Mitigation of breathing contaminants: Exhaust location optimization for indoor space with impinging jet ventilation supply

Densely occupied spaces (e.g., classrooms) are generally over-crowded and pose a high risk of cross-infection during the pandemic of COVID-19. Among various ventilation systems, impinging jet ventilation (IJV) system might be promising for such spaces. However, the exhaust location of the IJV system used for densely occupied classrooms is unclear. This study aims to investigate the effects of exhaust location on the removal of exhaled contaminants in a classroom (15 × 7 × 5 m3) occupied by 50 students. Exhaled contaminants are modeled by a tracer gas released at the top of each manikin. The reference case has three exhausts evenly distributed in the ceiling. The results indicate that: a) a recirculation airflow entraining exhaled contaminants exists above the occupied zone;b) this recirculation air flow entrains contaminants and accumulates them at the upper part of the room near the diffuser;c) locating merely one exhaust on the same side of the supply diffuser leads to the best indoor air quality, i.e., it reduces the mean age of air from 278 s to 243 s, the mass fraction of CO2 from 753 ppm to 726 ppm, and the concentration of tracer gas from 305 ppm to 266 ppm;d) this layout still performs the best when the supply velocity drops to 0.5 m/s. It is worth noting that the proposed layout has fewer exhausts than the reference case but performs better. These results conclude that the exhaust for large spaces is not evenly distributed but depends on the indoor airflow pattern: the key is locating the exhaust near the region with high contaminant concentration. Factors determining the recirculation airflow are suggested to be further studied. Graphical abstract Image 1

Reducing vaccine hesitancy by explaining vaccine science.

Vaccine hesitancy in the COVID-19 pandemic remained a problem long after mRNA vaccines became available. This may be due in part to misunderstandings about the vaccines, arising from complexities of the science involved. Two experiments, conducted on unvaccinated Americans at two periods postvaccine rollout in 2021, demonstrated that providing explanations, expressed in everyday language, and correcting known misunderstandings, reduced vaccine hesitancy compared to a no-information control group. Four explanations addressing misunderstandings about mRNA vaccine safety and effectiveness were tested in Experiment 1 (n = 3,787). Some included expository text while others included refutational text, explicitly stating and refuting the misunderstanding. Vaccine effectiveness statistics were expressed either as text or an icon array. Although all four explanations reduced vaccine hesitancy, the refutational format of those addressing vaccine safety (explaining the mRNA mechanism and mild side effects) was the most effective. These two explanations were retested individually and jointly in Experiment 2 (n = 1,476) later in the summer of 2021. Again, vaccine hesitancy was significantly reduced by all explanations despite differences in political ideology, trust, and prior attitudes. These results suggest that nontechnical explanations of critical issues in vaccine science can reduce vaccine hesitancy, especially when accompanied by refutational text. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Transmission mitigation of COVID-19: Exhaled contaminants removal and energy saving in densely occupied space by impinging jet ventilation.

The pandemic of COVID-19 and its transmission ability raise much attention to ventilation design as indoor-transmission outstrips outdoor-transmission. Impinging jet ventilation (IJV) systems might be promising to ventilate densely occupied large spaces due to their high jet momentum. However, their performances in densely occupied spaces have rarely been explored. This study proposes a modified IJV system and evaluates its performance numerically in a densely occupied classroom mockup. A new assessment formula is also proposed to evaluate the nonuniformity of target species CO2. The infector is assumed as the manikin with the lowest tracer gas concentration in the head region. The main results include: a) Indoor air quality (IAQ) in the classroom is improved significantly compared with a mixing ventilation system, i.e., averaged CO2 in the occupied zone (OZ) is reduced from 1287 ppm to 1078 ppm, the OZ-averaged mean age of air is reduced from 439 s to 177 s; b) The mean infection probability is reduced from 0.047% to 0.027% with an infector, and from 0.035% to 0.024% with another infector; c) Cooling coil load is reduced by around 21.0%; d) Overall evaluation indices meet the requirements for comfortable environments, i.e., the temperature difference between head and ankle is within 3 °C and the OZ-averaged predictive mean vote is in the range of -0.5 - 0.5; e) Thermal comfort level and uniformity are decreased, e.g., overcooling near diffuser at ankle level. Summarily, the target system effectively improves IAQ, reduces exhaled-contaminant concentration in head regions, and saves energy as well.

Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection.

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa inhibitor fondaparinux does not. In the lethal SARS-CoV-2 K18-hACE2 model, FXa prolongs survival yet its combination with rivaroxaban but not fondaparinux abrogates that protection. These results identify both a previously unknown function for FXa and an associated antiviral host defense mechanism against SARS-CoV-2 and suggest caution in considering direct FXa inhibitors for preventing or treating thrombotic complications in COVID-19 patients.

Transmission mitigation of COVID-19: Exhaled contaminants removal and energy saving in densely occupied space by impinging jet ventilation

The pandemic of COVID-19 and its transmission ability raise much attention to ventilation design as indoor-transmission outstrips outdoor-transmission. Impinging jet ventilation (IJV) systems might be promising to ventilate densely occupied large spaces due to their high jet momentum. However, their performances in densely occupied spaces have rarely been explored. This study proposes a modified IJV system and evaluates its performance numerically in a densely occupied classroom mockup. A new assessment formula is also proposed to evaluate the nonuniformity of target species CO2. The infector is assumed as the manikin with the lowest tracer gas concentration in the head region. The main results include: a) Indoor air quality (IAQ) in the classroom is improved significantly compared with a mixing ventilation system, i.e., averaged CO2 in the occupied zone (OZ) is reduced from 1287 ppm to 1078 ppm, the OZ-averaged mean age of air is reduced from 439 s to 177 s;b) The mean infection probability is reduced from 0.047% to 0.027% with an infector, and from 0.035% to 0.024% with another infector;c) Cooling coil load is reduced by around 21.0%;d) Overall evaluation indices meet the requirements for comfortable environments, i.e., the temperature difference between head and ankle is within 3 °C and the OZ-averaged predictive mean vote is in the range of −0.5 - 0.5;e) Thermal comfort level and uniformity are decreased, e.g., overcooling near diffuser at ankle level. Summarily, the target system effectively improves IAQ, reduces exhaled-contaminant concentration in head regions, and saves energy as well. Graphical Image 1

Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection: Bioinformatics and molecular simulation analyses.

Objective: The novel coronavirus (severe acute respiratory syndrome coronavirus 2) has been spreading worldwide since December 2019, posing a serious danger to human health and socioeconomic development. A large number of clinical trials have revealed that coronavirus disease 2019 (COVID-19) results in multi-organ damage including the urogenital system. This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis. Methods: We used multiple publicly available databases to explore the expression patterns of ACE2, TMPRSS2, and CD147 (Basigin [BSG]) in major organs in the healthy and disease-specific populations, particularly the genitourinary organs. Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2, TMPRSS2, CD147, cytokine receptors, and cytokine interacting proteins in genitourinary organs, such as the bladder, kidney, prostate, and testis. Additionally, gene set enrichment analysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer. Results: The results revealed that ACE2, TMPRSS2, and CD147 were highly expressed in normal urogenital organs. Then, they were also highly expressed in multiple tumors and chronic kidney diseases. Additionally, ACE2, TMPRSS2, and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing. Cytokine receptors and cytokine interacting proteins, especially CCL2, JUN, and TIMP1, were commonly highly expressed in urogenital organs. Finally, gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK/STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19. Conclusion: Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives, which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness.

During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A, APOBEC1, and APOBEC3G can edit on specific sites of SARS-CoV-2 RNA to produce C-to-U mutations. However, SARS-CoV-2 replication and viral progeny production in Caco-2 cells are not inhibited by the expression of these APOBECs. Instead, expression of wild-type APOBEC3 greatly promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the random mutations, this study suggests the predictability of all possible viral genome mutations by these APOBECs based on the UC/AC motifs and the viral genomic RNA structure.

Do learners with higher readiness feel less anxious when studying online at home?

In response to the COVID-19 outbreak in many parts of the world, online education has become a more viable option. Some studies have assessed undergraduate students’ readiness for online learning, while others examined students’ anxiety about online learning at home. The relationship between readiness and anxiety about online learning is, however, not well explored. This paper has two purposes: (1) to develop a new and valid instrument—the Home-based Online Learning Readiness Questionnaire (HOLRQ)—to measure students’ readiness to study online at home based on a theoretical framework of self-regulated learning. As a replacement for the previous readiness scale, this new instrument adds a section on learning strategies and updates and develops new items. (2) to investigate the relationship between readiness and anxiety in online learning. In order to explore those issues, 527 undergraduate students in China were surveyed in this study. The results indicated that HOLRQ was validated in the following six domains: motivation, self-efficacy, information technology skills, resource management, learning strategies and help-seeking. Chinese undergraduate students were more prepared in resource management, motivation, and help seeking, but less prepared in learning strategies, information technology skills, and self-efficacy. However, the regression analysis showed that readiness did not predict online learning anxiety. It means even highly prepared self-regulated learners may experience anxiety when learning online from home. The findings provide insights for instructors and administrators to determine how students really feel about learning from home with online education.

One-Pot Visual Detection of African Swine Fever Virus Using CRISPR-Cas12a.

African swine fever virus (ASFV) is a leading cause of worldwide agricultural loss. ASFV is a highly contagious and lethal disease for both domestic and wild pigs, which has brought enormous economic losses to a number of countries. Conventional methods, such as general polymerase chain reaction and isothermal amplification, are time-consuming, instrument-dependent, and unsatisfactorily accurate. Therefore, rapid, sensitive, and field-deployable detection of ASFV is important for disease surveillance and control. Herein, we created a one-pot visual detection system for ASFV with CRISPR/Cas12a technology combined with LAMP or RPA. A mineral oil sealing strategy was adopted to mitigate sample cross-contamination between parallel vials during high-throughput testing. Furthermore, the blue fluorescence signal produced by ssDNA reporter could be observed by the naked eye without any dedicated instrument. For CRISPR-RPA system, detection could be completed within 40 min with advantageous sensitivity. While CRISPR-LAMP system could complete it within 60 min with a high sensitivity of 5.8 × 102 copies/µl. Furthermore, we verified such detection platforms display no cross-reactivity with other porcine DNA or RNA viruses. Both CRISPR-RPA and CRISPR-LAMP systems permit highly rapid, sensitive, specific, and low-cost Cas12a-mediated visual diagnostic of ASFV for point-of-care testing (POCT) applications.

SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.

COVID-19: Risk perception, risk communication, and behavioral intentions.

Critical to limiting the spread of Coronavirus disease 2019 (COVID-19) and future pandemics is compliance with behavioral recommendations such as mask wearing and social distancing. Compliance may depend upon understanding the seriousness of the health consequences and the likelihood they will occur. However, the statistics that speak to these issues in an ongoing pandemic are complex and may be misunderstood. An online experiment with a U.S. sample tested the impact on perceived likelihood, trust, concern, behavioral intentions, and agreement with government response of numeric (mortality/infection percentage by age group) and gist expressions (which age group was smaller [mortality] or roughly equivalent [infected]). While the differences in risk perception and willingness to engage in activities between younger and older participants were small, "gist infection and mortality" increased willingness to wear a mask among younger participants. Government restrictions (e.g., social distancing) impacted willingness to engage is risk-reduction and risk-seeking activities. The biggest differences were due to political ideology. Although conservatives perceived similar levels of risk as did liberals, they were much less willing to engage in protective behaviors and support government policies. However, conservatives were affected by some risk communication formats and restrictions suggesting that future work should be aimed at this issue. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Liposomal remdesivir inhalation solution for targeted lung delivery as a novel therapeutic approach for COVID-19.

Strong infectivity enables coronavirus disease 2019 (COVID-19) to rage throughout the world. Moreover, the lack of drugs with definite therapeutic effects further aggravates the spread of the pandemic. Remdesivir is one of the most promising anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. However, the limited clinical effects make its therapeutic effect controversial, which may result from the poor accumulation and activation of remdesivir in the lung. Therefore, we developed lyophilized remdesivir liposomes (Rdv-lips) which can be reconstituted as liposomal aerosol for pulmonary delivery to improve the in vivo behavior of existing remdesivir cyclodextrin conclusion compound (Rdv-cyc) injections. Liposome encapsulation endowed remdesivir with much higher solubility and better biocompatibility. The in vitro liposomal aerosol characterization demonstrated that Rdv-lips possessed a mass median aerodynamic diameter of 4.118 µm and fine particle fraction (<5 µm) higher than 50%, indicating good pulmonary delivery properties. Compared to the Rdv-cyc intravenous injection group, the Rdv-lips inhalation group displayed a nearly 100-fold increase in the remdesivir-active metabolite nucleotide triphosphate (NTP) concentration and better NTP accumulation in the lung than the Rdv-cyc inhalation group. A faster transition from remdesivir to NTP of Rdv-lips (inhalation) could also be observed due to better cell uptake. Compared to other preparations, the superiority of Rdv-lips was further evidenced by the results of an in vivo safety study, with little possibility of inducing inflammation. In conclusion, Rdv-lips for pulmonary delivery will be a potent formulation to improve the in vivo behavior of remdesivir and exert better therapeutic effects in COVID-19 treatment.

SARS-CoV-2 Nsp5 Demonstrates Two Distinct Mechanisms Targeting RIG-I and MAVS To Evade the Innate Immune Response.

Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic with astonishing mortality and morbidity. The high replication and transmission of SARS-CoV-2 are remarkably distinct from those of previous closely related coronaviruses, and the underlying molecular mechanisms remain unclear. The innate immune defense is a physical barrier that restricts viral replication. We report here that the SARS-CoV-2 Nsp5 main protease targets RIG-I and mitochondrial antiviral signaling (MAVS) protein via two distinct mechanisms for inhibition. Specifically, Nsp5 cleaves off the 10 most-N-terminal amino acids from RIG-I and deprives it of the ability to activate MAVS, whereas Nsp5 promotes the ubiquitination and proteosome-mediated degradation of MAVS. As such, Nsp5 potently inhibits interferon (IFN) induction by double-stranded RNA (dsRNA) in an enzyme-dependent manner. A synthetic small-molecule inhibitor blunts the Nsp5-mediated destruction of cellular RIG-I and MAVS and processing of SARS-CoV-2 nonstructural proteins, thus restoring the innate immune response and impeding SARS-CoV-2 replication. This work offers new insight into the immune evasion strategy of SARS-CoV-2 and provides a potential antiviral agent to treat CoV disease 2019 (COVID-19) patients. IMPORTANCE The ongoing COVID-19 pandemic is caused by SARS-CoV-2, which is rapidly evolving with better transmissibility. Understanding the molecular basis of the SARS-CoV-2 interaction with host cells is of paramount significance, and development of antiviral agents provides new avenues to prevent and treat COVID-19 diseases. This study describes a molecular characterization of innate immune evasion mediated by the SARS-CoV-2 Nsp5 main protease and subsequent development of a small-molecule inhibitor.

Integrated Analysis of the Prognosis-Associated RNA-Binding Protein Genes and Candidate Drugs in Renal Papillary Cell Carcinoma.

RNA-binding proteins (RBPs) play significant roles in various cancer types. However, the functions of RBPs have not been clarified in renal papillary cell carcinoma (pRCC). In this study, we identified 31 downregulated and 89 upregulated differentially expressed RBPs on the basis of the cancer genome atlas (TCGA) database and performed functional enrichment analyses. Subsequently, through univariate Cox, random survival forest, and multivariate Cox regression analysis, six RBPs of SNRPN, RRS1, INTS8, RBPMS2, IGF2BP3, and PIH1D2 were screened out, and the prognostic model was then established. Further analyses revealed that the high-risk group had poor overall survival. The area under the curve values were 0.87 and 0.75 at 3 years and 0.78 and 0.69 at 5 years in the training set and test set, respectively. We then plotted a nomogram on the basis of the six RBPs and tumor stage with the substantiation in the TCGA cohort. Moreover, we selected two intersectant RBPs and evaluate their biological effects by GSEA and predicted three drugs, including STOCK1N-28457, pyrimethamine, and trapidil by using the Connectivity Map. Our research provided a novel insight into pRCC and improved the determination of prognosis and individualized therapeutic strategies.

SARS-CoV-2 effects in the genitourinary system and prospects of sex hormone therapy.

OBJECT: Corona virus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to acute respiratory infection symptoms. SARS-CoV-2 infection is not always limited to the respiratory tract, and renal infection and dysfunction have been shown to be specific risk factors for death. In addition, COVID-19 has a higher incidence, severity and mortality in men than women. This disparity is due to biological rather than comorbid or behavioral sex differences. Because the male reproductive system is unique, the function of sex hormones in COVID-19 infection may explain the differences between males and females. Understanding these factors will provide appropriate prevention measures and adequate triage strategies and guide the drug discovery process. METHODS: An electronic search was completed in PubMed, ARXIV, MEDRXIV and BIORXIV. The most relevant articles were systematically reviewed. In addition, single cell RNA sequencing analysis of tissue samples from human cell landscape was conducted. RESULTS: The influence of SARS-CoV-2 on the urogenital system, the possibility of urinary tract transmission and the functions of sex hormones were discussed in this review. CONCLUSION: Corona viruses can invade the genitourinary system, causing urological symptoms. Identifying the potential genitourinary organ impairments and protecting them from damage are necessary. Since sex hormones have potential as specific drugs, the gonadal hormones substitution therapy should be considered in both sexes in the COVID-19 pandemic.

Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19.

BACKGROUND: Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. Based on previously published evidence, ACE2 and TMPRSS2 are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Also, increased expression of pro-inflammatory cytokines, or a "cytokine storm," is associated with multiple organ dysfunction syndrome often observed in critically ill patients. METHODS: We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially in specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2-specific signature. RESULTS: Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were notably concentrated in endothelial cells, macrophages, spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging autoimmune mechanisms. CONCLUSION: This study provided new insights into the pathogenic mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.