SARS-CoV-2 VARIANTS EVOLVED CONVERGENT STRATEGIES TO REMODEL THE HOST RESPONSE

Background: Five variants of concern (VOCs) have dominated COVID-19 disease etiology since 2020-Alpha, Beta, Gamma, Delta, and Omicron-possessing over 150 defining genomic alterations. Here, we used global proteomic and genomic approaches to study the host responses and selective forces driving VOC evolution. Method(s): We infected Calu-3 human lung epithelial cells with 5 VOCs and 2 wave 1 (W1) controls and performed mass spectrometry abundance proteomics, phosphoproteomics, and mRNA sequencing at 10 and 24 hours post infection. We additionally performed affinity purification mass spectrometry (APMS) by individually expressing all VOC mutant viral proteins (52) and corresponding W1 forms in human cells to quantify differential virus-host protein-protein interactions. Data was integrated using network modeling and bioinformatics to pinpoint VOC-specific differences. Four novel mutant viruses were developed using reverse genetics technology to validate the impact of specific genomic alterations. Result(s): We discovered VOCs evolved convergent molecular strategies to remodel the host response by modulating viral RNA and protein levels (most notably of N, Orf9b, and Orf6), altering nucleocapsid phosphorylation, and rewiring virus-host protein complexes. Integrative systems analyses revealed that Alpha, Beta, Gamma, and Delta ultimately converged in the suppression of interferon stimulated genes (ISGs) relative to W1 viruses, but Omicron BA.1 did not, and Delta induced more pro-inflammatory genes compared to other VOCs. Altered regulation of ISGs correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b;for example, Omicron BA.1 depicted a 2-fold decrease in Orf6 expression. We identified mutations that alter expression of Orf9b (N D3L and N -3A del) and the novel VOC protein N* (N R203K/G204R), and confirmed Orf6 innate immune antagonism using recombinant virus technology. Remarkably, Omicron BA.4 and BA.5 regained strengthened innate immune antagonism compared to BA.1, which again correlated with enhanced Orf6 expression, though dampened in BA.4 by a mutation (D61L) that we discovered disrupts the Orf6-nuclear pore interaction. Conclusion(s): Collectively, our findings suggest SARS-CoV-2 convergent evolution overcomes human innate immune barriers, laying the groundwork to understand future coronavirus evolution associated with immune escape and enhanced human-to-human transmission.

A nanofiber Murray membrane with antibacterial properties for high efficiency oily particulate filtration

Particulate air pollution represented by PM2.5 is one of the biggest environmental challenges in the 21st century. Especially in 2020, the global outbreak of COVID-19 has brought new challenges to melt-blown filter materials, such as the attenuation of filtration efficiency with breathing, even no filtration effect for viruses as their smaller diameter, the sharp decline of filter efficiency after oily filtration cycle, and its limit in some explosive occasions. Here, using the diameter difference of polystyrene (PS), polyvinylidene fluoride (PVDF) and nylon 6(PA6) fibers, we report a multistage structure nanofiber membrane (PS/PVDF/PA6&Ag MSNMs) with high efficiency, low resistance and antibacterial effect by constructing gradient pore structure and introducing silver nanoparticles (Ag NPs), overcoming the above defects. The average filtration efficiency of PS/PVDF/PA6&Ag MSNMs for diisooctyl sebacate (DEHS) monodisperse particles from 0.2 μm to 4.9 μm was 99.88%, and the pressure drop was only 128 Pa. After repeated circulation for 100 times, the filtration efficiency and pressure drop remained stable. Above all, the antibacterial nanofiber membrane with high efficiency and low resistance has been preliminarily constructed, the future research will further focus on the performance after circulation. © 2023 Elsevier Ltd

Influence of membrane pore-size on the recovery of endogenous viruses from wastewater using an adsorption-extraction method.

The ongoing COVID-19 pandemic has emphasized the significance of wastewater surveillance in monitoring and tracking the spread of infectious diseases, including SARS-CoV-2. The wastewater surveillance approach detects genetic fragments from viruses in wastewater, which could provide an early warning of outbreaks in communities. In this study, we determined the concentrations of four types of endogenous viruses, including non-enveloped DNA (crAssphage and human adenovirus 40/41), non-enveloped RNA (enterovirus), and enveloped RNA (SARS-CoV-2) viruses, from wastewater samples using the adsorption-extraction (AE) method with electronegative HA membranes of different pore sizes (0.22, 0.45, and 0.80 µm). Our findings showed that the membrane with a pore size of 0.80 µm performed comparably to the membrane with a pore size of 0.45 µm for virus detection/quantitation (repeated measurement one-way ANOVA; p > 0.05). We also determined the recovery efficiencies of indigenous crAssphage and pepper mild mottle virus, which showed recovery efficiencies ranging from 50% to 94% and from 20% to 62%, respectively. Our results suggest that the use of larger pore size membranes may be beneficial for processing larger sample volumes, particularly for environmental waters containing low concentrations of viruses. This study offers valuable insights into the application of the AE method for virus recovery from wastewater, which is essential for monitoring and tracking infectious diseases in communities.

New generation washable PES membrane face mask for virus filtration

Membrane materials might be used for face protection because they can decontaminate the inhaled air from particle pollution and viruses like the SARS-Cov0-2 which damages our respiration system. In this study, plyethersulfone membranes (PES) were synthesized with green solvent at room temperature and its filtration effectiveness was investigated against nano-bacteria (size 0.05 to 0.2 µm) by measuring their Bacterial Filtration Efficiency (BFE) and micro aerosol size (0.3 µm), and Particulate Filtration Efficiency (PFE). The average SARS-CoV-2 diameters are between 50 nm to 160 nm. A series of experiments were performed to accomplish between 0.03 to 0.21 µm PES sponge like diameters so that can be used for SARS-CoV-2 filtration. Results showed that nanofiltration/ultrafiltration could filter 99.9% of bacteria and aerosol from contaminated air the size of the Covid-19 molecule.

SARS-COV-2 viroporins activate the NLRP3-inflammasome by the mitochondrial permeability transition pore.

Background: Compared to healthy controls, severe COVID19 patients display increased levels of activated NLRP3-inflammasome (NLRP3-I) and interleukin (IL)-1ß. SARS-CoV-2 encodes viroporin proteins E and Orf3a(2-E+2-3a) with homologs to SARS-CoV-1, 1-E+1-3a, which elevate NLRP3-I activation; by an unknown mechanism. Thus, we investigated how 2-E+2-3a activates the NLRP3-I to better understand the pathophysiology of severe COVID-19. Methods: We generated a polycistronic expression-vector co-expressing 2-E+2-3a from a single transcript. To elucidate how 2-E+2-3a activates the NLRP3-I, we reconstituted the NLRP3-I in 293T cells and used THP1-derived macrophages to monitor the secretion of mature IL-1ß. Mitochondrial physiology was assessed using fluorescent microscopy and plate reader assays, and the release of mitochondrial DNA (mtDNA) was detected from cytosolic-enriched fractions using Real-Time PCR. Results: Expression of 2-E+2-3a in 293T cells increased cytosolic Ca++ and elevated mitochondrial Ca++, taken up through the MCUi11-sensitive mitochondrial calcium uniporter. Increased mitochondrial Ca++ stimulated NADH, mitochondrial reactive oxygen species (mROS) production and the release of mtDNA into the cytosol. Expression of 2-E+2-3a in NLRP3-I reconstituted 293T cells and THP1-derived macrophages displayed increased secretion of IL-1ß. Increasing mitochondrial antioxidant defenses via treatment with MnTBAP or genetic expression of mCAT abolished 2-E+2-3a elevation of mROS, cytosolic mtDNA levels, and secretion of NLRP3-activated-IL-1ß. The 2-E+2-3a-induced release of mtDNA and the secretion of NLRP3-activated-IL-1ß were absent in cells lacking mtDNA and blocked in cells treated with the mitochondrial-permeability-pore(mtPTP)-specific inhibitor NIM811. Conclusion: Our findings revealed that mROS activates the release of mitochondrial DNA via the NIM811-sensitive mitochondrial-permeability-pore(mtPTP), activating the inflammasome. Hence, interventions targeting mROS and the mtPTP may mitigate the severity of COVID-19 cytokine storms.

Microporous Matrimid/PIM-1 Thin Film Composite Membranes with Narrow Pore Size Distribution used for Molecular Separation in Organic Solvents.

Polymers of intrinsic microporosity (PIMs) are a class of microporous organic materials that contain interconnected pores of less than 2 nm in diameter. Such materials are of great potential used in membranes for molecular separation, such as drug fractionation in pharmaceutical industry. However, the PIMs membranes are often susceptible to low separation selectivity toward different molecules due to their wide pore size distribution. Herein, a linear polyimide, Matrimid, is incorporated with PIM-1 (a typical member of PIMs) by solution blending, and the blends are dip-coated onto a polyimide P84 support membrane to prepare thin-film composite (TFC) membranes to control pore size distribution while keep high microporosity. The component miscibility, pore characteristics, and molecular separation performances of the Matrimid/PIM-1 TFC membranes are investigated in detail. The Matrimid and PIM-1 are partially miscible due to their similar Hansen solubility parameters. The Matrimid endows the selective layers (coatings) with narrower pore size distribution due to more compact chain packing. The prepared Matrimid/PIM-1 TFC membranes show high selectivity for separation of riboflavin (80% of retention) and isatin (only 5% of retention). The developed membranes exhibit great potential for separating molecules with different molecular weights.

Selected dechlorination of triclosan by high-performance g-C3N4/Bi2MoO6 composites: Mechanisms and pathways

Environmental-friendly and efficient strategies for triclosan (TCS) removal have received more attention. Influenced by COVID-19, a large amount of TCS contaminants were accumulated in medical and domestic wastewater discharges. In this study, a unique g-C3N4/Bi2MoO6 heterostructure was fabricated and optimized by a novel and simple method for superb photocatalytic dechlorination of TCS into 2-phenoxyphenol (2-PP) under visible light irradiation. The as-prepared samples were characterized and analyzed by XRD, BET, SEM, XPS, etc. The rationally designed g-C3N4/Bi2MoO6 (4:6) catalyst exhibited notably photocatalytic activity in that more than 95.5% of TCS was transformed at 180 min, which was 3.6 times higher than that of pure g-C3N4 powder. This catalyst promotes efficient photocatalytic electron-hole separation for efficient dechlorination by photocatalytic reduction. The samples exhibited high recyclable ability and the dechlorination pathway was clear. The results of Density Functional Theory calculations displayed the TCS dechlorination selectivity has different mechanisms and hydrogen substitution may be more favorable than hydrogen ion in the TCS dechlorination hydrogen transfer process. This work will provide an experimental and theoretical basis for designing high-performance photocatalysts to construct the systems of efficient and safe visible photocatalytic reduction of aromatic chlorinated pollutants, such as TCS in dechlorinated waters. © 2022 Elsevier Ltd

Controlled release nanomedicine (CRNM) of aspirin using "biomimetic niosomal nanoparticles (BNNs)”for Covid-19 and cardiovascular treatment: DOE based optimization

Biomimetic strategies can be adopted to improve biopharmaceutical aspects. Subsequently, Biomimetic reconstitutable pegylated amphiphilic lipid nanocarriers have high translational potential for systemic controlled drug delivery;however, such an improvised system for systemic aspirin delivery exploring nanotechnology is not available. Systemic administration of aspirin and its controlled delivery can significantly control blood clotting events, leading to stroke, which has immediate applications in cardiovascular diseases and Covid-19. In this work, we are developing aspirin sustained release pegylated amphiphilic self-assembling nanoparticles to develop reconstitutable aspirin injections by solvent-based co-precipitation method with phase inversion technique that leads to novel "biomimetic niosomal nanoparticles (BNNs).” DOE led optimization is done to develop Design of space for optimized particles. Upon reconstitution of solid powder, the particle size was 144.8 ± 12.90 nm with a surface charge of -29.2 ± 2.24 mV. The entrapment efficiency was found to be 49 ± 0.15%, wherein 96.99 ± 1.57% of the drug was released in 24hr showing super case II transport-based drug release mechanism. The formulation has the least hemolysis while showing significant suppression of platelet aggregation. MTT assay does not show any significant cytotoxicity. This is a potential nanoparticle that can be explored for developing aspirin injection, which is not available.

Biobased polymer SF/PHBV composite nanofiber membranes as filtration and protection materials

With the emergence of the COVID-19, masks and protective clothing have been used in huge quantities. A large number of non-degradable materials have severely damaged the ecological environment. Now, people are increasingly pursuing the use of environmentally friendly materials to replace traditional chemical materials. Silk fibroin (SF) and Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) have received increasing attention because of their unique biodegradability and biocompatibility. In this paper, a series of biodegradable SF/PHBV nanofiber membranes with different PHBV content were fabricated by using electrospinning technology. The morphology of the electrospun SF/PHBV composite nanofiber was observed by scanning electron microscopy (SEM). The average diameters of the pure SF, SF/PHBV (4/1), SF/PHBV (3/1), and SF/PHBV (2/1) nanofibers were 55.16 ± 12.38 nm, 75.93 ± 21.83 nm, 69.35 ± 21.55 nm, and 61.40 ± 12.31 nm, respectively. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) were used to explore the microstructure of the electrospun SF/PHBV composite nanofiber. The crystallization ability of the composite nanofiber was greatly improved with the addition of PHBV. The results of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) indicated that the thermal stability of SF was better than PHBV obviously, so SF could improve the thermal stability of the composite materials within a certain range. The mechanical properties of the electrospun nanofiber membranes were evaluated by using a universal testing machine. In general, the elongation of the composite nanofiber membranes decreased, and the breaking strength increased with the addition of PHBV. The small pore size of the nanofiber membranes ensured that they had good application prospects in the field of filtration and protection. When the spinning time was 1 h, the filtration efficiency of SF/PHBV/PLA composite materials remained above 95%. © 2021 The Textile Institute.

A review on production and application of activated carbon from discarded plastics in the context of ‘waste treats waste'

In the post-COVID scenario, the annual increase in plastic waste has taken an upsurge due to the disposal of plastic masks, gloves and other protective equipment. To reduce the plastic load ending up in landfills and oceans or dumped at roadsides, the potential of using plastic polymers in different sectors has been investigated over the years leading to their potential application in pavement laying, concrete industry, fuel generation and production of carbon-based compounds among which activated carbons (AC) is a prime example. As one of the most recommended adsorbents for removing contaminants from water and adsorbing greenhouse gases, AC creates a potential sector for using discarded plastic to further treat pollutants and approach closer to a circular economy for plastics. This paper analyses the production process, the effect of production parameters on AC characteristics and properties that aid in adsorption. The interdependence of these factors determines the surface area, porosity, relative micropore and mesopore volume, thereby defining the utility for removing contaminant molecules of a particular size. Furthermore, this work discusses the application of AC along with a summary of the earlier works leading to the existing gaps in the research area. Production costs, formation of by-products including toxic substances and adsorbate selectivity are the major issues that have restricted the commercial application of this process towards its practical use. Research aimed at valorization of plastic waste into ACs would minimize the solid waste burden, along with treating other pollutants. © 2022 Elsevier Ltd

Efficient selective adsorption of cytokine IL-6 and other middle-macromolecular toxins in the serum of uremia patients with specially designed porous hollow carbon spheres

[Display omitted] • Porous hollow carbon spheres (HCSs) with adjustable size and pore width distribution were synthesized. • The clearance rate of HCSs to interleukin 6 (IL-6) in PBS buffer solution was up to 99.8%. • HCSs had a high adsorption rate and removal efficiency for PTH, β 2 -MG, IL-6 and TNF-α in the serum of uremic patients. • The selective adsorption of middle-macromolecular toxins or cytokines was achieved by regulating the pore structure of HCSs. Abnormally elevated middle-macromolecular toxins such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF- α) in human blood are fatal precipitating factors for patients suffered from immune-related diseases, especially for uremia and COVID-19 critical patients, while the effective clearance of them has always been problematic in clinic. In this work, porous hollow carbon spheres (HCSs) with different size and pore structure has been successfully prepared. The removal efficiency for IL-6 in PBS solution is about 99.8 %, even in the serum of uremic patients, HCSs could remove 94.75 % and 98.33 % of parathyroid hormone (PTH) and β 2 -microglobulin (β 2 -MG) efficiently within 5–10 min, and particularly, the adsorption of IL-6 and TNF- α is 17.6 and 11.4 times higher over that of the existing commercial hemoperfusion adsorbents. The adsorption balance can be achieved in 60 min, which would greatly shorten the current clinical treatment duration. Moreover, HCSs with different pore structure exhibit distinct adsorption selectivity for IL-6 and TNF- α, which is of special significance for modifying the middle-macromolecular cytokine level in the complicated human blood environment. [ FROM AUTHOR]

NucEnvDB: A Database of Nuclear Envelope Proteins and Their Interactions.

The nuclear envelope (NE) is a double-membrane system surrounding the nucleus of eukaryotic cells. A large number of proteins are localized in the NE, performing a wide variety of functions, from the bidirectional exchange of molecules between the cytoplasm and the nucleus to chromatin tethering, genome organization, regulation of signaling cascades, and many others. Despite its importance, several aspects of the NE, including its protein-protein interactions, remain understudied. In this work, we present NucEnvDB, a publicly available database of NE proteins and their interactions. Each database entry contains useful annotation including a description of its position in the NE, its interactions with other proteins, and cross-references to major biological repositories. In addition, the database provides users with a number of visualization and analysis tools, including the ability to construct and visualize protein-protein interaction networks and perform functional enrichment analysis for clusters of NE proteins and their interaction partners. The capabilities of NucEnvDB and its analysis tools are showcased by two informative case studies, exploring protein-protein interactions in Hutchinson-Gilford progeria and during SARS-CoV-2 infection at the level of the nuclear envelope.

Near-Native Visualization of SARS-CoV-2 Induced Membrane Remodeling and Virion Morphogenesis.

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, leads to profound remodeling of cellular membranes, promoting viral replication and virion assembly. A full understanding of this drastic remodeling and the process of virion morphogenesis remains lacking. In this study, we applied room temperature transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) tomography to visualize the SARS-CoV-2 replication factory in Vero cells, and present our results in comparison with published cryo-EM studies. We obtained cryo-EM-like clarity of the ultrastructure by employing high-pressure freezing, freeze substitution (HPF-FS) and embedding, allowing room temperature visualization of double-membrane vesicles (DMVs) in a near-native state. In addition, our data illustrate the consecutive stages of virion morphogenesis and reveal that SARS-CoV-2 ribonucleoprotein assembly and membrane curvature occur simultaneously. Finally, we show the tethering of virions to the plasma membrane in 3D, and that accumulations of virus particles lacking spike protein in large vesicles are most likely not a result of defective virion assembly at their membrane. In conclusion, this study puts forward a room-temperature EM technique providing near-native ultrastructural information about SARS-CoV-2 replication, adding to our understanding of the interaction of this pandemic virus with its host cell.

Shrunken Pore Syndrome Is Frequently Occurring in Severe COVID-19.

A selective decrease in the renal filtration of larger molecules is attributed to the shrinkage of glomerular pores, a condition termed Shrunken Pore Syndrome (SPS). SPS is associated with poor long-term prognosis. We studied SPS as a risk marker in a cohort of patients with COVID-19 treated in an intensive care unit. SPS was defined as a ratio < 0.7 when the estimated glomerular filtration rate (eGFR), determined by cystatin C, calculated by the Cystatin C Caucasian-Asian-Pediatric-Adult equation (CAPA), was divided by the eGFR determined by creatinine, calculated by the revised Lund−Malmö creatinine equation (LMR). Clinical data were prospectively collected. In total, SPS was present in 86 (24%) of 352 patients with COVID-19 on ICU admission. Patients with SPS had a higher BMI, Simplified Physiology Score (SAPS3), and had diabetes and/or hypertension more frequently than patients without SPS. Ninety-nine patients in the total cohort were women, 50 of whom had SPS. In dexamethasone-naïve patients, C-reactive protein (CRP ), TNF-alpha, and interleukin-6 did not differ between SPS and non-SPS patients. Demographic factors (gender, BMI) and illness severity (SAPS3) were independent predictors of SPS. Age and dexamethasone treatment did not affect the frequency of SPS after adjustments for age, sex, BMI, and acute severity. SPS is frequent in severely ill COVID-19 patients. Female gender was associated with a higher proportion of SPS. Demographic factors and illness severity were independent predictors of SPS.

Neuromasts and Olfactory Organs of Zebrafish Larvae Represent Possible Sites of SARS-CoV-2 Pseudovirus Host Cell Entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the acute respiratory disease coronavirus disease 2019 (COVID-19), which has resulted in millions of deaths globally. Here, we explored the mechanism of host cell entry of a luciferase-ZsGreen spike (SARS-CoV-2)-pseudotyped lentivirus using zebrafish embryos/larvae as an in vivo model. Successful pseudovirus entry was demonstrated via the expression of the luciferase (luc) gene, which was validated by reverse transcription-PCR (RT-PCR). Treatment of larvae with chloroquine (a broad-spectrum viral inhibitor that blocks membrane fusion) or bafilomycin A1 (a specific inhibitor of vacuolar proton ATPases, which blocks endolysosomal trafficking) significantly reduced luc expression, indicating the possible involvement of the endolysosomal system in the viral entry mechanism. The pharmacological inhibition of two-pore channel (TPC) activity or use of the tpcn2dhkz1a mutant zebrafish line also led to diminished luc expression. The localized expression of ACE2 and TPC2 in the anterior neuromasts and the forming olfactory organs was demonstrated, and the occurrence of endocytosis in both locations was confirmed. Together, our data indicate that zebrafish embryos/larvae are a viable and tractable model to explore the mechanism of SARS-CoV-2 host cell entry, that the peripheral sense organs are a likely site for viral host cell entry, and that TPC2 plays a key role in the translocation of the virus through the endolysosomal system. IMPORTANCE Despite the development of effective vaccines to combat the COVID-19 pandemic, which help prevent the most life-threatening symptoms, full protection cannot be guaranteed, especially with the emergence of new viral variants. Moreover, some resistance to vaccination remains in certain age groups and cultures. As such, there is an urgent need for the development of new strategies and therapies to help combat this deadly disease. Here, we provide compelling evidence that the peripheral sensory organs of zebrafish possess several key components required for SARS-CoV-2 host cell entry. The nearly transparent larvae provide a most amenable complementary platform to investigate the key steps of viral entry into host cells, as well as its spread through the tissues and organs. This will help in the identification of key viral entry steps for therapeutic intervention, provide an inexpensive model for screening novel antiviral compounds, and assist in the development of new and more effective vaccines.

SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.

RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypoxemia by damaging mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC), triggering apoptosis and bioenergetic impairment, and impairing hypoxic pulmonary vasoconstriction (HPV), respectively. OBJECTIVES: We examined the effects of: A) human betacoronaviruses, SARS-CoV-2 and HCoV-OC43, and individual SARS-CoV-2 proteins on apoptosis, mitochondrial fission, and bioenergetics in AEC; and B) SARS-CoV-2 proteins and mouse hepatitis virus (MHV-1) infection on HPV. METHODS: We used transcriptomic data to identify temporal changes in mitochondrial-relevant gene ontology (GO) pathways post-SARS-CoV-2 infection. We also transduced AECs with SARS-CoV-2 proteins (M, Nsp7 or Nsp9) and determined effects on mitochondrial permeability transition pore (mPTP) activity, relative membrane potential, apoptosis, mitochondrial fission, and oxygen consumption rates (OCR). In human PASMC, we assessed the effects of SARS-CoV-2 proteins on hypoxic increases in cytosolic calcium, an HPV proxy. In MHV-1 pneumonia, we assessed HPV via cardiac catheterization and apoptosis using the TUNEL assay. RESULTS: SARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. SARS-CoV-2 downregulated ETC Complex I and ATP synthase genes, and upregulated apoptosis-inducing genes. SARS-CoV-2 and HCoV-OC43 upregulated and activated dynamin-related protein 1 (Drp1) and increased mitochondrial fission. SARS-CoV-2 and transduced SARS-CoV-2 proteins increased apoptosis inducing factor (AIF) expression and activated caspase 7, resulting in apoptosis. Coronaviruses also reduced OCR, decreased ETC Complex I activity and lowered ATP levels in AEC. M protein transduction also increased mPTP opening. In human PASMC, M and Nsp9 proteins inhibited HPV. In MHV-1 pneumonia, infected AEC displayed apoptosis and HPV was suppressed. BAY K8644, a calcium channel agonist, increased HPV and improved SpO2. CONCLUSIONS: Coronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.

Experimental study on the cyclic behavior of silty sands reinforced by disposal of shredded facemask

Due to the COVID-19 pandemic, personal protective waste generation has increased worldwide. Given this problem,urgent waste management methods are required to reduce waste surcharge to the environment. The present study tries to clarify the question using particle-level modeling combined with 36 undrained cyclic triaxial shear tests. The physical properties of the base materials and the face mask (FM) are first investigated and scanning electron microscopy is used to image the soil particles.This study used two kinds of sand with different median grain (D50) sizes.In doing so, shredded face mask (FM) contenthas been modifiedfrom 0 % to 1 %. In a Small silt system (fine content ≤ 40 %), liquefaction resistance decreased with silt content addition and had an opposite behavior in a Large silt system (fine content ≥ 40 %) for both sands. FM addition to silty samples leads to sustainable improvements such as more dilatative behavior and dissipation of excess pore water pressure, and enhanced liquefaction resistance. The effectiveness of FM reinforcement diminished with increasing the median grain size (D50). Also, the shear modulus of clean and silty sands improved with FM addition.

MinION Nanopore Sequencing Accelerates Progress towards Ubiquitous Genetics in Water Research

In 2014, Oxford Nanopore Technologies (ONT) introduced an affordable and portable sequencer called MinION. We reviewed emerging applications in water research and assessed progress made with this platform towards ubiquitous genetics. With >99% savings in upfront costs as compared to conventional platforms, the MinION put sequencing capacity into the hands of many researchers and enabled novel applications with diverse remits, including in countries without universal access to safe water and sanitation. However, to realize the MinION’s fabled portability, all the auxiliary equipment items for biomass concentration, genetic material extraction, cleanup, quantification, and sequencing library preparation also need to be lightweight and affordable. Only a few studies demonstrated fully portable workflows by using the MinION onboard a diving vessel, an oceanographic research ship, and at sewage treatment works. Lower nanopore sequencing read accuracy as compared to alternative platforms currently hinders MinION applications beyond research, and inclusion of positive and negative controls should become standard practice. ONT’s EPI2ME platform is a major step towards user-friendly bioinformatics. However, no consensus has yet emerged regarding the most appropriate bioinformatic pipeline, which hinders intercomparison of study results. Processing, storing, and interpreting large data sets remains a major challenge for ubiquitous genetics and democratizing sequencing applications.

Environmental and Pharmacokinetic Aspects of Zeolite/Pharmaceuticals Systems—Two Facets of Adsorption Ability

Zeolites belong to aluminosilicate microporous solids, with strong and diverse catalytic activity, which makes them applicable in almost every kind of industrial process, particularly thanks to their eco-friendly profile. Another crucial characteristic of zeolites is their tremendous adsorption capability. Therefore, it is self-evident that the widespread use of zeolites is in environmental protection, based primarily on the adsorption capacity of substances potentially harmful to the environment, such as pharmaceuticals, pesticides, or other industry pollutants. On the other hand, zeolites are also recognized as drug delivery systems (DDS) carriers for numerous pharmacologically active agents. The enhanced bioactive ability of DDS zeolite as a drug carrying nanoplatform is confirmed, making this system more specific and efficient, compared to the drug itself. These two applications of zeolite, in fact, illustrate the importance of (ir)reversibility of the adsorption process. This review gives deep insight into the balance and dynamics that are established during that process, i.e., the interaction between zeolites and pharmaceuticals, helping scientists to expand their knowledge necessarily for a more effective application of the adsorption phenomenon of zeolites.

Microbe Penetration Levels on Facial Masks Fabricated at the University of Dodoma versus the Surgical Ones

Background: Coronavirus disease 2019 is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak was first identified in the city of Wuhan, Hubei, China in December 2019, and was recognized as a pandemic by the World Health Organization on 11 March 2020. The virus primarily spreads among people via respiratory droplets from coughing, breathing, or sneezing. To reduce virus transmission, close contact between people is discouraged. In response to advice by health practitioners, individuals are advised to wear face masks, regularly wash their hands, and apply sanitisers. However, the effectiveness of locally manufactured masks against COVID 19 and other microbes has not been investigated. Aims and methods: The current study aimed to experimentally determine and compare the effectiveness of two approved surgical masks and two face masks fabricated at the University of Dodoma (UDOM). Results: The effectiveness of the UDOM-made mask was similar when compared to surgical masks (Mann-Whitney, U = 390.000, p > 0.05;Mean ranks: Japan fabric = 32.5;N95 surgical mask = 28.50). However, the Japan fabric mask made at UDOM was more effective than BBL surgical mask made in China (Mann-Whitney, U = 270.000, p < 0.05;Mean ranks: Japan fabric = 24.50;BBL surgical mask = 36.50). Whereas the handkerchief mask made at UDOM and BBL surgical mask had similar levels of effectiveness (Mann-Whitney, U = 369.500, p > 0.05;Mean Ranks: Handkerchief = 27.82;BBL surgical mask = 33.18). The results obtained suggest that the two UDOM types were as effective as the N95 and BBL masks in reducing virus spread. Conclusion: The study recommends the determination of pore sizes of the materials used to make the mask to explain the effectiveness of the single layer, double layers, and double layers with cotton blends in the prevention of different microbes inhalable.