The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

Various products of the Integrated Multisatellite Retrievals for GPM (IMERG) and passive mi-crowave (PMW) sensors are assessed with respect to near-surface wet-bulb temperature (Tw), precipitation intensity, and surface type (i.e., with and without snow and ice on the surface) over the CONUS and using Stage-IV product as reference precipitation. IMERG products include precipitation estimates from infrared (IR), combined PMW, and their combination. PMW products generally have higher skills than IR over snow- and ice-free surfaces. Over snow- and ice-covered surfaces (1) PMW products (except AMSR-2) show a higher correlation coefficient than IR, (2) IR and PMW precipitation products tend to overestimate precipitation, but at colder temperatures (e.g., Tw<-10oC) PMW products tend to underestimate and IR product continues to show large overestimations, and (3) PMW sensors show higher overall skill in detecting precipitation oc-currence, but not necessarily at very cold Tw. The results suggest that the current approach of IMERG (i.e., replacing PMW with IR precipitation estimates over snow- and ice-surfaces) may need to be revised.

The study aimed to estimate the prevalence and association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with Type 2 Diabetes Mellitus (T2DM). According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged: 50–80 years) were divided into three groups: Non-sarcopenia (n = 38), Possible Sarcopenia (n = 31, 28.2%), and Sarcopenia (n = 41, 37.3%). Blood samples were collected and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D3 levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, there was a significant association between sarcopenia with BMI, body fat percentage (BF%), and dietary energy and protein intake. Low serum vitamin D3 is a significant risk factor for possible sarcopenia.

Metabolomics profiling for accurate and reliable quantification of organic acids that carry a carboxylic acid functional group in complex biological samples, remains a major analytical challenge in clinical chemistry research. Several procedural barriers associated with quantification of clinically important carboxylic containing metabolites (CCMs) including spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column, limit the sensitivity, specificity, and reproducibility of multiple-reaction monitoring (MRM) based LC-MS assay development. We report a targeted metabolomics-based analytical method for the quantification of CCMs using phenylenediamine derivatization. Accurate and sensitive quantification of CCMs is successfully demonstrated in an array of biological matrices. Recovery of metabolites from different matrices (plasma, serum, urine, saliva, tissues, and cell extracts), ranged from 90% to 105%, with all the CVs ≤ 10%. The method showed linearity over a broad dynamic range from 0.1 ng/mL to 10 µg/mL with linear regression coefficients of 0.99 for most of the metabolites tested herein, that covers broad-based applicability with the analysis of biological samples. In most cases the LODs were as low as 0.01 ng/mL. The phenylenediamine-based derivatization of carboxyl acid library consisting of more than 70 endogenous metabolites was constructed for metabolite identification, which spanned more than 40 biological pathways. The library included a wide-variety of structurally variant CCMs such as amino acids/conjugates, short to medium chain organic acids, di/tri-carboxylic acids/conjugates, fatty acids and some ring-containing CCMs. We compared the CCMs profiles of pancreatic cancer cells with normal pancreatic epithelial cells to test and validate the biological utility of this method. The comparative profiling between cancerous and normal cells resulted in the identification of potential biomarkers in pancreatic cancer, and their correlation with several key metabolic pathways such as central carbon energy metabolism, protein metabolism, including TCA cycle, glycolysis, Gln-Glu pathway, and biosynthesis of amino acids and unsaturated fatty acids was established. The method, described herein, for the first time enables the sensitive and highly specific quantification of CCMs on small sample size with high reproducibility in a high throughput manner. Given the biological and functional significance of this class of metabolites, this mass spectrometry based targeted quantitative assay, fills an important gap and is likely to support a wide range of applications for basic, clinical, and translational research.

Chemical substances such us CS-gas used in military operations are chemical compounds that present a series of peculiarities that affect the ecosystem by disrupting the ecological balance. This study evaluated the toxicological character of O-chlorobenzylidenemalonitrile (CBM), (substance present in CS-gas) on the algae Cholrella sp. and analyzed the toxicity limit and the response of the microorganism to the oxidative stress caused by this substance. In order to under-stand the toxicological mechanisms of CBM on algal culture, a series of parameters were analyzed such as: the cell growth curve, the average specific growth rate (µ), percent inhibition in yield(I%), dry cell weight (DCW), percent viability and productivity of algal biomass flocculation activity(FA), change in oxygen production. The content of chlorophyll pigments, was characterized by Fourier transform infrared spectroscopy (FTIR) fluorescence spectroscopy and analysis of the surface structure of algal cells by SEM spectroscopy. This study aims to provide fundamental data for understanding the toxicity of CBM to aquatic organisms and provides a basis for assessing the potential for impact on aquatic ecosystems. The results obtained could be taken into account in the management of the decontamination of the affected areas.

The use of bacteriophage is reemerging as a tool for combatting multi-drug resistant bacterial infections. In our previous study, we showed that colistin resistant carbapenem-resistant Klebsiella pneumoniae (ColR-CRKP) is more susceptible to killing by lytic tailed phages, including ФNJS1 specific for nonmucoid K. pneumoniae. Although we demonstrated that alteration on surface charges of ColR-CRKP promotes phage adherence and infection, the receptor for ФNJS1 was still unknown. In current study, we identified O-antigen was involved in the reversible adsorption, and outer membrane protein (OMP) FepA may be served as one of the irreversible receptors for ФNJS1. We firstly found accelerated reversible phage adsorption to ColR-CRKP cells, and that periodate treatment of bacteria inhibited the phage binding, indicating LPS may be involved in phage reversible adsorption. ФNJS1-resistant bacterial mutants screening revealed that mutants in ∆wecG(mTn5) and ∆wecA(mTn5), two genes responsible for LPS biosynthesis, affected phage adsorption capacity and phage infectivity. The loss of wzyE encoding O-antigen polymerase showed no significant difference in phage adsorption but increased phage infectivity, suggesting the long chain length of O-antigen may also be a barrier for bacteriophage infection. Among four OMP mutants including ∆fepA, ∆fhuA, ∆ompA and ∆ompC, only ∆fepA slowed phage lysis rate, suggesting FepA may be as one of irreversible receptors for ФNJS1. The results are helpful to better understand why ColR-CRKP sensitizes phage infection and to combat multi-drug resistant K. pneumoniae infections in the future.

Tocilizumab against interleukin-6 receptor (IL-6R) has been demonstrated to inhibit the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of Tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels re-mains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as our human CRC xenograft models with anti-IL-6R antibody (Tocilizumab) therapy. IL-6R expression levels, the histology of CRC growth/ invasiveness and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels exerted better responsiveness in Tocilizumab therapy than the treated HT-29 group. Likewise, therapeutic effects of Tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, the invasiveness with MMP-9 proteinase expressions, ERK 1/2 and STAT3 signaling transduction in SW480 treatment group were superior to HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of Tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, Tocilizumab may serve as a targeted and promising anti-CRC therapy.

The role of the immune response to SARS-CoV-2 infection is not yet well known, in particular about the persistence of circulating antibodies. The aim of the study is to compare the results of two automated systems for the determination of IgG antibodies against SARS CoV-2 and to assess the time course of the IgG response after the onset of symptoms for a period longer than that evaluated to date. IgG were measured in 98 specimens of 55 subjects with COVID-19 (time from the onset of symptoms from 3 to 109 days) using the automated tests "Abbott SARS-COV-2 IgG" and the "MAGLUMI 2019-nCoV IgG". The two methods had a concordance of 91.8%, but the quantitative correlation showed very dispersed results. All the specimens resulted positive after 17 days from the onset of the synptoms. However, the median concentrations of IgG, after a rapid increase up to about 20 days, quickly decrease to about 15% of the maximum for Maglumi. The same samples measured by Architect showed a quite constant trend up to 80 day, and then an only moderate decline. The titer of IgG against SARS-CoV-2 in patients exposed to COVID-19 may significantly and rapidly decrease, with a different time-course depending on the method used for the determination.

Among the many approaches to COVID-19 prevention, the possible role of diet has so far been somewhat marginal. Nutrition is very rich in substances with a potential beneficial effect on health and some of these could have an antiviral action or in any case be important in modulating the immune system and in defending cells from the oxidative stress associated with infection. This short review draws the attention on some components of Citrus fruits and especially of the orange (Citrus sinensis), well known for its vitamin content, but less for the function of its flavonoids. Among the latter, hesperidin has recently attracted the attention of researchers, because it binds to the key proteins of the SARS-CoV-2 virus. Several computational methods, independently applied by different researchers, showed that hesperidin has a low binding energy both with the coronavirus "spike" protein, and with the main protease that transforms the early proteins of the virus (pp1a and ppa1b) into the complex responsible for viral replication. The affinity of hesperidin for these proteins is comparable if not superior to that of common chemical antivirals. The preventive efficacy of vitamin C, at dosage attainable by diet, against viral infections is controversial, but recent reviews suggest that this substance may be useful in case of increased stress on the immune system. Finally, the reasons that suggest undertaking appropriate research on the Citrus fruits addition in the diet, as a complementary prevention and treatment of COVID-19, are discussed.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

The coronavirus of severe acute respiratory syndrome 2 (SARS-CoV-2), known as COVID-19, has spread rapidly around the world, leading to social detachment and the home office replacing face-to-face work. The performance of police officers faces limitations to the new requirements, while recognizing the need to ensure health and quality of life. Thus, the present study aimed to verify the panorama of the spread of COVID-19 among federal police officers by analyzing the presence of symptoms, individual protection measures (IPM), suspect screening measures (SSM) and examination for total antibodies (IgA, IgG and IgM). For this, data were collected through a questionnaire customized for this situation, blood for serological testing and measurements of clinical data from 56 federal police officers in the municipality of Marília (São Paulo, Brazil). There was no positive result in the Anti-SARS-CoV-2 serological test in any sample participant. The mean value of the Body Mass Index (27.2 ± 5.4 kg / m2) suggests overweight and obesity, in addition to the presence of hypertension in 16.1%, diabetes in 3.6%, asthma in 3.6 % and obesity by 25%, which represents an important risk of complications for COVID-19. The use of a mask is the most frequent IPM (96.4%) and most of the sample has used a cloth or home mask (90.9%). However, 47.3% have not performed the correct cleaning of the masks and 5.5% have not taken any care with mask hygiene. It can be concluded that care in relation to the professional activities of federal police to date has prevented the spread of SARS-CoV-2 and that they must be maintained or increased because risk factors, which involve quality of life and worsening of the contamination condition, were detected in the participants.

Alginate-silver nanocomposites in the form of spherical beads and films were prepared using a green approach by using the aqueous extract of Ajwa dates seeds. The nanocomposites were fabricated by in situ reduction and gelation method by ionotropic crosslinking using calcium ions in solution. The rich phytochemicals of the dates seeds extract played a dual role as reducing and stabilizing agent in the synthesis of silver nanoparticles. The formation of silver nanoparticles was studied using UV-Vis absorption spectroscopy and a distinct surface plasmon resonance (SPR) peak at 421 nm characteristic of silver nanoparticles confirmed the green synthesis of silver nanoparticles. The morphology of the nanocomposite beads and film was compact with even distribution of silver nanoclusters. The catalytic property of the nanocomposite beads was evaluated for the degradation of 2-nitrophenol in the presence of sodium borohydride. The degradation followed pseudo-first order kinetics with a rate constant of 1.40 ´ 10^-3 s^-1 at 23 °C with an activation energy of 18.45 kJ mol^-1. The thermodynamic parameters such as changes in enthalpy and entropy were evaluated to be 15.22 kJ mol^-1 and -197.50 J mol^-1 K^-1, respectively. The nanocomposite exhibited properties against three clinically important pathogens (Gram-positive and Gram-negative bacteria)

Aim: Aging is companied by deteriorations of insulin resistance (IR) and insulin secretion. However, little is known about the roles of aging on different phases of insulin secretion (ISEC); i.e., the first- and second-phase of insulin secretion (FPIS, SPIS) and glucose effectiveness (GE). Methods: Totally 169 individuals (43 men and 126 women) with the similar fasting plasma glucose (FPG: 90 mg/dL) and BMI (men: 23 kg/m2, women 22 kg/m2) were enrolled. IR, FPIS, SPIS, and GE were estimated using our previously developed equations shown below. Pearson correlation analysis was conducted to assess the correlations between age and four diabetes factors (DFs: IR, FPIS, SPIS and GE). The equations that are used to calculate the DF in the present study were built and published by our group. Results: The age of the participants ranged from 18- to 78-year-old. Men had higher FPIS but lower HDL-C levels than women (2.067±0.159, 1.950±0.186 μU/min and 1.130±0.306, 1.348±0.357 mmol/dl, accordingly). The results of Pearson correlation revealed that age was negatively related to IR and GE in both genders (IR: r = -0.39, p < 0.001 for men, r = -0.24, p < 0.003 for women; GE: r = 0.66, p < 0.001 for men, r = 0.78, p < 0.001 for women). In the meanwhile, FPIS was also only found to be negatively correlated with age in female (r = -0.238, p = 0.003). But there was no different with SPIS and age in both of genders. Conclusions: We have found that in Chinese with normal FPG level (90 mg/dl) and body mass index (men: 23 kg/m2, women: 22: kg/m2), age is negatively related to IR and GE in both genders. At the same time, only FPIS was found to be negatively related to age in women. The tightness of their relationships, from the highest to the lowest are, GE, FPIS and IR accordingly. The importance of GE should be re-evaluated. These results should be interpreted with caution because of the small sample size.

Previous studies found high but very variable levels of tetranor-PGEM and PGD-M (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF), which correlated with the severity of the CF transmembrane receptor (CFTR) genetic alteration. This study aims to assess the potential role of cyclooxygenase (COX)-1 and COX-2 genetic polymorphisms in the variability of PG production, and determine the potential role of PG metabolites as markers of symptoms severity and imaging findings. Thirty healthy subjects and 103 pwCF were included in the study. Clinical and radiological CF severity was evaluated using clinical scoring methods and the extent of bronchiectasis and air trapping were assessed by chest computed tomography (CT). Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. The presence of variants in the COX-1 gen (PTGS1 639 C>A, PTGS1 762+14delA, and COX-2 gen: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were analysed. PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in healthy controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Taken together, the present study suggests that urinary PG level testing can be used as a biomarker of CF severity. We found no relationship between COX-1 and COX-2 genetic polymorphisms in the variability of PG production.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiologic agent of the respiratory disease in humans that is known as coronavirus disease 2019 (COVID19). The first outbreak of the disease was initially documented in Wuhan, Hubei Province, China in late December 2019 where people had experienced SARS pneumonia-like symptoms with unknown etiology. Since then it has been observed that COVID-19 positive patients have been showing mild to severe upper respiratory illness symptoms. The type of virus is known to make its transfer from animals to humans and for the concerned virus; researchers have claimed its origin from bat coronavirus at whole-genome level with a 96 % sequence identity. The COVID-19 virus is very contagious and communicable in nature and has been spread throughout the globe since its first outbreak in China. On March 9, 2020, WHO declared it as a Pandemic, and within a month it was already reported to have shown its presence in 213 countries and territories or areas. As of April 29, 2020, this novel virus infected 3,218,183 people and caused 228,029 mortalities worldwide with a variable mortality rate from 3-13 % across the planet and also varied by age and gender. Diagnosis of the disease is a key component in understanding and controlling the spread of the virus and several techniques have been devised including RT-PCR, ELISA, and sequencing-based approaches. To cure COVID-19 patients as of now we do not have proven to be a safe and effective treatment. Therapeutic options currently under investigation in various parts of the world. However, there are various effective therapeutic targets to repurpose the present antiviral therapy for developing potential interventions against SARS-CoV-2. Boosting the immune system can also help to prevent and spread of COVID-19 using various medication and exercises. In this review, our goal to summarize and discussed the present scientific advancements to fight against this novel pandemic.

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th Feb and 15th Feb. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a `delayed positive' test during isolation after initially testing negative, at least 7 days after last possible contact.

Supplier selection is one of the most important multi criteria decision making (MCDM) problems for decision makers in competitive market. Organizations of today’s world are seeking new ways to reduce negative effects of their organizations to the environment and to reach a greener system. At this point, green supplier selection concept has gained great importance with its ability on incorporating environmental or green criteria into the classical supplier selection practices. Therefore, in this study, it is aimed at proposing a multi-phase MCDM model based on Best-Worst Method (BWM) and interval type-2 fuzzy technique for order preference by similarity to ideal solution (TOPSIS). A case study in a plastic injection molding facility in Turkey is performed to show the applicability of the proposed integrated methodology. The paper ensures insights into the decision making, methodology, and managerial implications. Results of the case study are examined and suggestions for future research are provided.

Introduction The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies, as well as to evaluate published data on the addition of some of HMOs to infant formula. Method PubMed was searched from inception to April 2018 Results The presence of HMOs is a dynamic process, determined by many factors such as duration of lactation, environmental and genetic factors. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. Only a few of the many HMOs can be made industrially, and are added to infant formula. They have been shown to be safe and well tolerated, including normal growth and a trend towards health benefit. Conclusions HMOs are one of the major differences between cow’s milk and human milk , and evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk.

Since December 2019, a rapid increase in the number of SARS-CoV-2 (COVID-19) cases was reported worldwide, despite strict infection control and lock down measures. Current paper investigated the actual facts behind this rapid increase in the number of cases. Study of genomic sequence reveals that domestic and wild animals were likely ancestors and zoonotic source for SARS-CoVs, MERS-CoVs, and SARS-CoV-2. Strong evidence suggest that these viruses already existed and replicated in animals and humans during past several decades, exhibiting diverse mutations, evolutions and self-limiting diseases, except during outbreaks. Serious zoonotic reservoir investigations are required to investigate animal transmission of SARS-CoVs and SARS-CoV-2 to limit current pandemic. This might be the reason of increasing number of cases via animals. SARS-CoV-2 has been retrospectively isolated in different studies in August 2019, several months before Wuhan announced. Hence, there is a possibility that viruses existed, went undetected, infecting subclinically, in past several years, and SARS-CoV-2 antigens and neutralizing antibodies may have been present in humans since long time. This might be another reason of increasing number of cases by screening as mass screening and antigen or antibody testing was not carried out in the past years. Randomized controlled trials are required to investigate human to human transmission by touch, as the current evidence is limited with conflicting results. As all SARS-CoVs are basically respiratory viruses, droplet precautions and infection control measures are essential, especially for hospital staff. Increased number of SARS-CoV-2 asymptomatic, or subclinical cases are detected worldwide. This silent phase of transmission can be beneficial for humans. Lack of symptoms eventually lessen virus transmission and reduce the pathogen's long-term survival and provide humoral herd immunity up to several years. Hence, seropositivity with diverse antibodies develops against mutating SARS-CoVs which will confer strong immunity during epidemics. Strategies such as identification, contact tracing and quarantine are costly and practically difficult. Hence, asymptomatic persons can continue their work with droplet precautions and standard infection control procedures, while symptomatic or sick persons can isolate themselves in their homes without the need for strict quarantine until clinical recovery, with reduced hospital visits and minimizing chances of hospital acquired infections. RT-PCR has low sensitivity and specificity, carries a high risk of handling live virus antigens, and requires difficult protocols. As viral load also sharply declines after few days of onset of infection, this technique might overlook infection. Furthermore, SARS-CoV-2 infection may be present in blood when oropharyngeal swabs are negative by RT-PCR. Additionally, RT-PCR usually gives false negative and false positive results and must be interpreted cautiously. This might be again a reason of increasing number of cases by false positive RT-PCR reporting. Moreover, antibodies against SARS-CoVs develop robustly in serum even by reduced amount of antigens. In contrast to RT-PCR, ELISA for diagnosing antibodies against SARS-CoV-2 demonstrates 100% specificity and 100% sensitivity, even in clinically asymptomatic individuals. These antibodies can be used for serologic surveys, monitoring and screening. However, screening tests for SARS-COV-2 should be avoided in unhygienic public places by nasopharyngeal swabs, which carry a high risk of further transmission, co-infection or superinfection. Such highly infectious virus must be isolated and tested in highly sterilized laboratory. Further strict international laws and policies are required to stop the possible spread of experimental viruses, biological warfare and bioterrorism.

Background: Antibiotic-containing carrier systems are one option that offers the advantage of releasing active ingredients over a longer period of time. In vitro sustained drug release from a carrier system consisting of microporous β-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a β-TCP ceramic and higher biodegradability than pure alginate. Methods: Dual release of daptomycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21, and 28 by HPLC and ELISA. After release, the microbial efficacy of the daptomycin was verified and the biocompatibility of the composite was tested in cell culture. Results: Daptomycin and the model compound FITC protein A (n=30) were released from the composite over 28 days. A Daptomycin release above the minimum inhibitory concentration (MIC) by day 9 and a burst release of 71.7 ± 5.9 % were observed in the loaded ceramics. Low concentrations of BMP-2 were released from the loaded ceramics over 28 days.

The effect of transition metal substitution for Fe and the structural and magnetic properties of Gd2Fe16Ga0.5TM0.5 (TM=Cr, Mn, Co, Ni, Cu, and Zn) compounds were investigated. Rietveld analysis of X-ray diffraction indicates that all the samples crystallize in the hexagonal Th2Ni17 structure. The lattice parameters: a, c and unit cell volume show TM ionic radii dependence. Both Ga and TM atoms show preferred site occupancy for 12j and 12k sites. The saturation magnetization at maximum room temperature was observed for Co, Ni, and Cu of 69, 73, and 77 emu/g, respectively while minimum value was observed for Zn (62emu/g) doping Gd2Fe16Ga0.5TM0.5. Highest Curie temperature of 590 K was observed for Cu doping which is 15% and 5% and thesehigher than Gd2Fe17 and Gd2Fe16Ga compounds, respectively. The hyperfine parameters viz. hyperfine field and isomer shift, show systematic dependence on the TM atomic number. The observed magnetic and Curie temperature behavior in Gd2Fe16Ga0.5TM0.5 is explained on the basis of Fe(3d)-TM(3d) hybridization. The superior Curie temperature and magnetization value of Co, Ni, and Cu doped Gd2Fe16Ga0.5TM0.5 compounds as compared to pure Gd2Fe17 or Gd2Fe16Ga makes Gd2Fe16Ga0.5TM0.5 a potential candidate for high-temperature industrial magnet applications.

Cross-sectional survey was conducted to capture the true extent of COVID-19 exposure among students and staff of Polytechnic High School (PHS). Random cluster sampling was carried out between May 19 and August 18, 2022, after the fourth wave of COVID-19 transmission. IgM and IgG SARS-CoV-2 antibodies were screened using WANTAI SARS-CoV-2 ELISA assays. Seroprevalence and descriptive statistics were calculated. Moreo-ver, the association between seropositivity and different factors (age, gender, preventive measures comorbidity, and symptoms, etc.) was determined using Logistic Regression. The overall IgG and IgM seroprevalence were 92% and 6.91% respectively. We found a higher IgM seroprevalence in men than women (9.4% vs. 5.6%) and a lower IgM seroprevalence in (18-25) age group compared to (55-65) years. Low compliance with preventive measures was found with a significant IgM seroprevalence depending on non-respect of social distancing (p = 0.008). A total of 70% of participants presented symptoms linked to COVID-19 at the moment of the survey. Results revealed a significant difference according to IgG seroprevalence among participants who declared fa-tigue symptoms 92.06% compared to those who did not 80.39% (p = 0.0027). IgM seropositivity was associated with Body Mass Indice (BMI) categorized (O.R. 0.238, p = 0.043), ethnic group (O.R. 0.723, p = 0.046) and marital status (O.R. 2.399, p = 0.021). Moreover, IgG seropositivity was associated with Chronic sinusitis comorbidity (O.R. 0.238, p = 0.043) and vaccination status (O.R. 4.741, p < 0.001). The majority of students and staff have al-ready been exposed to SARS-CoV-2 and confirm the circulation of SARS-CoV-2 in PHS at the time of the survey. Our results underline the importance of sero-epidemiological surveys to estimate the real impact of the COVID-19 pandemic in a community and to monitor disparities in antibody response in the population.

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

As a critical transmitter, the compact 532 nm lasers operating on high repetition and narrow pulse widths have been used widely for airborne or space-borne laser active remote sensing. We developed a free space pumped TEM₀₀ mode sub-nanosecond 532 nm laser that occupied a volume of less than 125 mm × 50 mm × 40 mm (0.25 liters). The fundamental 1064 nm laser consists of a passively Q-switched composite crystal microchip laser and an off-axis, two-pass power amplifier. The pump sources were two single-emitter semiconductor laser diodes (LD) of 808 nm with a maximum continuous wave (CW) power of 10 W each. The average power of fundamental 1064 nm laser was 1.26 W with the laser operating at 16 kHz repetition rates, and 857ps pulse widths. Since the beam distortion would be severe in microchip lasers in terms of the increase in heat load, for obtaining a high beam quality of 532 nm, the beam distortion was compensated by adjusting the distribution of pumping beam in our experiment of fundamental amplification. Furthermore, better than 0.6 W average power, 770 ps, beam quality of M² ＜1.2, and 16 kHz pulse output at 532 nm was obtained by a Type I LiB₃O₅ (LBO) crystal in the critical phase matching (CPM) regime for second harmonic generation (SHG).

As yin and yang, cancer and diabetes are metabolic disorders characterized by deregulated, yet opposing, metabolic alterations. These metabolic shifts reflect a complex network of defective underlying signaling pathways, which ultimately orchestrate both disease pathogenesis and progression. The Warburg effect portrays the chief metabolic phenotype in cancer and is reflected by the dominance of aerobic glycolysis over minimal-to-no viable oxidative phosphorylation in cancer. Conversely, during the pathogenesis of type 2 diabetes (T2D), oxidative phosphorylation is constantly heightened. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, with exacerbating metabolic alterations affecting oxidative phosphorylation in a tissue-specific manner. Promising nutritional adjuvants, such as alpha-lipoic acid and flavonoids, can reprogram metabolism and exert antitumor and antidiabetic effects. Other pharmacological agents, such as metformin, have therapeutic effects on cancer and T2D. Herein, we discuss the molecular mechanisms and signaling pathways involved in the metabolic shifts in cancer and T2D, and explore the therapeutic strategies under investigation that aim to reverse the metabolic shift in both disease scenarios.

In this study, Cu2O nanoparticles were synthesized using the sol-gel technique and subsequently functionalized with extracts from plants of the Rauvolfioideae subfamily and citrus fruits. Com-prehensive characterization techniques, including UV-Vis spectroscopy, FT-IR, XRD, BET, SEM, and TEM, were employed to evaluate the structural and surface properties of the synthesized nanoparticles. The results demonstrated that both functionalized Cu2O nanoparticles exhibit mesoporous structures, as confirmed by nitrogen adsorption-desorption isotherms and pore size distribution analysis. The Green Extract functionalized nanoparticles displayed a more uniform pore size distribution compared to those functionalized with the Orange Extract. The study un-derscores the potential of these functionalized Cu2O nanoparticles for applications in drug de-livery, catalysis, and adsorption processes, highlighting the influence of the functionalization method on their textural properties and performance in antibacterial efficacy.

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100nm) can be used in the treatment of cancer owing to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nano-formulations have created brand new perspectives for cancer treatment. However, a majority of the research is limited to in vivo and in vitro studies, and the number of nano-drugs that are approved has not much amplified over the years. In this review, we discuss numerous types of nanoparticles, targeting mechanisms along with approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

In recent years, the nanoparticles applications have been well recognized in various fields. It is known that nanoparticles as an active ingredient in sunscreens are widely used. Zinc oxide and titanium oxide nanoparticles are common nanoparticles utilized in sunscreens. In this study, we aimed to suggest new nanoparticles for this purpose. Cerium oxide nanoparticles (CeO2-NPs) were synthesized by using Musa sapientum fruit peel extract. Synthesized nanoparticles were identified through Raman, Powder X-ray Diffraction (PXRD), Fourier Transform Infrared spectroscopy (FT-IR), Field Energy Scanning Electron Microscopy (FESEM) and Energy-Dispersive Spectroscopy (EDX). The results showed that size of synthesized nanoparticles are in range 4-13 nm. The cytotoxic activity of synthesized nanoparticles on lung (A549) cancer cell line was performed through MTT assay. The results showed that synthesized nanoparticles are non-toxicity against A549 cell line to below 500 μg/mL of nanoparticles concentration. The Sun protection factor (SPF) was estimated ~ 40 for synthesized CeO2-NPs. So, synthesized nanoparticles can be a good option for use in the cosmetics industry.

Metallic nanoparticles (NPs), among polymeric NPs, liposomes, micelles, quantum dots, dendrimers, or fullerenes, are becoming more and more important due to their potential use in the novel medical therapies. Titanium dioxide (titanium(IV) oxide, titania, TiO2) is an inorganic compound that owes its recent rise in scientific interest to photoactivity. After the illumination in aqueous media with UV light, TiO2 produces an array of reactive oxygen species (ROS). The capability to produce ROS and thus induce cell death has found application in the photodynamic therapy (PDT) for the treatment of a wide range of maladies, from psoriasis to cancer. Titanium dioxide NPs were studied as photosensitizing agents in the treatment of malignant tumors as well as in photodynamic inactivation of antibiotic-resistant bacteria. Both TiO2 NPs themselves, as well as their composites with other molecules, can be successfully used as photosensitizers in PDT. Moreover, various organic compounds can be grafted on TiO2 NPs, leading to hybrid materials. These nanostructures can reveal increased light absorption allowing their further use in targeted therapy in medicine. In order to improve efficient anticancer therapy, many approaches utilizing titanium dioxide were tested. The most significant studies are discussed in this review.

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case-control study aimed to investigate the association between the rs9896052 polymorphism (A>C) upstream of GRB2 and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (< 10 years or ≥ 10 years). Genotypes were determined using real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between the cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, p = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17-6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near GRB2 is associated with PDR in Brazilian patients with T2DM.

Introduction: This population-based retrospective cohort study assesses rates of adverse events (AEs) involving cerebral thromboembolism (CTE) after COVID-19 vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) database from January 1, 1990 to December 31, 2023. CTE AEs after COVID-19 vaccines were compared to those after influenza vaccines and after all other vaccines using proportional reporting ratio (PRR) analysis by time. Results: There are 5137 cerebral thromboembolism AEs reported in the 3 years (36 months) after COVID-19 vaccines compared to 52 AEs for the influenza vaccines over the past 34 years (408 months) and 282 AEs for all other vaccines (excluding COVID-19) over the past 34 years (408 months). The PRR’s are significant when comparing AEs by time from COVID-19 vaccines to that of the influenza vaccines (p < 0.0001) or to that of all other vaccines (p < 0.0001). The CTE AEs PRR by time (95% confidence intervals) for the COVID-19 vaccine AEs vs influenza AEs is 1120 (95% confidence interval (723-1730), p < 0.0001) and for COVID-19 vaccines vs all others is 207 (95% confidence interval (144-296), p < 0.0001). Cerebral venous thromboembolism AEs are female predominant with a female/male odds ratio of 1.63 (95% confidence interval (1.52-1.74), p < 0.0001). Conversely, cerebral arterial thromboembolism has a nonsignificant male preponderance. Cerebral venous thromboembolism is far more common than cerebral arterial thromboembolism over 36 months with an odds ratio (OR) of 14.8 (95% confidence interval 14.0-15.5, p < 0.0001). Atrial fibrillation, the most common identifiable cause of cerebral arterial thromboembolism, occurs far more commonly after the COVID-19 as compared to all other vaccines with a PRR of 123 (95% CI 88.3-172, p < 0.0001) Conclusions: There is an alarming breach in the safety signal threshold concerning cerebral thrombosis AEs after COVID-19 vaccines compared to that of the influenza vaccines and even when compared to that of all other vaccines. An immediate global moratorium on the use of COVID-19 vaccines is necessary with an absolute contraindication in women of reproductive age.

SARS-CoV-2 is an obligatory intracellular pathogen that requires of a lipid bilayer membrane for its transport, to build its nucleocapsid envelope and to fuse with the host cell. The biological membranes are constituted by phospholipids (PLs) and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if the treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFA), fatty acid of the phospholipids (FAPL), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6) and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HS). COVID-19 patients showed a decrease in Vit E, TPLs, FAPL and TFA in serum in comparison to HS (p≤0.01) and Vit E treatment restored their levels (p≤0.04). Likewise, there was an increase IL-6 and CRP in COVID-19 patients in comparison with HS (p≤0.001) and the treatment with Vit E decreased their levels (p≤0.001). Treatment with Vit E contributes to restore the modified profile of the PLs in the SARS-CoV-2 infection and this leads to a decrease of OS and of the inflammatory process.

The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in treatment-naive subjects with T2DM. A total of 212 subjects were assigned to receive either a tight Japanese diet (n=65), pioglitazone at doses ranging from 15-30 mg/day (n=70), or canagliflozin at doses ranging from 50-100 mg/day (n=77) for a duration of three months. Correlations and changes (Δ) in metabolic parameters relative to insulin resistance were investigated. Across these distinct therapeutic interventions, ΔHOMA-R exhibited significant correlations with ΔFBG and ΔHOMA-B, while demonstrating a negative correlation with baseline HOMA-R. However, other parameters such as ΔHbA1c, ΔBMI, ΔTC, ΔTG, Δnon-HDL-C, or ΔUA displayed varying patterns depending on the treatment regimens. Participants were stratified into two groups based on the median value of ΔHOMA-R: the lower half (X) and upper half (Y). Group X consistently demonstrated more pronounced reductions in FBG compared to Group Y across all treatments, while other parameters including HbA1c, HOMA-B, TC, TG, HDL-C, non-HDL-C, TG/HDL-C ratio, or UA exhibited distinct regulatory responses depending on the treatment administered These findings suggest that 1) regression to the mean is observed in the changes of insulin resistance across these therapies. 2) modulation of insulin resistance with these therapies, either causally or consequentially, results in differential effects on glycemic parameters, beta-cell function, specific lipids, body weight or UA.

Network centrality analyses have proven successful in identifying important nodes in diverse host-pathogen interactomes. The current study presents a comprehensive investigation of the human interactome and SARS-CoV-2 host targets. We first constructed a comprehensive human interactome by compiling experimentally validated protein-protein interactions (PPIs) from eight distinct sources. Additionally, we compiled a comprehensive list of 1,449 SARS-CoV-2 host proteins and analyzed their interactions within the human interactome, which identified enriched biological processes and pathways. Seven diverse topological features were employed to reveal the enrichment of SARS-CoV-2 targets in the human interactome, with Load centrality emerging as the most effective metric. Furthermore, a novel approach called CentralityCosDist was employed to predict SARS-CoV-2 targets, which proved effective in expanding the pool of predicted targets. Pathway enrichment analyses further elucidated the functional roles and potential mechanisms associated with predicted targets. Overall, this study provides valuable insights into the complex interplay between SARS-CoV-2 and the host cellular machinery, contributing to a deeper understanding of viral infection and immune response modulation.

In Tropical Monsoon climates, precipitation exceeds evapotranspiration, leading to increased surface runoff, especially in floodplain regions. The Bhagirathi-Hooghly River in India is the focus of the study, which analyses hydrology, sediment yield, and water balance in this floodplain area. This investigation employs the Soil and Water Assessment Tool (SWAT) model within the ArcGIS environment, using remote sensing data. The study area is divided into 4 sub-basins and 40 Hydrological Response Units (HRUs), with a focus on Land Use/Land Cover (LULC) parameters, soil attributes, and slope characteristics. Calibration (1998-2010) and validation (2011-2018) of river discharge and sediment yield are performed using the SUFI-2 algorithm within SWAT-CUP. The calibration process shows a strong correlation between observed and simulated data points, indicating the model's accuracy. The study reveals a pattern of early-year evapotranspiration followed by increasing rainfall during the monsoon season, leading to heightened surface runoff and sediment yield. Excessive rainfall, therefore, emerges as a pivotal driver of flood incidences within the floodplain. The insights derived from the SWAT model's floodplain data have the potential to inform flood control and sedimentation mitigation strategies. The assimilation of this data can empower local stakeholders and contribute to sustainable livelihoods and improved living conditions, offering guidance for future governmental policies.

Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. To explore this issue, general practitioners dislocated in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e. with a Findrisc score > 9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalized prescription of physical activity. Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8 %) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalized program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 minutes to perform the screening. Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web-app to intercept individuals with prediabetes.

Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two Phase III trials, demonstrating favorable results in diabetes treatment. The hepato-selective GKA—TTP399— emerges as a strong contender, displaying clinically noteworthy outcomes with minimal adverse effects. This paper seeks to review the current literature, delve into the mechanisms of action of these new-generation GKAs, and assess their efficacy and safety in treating T2DM based on published pre-clinical studies and clinical trials.

During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral thera-pies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants, which strongly challenged the containment measures and some therapeutic treatments. To assess whether an impaired immunity could lead to an increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimize the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients expe-rienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low frequency mutations. This study suggests that a compro-mised immune system alone does not affect SARS-CoV-2 within-host genomic variability.

This study is to explore the feasibility using neural network (NN) and deep learning to diagnose three common respiratory diseases with only few symptom words. These three diseases are nasopharyngitis, upper respiratory infection, and bronchitis/bronchiolitis. Through natural language processing, the symptom word vectors are encoded by GPT-2 and classified by the last linear layer of the NN. The experimental results are promising, showing that this model achieves a high performance in predicting all these three diseases. They reach 90% in accuracy, which suggests the implications of the developed model, highlighting its potential use in assisting patients understanding their conditions via a remote diagnosis. Unlike previous studies that focus on extracting various categories of information from medical records, this study directly extracts sequential features from unstructured text data, reducing the effort required for data pre-process.

To study the fermentation process of biocatalyzing decanoic acid to synthesize trans-2-decenoic acid, this study was based on the engineering E.coli constructed in the laboratory in the early stage and studied the effect of seed liquid culture time, culture temperature, inoculum amount, induction temperature, dissolution effects of substrate solvent, metal ions, and substrate loading on the yield of trans-2-decenoic acid. Based on single-factor experimental optimization, the Box–Behnken design was used to conduct response surface testing using the substrate feeding concentration, inducer concentration, and MnCl2 concentration as response variables and trans-2-decenoic acid production as the response value. The optimal fermentation process was determined through experiments: seed culture time 20 h, culture temperature 37°C, inoculation amount 1%, induction temperature 30°C, substrate flow amount 0.15 g/L, inducer concentration 5.60 g/L, MnCl2 concentration was 0.10 mM. Under these conditions, the average production of trans-2-decenoic acid was 1.982 ± 0.110 g/L. Compared with the basic LB medium, the production of trans-2-decenoic acid increased by 1.042 g/L; compared with the previous period, the yield of trans-2-decenoic acid studied increased by 1.501 ± 0.110 g/L, which provides a reliable basis for further research on the fermentation process of biocatalytic decanoic acid synthesis of trans-2-decenoic acid.

In this paper, we give all non splitting bi-unitary superperfect polynomials divisible by one or two irreducible polynomials over the prime field of two elements. We prove the nonexistence of odd bi-unitary superperfect polynomials over F2.

The liver is not only a digestive gland, but also an immune tissue that receives a double infusion from the hepatic artery and the hepatic portal vein. Receiving 80% of its blood supply from the intestine through the hepatic portal vein system, the liver is enriched with a large number of innate immune cells, which carry out the process of immune response by detecting pathogens entering the organism through the intestine. The intestine and liver communicate extensively through the bile ducts, portal vein and the somatic circulation, a bidirectional communication known as the intestinal-liver axis. The mammalian gut is considered an important microbial ecosystem. The interplay between the natural immune system and microbes coordinates the physiology of the whole organism, and in specific mammalian lineages, there is a dependency between the host and its associated microbes. To this end, we explored the regulatory mechanisms of natural immunity genes at the genome-wide level. Based on comparative genomics, 1473 bovine natural immunity genes were obtained by collecting the latest reports of human natural immunity genes and updated bovine genomic data for comparison, and a bovine natural immunity gene database was initially constructed to screen and match calf liver natural immunity differential genes mainly affected by the phylum Mimosoidea and the phylum Thick-walled Bacteria, and 16 differentially expressed natural immunity genes were obtained. In addition, the results of IPA analysis indicated that the upstream factor IL-2 initiated the PI3K/AKt/mTOR, mitogen-activated protein kinase (MAPK) pathway and JAK/STAT5 pathway, leading to the liver's involvement in gut microbial immune regulation.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Preterm birth (PB) is a leading cause of perinatal morbidity and mortality. PB prediction is per-formed by measuring cervical length, with a detection rate of around 70%. Although it is known that a cytokine-mediated inflammatory process is involved in the pathophysiology of PB, no screening method implemented in clinical practice includes cytokine levels as a predictor varia-ble. Here, we quantified cytokines in cervical-vaginal mucus of pregnant women (18-23.6 weeks of gestation) with high- or low-risk for PB determined by cervical length, collecting relevant obstetric information. IL-2, IL-6, IFN-γ, IL-4, and IL-10 were significantly higher in the high-risk group, while IL-1ra was lower. Two different models for PB prediction were created using the Random Forest machine-learning algorithm: the full model with 12 clinical variables and cyto-kine values, and the adjusted model, including the most significant variables -maternal age, IL-2, and cervical length- (detection rate 66 vs 87%, false positive rate 12 vs 3.33%, false negative rate 28 vs 6.66%, and area under the curve 0.722 vs 0.875, respectively). The adjusted model integrat-ing cytokines showed a detection rate 8 points higher than the gold standard calculator, which may allow us to identify PB risk more accurately and implement strategies for preventive in-terventions

Kidney transplant recipients (KTR) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTR. Between February 1, 2020 and July 1, 2022, 578 KTR were infected with SARS-CoV-2, with 25 (4%) recurrent infections. 208 KTR (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU-admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed, being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both, virological changes in the Omicron variant and vaccination, reduce the risk for morbidity and mortality from COVID-19 in KTR. Our data extend the knowledge from the general population to KTR and provide important insights into outcome during the Omicron era.

The COVID-19 pandemic has posed a significant threat to society in recent times, endangering human health, life, and economic well-being. The disease spreads quickly due to the highly infectious SARS-CoV-2 virus, which has undergone numerous mutations. Despite intense research efforts by the scientific community since its emergence in 2019, no effective therapeutics have been discovered yet. While some repurposed drugs have been used to control the global outbreak and save lives, none have proven universally effective, particularly for severely infected patients. Although the spread of the disease is generally under control, anti-SARS-CoV-2 agents are still needed to combat current and future infections. This study reviews some of the most promising repurposed drugs containing indolyl heterocycle, which is an essential scaffold of many alkaloids with diverse bio-properties in various biological fields. The study also discusses natural and synthetic indole-containing compounds with anti-SARS-CoV-2 properties, as well as computer-aided drug design (in-silico studies) for optimizing anti-SARS-CoV-2 hits/leads.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 enters the host by infecting nasal ciliated cells. Then, the virus can spread towards the oropharyngeal cavity and the pulmonary tissues. The antiviral adaptive immunity is promptly induced in response to virus detection, with virus-specific T lymphocytes appearing before antiviral antibodies. Both breadth and potency of the antiviral CD8+ T cell immunity have a key role in containing viral spread and disease severity. Current anti-SARS-CoV-2 vaccines do not impede the virus replication in the upper respiratory tract, and there is consensus on the fact that the best potency of the antiviral immune response in both blood and upper respiratory tract can be reached upon infection in vaccinees (i.e., breakthrough infection). However, whether the antiviral CD8+ T cells developing in response to the breakthrough infection in the upper respiratory tract diffuse to the lungs also is still largely unknown. To fill the gap, we checked the CD8+ T cell immunity elicited after infection of K18-hACE2 transgenic mice both 3 weeks and 3 months after anti-Spike vaccination. The virus-specific CD8+ T cell immunity was monitored in both blood and the lungs before and after infection. By investigating the de novo generation of CD8+ T cells specific for SARS-CoV-2 viral proteins, we found that both membrane (M) and/or nucleocapsid (N)-specific CD8+ T cells were induced at comparable levels in blood of both unvaccinated and vaccinated mice. Conversely, N-specific CD8+ T cells were readily found in the lungs of control mice, but were either rare or absent in those of vaccinated mice. These results support the idea that the hybrid cell immunity developing after asymptomatic/mild breakthrough infection strengthens the antiviral cell immunity at lungs only marginally, implying that the direct exposition of the viral antigens is required for the induction of an efficient antiviral cell immunity in the lungs.

The COVID-19 pandemic cost 7-8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the SARS-CoV2 virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in ARDS and lung injury. Anti-inflammatory intervention with anti-IL6 (anti-IL-6 receptor monoclonal antibodies (mAbs) (e.g., sarilumab, tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and /or steroid-based approach lead to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this short review, we summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus–host immune cross talks and presenting the possibilities of therapeutic intervention.

During one of the worst global health crises, millions of people were vaccinated against SARS-CoV-2. In rare cases, new onset systemic inflammatory diseases were reported with temporal coincidence to the vaccination. We describe a case of severe Eosinophilic Granulomatosis with Polyangiitis (EGPA) in a young asthmatic woman, occurring after a 2nd dose of mRNA-1273 vaccine. She presented with multisystem EGPA with cardiac and central nervous system involve-ment, complicated by secondary immune thrombocytopenia (ITP). We review the reported cases of EGPA coinciding with SARS-CoV-2 mRNA vaccination. All potentially vaccine-related EGPA cases reported so far occurred within 14 days from immunization. EGPA is very rare with an incidence of 1:1’000’000 inhabitants and the number of reported post-vaccination EGPA cases lies within the expected incidence rate for the period. While we cannot prove a causal relationship between the vaccine and EGPA onset, the temporal relationship with the vaccine immune stimulation is intriguing, in a disease occurring almost always in adults with asthma and/or chronic rhinosinusitis and driven by an aberrant Th2 lym-phocyte activation with hypereosinophilia. Nevertheless, cases of inflammatory diseases emerging in the context of vaccination remain rare and the benefits of preventing severe Covid presentations with SARS-CoV-2 mRNA vaccines remains unquestionable.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. The random forests algorithm correctly identified 88% of polygon pixels reserved for testing. The developed workflow relied solely on open source software and acquired ground observations. Space organization was directed by the altitude as demonstrated by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 shows some trends of vegetation cover evolution in response to climate change in the considered area.

Polymorphism in cytochrome P450 (CYP) 2C9 enzyme is known to cause significant inter-individual differences in drug response and occurrence of adverse drug reactions. Different alleles of the CYP2C9 gene have been identified but the notable alleles responsible for reduced enzyme activity are CYP2C9*2 and CYP2C9*3. No pharmacogenetic data is available on CYP2C9*2 and CYP2C9*3 alleles in Pakistani population. In Pakistan pharmacogenetics which examines the relationship between genetic factors and drug response, are in the early stages of development. We for the first time investigated the association between the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 and the incidence of hypoglycemia in diabetic patients who were receiving the sulfonylurea medications. A total of n=400 individuals of Pashtun ethnicity were recruited from ten different districts of Khyber Pakhtunkhwa, Pakistan to participate in the study. The study participants were divided into two distinct groups: the case group (n=200) and the control group (n=200). The case group consisted of individuals with Type 2 Diabetes Mellitus (T2DM) who were receiving sulfonylurea medications and experience hypoglycaemia with it whereas the control group included individuals with T2DM who were receiving sulfonylurea medication but did not experience sulfonylurea-induced hypoglycaemia (SIH). Blood samples were obtained from study participants following informed consent. DNA was isolated from whole blood samples using Wiz-Prep DNA extraction kit. Following DNA isolation, CYP2C9 alleles were genotyped using MassARRAY sequencing platform at centre of genomics Rehman Medical Institute (RMI). The frequency of CYP2C9*2 (low activity allele) was more frequent in the diabetic patients with sulphonylurea-induced hypoglycaemia (SIH) compared to the control group (17.5% vs. 6.0%, p=0.021). The frequency of its corresponding genotype CYP2C9*1/*2 was higher in cases compared to control group (10% vs. 6% with P=0.036), same was true for genotype CYP2C9*2/*2 (7% vs. 3.5 % with P=0.028). Logistic regression analysis evident potential association of CYP2C9*2 allele and its genotypes with SIH. When adjusted for confounding factors such age, weight, sex, daily dose of sulphonylurea and triglyceride level the association between the CYP2C9*2 allele and hypoglycemia remains consistent. Confounding factors played no role in SIH because both groups (cases and controls) were closely matched in term of age, weight, sex, mean daily dose of sulphonylurea and trigyleride levels. Our study suggests that genetic information about a patient's CYP2C9 gene/enzyme can potentially assist physicians in prescribing the most suitable and safest drug based on their genetic make-up.

Background: The therapeutic benefits of fermented foods in the treatment and prevention of Type 2 diabetes mellitus have been reported. Aim: Inhibitory effect of fermented rice beverages on α-amylase, α-glucosidase and pancreatic lipase was evaluated. Method: Two fermented rice beverages-fermented rice alone (FKR) and fermented rice plus roasted peanuts (FKRG) were produced using spontaneous fermentation. Capacity of the beverages to inhibit al-pha-glucosidase, alpha-amylase and pancreatic lipase in vitro was evaluated and compared with standards (positive controls). Results: FKR exerted inhibition of α-glucosidase between 9.23-21.11% and FKRG 1.11-17.36% at the various concentrations respectively, with both samples showing the most significant inhibition (about 20%) at 125 μg/mL. FKRG exhibited greater alpha-amylase inhibition activity than FKR, but for both samples, the most significant (P < 0.05) inhibition occurred at 500 μg/mL. With pancreatic lipase, no significant inhibition was observed for both FKR and FKRG at the tested concentrations compared to Orlistat used as control; how-ever, at 31.25 μg /mL FKRG showed an inhibitory effect of approximately 15%, which was not evident at higher concentrations. Conclusion: Low to moderate inhibition of α-amylase, α-glucosidase and pancreatic lipase by both FKR and FKRG, showed that the fermented rice beverages have potential to modulate hyperglycemia in type 2 diabetes in vitro. This is an indi-cation that fermented rice beverage could prevent postprandial hyperglycemia in vivo.

The Shisa family is a type of single-transmembrane adaptor proteins containing an N-terminal cysteine-rich domain and a proline-rich C-terminal region. Nine Shisa subfamily genes have been proposed in most vertebrates; however, some of them might be species-specific. The number of Shisa genes present in zebrafish remains unclear. The purpose of this study was to investigate the evolutionary relationships among Shisa family genes in zebrafish (TU strain) using phylogenetic and syntenic analyses. The function of shisa-2 was preliminarily examined via CRISPR/Cas13d-mediated knockdown. Following identification in zebrafish,10 Shisa family genes, namely shisa-1, 2, 3, 4, 5, 6, 7, 8, 9a, and 9b, were classified into three main clades and six subclades. Their encoding proteins contained a cysteine-rich N-terminal domain and a proline-rich C-terminal region containing different motifs. A specific syntenic block containing atp8a2 and shisa-2 was observed to be conserved across all species. Furthermore, all these genes were found to be expressed during embryogenesis. shisa-2 was expressed in the presomitic mesoderm, somites, and so on. shisa-2 was identified as a regulator of the expression of the somite formation marker mesp-ab. Overall, our study provides new insights into the evolution of Shisa family genes and the control of shisa-2 over the convergent extension cells of somatic precursors in zebrafish.

Periodontitis is a widely spread chronic inflammatory disease caused by a changed oral microbiome. Although multiple species and risk factors have been associated with periodontitis, Porphyromonas gingivalis undoubtedly stands in the center as a keystone pathogen. The immune-modulatory function of P. gingivalis has been well characterized, but the mechanism by which peptidyl arginine deiminase (PPAD), a citrullinating enzyme, contributes to the infinite loop of inflammation is not fully understood. To determine the functional role of hypercitrullination in the context of periodontitis, we performed a comparative analysis on neutrophils stimulated by the wild type and the PPAD mutant strain that lacks an active enzyme. Our flow cytometric analysis revealed that PPAD contributes to the prolonged neutrophil survival upon bacteria stimulation, which was accompanied by aberrant IL-6 and TNF-α secretion in the experimental environment. To further elaborate on the complex mechanism by which citrullination sustains the chronic inflammatory state, we assessed the ROS production and phagocytic activity of neutrophils. Flow cytometry and colony formation assay demonstrated that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines while making the bacteria itself more resilient to phagocytosis.

Following the well-known pandemic, declared on 30 January 2020 by the World Health Organi-zation, the request for new global strategies for the prevention and mitigation of the spread of the infection has come to the attention of the scientific community. Nanotechnology has often managed to provide solutions, effective responses, and valid strategies to support the fight against SARS-CoV-2. This work reports a collection of information on nanomaterials that have been used to counter the spread of the SARS-CoV-2 virus. In particular, the objective of this work is to illustrate the strategies that have made it possible to use the particular properties of nanomaterials, for the production of personal protective equipment (DIP) for the defense against the SARS-CoV-2 virus.

Evaluating the performance of water indices and mapping the spatial distribution of water-related ecosystems are important for monitoring surface water resources. This is particularly the case for Ethiopia since there is limited information available on water resources development over time despite its relevance for the people and ecosystems. To address this problem, this paper evaluates the performance of seven water indices for country-scale surface water detection based on high spatial and multi-temporal resolution Sentinel-2 data, processed using the Google Earth Engine cloud computing system. Results show that the water index (WI) and automatic water extraction index with shadow (AWEIsh) are the most accurate ones to extract surface water. Comparisons are based on qualitative visual inspections and quantitative accuracy indicators. For the latter, WI and AWEIsh obtained kappa coefficients of 0.96 and 0.95, respectively, and an overall accuracy of 0.98 each. Both indices accounted for similar spatial coverages of surface waters with 82,650 km2 (WI) and 86,530 km2 (AWEIsh) for the whole of Ethiopia.

The main problem in creating anti-coronavirus vaccines that target mainly proteins of the outer membrane of the virus remains the rapid variability of the RNA genome of the pathogen that encodes these proteins. In addition, the introduction of technologies that can provide affordable and fast production of flexible vaccine formulas that easily adapt to the emergence of new subtypes of SARS-CoV-2 is required. Universal oligonucleotide vaccine can take into account the dynamics of rapid changes in the virus genome, as well as be synthesized on automatic DNA synthesizers in large quantities in a short time. In this brief report, the effectiveness of four phosphorothioate constructs of the La-S-so type oligonucleotide vaccine will be evaluated for the first time on transgenic mice [B6.Cg-Tg (K18-ACE2)2]. In our primary trials, the oligonucleotide vaccine increased the survival rate of animals infected with SARS-CoV-2 and also reduced the destructive effects of the virus on the lung tissue of mice. The obtained results show the perspective of the development of vaccine constructs of the La-S-so type for the prevention of coronavirus infections, including those caused by SARS-СoV-2.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2’-fucosyllactose (2’-FL), a human milk oligosaccharide, has anti-inflammatory effects and plays a protective role in arterial thrombosis, but its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2’-FL and its potential mechanisms in a mouse model of ischemic stroke. The administration of 2’-FL led to a reduction in the size of cerebral infarct and reactive oxygen species (ROS)-related products in the brain of MCAO mice. Further, 2’-FL promotes the recovery of neurological deficits and motor function in neurological scores and behavior tests. Biochemical studies showed that 2’-FL reduced upregulated IL-10 and downregu-lated TNF-α. Additionally,2’-FL enhanced M2-type microglial polar2’-FL upregulated IL-10 and downregulated TNF-α ization at 7 days after MCAO, with an increase in IL-4 levels and STAT6 activation at 3 days after MCAO. Our data showed that 2’-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type mi-croglial polarization in MCAO mice. These results demonstrate that 2’-FL is a potentially effective therapeutic agent for ischemic stroke.

This study assesses the durability of severe acute respiratory coronavirus-2 (SARS-CoV-2) anti-nucleocapsid (anti-N) immunoglobulin G (IgG) after infection, and examines its association with established risk factors among South African healthcare workers (HCWs). Blood samples were obtained from 390 HCWs with diagnosis of coronavirus disease 2019 (COVID-19) for assay of the SARS-CoV-2 anti-N IgG at two time points (Phase 1 &amp; 2) between November 2020 and February 2021. Out of 390 HCWs with COVID-19 diagnosis, 267 (68.5%) had detectable SARS-CoV-2 anti-N IgG antibodies at the end of phase I. These antibodies persisted for 4-5 and 6-7 months in 76.4% and 16.1%, respectively. In the multivariate logistic regression model analysis, black participants were more likely to sustain SARS-CoV-2 anti-N IgG for 4-5 months. However, participants who were HIV positive were less likely to sustain SARS-CoV-2 anti-N IgG antibodies for 4-5 months. In addition, individuals who were &lt;45 years of age were more likely to sustain SARS-CoV-2 anti-N IgG for 6-7 months. Of the 202 HCWs selected for phase 2, 116 participants (57.4%) had persistent SARS-CoV-2 anti-N IgG for an extended mean period of 223 days (7.5 months). Findings support the longevity of vaccine responses against SARS CoV-2 in black Africans.

Due to species barriers and poor adaptability to new host environments, few pathogens cause global pandemics. But, SARS-CoV-2 is one exception with its high transmissivity and delayed onset of symptoms. Fortunately, the world was able to tap on the technologies especially the maturing RT-qPCR designed to combat SARS to launch an initial offensive on SARS-CoV-2. These initial efforts may have bought time for scientists to develop more refined diagnostic tests that specifically target SARS-CoV-2. This article describes the effort put forth by the biotech industry and academia in Singapore to develop diagnostic tests that aid the early detection of positive cases, and thereby help contain the virus. Direct tests such as RT-qPCR and antigen rapid test profile the virus nucleic acid and surface proteins, respectively. But, of equal importance in case detection and treatment is serological tests that measure the relative abundance of IgM and IgG which is indicative of infection phase and quality of immune response in positive cases. Other tests such as isothermal amplification, CRISPR-based diagnostics and breath tests are also in development or at initial field deployment, and would undoubtedly provide valuable use experience useful for the development of molecular assays to detect and combat the next pathogen of global concern.

In 2018, the author identified a previously unknown/unreported association between dexrazoxane and poly(ADP-ribose) (PAR). Interestingly, PAR is a close structural analogue of the polyadenine nucleotide polymer, polyadenosine monophosphate (poly(A)). In this report, subsequent in silico modelling of the interaction between dexrazoxane and poly(A) reveals some notable differences from the previously reported interaction between dexrazoxane and PAR. Significantly, the supramolecular self-assembly of dexrazoxane and poly(A) is distinguished by vertically-orientated nonelectrostatic forces comparable to the stabilizing interactions between stacked bases within DNA. Notably, the vertical separation of 3.4 Å between each stack is consistent with solvent entropy as a dominant driving force in stabilising the interaction. Additionally, concomitant conformational analysis by the author reveals the existence of low energy planar conformers of dexrazoxane. This analysis enables an explanation for the considerable discrepancies and conflicts that exist within the reported pharmacokinetic data for dexrazoxane. Exploring the significance of the interaction between dexrazoxane and poly(A), the author illustrates that survival, translation and replication of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) is absolutely dependent upon the mature and unhindered poly(A) tail of the SARS-CoV-2 genome. The proposition herein, that dexrazoxane, as a chameleonic agent sequesters the poly(A) tail of the SARS-CoV-2 genome by the catalysis of a supramolecular hybrid assembly establishes SARS-CoV-2 infected cells as deep compartments for the accumulation of dexrazoxane. Taken together, dexrazoxane or its demethylated analogue, represent a novel treatment to kill the SARS-CoV-2 virus by irreversible destabilization of the SARS-CoV-2 poly(A) tail.

Background: The duration of the vaccine's protective efficacy against SARS-CoV-2 is unknown. Evaluation of the clinical performance of available tests is required. Objectives: To evaluate the clinical performance of three immunoassays for the detection of IgG antibodies generated by mRNA vaccines against SARS-CoV-2. Methods: Two automated immunoassays (Euroimmun Anti-SARS-CoV-2 ELISA IgG and Abbott SARS-CoV-2 CLIA IgG) and one lateral flow immunoassay (LFIA Test Livzon IgG) were tested. 300 samples distributed in 3 groups were analyzed: 100 subjects over 18 years old and under 45 years old, 100 subjects between 45-65 years old and another 100 over 65 years old. collected before vaccination, at 21 days, 1, 2, 3 and 6 months post-vaccination. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and agreement (I. Kappa) were calculated for each serological test. Results: Maximum sensitivity for IgG was 98.7%, 98.1%, and 97.8% for the ELISA Euroimmun, CLIA Abbott, and Livzon LFIA assays and maximum specificity for IgG was 99.4%, 99.9%. % and 98.4% ELISA, CLIA and LFIA respectively at 3 months after vaccination with a decrease in antibody levels from the sixth month. The best agreement was observed between ELISA and CLIA 100%; (k = 1.00). The agreement between ELIA, CLIA and LIFIA was 99% (k = 0964) at the second and third month after vaccination. Seroconversion was faster and longer lasting in the younger age groups. Conclusion: Our study showed an equivalent and homogeneous clinical performance for IgG of three immunoassays after vaccination and that the LIFIA assay is the most cost-effective, reliable and accurate for routine use in population studies of seroconversion and seroprevalence.

The unprecedented growth of publicly available SARS-CoV-2 genome sequence data has increased demand for effective and accessible SARS-CoV-2 data analysis and visualization tools. A majority of the currently available tools either require computational expertise to deploy or limit user input to pre-selected subsets of SARS-CoV-2 genomes. To address these limitations, we developed ViralVar, a publicly available, point-and-click webtool that gives users the freedom to investigate and visualize user-selected subsets of SARS-CoV-2 genomes obtained from the GISAID public database. ViralVar has two primary features that enable: 1) visualization of spatiotemporal dynamics of SARS-CoV-2 lineages, and 2) structural/functional analysis of genomic mutations. As proof-of-principle, ViralVar was used to explore the evolution of the SARS-CoV-2 pandemic in the USA in the pediatric, adult, and elderly population (n > 1.7 million genomes). While the spatiotemporal dynamics of variants did not differ between these age groups, several USA-specific sublineages arose relative to the rest of the world. Our development and utilization of ViralVar to provide insights on the evolution of SARS-CoV-2 in the USA demonstrates the importance of developing accessible tools to facilitate and accelerate large-scale surveillance of circulating pathogens. The ViralVar webserver is freely available at http://viralvar.org/.

A human case of dengue virus 2 was detected from a febrile patient living in the Sare yoba, Kolda region (Southern Senegal). Phylogenetic analysis based on the partial sequence of the NS5 gene reveals that the virus belongs to the DENV2 Sylvatic genotype and is closely related to a strain (JF260983/ 98.98% identity) detected in Spain from a tourist who travelled to Guinee Bissau (bordering Kolda region) in 2009. This highlights a potential recent underreported circulation of sylvatic Dengue in the southern part of Senegal and calls for re-enforced integrated surveillance among humans, non-human primates and arboreal mosquitoes throughout a one-health approach.

The detection of waste plastics in the marine and terrestrial environment using satellite Earth Observation data offers the possibility of large-scale mapping, and reducing on-the-ground manual investigation. In addition, costs are kept to a minimum by utilizing free-to-access Copernicus data. A Machine Learning based classifier was developed to run on Sentinel-1 and -2 data. In support of the training and validation, a dataset was created with terrestrial and aquatic cases by manually digitizing varying landcover classes alongside plastics under the sub-categories of greenhouses, plastic, tyres and waste sites. The trained classifier, including an Artificial Neural Network and post-processing decision tree, was verified using five locations encompassing these different forms of plastic. Although exact matchups are challenging to digitize, the performance has generated high accuracy statistics, and the resulting land cover classifications have been used to map the occurrence of plastic waste in aquatic and terrestrial environments.

Background: Some viruses cause outbreaks which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, development of monoclonal antibodies is often long, laborious, and unprofitable. Here we report a Norwegian platform for development of chicken polyclonal neutralizing antibodies with powerful therapeutic potential. Methods: Layers were immunized twice with 14-day interval using purified RBD of SARS-CoV-2. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgY to RBD was measured by indirect ELISA. Neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry strain using fluorescence and cell viability assay. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bind RBD of S protein of SARS-CoV-2 in situ, neutralize the virus in vitro, and lower viral RNA amplification without significant alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicated that chicken polyclonal IgYs can be attractive targets for pre-clinical and clinical development for rapid management of outbreaks of emerging and re-emerging viruses.

The worldwide outbreak of SARS-CoV-2 in early 2020 caused numer- ous deaths and unprecedented measures to control its spread. We employed our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery, repurposing, and design platform to identify small molecule inhibitors of the virus to treat its resulting indication, COVID-19. Initially, few experimental studies existed on SARS-CoV-2, so we optimized our drug candidate prediction pipelines using results from two independent high-throughput screens against prevalent human coronaviruses. Ranked lists of candidate drugs were generated using our open source cando.py software based on viral protein inhibition and proteomic interaction similarity. For the former viral protein inhibition pipeline, we computed interaction scores between all compounds in the corresponding candidate library and eighteen SARS-CoV proteins using an interaction scoring protocol with extensive parameter optimization which was then applied to the SARS-CoV-2 proteome for prediction. For the latter similarity based pipeline, we computed interaction scores between all compounds and human protein structures in our libraries then used a consensus scoring approach to identify candidates with highly similar proteomic interaction signatures to multiple known anti-coronavirus actives. We published our ranked candidate lists at the very beginning of the COVID-19 pandemic. Since then, 51 of our 276 predictions have demonstrated anti-SARS-CoV-2 activity in published clinical and experimental studies. These results illustrate the ability our platform to rapidly respond to emergent pathogens and provide greater evidence that treating compounds in a multitarget context more accurately describes their behavior in biological systems.

Background: Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. The aim was to assess the threshold of 264 binding antibody units (BAU)/ml using four different SARS-CoV-2 antibody assays (Abbott, Beckman, Roche, and Siemens) and to establish a new optimal threshold of protection for each of the four antibody assays. Methods: This study was performed on data retrieved from 69 individuals, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) at the Alphabio Laboratory in Marseille, France (European Hospital, Alphabio – Biogroup). The results were compared to the percent inhibition calculated using a functional surrogate of a standardized virus neutralization test (Genscript). Results: Samples from 69 patients were analyzed. For a reference cutoff of 264 BAU/ml, assays showed moderate to good overall concordance with Genscript: 87% concordance for Abbott, 78% for Beckman, 75% for Roche, and 88% for Siemens. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). Conclusion: We suggest specific adjusted thresholds (BAU/ml) for the four commercial antibody assays that are used to assess pre-exposure prophylaxis in immunocompromised patients.

The current pandemic is urgently demanding to discover alternative materials capable of inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus 2019 (COVID-19) disease. Calcium alginate is a crosslinked hydrophilic biopolymer with an immense range of biomedical applications due to its excellent chemical, physical and biological properties. In this study, the cytotoxicity and antiviral activity of calcium alginate in the form of films were studied. The results showed that these films are biocompatible in human keratinocytes and are capable of inactivating enveloped viruses such as bacteriophage phi 6 with a 1.43-log reduction (94.92% viral inactivation) and SARS-CoV-2 Delta variant with a 1.64-log reduction (96.94% viral inactivation) in virus titers. The antiviral activity of these calcium alginate films can be attributed to its negative charge density that may bind to viral envelopes inactivating membrane receptors.

Crop-type mapping is an important intermediate step for cost-effective crop management at the field level, as an overview of all fields with a particular crop type can be used for monitoring or yield forecasting, for instance. Our study used a data set with 2400 fields and corresponding satellite observations from the federal state of Bavaria, Germany. The study classified corn, winter wheat, winter barley, sugar beet, potato, and winter rapeseed as the main crops grown in Upper Bavaria. We additionally experimented with a rejection class "Other", which summarised further crop types. Corresponding Sentinel-2 data included the normalised difference vegetation index (NDVI) and raw bands from 2016 to 2018 for each selected field. The influence of raw bands compared to NDVI was analysed and the classification algorithms, i.e. support vector machine (SVM) and random forest (RF), were compared. The study showed that the use of an index should be critically questioned and that raw bands provided a wider spectral bandwidth, which significantly improved the mapping of crop types. The results underline the use of RF with raw bands and achieved overall accuracies (OA) of up to 92%. We also predicted crop types in an unknown year with significantly different weather conditions and several months before the end of the growing season. Thus, the influence of climate anomalies and the accuracy depending on the time of prediction were assessed. The crop types of a test site and year without labels could be determined with an OA of up to 86%. The results demonstrate the usefulness of the proof-of-concept and its readiness for use in real applications.

Diabetes and chronic kidney disease (CKD) are a major public health burden in low-and-middle-income countries. This study aimed to explore factors associated with CKD in patients with type 2 diabetes (T2D) in Bangladesh. A cross-sectional study was conducted among 315 adults with T2D presenting at the outpatient department of Bangladesh Institute of Health Sciences (BIHS) hospital between July 2013 to December 2013. CKD was diagnosed based on estimated Glomerular Filtration Rate using the ‘Modification of Diet in Renal Disease’ equations and presence of albuminuria estimated by the albumin-to-creatinine ratio. Multivariate logistic regression analysis was used to determine the factors associated with CKD. The overall prevalence of CKD among patients with T2D was 21.3%. In the unadjusted model Factors associated with CKD were: aged 40-49 years (OR: 5.7, 95% CI: 1.3-25.4), age 50-59 years (7.0, 1.6-39), age ≥60 years (7.6, 1.7-34); being female (2.2, 1.2-3.8), hypertensive (1.9, 1.1-3.5) and household income between 128.2-256.4 US$ (2.9, 1.0-8.2) compared with income ≤128.2$. However, after adjustment of other covariates, only duration of hypertension and household income (128.2-256.4 US$) remained statistically significant. There is a need to implement policies and programs for early detection and management of hypertension and CKD in T2D patients in Bangladesh.

The furin cleavage site, with an arginine doublet (RR), is one of the clues of the SARS-CoV-2 origin. This furin-RR is encoded by the CGG-CGG sequence. Because arginine can be encoded by six codons, in a previous work we found that in SARS-CoV-2, CGG was the minority arginine codon (3%). Also, analyzing the RR doublet from a large sample of furin cleavage sites of several kinds of viruses, we found that none of them were encoded by CGG-CGG. Here, we come back to the core of the matter, but from the perspective that in the human genome, in contrast, CGG is the majoroty arginine codon (21%). Here, we highlighted that the 6 arginine codons provide genetic markers to a traceability on the RR origin in the furin site, as well as, to weigh the probability of the theories about the origin of the virus.

Abstract: An efficient and environmentally Pumice as a new catalyst for designing of 3,4- dihydropyrimidin-2(1H) ones / thiones via one-pot multi component condensation of aromatic aldehydes, urea/ thiourea and ethyl acetoacetate or acetyl acetone in excellent yields (96-99 %). The advantages using of this new catalyst is very cheap, available, non-toxic, stable under thermal conditions, easy work-up, improved yields, the product of reaction is very pure without using chromatographic methods and solvent free conditions.

Background: the devastating outbreak of COVID-19 poses serious challenges for the diagnostics laboratories, which are often facing global shortage of reagents and equipment. With the aim of increasing the diagnostic throughput for SARS-CoV-2 molecular test, the purpose of this study was to validate an additional RNA extraction method respect to those already recommended by WHO and the US Centers for Disease Control and Prevention (CDC). Methods: a new protocol for RNA extraction from nasopharyngeal swab was set up, adapting the Qiagen RNeasy 96 plate and validated on a set of 100 clinical samples analyzed in parallel by Roche-Magnapure method (already recommended by CDC guidelines). Results: the internal control and target genes analysis showed a good agreement between the two extraction methods indicating that the two methods can be considered equivalent and that the RNeasy-adapted method can be applied for the SARS-CoV-2 diagnostics. The addition of this new extraction method resulted in a throughput increase for SARS-CoV-2 molecular test of about 2000 samples/month during the initial months of the pandemic emergency in which the lack of reagents for the extraction led to an insufficient sample processing throughput of the analysis of the swabs.

Hadhramout Initiative Against Corona (HIAC ) formed a working group of clinicians relevant to the management of COVID-19 to formulate clinical practice guidelines (CPG) for clinicians caring for the patients infected with COVID-19 in Yemen. The regional guidelines on the management of COVID-19 were thoroughly reviewed and its applicability was assessed for Yemen. HIAC’s recommendations covered (2) sections: the first one is the diagnosis, including case definition, risk stratification of the affected cases, investigations (prioritization of reverse transcription-polymerase chain reaction (RT-PCR) testing, D-dimer, chest x-ray, and chest computed tomography, while the second part covers the treatments (mainly Favipiravir, Remdesivir, Hydroxychloroquine, and Glucocorticoid, Anticoagulants, and Supportive measures). In conclusion, the adoption of cost-effective and evidence-based guidelines in Yemen will standardize the management of the patients infected with COVID-19 and protect both the patients and the health care workers from malpractice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19 , is considered a pathogen with animal origin, mainly transmitted human to human. It has been experimentally and naturally demonstrated that several animals can be infected by SARS-CoV-2. There are strong evidences that minks are highly susceptible to SARS-CoV-2 infection, since several cases of human to mink infection have been reported, and it has been suggested mink to human infection exists, which so far it is the most reliable example of a zoonotic event of COVID-19 . However, all these cases reported are form mink farms, with the exception of one case in the USA in which the virus was detected in a mink located in the wild, but it was demonstrated that the animal was infected on a fur farm. In the present work, we have detected SARS-CoV-2 RNA in two wild American minks (Neovison vison) in Valencian Community (Eastern Spain) during invasive species trapping campaigns. The animals were trapped from areas known for harbouring self-sustained populations, far away from the nearest fur farm. SARS-CoV-2 RNA was detected in mesenteric lymph nodes samples by RT-PCR. A partial region of the Spike protein gene was amplified and sequence obtaining a 397 nt size sequence. Phylogenetic analysis shown that both sequences were identical to the consensus variant SARS CoV-2 sequence (from Wuhan). This research describes the first infection report of a true wild American mink not related to infected fur farms or direct contact with humans, which is believed to be the first example of wild animals in which SARS-CoV-2 has been detected.

In December 2019, an unusual cluster of pneumonia cases were reported in Wuhan and promptly confirmed to be caused by a new virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of which the disease it caused would be known as COVID-19. In March 2020, in the absence of any vaccines, and in response to the global spread of SARS-CoV-2 the UK implemented non-pharmaceutical intervention (NPI) measures in the form of a national lockdown to decelerate the spread. Compliance with NPIs can have significant impact on reducing disease transmission however there are currently no studies measuring compliance within the horse ownership world which naturally brings groups of people together during everyday caregiving activities. This article describes the reported horse owner compliance during the COVID-19 pandemic from March 2020 to December 2020 as deduced from 1036 respondents which completed an anonymous online survey between December 30th, 2020 and January 11th, 2021. Where rules/guidance did exist, there was good compliance with 92.76% of respondents indicating that they were following them. The most common rule/guidance implemented was social distancing, which was also the most common rule/guidance to be breached. Riding with others whilst at the yard (hacking or in an arena) and meeting up with non-household members (family and friends) when off the yard were also common rules/guidelines breached. Respondents who kept their horses at either DIY livery, or on a private yard were most likely to breach rules/regulations whereas respondents who kept their horses at full livery were least likely to breach rules/regulations. The results indicate that compliance of horse owners with COVID-19 rules/guidance is high when rules/guidance exists. However, just under half of respondents indicated that there were no rules/guidelines on their yards indicating that there is room for an increased contribution from the horse owning community by encouraging more yards to impose control measures where they currently do not exist.

Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is sufficient experimental evidence to confirm that SARS-CoV-2 infection produces states of ciliary and flagellar dysfunction. However, these studies are unable to explain the observed effects molecularly, because they lack a sufficient understanding of the interaction between human proteins and virus proteins. Using the physical-chemical study of the human interactome in interaction with the SARS-CoV-2 proteome, we found evidence of interactions to explain the experimental effects from a molecular perspective. We found that ten viral proteins interact with key components in the maintenance of the molecular structure of axoneme. Additionally, we evaluated the pulmonary and extrapulmonary pathogenesis of COVID-19 from the point of view of ciliary dysfunction, and warned about other possible complications such as episodes of transient infertility that, due to the limitations of our work, would need verification.

The COVID-19 pandemic caused by SARS-CoV-2 has been showing a speedy growth in the number of infected patients with a remarkable mortality rate, thus it has become a worldwide public health concern. From March 8, 2020, the disease was confirmed to start spreading in Bangladesh. Since then, people got infected so exponentially that the country positions at the list of top infected countries in the world. Therefore, the objective of this comprehensive review was representing overall scenario of COVID-19 in different sectors of Bangladesh, particularly prioritizing the health sector. Up to 14 September 2020, 339,332 confirmed cases and 4,759 deaths were reported. An alarming fact is that while the global mutation rate of coronavirus is 7.23 % in average, the rate is 12.6 % in Bangladesh. Although the government ruled preventive strategies such as nationwide lockdown, social distancing, contact monitoring, quarantine and isolation, it was difficult to implement those due to lack of public awareness, inappropriate attitudes and so on. Moreover, the overburdened healthcare system had a weak response at initial stage because of insufficient healthcare facilities. Consequently, this pandemic affected severely almost all the important sectors of the country, specifically the economy, agriculture and health sectors. Hence, focusing on healthcare system as well as maintaining social distance and other essential precautions can limit the spread of infection and help to alleviate the severity of the pandemic.

The developments of confirmed daily Sars-CoV-2 infections can be modeled a posteriori in a comparatively simple and satisfactory way by means of a special exponential function: its exponential coefficient varies exponentially with time itself. This property enables the function to directly simulate the „daily case“ curve fragments observed for the first waves of the current epidemics in a number of counties and countries. Linear combinations of two or more of the functions allow for the modeling of the complete curves observed in the vast majority of all regions for which case number developments have been tabulated.

(1) Background: A global pandemic due to COVID-19 emerged in November 2019 and hit France in early March 2020. It not only resulted in a loss of lives but also in very strict confinement measures. The objective of this study was to understand what the determinants of the change in participants’ behavior and mental state were during the confinement. (2) Methods: An online survey was launched on April 23rd, 2020, and closed on May 7th, 2020. The final sample included 1454 participants from 24 to 65 years old. Descriptive and multivariate analyses were then performed. (3) Results: 28.7% reported having a more balanced diet, against 17.1% with a less balanced diet. 22.7% of respondents reported an increased alcohol consumption, as opposed to only 12.2% declaring a decrease and 11.2% of respondents increased their tobacco consumption, while 6.3% decreased it. 50.6% of the participants reported being more depressed, stressed, or irritable since the beginning of the lockdown. Confinement had a negative effect on every behavior studied in this survey, except for nutrition. We also found that negative mental state changes were strongly associated with nutrition, sleep, physical activity, and alcohol consumption changes.

For more than ten years, Central Chile faces drought conditions, which impact crop production and quality, increasing food security risk. Under this scenario, implementing management practices that allow increasing water use efficiency is urgent. The study was carried out in kiwifruit trees, located in the O’Higgins region, Chile; for season 2018-2019 and 2019-2020. We evaluate nine vegetation indices in the VNIR and SWIR regions derived from Sentinel-2 (A/B) satellites to know how much variability in the canopy water status could explain. Over the study's site were installed sensors that continuously measure the leaf's turgor pressure (Yara Water-Sensor). A strong correlation between turgor pressure and vegetation indices was obtained with the Spearman's rho coefficient ($\rho$). However, the NIR range's indices were influenced by the vegetative development of the crop rather than its water status. Red-edge showed better performance as the vegetative growth did not affect it. It is necessary to expand the study to consider higher variability in kiwifruit's water conditions and incorporate the sensitivity of different wavelengths.

Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19). Most of reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (a country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On May 25th, we have launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4th March 2020) and prospective data collection. Up to 28th July, 39 reported children met inclusion criteria. We stratified them according to age (&lt;5 and ≥ 5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and 9 children had COVID-19 confirmation. This is the first to our knowledge report of PIMS register from the country with low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g. older age should be considered in the differential diagnosis of inflammatory syndromes in children.

COVID-19, previously known as “2019 novel coronavirus”, is a newly discovered virus which causes severe acute respiratory syndrome, similar to corona virus 2 (SARS-CoV-2), which has spread widely through human to human contact and was declared a pandemic by the WHO in March 2020. To cope with this pandemic many countries have adopted nationwide lockdowns which restrict nonessential activities and encourage their populations to avoid public transport, work from hone wherever possible, and to maintain social distancing at all times. While the severity of these shutdowns has varied with country, large geographic regions of the world (including China, India, Iran, Italy, Spain, and the USA) have all been severely affected, not just in the loss of human life, but also in terms of the financial impacts the lockdowns will have on their countries future prosperityIt was previously reported that a number of environmental factors, including humidity and temperature, played an important role in development and spread of the SARS-Corona Virus infection with the virus retaining viability for over 5 days at temperatures between 22–25^oC and relative humidity (RH) of 40–50%. Whereas, elevated temperatures and higher RH (38^oC, and >95% RH) decreased virus viability (Kroumpouzos et al., 2020). The spread of COVID-19 started in low temperature areas of China, with major outbreaks subsequently occurring in Iran, Japan, Northern Italy and South Korea. These new virus epicenters all had similar temperature and latitude, along the 30-50^◦N” zone. Subsequently, the virus was spread to regions of elevated temperature, such as India, the Middle East and Thailand, due to international travel (Kroumpouzos et al., 2020).The aim of this study was to consider the environmental impact of COVID-19, including water pollution. The paper is divided into four sections. In the first section the current literature related to COVID-19 is reviewed. In the second section a recent update on COVID-19 globally is presented, followed by a descriptive impact on the environment in the third section and finally in the fourth section the COVID-19 related worldwide environmental impact is discussed. Since COVID-19 is a currently an active pandemic with no end in sight, while constructive conclusions can only be made on the limited data currently, which may be prone to high errors. However, these conclusions may provide some preliminary suggestions for assisting in assessing spreading patterns of COVID-19 across the globe, and may be of long-term significances with respect to assessing the environmental impact of lockdown policies due to COVID-19 worldwide.

The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large majority of the population. Structural equation modelling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. The survey was administered to 316 respondents across the United States by a survey corporation. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy, and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short and long-term side effects before a vaccine is released.

The ongoing mutations in the structural proteins of SARS-CoV-2 is the major impediment for prevention and control of the COVID-19 disease. The envelope (E) protein of SARS-CoV-2 is a structural protein existing in both monomeric and homopentameric forms, associated with a multitude of functions including virus assembly, replication, dissemination, release of virions, infection, pathogenesis, and immune response stimulation. In the present study, 81,818 high quality E protein sequences retrieving from the GISAID were subjected to mutational analyses. Our analysis revealed that only 0.012 % (982/81818) stains possessed amino acid (aa) substitutions in 63 sites of the genome while 58.77% mutations in the primary structure of nucleotides in 134 sites. We found the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. We also observed a triple cysteine motif harboring mutations (L39M, A41S, A41V, C43F, C43R, C43S, C44Y, N45R) which may hinder the binding of E protein with spike glycoprotein. These results therefore suggest the continuous monitoring of each structural protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing.

The short study implicates few basic similarities of COVID-19 such as diseases origination, symptoms, diagnosis with other relatable viral diseases viz SARS-CoV, common Flu, pneumonia etc. In the present situation, other viral diseases are frequently chaotic and misled with COVID-19 disease because of few clinical features similarities in signs and symptoms and also due to lack of specific diagnostic test. To avoid unnecessary suspects, quarantines of false positive results and to prevent the spread of COVID-19 diseases, the scientific technical research field are highly encourage to implement an efficient, rapid and sophisticated superior test for early stages of infection detection. It will be significantly convenient for physician, laboratory technicians and most importantly the common population facing a psychological disturbance.

This paper presents the super-twisting algorithm (STA) direct power control (DPC) scheme for the control of active and reactive powers of grid-connected DFIG. Simulations of 5 KW DFIG has been presented to validate the effectiveness and robustness of the proposed approach in the presence of uncertainties with respect to vector control (VC). The proposed controller schemes with fixed gains are effective in reducing the ripple of active and reactive powers, effectively suppress sliding-mode chattering and the effects of parametric uncertainties not affecting system performance.

Nigeria is the most populous country in the African continent. The aim of this study was to analyze risk factors for COVID-19 prevalence and deaths in all 6 geopolitical regions and 37 states in Nigeria. We analyzed the data retrieved from various sources, including Nigeria CDC, Nigeria National Bureau of Statistics, Unicef-Nigeria multiple indicator cluster survey and the Institute of Health Metrics and Evaluation, University of Washington. We examined 4 clinical risk factors (prevalence of TB, HIV, smoking and BCG vaccination coverage) and 5 sociodemographic factors (age ≥65, population density, literacy rate, unemployment and GDP per capita). Multivariate modeling was conducted using generalized linear model. Our analysis showed that the incidence of confirmed COVID-19 cases differed widely across the 37 states, from 0.09 per 100,000 in Kogi to 83.7 in Lagos. However, more than 70% of confirmed cases were concentrated in just 7 states: Lagos, Abuja, Oyo, Kano, Edo, Rivers and Delta. Case mortality rate (CMR) per million population also varied considerably, with Lagos, Abuja and Edo having CMR above 9. On bivariate analysis, higher CMR correlated positively with GDP and to a lesser extent with TB and population density. On multivariate analysis, which is more definitive, states with higher HIV prevalence and BCG coverage had lower CMR, while high GDP states had a greater CMR. This study indicates that COVID-19 has disproportionately affected certain states in Nigeria. Population susceptibility factors include higher economic development but not literacy or unemployment. Death rates were mildly lower in states with higher HIV prevalence and BCG vaccination coverage.

In Wuhan city of China, an episode of novel coronavirus (COVID-19) happened. during late December and it has quickly spread to all places in the world. Until May 29, 2020, cases were high in the USA with 1.7 Million, Russia with approximately 387 thousand, the UK with 271 thousand confirmed cases. Everybody on the planet is anxious to know when the coronavirus pandemic will end. In this scourge, most nations force extreme medication measures to contain the spread of COVID-19. Modeling has been utilized broadly by every national government and the World Health Organization in choosing the best procedures to seek after in relieving the impacts of COVID-19. Many epidemiological models are studied to understand the spread of the illness and its prediction to find maximum capacity for human-to-human transmission so that control techniques can be adopted. Also, arrangements for the medical facilities required such as hospital beds and medical supplies can be made in advance. Many models are used to anticipate the results keeping in view the present scenario. There is an urgent need to study the various models and their impacts. In this study, we present a systematic literature review on epidemiological models for the outbreak of novel coronavirus in India. The epidemiological dynamics of COVID-19 is also studied. Here, In addition, an attempt to take out the results from the exploration and comparing it with the real data. The study helps to choose the models that are progressive and dependable to predict and give legitimate methods for various strategies.

Summary CoV-GLUE is an online web application for the interpretation and analysis of SARS-CoV-2 virus genome sequences, with a focus on amino acid sequence variation. It is based on the GLUE data-centric bioinformatics environment and provides a browsable database of amino acid replacements and coding region indels that have been observed in sequences from the pandemic. Users may also analyse their own SARS-CoV-2 sequences by submitting them to the web application to receive an interactive report containing visualisations of phylogenetic classification and highlighting genomic variation of potentially high impact, for example linked to primer mismatches.Availability and implementation Available at http://cov-glue.cvr.gla.ac.uk. Implemented using GLUE, an open source framework for the development of virus sequence data resources. Contact [email protected]

Our first modern global pandemic is caused by a nanosized lipid vesicle, called SARS-CoV-2. Its molecular structure and biogenesis have remarkable similarities with Extracellular Vesicles (EVs, most notably exosomes) that are constantly shed by all cells during their life. Their resemblance may not be a coincidence. Growing body of evidence has shown that EVs have significant roles in various biological processes, including viral infection, transmission and anti-viral response. Drawing comparison with the virus might shed light on how we could fight the COVID-19 disease. This may include novel EV research and diagnostics technologies as well as novel EV-based treatments.

The ongoing COVID-19 pandemic is one of the biggest health and societal challenges of the recent decades. Among the causes of mortality triggered by SARS-CoV-2 infection, the presence of an inflammatory "cytokine storm" (CS) at later stages of the disease has been found to play a determinant role. Here, we used available transcriptomic data from the bronchoalveolar lavage fluid (BALF) of COVID-19 patients suffering from a CS to obtain gene-signatures associated to this pathological process. Using these signatures, we interrogated the Connectivity MAP (CMap) dataset that contains the effects of over 5,000 small molecules on the transcriptome of human cancer cell lines, and looked for molecules which effects on transcription mimic or oppose those associated to the CS. Consistent with their medical use, this analysis found a significant enrichment of glucocorticoids or inhibitors of the Janus Kinases (JAK) as drugs that could revert the CS. On the other hand, molecules that potentiate the immune response such as PKC activators are predicted to worsen the CS. Besides these expected findings, our analysis also reveals a potential effect of the antibiotic doxycycline or MAPK/RAF/MEK inhibitors in reverting the CS, or of topoisomerase inhibitors and the anti-alcohol abuse drug disulfiram in potentiating its effects. Finally, our analyses support that the gender-related differences in the severity of COVID-19 are related to the anti-inflammatory properties of female hormones. While acknowledging that this is an analysis based on limited available data, we decided to share it as a resource that might help others in the selection of drugs that could be tested in the context of experimental models of CS triggered by viral infections.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

COVID-19 pandemic that started in China has spread within 3 months to the entire globe. We tested the hypothesis that the vaccination against tuberculosis by BCG correlates with a better outcome for COVID-19 patients. Our analysis covers 55 countries complying with predetermined thresholds on the population size and number of deaths per million (DPM). We found a strong negative correlation between the years of BCG administration and the DPM along with the progress of the pandemic, corroborated by permutation tests. The results from multivariable regression tests with 23 economic, demographic, health-related, and pandemic restriction quantitative properties, substantiate the dominant contribution of BCG years to the COVID-19 outcomes. The analysis of countries according to an age-group partition reveals that the strongest correlation is attributed to the coverage in BCG vaccination of the young population (0-24 years). Furthermore, a strong correlation and statistical significance are associated with the degree of BCG coverage for the most recent 15 years, but no association was observed in these years for other broadly used vaccination protocols for measles and rubella. We propose that BCG immunization coverage, especially among the most recently vaccinated contributes to attenuation of the spread and severity of the COVID-19 pandemic.

As the first initiative of its kind in Algeria, here is presented a solar-powered mobile “Ultraviolet Germicidal Irradiation” disinfection unit (UVGI) based on a special germicidal ultraviolet-C (UVC) radiator. The system was designed to disinfect several objects such as: medical tools, reusable masks, face-shields, gloves, phones, laptops, keys, money and many other portable devices that need to be disinfected/sterilized. It offers the advantage of complete autonomy through the built-in photovoltaic (PV) system that includes a solar panel, a gel battery, a charge controller and a power inverter. The system provides an extra 220V-50Hz outlet with 375VA maximum power to be used when energy is needed. The system is easily scalable to generate higher ultraviolet dosages by adding more UVC lamps. The chemical-free germicidal UVC sanitizing method employed by this device effectively disactivates a very wide range of microorganisms (microbes, bacteria and fungi and viruses including the actual SARS-CoV-2 that causes COVID-19 respiratory disease) and it has several advantages in comparison to chemical-based sanitizing methods. The total cost to make this open source device is below 1000 € and is easily customizable and scalable. This device is an open source, secure and fast equipment for objects and surface disinfection. The device will be fully automated by adding PIR sensors or remote control after further funding will be received.

Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% ¹. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase (RdRp) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp ². BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang ². Both the publications ^1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China ³. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 ¹ where novel corona virus was first described. Based on the RdRp sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces ^3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin ⁴. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted.