Mitigation of SARS-CoV-2 by Using Transition Metal Nanozeolites and Quaternary Ammonium Compounds as Antiviral Agents in Suspensions and Soft Fabric Materials.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the need for novel, affordable, and efficient reagents to help reduce viral transmission, especially in high-risk environments including medical treatment facilities, close quarters, and austere settings. We examined transition-metal nanozeolite suspensions and quaternary ammonium compounds as an antiviral surface coating for various textile materials. Methods: Zeolites are crystalline porous aluminosilicate materials, with the ability of ion-exchanging different cations. Nanozeolites (30 nm) were synthesized and then ion-exchanged with silver, zinc and copper ions. Benzalkonium nitrate (BZN) was examined as the quaternary ammonium ion (quat). Suspensions of these materials were tested for antiviral activity towards SARS-CoV-2 using plaque assay and immunostaining. Suspensions of the nanozeolite and quat were deposited on polyester and cotton fabrics and the ability of these textiles towards neutralizing SARS-CoV-2 was examined. Results: We hypothesized that transition metal ion containing zeolites, particularly silver and zinc (AM30) and silver and copper (AV30), would be effective in reducing the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Additionally, AM30 and AV30 antiviral potency was tested when combined with a quaternary ammonium carrier, BZN. Our results indicate that exposure of SARS-CoV-2 to AM30 and/or AV30 suspensions reduced viral loads with time and exhibited dose-dependence. Antiviral activities of the combination of zeolite and BZN compositions were significantly enhanced. When used in textiles, AM30 and AV30-coated cotton and polyester fabrics alone or in combination with BZN exhibited significant antiviral properties, which were maintained even after various stress tests, including washes, SARS-CoV-2-repeated exposures, or treatments with soil-like materials. Conclusion: This study shows the efficacy of transition metal nanozeolite formulations as novel antiviral agents and establishes that nanozeolite with silver and zinc ions (AM30) and nanozeolite with silver and copper ions (AV30) when combined with benzalkonium nitrate (BZN) quickly and continuously inactivate SARS-CoV-2 in suspension and on fabric materials.

Causes of the unexpected slowness in reducing winter PM2.5 for 2014-2018 in Henan Province.

Toughest-ever clean air actions in China have been implemented nationwide to improve air quality. However, it was unexpected that from 2014 to 2018, the observed wintertime PM2.5 (particulate matter with an aerodynamic diameter of less than 2.5 µm) concentrations showed an insignificant decrease in Henan Province (HNP), a region in the west of the North China Plain. Emission controls seem to have failed to improve winter air quality in HNP, which has caused great confusion in formulating the next air improvement strategy. We employed a deweathering technique to decouple the impact of meteorological conditions. The results showed that the deweathered PM2.5 trend was -3.3%/yr in winter from 2014 to 2018, which had a larger decrease than the observed concentrations (-0.9%/yr), demonstrating that emission reduction was effective at improving air quality. However, compared with the other two megacity clusters, Beijing-Tianjin-Hebei (BTH) (-8.4%/yr) and Yangtze River Delta (YRD) (-7.4%/yr), the deweathered decreasing trend of PM2.5 for HNP remained slow. The underlying mechanism driving the changes in PM2.5 and its chemical components was further explored, using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem). Model simulations indicated that nitrate dominated the increase of PM2.5 components in HNP and the proportions of nitrate to total PM2.5 increased from 22.4% in January 2015 to 39.7% in January 2019. There are two primary reasons for this phenomenon. One is the limited control of nitrogen oxide emissions, which facilitates the conversion of nitric acid to particulate nitrate by ammonia. The other is unfavourable meteorological conditions, particularly increasing humidity, further enhancing nitrate formation through multiphase reactions. This study highly emphasizes the importance of reducing nitrogen oxide emissions owing to their impact on the formation of particulate nitrate in China, especially in the HNP region.

[Variations in PM2.5 Composition and Sources During 2020-2021 COVID-19 Epidemic Periods in Nanjing].

To understand the changes in chemical composition and sources of PM2.5 under the extreme reduction background during the COVID-19 epidemic periods in Nanjing, hourly observation results of PM2.5 components (water-soluble inorganic ions, carbonaceous components, and inorganic elements) of two epidemic events from January to March 2020 and June to August 2021 were analyzed. In comparison to that during pre-epidemic periods, the concentration of NO3- during the two epidemic control periods decreased by 52.9% and 43.0%, respectively, which was larger than the decreases in NH4+(46.4% and 31.6%) and SO42-(33.8% and 16.5%). Since the observation site was located close to a main road, the decrease in elemental carbon (EC, 35.4% and 20.6%) was higher than that in organic carbon (OC, 11.1% and 16.2%). In reference to the variations in the characteristic ratios of the bulk components mentioned above, the epidemic control showed a more substantial influence on traffic emissions than industrial activities. The concentration time series of PM2.5 major components over the epidemic periods indicated that NOx from local traffic emissions had substantial contributions to the formation of NO3-, which led to local short-term PM2.5 pollution. In addition, the positive matrix factorization (PMF) model was used to analyze the hourly observation data of PM2.5 components. The seven identified factors were linked with metallurgy, firework and firecracker combustions, road traffic emissions, coal combustion, dust resuspension, secondary sulfate, and secondary nitrate. Because the nitrate was unstable under high temperature, the contribution of secondary nitrate to PM2.5 during the epidemic control period of 2021 (summer, 21.2%) was much lower than that during the epidemic control period of 2020 (winter, 60.6%); however, the formation of secondary components always dominated the contribution of PM2.5 sources. Therefore, emissions of NOx and SO2 should be further controlled to continuously reduce ambient PM2.5 concentrations in Chinese cities.

Renal replacement therapy removes a large number of nitric oxide donors responsible for the nitrate-nitrite-nitric oxide pathway.

BACKGROUNDS: Nitric oxide has a broad-spectrum antibacterial property promising as a new therapeutic agent for severe acute respiratory syndrome coronavirus-2 because nitric oxide donor (such as S-nitroso-N-acetylpenicillamine) reduces the replication of coronavirus-2. Patients with coronavirus disease 2019 undergoing dialysis generally have a higher mortality rate than the general population. Although the higher mortality rate in these patients may be related to their advanced age, it has been suggested that plasma nitrite and nitrate levels (products of nitric oxide metabolism) are significantly decreased after hemodialysis which may compromise the nitrate-nitrite-nitric oxide pathway and impair nitric oxide homeostasis. It results in increased cardiovascular mortality in patients undergoing dialysis. However, the profile of nitric oxide-producing substances is poorly understood during renal replacement therapy. METHODS: We simulated continuous hemodialysis and hemodiafiltration to measure the amount of nitric oxide (nitric oxide-producing substance) clearance in vitro. RESULTS: The results demonstrated increased nitric oxide clearance and higher clearance than creatinine (molecular weight: 113) and vitamin B12 (molecular weight: 1355) using highly efficient renal replacement therapy modes. CONCLUSION: The high nitric oxide clearance may have partly contributed to the high cardiovascular and coronavirus-2 mortality risk in patients on dialysis.

The potential human health hazard of nitrates in drinking water: a media discourse analysis in a high-income country.

BACKGROUND: Recent studies linking low levels of nitrate in drinking water to colorectal cancer have raised public concerns over nitrate contamination. The aim of this study was to analyze the media discourse on the potential human health hazard of nitrates in drinking water in a high-income country with a large livestock industry: New Zealand (NZ). METHODS: Searches of media sources ("major newspapers") held by the Factiva database for the NZ setting in the five-year period 17 December 2016 to 20 December 2021. RESULTS: The largest number of media items was observed for 2017 (n = 108), the year of a NZ general election, with a notable decrease in 2020 (n = 20) that was likely due to the Covid-19 pandemic, which dominated health media. However, the percentage of these media items with a health focus steadily increased over time, from 11.1% of all articles in 2017 to 51.2% in 2021. The most commonly mentioned health hazard was colorectal cancer, followed by methemoglobinemia. The temporal pattern of media items suggests that the release of scientific studies and scholarly blogs was associated with the publication of subsequent media items. Major stakeholders involved in the discourse included representatives of local and central government, environmental and recreational interest groups, researchers, local residents, agricultural interest groups, and health organizations. Maori (Indigenous New Zealanders) values or perspectives were rarely mentioned. CONCLUSIONS: Analysis of major newspapers for a five-year period indicated that a wide range of expert comment and opinions were made available to the public and policy makers on the issue of nitrates in water. While many different stakeholder views were captured in the media discourse, there is scope for the media to better report the views of Maori on this topic. There is also a need for articles detailing the health issues to also refer to the environmental, recreational, and cultural aspects of protecting water quality to ensure that the public, policy makers, and regulators are aware of co-benefits.

Air pollution and meteorology as risk factors for COVID-19 death in a cohort from Southern California.

BACKGROUND: Recent evidence links ambient air pollution to COVID-19 incidence, severity, and death, but few studies have analyzed individual-level mortality data with high quality exposure models. METHODS: We sought to assess whether higher air pollution exposures led to greater risk of death during or after hospitalization in confirmed COVID-19 cases among patients who were members of the Kaiser Permanente Southern California (KPSC) healthcare system (N=21,415 between 06-01-2020 and 01-31-2022 of whom 99.85 % were unvaccinated during the study period). We used 1 km resolution chemical transport models to estimate ambient concentrations of several common air pollutants, including ozone, nitrogen dioxide, and fine particle matter (PM2.5). We also derived estimates of pollutant exposures from ultra-fine particulate matter (PM0.1), PM chemical species, and PM sources. We employed Cox proportional hazards models to assess associations between air pollution exposures and death from COVID-19 among hospitalized patients. FINDINGS: We found significant associations between COVID-19 death and several air pollution exposures, including: PM2.5 mass, PM0.1 mass, PM2.5 nitrates, PM2.5 elemental carbon, PM2.5 on-road diesel, and PM2.5 on-road gasoline. Based on the interquartile (IQR) exposure increment, effect sizes ranged from hazard ratios (HR) = 1.12 for PM2.5 mass and PM2.5 nitrate to HR âˆ¼ 1.06-1.07 for other species or source markers. Humidity and temperature in the month of diagnosis were also significant negative predictors of COVID-19 death and negative modifiers of the air pollution effects. INTERPRETATION: Air pollution exposures and meteorology were associated the risk of COVID-19 death in a cohort of patients from Southern California. These findings have implications for prevention of death from COVID-19 and for future pandemics.

Dietary nitrate supplementation for preventing and reducing the severity of winter infections, including COVID-19, in care homes (BEET-Winter): a randomised placebo-controlled feasibility trial.

PURPOSE: Infections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in care home residents. METHODS: We performed a cluster-randomised placebo-controlled trial in UK residential and nursing care home residents and compared nitrate containing (400 mg) versus free (0 mg daily) beetroot juice given for 60 days. Outcomes comprised feasibility of recruitment, adherence, salivary and urinary nitrate, and ordinal infection/clinical events. RESULTS: Of 30 targeted care homes in late 2020, 16 expressed interest and only 6 participated. 49 residents were recruited (median 8 [interquartile range 7-12] per home), mean (standard deviation) age 82 (8) years, with proxy consent 41 (84%), advance directive for hospital non-admission 8 (16%) and ≥ 1 doses of COVID-19 vaccine 37 (82%). Background dietary nitrate was < 30% of acceptable daily intake. 34 (76%) residents received > 50% of juice. Residents randomised to nitrate vs placebo had higher urinary nitrate levels, median 50 [18-175] v 18 [10-50] mg/L, difference 25 [0-90]. Data paucity precluded clinical between-group comparisons; the outcome distribution was as follows: no infection 32 (67%), uncomplicated infection 0, infection requiring healthcare support 11 (23%), all-cause hospitalisation 5 (10%), all-cause mortality 0. Urinary tract infections were most common. CONCLUSIONS: Recruiting UK care homes during the COVID-19 pandemic was partially successful. Supplemented dietary nitrate was tolerated and elevated urinary nitrate. Together, infections, hospitalisations and deaths occurred in 33% of residents over 60 days. A larger trial is now required. TRIAL REGISTRATION: ISRCTN51124684. Application date 7/12/2020; assignment date 13/1/2021.

Redox imbalance in COVID-19 pathophysiology.

BACKGROUND: The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. METHODS: COVID-19 subjects (n = 64) and control subjects (n = 19) were enrolled, and blood was drawn within 72 h of diagnosis. Serum multiplex assays and peripheral blood mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. RESULTS: Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects. CONCLUSION: Herein we demonstrate a significant redox imbalance during COVID-19 infection affirming the potential for manipulation of oxidative stress pathways as a new therapeutic strategy COVID-19. However, further work is requisite for detailed identification of oxidants (O2•-, H2O2 and/or circulating transition metals such as Fe or Cu) contributing to this imbalance to avoid the repetition of failures using non-specific antioxidant supplementation.

Spatial and biological oceanographic insights into the massive fish-killing bloom of the haptophyte Chrysochromulina leadbeateri in northern Norway.

A bloom of the fish-killing haptophyte Chrysochromulina leadbeateri in northern Norway during May and June 2019 was the most harmful algal event ever recorded in the region, causing massive mortalities of farmed salmon. Accordingly, oceanographic and biodiversity aspects of the bloom were studied in unprecedented detail, based on metabarcoding and physico-chemical and biotic factors related with the dynamics and distribution of the bloom. Light- and electron-microscopical observations of nanoplankton samples from diverse locations confirmed that C. leadbeateri was dominant in the bloom and the primary cause of associated fish mortalities. Cell counts by light microscopy and flow cytometry were obtained throughout the regional bloom within and adjacent to five fjord systems. Metabarcoding sequences of the V4 region of the 18S rRNA gene from field material collected during the bloom and a cultured isolate from offshore of Tromsøy island confirmed the species identification. Sequences from three genetic markers (18S, 28S rRNA gene and ITS region) verified the close if not identical genetic similarity to C. leadbeateri from a previous massive fish-killing bloom in 1991 in northern Norway. The distribution and cell abundance of C. leadbeateri and related Chrysochromulina species in the recent incident were tracked by integrating observations from metabarcoding sequences of the V4 region of the 18S rRNA gene. Metabarcoding revealed at least 14 distinct Chrysochromulina variants, including putative cryptic species. C. leadbeateri was by far the most abundant of these species, but with high intraspecific genetic variability. Highest cell abundance of up to 2.7 × 107 cells L - 1 of C. leadbeateri was found in Balsfjorden; the high cell densities were associated with stratification near the pycnocline (at ca. 12 m depth) within the fjord. The cell abundance of C. leadbeateri showed positive correlations with temperature, negative correlation with salinity, and a slightly positive correlation with ambient phosphate and nitrate concentrations. The spatio-temporal succession of the C. leadbeateri bloom suggests independent initiation from existing pre-bloom populations in local zones, perhaps sustained and supplemented over time by northeastward advection of the bloom from the fjords.

Evaluating the influence of constant source profile presumption on PMF analysis of PM2.5 by comparing long- and short-term hourly observation-based modeling.

Hourly PM2.5 speciation data have been widely used as an input of positive matrix factorization (PMF) model to apportion PM2.5 components to specific source-related factors. However, the influence of constant source profile presumption during the observation period is less investigated. In the current work, hourly concentrations of PM2.5 water-soluble inorganic ions, bulk organic and elemental carbon, and elements were obtained at an urban site in Nanjing, China from 2017 to 2020. PMF analysis based on observation data during specific pollution (firework combustion, sandstorm, and winter haze) and emission-reduction (COVID-19 pandemic) periods was compared with that using the whole 4-year data set (PMFwhole). Due to the lack of data variability, event-based PMF solutions did not separate secondary sulfate and nitrate. But they showed better performance in simulating average concentrations and temporal variations of input species, particularly for primary source markers, than the PMFwhole solution. After removing event data, PMF modeling was conducted for individual months (PMFmonth) and the 4-year period (PMF4-year), respectively. PMFmonth solutions reflected varied source profiles and contributions and reproduced monthly variations of input species better than the PMF4-year solution, but failed to capture seasonal patterns of secondary salts. Additionally, four winter pollution days were selected for hour-by-hour PMF simulations, and three sample sizes (500, 1000, and 2000) were tested using a moving window method. The results showed that using short-term observation data performed better in reflecting immediate changes in primary sources, which will benefit future air quality control when primary PM emissions begin to increase.

Tanneries impact on groundwater quality: a case study of Kasur city in Pakistan.

Leather industry is the second largest export-earning sector of Pakistan. However, because of poor waste management, this industry has been continuously polluting the environment. In this paper, the impact of tanneries on the groundwater quality of Kasur city (i.e., the second largest leather producing city) is examined. The study is conducted in the following three phases: (I) water samples collection, (II) determination of physio-chemical properties, and (III) application of data mining techniques. In phase I, groundwater samples were collected from various sources such as hand pumps, motor pumps, and tube wells. In phase II, several physio-chemical properties such as (i) total dissolved solids (TDS), (ii) pH, (iii) turbidity, (iv) electrical conductivity (EC), (v) total hardness (TH), (vi) total alkalinity (TA), (vii) nitrates, (viii) chromium, (ix) fluoride, and (x) chloride were estimated. The estimated values of all these foregoing parameters are then compared with the Punjab Environmental Quality Standards for Drinking Water (PEQSDW). In phase III, principle component analysis and cluster analysis of the estimated parameters were performed to elucidate the relation between various parameters and to highlight the highly vulnerable sites, respectively. The results exhibit that most of the sampling collections sites are at the threshold of losing quality water. Moreover, it is also found that Mangal Mandi carries the worst groundwater quality among all sampling locations. Overall, it is concluded that serious attention is due from the water and wastewater authorities to further investigate and monitor the groundwater quality of Kasur before the country strikes with another pandemic after COVID-19.

Changes in Some Vascular Biomarkers in Patients with Severe COVID-19 with Various Degrees of Pulmonary Hypertension.

The aim of the study was to evaluate the levels of cardiac biomarkers endothelin 1, B-natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (Nt-proBNP), NO2, and NO3 in patients with COVID-19 pneumonia and various degrees of pulmonary hypertension. Group 1 included patients with pulmonary artery systolic pressure <25 mm Hg, group 2 with 25-40 mm Hg, and group 3 with 40-60 mm Hg. In the group of patients with pulmonary artery systolic pressure <25 mm Hg, the level of NT-proBNP was higher than in the rest two groups by 41.3% (p=0.015) and 38.2% (p=0.015), respectively. The levels of nitrites and nitrates in group 1 patients were lower: NO2 was reduced by 31.1% (p=0.026) and 62.8% (p=0.008), and NO3 was reduced by 28% (p=0.029) and by 54.6% (p=0.006), respectively. No other changes in the parameters in patients receiving oxygen therapy were found. These findings suggest that severe course of COVID-19 in patients with severe pulmonary hypertension is associated with impaired nitrite and nitrate metabolism and reduced levels of Nt-proBNP.

Effect of plastic pollution in soil properties and growth of grass species in semi-arid regions: a laboratory experiment.

Since the year 2020, the use of plastic as a strategy to mitigate the spread of COVID-19 disease has been given substantial attention. Global environmental contamination of plastic creates waste and is a known threat to soil ecosystems as a main sink of microplastics. However, there is still considerable uncertainty about microplastics controlling soil properties alteration. Therefore, we carried out an incubation experiment with soil and Carex stenophylla Wahlenb., which are the dominant soil and grass species in semi-arid regions. We investigated the effect of polymer polyethylene terephthalate (PET) concentrations (0%, 1%, 3%, and 5%) on C. stenophylla growth and soil ammonium-N and nitrate-N, organic matter content, pH, soil aggregates, and soil respiration. When soils were exposed to PET microplastics, fewer seeds germinated (62.8 ± 32%) but not significantly (p value > 0.05) when soils were treated to 0, 1, 3, and 0.5% PET. Shoot height was also not effectively reduced with PET. The soil pH was considerably lower when exposed to higher PET compared to all other treatments with the soil exposed to 5% w/w PET for both unplanted and planted, being 0.84 and 0.54 units, respectively, lower than the controls. The soil microbial respiration under exposure to PET was considerably increased in comparison to control samples. Moreover, the presence of PET resulted in potential alterations of soil stability, and with PET present soil stability increased. In conclusion, PET microplastics cannot significantly affect the development of C. stenophylla but could affect crucial soil properties. In addition, changes occurred with increased variability in soil ammonium-N and nitrate-N, particularly at a high PET ratio.

Haze caused by NOx oxidation under restricted residential and industrial activities in a mega city in the south of North China Plain.

The formation of secondary aerosol species, including nitrate and sulfate, induces severe haze in the North China Plain. However, despite substantial reductions in anthropogenic pollutants due to severe restriction of residential and industrial activities in 2020 to stop the spread of COVID-19, haze still formed in Zhengzhou. We compared ionic compositions of PM2.5 during the period of the restriction with that immediately before the restriction and in the comparison period in 2019 to investigate the processes that caused the haze. The average concentration of PM2.5 was 83.9 µg m-3 in the restriction period, 241.8 µg m-3 before the restriction, and 94.0 µg m-3 in 2019. Nitrate was the largest contributor to the PM2.5 in all periods, with an average mass fraction of 24%-30%. The average molar concentration of total nitrogen compounds (NOx + nitrate) was 0.89 µmol m-3 in the restriction period, which was much lower than that in the non-restriction periods (1.85-2.74 µmol m-3). In contrast, the concentration of sulfur compounds (SO2 + sulfate) was 0.34-0.39 µmol m-3 in all periods. The conversion rate of NOx to nitrate (NOR) was 0.35 in the restriction period, significantly higher than that before the restriction (0.26) and in 2019 (0.25). NOR was higher with relative humidity in 40-80% in the restriction period than in the other two periods, whereas the conversion rate of SO2 to sulfate did not, indicating nitrate formation was more efficient during the restriction. When O3 occupied more than half of the oxidants (Ox = O3 + NO2), NOR increased rapidly with the ratio of O3 to Ox and was much higher in the daytime than nighttime. Therefore, haze in the restriction period was caused by increased NOx-to-nitrate conversion driven by photochemical reactions.

Unbalanced emission reductions and adverse meteorological conditions facilitate the formation of secondary pollutants during the COVID-19 lockdown in Beijing.

During the coronavirus disease 2019 (COVID-19) lockdown in 2020, severe haze pollution occurred in the North China Plain despite the significant reduction in anthropogenic emissions, providing a natural experiment to explore the response of haze pollution to the reduction of human activities. Here, we study the characteristics and causes of haze pollution during the COVID-19 outbreak based on comprehensive field measurements in Beijing during January and February 2020. After excluding the Spring Festival period affected by fireworks activities, we found the ozone concentrations and the proportion of sulfate and nitrate in PM2.5 increased during the COVID-19 lockdown compared with the period before the lockdown, and sulfate played a more important role. Heterogeneous chemistry and photochemistry dominate the formation of sulfate and nitrate during the whole campaign, respectively, and the heterogeneous formation of nitrate at night was enhanced during the lockdown. The coeffects of more reductions in NOx than VOCs, weakened titration of NO, and increased temperature during the lockdown led to the increase in ozone concentrations, thereby promoting atmospheric oxidation capacity and photochemistry. In addition, the increase in relative humidity during the lockdown facilitated heterogeneous chemistry. Our results indicate that unbalanced emission reductions and adverse meteorological conditions induce the formation of secondary pollutants during the COVID-19 lockdown haze, and the formulation of effective coordinated emission-reduction control measures for PM2.5 and ozone pollution is needed in the future, especially the balanced control of NOx and VOCs.

The Association Between Environmental Perchlorate, Nitrate, and Thiocyanate Exposure and Oral Pain in NHANES.

Aim: To examine the human exposure to perchlorate, nitrate, and thiocyanate, and their associations with oral pain (OP) in the general population from the U.S. Methods: A total of 13,554 participants were enrolled in the National Health and Nutrition Examination Survey. The urinary perchlorate, nitrate, and thiocyanate were measured using ion chromatography coupled with an electrospray tandem mass spectrometry. The multivariable linear and logistic regressions were performed to explore the associations of the urinary perchlorate, nitrate, and thiocyanate, with the prevalence of oral pain. Restricted cubic splines were used to explore the non-linearity. Results: There are 3,129 OP cases. There was a higher urinary level of perchlorate, nitrate, and thiocyanate in OP. We found that urinary thiocyanate was positively associated with OP (odds ratio [OR] = 1.06; [1, 1.13]; p = 0.049). Restricted cubic spines revealed that urinary thiocyanate was in a U-shape association with OP. Conclusions: Urinary thiocyanate was in a U-shape association with OP, suggesting that we should keep the exposure of thiocyanate under a reasonable range.

High serum nitrates levels in non-survivor COVID-19 patients.

OBJECTIVE: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. DESIGN: A prospective observation study was carried out. SETTING: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). PATIENTS: COVID-19 patients admitted to the ICU. INTERVENTIONS: Determination of serum nitrate levels at ICU admission. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006-1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006-1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73-92%; p<0.001), APACHE II (AUC=85%; 95%CI=75-96%; p<0.001) and SOFA (AUC=78%; 95%CI=63-92%; p=0.005) based on the DeLong method. The Kaplan-Meier analysis found patients with serum nitrates levels>68.4µmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3-863.9; p<0.001). CONCLUSIONS: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation.

Impact of 2nd wave of COVID-19-related lockdown on coastal water quality at Diu, western coast of India and role of total alkalinity on bacterial loads.

A detailed coastal water monitoring near Diu coast, western part of India was performed from October, 2020 to May, 2021 covering the 2nd lockdown time. Average monthly fluctuation from 7 different sampling stations of total 9 physico-chemical parameters such as pH, salinity, turbidity, nitrite (NO2), nitrate (NO3), ammonia (NH3), phosphate (PO4), total alkalinity and silicate were recorded. Initially, Mann-Kendall trend test for all the 9 parameters showed non-zero trend, which may be either linear or non-linear. During 2nd lockdown period, there was a fluctuation of value for parameters like pH, salinity, nitrate, nitrite and phosphate. Average total bacterial count and differential bacterial count also gradually decreased from March, 2021 sampling. Principal component analysis (PCA) plot covering all the physico-chemical parameters as well as the differential bacterial count showed a distinct cluster of all bacterial count with total alkalinity value. Subsequently, mathematical equation was formulated between total alkalinity value and all differential bacterial count. Upto our knowledge, this is the first report where mathematical equation was formulated to obtain value of different bacterial load based on the derived total alkalinity value of the coastal water samples near Diu, India.

The JAK inhibitor ruxolitinib abrogates immune hepatitis instigated by concanavalin A in mice.

Therapeutics that impair the innate immune responses of the liver during the inflammatory cytokine storm like that occurring in COVID-19 are greatly needed. Much interest is currently directed toward Janus kinase (JAK) inhibitors as potential candidates to mitigate this life-threatening complication. Accordingly, this study investigated the influence of the novel JAK inhibitor ruxolitinib (RXB) on concanavalin A (Con A)-induced hepatitis and systemic hyperinflammation in mice to simulate the context occurring in COVID-19 patients. Mice were orally treated with RXB (75 and 150 mg/kg) 2 h prior to the intravenous administration of Con A (20 mg/kg) for a period of 12 h. The results showed that RXB pretreatments were efficient in abrogating Con A-instigated hepatocellular injury (ALT, AST, LDH), necrosis (histopathology), apoptosis (cleaved caspase-3) and nuclear proliferation due to damage (PCNA). The protective mechanism of RXB were attributed to i) prevention of Con A-enhanced hepatic production and systemic release of the proinflammatory cytokines TNF-α, IFN-γ and IL-17A, which coincided with decreasing infiltration of immune cells (monocytes, neutrophils), ii) reducing Con A-induced hepatic overexpression of IL-1ß and CD98 alongside NF-κB activation, and iii) lessening Con A-induced consumption of GSH and GSH peroxidase and generation of oxidative stress products (MDA, 4-HNE, NOx) in the liver. In summary, JAK inhibition by RXB led to eminent protection of the liver against Con A-deleterious manifestations primarily via curbing the inflammatory cytokine storm driven by TNF-α, IFN-γ and IL-17A.

A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide.

Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied. Herein we aim to explore the feasibility and safety of delivering continuous high-dose iNO over an extended period of time using an in vivo animal model. Yorkshire pigs were randomized to one of the following two groups: group 1, standard ventilation; and group 2, standard ventilation + continuous iNO 160 ppm + methylene blue (MB) as intravenous bolus, whenever required, to maintain metHb <6%. Both groups were ventilated continuously for 6 hours, then the animals were weaned from sedation, mechanical ventilation and followed for 3 days. During treatment, and on the third post-operative day, physiologic assessments were performed to monitor lung function and other significative markers were assessed for potential pulmonary or systemic injury. No significant change in lung function, or inflammatory markers were observed during the study period. Both gas exchange function, lung tissue cytokine analysis and histology were similar between treated and control animals. During treatment, levels of metHb were maintained <6% by administration of MB, and NO2 remained <5 ppm. Additionally, considering extrapulmonary effects, no significant changes were observed in biochemistry markers. Our findings showed that high-dose iNO delivered continuously over 6 hours with adjuvant MB is clinically feasible and safe. These findings support the development of investigations of continuous high-dose iNO treatment of respiratory tract infections, including SARS-CoV-2.