Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer.

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

Ionizable drug delivery systems for efficient and selective gene therapy.

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.

Factors related to COVID-19 vaccine hesitancy among middle-income and low-income adults in the USA.

BACKGROUND: Vaccine hesitancy has been an ongoing challenge in campaigns, especially the rapid development and approval of the COVID-19 vaccines. The goal of this study was to understand the characteristics, perceptions and beliefs of COVID-19 vaccination prior to its widespread rollout among middle-income and low-income US adults. METHODS: Using a national sample of 2101 adults who completed an online assessment in 2021, this study examines the association of demographics, attitudes and behaviours related to COVID-19 vaccination intentions. Adaptive least absolute shrinkage and selection operator models were used to select these specific covariate and participant responses. Poststratification weights were generated using raking procedures and applied to improve generalisability. RESULTS AND CONCLUSION: Vaccine acceptance was high at 76% with 66.9% reporting intent to receive the COVID-19 vaccine when available. Only 8.8% of vaccine supporters screened positive for COVID-19-related stress compared with 9.3% among the vaccine hesitant. However, there were more people with vaccine hesitancy who screened positive for poor mental health and alcohol and substance misuse. The three main vaccine concerns were side effects (50.4%), safety (29.7%) and mistrust of vaccine distribution (14.8%).Factors influencing vaccine acceptance included age, education, children, region, mental health and social support, threat perception, opinion of governmental response, risk exposure and prevention activities and rejecting COVID-19 vaccine concerns. The results indicated acceptance was more strongly associated with beliefs and attitudes about the vaccine than sociodemographics, which are noteworthy and may lead to targeted interventions to increase COVID-19 vaccine acceptance among subgroups who are vaccine hesitant.

Roles of biomarkers in anti-MDA5-positive dermatomyositis, associated interstitial lung disease, and rapidly progressive interstitial lung disease.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5+ DM) is significantly associated with interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD) due to poor prognosis, resulting in high mortality rates. However, the pathogenic mechanism of MDA5+ DM-RPILD is unclear. Although some MDA5+ DM patients have a chronic course of ILD, many do not develop RPILD. Therefore, the related biomarkers for the early diagnosis, disease activity monitoring, and prediction of the outcome of RPILD in MDA5+ DM patients should be identified. Blood-based biomarkers are minimally invasive and can be easily detected. METHODS: Recent relative studies related to blood biomarkers in PubMed were reviewed. RESULTS: An increasing number of studies have demonstrated that dysregulated expression of blood biomarkers related to ILD such as ferritin, Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and cytokines, and some tumor markers in MDA5+ DM may provide information in disease presence, activity, treatment response, and prognosis. These studies have highlighted the great potentials of blood biomarker values for MDA5+ DM-ILD and MDA5+ DM-RPILD. This review provides an overview of recent studies related to blood biomarkers, besides highlighted protein biomarkers, including antibody (anti-MDA5 IgG subclasses and anti-Ro52 antibody), genetic (exosomal microRNAs and neutrophil extracellular traps related to cell-free DNA), and immune cellular biomarkers in MDA5+ DM, MDA5+ DM-ILD, and MDA5+ DM-RPILD patients, hopefully elucidating the pathogenesis of MDA5+ DM-ILD and providing information on the early diagnosis, disease activity monitoring, and prediction of the outcome of the ILD, especially RPILD. CONCLUSIONS: Therefore, this review may provide insight to guide treatment decisions for MDA5+ DM-RPILD patients and improve outcomes.

Effects of void deck on the airflow and pollutant dispersion in 3D street canyons.

In general, urban canyons are the areas most clearly affected by traffic pollutants since the ability of the canyon to self-ventilate is inhibited due to blockage of buildings or other urban structures. However, previous studies have aimed to improve the pedestrian-level wind speed with void deck in single buildings or short canyons. This study investigated the effects of void deck height and location, and the building height on the airflow field and the traffic pollutant diffusion in a long canyon with L/H = 10, validated by wind-tunnel experiment data. The results show that the void decks have a significant effect on the airflow and pollutant distribution inside the canyon. Air exchange rates (ACH) of the canyons with the void deck are much larger than that of regular canyons, and the perturbation changes of turbulence (ACH') decrease. For the windward void deck, purging flow rate (PFR) and normalized net escape velocity (NEV*) increase by 6.4 times compared to the regular canyon, and for the leeward void deck, increase by 13 times. In particular, when the void decks are at both buildings, they are increased by 38.3 times. Also, for the canyons with the void deck, traffic pollutants are removed out of the canyon by the strong airflow through the void deck. Therefore, unlike the regular canyons, as the void deck and the building height increases, the strength of the airflow through the void deck becomes stronger, and as a result, the mean pollutant concentration is significantly reduced at both walls and the pedestrian respiration level. The mean pollutant concentration on the wall of the building with the void deck and on the pedestrian respiration plane close to it is near zero. These findings can help ease traffic pollution inside the street canyons composed of high-rise buildings, especially in tropical cities.

Identification of coronaviruses in farmed wild animals reveals their evolutionary origins in Guangdong, southern China.

Coronavirus infections cause diseases that range from mild to severe in mammals and birds. In this study, we detected coronavirus infections in 748 farmed wild animals of 23 species in Guangdong, southern China, by RT-PCR and metagenomic analysis. We identified four coronaviruses in these wild animals and analysed their evolutionary origins. Coronaviruses detected in Rhizomys sinensis were genetically grouped into canine and rodent coronaviruses, which were likely recombinants of canine and rodent coronaviruses. The coronavirus found in Phasianus colchicus was a recombinant pheasant coronavirus of turkey coronavirus and infectious bronchitis virus. The coronavirus in Paguma larvata had a high nucleotide identity (94.6-98.5 per cent) with a coronavirus of bottlenose dolphin (Tursiops truncates). These findings suggested that the wildlife coronaviruses may have experienced homologous recombination and/or crossed the species barrier, likely resulting in the emergence of new coronaviruses. It is necessary to reduce human-animal interactions by prohibiting the eating and raising of wild animals, which may contribute to preventing the emergence of the next coronavirus pandemic.

A Five-Helix-Based SARS-CoV-2 Fusion Inhibitor Targeting Heptad Repeat 2 Domain against SARS-CoV-2 and Its Variants of Concern.

The prolonged duration of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has resulted in the continuous emergence of variants of concern (VOC, e.g., Omicron) and variants of interest (VOI, e.g., Lambda). These variants have challenged the protective efficacy of current COVID-19 vaccines, thus calling for the development of novel therapeutics against SARS-CoV-2 and its VOCs. Here, we constructed a novel fusion inhibitor-based recombinant protein, denoted as 5-Helix, consisting of three heptad repeat 1 (HR1) and two heptad repeat 2 (HR2) fragments. The 5-Helix interacted with the HR2 domain of the viral S2 subunit, the most conserved region in spike (S) protein, to block homologous six-helix bundle (6-HB) formation between viral HR1 and HR2 domains and, hence, viral S-mediated cell-cell fusion. The 5-Helix potently inhibited infection by pseudotyped SARS-CoV-2 and its VOCs, including Delta and Omicron variants. The 5-Helix also inhibited infection by authentic SARS-CoV-2 wild-type (nCoV-SH01) strain and its Delta variant. Collectively, our findings suggest that 5-Helix can be further developed as either a therapeutic or prophylactic to treat and prevent infection by SARS-CoV-2 and its variants.

Therapeutic Development in COVID-19.

Since the outbreak of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2, the disease has spread rapidly worldwide and developed into a global pandemic, causing a significant impact on the global health system and economic development. Scientists have been racing to find effective drugs and vaccines for the treatment and prevention of COVID-19. However, due to the diversity of clinical manifestations caused by COVID-19, no standard antiviral regimen beyond supportive therapy has been established. Ongoing clinical trials are underway to evaluate the efficacy of drugs that primarily act on the viral replication cycle or enhanced immunity of patients. This chapter will summarize the currently used antiviral and adjuvant therapies in clinical practice and provide a theoretical basis for the future treatment of COVID-19.

The State of Emergency in Public Health and the Exceptional Regulations in Administrative Law

It is a great shock to the legal system by COVID-19 or the spread of so-called severe acute respiratory syndrome coronavirus, which made it hard to react. Even though there might be some general principles for emergency in the Administrative Law, they belong to individual administrative cases. Moreover, the regulation for emergency in Constitution depends on the political decision of the decision-maker. Therefore, it is necessary to give the administrative agencies the possibility for the discretion in the field of the general theory of Administrative Law and of Public Health concerning to emergency due to the pandemic. The review of the norm-interpretating should be loose as well. Meanwhile, in order to avoid abusing rights, an regular examination on its validity and rationality should also be performed. Besides, administrative discretion should be made from the consensus decision by specialists.

Drug Repurposing of Itraconazole and Estradiol Benzoate against COVID-19 by Blocking SARS-CoV-2 Spike Protein-Mediated Membrane Fusion.

SARS-CoV-2 caused the emerging epidemic of coronavirus disease in 2019 (COVID-19). To date, there are more than 82.9 million confirmed cases worldwide, there is no clinically effective drug against SARS-CoV-2 infection. The conserved properties of the membrane fusion domain of the spike (S) protein across SARS-CoV-2 make it a promising target to develop pan-CoV therapeutics. Herein, two clinically approved drugs, Itraconazole (ITZ) and Estradiol benzoate (EB), are found to inhibit viral entry by targeting the six-helix (6-HB) fusion core of SARS-CoV-2 S protein. Further studies shed light on the mechanism that ITZ and EB can interact with the heptad repeat 1 (HR1) region of the spike protein, to present anti-SARS-CoV-2 infections in vitro, indicating they are novel potential therapeutic remedies for COVID-19 treatment. Furthermore, ITZ shows broad-spectrum activity targeting 6-HB in the S2 subunit of SARS-CoV and MERS-CoV S protein, inspiring that ITZ have the potential for development as a pan-coronavirus fusion inhibitor.

The adoption of self-driving delivery robots in last mile logistics.

Covid-19, the global pandemic, has taught us the importance of contactless delivery service and robotic automation. Using self-driving delivery robots can provide flexibility for on-time deliveries and help better protect both driver and customers by minimizing contact. To this end, this paper introduces a new vehicle routing problem with time windows and delivery robots (VRPTWDR). With the help of delivery robots, considerable operational time savings can be achieved by dispatching robots to serve nearby customers while a driver is also serving a customer. We provide a mathematical model for the VRPTWDR and investigate the challenges and benefits of using delivery robots as assistants for city logistics. A two-stage matheurisitic algorithm is developed to solve medium scale VRPTWDR instances. Finally, results of computational experiments demonstrate the value of self-driving delivery robots in urban areas by highlighting operational limitations on route planning.

Terminator or accelerator? Lessons from the peer-to-peer accommodation hosts in China in responses to COVID-19.

This study investigates how peer-to-peer accommodation (P2PA) hosts in China have responded to the COVID-19 pandemic. A multi-case study approach was adopted to depict the decision-making logic of three different types of hosts-speculators, diplomats, and entrepreneurs-based on an awareness-motivation-capability (AMC) framework under COVID-19. The findings highlight the role of owner motivation (profit/sharing/entrepreneurial-driven) and capabilities, such as having a unique value proposition and linkages with other hospitality experience, under COVID-19. Meanwhile, the platform collaboration capability failed to support survival during the pandemic. Moreover, the current study indicated that, after the COVID-19, entrepreneurs will continue to innovate, diplomats' operations will remain unchanged and speculators will quit hosting. Hence, COVID-19 is an accelerator of P2P industry that reserving the hosts who embrace the original features of the P2PA sector, e.g. sharing and a focus on the experience, and eliminating the hosts who have diluted the uniqueness of the sector.

A Bayesian Updating Scheme for Pandemics: Estimating the Infection Dynamics of COVID-19

Epidemic models play a key role in understanding and responding to the emerging COVID-19 pandemic. Widely used compartmental models are static and are of limited use to evaluate intervention strategies of combatting the pandemic. Applying the technology of data assimilation, we propose a Bayesian updating approach for estimating epidemiological parameters using observable information to assess the impacts of different intervention strategies. We adopt a concise renewal model and propose new parameters by disentangling the reduction of instantaneous reproduction number Rt into mitigation and suppression factors to quantify intervention impacts at a finer granularity. A data assimilation framework is developed to estimate these parameters including constructing an observation function and developing a Bayesian updating scheme. A statistical analysis framework is built to quantify the impacts of intervention strategies by monitoring the evolution of the estimated parameters. We reveal the intervention impacts in European countries and Wuhan and the resurgence risk in the United States.

Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19.

Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. In this review, we highlight recent research advance in the structure, function and development of antivirus drugs targeting the S protein.