Bilateral Spontaneous Pneumothorax in a Child with Multisystem Inflammatory Syndrome Associated with COVID-19

Introduction: Spontaneous pneumothorax is a rare complication of coronavirus disease 2019 (COVID-19), primarily reported in adults. Pediatric cases with bilateral pneumothorax are much less reported. Case Presentation: We presented the case of a five-year-old previously healthy boy who developed persistent fever, abdominal pain, generalized maculopapular rash, and dyspnea before admission. His chest computed tomography (CT) showed a viral involvement pattern of pneumonia suggestive of COVID-19. Subsequently, he was confirmed with multisystem inflammatory syndrome in children (MIS-C). While he responded well to the therapies, on the fifth day of admission, he developed respiratory distress again. A chest roentgenogram showed bilateral spontaneous pneumothorax. Bilateral chest tubes were inserted, and his condition improved sig-nificantly after five days of admission to the intensive care unit. Two weeks later, he was discharged in good condition. Conclusion(s): Children with MIS-C associated with COVID-19 may develop primary spontaneous pneumothorax. Owing to the clinical picture overlapping with MIS-C associated with COVID-19, the timely diagnosis of pneumothorax may be challenging in such patients.Copyright © 2022, Author(s).

Memory B cell differentiation from germinal centers.

Establishment of humoral immune memory depends on two layers of defense: pre-existing antibodies secreted by long-lived plasma cells; and the antibodies produced by antigen-reactivated memory B cells. Memory B cells can now be considered as a second layer of defense upon re-infection by variant pathogens that have not been cleared by the long-lived plasma cell-mediated defense. Affinity-matured memory B cells are derived from the germinal center (GC) reaction, but the selection mechanism of GC B cells into the memory compartment is still incompletely understood. Recent studies have revealed the critical determinants of cellular and molecular factors for memory B cell differentiation from the GC reaction. In addition, the contribution of antibody-mediated feedback regulation to B cell selection, as exemplified by the B cell response upon COVID-19 mRNA vaccination, has now garnered considerable attention, which may provide valuable implications for future vaccine design.

Topic: AS04-MDS Biology and Pathogenesis/AS04a-Normal, MDS, and leukemic stem cells: CALPROTECTIN (S100A8/A9) EFFECTS ON HEALTHY CD34+ HEMATOPOIETIC STEM AND PROGENITOR CELLS ARE AMPLIFIED IN CHRONIC MYELOID MALIGNANCIES

Background And Aims: S100A8 and S100A9 alarmins and their heterodimer calprotectin are diversely involved in myeloid neoplasm pathophysiology as well as infectious and inflammatory diseases. In the context of COVID-19, circulating calprotectin was identified as a powerful biomarker of disease severity. Calprotectin impact on CD34+ hematopoietic stem and progenitor cells remains poorly understood. Method(s): Calprotectin effects on healthy donor and chronic myeloid neoplasm-derived CD34-positive hematopoietic stem and progenitor cells were tested in liquid culture for up to 7 days. The pro-inflammatory cytokine IL-6 was used as a control. Cytokine effects alone or in combination were explored by the use of bulk and single cell RNA sequencing, Assay for Transposase-Accessible Chromatin with high-throughput sequencing, cytokine secretion analyses and semi-solid cultures. Result(s): CD34+ cells exposed to IL-6 generate monocytic cells that overproduce calprotectin. Calprotectin inhibits erythroid differentiation of healthy CD34+ cells, possibly through CD36 receptor. Chronic myeloid neoplasm CD34+ cells over-react to calprotectin, with large transcriptomic rewiring of erythro-megakarocytic and granulo-monocytic populations. Calprotectin-induced inhibition of erythroid progenitor proliferation correlates with increased synthesis of ribosomal subunits and p53 pathway activation, while the cytokine impact on granulo-monocytic cells indicates an autocrine or paracrine amplification loop. Conclusion(s): Calprotectin secreted by monocytes generated by CD34+ cells upon IL-6 stimulation may be a pathophysiological component of inflammatory anemia, a role that is amplified in the context of myeloid neoplasms in which calprotectin effects extend to the granulo-monocytic lineage.Copyright © 2023 Elsevier Ltd. All rights reserved.

Nasal mucoadhesive in situ gelling liquid crystalline fluid precursor system of polyene antibiotic for potential treatment of localized sinuses aspergillosis post COVID infection

Nasal mucoadhesive in situ gelling liquid crystalline precursor system (IGFPS) of nystatin was developed for localized treatment of nasal aspergillosis post COVID infection. The stimuli-sensitive sol system comprising of Monoolein (60%w/w), Oleic acid (10%w/w), Dimethyl sulfoxide (15%w/w), Poloxamer 407 (9%w/w), and the drug (2.23%w/w) exhibited a faster sol–gel transformation in situ with good swelling ability. The small angle X-ray scattering study identified the coexistence of Im3m cubic phase with hexagonal closed pack P63/mmc structures. The subzero differential scanning calorimetry studies identified entrapped interphasal water and free water in the gels with confirmation of gelation due to micellization. Mucoadhesive properties of the gel indicate these systems to prolong the residence time at the site of absorption. The gels followed Non-Newtonian flow pattern characteristic of pesudoplastic type. The oscillatory rheology revealed that high complex viscosity and lower tanδ value provided superior adhesiveness and mucoadhesion ability to the gel. The gel exhibited a drug release of 86% at the end of 8h and of Higuchi kinetics with anomalous transport. The IGFPS exhibited better in vitro antifungal activity in comparison to drug solution. The system demonstrated permeation enhancing effect undamaged cilia and no serious histological changes. Post intranasal administration the maximum concentration (11.79 ± 2.31 μg/ml) was realized in 20 min and the curve showed a decline similar to intravenous. The storage stability of the IGFPS was found to be within acceptable limits for stability. Thus, a nasal mucoadhesive in situ gelling fluid liquid crystalline precursor formulation may represent a promising novel alternative for the localized and systemic delivery of nystatin. [ FROM AUTHOR] Copyright of Journal of Dispersion Science & Technology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Dependence of SARS-CoV-2 (COVID-19) inactivation ability on the crystallinity level of transparent Cu2O thin films

The inactivation ability of SARS-CoV-2 (COVID-19) was examined using two types of transparent Cu2O thin films with different crystallinities on a Na-free glass substrate. The low-crystallinity Cu2O thin film, which was fabricated by irradiating 254 nm ultraviolet (UV)-light with an intensity of 6.72 mW cm(-2) onto a spin-coated precursor film involving Cu2+ complexes at room temperature, exhibited an outstanding COVID-19 inactivation ability to reduce 99.999% of the virus after 1 h of incubation. The X-ray diffraction results of the UV-irradiated thin film indicated a cubic Cu2O lattice with a small crystallite size of 2 +/- 1 nm. Conversely, the high-crystallinity Cu2O thin film with a crystallite size of 16 +/- 3 nm, obtained by heating a spin-coated precursor film containing another Cu2+ complex, showed a negligibly low inactivation activity at the same level as the Na-free glass substrate. The eluted concentrations of Cu ions from both Cu2O thin films were analyzed after immersion in Dulbecco's modified Eagle's medium (DMEM) for 0.25-2 h. The eluted Cu-ion concentration of 1.16 ppm was observed for the UV-irradiated thin film by DMEM immersion after 1 h, but that of 0.04 ppm was observed for the heat-treated thin film. This indicated that an important factor of virus inactivation on Cu2O thin films is highly related to the elution of Cu ions that occurred from the surface in the medium.

Effect of vegetation and land surface temperature on NO2 concentration: A Google Earth Engine-based remote sensing approach

With the increasing tension on the global sustainable environment in the urban areas, it is essential to monitor the airborne pollutants and understand the underlying factors that can trigger the situation in a worst-case scenario. Because of its cramped living conditions, excessive coal and fuel usage, and rapid deforestation, the southeast Asian region has historically had worse air quality than the rest of the world. The economic hubs of India and Bangladesh, in particular, have drawn so much attention away from rural regions that unrestrained urbanization is becoming controversial for planners, engineers, and stakeholders in sustainable development. This research combines the two main Asian capital regions, Delhi and Dhaka. It analyzes the change in nitrogen dioxide (NO2) concentration, land surface temperature (LST), and vegetation dynamics across three years (2019-2021) for summer and winter. The NO2 concentration data from Sentinel-5P has been extracted using Google Earth Engine (GEE), and Landsat-8 imagery was utilized for LST, Normalizer Vegetation Index (NDVI), and Enhance Vegetation Index (EVI). The statistical analysis has been carried out by dividing the research regions into one sq. km grid (1512 grids for Delhi and 1485 grids for Dhaka). According to descriptive research, Dhaka's condition is worse than Delhi's, with significant vegetation loss with LST and NO2 concentrations rising. In both research regions, the NO2 concentration is high throughout the winter. The Pearson correlation value demonstrates a negative association between total NO2 concentration and mean NDVI and EVI values and a positive relationship between total NO2 concentration and mean LST. The data have been further assessed using linear regression, which overlaps the correlation result with a maximum R-squared value of 0.2998 for NO2 and EVI in winter 2019.

Amyloidogenesis: What Do We Know So Far?

The study of protein aggregation, and amyloidosis in particular, has gained considerable interest in recent times. Several neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) show a characteristic buildup of proteinaceous aggregates in several organs, especially the brain. Despite the enormous upsurge in research articles in this arena, it would not be incorrect to say that we still lack a crystal-clear idea surrounding these notorious aggregates. In this review, we attempt to present a holistic picture on protein aggregation and amyloids in particular. Using a chronological order of discoveries, we present the case of amyloids right from the onset of their discovery, various biophysical techniques, including analysis of the structure, the mechanisms and kinetics of the formation of amyloids. We have discussed important questions on whether aggregation and amyloidosis are restricted to a subset of specific proteins or more broadly influenced by the biophysiochemical and cellular environment. The therapeutic strategies and the significant failure rate of drugs in clinical trials pertaining to these neurodegenerative diseases have been also discussed at length. At a time when the COVID-19 pandemic has hit the globe hard, the review also discusses the plausibility of the far-reaching consequences posed by the virus, such as triggering early onset of amyloidosis. Finally, the application(s) of amyloids as useful biomaterials has also been discussed briefly in this review.

Procalcitonin and Adrenomedullin in Infectious Diseases

Calcitonin (CT) and adrenomedullin (ADM) are members of the CT family. Procalcitonin (PCT) is a prohormone of CT. Elevations in serum PCT and ADM levels are associated with severe sepsis and coronavirus disease 2019 (COVID-19). PCT enhances sepsis mortality and it binds to the CGRP receptor, which is a heterodimer of CT receptor-like receptor and receptor activity-modifying protein 1. The N-terminal truncated form of PCT, PCT3-116, is produced by the cleavage of PCT by dipeptidyl peptidase 4 (DPP-4) and is the main form of PCT in serum during sepsis, inducing microvascular permeability. Mid-regional pro-adrenomedullin (MR-proADM) is used instead of ADM as a biological indicator because ADM is rapidly degraded, and MR-proADM is released at the same rate as ADM. ADM reduces endothelial permeability and promotes endothelial stability. Endothelial dysfunction is responsible for multiple organ failure in sepsis and COVID-19 patients. Therefore, ADM may be an important molecule for improving the severity associated with sepsis and COVID-19. This review focuses on the current knowledge of PCT and ADM in sepsis and COVID-19.Copyright © 2023 by the authors.

Revealing Potential Binding Affinity of FDA Approved Therapeutics Targeting Main Protease (3CLpro) in Impairing Novel Coronavirus (SARS-CoV-2) Replication that Causes COVID-19

Background: Spread of COVID-19 attains a crucial transition in reveling its pandemic across the boundaries. In combating the infection caused by SARS-CoV-2, there is a spectrum of ideal strategies that have been adopted globally, of which repurposing of approved drugs considerably having high clinical relevance. 3-chymotrypsin-like protease (3CL pro) is considered to be the potential target for the researchers as it is highly essential for cleavage of polyprotein to get 16 nonstructural proteins (called nsp1-nsp16). These proteins are highly essential for viral replication and hence become a primary target for enzyme inhibitors. 3CL pro, having a structural projectile helical chain with biologically active site involved in processing viral polyproteins that are evolved from RNA genome translation. Objective(s): The major objective of the present investigation is to evaluate the enzyme inhibition potential of FDA approved therapeutic leads in targeting 3CLpro that medicates the viral replication. Method(s): Docking calculations were carried out for an array of FDA approved molecules which leads to a notable few molecules such as Emtricitabine, Oseltamivir, Ganciclovir, Chloroquine, Baricitinib, Favipiravir, Lopinavir, Ritonavir, Remdesivir, Ribavirin, Tenofovir, Umifenovir, Carbapenam, Ertap-enem and Imipenam which have both specificity and selectivity in terms of binding efficiency against 3CL proenzyme. Result(s): A combinatorial evaluation employing in-silico screening shows a major lead for remdesivir which possesses a substantial affinity to 3CL pro binding on core amino acid residues, such as Leu 27, His 41, Gly 143, Cys 145, His 164, Met 165, Glu 166, Pro 168 and His 172 which share the biological significance in mediating enzymatic action. Results of docking simulation by Autodock over a host of FDA approved molecules show high degree of selectivity and specificity in the increasing order of binding capacity;Remdesivir> Ertapenem> Imipenam> Tenofovir> Umifenovir> Chloroquine> Lopinavir> Ritonavir> Emtricitabine> Ganciclovir> Baricitinib> Ribavirin>Oseltamivir>Favipiravir> Carbapenam. Conclusion(s): Till date, there is no known cure attained for treating COVID-19 infection. In conclusion, lead molecules from already approved sources provoke promising potential which grabs the attention of the clinicians in availing potential therapeutic candidate as a drug of choice in the clinical management of COVID-19 time-dependently.Copyright © 2020 Bentham Science Publishers.

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

COVID-19 infection during blinatumomab therapy: Is safety a dilemma?

Patients with acute lymphoblastic leukemia may be particularly vulnerable to SARS-CoV-2 infection and severe illness. The mainstay of current treatment is the use of blinatumomab in patients with refractory or relapsed B-cell precursor acute lymphoblastic leukemia. We discuss the case of a patient with relapsed acute lymphoblastic leukemia who became positive for SARS-CoV-2 during blinatumomab therapy. There are no formal recommendations on the decision to continue, withhold, or delay blinatumomab treatment in these patients. More studies exploring this issue are warranted, as SARS-CoV-2 is expected to be here to stay.

SARS-CoV-2 infects red blood cell progenitors and dysregulates hemoglobin and iron metabolism

Background: COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes acute respiratory symptoms and is reported to affect the vascular system, which may be underlying the systemic symptoms observed in affected patients. However, severe cases were reported to be associated with reduced erythrocyte (RBCs) turnover, low hemoglobin (Hb) levels along with increased total bilirubin and ferritin serum concentrations. Moreover, expansion of erythroid progenitors in peripheral blood together with hypoxia, anemia, and coagulopathies highly correlates with severity and mortality. We demonstrate that SARS-CoV-2 directly infects erythroid precursor cells, impairs Hb homeostasis and aggravates COVID19 disease. Method(s): RBC precursors derived from peripheral CD34+ blood stem cells of healthy donors were infected in vitro with SARS-CoV-2 alpha variant and differentiated into RBCs. Hb and iron metabolism in more than 20 hospitalized Covid-19 patients and controls were analyzed in plasma-reduced whole blood samples using different approaches. Result(s): RBC precursors express ACE2 receptor, CD26 and CD147 at day 5 of differentiation, which makes them susceptible to SARS-CoV-2 infection, but virus is not able o replicate in these cell. qPCR analysis of differentiated RBCs revealed increased HAMP mRNA expression levels, encoding for hepcidin, which inhibits iron uptake. Furthermore, we found significantly changes in spin state of the iron in Hb as well as the tertiary structure shown by the formation of disulfide bridges in samples of COVID-19 patients. In addition, COVID-19 patients showed impaired Hb biosynthesis, enhanced formation of zinc-protoporphyrine IX, heme-CO2, and CO-Hb as well as degradation of Fe-heme. Moreover, significant iron dysmetablolism with high serum ferritin and low iron and transferrin levels occurred, explaining disturbances of oxygen-binding capacity observed in severely ill COVID-19 patients. Conclusion(s): Our data identify RBC precursors as a direct target of SARSCoV- 2 and suggest that SARS-CoV-2 induced dysregulation in Hb- and iron-metabolism contributes to the severe systemic course of COVID-19. Because changes in Hb structure may also be significantly involved in the development of Long-COVID symptoms such as fatigue and exhaustion, our findings may open the door for new diagnostic and therapeutic strategies for both intensive care COVID-19 patients and Long-COVID patients.

Dependence of SARS-CoV-2 (COVID-19) inactivation ability on the crystallinity level of transparent Cu2O thin films

The inactivation ability of SARS-CoV-2 (COVID-19) was examined using two types of transparent Cu2O thin films with different crystallinities on a Na-free glass substrate. The low-crystallinity Cu2O thin film, which was fabricated by irradiating 254 nm ultraviolet (UV)-light with an intensity of 6.72 mW cm(-2) onto a spin-coated precursor film involving Cu2+ complexes at room temperature, exhibited an outstanding COVID-19 inactivation ability to reduce 99.999% of the virus after 1 h of incubation. The X-ray diffraction results of the UV-irradiated thin film indicated a cubic Cu2O lattice with a small crystallite size of 2 +/- 1 nm. Conversely, the high-crystallinity Cu2O thin film with a crystallite size of 16 +/- 3 nm, obtained by heating a spin-coated precursor film containing another Cu2+ complex, showed a negligibly low inactivation activity at the same level as the Na-free glass substrate. The eluted concentrations of Cu ions from both Cu2O thin films were analyzed after immersion in Dulbecco's modified Eagle's medium (DMEM) for 0.25-2 h. The eluted Cu-ion concentration of 1.16 ppm was observed for the UV-irradiated thin film by DMEM immersion after 1 h, but that of 0.04 ppm was observed for the heat-treated thin film. This indicated that an important factor of virus inactivation on Cu2O thin films is highly related to the elution of Cu ions that occurred from the surface in the medium.

Safety and Efficacy of Turmeric in Children With Acute Lymphoblastic Leukemia

CONTEXT: Gut microbiota may have a role in regulating the progress of cancer. Curcumin and its metabolites may have various effects on cancer treatments by eliminating intestinal microflora dysbiosis. OBJECTIVES: To assess the safety and efficacy of curcumin in children with acute lymphoblastic leukemia (ALL) and determine whether gut microbiota can be used to predict therapy-related complications. DESIGN: Single-center, open-label prospective randomized controlled clinical trial. SETTING: Pediatric Hematology Oncology Department, Ain Shams University Hospitals, Cairo, Egypt. METHODS: All patients underwent detailed clinical assessment and anthropometric measurement. Nutritional assessment was performed using the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), and nutrition risk were assigned based on 3 parameters: nutrition implication of the patient's medical diagnoses, recent nutrition intake, and anthropometrics. Complete blood count, total protein, and albumin were gathered. Fecal samples were collected to detect microbiota quantity. INTERVENTION: A block-randomization scheme was generated by computer software;patients were randomized between curcumin plus the nutritional standard of care (SOC) and the nutritional SOC only, which consisted of a nutrition program through supplementation of a high-caloric, high-protein diet, tailored according to patients' age and sex for both groups. Curcumin 500 mg was supplemented per oral capsule twice daily for 1 month starting at week 1 of the maintenance phase of chemotherapy. Patients were followed up with once weekly during the curcumin supplementation to monitor compliance and adverse events. All assessments were performed at ALL diagnosis, at week 1 of maintenance phase of chemotherapy, and after 1 month of intervention. RESULTS: Thirty pediatric patients with confirmed ALL were recruited from day 0 of presentation and followed over a 12-month period. The majority of patients were under 10 years of age and presented mainly with fever at time of diagnosis. Their initial nutritional assessment showed STAMP scores of mainly 3 and 4. The curcumin showed a safety profile and was tolerated by most patients. The effects of curcumin on microbiota were studied through assessment of the proportions of Lactobacillus and Bifidobacterium in fecal samples, and the results are in the statistical analysis phase. CONCLUSIONS: This interim analysis showed a promising role of curcumin as a nutritional supplement in children with ALL.

Unraveling the mystery of efficacy in Chinese medicine formula: New approaches and technologies for research on pharmacodynamic substances.

Traditional Chinese medicine (TCM) is the key to unlock treasures of Chinese civilization. TCM and its compound play a beneficial role in medical activities to cure diseases, especially in major public health events such as novel coronavirus epidemics across the globe. The chemical composition in Chinese medicine formula is complex and diverse, but their effective substances resemble "mystery boxes". Revealing their active ingredients and their mechanisms of action has become focal point and difficulty of research for herbalists. Although the existing research methods are numerous and constantly updated iteratively, there is remain a lack of prospective reviews. Hence, this paper provides a comprehensive account of existing new approaches and technologies based on previous studies with an in vitro to in vivo perspective. In addition, the bottlenecks of studies on Chinese medicine formula effective substances are also revealed. Especially, we look ahead to new perspectives, technologies and applications for its future development. This work reviews based on new perspectives to open horizons for the future research. Consequently, herbal compounding pharmaceutical substances study should carry on the essence of TCM while pursuing innovations in the field.

Donepezil Beyond Alzheimer’s Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer’s disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson’s disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer’s and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer’s diseases, and more comprehensive studies are needed.

Engineered Sleeping Beauty Transposon as Efficient System to Optimize Chimp Adenoviral Production.

Sleeping Beauty (SB) is the first DNA transposon employed for efficient transposition in vertebrate cells, opening new applications for genetic engineering and gene therapies. A transposon-based gene delivery system holds the favourable features of non-viral vectors and an attractive safety profile. Here, we employed SB to engineer HEK293 cells for optimizing the production of a chimpanzee Adenovector (chAd) belonging to the Human Mastadenovirus C species. To date, chAd vectors are employed in several clinical settings for infectious diseases, last but not least COVID-19. A robust, efficient and quick viral vector production could advance the clinical application of chAd vectors. To this aim, we firstly swapped the hAd5 E1 with chAd-C E1 gene by using the CRISPR/Cas9 system. We demonstrated that in the absence of human Ad5 E1, chimp Ad-C E1 gene did not support HEK293 survival. To improve chAd-C vector production, we engineered HEK293 cells to stably express the chAd-C precursor terminal protein (ch.pTP), which plays a crucial role in chimpanzee Adenoviral DNA replication. The results indicate that exogenous ch.pTP expression significantly ameliorate the packaging and amplification of recombinant chAd-C vectors thus, the engineered HEK293ch.pTP cells could represent a superior packaging cell line for the production of these vectors.

Mechanism and Clinical Research Progress of Nirmatrelvir Tablets/Ritonavir Tablets: A New Therapeutic Agent for COVID-19

OBJECTIVE: To review the mechanism and the clinical research progress of nirmatrelvir tablets/ritonavir tablets(PaxlovidTM), so as to provide references for its rational usage. METHODS: Literatures related to nirmatrelvir tablets/ritonavir tablets in the official website of US Food and Drug Administration, Pubmed, Embase, CNKI, CBM and Wanfang were systematically searched. The basic information, mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy evaluation, safety, drug interaction, drug use in special populations were reviewed. RESULTS AND CONCLUSIONS: Nirmatrelvir tablets/ritonavir tablets inhibit the replication of SARS-COV-2 virus by inhibiting the processing of SARS-CoV-2 protein precursor mediated by the main protease. Based on current trial results, nirmatrelvir tablets/ritonavir tablets can significantly reduce hospitalization and mortality rates in adult patients with mild and moderate COVID-19. More research is required to determine whether the drug is appropriate for the clinical treatment of all COVID-19 patients.

Co3O4/MoS2Nanostructures for NOxSensing

2D transition metal dichalcogenides have performed exceptionally as the active layer for chemiresistive gas sensors. Combining these materials with semiconductor oxides of tunable properties has proved to improve gas sensing and overall device performance due to the synergizing effect of the hybrid nanostructures. In this manuscript, we report the synthesis of a Co3O4/MoS2 nanostructure-based highly sensitive chemiresistive gas sensor selective toward NOx gases. An increase in air pollution has caused an equal increase in the concentrations of toxic NOx gases in the atmosphere. Exposure to these gases leads to grave health hazards such as pulmonary diseases and cardiovascular diseases. Furthermore, recent studies prove that NOx gases are also a contributor to COVID-19 fatality. We investigated the effect of the change in precursor concentration of cobalt nitrate (CoN2O6) and temperature on the gas sensor response. The precursor concentration was varied over an increasing range of molarities (1, 5, 10, and 25 mM), and it was observed that the gas sensor with a precursor concentration of 25 mM and an operating temperature of 200 °C exhibited the highest response of 145.7% toward NO2 gas (4.3 ppm) and then 105.37% toward NO (2.75 ppm). It was also noted that the device responded to NO2 gas of concentration as low as 300 ppb. This device was then subjected to an increasing range of temperatures (50, 100, 150, 200, 250, and 300 °C). A clear increase in the device performance was observed with an increase in temperature. It was found that the gas sensor was the most sensitive toward NO2 gas (4.3 ppm) and exhibited a response of 186.2% at 250 °C followed by NO (2.75 ppm) with a response of 141.6%. A stable and excellent response toward a low concentration of 50 ppb of NO2 was observed. Two activation energies (Ea) were calculated from the Arrhenius plot Ea1 (0.846 eV) between 150 and 200 °C and Ea2 (1.316 eV) between 200 and 250 °C, indicating multiple energy trapping. These results pave a way for a plausible application of Co3O4/MoS2 hybrid nanostructures for the detection and monitoring of NOx gases in the air. ©

Hemophagocytic lymphohistiocytosis sans triggers

Case Report Hemophagocytic Lymphohistiocytosis (HLH) is an hyperinflammatory state due to hyperactivation of macrophages and T-cells which rarely affects adults. It can be familial or sporadic. Triggers are infections, auto-immune diseases, malignancies, and immune checkpoint inhibitors. HLH diagnostic criteria are fever, splenomegaly, bicytopenia, hypertriglyceridemia, hemophagocytosis, low/absent NK-cellactivity, elevated ferritin, and high-soluble interleukin-2-receptor (IL-2R). Five out of eight criteria are required for diagnosis. A 54-year-old female was noted to have leukopenia during a routine visit with her family physician. Follow up labs revealed worsening leukopenia, anemia and a normal platelet count. She received Amoxicillin/Clavulanic acid for a presumed upper respiratory infection and developed nausea, diarrhea and decreased appetite. She was referred to Hematology Oncology for leukopenia. During workup she developed fatigue, night sweats and high fevers. Workup revealed WBC 2400 mcL, microcytic anemia, transaminitis with lactate dehydrogenase of 1725 U/L and ferritin of >15000 ng/ mL . Peripheral blood smear showed leukopenia without immature cells or blasts and mild microcytic erythrocytes. Further tests detected CXCL-9 of 125050 pg/mL, D-dimer of >5000 ng/mL and interleukin-2-receptor of 20604 pg/ mL. EBV, CMV, HSV, HHV-6, parvovirus, bartonella, leishmaniasis, bacteria and COVID-19 were negative. Computed tomography of the chest, abdomen and pelvis did not reveal lymphadenopathy. Brain imaging showed no abnormalities. Cerebrospinal fluid cytology was unremarkable. Bone marrow biopsy (BMBX) showed prominent histiocytic phagocytosis of erythroid precursors and platelets. HLH-94 treatment protocol including weekly steroid and etoposide initiated. Patient's fever, night sweats and leukopenia resolved during hospitalization, with subsequent down trending of ferritin to 103 ng/ml, CXCL-2 to 2663 pg/mL and interleukin-2-receptor to 2,265 pg/mL. Repeat BMBX revealed significant improvement. HLH is a rare life-threatening diagnosis. This patient with nonspecific symptoms was diagnosed with HLH (fever, bicytopenia, elevated ferritin, high-soluble IL-2R and hemophagocytic lymphohistiocytosis on BMBX). Several HLH gene mutations were tested including PRF1, UNC13D, STXBP2, although none was mutated. No infectious, rheumatologic or oncologic triggers were detected. Early diagnosis and treatment are critical. Without treatment, survival is measured in months due to multiorgan failure. This syndrome rarely presents in the absence of triggers which may cause delay in diagnosis and successful treatment. 5-year overall survival with HLH 94 protocol is 54% as opposed to 0% prior to the advent of this protocol. Etoposide and steroids are the mainstay of HLH-94. Cyclosporine can be added in the maintenance phase and hematopoietic stem cell transplant is reserved for familial or relapsed HLH.