An Electric Vehicle Assisted Charging Mechanism for Unmanned Aerial Vehicles

The global greenhouse effect and air pollution problems have been deteriorating in recent years. The power generation in the future is expected to shift from fossil fuels to renewables, and many countries have also announced the ban on the sale of vehicles powered by fossil fuels in the next few decades, to effectively alleviate the global greenhouse effect and air pollution problems. In addition to electric vehicles (EVs) that will replace traditional fuel vehicles as the main ground transportation vehicles in the future, unmanned aerial vehicles (UAVs) have also gradually and more recently been widely used for military and civilian purposes. The recent literature estimated that UAVs will become the major means of transport for goods delivery services before 2040, and the development of passenger UAVs will also extend the traditional human ground transportation to low-altitude airspace transportation. In recent years, the literature has proposed the use of renewable power supply, battery swapping, and charging stations to refill the battery of UAVs. However, the uncertainty of renewable power generation cannot guarantee the stable power supply of UAVs. It may even be very possible that a large number of UAVs need to be charged during the same period, causing congestion in charging stations or battery swapping facilities and delaying the arranged schedules of UAVs. Although studies have proposed the method of that employing moving EVs along with wireless charging technology in order to provide electricity to UAVs with urgent needs, the charging schemes are still oversimplified and have many restrictions. In addition, different charging options should be provided to fit the individual need of each UAV. In view of this, this work attempts to meet the mission characteristics and needs of various UAVs by providing an adaptive flight path and charging plan attached to individual UAVs, as well as reducing the power load of the renewable power generation during the peak period. We ran a series of simulations for the proposed flight path and charging mechanism to evaluate its performance. The simulation results revealed that the solutions proposed in this work can be used by UAV operators to fit the needs of each individual UAV.

Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2 (preprint)

Analyses of the genomic diversity of SARS-CoV-2 found that some sites across the genome appear to have mutated independently multiple times with frequency significantly higher than four-fold sites, which can be either due to mutational bias, i.e., elevated mutation rate in some sites of the genome, or selection of the variants due to antagonistic pleiotropy, a condition where mutations increase some components of fitness at a cost to others. To examine how different forces shaped evolution of SARS-CoV-2 in 2020-2021, we analyzed a large set of genome sequences (~ 2 million). Here we show that while evolution of SARS-CoV-2 during the pandemic was largely mutation-driven, a group of nonsynonymous changes is probably maintained by antagonistic pleiotropy. To test this hypothesis, we studied the function of one such mutation, spike M1237I. Spike I1237 increases viral assembly and secretion, but decreases efficiency of transmission in vitro. Therefore, while the frequency of spike M1237I may increase within hosts, viruses carrying this mutation would be outcompeted at the population level. We also discuss how the antagonistic pleiotropy might facilitate positive epistasis to promote virus adaptation and reconcile discordant estimates of SARS-CoV-2 transmission bottleneck sizes in previous studies.

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.

Clinical Spectrum and Trajectory of Innovative Therapeutic Interventions for Insomnia: A Perspective.

Increasing incidences of insomnia in adults, as well as the aging population, have been reported for their negative impact on the quality of life. Insomnia episodes may be associated with neurocognitive, musculoskeletal, cardiovascular, gastrointestinal, renal, hepatic, and metabolic disorders. Epidemiological evidence also revealed the association of insomnia with oncologic and asthmatic complications, which has been indicated as bidirectional. Two therapeutic approaches including cognitive behavioral therapy (CBT) and drugs-based therapies are being practiced for a long time. However, the adverse events associated with drugs limit their wide and long-term application. Further, Traditional Chinese medicine, acupressure, and pulsed magnetic field therapy may also provide therapeutic relief. Notably, the recently introduced cryotherapy has been demonstrated as a potential candidate for insomnia which could reduce pain, by suppressing oxidative stress and inflammation. It seems that the synergistic therapeutic approach of cryotherapy and the above-mentioned approaches might offer promising prospects to further improve efficacy and safety. Considering these facts, this perspective presents a comprehensive summary of recent advances in pathological aetiologies of insomnia including COVID-19, and its therapeutic management with a greater emphasis on cryotherapy.

Radiation Recall Pneumonitis: A Rare Syndrome That Should Be Recognized.

Radiation recall pneumonitis (RRP) is a rare but severe condition which has been mainly detected in the previously irradiated lung of patients with cancer after administering inciting agents, most commonly antineoplastic regimens including chemotherapy, targeted therapy, or immunotherapy. More recently, coronavirus disease vaccines were found to induce RRP. In addition to typical radiation pneumonitis (RP) or drug-induced interstitial lung disease, the management of RRP requires withholding inciting agents and steroid therapy. Thus, the occurrence of RRP could significantly impact cancer treatment, given that inciting agents are withheld temporarily and even discontinued permanently. In the present review, we discuss the current understanding and evidence on RRP and provide additional insights into this rare but severe disease.

Exploring and Developing a New Culturally-Appropriate Diabetes Distress Scale in Taiwan.

Introduction: The aim of this study was to develop and validate a new diabetes distress scale suitable for Chinese and Taiwanese culture. Methods: This study collected the current diabetes distress measurement tools, re-organized current definitions about the domains of diabetes distress, and then developed a new tool. Three hundred and ninety-five participants from four hospitals in northern Taiwan were recruited by cluster randomized sampling for validity test. Results: We found the new diabetes distress scale had appropriate reliability and validity, including an acceptable model fit for the 12-item scale. Conclusions: This new diabetes distress scale might be more directly related to emotional distress issues blood glucose control, improve the clinical conspicuity of diabetes distress, and even benefit the overall care of diabetic patients in Taiwan. Further studies about the validity and reliability of this new tool in a nationwide setting are needed.

Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro.

BACKGROUND: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. METHODS: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. FINDINGS: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. INTERPRETATION: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Association between Early Absolute Neutrophil Count and Level of D-Dimer among Patients with COVID-19 Infection in Central Taiwan.

Thromboembolism is a critical event in patients with coronavirus disease (COVID)-19 infection and highly associated with neutrophil extracellular traps. D-dimer has been found to be an essential thromboembolism-associated biomarker; however, the association between absolute neutrophil count (ANC) and level of D-dimer in patients with COVID-19 infection remains unclear. In this study, we enrolled consecutive patients with COVID-19 admitted to Taichung Veterans General Hospital (TCVGH), a referral center in central Taiwan with 20 airborne infection isolation rooms. Spearman correlation was used to determine the association between ANC and level of D-dimer in distinct time periods. A total of 28 consecutive patients with COVID-19 infection were enrolled, and 32.1% (9/28) of them required mechanical ventilation. Patients requiring mechanical ventilation had a higher ANC (8225 vs. 3427/µL, p < 0.01) and levels of D-dimer (6.0 vs. 0.6 mg/L, p < 0.01) compared with those without mechanical ventilation. Notably, we identified five patients with image-proven thromboembolic events during the hospital course, with the number of patients with pulmonary embolism, venous thrombosis and acute ischemic stroke were 2, 1, and 2, respectively. We found that ANC within 4 days correlated with the level of D-dimer to a moderate level (r = 0.71, p < 0.05), and the association between ANC and D-dimer no longer exist after day 5. In conclusion, we found highly prevalent thromboembolic events among patients with severe COVID-19 infection in central Taiwan and identified the association between early ANC and D-dimer. More studies are warranted to elucidate the underlying mechanism.

Assessing the Knowledge, Attitudes and Practices of COVID-19 among Quarantine Hotel Workers in China.

During the pandemic, quarantine hotel workers face a higher risk of infection while they host quarantine guests from overseas. This study's aim is to gain an understanding of the knowledge, attitudes, and practices (KAP) of quarantine hotel workers in China. A total of 170 participants took part in a cross-sectional survey to assess the KAP of quarantine hotel workers in China, during the COVID-19 pandemic. The chi-square test, independent t-test, one-way analysis of variance (ANOVA), descriptive analysis, and binary logistic regression were used to examine the sociodemographic factors associated with KAP levels during the COVID-19 pandemic. The results show that 62.41% have good knowledge, 94.7% have a positive attitude towards COVID-19, but only 78.2% have good practices. Most quarantine hotel workers (95.3%) are confident that COVID-19 will be successfully controlled and that China is handling the COVID-19 crisis well (98.8%). Most quarantine hotel workers are also taking personal precautions, such as avoiding crowds (80.6%) and wearing facemasks (97.6%). The results evidence that quarantine hotel workers in China have acquired the necessary knowledge, positive attitudes and proactive practices in response to the COVID-19 pandemic. The results of this study can provide a reference for quarantine hotel workers and their targeted education and intervention.

Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. TRIAL REGISTRATION: PROSPERO 2020 CRD42020175648.

Management and implementation strategies of pre-screening triage in children during coronavirus disease 2019 pandemic in Guangzhou, China.

BACKGROUND: Emerging infectious diseases are a constant threat to the public's health and health care systems around the world. Coronavirus disease 2019 (COVID-2019), which was defined by the World Health Organization as pandemic, has rapidly emerged as a global health threat. Outbreak evolution and prevention of international implications require substantial flexibility of frontline health care facilities in their response. AIM: To explore the effect of the implementation and management strategy of pre-screening triage in children during COVID-19. METHODS: The standardized triage screening procedures included a standardized triage screening questionnaire, setup of pre-screening triage station, multi-point temperature monitoring, extensive screenings, and two-way protection. In order to ensure the implementation of the pre-screening triage, the prevention and control management strategies included training, emergency exercise, and staff protection. Statistical analysis was performed on the data from all the children hospitalized from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. Data were obtained from questionnaires and electronic medical record systems. RESULTS: A total of 17561 children, including 2652 who met the criteria for screening, 192 suspected cases, and two confirmed cases without omission, were screened from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. There was zero transmission of the infection to any medical staff. CONCLUSION: The effective strategies for pre-screening triage have an essential role in the prevention and control of hospital infection.

Lung Function In Discharged Patients After Coronavirus Infection (SARS, MERS, COVID-19): A Systemic Review And Meta-Analysis (preprint)

Background: To date, coronaviruses have caused three pandemics. Fewer studies concentrated on the prognosis of lung function.Objective: To summarize the lung function of the discharged after coronavirus infection.Methods: We systematically searched PubMed, Cochrane Library, Web of Science, and EMBASE. Two authors independently screened articles and extracted data. On average, predicted values and damage rates of seven lung function indices were pooled by single-arm meta-analysis. And, in severe/critical vs. non-severe/critical and one-year follow-up, they were pooled by two-arm meta-analysis. The source of high heterogeneity was explored by meta-regression or subgroup analysis. Results: Of the 7798 articles identified, 34 studies were included. On average, the pooled predicted values of the seven indices were within normal except for DLCO (79.2, 95% CI (76.2－82.2 )). Damage of lung function indices accounted for 6.2－35.2% of the discharged with DLCO most, and 83－100% of the damage was mild. Meta-regression showed that different viruses, countries, disease settings, and measurement times were not the source of high heterogeneities. In severe/critical illness vs. non-severe/critical, predicted values of seven indices were significantly lower (largest gap in DLCO (WMD -11.60, 95% CI -14.23－-8.98)). However, damage rates got rises only in DLCO (RR 1.74, 95% CI 1.46－2.07) and TLC, having no differences in the other indices. In one-year follow-up, predicted values were significantly improved in the severe/critical subgroup, while having no change in the non-severe/critical subgroup. Damage rates got no improvement in all indices.Interpretation: A single predicted value or damage rate can't give a clear description of lung function after coronavirus infection, and the trends of the two are sometimes inconsistent. We suggest more prospective cohort or follow-up studies in the future to lessen the influence of differences in lung function measurements across studies.Registration: PROSPERO (CRD42020192843)

COVID-19 infection in patients with connective tissue disease: A multicity study in Hubei province, China.

Novel Coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID-19 patients hospitalized in 23 centers affiliated to Hubei COVID-19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID-19 infection (p = 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts (p values were 0.033, < 0.001, and 0.071, respectively). Hydroxychloroquine therapy and low- to medium-dose glucocorticoids before COVID-19 diagnosis reduced the progression of COVID-19 to severe/critical conditions (p = 0.001 for hydroxychloroquine; p = 0.006 for glucocorticoids). Our data suggests that COVID-19 in CTD patients may be more severe compared to patients with AS or gout.

D614G Substitution of SARS-CoV-2 Spike Protein Increases Syncytium Formation and Viral Transmission via Enhanced Furin-mediated Spike Cleavage (preprint)

ABSTRACT Since the D614G substitution in the spike (S) of SARS-CoV-2 emerged, the variant strain underwent rapid expansion to become the most abundant strain worldwide. Therefore, this substitution may provide an advantage of viral spreading. To explore the mechanism, we analyzed 18 viral isolates containing S proteins with either G614 or D614. Both the virus titer and syncytial phenotype were significantly increased in S-G614 than in S-D614 isolates. We further showed increased cleavage of S at the furin substrate site, a key event that promotes syncytium, in S-G614 isolates. These functions of the D614G substitution were validated in cells expressing S protein. The effect on syncytium was abolished by furin inhibitor treatment and mutation of the furin-cleavage site, suggesting its dependence on cleavage by furin. Our study provides a mechanistic explanation for the increased transmissibility of S-G614 containing SARS-CoV-2 through enhanced furin-mediated S cleavage, which increases membrane fusion and virus infectivity.

Symptomatic and optimal supportive care of critical COVID-19: A case report and literature review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) severity is classified as asymptomatic, mild, moderate, severe, and critical. Mild cases account for a large percentage of cases in the epidemic and typically exhibit a favorable prognosis. However, a 49%-67% mortality is noted in critical cases. No COVID-19-specific drug has been reported to date, and symptomatic and optimal supportive care, including oxygenation, anti-coinfection treatments, and ventilation, represent the mainstay of treatment for this disease, especially in critical patients. CASE SUMMARY: In the above-mentioned context, we share our experience with the treatment of one critical COVID-19 case and review the relevant literature. CONCLUSION: Timely tracheal intubation, reasonable mechanical ventilation support, appropriate anti-infection treatment, and early anticoagulation and immunity support are key factors in the successful treatment of this case.

Drug screening and development from the affinity of S protein of new coronavirus with ACE2.

Recently, various studies have shown that angiotensin-converting enzyme 2 (ACE2) acts as the "doorknob" that can be bound by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which conduces to its entrance to the host cells, and plays an important role in corona virus disease 2019 (COVID-19). This paper aims to collect and sorts out the existing drugs, which exert the ability to block the binding of S protein and ACE2 so as to provide directions for the later drug development. By reviewing the existing literature, we expound the pathogenesis of SARS-CoV-2 from the perspective of S protein and ACE2 binding, and summarize the drugs and compounds that can interfere with the interaction of spike protein and ACE2 receptor from different ways. We summarized five kinds of substances, including peptide P6, griffithsin, hr2p analogs, EK1, vaccine, monoclonal antibody, cholesterol-depleting agents, and extracts from traditional Chinese medicine. They can fight SARS-CoV-2 by specifically binding to ACE2 receptor, S protein, or blocking membrane fusion between the host and virus. ACE2 is the key point for SARS-CoV-2 to enter the cells, and it is also the focus of drug intervention. Our drug summary on this pathomechanism is expected to provide ideas for the drug research on SARS-CoV-2 and help to develop anti-coronavirus drugs of broad spectrum for future epidemics.