Mucormycosis Metabolic Network Modeling: A Constraint-Based Approach

Mucormycosis is an uncommon illness caused by the fungus Mucorales. India was concerned about mucormycosis and COVID-19 in 2020. To minimize morbidity and occurrence, prevent, and treat mucormycosis, analysis is required. Combining systems biology and bioinformatics-based mucormycosis research, this study simulates the Genome-scale metabolic model (GSSM) of a Rhizopus oryzae strain for the comprehension of the organism's metabolic mechanism. Several key metabolic pathways for a mucormycosis-causing fungus strain were identified in research publications and targeted for inclusion in a model of a metabolic network. Based on the Flux Balance Analysis (FBA) approach, an integrated model of these pathways at the scale of the genome's metabolism was developed and appropriate constraints were applied to the numerous reactions involved in Rhizopus oryzae's metabolism using the COBRA package in MATLAB. Hence, unique evidence of pharmacological targets and biomarkers that may function as diagnostic, early analytic, and therapeutic agents in mucormycosis was discovered. Our study investigates the role of key metabolites in the model by applying constraints and altering fluxes, which provides valuable candidates for drug development. . © 2023 IEEE.

Medium Cut-Off versus Low-Flux Dialyzers in Hemodialysis Patients with COVID-19: Clinical Outcomes and Reduction in Interleukin-6.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused extensive morbidity and mortality worldwide. Hemodialysis (HD) patients are both vulnerable to COVID-19 infection and tend to suffer greater disease severity and mortality. This retrospective study aimed to compare medium cut-off (MCO) and low-flux (LF) membrane dialyzers in terms of interleukin-6 (IL-6) reduction, change in inflammatory state, intradialytic complications, and mortality in chronic HD patients with COVID-19. METHOD: HD patients with a confirmed COVID-19 infection were admitted to the hospital for 10-14 days and underwent HD at the COVID-HD unit. Choice of dialyzer membrane used (MCO vs. LF) depended on the primary nephrologist(s). We collected data on demographics, baseline characteristics, laboratory results, diagnosis, treatments, HD prescription, hemodynamic status during HD, and mortality at 14 and 28 days after. RESULTS: IL-6 reduction ratio (RR) in the MCO group was 9.7 (interquartile range, 71.1) percent, which was significantly higher than that of the LF group (RR, -45.7 [interquartile range, 70.2] percent). The incidence rate of intradialytic hypotension in the MCO group was 3.846 events per 100 dialysis hours (95% confidence interval [CI], 1.954-6.856), which was significantly lower than that of the LF group (9.057; 95% CI, 5.592-13.170). Overall, mortality was not significantly different between the two groups. CONCLUSION: The MCO membrane was more effective in removing IL-6 and was better tolerated than the LF membrane. Large, randomized controlled trials are required to confirm the relative benefits of the MCO membrane, especially mortality. However, due to the COVID-19 pandemic, our results suggest that the MCO membrane may be beneficial in chronic HD patients with COVID-19.

Dissecting Rubella Placental Infection in an In Vitro Trophoblast Model.

Vertical transmission of rubella virus (RuV) occurs at a high rate during the first trimester of pregnancy. The modes of vertical transmission including the response of trophoblasts to RuV are not well understood. Here, RuV-trophoblast interaction was studied in the BeWo trophoblast cell line. Analysis included early and late time-point kinetics of virus infection rate and the antiviral innate immune response at mRNA and protein level. BeWo characteristics were addressed through metabolic activity by extracellular flux analysis and syncytiotrophoblast formation through incubation with forskolin. We found that RuV infection of BeWo led to profuse type III interferon (IFN) production. Transfecting trophoblast cells with dsRNA analog induced an increase in the production of type I IFN-ß and type III IFNs; however, this did not occur in RuV-infected BeWo trophoblasts. IFN-ß and to a lesser extent type III IFN-λ1 were inhibitory to RuV. While no significant metabolic alteration was detected, RuV infection reduced the cell number in the monolayer culture in comparison to the mock control and resulted in detached and floating cells. Syncytia formation restricted RuV infection. The use of BeWo as a relevant cell culture model for infection of trophoblasts highlights cytopathogenicity in the absence of a type I IFN response as a pathogenic alteration by RuV.

COVID-19 Impact on the Italian Community-based System of Mental Health Care: Reflections and Lessons Learned for the Future

Surface longwave downward radiation (LWDR) is a key factor affecting the surface energy balance. The daily LWDR and the diurnal variations of LWDR are of great significance for studies of climate change and surface processes. How to obtain LWDR at an averaged temporal scale from instantaneous LWDR is one of the longstanding problems in the field of radiation budget from remote sensing. In this paper, two temporal upscaling methods are introduced, namely, a method based on the diurnal variations of LWDR (diurnal variation based, DVB) and a method based on random forest regression (RFR). The results reveal that: (1) The DVB method has a global hourly and daily LWDR root-mean-square error (RMSE) of less than 21 W/m2 and 15 W/m2, respectively, and the RMSE of the daily LWDR based on RFR is less than 7 W/m2;(2) When compared with four existing statistical interpolation methods, the DVB method can not only ensure the accuracy, but also can overcome the problem of missing samples and/or an abnormal samples during upscaling;(3) Except for directly predict daily LWDR, the DVB methods can also obtain more accurate LWDR diurnal variations such as hourly, half-hourly etc. The RFR method enables high-efficiency and accurate estimation of daily averaged LWDR from instantaneous measurements. Compared with existing methods and products, the proposed methods are not only efficient, but also have a superior applicability and reliable accuracy. The proposed strategies provide new ideas for the community in estimating LWDR at continuous temporal scales from remotely sensed measurements.

Effect of Replacing Feldspar by Philippine Black Cinder on the Development of Low-Porosity Red Stoneware

Stoneware is a ceramic material with low porosity and high mechanical properties, such as the modulus of rupture. It is essentially made of clay, feldspar and quartz and is sintered to create a mixture of glass and crystalline phases. With the projected growth rate of the global ceramics market size and the country's development plan for 2023–2028, it is imperative that alternative raw materials for the manufacture of ceramic products be sourced so that the importation of these materials, such as feldspar, be minimized, if not eliminated. Cinder in the Philippines is mainly used as a filling material in pavements and residential areas. In this study, this resource is utilized as partial and full replacement of feldspar in a typical ternary diagram for stoneware production. Bars were formed from different formulations by the slip casting method and were sintered at 1200 °C. Physical and mechanical properties of the bars, such as shrinkage, loss on ignition, water absorption, apparent porosity and modulus of rupture were determined. Thermo-physical analyses were also carried out on the raw materials and on formulated powders. Meeting the requirements of the various quality standards for ceramics, the partial replacement of feldspar with black cinder (LF, LFBQ and LFBH) is feasible for wall and roof applications while full replacement of feldspar with black cinder (LB) is suitable for wider use as wall, floor, vitrified, industrial and roof tiles.

Systematizing Microbial Bioplastic Production for Developing Sustainable Bioeconomy: Metabolic Nexus Modeling, Economic and Environmental Technologies Assessment.

The excessive usage of non-renewable resources to produce plastic commodities has incongruously influenced the environment's health. Especially in the times of COVID-19, the need for plastic-based health products has increased predominantly. Given the rise in global warming and greenhouse gas emissions, the lifecycle of plastic has been established to contribute to it significantly. Bioplastics such as polyhydroxy alkanoates, polylactic acid, etc. derived from renewable energy origin have been a magnificent alternative to conventional plastics and reconnoitered exclusively for combating the environmental footprint of petrochemical plastic. However, the economically reasonable and environmentally friendly procedure of microbial bioplastic production has been a hard nut to crack due to less scouted and inefficient process optimization and downstream processing methodologies. Thereby, meticulous employment of computational tools such as genome-scale metabolic modeling and flux balance analysis has been practiced in recent times to understand the effect of genomic and environmental perturbations on the phenotype of the microorganism. In-silico results not only aid us in determining the biorefinery abilities of the model microorganism but also curb our reliance on equipment, raw materials, and capital investment for optimizing the best conditions. Additionally, to accomplish sustainable large-scale production of microbial bioplastic in a circular bioeconomy, extraction, and refinement of bioplastic needs to be investigated extensively by practicing techno-economic analysis and life cycle assessment. This review put forth state-of-the-art know-how on the proficiency of these computational techniques in laying the foundation of an efficient bioplastic manufacturing blueprint, chiefly focusing on microbial polyhydroxy alkanoates (PHA) production and its efficacy in outplacing fossil based plastic products.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Comparing airborne infectious aerosol exposures in sparsely occupied large spaces utilizing large-diameter ceiling fans

In sparsely occupied large industrial and commercial buildings, large-diameter ceiling fans1 (LDCFs) are commonly utilized for comfort cooling and destratification;however, a limited number of studies were conducted to guide the operation of these devices during the COVID-19 pandemic. This study conducted 223 parametrical computational-fluid-dynamics (CFD) simulations of LDCFs in the U.S. Department of Energy warehouse reference building to compare the impacts of fan operations, index-person, and worker-packing-line locations on airborne exposures to infectious aerosols under both summer and winter conditions. The steady-state airflow fields were modeled while transient exposures to particles of varying sizes (0.5–10 μm) were evaluated over an 8-h period. Both the airflow and aerosol models were validated by measurement data from the literature. It was found that it is preferable to create a breeze from LDCFs for increased airborne dilution into a sparsely occupied large warehouse, which is more similar to an outdoor scenario than a typical indoor scenario. Operation of fans at the highest feasible speed while maintaining thermal-comfort requirements consistently outperformed the other options in terms of airborne exposures. There is no substantial evidence that fan reversal is beneficial in the current large space of interest. Reversal flow direction to create upward flows at higher fan speeds generally reduced performance compared with downward flows, as there was less airflow through the fan blades at the same rotational speed. Reversing flow at lower fan speeds decreased airflow speeds and dilution in the space and, thus, increased whole-warehouse concentrations. © 2023 Elsevier Ltd

From city to sea: Spatiotemporal dynamics of floating macrolitter in the Tiber River

Rivers are undoubtedly the main pathway of waste dispersed in the environment that from land reaches oceans and seas increasing the amount of marine litter. Major cities are a great source of riverine litter as large urbanization can originate pressure on the integrated waste management resulting in litter entering the rivers. Within this study, we aim to investigate the dynamic of floating riverine macrolitter (items >2.5 cm) in the city of Rome before it reaches the sea by assessing the composition, amount, and seasonal trends of litter transported from the urban centre to the main river mouth of Tiber River. Visual surveys for a whole year (March 2021–February 2022) were conducted from two bridges, Scienza Bridge (in the city) and Scafa Bridge (at the main river mouth) and followed JRC/RIMMEL protocol for riverine litter monitoring. Overall, similar litter composition was observed from the city centre to the mouth with a prevalence of plastic material, mainly related to fragmentation process (i.e. plastic pieces) and single use items, mainly in food and beverage sectors. An extrapolated annual loading of 4 × 105 items/year was estimated at the main mouth of Tiber River. The litter flux seems to be influenced by the seasonal variability and hydrometeorological parameters. The frequency of size classes decreases with increasing size in both sites, and more than half of the recorded items were below 10 cm. Specific categories belonging to "other plastics” have been reported related to anti-Covid-19 behaviour such as face masks and beverage sector, e.g. bottle lids and rings. The main colour of plastics was white, suggesting weathering process of floating riverine litter. This study contributes to increasing knowledge of the origin, composition and spatiotemporal dynamics of riverine floating litter from the city and entering the sea. © 2022 Elsevier B.V.

Exploring the effect of COVID-19 pandemic lockdowns on urban cooling: A tale of three cities.

COVID-19 pandemic has had a major impact on our society, environment and public health, in both positive and negative ways. The main aim of this study is to monitor the effect of COVID-19 pandemic lockdowns on urban cooling. To do so, satellite images of Landsat 8 for Milan and Rome in Italy, and Wuhan in China were used to look at pre-lockdown and during the lockdown. First, the surface biophysical characteristics for the pre-lockdown and within-lockdown dates of COVID-19 were calculated. Then, the land surface temperature (LST) retrieved from Landsat thermal data was normalized based on cold pixels LST and statistical parameters of normalized LST (NLST) were calculated. Thereafter, the correlation coefficient (r) between the NLST and index-based built-up index (IBI) was estimated. Finally, the surface urban heat island intensity (SUHII) of different cities on the lockdown and pre-lockdown periods was compared with each other. The mean NLST of built-up lands in Milan (from 7.71 °C to 2.32 °C), Rome (from 5.05 °C to 3.54 °C) and Wuhan (from 3.57 °C to 1.77 °C) decreased during the lockdown dates compared to pre-lockdown dates. The r (absolute value) between NLST and IBI for Milan, Rome and Wuhan decreased from 0.43, 0.41 and 0.16 in the pre-lockdown dates to 0.25, 0.24, and 0.12 during lockdown dates respectively, which shows a large decrease for all cities. Analysis of SUHI for these cities showed that SUHII during the lockdown dates compared to pre-lockdown dates decreased by 0.89 °C, 1.78 °C, and 1.07 °C respectively. The results indicated a high and substantial impact of anthropogenic activities and anthropogenic heat flux (AHF) on the SUHI due to the substantial reduction of huge anthropogenic pressure in cities. Our conclusions draw attention to the contribution of COVID-19 lockdowns (reducing the anthropogenic activities) to creating cooler cities.

Near-real-time CO2 fluxes from CarbonTracker Europe for high-resolution atmospheric modeling

We present the CarbonTracker Europe High-Resolution (CTE-HR) system that estimates carbon dioxide (CO2) exchange over Europe at high resolution (0.1 × 0.2∘) and in near real time (about 2 months' latency). It includes a dynamic anthropogenic emission model, which uses easily available statistics on economic activity, energy use, and weather to generate anthropogenic emissions with dynamic time profiles at high spatial and temporal resolution (0.1×0.2∘, hourly). Hourly net ecosystem productivity (NEP) calculated by the Simple Biosphere model Version 4 (SiB4) is driven by meteorology from the European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis 5th Generation (ERA5) dataset. This NEP is downscaled to 0.1×0.2∘ using the high-resolution Coordination of Information on the Environment (CORINE) land-cover map and combined with the Global Fire Assimilation System (GFAS) fire emissions to create terrestrial carbon fluxes. Ocean CO2 fluxes are included in our product, based on Jena CarboScope ocean CO2 fluxes, which are downscaled using wind speed and temperature. Jointly, these flux estimates enable modeling of atmospheric CO2 mole fractions over Europe.We assess the skill of the CTE-HR CO2 fluxes (a) to reproduce observed anomalies in biospheric fluxes and atmospheric CO2 mole fractions during the 2018 European drought, (b) to capture the reduction of anthropogenic emissions due to COVID-19 lockdowns, (c) to match mole fraction observations at Integrated Carbon Observation System (ICOS) sites across Europe after atmospheric transport with the Transport Model, version 5 (TM5) and the Stochastic Time-Inverted Lagrangian Transport (STILT), driven by ECMWF-IFS, and (d) to capture the magnitude and variability of measured CO2 fluxes in the city center of Amsterdam (the Netherlands).We show that CTE-HR fluxes reproduce large-scale flux anomalies reported in previous studies for both biospheric fluxes (drought of 2018) and anthropogenic emissions (COVID-19 pandemic in 2020). After applying transport of emitted CO2, the CTE-HR fluxes have lower median root mean square errors (RMSEs) relative to mole fraction observations than fluxes from a non-informed flux estimate, in which biosphere fluxes are scaled to match the global growth rate of CO2 (poor person's inversion). RMSEs are close to those of the reanalysis with the CTE data assimilation system. This is encouraging given that CTE-HR fluxes did not profit from the weekly assimilation of CO2 observations as in CTE.We furthermore compare CO2 concentration observations at the Dutch Lutjewad coastal tower with high-resolution STILT transport to show that the high-resolution fluxes manifest variability due to different emission sectors in summer and winter. Interestingly, in periods where synoptic-scale transport variability dominates CO2 concentration variations, the CTE-HR fluxes perform similarly to low-resolution fluxes (5–10× coarsened). The remaining 10 % of the simulated CO2 mole fraction differs by >2 ppm between the low-resolution and high-resolution flux representation and is clearly associated with coherent structures ("plumes”) originating from emission hotspots such as power plants. We therefore note that the added resolution of our product will matter most for very specific locations and times when used for atmospheric CO2 modeling. Finally, in a densely populated region like the Amsterdam city center, our modeled fluxes underestimate the magnitude of measured eddy covariance fluxes but capture their substantial diurnal variations in summertime and wintertime well.We conclude that our product is a promising tool for modeling the European carbon budget at a high resolution in near real time. The fluxes are freely available from the ICOS Carbon Portal (CC-BY-4.0) to be used for near-real-time monitoring and modeling, for example, as an a priori flux product in a CO2 data assimilation system. The data are available at 10.18160/20Z1-AYJ2 .

Increased mTOR Signaling and Impaired Autophagic Flux Are Hallmarks of SARS-CoV-2 Infection.

The COVID-19 (Coronavirus Disease 2019), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affects mainly individuals with pre-existing comorbidities. Here our aim was to correlate the mTOR (mammalian/mechanistic Target of Rapamycin) and autophagy pathways with the disease severity. Through western blotting and RNA analysis, we found increased mTOR signaling and suppression of genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2 as well as in transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients. Immunofluorescence co-localization assays also indicated that SARS-CoV-2 colocalizes within autophagosomes but not with a lysosomal marker. Our findings indicate that SARS-CoV-2 can benefit from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling.

Comparing airborne infectious aerosol exposures in sparsely occupied large spaces utilizing large-diameter ceiling fans

In sparsely occupied large industrial and commercial buildings, large-diameter ceiling fans1 (LDCFs) are commonly utilized for comfort cooling and destratification;however, a limited number of studies were conducted to guide the operation of these devices during the COVID-19 pandemic. This study conducted 223 parametrical computational-fluid-dynamics (CFD) simulations of LDCFs in the U.S. Department of Energy warehouse reference building to compare the impacts of fan operations, index-person, and worker-packing-line locations on airborne exposures to infectious aerosols under both summer and winter conditions. The steady-state airflow fields were modeled while transient exposures to particles of varying sizes (0.5–10 μm) were evaluated over an eight-hour period. Both the airflow and aerosol models were validated by measurement data from the literature. It was found that it is preferable to create a breeze from LDCFs for increased airborne dilution into a sparsely occupied large warehouse, which is more similar to an outdoor scenario than a typical indoor scenario. Operation of fans at the highest feasible speed while maintaining thermal-comfort requirements consistently outperformed the other options in terms of airborne exposures. There is no substantial evidence that fan reversal is beneficial in the current large space of interest. Reversal flow direction to create upward flows at higher fan speeds generally reduced performance compared with downward flows, as there was less airflow through the fan blades at the same rotational speed. Reversing flow at lower fan speeds decreased airflow speeds and dilution in the space and, thus, increased whole-warehouse concentrations.

Increasing secondary metabolites production of Phyllanthus sp to support development of herbal medicine industry

This study aim to improve the quality of Phyllanthus sp production by increasing the content of secondary metabolites as a bioactive compound. Phyllanthus sp contains various secondary metabolites that enhance immunity and treat diabetes, hypertension, antioxidants, anti-cancer, kidney disorders, and other illnesses. Since the Covid-19 pandemic, Phyllanthus sp widely used as a raw material for making herbal medicines. The trade value of Indonesian herbal medicines is estimated to increase in 2022, and the price will reach around the US $ 910 million, so it has very bright business prospects. These relatively limited phytopharmaceutical products constrain the supply of high-quality raw materials under the requirements of the herb medicine industry. Therefore, conducting a depth assessment related to efforts to improve the quality of Phyllanthus sp production by increasing the content of secondary metabolites is necessary. The efforts to enhance the quality of Phyllanthus sp as a source of herbal medicine raw materials can be made through plant breeding such as genetic mutations and in combination with the environmental arrangements of soil water content and solar radiation intensity. The efforts to increase the quality of herbal medicine raw materials are critical to support the development of the herbal medicine industry.

Measurement of the muon flux in the bunker of Monte Soratte with the CRC detector

The Cosmic Ray Cube is a portable tracking device conceived for outreach activities allowing a direct scientific experience for secondary school students. In the context of the PTOLEMY project, the detector was used to measure the differential muon flux inside the bunker of Monte Soratte, a suitable location at about 50 km north of Rome (Italy). Its simple operation was crucial to finalise the measurements, carried out during the Covid-19 lockdown in a site devoid of scientific equipment. The fine scanning of the differential muon rate highlights the details of the mountain above the bunker providing a map of the thickness of the rock which surrounds the detector. The result shows a muon flux at the Soratte hypogeum of about two orders of magnitude lower than the one observed on the surface. © 2022 Elsevier B.V.

MERS-CoV nsp1 regulates autophagic flux via mTOR signalling and dysfunctional lysosomes.

Autophagy, a cellular surveillance mechanism, plays an important role in combating invading pathogens. However, viruses have evolved various strategies to disrupt autophagy and even hijack it for replication and release. Here, we demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) non-structural protein 1(nsp1) induces autophagy but inhibits autophagic activity. MERS-CoV nsp1 expression increased ROS and reduced ATP levels in cells, which activated AMPK and inhibited the mTOR signalling pathway, resulting in autophagy induction. Meanwhile, as an endonuclease, MERS-CoV nsp1 downregulated the mRNA of lysosome-related genes that were enriched in nsp1-located granules, which diminished lysosomal biogenesis and acidification, and inhibited autophagic flux. Importantly, MERS-CoV nsp1-induced autophagy can lead to cell death in vitro and in vivo. These findings clarify the mechanism by which MERS-CoV nsp1-mediated autophagy regulation, providing new insights for the prevention and treatment of the coronavirus.

Changes in aerosol loading before, during and after the COVID-19 pandemic outbreak in China: Effects of anthropogenic and natural aerosol.

Anthropogenic emissions reduced sharply in the short-term during the coronavirus disease pandemic (COVID-19). As COVID-19 is still ongoing, changes in atmospheric aerosol loading over China and the factors of their variations remain unclear. In this study, we used multi-source satellite observations and reanalysis datasets to synergistically analyze the spring (February-May) evolution of aerosol optical depth (AOD) for multiple aerosol types over Eastern China (EC) before, during and after the COVID-19 lockdown period. Regional meteorological effects and the radiative response were also quantitatively assessed. Compared to the same period before COVID-19 (i.e., in 2019), a total decrease of -14.6 % in tropospheric TROPOMI nitrogen dioxide (NO2) and a decrease of -6.8 % in MODIS AOD were observed over EC during the lockdown period (i.e., in 2020). After the lockdown period (i.e., in 2021), anthropogenic emissions returned to previous levels and there was a slight increase (+2.3 %) in AOD over EC. Moreover, changes in aerosol loading have spatial differences. AOD decreased significantly in the North China Plain (-14.0 %, NCP) and Yangtze River Delta (-9.4 %) regions, where anthropogenic aerosol dominated the aerosol loading. Impacted by strong wildfires in Southeast Asia during the lockdown period, carbonaceous AOD increased by +9.1 % in South China, which partially offset the emission reductions. Extreme dust storms swept through the northern region in the period after COVID-19, with an increase of +23.5 % in NCP and + 42.9 % in Northeast China (NEC) for dust AOD. However, unfavorable meteorological conditions overwhelmed the benefits of emission reductions, resulting in a +20.1 % increase in AOD in NEC during the lockdown period. Furthermore, the downward shortwave radiative flux showed a positive anomaly due to the reduced aerosol loading in the atmosphere during the lockdown period. This study highlights that we can benefit from short-term controls for the improvement of air pollution, but we also need to seriously considered the cross-regional transport of natural aerosol and meteorological drivers.

A delayed modulation of solar ultraviolet radiation on the COVID-19 transmission reflects an incubation period

Laboratory experiments have revealed the meteorological sensitivity of the coronavirus disease 2019 (COVID-19) virus. However, no consensus has been reached about how outdoor meteorological conditions modulate the virus transmission as it is also constrained by non-meteorological conditions. Here, we identify the outbreak's evolution stage, constrained least by non-meteorological conditions, by searching the maximum correlation coefficient between the ultraviolet flux and the growth rate of cumulative confirmed cases at the country level. At this least-constrained stage, the cumulative cases count around 1300-3200, and the count's daily growth rate correlates with the ultraviolet flux and temperature significantly (correlation coefficients r = -0.54 +/- 0.09 and -0.39 +/- 0.10 at p<0.01$$ p, respectively), but not with precipitation, humidity, and wind. The ultraviolet correlation exhibits a delay of about 7 days, providing a meteorological measure of the incubation period. Our work reveals a seasonality of COVID-19 and a high risk of a pandemic resurgence in winter, implying a need for seasonal adaption in public policies.

Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients.

BACKGROUND: Thyroid hormones (TH)s are master regulators of mitochondrial activity and biogenesis. Nonthyroidal illness syndrome (NTIS) is generally considered an adaptative response to reduced energy that is secondary to critical illness, including COVID-19. COVID-19 has been associated with profound changes in the cell energy metabolism, especially in the cells of the immune system, with a central role played by the mitochondria, considered the power units of every cell. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects and alters mitochondrial functions, both to influence its intracellular survival and to evade host immunity. AIM OF THE STUDY: This study was undertaken to analyze the oxidative balance and mitochondrial respiration in COVID-19 patients with and without NTIS to elucidate the role that thyroid hormones (TH)s play in this context. METHODS: In our cohort of 54 COVID-19 patients, admitted to our University Hospital during the COVID-19 pandemic, we evaluated the generation of reactive oxygen species (ROS) by measuring the serum levels of derivatives of reactive oxygen metabolites (dROMs), and we analyzed the antioxidant capacity by measuring the serum biological antioxidant potential (BAP). We then analyzed the mitochondrial respiration in peripheral blood mononuclear cells (PBMC)s of 28 of our COVID-19 patients, using the seahorse instrument (Agilent). Results were correlated with the serum levels of THs and, in particular, of FT3. In addition, the role of T3 on bioelectrical impedance analysis (BIA) and mitochondrial respiration parameters was directly evaluated in two COVID-19 patients with NTIS, in which treatment with synthetic liothyronine (LT3) was given both in vivo and in vitro. RESULTS: In our COVID-19 patients with NTIS, the dROMs values were significantly lower and the BAP values were significantly higher. Consequently, the oxidative stress index (OSi), measured as BAP/dROMs ratio was reduced compared to that observed in COVID-19 patients without NTIS, indicating a protective role exerted by NTIS on oxidative stress. In our COVID-19 patients, the mitochondrial respiration, measured in PBMCs, was reduced compared to healthy controls. Those with NTIS showed a reduced maximal respiratory capacity and a reduced proton leak, compared to those with normal FT3 serum values. Such lowered mitochondrial respiratory capacity makes the cells more vulnerable to bioenergetic exhaustion. In a pilot study involving two COVID-19 patients with NTIS, we could reinforce our previous observation regarding the role of T3 in the maintenance of adequate peripheral hydroelectrolytic balance. In addition, in these two patients, we demonstrated that by treating their PBMCs with LT3, both in vitro and in vivo, all mitochondrial respiration parameters significantly increased. CONCLUSIONS: Our results regarding the reduction in the serum levels of the reactive oxygen species (ROS) of COVID-19 patients with NTIS support the hypothesis that NTIS could represent an adaptative response to severe COVID-19. However, beside this beneficial effect, we demonstrate that, in the presence of an acute reduction of FT3 serum levels, the mitochondrial respiration is greatly impaired, with a consequent establishment of a hypoenergetic state of the immune cells that may hamper their capacity to react to massive viral infection.