dose-dependent manner. Through bioinformatics analysis and validation, we revealed that ORF3 is an unstable protein and has a shorter half-life in cells compared to that of severe acute respiratory syndrome coronavirus and SARS-CoV-2 ORF3a proteins. After screening, we identified a host E3 ligase, HUWE1, that specifically induces MERS-CoV ORF3 protein ubiquitination and degradation through the ubiquitin-proteasome system. This results in the diminished ability of ORF3 to induce apoptosis, which might partially explain the lower spread of MERS-CoV compared to other coronaviruses. In summary, this study reveals a pathological function of MERS-CoV ORF3 protein and identifies a potential host antiviral protein, HUWE1, with an ability to antagonize MERS-CoV pathogenesis by inducing ORF3 degradation, thus enriching our knowledge of the pathogenesis of MERS-CoV and suggesting new targets and strategies for clinical development of drugs for MERS-CoV treatment.

Taiwan's Response to Influenza: A Seroepidemiological Evaluation of Policies and Implications for Pandemic Preparedness.

OBJECTIVES: To evaluate class suspension and mass vaccination implemented among Taipei schoolchildren during the 2009 influenza pandemic and investigate factors affecting antibody responses. METHODS: We conducted 2 cohort studies on: (1) 972 schoolchildren from November 2009-March 2010 to evaluate pandemic policies and (2) 935 schoolchildren from November 2011-March 2012 to verify factors in antibody waning. Anti-influenza H1N1pdm09 hemagglutination inhibition antibodies (HI-Ab) were measured from serum samples collected before vaccination, and at 1 and 4 months after vaccination. Factors affecting HI-Ab responses were investigated through logistic regression and generalized estimating equation. RESULTS: Seroprevalence of H1N1pdm09 before vaccination was significantly higher among schoolchildren who experienced class suspensions than those who did not (59.6% vs 47.5%, p<0.05). Participating in after-school activities (adjusted odds ratio [aOR]=2.47, p=0.047) and having ≥3 hours per week of exercise (aOR=2.86, p=0.019) were significantly correlated with H1N1pdm09 infection. Two doses of the H1N1pdm09 vaccine demonstrated significantly better antibody persistence than 1 dose (HI-Ab geometric mean titer: 132.5 vs 88.6, p=0.047). Vaccine effectiveness after controlling for preexisting immunity was 86% (32%-97%). Exercise ≥3 hours per week and preexisting immunity were significantly associated with antibody waning/maintenance. CONCLUSIONS: This study is the first to show that exercise and preexisting immunity may affect antibody waning. Further investigation is needed to identify immune correlates of protection.

In silico prediction of Severe Acute Respiratory Syndrome Coronavirus 2 main protease cleavage sites.

One of the emerging subjects to combat the SARS-CoV-2 virus is to design accurate and efficient drug such as inhibitors against the viral protease to stop the viral spread. In addition to laboratory investigation of the viral protease, which is fundamental, the in silico research of viral protease such as the protease cleavage site prediction is critically important and urgent. However, this problem has yet to be addressed. This article has, for the first time, investigated this problem using the pattern recognition approaches. The article has shown that the pattern recognition approaches incorporating a specially tailored kernel function for dealing with amino acids has the outstanding performance in the accuracy of cleavage site prediction and the discovery of the prototype cleavage peptides.

Microbiome Profiling Using Shotgun Metagenomic Sequencing Identified Unique Microorganisms in COVID-19 Patients With Altered Gut Microbiota.

COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut-lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus, Bacteroides oleiciplenus, Fusobacterium ulcerans, and Prevotella bivia. The abundances of Bacteroides stercoris, B. vulgatus, B. massiliensis, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, Prevotella bivia, Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile, Streptococcus salivarius, Coprococcus catus, Eubacterium hallii, Enterobacter aerogenes, and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman's correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.

Syndrome differentiation and treatment of Severe acute respiratory syndrome Coronavirus 2 infected pneumonia from cold and dampness epidemic virus

Severe acute respira tory syndrome coronavirus 2 (SARS-CoV-2) infected pneumonia is a new acute infectious pneumonia, which outbroke in Wuhan City, Hubei Province at the end of 2019. It is highly consistent with the epidemic disease of TCM. According to the understanding of TCM epidemic disease, this article analyze d that cold and dampness epidemic virus is the important cause of SARS-CoV-2 infected pneumonia. Based on the general treatment principle of eliminating cold and dampness, avoiding filth and turbidity, this article discussed the TCM syndrome differentiation and treatment in different stages and protective measures of this disease, with the purpose to provide references and help for prevention and treatment of TCM.

Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2.

SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 µM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 µM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19.

Analysis of the management measures and effects in prevention and control of COVID-19 in outpatient service of a general hospital / 医学研究生学报

To preliminarily analyze the prevention and control of COVID-19, a general hospital outpatient service took six management measures, including setting up a leading group, building rules and regulations, infection control and supervision, special training, humanized service, public opinion propaganda. After nearly two months, the rates of both body temperature monitoring and epidemiological history screening are 100%, the medical staff infection rate is zero, and no cross infection between the patients due to adopting outpatient service comprehensive management measures which had strong organization and leadership, effective targeted training, effective control of all links in epidemic prevention and control work. During the fight against COVID-19, outpatient management played an important role in hospital management. The above approaches provide valuable experience for preventing the spread of infectious diseases effectively and winning the biological weapon wars in the future.

SARS-CoV-2: Mechanism of infection and emerging technologies for future prospects.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally to over 200 countries with more than 23 million confirmed cases and at least 800,000 fatalities as of 23 August 2020. Declared a pandemic on March 11 by World Health Organization, the disease caused by SARS-CoV-2 infection, called coronavirus disease 2019 (COVID-19), has become a global public health crisis that challenged all national healthcare systems. This review summarized the current knowledge about virologic and pathogenic characteristics of SARS-CoV-2 with emphasis on potential immunomodulatory mechanism and drug development. With multiple emerging technologies and cross-disciplinary approaches proving to be crucial in our global response against COVID-19, the application of PROteolysis TArgeting Chimeras strategy, CRISPR-Cas9 gene editing technology, and Single-Nucleotide-Specific Programmable Riboregulators technology in developing antiviral drugs and detecting infectious diseases are proposed here. We also discussed the available but still limited epidemiology of COVID-19 as well as the ongoing efforts on vaccine development. In brief, we conducted an in-depth analysis of the pathogenesis of SARS-CoV-2 and reviewed the therapeutic options for COVID-19. We also proposed key research directions in the future that may help uncover more underlying molecular mechanisms governing the pathology of COVID-19.

Recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients during medical isolation observation.

Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients is receiving more attention. Herein we report a cohort study on the follow-up of 182 recovered patients under medical isolation observation. Twenty (10.99%) patients out of the 182 were detected to be SARS-CoV-2 RNA positive (re-positives), although none showed any clinical symptomatic recurrence, indicating that COVID-19 responds well to treatment. Patients aged under 18 years had higher re-positive rates than average, and none of the severely ill patients re-tested positive. There were no significant differences in sex between re-positives and non-re-positives. Notably, most of the re-positives turned negative in the following tests, and all of them carried antibodies against SARS-CoV-2. This indicates that they might not be infectious, although it is still important to perform regular SARS-CoV-2 RNA testing and follow-up for assessment of infectivity. The findings of this study provide information for improving the management of recovered patients, and for differentiating the follow-up of recovered patients with different risk levels.

Recurrence of Positive SARS-CoV-2 Viral RNA in Recovered COVID-19 Patients During Medical Isolation Observation (preprint)

Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients get more attention. Here we report a cohort study on the follow up of 182 recovered patients under medical isolation observation. There are 20 (10.99 %) patients out of the 182 were detected SARS-CoV-2 RNA turned positive, but none of them shows any clinical symptomatic recurrence indicating that COVID-19 has a good prognosis. Females and young patients aged under 15 have higher re-positive rate than the average, and none of the severe patients turned re-positive. Notably, most of the re-positive cases turn negative in the followed tests, suggesting that the importance of dynamic surveillance of SARS-CoV-2 RNA for infectivity assessment.