Association of genetic polymorphisms in glucocorticoid pathway with dexamethasone treatment in COVID-19 patients

Background/Objectives: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19 caused by SARS-CoV- 2 as they attenuate the immune response with their antiinflammatory properties. Genetic polymorphisms of glucocorticoid receptor, metabolizing enzymes or transporters may affect treatment response to dexamethasone. The aim of this study was to evaluate the association of polymorphisms in glucocorticoid pathway with disease severity and duration of dexamethasone treatment in COVID-19 patients. Method(s): Our study included 107 hospitalized COVID-19 patients treated with dexamethasone. We isolated DNA from peripheral blood and genotyped all samples for polymorphisms in NR3C1 (rs6198, rs33388), CYP3A4 (rs35599367), CYP3A5 (rs776746), GSTP1 (rs1695, rs1138272), GSTM1/GSTT1 deletions and ABCB1 (1045642, rs1128503, rs2032582 Fisher's and Mann- Whitney tests were used in statistical analysis. Result(s): The median (min-max) age of the included patients was 62 (26-85) years, 69.2 % were male and 30.8 % female and they had moderate (1.9 %), severe (83 %) or critical (15.1 %) disease. NR3C1 rs6198 polymorphism was associated with more severe disease in additive genetic model (P = 0.022). NR3C1 rs6198, ABCB1 rs1045642 and ABCB1 rs1128503 polymorphisms were associated with a shorter duration of dexamethasone treatment in additive (P = 0.048, P = 0.047 and P = 0.024, respectively) and dominant genetic models (P = 0.015, P = 0.048 and P = 0.020, respectively), while carriers of the polymorphic CYP3A4 rs35599367 allele required longer treatment with dexamethasone (P = 0.033). Other polymorphisms were not associated with disease severity or dexamethasone treatment duration. Conclusion(s): Genetic variability of glucocorticoid pathway genes was associated with the duration of dexamethasone treatment of COVID-19 patients.

Association between Type 2 Diabetes Mellitus and Covid-19 Severity: A Literature Review

We conducted a review and evaluated the already documents reports for the relationship among diabetes and COVID-19. The review outcome shows that the COVID-19 severity seems to be greater among patients with diabetes as comorbidity. So, strict glycemic control is imperative in patients infected with COVID-19. Thus, world-wide diabetes burden and COVID-19 pandemic must be deliberated as diabetes increases the COVID-19 severity. Established on this, it is precise significant to follow specific treatment protocols and clinical management in COVID-19 patients affected with diabetes to prevent morbidity and mortality.Copyright © 2023 The Authors.

Emerging Invasive Group A Streptococcus M1UK Lineage Detected by Allele-Specific PCR, England, 20201.

Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.

Strategic management and organizational culture of medical device companies in relation to corporate performance.

AIMS: Strategies focus on securing the competitiveness of medical device corporations by strengthening their organizational capabilities, which, in turn, ensure their continuous development. This study aims to investigate both management strategies and organizational culture, which may affect the performance of these companies, and analyzes the influence of education and training investment. MATERIALS AND METHODS: We used data from the 3rd to 6th Human Capital Corporate Panel surveys by the Korea Research Institute for Vocational Education and Training as well as data from the Korea Information Service and 6,112 workers and 260 companies were analyzed. For the analysis, management strategy and organizational culture were set as independent variables, and corporation performance was set as the dependent variable. Additionally, investment in education and training was set as a control variable between the independent and dependent variables. Corporate performance was analyzed by dividing into organizational satisfaction and organizational commitment. RESULTS: Differentiation strategy and innovative culture had a positive (+) effect on organizational satisfaction, while cost leadership strategy and hierarchical culture had a negative (-) effect. On the other hand, in the case of interaction with education and training investment, cost leadership strategy and hierarchical culture had a positive (+) effect, while differentiation strategy and innovation culture had a negative (-) effect. In organizational commitment, innovation culture had a positive (+) effect, and hierarchical culture had a negative (-) effect. In the case of interaction with investment in education and training, only the hierarchical culture had a positive (+) effect. CONCLUSIONS: The innovation culture positively influenced the performance of medical device companies. Furthermore, cost leadership strategy, hierarchical culture, education and training investment improved the corporate performance of these companies. To enhance corporate performance, these companies should create an innovation culture and invest in education and training in accordance with the organizational culture.

COVID-19 has proven the excellence of Korea's medical devices, and the medical device industry is expected to continue to grow due to the increase in chronic disease and non-face-to-face treatment. However, the current medical device industry is monopolized by global companies with capital and technological prowess. To overcome this, Korean medical device companies are developing innovative medical devices centered on start-ups, but now is the time to strategically respond to them in order to compete with global companies. In general, companies establish management strategies for survival and growth by analyzing threats and opportunities based on the market environment to maintain the optimal organization according to market competition, government policies, and changes in consumer needs. Strategies are often established based on the culture of the organizations that make up the company. When it comes to strategy establishment, the medical device industry has special characteristics compared to other industries. The medical device industry is based on advanced technology and puts patient safety first, requiring continuous product upgrades. Therefore, it is an essential industry for employees to invest in education and training. The analysis shows the effectiveness of investment in education and training according to the management strategy and organizational culture of medical device companies. It was confirmed that when medical device companies create an Innovation culture, their performance improves. It also shows that when medical device companies adopt a cost leadership strategy, they need to increase their investment in education and training to improve corporate performance.

Antibacterial Activity and in Silico Investigation of 2-[(3-Substitutedphenyl) Azomethine] Phenol as anti-SARS-CoV-2 Mpro and anti-Plasmodium falciparum Agents

Imine derivatives are widely used in medicine for the treatment of several diseases causing human infections;we examined Schiff's bases derivatives: 2-[(3-methylphenyl) azomethine] phenol (L1), 2-[(3-chlorophenyl) azomethine] phenol (L2) and 2-[(3-nitrophenyl) azomethine] phenol (L3) against three human pathogenic bacterial strains according to the disk diffusion test. In addition, to revealing the importances of the in silico study of these derivatives, in particular the molecular docking which is based on the protein structures: the main protease 3CL of SARS-CoV-2 and the aminopeptidase of the M1 family. Also, a molecular dynamics simulation was performed to examine the structural stability of the best docked conformation. The evaluation of the global reactivity parameters of the molecular system of Schiff base derivatives was applied by the DFT method with the hybrid functional (B3LYP)/6-31G (d) basis set. The results of the antibacterial activity showed a strong activity in the presence of the L3 ligand against Escherichia coli (ATCC 25922) with a diameter inhibition zone equal to 11 ± 0.61 mm. Molecular docking shows that the L3 ligand formed with protein targets more stable complexes by predicting interesting interactions: hydrogen, hydrophobic and electrostatic bonds with the residues of these targets 3CLpro and PfA-M1. Further, molecular dynamics simulations confirm a strong energy contribution with these interactions. Therefore, suggesting that our ligands could contribute to the development of anti-coronavirus-2 and anti-malarial drug properties. [ FROM AUTHOR] Copyright of Polycyclic Aromatic Compounds 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.)

A Machine Learning-driven IoT Architecture for Predicting the Growth and Trend of Covid-19 Epidemic Outbreaks to Identify High-risk Locations

Covid-19 has had a destructive influence on global economics, social life, education, and technologies. The rise of the Covid-19 pandemic has increased the use of digital tools and technologies for epidemic control. This research uses machine learning (ML) models to identify populated areas and predict the disease's risk and impact. The proposed system requires only details about mask utilization, temperature, and distance between individuals, which helps protect the individual's privacy. The gathered data is transferred to an ML engine in the cloud to determine the risk probability of public areas concerning Covid-19. Extracted data are input for multiple ML techniques such as Random Forest (RF), Decision tree (DT), Naive Bayes classifier(NBC), Neural network(NN), and Support vector machine (SVM). Expectation maximization (EM), K-means, Density, Filtered, and Farthest first (FF) clustering algorithms are applied for clustering. Compared to other algorithms, the K-means produces better superior accuracy. The regression technique is utilized for prediction. The outcomes of several methods are compared, and the most suitable ML algorithms utilized in this study are used to identify high-risk locations. In comparison to other identical architectures, the suggested architecture retains excellent accuracies. It is observed that the time taken to build the model using locally weighted learning(LWL) was 0.02 seconds, and the NN took more time to build, which is 0.90 seconds. To test the model, an LWL algorithm took more time which is 1.73 seconds, and the NN took less time to test, which is 0.02 seconds. The NBC has a 99.38 percent accuracy, the RF classifier has a 97.33 percent accuracy, and the DT has a 94.51 percent accuracy for the same data set. These algorithms have significant possibilities for predicting the likelihood of crowd risks of Covid-19 in a public space. This approach generates automatic notifications to concerned government authorities in any aberrant detection. This study is likely to aid researchers in modeling healthcare systems and spur additional research into innovative technology. © 2023 IEEE.

Immunogenetic studies on SARS-CoV-2: Our experience at SKIMS

Background: The pathophysiology of viral-infections is highly complex and involves host immunocompetence, host genetics, and gene-environment interactions. We hypothesized that polymorphic variants in host genes, blood group and previous vaccination status against H1N1 may affect the clinical course of covid-19 infection. Method(s): A total of 202 subjects who were RT-PCR negative after Covid-19 infection were recruited. We investigated association between Covid-19 infection (Severity and recovery period) and multiple factors including ABO and Rh blood groups, H1N1 vaccination, polymorphism in Viral susceptibility genes (ACE2 G8790A), and polymorphism in host response genes (ACE I/D rs4646994, IL6- 174G/C, GSTT1/GSTM1 I/D and GSTP1 Ile 105 Val). Result(s): B-ve and O-ve ABO and Rh blood groups had significantly higher Covid-19 recovery period applied on one-vs.-all in a nonparametric t-test (p<0.05). Subjects who had vaccinated themselves against H1N1 presented with a lower recovery-period (p<0.05). Both variables (blood group and H1N1 vaccination) were not however associated with Covid-19 severity. Out of the studied polymorphisms, ACE2 G8790A and GSTT1/GSTM1 were significantly associated with covid-19 infection. Our results indicated that G/G genotype of ACE2 G8790A (OR 3.52, P 0.007) and GSTT1/ GSTM1 null (M1 - / - OR = 3.98, P = 0.0004;T1 - / - OR 3.84, P = 0.004) and double null (M1 - / - /T1 - / - OR = 9.66, P = 0.001) are likely to be associated with an increased risk for severe-critical outcomes in individuals with COVID-19. Other polymorphisms analyzed in this study were found to have no significant association with Covid-19 outcome. Conclusion(s): This study suggests that outcome of Covid-19 infection is affected by both clinical and genetic factors. Thus it seems plausible to utilize these factors as prediction and susceptibility markers in the prognosis of COVID-19, which may help to personalize the treatment.

Relationship among leadership styles, employee's well-being and employee's safety behavior: an empirical evidence of COVID-19 from the frontline healthcare workers

The study investigates the association among leadership styles, employee well-being and employee's safety behavior of healthcare workers. The study used social learning theory (SLT) for examining the relationship between leadership styles and employee safety behavior. Moreover, social exchange theory (SET) has been incorporated to narrate the moderating effect of employee well-being on the relationship between leadership styles and employee safety behavior. Data have been collected with the help of questionnaires from 515 healthcare workers working in the public hospitals of Punjab, Pakistan. Structural equation modeling has been utilized to test the study hypothesis. Findings indicate that both transactional and transformational leaderships have significant and positive relationship with employee safety behavior. Interestingly, employee well-being negatively moderates the relationship between transformational leadership and employee safety behavior. Furthermore, no moderation was found on the relationship between transactional leadership and employee safety behavior. The findings propose that healthcare management should invest to aware employees regarding their well-being. The findings also suggest that leaders should influence their followers to adopt safety measures at workplace. Furthermore, leaders must be role models in order to attain a competitive advantage and make a balance between management and workers. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers. © 2022 The Authors

Inhalation of L-arginine-modified liposomes targeting M1 macrophages to enhance curcumin therapeutic efficacy in ALI.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), characterized by uncontrolled lung inflammation, is one of the most devastating diseases with high morbidity and mortality. As the first line of defense system, macrophages play a crucial role in the pathogenesis of ALI/ARDS. Therefore, it has great potential to selectively target M1 macrophages to improve the therapeutic effect of anti-inflammatory drugs. L-arginine plays a key role in regulating the immune function of macrophages. The receptors mediating L-arginine uptake are highly expressed on the surface of M1-type macrophages. In this study, we designed an L-arginine-modified liposome for aerosol inhalation to target M1 macrophages in the lung, and the anti-inflammatory drug curcumin was encapsulated in liposomes as model drug. Compared with unmodified curcumin liposome (Cur-Lip), L-arginine functionalized Cur-Lip (Arg-Cur-Lip) exhibited higher uptake by M1 macrophages in vitro and higher accumulation in inflamed lungs in vivo. Furthermore, Arg-Cur-Lip showed more potent therapeutic effects in LPS-induced RAW 264.7 cells and the rat model of ALI. Overall, these findings indicate that L-arginine-modified liposomes have great potential to enhance curcumin treatment of ALI/ARDS by targeting M1 macrophages, which may provide an option for the treatment of acute lung inflammatory diseases such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome and middle east respiratory syndrome.

Matrix-Encoding Gene Diversity of 624 Influenza A/H3N2 Genomes Does Not Show Association with Impaired Viral Detection by Commercialized qPCR Assays.

As for the case of SARS-CoV-2, genome sequencing of influenza viruses is of potential interest to raise and address virological issues. Recently, false-negativity of real-time reverse transcription-PCR (qPCR) assays that detect influenza A/H3N2 virus RNA were reported and associated with two mutations (A37T and C161T) in the Matrix-encoding (M1) gene located on viral segment 7. This triggered a national alert in France. The present study sought to assess the association between the presence of these mutations and potential false negative results of influenza A/H3N2 virus RNA detection by commercialized qPCR assays at the clinical virology laboratory of our university hospitals in southern France. This study focused on the genetic diversity in the M1 gene and segment 7 of 624 influenza A/H3N2 virus genomes obtained from respiratory samples having tested qPCR-positive with M1 gene-targeting assays in our clinical virology laboratory. A total of 585 among the 624 influenza A/H3N2 virus genomes (93.7%) were of clade 3C.2a1b.2a.2, and 39 (6.3%) were of clade 3C.2a1b.1a. M1 gene substitutions A37T and C161T were both present in 582 (93.3%) genomes, only of clade 3C.2a1b.2a.2. Substitution A37T was present in 621 (99.5%) genomes. Substitution C161T was present in 585 genomes (93.8%), all of clade 3C.2a1b.2a.2. Moreover, 21 other nucleotide positions were mutated in ≥90% of the genomes. The present study shows that A37T/C and C161T mutations, and other mutations in the M1 gene and segment 7, were widely present in influenza A/H3N2 virus genomes recovered from respiratory samples diagnosed qPCR-positive with commercialized assays.

Tubuloside B, isolated from Cistanche tubulosa, a promising agent against M1 macrophage activation via synergistically targeting Mob1 and ERK1/2.

Targeting macrophage M1 polarization is a promising strategy with fewer detrimental effects in COVID-19 curation. Phenylethanoid glycosides (PhGs) of Cistanche tubulosa are a botanical drug to possess various anti-inflammation-related functions, such as immunomodulating, hepatoprotective or neuroprotective functions, whereas their anti-inflammatory activity is rarely understood. A search into their anti-inflammatory characteristics led to the isolation of 49 PhGs along with 15 new PhGs. Their inhibitory effects against M1 polarization induced by LPS plus IFN-γ were explored in RAW264.7 macrophages. Of these PhGs, tubuloside B (Tub B) exerted substantial NO scavenging effect both in chemical- and cell-based assays, and it inhibited massive production of cytokines and chemokines. Tub B decreased ERK1/2 phosphorylation via direct binding and inhibited the MAPK signaling pathway. Tub B also directly binded to Mob1 protein, thereby increased the stability and level of Mob1 protein by inhibiting ubiquitinated degradation. Mob1 was pivotal for the anti-inflammatory activity of Tub B, and it acted independently of the canonical Hippo-YAP pathway. Moreover, ERK1/2 and Mob1 also had a synergic effect on modulating the inflammatory response. Finally, these effects of Tub B were verified in mice with LPS-induced systemic inflammatory response syndrome. Taken together, these results indicated that Tub B acted as a promising agent against M1 macrophage activation by synergistically targeting ERK1/2 and Mob1, and that it may potentially be a drug candidate to prevent/treat inflammatory diseases, especially in COVID-19.

Analysis of patient arrivals for COVID-19 test at healthcare center in Vijayanagara District

Patient queues are frequent in medical care, and one indicator of access to healthcare is waiting time. We explain queuing theory - an empirical method that provides service providers with a lot of experience in the design and management of existing services. This paper focuses on the pattern of arrival and the facilities available in the hospital in Vijayanagara District. The most important purpose of this research was to provide policymakers with knowledge to contribute to the well-being of the population by reducing waiting time for service, since long queues in exceeding cases will delay effective decisions about a particular disease that may cause death while waiting for service by patients. In this study, the waiting time of patients in the ambient department was first analyzed with the M / M/1 queuing method after measuring the mean number of patients served per hour and their median number in the hour. Additional findings of the workers questionnaire were evaluated to know. © 2022 Author(s).

Is aflatoxin more in the milk of lactating mothers who have previously had COVID-19?

Background: Breast milk provides the ideal nutrition for infants. It has a nearly perfect mix of vitamins, protein, and fat. Breastfeeding has many health benefits for both the mother and infant. Breast milk contains all the nutrients an infant needs in the first six months of life. The present study aimed to measure aflatoxin M1 (AFM1) levels in breast milk and identify nutritional and socio-demographic factors associated with AFM1 levels.

Macrophage Polarity and Disease Control.

Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.

An Exploratory Study of Refining TNM-8 M1 Categories and Prognostic Subgroups Using Plasma EBV DNA for Previously Untreated De Novo Metastatic Nasopharyngeal Carcinoma.

(1) Background: NPC patients with de novo distant metastasis appears to be a heterogeneous group who demonstrate a wide range of survival, as suggested by growing evidence. Nevertheless, the current 8th edition of TNM staging (TNM-8) grouping all these patients into the M1 category is not able to identify their survival differences. We sought to identify any anatomic and non-anatomic subgroups in this study. (2) Methods: Sixty-nine patients with treatment-naive de novo M1 NPC (training cohort) were prospectively recruited from 2007 to 2018. We performed univariable and multivariable analyses (UVA and MVA) to explore anatomic distant metastasis factors, which were significantly prognostic of overall survival (OS). Recursive partitioning analysis (RPA) with the incorporation of significant factors from MVA was then performed to derive a new set of RPA stage groups with OS segregation (Set 1 Anatomic-RPA stage groups); another run of MVA was performed with the addition of pre-treatment plasma EBV DNA. A second-round RPA with significant prognostic factors of OS identified in this round of MVA was performed again to derive another set of stage groups (Set 2 Prognostic-RPA stage groups). Both sets were then validated externally with an independent validation cohort of 67 patients with distant relapses of their initially non-metastatic NPC (rM1) after radical treatment. The performance of models in survival segregation was evaluated by the Akaike information criterion (AIC) and concordance index (C-index) under 1000 bootstrapping samples for the validation cohort; (3) Results: The 3-year OS and median follow-up in the training cohort were 36.0% and 17.8 months, respectively. Co-existence of liver-bone metastases was the only significant prognostic factor of OS in the first round UVA and MVA. Set 1 RPA based on anatomic factors that subdivide the M1 category into two groups: M1a (absence of co-existing liver-bone metastases; median OS 28.1 months) and M1b (co-existing liver-bone metastases; median OS 19.2 months, p = 0.023). When pre-treatment plasma EBV DNA was also added, it became the only significant prognostic factor in UVA (p = 0.001) and MVA (p = 0.015), while co-existing liver-bone metastases was only significant in UVA. Set 2 RPA with the incorporation of pre-treatment plasma EBV DNA yielded good segregation (M1a: EBV DNA ≤ 2500 copies/mL and M1b: EBV DNA > 2500 copies/mL; median OS 44.2 and 19.7 months, respectively, p < 0.001). Set 2 Prognostic-RPA groups (AIC: 228.1 [95% CI: 194.8-251.8] is superior to Set 1 Anatomic-RPA groups (AIC: 278.5 [254.6-301.2]) in the OS prediction (p < 0.001). Set 2 RPA groups (C-index 0.59 [95% CI: 0.54-0.67]) also performed better prediction agreement in the validation cohort (vs. Set 1: C-index 0.47 [95% CI: 0.41-0.53]) (p < 0.001); (4) Conclusions: Our Anatomic-RPA stage groups yielded good segregation for de novo M1 NPC, and prognostication was further improved by incorporating plasma EBV DNA. These new RPA stage groups for M1 NPC can be applied to countries/regions regardless of whether reliable and sensitive plasma EBV DNA assays are available or not.

SARS-CoV-2 Infection of Microglia Elicits Proinflammatory Activation and Apoptotic Cell Death.

Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes various neurological symptoms in patients with coronavirus disease 2019 (COVID-19). The most dominant immune cells in the brain are microglia. Yet, the relationship between neurological manifestations, neuroinflammation, and host immune response of microglia to SARS-CoV-2 has not been well characterized. Here, we reported that SARS-CoV-2 can directly infect human microglia, eliciting M1-like proinflammatory responses, followed by cytopathic effects. Specifically, SARS-CoV-2 infected human microglial clone 3 (HMC3), leading to inflammatory activation and cell death. RNA sequencing (RNA-seq) analysis also revealed that endoplasmic reticulum (ER) stress and immune responses were induced in the early, and apoptotic processes in the late phases of viral infection. SARS-CoV-2-infected HMC3 showed the M1 phenotype and produced proinflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNF-α), but not the anti-inflammatory cytokine IL-10. After this proinflammatory activation, SARS-CoV-2 infection promoted both intrinsic and extrinsic death receptor-mediated apoptosis in HMC3. Using K18-hACE2 transgenic mice, murine microglia were also infected by intranasal inoculation of SARS-CoV-2. This infection induced the acute production of proinflammatory microglial IL-6 and TNF-α and provoked a chronic loss of microglia. Our findings suggest that microglia are potential mediators of SARS-CoV-2-induced neurological problems and, consequently, can be targets of therapeutic strategies against neurological diseases in patients with COVID-19. IMPORTANCE Recent studies reported neurological and cognitive sequelae in patients with COVID-19 months after the viral infection with several symptoms, including ageusia, anosmia, asthenia, headache, and brain fog. Our conclusions raise awareness of COVID-19-related microglia-mediated neurological disorders to develop treatment strategies for the affected patients. We also indicated that HMC3 was a novel human cell line susceptible to SARS-CoV-2 infection that exhibited cytopathic effects, which could be further used to investigate cellular and molecular mechanisms of neurological manifestations of patients with COVID-19.

EMS: Fast track development of a miniaturized mass spectrometer for lunar applications

The Astrobotic M1 mission, as the first mission of NASA s Commercial Lunar Payload Services (CLPS) program, is scheduled to land in the Lacus Mortis region of the Moon in early 2022. Among its payloads it will carry the Peregrine Ion Trap Mass Spectrometer (PITMS), an instrument supplied by NASA GSFC that is dedicated to the investigation of the lunar exosphere, and which includes as its core component the ESA-provided Exospheric Mass Spectrometer (EMS). EMS was developed under an ESA contract by an academic/industrial consortium led by Open University (UK) using a fast track development approach that aimed at delivery of a Proto-Flight Model (PFM) instrument with drastically reduced development time. The chosen development approach and the demanding project schedule (18 months from contract start to flight hardware delivery) posed a number of specific project management challenges for successful development of the instrument within the ESA flight hardware development framework and under constraints imposed by the Covid-19 pandemic. With an as-built envelope of HWD of 168 149 127mm, a mass of 1.48kg and a typical power consumption during measurement not exceeding 9.5 Watts the instrument has modest resource requirements. EMS can be re-used in different future application scenarios, including investigations of the lunar exosphere, analysis of gases evolved from acquired samples, and monitoring aspects of the environmental impact of landers and robotic and human activities on the lunar environment. © 2021 International Astronautical Federation, IAF. All rights reserved.

Research on the mechanism of berberine in the treatment of COVID-19 pneumonia pulmonary fibrosis using network pharmacology and molecular docking.

Purpose Pulmonary fibrosis caused by COVID-19 pneumonia is a serious complication of COVID-19 infection, there is a lack of effective treatment methods clinically. This article explored the mechanism of action of berberine in the treatment of COVID-19 (Corona Virus Disease 2019, COVID-19) pneumonia pulmonary fibrosis with the help of the network pharmacology and molecular docking. Methods We predicted the role of berberine protein targets with the Pharmmapper database and the 3D structure of berberine in the Pubchem database. And GeneCards database was used in order to search disease target genes and screen common target genes. Then we used STRING web to construct PPI interaction network of common target protein. The common target genes were analyzed by GO and KEGG by DAVID database. The disease-core target gene-drug network was established and molecular docking was used for prediction. We also analyzed the binding free energy and simulates molecular dynamics of complexes. Results Berberine had 250 gene targets, COVID-19 pneumonia pulmonary fibrosis had 191 gene targets, the intersection of which was 23 in common gene targets. Molecular docking showed that berberine was associated with CCl2, IL-6, STAT3 and TNF-α. GO and KEGG analysis reveals that berberine mainly plays a vital role by the signaling pathways of influenza, inflammation and immune response. Conclusion Berberine acts on TNF-α, STAT3, IL-6, CCL2 and other targets to inhibit inflammation and the activation of fibrocytes to achieve the purpose of treating COVID-19 pneumonia pulmonary fibrosis.

Cinnamomum camphora: A long history for epidemics control

Camphor (C10H16O) is a white crystalline solid exist in enantiomeric form R and S camphor. It is a terpenoid obtained from turpentine oil. Synthetically it is synthesized by catalytic process as alpha pinene. Naturally camphor is obtained by steam distillation of woods of Cinnamomum camphora tree, also known as Camphor tree, camphor laure and camphor wood. Camphor has many pharmacological properties. It acts as antiviral, anticancerous, antimicrobial, insecticidal, anticoccidial, anti-nociceptive and antitussive drug. In addition, it can be used as skin penetrating enhancer. Camphor gives a soothing and cooling effect, which helps to reduce pain. The reason behind its soothing effect is camphor act as a counter-irritant by activating heat sensitive transient receptor potential vanilloid subtype 1 and transient receptor potential vanilloid subtype 3 receptors and inhibits the transient receptor potential melastatin-subfamily member 8 receptor. As a result, these receptors provide a sensation of scalding heat and pain (nociception) and could be used to treat neuropathic pain associated with multiple sclerosis, chemotherapy, or amputation, as well as pain associated with the inflammatory response of damaged tissue such as in osteoarthritis. Camphor has a history of epidemics cure. During leishmaniosis (kala-azar) pandemic in 14th century, camphor was used as fumigant to control the spread of plague in European countries. In 19th century when cholera, small pox and influenza spreads, camphor was used as mothballs in Indian subcontinent as a (cough reliever) agent. During 18th century Russian influenza “flu pandemic” founder of Homeopathy Hahnemann in 1831, published his research work on camphor and suggested camphor as a “divine remedy” for influenza given in extremely small doses. In the same year, several companies launched to sell menthol rub as natural rub ointment consisting camphor as prevention measures for spread of influenza. As the recent epidemic of COVID-19 arises, prevention and control of spread of disease is an alarming issue. This article covered the glimpse of uses and importance of camphor in the history of epidemic cure.