One-step-one-pot hydrothermally derived metal-organic-framework-nanohybrids for integrated point-of-care diagnostics of SARS-CoV-2 viral antigen/pseudovirus utilizing electrochemical biosensor chip.

The COVID-19 pandemic has become a global catastrophe, affecting the health and economy of the human community. It is required to mitigate the impact of pandemics by developing rapid molecular diagnostics for SARS-CoV-2 virus detection. In this context, developing a rapid point-of-care (POC) diagnostic test is a holistic approach to the prevention of COVID-19. In this context, this study aims at presenting a real-time, biosensor chip for improved molecular diagnostics including recombinant SARS-CoV-2 spike glycoprotein and SARS-CoV-2 pseudovirus detection based on one-step-one-pot hydrothermally derived CoFeBDCNH2-CoFe2O4 MOF-nanohybrids. This study was tested on a PalmSens-EmStat Go POC device, showing a limit of detection (LOD) for recombinant SARS-CoV-2 spike glycoprotein of 6.68 fg/mL and 6.20 fg/mL in buffer and 10% serum-containing media, respectively. To validate virus detection in the POC platform, an electrochemical instrument (CHI6116E) was used to perform dose dependent studies under similar experimental conditions to the handheld device. The results obtained from these studies were comparable indicating the capability and high detection electrochemical performance of MOF nanocomposite derived from one-step-one-pot hydrothermal synthesis for SARS-CoV-2 detection for the first time. Further, the performance of the sensor was tested in the presence of Omicron BA.2 and wild-type D614G pseudoviruses.

Zirconium-Based Metal-Organic Frameworks as Reusable Antibacterial Peroxide Carriers for Protective Textiles

Countries around the world have sought efficient protective coverings, including masks, gowns, and fabrics, for air purification to protect people against infectious diseases. However, the demand for significant quantities of disposable protective textiles poses a global challenge, especially when the production of protective gear is suspended due to COVID-19 outbreaks in factories and along supply lines. Therefore, the development of reusable, self-decontaminating protective masks and coverings loaded with disinfectants, such as antibacterial peroxide species, presents an attractive strategy to fight against bacteria risks. In this work, we incorporated persulfate ions, which serve as stable active peroxide precursors, into two porous zirconium-based metal-organic frameworks (Zr-MOFs), enabling these materials to act as regenerable reservoirs for the slow release of biocidal hydrogen peroxide upon hydrolysis by contact with humid air. Single-crystal X-ray diffraction studies reveal the two different coordination motifs for the persulfate ions, which can either bridge between two adjacent nodes or coordinate to a single node depending on both the node connectivity and the distances between open metal sites. The active peroxide precursors within the porous Zr-MOF carriers are stable during storage and easily regenerated once consumed. Importantly, these persulfate-loaded Zr-MOFs can be integrated onto textiles using a facile aqueous in-situ growth procedure, and these composites demonstrate potent and reusable biocidal activity against both Gram-negative bacteria and Gram-positive bacteria. Overall, this approach presents a viable strategy to develop robust protective textiles capable of rapidly deactivating pathogens.

Electrospray-on-Electrospun Breathable, Biodegradable, and Robust Nanofibrous Membranes with Photocatalytic Bactericidal Activity

The increasing emergence of infectious diseases like COVID-19 has created an urgent need for filtration/purification materials coupled with multifunctional features such as mechanical integrity, excellent airflow/filtration, and antibacterial/antimicrobial properties. Polymer membranes and metal-organic frameworks (MOFs) have demonstrated high effectiveness in air filtration and purification. MOF nanoparticles have been introduced into electrospun polymer nanofibrous membranes through embedding or postsolution growth. However, the derived hybrids are still facing the issue of (1) limited MOF exposure, which leads to low efficacy;and (2) uncontrollable growth, which leads to pore blocking and low breathability. In this work, we customized an electrospray-on-electrospinning in situ process to dynamically integrate MOF nanoparticles into a robust and elastic continuous nanofibrous membrane for advanced properties including high mechanical strength and flexibility, excellent breathability, particle filtration, and good antimicrobial performance. Biodegradable polylactic acid was reinforced by the poly(hydroxybutyrate)-di-poly(DLA-CL)x copolymer (PHBR) and used as an electrospinning matrix, while MOF nanoparticles were simultaneously electrically sprayed onto the nanofibers with easily controllable MOF loading. The MOF nanoparticles were homogeneously deposited onto nanofibers without clogging the pores in the membrane. The collision of PLA and MOF under the wet status during electrospinning and the hydrogen bonding through C=O and N-H bonds strengthen the affinity between PLA nanofibers and MOF nanoparticles. Because of these factors, the MOF-incorporated PLA/PHBR nanofibrous membrane achieved over 95% particle filtration efficiency with enhanced mechanical properties while maintaining high breathability. Meanwhile, it exhibits excellent photocatalytic antibacterial performance, which is necessary to kill microbes. The electrospray-on-electrospinning in situ process provides an efficient and straightforward way to hybridize one-dimensional (1D) or two-dimensional (2D) nanomaterials into a continuous nanofibrous membrane with strong interaction and controllable loading. Upon integrating proper functionalities from the materials, the obtained hybrids are able to achieve multifunctionalities for various applications.

Autophagy in Inflammatory Response against SARS-CoV-2.

The coronavirus disease pandemic, which profoundly reshaped the world in 2019 (COVID-19), and is currently ongoing, has affected over 200 countries, caused over 500 million cumulative cases, and claimed the lives of over 6.4 million people worldwide as of August 2022. The causative agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Depicting this virus' life cycle and pathogenic mechanisms, as well as the cellular host factors and pathways involved during infection, has great relevance for the development of therapeutic strategies. Autophagy is a catabolic process that sequesters damaged cell organelles, proteins, and external invading microbes, and delivers them to the lysosomes for degradation. Autophagy would be involved in the entry, endo, and release, as well as the transcription and translation, of the viral particles in the host cell. Secretory autophagy would also be involved in developing the thrombotic immune-inflammatory syndrome seen in a significant number of COVID-19 patients that can lead to severe illness and even death. This review aims to review the main aspects that characterize the complex and not yet fully elucidated relationship between SARS-CoV-2 infection and autophagy. It briefly describes the key concepts regarding autophagy and mentions its pro- and antiviral roles, while also noting the reciprocal effect of viral infection in autophagic pathways and their clinical aspects.

Ln-MOF Based Ratiometric Luminescent Sensor for the Detection of Potential COVID-19 Drugs.

Countless people have been affected by the COVID-19 pandemic on a global scale. Favipiravir, has shown potential as an effective drug for SARS-CoV-2, attracting scientists' attention. However, overuse of Favipiravir easily leads to serious side effects, requiring real-time monitoring in body fluids. Given this, a new lanthanide metal organic framework (MOF) was prepared under solvothermal conditions from either Eu (Eu-MOF or (1)) or Tb (Tb-MOF or (2)) using the highly delocalized imidazoledicarboxylic acid linker H2L (H2L = 5-(4-(imidazol-1-yl) phenyl) isophthalic acid) and could be successfully applied to selective optical detection of Favipiravir. In this MOF framework, the organic linker H2L provides a high excitation energy transfer efficiency that can sensitize luminescence in lanthanides. In addition, through deliberate tuning of Eu/Tb molar ratio and reaction concentration in the lanthanide framework, ratiometric recyclable luminescent EuxTb1-x-MOF nanoparticles with open metal sites have been constructed, which present a high detection sensitivity (Ksv = 1×107 [M-1], detection limit is 4.63 nM) for Favipiravir. The detection mechanism is discussed with the help of Density Functional Theory (DFT) calculations that sheds light over the selective sensing of Favipiravir over other related COVID-19 drug candidates. Finally, to explore the practical application of Favipiravir sensing, MOF based thin films have been used for visual detection of Favipiravir and recycled 5 times.

Prussian Blue@Zeolitic imidazolate framework composite toward solar-triggered biodecontamination

Metal-organic frameworks (MOFs) featuring composition and bandstructure diversity, are an emerging class of photoresponsive disinfectants. In this study, we demonstrated the superiority of core–shell arranged photoactive MOFs (prussian blue (PB) and zeolitic imidazolate framework (ZIF-8)) for pathogen inactivation in terms of biocidal efficiency and broad-spectrum sensitivity. Reactive oxygen species (ROS) production was significantly promoted after the integration of PB due to the photosensitization effect and initiation of in situ Fenton reaction. Favorably, another inactivation channel was also opened owing to the unique photothermal effect of PB. Attributed to the facilitated ROS intracellular penetration by heat, the composite outperforms not only individual component but anatase TiO2 in pathogen elimination. Specifically, the Staphylococcus aureus (S. aureus) inactivation efficiency of the composite (6.6 log) is 2, 1.8 and 5.1 times higher than that of PB (3.3 log), ZIF-8 (3.7 log) and TiO2 (1.3 log) over 45 min of simulated sunlight illumination. Significantly, the infectivity of Bacillus anthracis and murine coronavirus in droplets on composite-coated filter surface could be greatly reduced (approximately 3 log reduction in colony number/coronavirus titer) within few minutes of solar exposure, indicative of the great potential of MOF composites toward life-threatening microbial infection prevention. © 2022 Elsevier B.V.

Electrospray-on-Electrospun Breathable, Biodegradable, and Robust Nanofibrous Membranes with Photocatalytic Bactericidal Activity

The increasing emergence of infectious diseases like COVID-19 has created an urgent need for filtration/purification materials coupled with multifunctional features such as mechanical integrity, excellent airflow/filtration, and antibacterial/antimicrobial properties. Polymer membranes and metal-organic frameworks (MOFs) have demonstrated high effectiveness in air filtration and purification. MOF nanoparticles have been introduced into electrospun polymer nanofibrous membranes through embedding or postsolution growth. However, the derived hybrids are still facing the issue of (1) limited MOF exposure, which leads to low efficacy;and (2) uncontrollable growth, which leads to pore blocking and low breathability. In this work, we customized an electrospray-on-electrospinning in situ process to dynamically integrate MOF nanoparticles into a robust and elastic continuous nanofibrous membrane for advanced properties including high mechanical strength and flexibility, excellent breathability, particle filtration, and good antimicrobial performance. Biodegradable polylactic acid was reinforced by the poly(hydroxybutyrate)-di-poly(DLA-CL)x copolymer (PHBR) and used as an electrospinning matrix, while MOF nanoparticles were simultaneously electrically sprayed onto the nanofibers with easily controllable MOF loading. The MOF nanoparticles were homogeneously deposited onto nanofibers without clogging the pores in the membrane. The collision of PLA and MOF under the wet status during electrospinning and the hydrogen bonding through C═O and N-H bonds strengthen the affinity between PLA nanofibers and MOF nanoparticles. Because of these factors, the MOF-incorporated PLA/PHBR nanofibrous membrane achieved over 95% particle filtration efficiency with enhanced mechanical properties while maintaining high breathability. Meanwhile, it exhibits excellent photocatalytic antibacterial performance, which is necessary to kill microbes. The electrospray-on-electrospinning in situ process provides an efficient and straightforward way to hybridize one-dimensional (1D) or two-dimensional (2D) nanomaterials into a continuous nanofibrous membrane with strong interaction and controllable loading. Upon integrating proper functionalities from the materials, the obtained hybrids are able to achieve multifunctionalities for various applications. © 2023 American Chemical Society.

Surfactant-Impregnated MOF-Coated Fabric for Antimicrobial Applications.

Since the onset of the SARS-CoV-2 pandemic, the world has witnessed over 617 million confirmed cases and more than 6.54 million confirmed deaths, but the actual totals are likely much higher. The virus has mutated at a significantly faster rate than initially projected, and positive cases continue to surge with the emergence of ever more transmissible variants. According to the CDC, and at the time of this manuscript submission, more than 77% of all current US cases are a result of the B.5 (omicron). The continued emergence of highly transmissible variants makes clear the need for more effective methods of mitigating disease spread. Herein, we have developed an antimicrobial fabric capable of destroying a myriad of microbes including betacoronaviruses. We have demonstrated the capability of this highly porous and nontoxic metal organic framework (MOF), γ-CD-MOF-1, to serve as a host for varied-length benzalkonium chlorides (BACs; active ingredient in Lysol). Molecular docking simulations predicted a binding affinity of up to -4.12 kcal·mol-1, which is comparable to that of other reported guest molecules for this MOF. Similar Raman spectra and powder X-ray diffraction patterns between the unloaded and loaded MOFs, accompanied by a decrease in the Brunauer-Emmett-Teller surface area from 616.20 and 155.55 m2 g-1 respectively, corroborate the suggested potential for pore occupation with BAC. The MOF was grown on polypropylene fabric, exposed to a BAC-loading bath, washed to remove excess BAC from the external surface, and evaluated for its microbicidal activity against various bacterial and viral classes. Significant antimicrobial character was observed against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, bacteriophage, and betacoronavirus. This study shows that a common mask material (polypropylene) can be coated with BAC-loaded γ-CD-MOF-1 while maintaining the guest molecule's antimicrobial effects.

Sensitive fluorescence biosensor for SARS-CoV-2 nucleocapsid protein detection in cold-chain food products based on DNA circuit and g-CNQDs@Zn-MOF.

SARS-CoV-2 isolation from cold-chain food products confirms the possibility of outbreaks through cold-chain food products. RNA extraction combined with RT-PCR is the primary method currently utilized for the detection of SARS-CoV-2. However, the requirement of hours of analytical time and the high price of RT-PCR hinder its worldwide implementation in food supervision. Here, we report a fluorescence biosensor for detection of SARS-CoV-2 N protein. The fluorescence biosensor was fabricated by aptamer-based conformational entropy-driven circuit where molecular beacon strands were labeled with graphitic carbon nitrides quantum dots@Zn-metal-organic framework (g-CNQDs@Zn-MOF) and Dabcyl. The detection of the N protein was achieved via swabbing followed by competitive assay using a fixed amount of N-48 aptamers in the analytical system. A fluorescence emission spectrum was employed for the detection. The detection limit of our fluorescence biosensor was 1.0 pg/mL for SARS-CoV-2 N protein, indicating very excellent sensitivity. The fluorescence biosensor did not exhibit significant cross-reactivity with other N proteins. Finally, the biosensor was successfully applied for the detection of SARS-CoV-2 N protein in actual cold-chain food products showing same excellent accuracy as RT-PCR method. Thus, our fluorescence biosensor is a promising analytical tool for rapid and sensitive detection of SARS-CoV-2 N protein.

Ultrasensitive aptamer-functionalized Cu-MOF fluorescent nanozyme as an optical biosensor for detection of C-reactive protein.

In the present work, an aptasensing method based on integration of RNA on Cu-MOF was developed for detection of C-Reactive Protein (CRP). Cu-MOF showed stimulated fluorescence and mimetic peroxidase enzymatic activity at the time and can be used as dual-signal transduction. CRP binding RNA was used as a highly selective recognition element and immobilized on the Cu-MOF. The immobilized RNA can block the peroxidase activity and fluorescence of the signal traducer probe. Adding CRP to the RNA/Cu-MOF will release RNA from the surface of Cu-MOF and recover both the stimulated fluorescence and peroxidase activity. A biosensor was built for detection of CRP using the two modes of transduction, either colorimetry or fluorometry. A dynamic linear range was obtained from 0.1 to 50 ng mL -1with a limit of detection (LOD) as small as 40 pg mL -1was calculated in fluorescence mode and 240 pg mL -1 as LOD in colorimetry mode. The LODs are lower than the LOD of nephelometric techniques used in clinical practice and is comparable to the normal clinical cutoff value in high-sensitivity CRP assays (1 µg/mL). The aptasensor was successfully applied for detection of CRP in Covid-19 patients with spike recoveries between 84 and 102% and RSD from 0.94% to 2.05%.

Prussian Blue@Zeolitic Imidazolate Framework Composite Toward Solar-triggered Biodecontamination

Metal-organic frameworks (MOFs) featuring composition and bandstructure diversity, are an emerging class of photoresponsive disinfectants. In this study, we demonstrated the superiority of core-shell arranged photoactive MOFs (prussian blue (PB) and zeolitic imidazolate framework (ZIF-8)) for pathogen inactivation in terms of biocidal efficiency and broad-spectrum sensitivity. Reactive oxygen species (ROS) production was significantly promoted after the integration of PB due to the photosensitization effect and initiation of in situ Fenton reaction. Favorably, another inactivation channel was also opened owing to the unique photothermal effect of PB. Attributed to the facilitated ROS intracellular penetration by heat, the composite outperforms not only individual component but anatase TiO2 in pathogen elimination. Specifically, the Staphylococcus aureus (S. aureus) inactivation efficiency of the composite (6.6 log) is 2, 1.8 and 5.1 times higher than that of PB (3.3 log), ZIF-8 (3.7 log) and TiO2 (1.3 log) over 45 min of simulated sunlight illumination. Significantly, the infectivity of Bacillus anthracis and murine coronavirus in droplets on composite-coated filter surface could be greatly reduced (approximately 3 log reduction in colony number/coronavirus titer) within few minutes of solar exposure, indicative of the great potential of MOF composites toward life-threatening microbial infection prevention.

SARS-CoV-2 virus label-free electrochemical nanohybrid MIP-aptasensor based on Ni3(BTC)2 MOF as a high-performance surface substrate.

A dual recognition biosensor was developed via introducing aptamer strings and molecular imprinting polymer (MIP) for the selective detection of intact SARS-CoV-2 virus based on screen printed carbon electrode (SPCE) modified with nickel-benzene tricarboxylic acid-metal-organic framework (Ni3(BTC)2 MOF) synthesized by in situ growth method, SARS-CoV-2 S protein-specific amino-aptamer and electropolymerization of dopamine (ePDA). The proposed biosensor showed an excellent linear relationship between charge transfer resistance (Rct) and increase in virus concentration in the range 10 to 108 plaque-forming units/mL (PFU/mL) with a low detection limit of 3.3 ± 0.04 PFU/mL and response time of 20 min. Compared with single-element sensors (aptamer or MIP), it showed higher selectivity for  the SARS-CoV-2 virus and facilitated detection in real samples.

Peroxymonosulphate Activation by Basolite® F-300 for Escherichia coli Disinfection and Antipyrine Degradation.

In this study, the removal of persistent emerging and dangerous pollutants (pharmaceuticals and pathogens) in synthetic wastewater was evaluated by the application of heterogeneous Advanced Oxidation Processes. To do that, a Metal-Organic Framework (MOF), Basolite® F-300 was selected as a catalyst and combined with peroxymonosulfate (PMS) as oxidants in order to generate sulphate radicals. Several key parameters such as the PMS and Basolite® F-300 concentration were evaluated and optimized using a Central Composite Experimental Design for response surface methodology for the inactivation of Escherichia coli. The assessment of the degradation of an analgesic and antipyretic pharmaceutical, antipyrine, revealed that is necessary to increase the concentration of PMS and amount of Basolite® F-300, in order to diminish the treatment time. Finally, the PMS-Basolite® F-300 system can be used for at least four cycles without a reduction in its ability to disinfect and degrade persistent emerging and dangerous pollutants such as pharmaceuticals and pathogens.

Association between thrombocytopenia and the severity of Covid-19 infection among hospitalized Egyptian patients.

Background: COVID-19, which is caused by the corona virus 2 that causes severe acute respiratory syndrome, causes a respiratory and systemic illness that in 10-15% of patients escalates to a severe form of pneumonia. Thrombocytopenia is frequent in patients with COVID-19. We aimed to evaluate the association between thrombocytopenia and the severity of COVID-19 infection in hospitalized patients. Methods: A cross-sectional study was done on 800 Egyptian patients with confirmed covid-19 infection. They were divided into Group I (Mild): 200 symptomatic patients meeting the case definition for COVID-19 without radiological evidence of pneumonia or hypoxia. Group II (Moderate): 200 patients with clinical signs of non-severe pneumonia and radiological evidence of pneumonia. Group III (Severe): 200 patients with clinical signs of pneumonia plus: respiratory or lung dysfunction. Group IV: 200 critically ill patient in ICU: Acute respiratory distress syndrome (ARDS).Results: there was a highly statistically significant difference between the studied groups regarding thrombocytopenia (p < 0.001). Thrombocytopenia was statistically higher in severe and critically ill patients. In addition, a statistically significant difference found in outcome among the studied groups (p < 0.05) {critically ill (40%), severe (17.5%)}. The most common cause of death was respiratory failure, which occurred in 28 severe patients (80%) and 65 critically ill patients (81.25%), followed by hemorrhage due to thrombocytopenia, which occurred in 7 severe patients (20%) and 15 critically ill patients, respectively (18.75%). Conclusion: The Platelet count is a straightforward, inexpensive, as well as easily available laboratory parameter that is frequently linked to severe covid-19 infection and a significant death risk.

Integration of sustained low-efficiency dialysis into extracorporeal membrane oxygenation circuit in critically ill COVID-19 patients: A feasibility study.

BACKGROUND: Severe COVID-19 can necessitate multiple organ support including veno-venous extracorporeal membrane oxygenation (vvECMO) and renal replacement therapy. The therapy can be complicated by venous thromboembolism due to COVID-19-related hypercoagulability, thus restricting vascular access beyond the vvECMO cannula. Although continuous renal replacement therapy can be performed via a vvECMO circuit, studies addressing sustained low-efficiency dialysis (SLED) integration into vvECMO circuits are scarce. Here we address the lack of evidence by evaluating feasibility of SLED integration into vvECMO circuits. METHODS: Retrospective cohort study on nine critically ill COVID-19 patients, treated with integrated ECMO-SLED on a single intensive care unit at a tertiary healthcare facility between December 2020 and November 2021. The SLED circuits were established between the accessory arterial oxygenator outlets of a double-oxygenator vvECMO setup. Data on filter survival, quality of dialysis, and volume management were collected and compared with an internal control group receiving single SLED. RESULTS: This study demonstrates general feasibility of SLED integration into existing vvECMO circuits. Filter lifespans of ECMO-SLED compared with single SLED are significantly prolonged (median 18.3 h vs. 10.3 h, p < 0.01). ECMO-SLED treatment is furthermore able to sufficiently normalize creatinine, blood urea nitrogen, and serum sodium, and allows for adequate ultrafiltration rates. CONCLUSIONS: We can show that ECMO-SLED is practical, safe, results in adequate dialysis quality and enables sufficient electrolyte and volume management. Our data indicate that SLED devices can serve as potential alternative to continuous-veno-venous-hemodialysis for integration in vvECMO circuits.

Metal-organic frameworks encapsulated with an anticancer compound as drug delivery system: Synthesis, characterization, antioxidant, anticancer, antibacterial, and molecular docking investigation

Metal organic framework (MOF) hybrid materials could be one of the answers in this investigation. We describe a simple and effective encapsulation of doxorubicin (DOX), an anticancer drug, inside Zr-MOF, which have been little studied as drug delivery organizations. We investigated the measured release of the drug from Zr-MOF in response to external incentives such as pH changes and interaction with biomimetic schemes. Zr-MOF with encapsulated doxorubicin (DOX@Zr-MOF) can be manufactured in one pot by addition the anticancer medication DOX to the reaction combination. They demonstrated pH-responsive medication release and cancer cell killing capability. MOFs can be designed as multifunctional distribution vehicles for a diversity of loads, including medicinal and imaging agents, using our simple one-pot approach. Fourier transform infrared (FTIR), X-ray diffraction, scanning electron microscopy, and N-2 sorption isotherm were used to analyze MOF and the developed drug delivery (DOX@Zr-MOF) scheme. It investigated the effects of MOF and a bespoke drug delivery system on the feasibility of patient breast as well as liver tumor cell lines. At pH 5, the trapped drug can be released more quickly than at pH 7.4. Zr-MOF nanoparticles had modest cytotoxicity;however, DOX@Zr-MOF has higher cytotoxicity in MCF-7 and HepG-2 cells than DOX at concentrations greater than 31.25 mu g ml(-1). These results were discovered that DOX@Zr-MOF could be a promising technique for delivering medicines to cancer cells. Furthermore, using the agar well dispersion technique, Zr-MOF, DOX, and captured DOX@Zr-MOF samples were assessed for their potential antibacterial activity against pathogenic bacteria in comparison to traditional antibiotics. In compared to the reference medication Gentamycin, the DOX@Zr-MOF exhibits a large inhibitory zone against Gram negative organisms (Escherichia coli). The docking active place interactions were assessed to see if DOX might bind to the breast cancer 3hb5-oxidoreductase receptor, prostate cancer protein 2q7k, and SARS-CoV-2 protease 6YB7 for anticancer and anticovid-19 activities.

Bioactive hybrid metal-organic framework (MOF)-based nanosensors for optical detection of recombinant SARS-CoV-2 spike antigen.

Fast, efficient, and accurate detection of SARS-CoV-2 spike antigen is pivotal to control the spread and reduce the mortality of COVID-19. Nevertheless, the sensitivity of available nanobiosensors to detect recombinant SARS-CoV-2 spike antigen seems insufficient. As a proof-of-concept, MOF-5/CoNi2S4 is developed as a low-cost, safe, and bioactive hybrid nanostructure via the one-pot high-gravity protocol. Then, the porphyrin, H2TMP, was attached to the surface of the synthesized nanomaterial to increase the porosity for efficient detection of recombinant SARS-CoV-2 spike antigen. AFM results approved roughness in different ranges, including 0.54 to 0.74 µm and 0.78 to ≈0.80 µm, showing good physical interactions with the recombinant SARS-CoV-2 spike antigen. MTT assay was performed and compared to the conventional synthesis methods, including hydrothermal, solvothermal, and microwave-assisted methods. The synthesized nanodevices demonstrated above 88% relative cell viability after 24 h and even 48 h of treatment. Besides, the ability of the synthesized nanomaterials to detect the recombinant SARS-CoV-2 spike antigen was investigated, with a detection limit of 5 nM. The in-situ synthesized nanoplatforms exhibited low cytotoxicity, high biocompatibility, and appropriate tunability. The fabricated nanosystems seem promising for future surveys as potential platforms to be integrated into biosensors.

Porphyrin Molecules Decorated on Metal-Organic Frameworks for Multi-Functional Biomedical Applications.

Metal-organic frameworks (MOFs) have been widely used as porous nanomaterials for different applications ranging from industrial to biomedicals. An unpredictable one-pot method is introduced to synthesize NH2-MIL-53 assisted by high-gravity in a greener media for the first time. Then, porphyrins were deployed to adorn the surface of MOF to increase the sensitivity of the prepared nanocomposite to the genetic materials and in-situ cellular protein structures. The hydrogen bond formation between genetic domains and the porphyrin' nitrogen as well as the surface hydroxyl groups is equally probable and could be considered a milestone in chemical physics and physical chemistry for biomedical applications. In this context, the role of incorporating different forms of porphyrins, their relationship with the final surface morphology, and their drug/gene loading efficiency were investigated to provide a predictable pattern in regard to the previous works. The conceptual phenomenon was optimized to increase the interactions between the biomolecules and the substrate by reaching the limit of detection to 10 pM for the Anti-cas9 protein, 20 pM for the single-stranded DNA (ssDNA), below 10 pM for the single guide RNA (sgRNA) and also around 10 nM for recombinant SARS-CoV-2 spike antigen. Also, the MTT assay showed acceptable relative cell viability of more than 85% in most cases, even by increasing the dose of the prepared nanostructures.

Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19.

BACKGROUND: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). METHODS: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n = 17), severe (n = 40) and critical groups (n = 43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. RESULTS: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 µg/L vs. 501.90 µg/L, p < 0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p = 0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP. CONCLUSION: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la hiperferritinemia podría ser un factor predictivo de la mortalidad en pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19). MÉTODOS: Se incluyó un total de 100 pacientes hospitalizados con COVID-19 en la unidad de cuidados intensivos (UCI), clasificándose como grupos moderado (n = 17), grave (n = 40) y crítico (n = 43). Se recopiló la información clínica y de laboratorio, comparándose los niveles de ferritina entre los diferentes grupos. Se evaluó la asociación entre ferritina y mortalidad mediante un análisis de regresión logística. Además, se evaluó la eficacia del valor predictivo utilizando la curva ROC (receiver operating characteristic). RESULTADOS: La cantidad de ferritina fue significativamente superior en el grupo de pacientes críticos en comparación con el grupo de pacientes graves. La media de concentración de ferritina fue cerca de 3 veces superior en el grupo de muerte que en el grupo de supervivientes (1.722,25 µg/L vs. 501,90 µg/L, p < 0,01). La concentración de ferritina guardó una correlación positiva con otras citoquinas inflamatorias tales como interleucina (IL)-8, IL-10, proteína C reactiva (PRC) y factor de necrosis tumoral (TNF)-α. El análisis de regresión logística demostró que la ferritina era un factor predictivo independiente de la mortalidad intrahospitalaria. En especial, el grupo de ferritina alta estuvo asociado a una mayor incidencia de la mortalidad, con un valor de odds ratio ajustado de 104,97 [intervalo de confianza (IC) del 95% 2,63-4.185,89; p = 0,013]. Además, el valor de ferritina tuvo una ventaja de capacidad discriminativa en el área bajo la curva ROC (AUC) de 0,822 (IC 95% 0,737-0,907] superior al de procalcitonina y PRC. CONCLUSIÓN: El valor de ferritina medido durante el ingreso puede servir de factor independiente para prevenir la mortalidad intrahospitalaria en los pacientes de COVID-19 en la UCI.

Prevalence and Characteristics of Hypoxic Hepatitis in COVID-19 Patients in the Intensive Care Unit: A First Retrospective Study.

Purpose: Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury in reports worldwide. But no studies to date have described hypoxic hepatitis (HH) in patients with COVID-19. We aim to identify the prevalence of and possible mechanisms of HH in COVID-19 patients in the Intensive Care Unit (ICU). Methods: This retrospective study was conducted on 51 patients with confirmed SARS-CoV-2 infection in the ICU at Zhongnan Hospital of Wuhan University from December 21, 2019, to March 11, 2020. Information on clinical features of enrolled patients was collected for analysis. Results: HH was observed in 5.88% of the ICU patients with SARS-CoV-2 infection. All HH patients were progressing to respiratory failure and peak alanine aminotransferase (ALT) values were 1665, 1414, and 1140 U/L during hospitalization, respectively. All patients with HH died as a result of the deterioration of multiple organ failure (MOF). The dynamic changes of ALT, aspartate transaminase (AST), and total bilirubin (TBIL) levels were more dramatic in HH groups. Levels of TBIL, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6(IL-6) showed statistically significant elevation in HH cases compared with that in non-HH cases (P < 0.001). Besides, the median survival time of the HH group was significantly shorter than the non-HH group (P < 0.05). Conclusions: In ICU, HH was not a rare condition in patients with severe COVID-19 and has a high mortality. The main causes of HH are respiratory and cardiac failure and may be associated with the immune-mediated inflammatory response. Clinicians should search for any underlying hemodynamic or respiratory instability even in patients with normal ALT levels on admission.