Air quality changes in Shijiazhuang during COVID-19 outbreak

[Background] The coronavirus disease 2019 (COVID-19) was first detected in December 2019. To combat the disease, a series of strict measures were adopted across the country, which led of improved air quality. This provides an opportunity to discuss the impact of human activities on air quality. [Objective] This study investigates the air quality changes in Shijiazhuang, and analyzes the impacts of epidemic prevention and control measures on air quality, so as to provide reference and ideas for further improving air quality and prevention and control measures. [Methods] The air quality data were collected online from https://www.zq12369.com/ and https://aqicn.org/city/shijiazhuang/cn/. Comparisons in air quality index (AQI) and the concentrations of air pollutants (PM2.5, PM10, SO2, CO, NO2, and O3) were made between the period from December 2019 to June 2020 (reference) and the same period from 2016 to 2019 by t-test and chi-square test. [Results] The daily average AQI dropped by 25.38% in Shijiazhuang during the COVID-19 prevention and control compared with the some period from 2016 to 2019 (t=6.28, P < 0.05). The proportions of pollution days during the COVID-19 outbreak in Shijiazhuang were PM2.5 (44.56%), O3 (31.09%), PM10 (23.83%), and NO2 (2.59%) successively, the pollution days of PM10 decreased significantly (chi2=3.86, P < 0.05) compared with 2016-2019, but during traffic lockdown the numbers of pollution days of PM2.5 and in the mid stage of prevention the number of pollution days of O3 increased (P < 0.05). Compared with the control period, the concentrations of the six air pollutants decreased to varying degrees (P < 0.05), especially SO2 dropped by 55.36%. [Conclusion] The measures taken for COVID-19 control and prevention have reduced the pollution sources and emissions, which resulted in better general air quality of Shijiazhuang City, but have aggravated the pollution of O3 and other pollutants. It is necessary to further explore the causes for the aggravation of O3 pollution in order to formulate reasonable air quality control strategies.Copyright © 2021, Shanghai Municipal Center for Disease Control and Prevention. All rights reserved.

Structure-Based Identification and Analysis of Viral Protease Inhibitors Targeting SARS CoV-2 Virus Replication

The re-emergence of SARS-CoV, known as SARS-CoV-2, has proven extremely infectious that has infected a huge population worldwide. SARS-CoV-2 genome is translated into polyproteins that is processed by virus-specific protease enzymes. 3CLprotease is named as the main protease (Mpro) enzyme that cleaves nsp4 to nsp16. This crucial role of Mpro makes this enzyme a prime and promising antiviral target. Till date, there is no effective commercially available drug against COVID-19 and launching a new drug into the market is a complicated and time-consuming process. Therefore, drug repurposing is a new but familiar approach to reduce the time and cost of drug discovery. We have used a high-throughput virtual screening approach to examine FDA approved library, natural compound library, and LOPAC 1280 (Library of Pharmacologically Active Compounds, Sigma-Aldrich, St. Louis, MO) library against Mpro. Primary screening identified potential drug molecules for the target, among which ten molecules were studied further using biophysical and biochemical techniques. SPR was used to validate the binding of inhibitors to purified Mpro and using FRET-based biochemical protease assay these inhibitors were confirmed to have Mpro inhibitory activity. Based on the kinetic studies, the antiviral efficacy of these compounds was further analysed by cell-culture based antiviral assays. Four out of ten molecules inhibited SARS-CoV-2 replication in Vero cells at a concentration range of 12.5 to 50 muM. The antiviral activity was evaluated by RT-PCR assay and TCID50 experiments. The co-crystallization of Mpro in complex with inhibitor for determining their structures is being carried out. Collectively, this study will provide valuable mechanistic and structural insights for development of effective antiviral therapeutics against SARS-CoV-2.

Development and Validation of a Novel Stability Indicating Reverse Phase High Performance Liquid Chromatographic Method for Related Substances and Assay Analysis of Molnupiravir Drug Substance and Drug Product

Molnupiravir, a broad-spectrum antiviral is an isopropyl ester prodrug of beta-D-N4-hydroxycytidine. Molnupiravir targets RNA-dependent RNA-polymerase enzyme of the viruses. A new stability-indicating HPLC-method was developed to determine related substances and assay of molnupiravir. Separation was achieved by using Shim-pack GWS C18 column. The method was validated according to current ICH requirements. The calibration plot gave a linear relationship for all known analytes over the concentration range from LOQ to 200%. LOD and LOQ for all known analytes were found in 0.05-0.08 microg mL-1 and 0.12-0.20 microg mL-1, respectively, the mean recovery was found to be 97.79-102.44 %. Study showed that the method, results of robustness, solution stability studies are precise and within the acceptable limits. Molnupiravir was found to degrade in acid, alkali, and oxidative conditions, and was stable in thermal, moisture, and photolytic degradation condition. The method is simple, accurate, precise, and reproducible for routine purity analysis of drug-samples.Copyright © 2022 Indian Drug Manufacturers' Association. All rights reserved.

Levels and drivers of urban black carbon and health risk assessment during pre- and COVID19 lockdown in Augsburg, Germany

This study aimed to evaluate the levels and phenomenology of equivalent black carbon (eBC) at the city center of Augsburg, Germany (01/2018 to 12/2020). Furthermore, the potential health risk of eBC based on equivalent numbers of passively smoked cigarettes (PSC) was also evaluated, with special emphasis on the impact caused by the COVID19 lockdown restriction measures. As it could be expected, peak concentrations of eBC were commonly recorded in morning (06:00–8:00 LT) and night (19:00–22:00 LT) in all seasons, coinciding with traffic rush hours and atmospheric stagnation. The variability of eBC was highly influenced by diurnal variations in traffic and meteorology (air temperature (T), mixing-layer height (MLH), wind speed (WS)) across days and seasons. Furthermore, a marked "weekend effect” was evidenced, with an average eBC decrease of ∼35% due to lower traffic flow. During the COVID19 lockdown period, an average ∼60% reduction of the traffic flow resulted in ∼30% eBC decrease, as the health risks of eBC exposure was markedly reduced during this period. The implementation of a multilinear regression analysis allowed to explain for 53% of the variability in measured eBC, indicating that the several factors (e.g., traffic and meteorology) may contribute simultaneously to this proportion. Overall, this study will provide valuable input to the policy makers to mitigate eBC pollutant and its adverse effect on environment and human health. © 2022 Elsevier Ltd

Satellite-based estimates of daily NO2 exposure in urban agglomerations of China and application to spatio-temporal characteristics of hotspots

The analysis of the daily spatial patterns of near-surface Nitrogen dioxide (NO2) concentrations can assist decision makers mitigate this common air pollutant in urban areas. However, comparative analysis of NO2 estimates in different urban agglomerations of China is limited. In this study, a new linear mixed effect model (LME) with multi-source spatiotemporal data is proposed to estimate daily NO2 concentrations at high accuracy based on the land-use regression (LUR) model and Ozone Monitoring Instrument (OMI) and TROPOspheric Monitoring Instrument (TROPOMI) products. In addition, three models for NO2 concentration estimation were evaluated and compared in four Chinese urban agglomerations from 2018 to 2020, including the COVID-19 closed management period. Each model included a unique combination of methods and satellite NO2 products: ModelⅠ: LUR model with OMI products;Model Ⅱ: LUR model with TropOMI products;Model Ⅱ: LME model with TropOMI products. The results show that the LME model outperformed the LUR model in all four urban agglomerations as the average RMSE decreased by 16.09% due to the consideration of atmospheric dispersion random effects, and using TropOMI instead of OMI products can improve the accuracy. Based on our NO2 estimations, pollution hotspots were identified, and pollution anomalies during the COVID-19 period were explored for two periods;the lockdown and revenge pollution periods. The largest NO2 pollution difference between the hotspot and non-hotspot areas occurred in the second period, especially in the heavy industrial urban agglomerations. © 2022 Elsevier Ltd

Impacts of the COVID-19 lockdown on atmospheric oxidizing capacity and secondary aerosol formation over the Beijing-Tianjin-Hebei region in Winter-Spring 2020

By using WRF-Chem coupled with a heterogeneous reaction mechanism for sulfate formation, this study investigated the impact of meteorological condition and emission changes on chemical species, atmospheric oxidizing capacity (AOC), and secondary aerosol formation during the COVID-19 lockdown period from 23 January to April 8, 2020, focusing on a severe haze event on 7-14 February. The model with the new sulfate formation scheme reasonably reproduces the spatial-temporal distribution of meteorological variables and chemical species, and significantly improves predictions for both sulfate and SO2 concentrations, as well as for PM2.5, ammonium, and nitrate to some extent. It is found that the adverse meteorological conditions were the main cause for the haze event formation, whereas emission reduction due to the lockdown somewhat decreased PM2.5 concentration on average in the Beijing-Tianjin-Hebei (BTH) region. Compared with the same period in 2019, increased surface air temperature and relative humidity (RH) and decreased planetary boundary layer height (PBLH) facilitated accumulation of pollutants and formation of secondary aerosols during the haze episode in 2020, whereas the emission reduction due to the lockdown led to decreases in SO2, NO2, primary PM2.5 (PPM2.5), black carbon (BC), primary organic aerosols (POA), nitrate and ammonium concentrations, but increases in O3, sulfate and secondary organic aerosol (SOA) concentrations, due to the combined effect of changes in emissions and AOC. Gas and aqueous phase oxidation of SO2 accounted for approximately 24% of sulfate formation, while the heterogeneous reaction of Mn-catalytic oxidation of SO2 on aerosol surfaces dominated sulfate formation (76%) during the haze episode in the BTH region. Both adverse meteorological conditions and emission reductions increased heterogeneous sulfate formation rate mainly through altering aerosol surface area (ASA), pH, and Mn2+ concentration. Chemical species varied diversely during the three subperiods before (Period-1, 15-22 January) and during the lockdown (Period-2, 23 January to 5 March and Period-3, 6 March to 8 April) over the BTH. NO2 concentration firstly decreased and then rebounded, whereas O3 concentration increased gradually from the Period-1 to Period-3. All aerosols except SOA decreased throughout the lockdown period, whereas SOA peaked in the Period-2 due to its strong sensitivity to increasing AOC. Sulfate concentration decreased from the Period-1 to Period-2, mainly due to more adverse meteorological conditions in the Period-1, although sulfate increased slightly due to increasing AOC in the Period-2. The large difference in the direction and magnitude of species variations during the COVID-19 lockdown indicates the complex interplay among meteorology, emission, and chemistry. Copyright © 2022 Elsevier Ltd

ANDROLOGY IN THE ERA OF COVID

OBJECTIVE: The last year has represented a challenging time for andrology laboratories due to the COVID-19 pandemic. Public health guidelines and government regulations intended to reduce the spread of COVID-19 caused a shift in patient practices across healthcare. They impacted the infertility laboratory by changing where and how semen samples are collected. The current study compared the quality of semen being collected for routine semen analysis (SA), and therapeutic IUI cycles, comparing the first year of the pandemic with the previous twelve-month period in a regional fertility center. MATERIALS AND METHODS: Institutional rules, public health guidelines, and government regulations required the majority (> 98%) of semen samples collected at a regional fertility center to be collected off-site starting March 18th, 2020. The center serves a catchment basin of approximately 300 miles in diameter, meaning some patients might travel for 1-2 hrs to deliver samples collected at home or have to make other arrangements for a collection location closer to the laboratory. To determine what impact the delay in processing and other factors, such as stress, might be having on semen quality, the center conducted a study comparing the standard semen parameters in two arms. The COVID-19 arm were patients seen from March 18th, 2020 to March 17th, 2021, and they were compared to the Pre-COVID-19 arm, who were seen from March 18th, 2019 to March 17th, 2020. Semen Analysis parameters analyzed for all samples included volume, concentration/mL, motility, morphology, total concentration, and total motile concentration. IUI samples were also analyzed for post-wash total concentration and total motile concentration. Resulting Data were compared using student's T-test. RESULTS: A total of 423 SA and 378 IUI records were compared. As expected, off-site collection significantly increased the time from collection to completion of the procedure (P < 0.001). Numerous semen parameters of the standard semen analysis were 10-20% lower in the pandemic year when collecting off-site than the same parameter in the 12 months before the pandemic when on-site collection was used. Focusing on IUI data, the average processing time from collection to finish increased 26 to 48 mins (p < 0.006). Average Total motile sperm has decreased from 49 to 42 million (14%;P < 0.05) between groups. Pregnancy data is pending. CONCLUSIONS: The pandemic has presented challenges to all reproductive centers. The challenges appear to have had a negative effect on the overall semen quality of patients. While it is unclear how much of an impact delays in processing are having, the data is highly suggestive they are impacting patient treatment. IMPACT STATEMENT: While delivery of reproductive health care continued during the pandemic, changes in public health guidelines and governmental regulations have impacted patient care thereby causing a reduction in semen quality. Public health officials and practices may need to reevaluate how semen samples are collected for diagnostics and treatment to mitigate this reduction in quality while maintaining the overall health of patients and staff.

MANNOSE-BINDING LECTIN (MBL) INHIBITS SARS-CoV-2 INFECTION and REPLICATION in VITRO

Background: Humoral innate immunity consists of a limited, but diverse, set of humoral fluid phase pattern recognition molecules (PRMs) that represent a first line of resistance against microbial invaders by promoting pathogen disposal by phagocytosis, complement activation and inflammation. These factors encompass complement, ficolin, collectin and pentraxin family of proteins. Methods: We have analyzed the activity of PRMs for their potential capacity of inhibiting SARS-CoV-2 entry and replication into epithelial cells by a microneutralization assay based on a lentiviral particles pseudotyped with the SARS-CoV-2 spike protein in HEK293T cells overexpressing the angiotensin converting enzyme 2 (ACE2). Either SARS-CoV-2 or target cells were incubated with Mannose Binding Lectin (MBL, concentration range: 1-50 μ g/ml) to further characterize its anti-viral activity for 1 h prior to infection in both human Calu-3 cells and air-liquid interface cultures of human bronchial epithelial cells (HBEC). Binding experiments were carried out with SARS-CoV-2 Spike protein and recombinant MBL to further investigate its antiviral action. Results: Among 12 PRMs tested, only MBL inhibited viral entry in the pseudotyped neutralization assay. Furthermore, MBL protein inhibited SARS-CoV-2 viral replication in Calu-3 and HBEC by ca. one log10 at the top concentration (10 μ g/ml and 50 μ g/ml, respectively). MBL antiviral activity was confirmed also against alpha, beta and gamma SARS-CoV-2 variants of concern. Binding experiments showed that MBL specifically interacts with the trimeric form of SARS-CoV-2 spike. Conclusion: MBL binds to the Spike protein in its active trimeric conformation leading to the inhibition of SARS-CoV-2 infection and replication in vitro. These results suggest that MBL possesses an antiviral activity against SARS-CoV-2 that could bear therapeutic potential.

EFFECT OF COVID-19 mRNA VACCINES ON SPERM QUALITY

OBJECTIVE: Fertility related safety data was neither reported in the clinical trials nor evaluated in animal models prior to emergency use authorization (EUA) for two novel mRNA vaccines, BNT162b2 and mRNA-127.1,2 Despite excellent safety profiles for both vaccines, 44% of Americans are hesitant in receiving the vaccine. Although the specific reasons for COVID-19 vaccine hesitancy are unknown, concerns over fertility has previously decreased other vaccine uptake. As COVID-19 vaccination in the United States opens to children and adolescents, evaluating any potential impact of the vaccine on male reproduction is imperative for public reassurance. We hypothesized that since both vaccines only contain mRNA encoding the SARS-CoV-2 spike protein without biologic ability to replicate live virus, the vaccines would not decrease semen parameters. MATERIALS AND METHODS: We conducted a single-center prospective cohort study after IRB approval from the University of Miami (#20201451). Healthy men aged 18-50 scheduled for mRNA COVID-19 vaccination in Miami, Florida were recruited.Participants provided a semen sample after 2-7 days of abstinence, prior to receiving the first dose of either vaccine and about 72 days after the second dose. Specimens were self-collected into a wide-mouth sterile container and semen analysis (SA) performed by HCLD trained andrology clinicians examined semen volume, concentration, motility, and total motile sperm count (TMSC). RESULTS: 45 men provided a semen sample. Neither median sperm concentration nor total motile sperm count (TMSC) declined post vaccination (Figure 1). There was no clinically significant change in TMSC. Only 12 (26.6%) men had a marginal decrease in TMSC. In fact, the remaining 33 (73.3%) men demonstrated normal sperm parameters. Importantly, 8 (17%) men with oligospermia prior to vaccination did not experience a decrease in spermatogenesis. Only one subject had an abnormal TMSC (TMSC ≤ 9) after vaccination. CONCLUSIONS: After receiving the two doses of the vaccines, we did not observe a clinically significant sperm parameter decline within the cohort, suggesting the vaccines do not negatively impact male fertility potential. IMPACT STATEMENT: This is the first male fertility evaluation of the COVID-19 mRNA vaccines, in which we found that the vaccines do not negatively impact semen parameters. (Table Presented).

Synthesis, role in antibacterial, antiviral, and hazardous effects of silver nanoparticles

Viral pathogen infections pose a major global health challenge: the emergence of bacteria and strains of viruses that are resistant to conventional antibiotics and antivirals, and undesirable side effects due to their long-term use, are slowing the use of many antiviral therapies. As a potentially useful tool in the prevention of various pathogens, silver nanoparticles have already demonstrated their potential as an effective antiviral agent thanks to their unique physical and chemical properties. Silver nanoparticles offer an excellent opportunity for new antiviral therapies as they can attack a wide variety of viruses. It has been suggested that AgNPs induces reactive oxygen species and free radicals that induce apoptosis, which leads to cell death and prevents cell replication and cell wall destruction, and smaller nanoparticles have also been shown to be more toxic than larger particles. The toxicity of AgNP depends on the size, concentration, pH of the medium and the duration of exposure to the pathogen. This review examines the antimicrobial mechanisms, deleterious effects, and synthesis of AgNPs.