Nitric oxide has been implicated in symptoms of ethanol withdrawal in animal models. Zebrafish have been used as models to study neurobehavioral effects of ethanol (EtOH) withdrawal, but the mechanisms associated with these effects are not yet clear. Adult zebrafish were treated with 1% EtOH for 20 min per day for 8 days, injected with the nitric oxide synthase 2 (NOS-2) inhibitor aminoguanidine (50 mg/kg), and allowed to experience withdrawal (WD) in their hometanks for 7 days. EtOH WD increased anxiety-like behavior in the novel tank test, an effect that was blocked by aminoguanidine. EtOH WD also increased brain levels of nitrite, an effect that was partially blocked by aminoguanidine. These results underline a novel mechanism by which NOS-2 controls anxiety-like responses to ethanol withdrawal, with implications for the mechanistic study of symptoms associated with chronic ethanol abuse.

We reelaborate on the basic properties of PT symmetry from a geometrical Perspective. The transfer matrix associated with these systems induces a Möbius transformation in the complex plane. The trace of this matrix classifies the actions into three types that represent rotations, translations, and parallel displacements. We find that a PT invariant system can be pictured as a complex conjugation followed by an inversion in a circle. We elucidate the physical meaning of these geometrical operations and link them with measurable properties of the system.

This study aims to determine the seroprevalence of SARS-CoV-2 in pregnant women attending antenatal consultations (ANC) in Senegal. A non-redundant consecutive recruitment of participants was carried out between, March and July 2021 during the Delta wave of COVID-19. The plasma samples biobanked at -80°C were subjected to an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of IgG and IgM antibodies of SARS-CoV-2 using the WANTAI SARS-CoV-2 Ab ELISA (Wantai Biological Pharmacy Enterprise, Beijing). To assess factors associated with seropositivity, bivariate analysis was per-formed with JMP® Pro Version 15.0.0 software (SAS Institute Inc., Cary, NC, 1989–2021). For frequencies below 5%, chi2 or Fischer tests were performed. In all cases, significant statistical threshold was set at p-values considered to be less than 0.05. A total of 1,227 pregnant women were recruited in five health facil-ities, including two in Dakar (n=166) and one in each of the following regional capitals: Saint-Louis (n=400), Ziguinchor (n=264) and Kédougou (n=397). The median age among was 25 years [18 - 50]. The overall sero-prevalence observed was 64.9% (797/1227), with higher exposure rates in Dakar with 71.6% (119/166) and Ziguinchor with 68.1% (180/264). Kédougou and Saint-Louis reported 62.9% (250/397) and 62% (248/400), respectively. According to age group, the seroprevalence was 62.6% (331/528), 66.6% (238/357), 63.5% (148/223) and 67.2% (80/119) respectively for [18-23], [24-29], [30-35] and ≥36 years old. This variability in the seroprevalence of SARS-CoV-2 according to the localities was not statistically significant (p=0.7024). We found no association between factors such as recruitment period, age, level of education, marital and pro-fessional status.

SARS-CoV-2 is severe acute respiratory syndrome coronavirus 2 which induces severe pneumonia that has considerable death rate. In this article, we summarised the evolution of SARS CoV-2 from alpha to omicron variant. The origin, transmission capability, and innate immunity potential of the Omicron variety remain unknown in the aftermath of its appearance. It's also unclear whether further varieties based on Omicron may emerge in the future. However, there is no question that the Omicron version of SARS-CoV-2 would not be the last. The COVID-19 pandemic has become more difficult to control due to the constant appearance of new SARS-CoV-2 mutations. We have discussed about the epidemiology, treatment plans for SARS CoV-2 and preventive strategies for future pandemic.

The pandemic history of pathogenic SARS-CoV-2 associated COVID-19 infection began in December 2019, with its emergence in Wuhan, China. Pertaining to its high transmissibility and wide host adaptability, this new and unique human coronavirus spread across the planet affecting almost every country, inflicting 91 million people and causing 1.9 million deaths (as of January 17th, 2021). Limited or negligible pre-existing immunity to multiple SARS-CoV-2 variants has resulted in severe morbidity and mortality worldwide, as well as a record-breaking surge in the use of medical-surgical supplies and personal protective equipments. In response to the global need for effective sterilization techniques, this study evaluated the virucidal efficacy of FATHHOME’s self-contained, ozone-based dry-sanitizing device, by dose and time response assessment. We tested inactivation of human coronavirus, HCoV-OC43, a close genetic model of SARS-CoV-2, on porous (N95 filtering facepiece respirator/FFR) and nonporous (glass) surfaces. We started our assays with 20 ppm of ozone for 10 min exposure, which was able to effectively reduce, 99.8% and 99.9% of virus from glass and N95 FFR surfaces, respectively. Importantly, the virus was completely inactivated, below the detection limit (over 6-log10 reduction) with 25 ppm ozone for 15 mins on both tested surfaces. As expected, a higher ozone concentration (50 ppm) resulted in faster inactivation of HCoV-OC43 with 100% inactivation in 10 mins from both the surfaces, with no residual ozone present after completion of the 5-minute post exposure recapture cycle and no measurable increase in ambient ozone levels. These results confirmed that FATHHOME’s device may provide a safe and viable solution for rapid decontamination of SARS-CoV-2- from worn items, frequently touched items, and PPE including N95 FFRs, face shields and other personal items.

The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from GISAID database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14,408C>T and 23,403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p<0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group. The 3,037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group. We concluded that RdRp P323L and spike protein D614G mutations predominate in severely affected COVID-19 patients. Further studies will be required to explore whether these mutations have any impact on the severity of COVID-19.

Abstract: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) and B-cell lymphoma 2 (Bcl-2) expression were evaluated in the normal human endometrium and myometrium. DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the proliferative, secretory, and atrophic endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle. The endometrium showed significantly higher DFF40 and DFF45 expression than that in the uterine myometrium; compared to the stroma, endometrial glands showed the highest expression in pre- and postmenopausal specimens. Glandular expression of DFF45 was dependent on the menstrual cycle, reaching its highest level in the secretory endometrium. The glandular expression of DFF40 and DFF45 was significantly lower in postmenopausal specimens than that in premenopausal tissue. No cycle-dependent changes were reported for stromal or myometrial DFF40 or DFF45 expression. Compared to the endometrial stroma and myometrium, Bcl-2 showed the highest expression in the glandular proliferative endometrium and the lowest expression in the stromal secretory endometrium and myometrium during the secretory phase of the cycle. DFF45 and Bcl-2 showed menstrual cycle-dependent expression, which was limited to the glandular layer of the endometrium.

Benzo[a]pyrene (B[a]P), is a family member of polycyclic aromatic hydrocarbons and a widespread environmental pollutant and neurotoxicant that contribute to the development of cancer. Microtubules are polymers of tubulin that form part of the cytoskeleton and target for anticancer drugs. Furthermore, NPY significantly increased the percentage of cells in S and G2/M phases. However, little is known about the specific role of NPY in proliferation and the underlying protective mechanism remains unclear. Hence, the aim of this work was to investigate the effect of B[a]P on SH-SY5Y neuroblastoma cells and to explore the potential mechanism for alteration of tubulin-microtubule equilibrium causing mitotic arrest and NPY expression. The present findings showed B[a]P treatment significantly increase number of SH-SY5Y cells in S and G2/M phase as compared to G1 phase and provokes cell cycle arrest that correlated with significant decrease in G0/G1 cells. Immunofluorescence study showed significantly distorted tubulin arrangement from metaphasic plate in formation of bipolar mitotic spindle apparatus. Further, higher doses of B[a]P treatment lead to chromosomal abnormalities accompanied by DNA damage due ROS causing oxidative stress showing significant decrease in tubulin protein around spindle. The results of present study demonstrated that NPY exerts a proliferative and protective effect on B[a]P-induced oxidative stress in a dose-dependent manner in vitro and importantly, these effects may be mediated via mitotic arrest and involved in spindle arrangement during cell division. Our findings addresses a novel pathological outcomes of B[a]P-induced NPY expression by oxidative stress through spindle abnormalities leading to microtubule disruption.

The development of effective vaccines against SARS-CoV-2 remains a critical challenge amidst the ongoing global pandemic. This study introduces a novel approach to enhance mRNA vaccine efficacy by leveraging the untranslated region (UTR) of TMSB10, a gene identified for its significant mRNA abundance in antigen-presenting cells. Utilizing the GEO database, we identified TMSB10 among nine genes with the highest mRNA abundance in dendritic cell subtypes. Subsequent experiments revealed that TMSB10's UTR significantly enhances the expression of a reporter gene in both antigen-presenting and 293T cells, surpassing other candidates and a previously optimized natural UTR. Comparative analysis demonstrated that TMSB10 UTR not only facilitated higher reporter gene expression in vitro but also showed marked superiority in vivo, leading to enhanced specific humoral and cellular immune responses against the SARS-CoV-2 Delta variant RBD antigen. Specifically, vaccines incorporating TMSB10 UTR induced significantly higher levels of specific IgG antibodies and promoted a robust T-cell immune response, characterized by increased secretion of IFN-γ and IL-4 and the proliferation of CD4+ and CD8+ T cells. These findings underscore the potential of TMSB10 UTR as a strategic component in mRNA vaccine design, offering a promising avenue to bolster vaccine-induced immunity against SARS-CoV-2 and potentially other pathogens.

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2’-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino acid residues from the hypervariable E region of the capsid in the cultured viruses provided no support for the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6 µM, TI 21; 2CMC EC50, 2.7-5.3 µM, TI >18; NITD-008, 0.5 to 0.9 µM, TI >111. Investigation of these antivirals for treatment of FCV-VSD is warranted.

SARS-CoV-2 is a novel and highly pathogenic coronavirus, which was first diagnosed in Wuhan city, China, in 2019, and spread to 185 countries and territories, and as of April 29, 2020, more than 3.11 million cases were recorded, and more than 217,000 people were killed. Despite all worldwide efforts, there is currently no vaccine, any drugs available to protect people against deadly SARS-CoV-2 coronavirus. The world urgently needs a SARS-CoV-2 coronavirus vaccine or effective antiviral drugs to relieve the human suffering associated with the pandemic that kills thousands of people every day. The SARS-CoV-2 genome encode a non-structural proteins named as ORF1a/b, and structural proteins such as spike (S) glycoprotein, nucleocapsid protein (N), small envelop protein (E) and matrix protein (M). A number of studies have been shown that CoV spike (S) glycoprotein and nucleocapsid protein (N) could be promising targets for vaccine, antibodies and therapeutic drug development to combat with deadly, pandemic SARS-CoV-2. Purposes of the present paper is the sequence analysis and amino acid variations of structural proteins deduced from novel coronavirus SARS-CoV-2 strains, isolated in different countries. Multiple sequence alignment of S, N and E proteins from four different coronavirus species, are also described. It is expected that the data from these studies will be very useful for the the designing and development of vaccines, antibodies and therapeutic agents that can be used to combat with the highly pathogenic SARS-CoV-2 coronavirus worldwide.

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL^-1 s^-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

Seven human coronaviruses (hCoVs) are known to infect humans. The most recent one, SARS-CoV-2, was isolated and identified in January 2020 from a patient presenting with severe respiratory illness in Wuhan, China. Even though viral coinfections have the potential to influence the resultant disease pattern in the host, very few studies have looked at the disease outcomes in patients infected with both HIV and hCoVs. Groups are now reporting that even though HIV-positive patients can be infected with hCoVs, the likelihood of developing severe CoV-related diseases in these patients is often similar to what is seen in the general population. This review aimed to summarize the current knowledge of coinfections reported for HIV and hCoVs. Moreover, based on the available data, this review aimed to theorize why HIV-positive patients do not frequently develop severe CoV-related diseases.

The outbreak of a novel coronavirus (SARS-CoV2) associated with acute respiratory disease called COVID-19 marked the introduction of the third spillover of an animal CoV to humans in the last 2 decades. The SARS-CoV2 genome analysis with various bioinformatics tools revealed that it belongs to beta CoVs genera, with highly similar genome as bat coronavirus and receptor binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS-CoV2 is likely to be originated from bat derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further spike protein S1/S2 cleavage site of SARS-CoV2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer. In the current review, we recapitulate a preliminary opinion about the disease, origin and life cycle of SARS-CoV2, roles of virus proteins in pathogenesis, commonalities and differences between different corona viruses. We have also highlighted the evidences regarding the potential drugs and vaccine candidates with their modes of action to cope with this viral outbreak. Our review provides comprehensive up-dated information on molecular aspects of the SARS-CoV2.

Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alter-ations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospi-talized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19 negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chro-matography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites al-tered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid seg-regated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify po-tential biomarkers for the diagnosis and prognosis of the disease.

Transferrin (TF) is a key iron carrier protein. Studies in human cohorts and in cultured adipocytes suggested that decreased transferrin expression and intracellular iron in adipocytes leads to impaired insulin responsiveness and causes differential expression of genes involved in metabolism, insulin action, and obesity. While suggestive, these studies did not definitively prove in an intact organism that altering TF expression in adipocytes is sufficient to affect glucose homeostasis and insulin resistance. In this study we created a mouse model of decreased transferrin expression only in adipocytes (Trf+/-Cre+/-) to test the hypothesis that iron trafficking in adipose tissue is sufficient to affect insulin sensitivity. Area under the glucose curve (AUCg) after intraperitoneal glucose administration was increased in the Trf+/-Cre+/- mice compared to wild type (WT) mice on a normal chow diet, and the mice were slightly heavier (p=0.02 for both). Homeostasis Model of Insulin Resistance (HOMA-IR) values were also significantly higher in the Trf+/- Cre+/- mice (p<0.05). Thus, supporting our hypothesis, analysis of mice with decreased expression of TF restricted to adipocytes showed that a decrease in adipocyte TF is sufficient to affect insulin resistance, weight, and glucose homeostasis.

Little is understood about the impact of nebulisation on the viability of SARS-CoV-2. In this study, a range of nebulisers with differing methods of aerosol generation were evaluated to determine SARS-CoV-2 viability following aerosolisation. The aerosol particle size distribution was assessed using an aerosol particle sizer (APS) and SARS-CoV-2 viability was determined after collection into liquid media using All-Glass Impingers (AGI). Viable particles of SARS-CoV-2 were further characterised using the Collison 6-jet nebuliser in conjunction with novel sample techniques in an Andersen size-fractioning sampler to predict lung deposition profiles. Results demonstrate that all the tested nebulisers can generate stable, polydisperse aerosols (Geometric standard deviation (GSD) circa 1.8) in the respirable range (1.2 to 2.2µm). Viable fractions (PFU/particle, the virus viability as a function of total particles produced) were circa 5x10^-3 and were not significantly affected by relative humidity. The novel Andersen sample collection methods successfully captured viable virus particles across all sizes; with most particle sizes below 3.3µm. MMADs (Mass Median Aerodynamic Diameters) were calculated from linear regression of log10-log10 transformed cumulative PFU data, and calculated MMADs accorded well with APS measurements and did not differ across collection method types. This data will be vital in informing animal aerosol challenge models, and infection prevention and control policies.

Background: Overcrowded housing, as well as inadequate sanitary conditions, contribute to making homeless people particularly vulnerable to the SARS-CoV-2 infection. We aimed to assess the seroprevalence of the SARS-CoV-2 infection among people experiencing homelessness on a large city-wide scale in France, taking into account different community settings. Methods: A consortium of outreach teams in 48 different locations including streets, slums, squats, emergency or transitional shelters and drop-in centres participated in the inclusion process. All participants consented to receive a validated rapid assay for immunoglobulins M (IgM) and G (IgG) antibodies and to answer a questionnaire on medical health conditions, comorbidities, historic of symptoms compatible with COVID-19, with a retrospective calendar of types of accommodation since COVID-19 crisis. Results: From June 01 to August 05, 2020, 1,156 homeless participants were enrolled in the study and tested. Seroprevalence of SARS-CoV-2 IgG/IgM antibodies was 5.6% (95%CI 2.3–7.0), with a range of 2.2% in people living on the streets to 8.1% in people living in emergency shelters (P=0.009). Around one third of the seropositive participants reported symptoms with COVID-19. Compared to the general population in Marseille (3.6%), the homeless population living in the same urban area experienced an significant increased risk of SARS-CoV-2 infection (|z|=3.65 > 1.96). Conclusion: These results highlight the need for organizing regular screening to prevent clusters forming in homeless accommodations and for providing basic resources for health maintenance.

Three patients with severe life-threatening COVID-19 who failed to achieve substantial improvement on tocilizumab, received pulse therapy with corticosteroids (methylprednisolone, 1000 mg/day IV for three consecutive days) and intravenous immunoglobulin (20 g/day IV). This was associated with a prompt resolution of respiratory failure, elimination of cytokine release syndrome, and reversal of pulmonary CT changes. The treatment was generally safe and well tolerated. There was no evidence of protracted persistence of the virus in the patients who received pulse therapy. Randomized controlled trials are necessary to specify the efficacy and safety of high-dose methylprednisolone and intravenous immunoglobulin in the treatment of severe life-threatening COVID-19 separately or in combination.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

Vaccination is the most promising approach for ending or containing the SARS-CoV2 pandemic. However, serious post-COVID vaccine reactions including immunocytopenia (ITP) syndrome has been increasingly reported. Several factors cause increased risks including multiple doses, age-dependent heterogeneity in immune-responses, platelet cross-reactions with microbial components, and Long-COVID syndrome. Thus, in the absence of a widely available specific therapeutics, vigilance is important while more studies are imperative. Using a structured questionnaire sent to different regions in Saudi Arabia, we conducted a comprehensive investigation on the frequency, rates, disease patterns, and patient demographics of post-COVID-19 side effects on febrile patients after three major vaccines. Results indicated the majority administered Pfizer BioNtech vaccine (81%, n=809); followed by AstraZeneca (16%, n=155); and Moderna (3%, n=34). In overall 998 participants, 74% (n=737) had no serious symptoms; however, 26.2% (n=261) revealed typical syndrome. In a focused group of 722, shortness of breath (20%), bruises or bleeding (18%), inattention (18%), GIT symptoms (17.6%), skin irritation (8.6%), and anosmia and ageusia (8%) were the most prominent. The onset time was mostly in 1-3 days in 49% (n=128), followed by 4-7 days in 21.8% (n=57), 8-14 days in 16.5% (n=43), and more than a month in 12.6% (n=33). The onsets occurred mostly after the first, second, or both doses 9%, 10%, and 7%, respectively. The frequency of symptoms was significantly higher among after Moderna ® vaccine (P-value = 0.00006) and it was significantly lower in participants who received Pfizer (P-value 0.00231). We did not find significant difference in symptoms related to differences in regions. Similarly, the region, age, gender, education, and nationality had no influence in the dose and onset timings. The findings of this study have significant clinical implications in disease management strategies, preventive measures, and vaccine development. Future vertical studies would reveal more insights into the mechanisms of post-COVID vaccine syndrome.

As the coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses. The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.

The probiotic bacterial strain Lactobacillus plantarum ZS2058 has been proved to manifest comprehensive functions, which were due to ability to synthesise conjugated fatty acids (CFAs). To investigate the specific functions of CFAs produced by this probiotic bacterium, α-linolenic acid was isomerized by Lactobacillus plantarum strain ZS2058, and two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated lipid peroxidation was related to the antiproliferation activity of CLNAs. Examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. And no sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first report showing the ability of CLNAs to activate antioxidant defenses resulting in pyroptosis.

The dynamical equations of the susceptible-infected-recovered/removed (SIR) epidemics model play an important role to predict and/or analyze the temporal evolution of epidemics outbreaks. Crucial input quantities are the time-dependent infection ($a(t)$) and recovery ($\mu (t)$) rates regulating the transitions between the compartments $S\to I$ and $I\to R$, respectively. Accurate analytical approximations for the temporal dependence of the rate of new infections $\dot{J}(t)=a(t)S(t)I(t)$ and the corresponding cumulative fraction of new infections $J(t)=J(t_0)+\int_{t_0}^tdx\dot{J}(x)$ are available in the literature for either stationary infection and recovery rates and for a stationary value of the ratio $k(t)=\mu (t)/a(t)$. Here a new and original accurate analytical approximation is derived for general, arbitrary and different temporal dependencies of the infection and recovery rates which is valid for not too late times after the start of the infection when the cumulative fraction $J(t)\ll 1$ is much less than unity. The comparison of the analytical approximation with the exact numerical solution of the SIR-equations for different illustrative examples proves the accuracy of the analytical approach.

The Coronavirus disease-19 (COVID-19) pandemic dramatically impacted on oncologic patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated also for oncologic population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy de-livery were not available. We aimed to evaluate potential factors influencing the outcome of COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing COVID-19 vaccination with gas-tro-entero-pancreatic and neuroendocrine neoplasms, treated at our Institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection 86.9% received two-doses of Pfizer-BioNTech and the remains Moderna vaccine. All patients obtained a subsequent im-mune-response. A significantly lower values of IgG for patients treated with chemotherapy versus other anti-cancer agents (p=0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs >7 days from the last systemic treatment (p=0.77) and lymphocytes count (p=0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue but rather the quality of the subset of lymphocytes before the vaccination to deter-mine the efficacy level of immune-response in this population.

Objective: The objective of the present study was to evaluate the activities of daily living using the Barthel Index, before and after the infection by SARS-COV-2 and to see if the results vary according to sex. Methods: The activities of daily living of 68 cohabiting geriatric patients, 34 men and 34 women, in 2 nursing homes were measured before and after SARS-COV-2 infection using the Barthel index. Results: The Covid 19 infection affects the performance of daily life activities in institutionalized elderly in nursing homes, and it does so especially the older the subject, regardless of sex. Conclusions: The Covid 19 pandemic, in addition to having claimed some victims, especially in the elderly population, has reduced the ability of these people to carry out their activities of daily life, considerably worsening their quality of life despite have been able to overcome the disease.

: During the period of COVID-19, the Chinese government implemented a series of actions to prevent the spread of the virus. It is noticed that these preventive actions have generated positive effects on air pollution in Wuhan and Beijing. And, due to the differences in city functions, geographic locations, meteorological conditions, and preventive action details between the two cities, noticeable difference is observed on how they reduced air pollution. This unfortunate incident has become a social sample for studying the industrial and livelihood activities impact on air pollution, otherwise would be highly impossible. This paper starts from observing data from NASA's real-time fine particulate matter (PM2.5) and NO2, and comparing the air pollution in this special time domain with previous years. It is discovered that both PM2.5 and NO2 have been reduced in Wuhan, while only NO2 has significant reduction in Beijing, during the COVID-19 responses. This suggests that the human activity suppression by the COVID-19 control yields different effects on different pollutants and in different cities. Possible reasons for such effects are analysed by considering the public health control levels as well as the pollutant migration, industrial activities, and the weather conditions.

Novel SARS-CoV-2, a bat based virus originated in Wuhan, China that caused a global pandemic in December, 2019 belongs to the Betacorona virus family and contains single stranded genome of ~29Kbp. The host cell invasion of SARS-CoV-2 is facilitated by interaction of C-Terminal Domain (CTD) of Spike (S) protein of virus and host ACE2 receptor in the presence of TMPRSS seine protease secreted by the host cell. In this study the mutation hotspots of S-protein will be identified and the impact of such mutation in the binding affinity will be studied. Additionally, the lead molecule which can bind to the mutated protein also will be identified. Multiple sequence alignment of the spike protein sequence of SARS-CoV-2 shows the number of single amino acid mutation hotspots such as L5F, R214L, R408I, G476S, V483A, H519Q, A520S, T572I, D614G and H655Y. Among these mutations D614G has 57.5% occurrence and G476S, V483A has 7.5% occurrence. The mutated proteins were modelled based on wild type homolog and docked to ACE2 receptor. When the mutated S protein is docked, the ∆G (binding free energy) value is very minimal in mutated protein showed the stability of variants. By the drug repurposing method, 1000 FDA approved drugs were virtually screened for its binding to RBD of S1 domain. Among these drugs Digitoxin, Gliquidone and Zorubicin Hcl binds to spike proteins with higher docking score (lesser than -8.5 Kcal/mol) to both wild type and mutants.

The synthesis, anticancer and antioxidant activity of a series of indole-derived hybrid chalcones are reported here. First, using well known Claisen-Schmidt condensation method a set of 29 chalcones has been designed, synthesized, and consequently characterized. Subsequently, screening for the antiproliferative activity of the synthesized hybrid chalcones was performed on the on five cancer (HCT116, HeLa, Jurkat, MDA-MB-231 and MCF7) and two non-cancer (MCF-10A and Bj-5ta) cell lines. Chalcone 18c bearing 1-methoxyindole and catechol structural features, exhibited selective activity against cancer cell lines with IC50 values of 8.0 ± 1.4 µM (Jurkat) and 18.2 ± 2.9 µM (HCT116) and showed no toxicity to non-cancer cells. Furthermore, antioxidant activity was evaluated using tree different methods. The in vitro studies of radical scavenging activity utilizing DPPH radicals, as well as FRAP method, demonstrated the strong activity of catechol derivatives 18a-c. According to the ABTS radical scavenging assay, the 3-methoxy-4-hydroxy substituted chalcones 19a–c were slightly more favorable. In general, a series of 3,4-dihydroxychalcone derivatives showed properties as a lead compound for both antioxidant and anticancer activity.

Abstract: RNase Y is an endoribonuclease that governs global mRNA turnover/processing in Ba-cillus subtilis and likely many other bacteria. The enzyme is anchored at the cell membrane, a pseudo-compartmentalization that appears coherent with its task to initiate decay of mRNAs translated predominantly at the cell periphery. However, the reason and consequence for RNase Y attachment to the membrane are largely unknown. We have studied a strain expressing wild-type levels of a cytoplasmic form of RNase Y from the chromosomal locus. This strain exhibits a slow growth phenotype similar to an RNase Y null mutant. Genome-wide data show a significant effect on the expression of hundreds of genes. Certain RNA substrates clearly require RNase Y membrane attachment but others do not. We found no correlation between mRNA stabilization and the cellular location or function of encoded proteins. The Y-complex, an RNase Y specificity factor, appears to also recognize the cytoplasmic form of the enzyme which is able to restore wild-type levels of the corresponding transcripts. We propose that membrane attachment of RNase Y is required for the functional interaction with many coding and non-coding RNAs, for limiting the cleavage of certain substrates and potentially to avoid unfavorable competition between RNase Y and other ribonucleases like RNase J that have a similar evolutionarily conserved cleavage speci-ficity.

As of 26 March 2020, Pakistan had 1179 cases of COVID-19, with most 421 cases from Sindh, 394 cases, 131 cases, 123 cases, 84 cases, 25 cases and 01 cases from Punjab, Balochistan, Khyber Pakhtunkhwa, Gilgit-Baltistan, Islamabad Capital Territory, and Azad Jammu and Kashmir respectively. Travel-related cases were the main source of SARS-CoV-2 infection during the early phase of the pandemic in Pakistan. Nevertheless, cases of local virus transmission are increasing day by day. As of 26 March 2020, nine deaths have been reported from COVID-19. The case fatality rate is 0.8%, which is less compare to China, Italy, USA, and Iran. The SIR (Susceptible-Infected-Recovered) model of epidemiological analysis predicts that almost 90 million population will be infected in the coming days with 5% critical cases that need health care facilities. However, the Pakistan health care system cannot provide services to this much population. Hence, we need to act timely to reduce this number by restricting local transmission of the disease. This can be done by mass testing, quarantine, isolation and social distancing of the active coronavirus cases in Pakistan. Moreover, better communication between the authorities is very much required to control disease transmission.

Following the WHO's declaration of a public health emergency due to the COVID-19 outbreak, the subsequent quarantine and confinement measures that were adopted, including distance learning measures, were shown to have caused a significant deterioration in the mental health of medical students. The goal of this study was to explore the mediating role of resilience and life satisfac-tion in the relationship between perceived stress and burnout among medical students in the con-text of COVID-19. A transversal assessment was performed using an online questionnaire, to which 462 students responded. The instruments applied were the Perceived Stress Scale-10, the Resilience Scale-25 items, the Satisfaction with Life Scale (SWLS) and the Burnout Scale (Olden-burg Inventory). A regression model was estimated for each dimension of burnout. The results revealed that resilience and life satisfaction play a mediating role in the association between stress and the dimensions of burnout. This suggests that measures of promoting mental health based on resilience and improving perceptions of life should be implemented.

In dentistry, maxillofacial surgery, traumatology, and orthopedics, there is a need to use osteoplastic materials that have not only osteoinductive and osteoconductive properties but are also convenient for use. In the study, compositions based on collagen hydrogel were developed. Polylactide granules (PLA) or a traditional bone graft, a mixture of hydroxyapatite and β-tricalcium phosphate (HAP/β-TCP), were used for gel filling to improve mechanical osteoconductive properties of compositions. The mechanical tests showed that collagen hydrogels filled with 12 wt% highly porous PLA granules (elastic modulus 373 ± 55 kPa) or 35 wt% HAP/β-TCP granules (elastic modulus 451 ± 32 kPa) had optimal manipulative properties. All composite components were cytocompatible. The cell’s viability was above 90%, and the components’ structure facilitated the cell’s surface adhesion. The bone morphogenetic protein-2 (BMP-2) provided osteoinductive composition properties. It was impregnated directly into the collagen hydrogel with the addition of fibronectin or inside porous PLA granules. The implantation of a collagen hydrogel with BMP-2 and PLA granules into a critical-size calvarial defect in rats led to the formation of the most significant volume of bone tissue: 61 ± 15%. It was almost 2.5 times more than in the groups where a collagen-fibronectin hydrogel with a mixture of HAP/β-TCP (25 ± 7%) or a fibronectin-free composition with porous PLA granules impregnated with BMP-2 (23 ± 8%) were used. Subcutaneous implantation of the compositions also showed their high biocompatibility and osteogenic potential in the absence of a bone environment. Thus, the collagen-fibronectin hydrogel with BMP-2 and PLA granules has optimal biocompatibility, osteogenic, and manipulative properties.

We reviewed the association between seasonal influenza vaccination and the risk of SARS-CoV-2 infection or complicated illness or poor outcome (e.g. severe disease, need for hospitalization or ventilatory support, or death) among COVID-19 patients. None of the studies that were reviewed (n=12) found a significant increase in the risk of infection or in the illness severity or lethality, while some reported significantly inverse associations. Our findings support measures aimed at raising influenza vaccination coverage in the coming months.

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants are dominating. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs. Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies. Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro by protein chemical methods, mass-spectrometry, circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study specific antibody and cytokine responses, safety and Omicron neutralization. Results: Defined and pure immunogens could be produced in large amounts as secreted and folded proteins in mammalian cells. Antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG levels induced by the different vaccines were comparable but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were 7- and 2-fold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively and 6-fold higher than those of the bivalent vaccine. Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.

Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs

The emergence of COVID-19 has prompted an unprecedented scientic publication with the aim of better understanding this new disease. This study assessed the scientic impact and disciplinary priorities of the published papers on the pandemic by comparing epidemiological (EP) and social sciences (SS) research interests. Papers were identified via keywords searching using Google Scholar and Scopus databases. From an initial 1720 papers, we identified 597 relevant articles, of which 347 were for EP researches and 250 for SS studies. We extracted information, such as authors' countries, and research thematic related to EP and SS. The results revealed that most papers were authored by Asian (37.5%), European (30.5%) and American (19.6%) scientists. Only 10.1% and 2.3% of authors were aliated with African and Oceanian institutions, respectively, indicating that the regions most affected by the pandemic mainly contributed to the scientic publications. In total, 26 research themes were recorded from both EP and SS studies. There was a high signicant dierence among themes in both research fields (Chi-square = 1204.3, df = 1, p-value < 0.001). EP papers mostly dealt with clinical trials (54.5%) and diagnosis (53.3%). These papers assessed the incidence and epidemiological characteristics of the disease (incubation period, symptomatic period, recovering or death), testing tests developed, drugs and vaccines used. SS papers were mainly concerned with the sociocultural analyses (78%) and economic impact (55.6%) of the pandemic. They mainly focused on behavioral changes induced by the pandemic and strategies developed to mitigate its impacts. This study highlights the difference between regions and gaps between scientific disciplines concerning the proposed responses to control the pandemic. It is important to promote collaborative and interdisciplinary studies for health emergencies.

Background: The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F ; mean ageSD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169+ monocytes, conventional CD1c+ and CD141+ (namely cDC2 and cDC1), and plasmacytoid CD303+ DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p

The abundant mechanical vibration energy in bridge road environment can be converted into electric energy by using the piezoelectric energy harvest technology, which could be an efficient way to provide energy required by the wireless sensor network in the bridge condition monitoring system. An autonomous energy harvesting system has been designed based on cantilever beams for sensing and acquiring the bridge vibration energy. After the analysis of the dynamic properties of the piezoelectric cantilever beam in the energy conversion, three kinds of interface circuits were compared through simulation and experimental results. It was shown that the VD interface circuit has less power loss. Furthermore, the proposed closed loop control method based on the VD circuit was simple, adaptive, and self-powered, which is suitable for the road energy harvesting application. Finally, the energy harvesting system based on VD circuit was realized with harvested power of around 0.8mW.

This study explores the synthesis and application of BODIPY-functionalized gold nanoparticles (AuNPs) for the sensitive detection of biothiols via an indicator displacement assay coupled with Surface-Enhanced Raman Scattering (SERS) techniques, alongside their efficacy for in vitro cancer cell imaging. Moreover, the assay allowed a visible colorimetric detection of biothiols under normal and ultraviolet light conditions. The BODIPY (boron-dipyrromethene) fluorophores were strategically conjugated to the surface of gold nanoparticles, forming a robust nanohybrid that leverages the plasmonic properties of AuNPs for enhanced spectroscopic sensitivity. The detection mechanism exploits the displacement of the BODIPY indicator upon interaction with biothiols, triggering a measurable change in fluorescence and SERS signals. This dual-mode sensing approach provides high selectivity and sensitivity for biothiol detection, with detection limits reaching nanomolar concentrations using fluorescence and femtomolar concentration for cysteine using SERS. Furthermore, the BODIPY-AuNP complexes demonstrated excellent biocompatibility and photostability, facilitating their use in fluorescence imaging of biothiol distribution within cellular environments and highlighting their potential for diagnostic and therapeutic applications in biomedical research.

Several methods can be used to evaluate antibody avidity, one of which is the modified ELISA, in which a chaotropic agent is added to disrupt the binding between the antigen and the antibody. Although the avidity index provides relevant information about the functionality of antibodies, it does not allow us to characterize which antigens the antibodies are strongly bound to. To this end, we adapted the Immunoblot and Dot-Blot techniques by adding potassium thiocyanate (KSCN) after incubating nitrocellulose membranes with serum from mice immunized with Neisseria meningitidis outer membrane vesicles (OMVs) or serum from mice immunized with recombinant receptor-binding domain (RBD) of SARS-CoV-2, with different adjuvants for each antigen. In terms of results, when standardizing the incubation time of sera with KSCN, we observed that 5 minutes was the ideal time for both assays, however, when using different dilutions of serum from mice immunized with RBD, there was an influence on the strength of antigen-antibody binding. For the N. meningitidis assay, the antibodies maintained high avidity for the antigens present in the OMVs, PorA, NadA, and Opa, especially in the presence of the aluminum hydroxide adjuvant. The research showed that standardizing the Immunoblot and Dot-Blot in the same assay optimizes time and resources, allowing qualitative analysis for two different antigens, and resulting in more robust information for immunization studies against these pathogens.

Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs 3 days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4+-, and Treg CD8+-producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host’s capacity to deal with infection.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

Abstract The COVID-19 pandemic has tremendously affected the African continent and the rest of the world. Most businesses have closed and a lot of people have lost their jobs. The aviation industry has been shaken to the core with airlines losing millions of dollars and flights being cancelled. The tourism industry has consequently been affected due to restricted travel of tourists, impacting wildlife conservation and livelihoods. Schools, colleges and universities have been closed. The virus has infected millions of people and hundreds of thousands of people have died globally putting strain on health systems especially those of hard hit countries. Various countries all over the world have put measures to control the spread of the virus through lockdowns and social distancing policies. The reduced economic activities and mobility of people has resulted in improved air quality, cleaner water and beaches in some countries. However there are also negative impacts such as challenges in waste management, increased pharmaceutical and household waste and discovery of the corona virus in wastewater, a potential threat to public health. A considerable amount of research has been done on the socio-economic impacts of COVID-19 in Africa but there is still limited research on its impact on the environment. This paper serves to highlight the observed and potential environmental impacts of COVID-19 in Africa.

Recent advancements in communication technology have catalyzed the widespread adoption of realistic content, with augmented reality (AR) emerging as a pivotal tool for seamlessly inte-grating virtual elements into real-world environments. In construction, architecture, and urban design, the integration of mixed reality (MR) technology enables rapid interior spatial mapping, providing clients with immersive experiences to envision their desires. The rapid advancement of MR devices, or devices that integrate MR capabilities, offers users numerous opportunities for enhanced entertainment experiences. However, to support designers at a high level of expertise, it is crucial to ensure the accuracy and reliability of the data provided by these devices. This study explores the potential of utilizing spatial mapping within various methodologies for surveying architectural interiors. The objective is to identify optimized spatial mapping procedures and determine the most effective applications for their use. Experiments were conducted to evaluate the interior survey performance, using HoloLens 2, iPhone 13 Pro for spatial mapping, and photogrammetry. The findings indicate that HoloLens 2 is most well-suited for the tasks exam-ined in the scope of experiments. Nonetheless, based on the acquired parameters, the author also proposes approaches to apply the other technologies in specific real-world scenarios.

The anti-inflammatory effect of ginsenoside Rh2 (GRh2) is one of the most important ginsenosides. The purpose of this study is to identify the anti-inflammatory and antioxidant effects of GRh2 after LPS challenge lung injury animal model. GRh2 reduced LPS-induced NO, TNF-α, IL-1, IL-4, IL-6 and IL-10 productions in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and BALF protein content and total cells number also diminished in LPS-induced lung injury mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1 and MEK protein expression which is corresponded to the growth of HO-1, Nrf-2, catalase, SOD and GPx expressions in LPS-induce lung injury. An experimental study has suggested that GRh2 has provided with anti-inflammatory effects in vivo, and its potential therapeutic efficacy in major anterior segment lung diseases.

During the current COVID-19 pandemic caused by SARS-CoV-2, clinicians and scientists are working assiduously to unravel its pathophysiology and find effective treatments. An impressive number of papers has been published on SARS-CoV-2, exposing the complexity of the disease, the tendency of scientists to form hypotheses within their area of expertise, and the lack of orchestration of research. Hypotheses and research findings mainly complement each other, though sometimes controversies can be discerned among various theories and study results. Our overview aims to portray the ‘big picture’ of COVID-19, visualising the interwovenness of different pathophysiological pathways, with a focus on cytokine-induced pathology, the sequelae of ACE2 downregulation, and thrombosis associated with microvascular injury. It aids in overseeing the effects of repurposed drugs on intended targets, but also alerts to the (adverse) effects on interacting pathways. The overview shows how comorbidities probably increase susceptibility to (severe) COVID-19 and provides the possible pathophysiological origin of signs, symptoms, and biochemical abnormalities.

Home Security Systems are very important features of modern residential and office setups. This system is used to keep home safe from harmful gases, fire and intruders. It must be affordable, reliable and effective. In this paper, a GSM based home security system has been designed and implemented. The system consists of a GSM Module, MQ-2 smoke detector, Ultrasonic sonar sensor, LM35 temperature sensor, Arduino Uno and relay module. The MQ-2 smoke detector is used to detect harmful gases i.e. LPG, CH₄, CO, Alcohol, Smoke or Propane. Any of the harmful gases stated above is detected it will warn the owner by activating the buzzer and displaying a warning message on the LCD display. It will also send a SMS to the owner. Our system can also measure temperate and if the temperature is increased above a certain range it will compensate it by activating Air Conditioner through the relay module. The system will also send a SMS to the owner. It can also detect intruders using Ultrasonic sensor and warn us through buzzer, SMS and displaying message on the LCD. Our system is reliable as it has very fast response and cost effective and it has been developed using our own technologies.

Facilitative glucose transporters (GLUT) are transmembrane transporter of proteins involved in glucose transport across the plasma membrane. To date, there is no information about glucose transporter 2 (GLUT2) in blunt snout bream (Megalobram aamblycephala). In this study, GLUT2 were cloned and characterized from blunt snout bream, and its-expression in response to diets with different carbohydrate levels (17.1%; 21.8%; 26.4%; 32.0%; 36.3% and 41.9% of dry matter). In this study, the full-length cDNA of GLUT2 was 2577 bp, including a 5’-untranslated region (UTR) of 73 bp, a 3’-UTR of 992 bp, and an open reading frame of 1512 bp, encoding a polypeptide of 503 amino acids with predicted molecular weight of 55.046 kDa and theoretical isoelectric point of 7.52. GLUT2 has twelve across the membrane area locating at 7-29; 71-93; 106-123; 133-155; 168-190; 195-217; 282-301; 316-338; 345-367; 377-399; 412-434; 438-460 aimo acids respectively. Conservative structure domains located at 12-477 aimo acids belonging to sugar porter family major facilitator superfamily (MFS) transporter. The blunt snout bream GLUT2 showed high identity to their orthologs in other fish species and mammals. Quantitative real-time (qRT)-PCR assays revealed that GLUT2 expression was high in the liver, intestine and kidney; highest in the liver. Compared with the control group (17.1%), high dietary carbohydrate levels (32.0%; 36.3% and 41.9%) resulted in high plasma glucose at 3h after feeding, but high plasma glucose were back to basal at 24h after feeding. Furthermore, high dietary carbohydrate levels significantly improved the glycolysis and inhibitied gluconeogenesis by augmentation of GK and PK expression, inhibition of PEPCK and G6P mRNA levels (P<0.05). However, GLUT2; GK; PK; PEPCK and G6P mRNA levels were back to basal.

Studies carried out have revealed that every day around three thousand and twelve people lose their lives in the world due to traffic accidents and poor air quality. Large cities, with their millions of inhabitants and vehicles, face many problems relating to vehicular traffic. In 2015 the speed limit was modified on several roads in the city of São Paulo-Brazil. However, in 2017 the speed limits were increased again, but not on all previous routes. This study analyzed the impact of this change on the number of accidents and pollutant concentrations, over a period of ten years, comparing the periods before and after the implementation of the measure, using real data collected and provided by the authorities of the city and the state transit and environmental companies, on more than forty routes and two nearby air quality stations. The results show a clear reduction in the number of accidents without victims on the roads of the city of São Paulo starting in 2010. However, the restrictive measures imposed by government officials may have contributed to the decrease in the number of accidents, but the number of fatalities has not changed much. Air pollution has not improved substantially with speed changes, as new speed increases have been linked to new episodes of congestion. The average number of fatalities due to accidents has been increasing since 2010 and accidents are becoming more serious. The application of a general linear statistical model (GLM) estimated the impact of the speed reduction policy in terms of the number of injuries avoided per month: 43.4 and 14.1 on other roads and on Pinheiros marginal, respectively. The results highlight the need for a constant data collection by the authorities in cities with high vehicle traffic. The important temporal time trend in terms of reduction of injuries but not in terms of fatalities and air quality, shows the need to apply joint public policies, not only speed reduction, but also the use of new technologies and raising drivers’ awareness of the problem.

Purpose of this article is to project from the point of view of the scientific data concerning PAF and as a new approach by involving PAF, in order to contribute to clarification and proposal a possible mechanism of action of the coronavirus SARS-CoV-2 and to give a possible explanation for its observed side effects-complications of Covid-19 disease. The article is not intended to suggest any specific drugs, but clarifying the mechanism is the first step in illuminating the direction of prescribing the targets of medication that may be appropriate for the prevention, treatment, and cure of Covid-19 disease. More specifically, the purpose of this article is to provide unequivocal evidence indicating that: 1 It would not be unexpected for PAFR to participate in the entry of coronavirus SARS-CoV-2 into the cell. 2 There is interdependence and relationship of the receptors ACER and PAFR, which means the involvement of PAF in the processes related to coronavirus SARS-CoV-2 as well as to its effects exercised by the coronavirus SARS-CoV-2. 3 The receptors ACER, PAFR and TLRs are also involved in inflammation as well as in virus binding to stabilize and enter into the cell, and so they are "communicating vessels" with PAF being " a missing link" 4 Consequently there is a correlations of COVID-19 disease manifestations and biological characteristics with those caused by PAF, which shows the involvement of PAF in COVID-19 disease.

Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that lead to the activation of ATMs. We will discuss more novel metabolic mechanisms that influence macrophage polarisation in other disease or tissues contexts that may be relevant to future work in insulin resistance and T2D.

The global pandemic of COVID-19 accounts for more than 14,000 deaths worldwide. However, little is known about the host genetics interaction with infection and COVID-19 progression. To better understand the role of host genetics, we review the current literature, aggregate readily available genetic resources, and provide some updated analysis relevant to COVID-19 and associated phenotypes. Using the unrelated individuals in UK Biobank (total n = 337,579 across 5 populations), we aggregate human leukocyte antigen and ABO blood type frequencies. We find significant and consistent risk reduction of blood group O reported in Zhao et al. and encourage broad sharing of ABO blood type frequencies that are readily accessible across COVID-19 with mild, moderate, and severe/critical symptoms for robust inferences at https://tinyurl.com/abo-covid19. In addition, we generate polygenic risk scores (PRSs) weights for 29 blood measurements, including clinically relevant haematological measurements for COVID-19, such as lymphocyte count and percentage. Focusing on the 8 most COVID-19 clinically relevant blood measurements, we performed PRS-PheWAS analysis across 44 disease antigen measurements (n = 6,643 unrelated individuals in White British group), infectious diseases and acute respiratory infections (n = 20,928 cases and 349,000 controls across 3 population groups) and deaths (n = 1,846 cases and 368,082 controls), recorded in hospital inpatient record and death registry data, respectively, in UK Biobank, and find host genetic PRS associations with disease risk. Taken together, we anticipate these resources (https://github.com/rivas-lab/covid19) will aid in improving our understanding of host genetic risk factors playing a role in SARS-CoV-2 infection and COVID-19 disease severity.

Silver ion (Ag+) are recognized for their potent antibacterial properties; however, their utilization in food preservation is restricted by factors such as inadequate stability, a transient antibacterial impact, and the potential for human absorption. Hydrogel-based antibacterial agents are capable of exerting their antibacterial effects by establishing appropriate microenvironments, which facilitate the efficient delivery of antimicrobial molecules to the contaminated regions of food. In previous studies, we observed that chitosan (CS) and silver nitrate (AgNO3) were able to reduce Ag+ to silver nanoparticles (AgNPs) with enhanced antibacterial properties. This not only significantly extended the stability of the antibacterial agent but also demonstrated exceptional inhibitory capabilities against pathogenic bacteria, including common grape contaminants such as P. expansum, A. niger, and B. cinerea. Utilizing ultrasound-induced complexation technology, this study has successfully synthesized a chitosan-silver (CS-AgNPs) hydrogel. The efficacy of this hydrogel against the pathogenic fungus responsible for jujube black spot disease has been thoroughly investigated. The morphology structures of CS-AgNPs hydrogels were characterized by TEM, FTIR and UV-vis. The results indicated that AgNPs ranging from 80 to 110 nm were uniformly dispersed within the gel matrix and remained stable for extended periods at room temperature. In vitro antibacterial assays and fractional inhibitory concentration index (FICI) studies revealed that the pronounced antibacterial efficacy of the CS-AgNPs hydrogel was primarily attributed to the additive antibacterial effect of CS and AgNPs. These insights underscore the significant potential of CS-AgNPs hydrogels in combating fungal diseases of jujube, offering innovative strategies and materials for the management of agricultural pathogens.

In this paper, the computational fluid dynamics (CFD) method has been used to simulate the gas flow and the catalytic hydrogenation process of the C-2 hydrogenation adiabatic reactor in a practical ethylene production unit of a chemical plant. The laminar finite-rate model was used for the chemical reaction model. The standard two-equation model was used for the turbulence model. The exponent-function kinetic model was used for the reaction dynamics model. The simulation results were in good agreement with the actual industrial data obtained from the C-2 hydrogenation reactor, and the distributions of reaction parameters such as temperature and component concentrations in the reactor were further analyzed. Based on the validated CFD models, the structure and operating conditions of the reactor, as well as hydrogen load distribution ratios, are simulated for comparing the comprehensive performance metrics of ethylene selectivity and acetylene conversion rate; as a result, we can obtain the optimal temperature of 312 K, the optimal hydrogen/acetylene ratio of 0.10 as well as the optimal hydrogen load distribution ratio of 4:4:2, and the diameter/height ratio exerts a marginal effect on the selectivity, conversion rate and harmonic mean of the reactor.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) linked with coronavirus disease 2019 (COVID-19) poses a serious threat to public health worldwide. Firstly, the SARS-CoV-2 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of SARS-CoV-2 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19 associated pneumonia, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of SARS-CoV-2 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.

The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. By our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD) is a pervasive public health concern, intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and metabolic dysfunction-associated fatty liver disease (MAFLD) is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among metabolic dysfunction-associated fatty liver disease (MAFLD) patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.

Since the beginning of 2020, tetracycline (TC), such as minocycline (MINO), has been used to inhibit coronavirus disease 2019 (COVID-19). Traditional Japanese Kampo medicine, such as Saiko-keishi-to (SKT), has recently received a lot of attention for its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects. We describe a COVID-19 patient treated with MINO and SKT in anticipation of their anti-SARS-CoV-2 properties. A 90-year-old male patient with Alzheimer’s disease was referred to a medical clinic due to fever, appetite loss, and general malaise. Based on positive SARS-CoV-2 rapid antigen tests, he was diagnosed with COVID-19. He did not have COVID-19 pneumonia, but he had difficulty in eating on his own. As a result, he was referred to a hospital for admission. After admission, he was treated with molnupiravir to avoid aggravation. Seven days after his admission, he was discharged. After his discharge, he was referred to our hospital as an outpatient due to a prolonged mild fever and general malaise. As a precaution, a real-time reverse transcription-polymerase chain reaction (RT-PCR) test was performed, which yielded a positive result. Therefore, the aforementioned symptoms were thought to be caused by prolonged COVID-19. He was treated with MINO and SKT due to the anti-viral properties of these two drugs. The RT-PCR test became negative 7 days after receiving this treatment, and the fever and general malaise subsided.

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable global disruption to clinical practice. This article will review the impact that the pandemic has had on oncology clinical trials. It will assess the effect of the COVID-19 situation on the initial presentation and investigation of patients with suspected cancer. It will also discuss the impact of the pandemic on the subsequent management of cancer patients and how clinical trial approval, recruitment and conduct were affected during the pandemic. An intriguing aspect of the pandemic is that clinical trials investigating treatments for COVID-19 and vaccinations against the causative virus, SARS-CoV-2, have been approved and conducted at unprecedented speed. In light of this, this re-view will also discuss the potential that this enhanced regulatory environment could have on the running of oncology clinical trials in the future.

Vision is our primary sense as the human eye is the gateway for more than 65% of information reaching the human brain. Today’s increased exposure to different wavelengths and intensities of light from Light Emitting Diodes (LEDs) sources could induce retinal degeneration and accompanying neuronal cell death. Damage induced by chronic phototoxic reactions occurring in the retina accumulates over years and it has been suggested to be responsible for the etiology of many debilitating ocular conditions. In this work, we examined how LED stimulation affects vision by monitoring changes in the expression of death and survival factors as well as microglial activation in LED-induced damage (LID) of the retinal tissue. We found an LED exposure-induced increase in the mRNA levels of major apoptosis-related markers -BAX, Bcl-2, and Caspase-3 and an accompanying wide-spread microglial and Caspase-3 activation. Everyday LED light exposure was accounted for all the described changes in the retinal tissue of mice in this study, indicating that overuse of non-filtered direct LED light can have detrimental effects on the human retina as well.

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective is to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1, 48 h or continuously with 10-7 M Nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell counting, migration by cell migration assay, senescence by SA-beta-Gal activity, and anchorage-independent growth by cloning in soft agar. Expression of Ki67, p53/phospho-p53, VEGF, EGFR/pEGFR, phospho-p38, intracellular Ca+2, ATP and EMT were evaluated by ELISA and/or western blotting. (3) Results: Nicotine induced through α7-nAChR (i) increase in cell viability (ii) cell proliferation; (iii) Ki67 over-expression, (iv) phospho-p38 up-regulation (v) EGFR/pEGFR over-expression; (vi) increase in basal Ca+2 concentration, (vii) reduction of ATP production; (viii) decreased level of p53/phospho-p53, (ix) delayed senescence, (x) VEGF increase, (xi) EMT and consequent (xii) enhanced migration, and (xiii) ability to grow independently of the substrate. (4) Conclusions: Based on our results and on evidence showing that Nicotine potentiates viral infection it is likely that Nicotine is involved in SARS-CoV-2 infection and severity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Twenty-eight and 23 microRNA also target the SARS-CoV and MERS-CoV, respectively. In addition, 48 and 32 microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as cellular defence mechanism against pathogenic coronavirus infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to cause 2019-coronavirus disease (COVID-19) pandemic is a zoonotic coronavirus and crosses species to infect human populations, where an efficient transmission of virus occurs human-to-human. Nationwide lockdown is being adopted to stop public transport, keep people at their homes and out of their work, and maintain social distancing. In turn, large geographic areas in the world (including China, Italy, Spain, and USA) has been almost halted. This temporary halt is significantly slashing down the air pollution (air pollutants and warming gases) in most cities across the world. This paper: (i) introduces both COVID-19 and air pollution; (ii) overviews the relation of air pollution with respiratory/lung diseases; (iii) compiles and highlights major data appeared in media and journals reporting lowering of air pollution in major cities those have been highly impacted by the COVID-19; and also (iv) lists the way forward in the present context. Because COVID-19 is an ongoing pandemic and currently far from over, strong conclusions could not be drawn with very limited data at present. The temporary slashed down global air pollution as a result of COVID-19 restrictions are expected to stimulate the researchers, policy makers and governments for the judicious use of resources; thereby minimise the global emissions, and maintain their economies once the pandemic eases. On the other, lifting of the nationwide lockdown and eventual normalisation of the temporarily halted sectors may also reverse the currently COVID-19 pandemic-led significantly slashed down global air pollution that could make the future respiratory health crisis grimmer.

Aim: To perform a descriptive analysis of eating patterns and biophysical conditions of previously diagnosed and currently under treatment individuals from a semi-urban Mayan community of Yucatan, and to contrast them with T2DM therapeutic guidelines. Methods: The present study is derived from a randomized clinical trial conducted at Komchen, Yucatan. Participants’ diagnosed with T2DM were included. A 24-hour dietary recall, anthropometric parameters (weight, visceral fat, height, and waist circumference), biochemical (HbA1c) and clinical (blood pressure) variables were evaluated and compared via hypothesis test with T2DM treatment cut-off points (based on World Health Organization criteria). Results: Anthropometric characteristics differ significantly from the ideal criteria. Obesity prevalence within women with T2DM was 92.9%. Only 21% of the participants were under T2DM control (≤7%). Energy and carbohydrates consumption, significantly exceed therapeutic guidelines, whereas protein, fat, and fiber intake were lower than the recommendations. Conclusions: Komchen’s diet, concomitantly with food characteristics, could be related to glycemic decontrol. There is a disproportion in macronutrients consumption in favor of carbohydrates, probably associated with socioeconomic limitations, food availability, and price. Developing nutritional assistance programs which contemplate cultural and economic factors in this Mayan population must be taken into consideration.

Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declined within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants received ChAdOx1 and forty-two participants received BNT162b2 were enrolled into this study which evaluated the immune responses including anti-SARS-CoV-2 spike total antibodies (Elecsys®), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript) and five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization as well as 4 and 12 weeks after receiving the booster. This study showed a significantly higher B-cell response among the BNT162b2 than the ChAdOx1 booster group, particularly against the Omicron variant, as well as a trend of good T-cell immune response in the BNT162b2 group. Moreover, the immune response rapidly declined at 12 weeks after the booster. A fourth dose or a second booster should be recommended, especially for reducing Omicron severity.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

Intermittently Scanned Continuous Glucose Monitoring (isCGM) devices are increasingly being used in patients with type 2 diabetes mellitus (T2DM) on insulin therapy for their benefits regarding disease management. Evidence of isCGM use in patients with T2DM treated with basal insulin or oral antidiabetic drugs is lacking. The aim of this study was to assess the efficacy and safety of isCGM in this population. This was an observational, retrospective, real-world study enrolling patients with T2DM who were starting with the use of isCGM. Data from medical records (i.e. demographics, clinical characteristics, laboratory assessments, and isCGM metrics) were collected over three time periods (baseline, 3 and 6 months). The endpoints were glycated haemoglobin (HbA1c) changes, and changes in isCGM metrics as defined by the International Consensus from baseline to a 3-month and a 6-month follow-up. Overall, 132 patients were included (69% male; mean age 68.2±11.0 years; mean disease duration 19.0±9.3 years; 80% on basal insulin ± oral drugs at baseline; mean baseline HbA1c 8.1%±1.3%). The estimated mean change in HbA1c from baseline was statistically significant at three (-0.4±1.0%; p=0.003) and at six months (-0.6±1.3%; p&lt;0.0001). No statistical differences were found in the mean change of the isCGM metrics. Intermittently Scanned Continuous Glucose Monitoring is effective and safe in improving glycaemic control in patients with type 2 diabetes treated with basal insulin or oral antidiabetic drugs.

A hydrothermal pretreatment of the microalga Nannochloropsis gaditana at mild temperatures has been studied in order to reduce N and O content in the biocrude obtained by hydrothermal liquefaction (HTL). The work is focused on the evaluation of temperature, reactor loading and time (factors) to maximize the yield of the pretreated biomass and the heteroatom contents transferred from the microalga biomass to the aqueous phase (responses). The study followed the factorial design and response surface methodology. An equation for every response has been obtained, which leads to the accurate calculation of the operating conditions required to obtain a given value of these responses. Temperature and time are critical factors with a negative effect on the pretreated biomass yield, but a positive one on the N and O recovery in the aqueous phase. The slurry concentration has to be low to increase heteroatom recovery and high to maximize the pretreated microalga yields

Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing a Public Health Emergency of International Concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies, and also case reports, were included and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 660 articles were retrieved (1/1/2020-2/23/2020). After screening by abstract/title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), with 32.8% presenting acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) of hospitalized patients with fatal outcomes (case fatality rate, CFR).Conclusion: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and this group was associated with a CFR of over 13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure, and facilities to treat severe COVID-19.

Dengue is one the most significant mosquito-borne viral diseases globally, with its prevalence extending across tropical and subtropical regions, exerting a considerable financial strain on health systems. Despite decades of research leading to the development of a vaccine implemented in endemic countries, its usage remains restricted to a fraction of the population at risk of contracting dengue. Due to these limitations, there is a growing focus on research aimed at unraveling the cellular mechanisms crucial for Dengue virus (DENV) infection to pinpoint potential host targets. Multiple studies propose a pivotal role of cytoskeletal remodeling in DENV infection. Specifically, DENV alters the organization of actin to facilitate viral entry, replication, and release. In this study, we investigated the involvement of the protein c-Abl, a kinase crucial in actin dynamics, in the context of DENV infection. Our findings suggest that either silencing or pharmacological inhibition of the kinase c-Abl leads to accumulation of dengue ENV protein in vitro, associated with actin remodeling. These results illuminate cellular mechanisms that could serve as potential therapeutic alternatives for dengue management.

Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (r_s 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.

More than 1,000,000 confirmed cases of COVID-19 have been registered worldwide since the beginning of the pandemic in Wuhan on December 2019. The high mortality rate of COVID-19 is associated with age, gender and the presence of comorbidities. Biochemical data have shown that COVID-19 patients develop a local and systemic hyper-inflammatory response associated with poor outcome. Therefore, the understanding of the biological mechanisms underlying SARS-CoV-2-induced inflammation is a compelling need. Following this reasoning, here we will focus on the importance of the progressive age-related development of a pro-inflammatory state (aka inflamm-aging) in the understanding of the unbalanced inflammatory response against SARS-CoV-2 in aged people. In particular, we underpin the role of mitochondrial DNA and genomic DNA telomeric sequences in local and systemic mechanisms of inflammation. Indeed, the leakage of mtDNA out of its natural compartment (i.e. the mitochondrion), into the cytoplasm and in the extracellular environment is a powerful trigger of innate immunity and inflammation, as part of an evolutionary-conserved signaling mechanism of cellular damage (e.g. viral infection). High levels of circulating mtDNA are increased in aged people and set up as inflammatory markers of poor prognosis in intensive care unit patients. In turn, telomeric DNA, which can be released into the cytoplasm and in the extracellular environment upon cell damage, has been proven to exert potent anti-inflammatory activity. Since that aged people (particularly those affected by co-morbidity) are equipped with shortened telomeres, we posit that, in aged people affected by COVID-19 the release of mtDNA, coupled with insufficient telomeric DNA favors the onset of a detrimental inflammatory response. In this regard, we highlight that the mechanism of action of some currently used drugs, as well as potential new ones may be better understood under the light of the above-depicted theoretical framework thus explaining how studies on inflamm-aging may help to understand and combat COVID-19 pandemic.

COVID-19 pandemic is a serious problem in the world today. The SARS-CoV-2 virus that causes COVID-19 has important proteins used for its infection and development, namely the protease and spike glycoprotein. The RBD (Receptor Binding Domain) of spike glycoprotein (RBD-S) can bind to the ACE2 (Angiotensin Converting Enzyme-2) receptor at the protease domain (PD) (PD-ACE2) of the host cell, thereby leading to a viral infection. This study aims to reveal the potential of compounds contained in Curcuma sp., Citrus sp., Alpinia galanga, and Caesalpinia sappan as anti SARS-CoV-2 through its binding to 3 protein receptors. The study was conducted by molecular docking using the MOE 2010 program (licensed from Faculty of Pharmacy UGM, Indonesia). The selected protein targets are RBD-S (PDB ID:6LXT), PD-ACE2 (PDB ID: 6VW1), and SARS-CoV-2 protease (PDB ID:6LU7). The affinities of bonds formed is represented as a docking score. The results show that hesperidin, one of the compounds in Citrus sp., has the lowest docking score for all three protein receptors representing the highest affinity to bind the receptors. Moreover, all of the citrus flavonoids possess good affinity to the respected receptors as well as curcumin, brazilin, and galangin, indicating that those compounds perform inhibitory potential for the viral infection and replication. In general, the results of this study indicate that Citrus sp. exhibit the best potential as an inhibitor to the development of the SARS-CoV-2, followed by galangal, sappan wood, and Curcuma sp. that can be consumed in daily life as prophylaxis of COVID-19.

In the search of potent α-amylase inhibitors, we have synthesized seventeen derivatives of 2-mercaptobenzimidazole bearing sulfonamide (1-17) and evaluated for their α-amylase inhibitory potential. All compounds display a variable degree of α-amylase activity having IC50 values ranging between 0.90 ± 0.05 to 11.20 ± 0.30 µM when compared with the standard drug acarbose having IC50 value 1.70 ± 0.10 µM. Compound 1, 2, 11, 12 and 14 having IC50 values 1.40 ± 0.10, 1.30 ± 0.05, 0.90 ± 0.05, 1.60 ± 0.05 and 1.60 ± 0.10 µM respectively were found many folds better than the standard drug acarbose. The remaining analogs showed good inhibitory potentials. All the synthesized compounds were characterized by HREI-MS, 1H and 13C-NMR. Structure activity relationship (SAR) has been recognized for all newly synthesized analogs. Through molecular docking study, binding mode of active analogs with α-amylase enzyme was confirmed.

Mycotoxins are deleterious fungal secondary metabolites that contaminate food and feed, thereby creating concerns regarding food safety. Common fungal genera can easily proliferate in Indian tropical and sub-tropical conditions, and scientific attention is warranted to curb its growth. To address this, two nodal governmental agencies, namely the Agricultural and Processed Food Products Export Development Authority (APEDA) and Food Safety and Standards Authority of India (FSSAI), have developed and implemented analytical methods and quality control procedures to monitor mycotoxin levels in a range of food matrices and assess risks to human health over the past two decades. However, comprehensive information on such advancements in mycotoxin testing and issues in implementing these regulations is inadequately covered in recent literature. The aim of this review is thus to uphold a systematic picture of the role played by the FSSAI and APEDA for mycotoxin control at the domestic level and for the promotion of international trade along with certain challenges in dealing with mycotoxin monitoring. Additionally, it unfolds various regulatory concerns regarding mycotoxin mitigation in India. Overall, it provides valuable insights to the Indian farming community, food supply chain stakeholders, and researchers about India’s success story in arresting mycotoxins throughout the food supply chain.

Since the onset of coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time that also gained increased transmissibility and spread in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we have summarized the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, bringing up-to-date hints for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are located in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.

The COVID-19 pandemic first observed in December 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has influenced every individual on the planet. The virus has influenced our lifestyle, education, economy and the environment. Though the vaccines against COVID-19 have provided protection against the disease; new strains of the virus have lowered the efficiency of the vaccines. There is still no effective therapy for the treatment of the disease. Understanding the protein structure of the virus may lead to the development of effective therapies for the disease. We recently mapped the structural proteins and non-structural proteins of SARS-CoV-2. The accessory proteins (Open reading frames, Orfs) of SARS-CoV-2 modulate the host environment to favor virus replication. This paper reports mapping the accessory proteins (Orfs) of SARS-CoV-2.

Understanding how the coronaviruses invade our body is an essential point, and the expression profile of coronaviruses receptor may help us to find where the coronavirus infects our body. We found that the coronavirus receptors, including angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and SARS-Cov-2, are digestion-related enzymes in human enterocytes. Coronaviruses are continually altering the binding receptor and binding modes during their evolution, but the potential target cell in the small intestine is constant when in the lung is inconstant. Enterocytes may act as a conserved cell reservoir for coronaviruses, which may be partially explained by the Red Queen hypothesis. We also found that coronaviruses receptors could be elevated in the presence of both invasive bacteria and their counterpart, probiotics. We demonstrated here that enterocytes act as a conserved cell reservoir for coronaviruses during their evolutions, which should not be ignored in the investigation of coronavirus diagnosis and treatment strategies.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Byers Peninsula is considered one of the largest ice-free areas in Maritime Antarctica. Since 2006, the Spanish Polar Program has taken part in a large number of environmental studies involving effects of climate changes in lives cycles, limnology and microbiology. Soils from maritime Antarctica are generally weakly developed and have chemical, physical and morphological characteristics strongly influenced by the parent material. However, biological activity during the short Antarctic summer promotes intense transference of nutrients and organic matter in areas occupied by different species of birds and marine mammals. To mapping and monitoring those areas with high biological occupation, could be very useful to have models of edaphic properties prepared from satellite images. In this approach, Deep Learning and Linear Regression models of soil properties and spectral indexes as explicative variables were performed. We training models of soil properties closely related to biological activity such as Dissolved Organic Carbon (DOC) and the iron fraction associated with organic matter (Fe). We tested the best approach to model the spatial distribution of DOC, Fe and pH by training models of Linear Regression and Deep Learning over Sentinel2 and WorldView2 images. The most robust models were used to track possible areas with ornithogenic soils as well as areas of the Byers Peninsula that could support the highest biological development.

Potato virus Y (PVY) is one of the most important constraints to potato production worldwide. There is an increasing occurrence of recombinant PVY strains PVYNTN and PVYN-Wi and a decline in the incidence of the nonrecombinant PVYO. We hypothesized that this may be due to the ability of these recombinant strains to antagonize and/or outcompete PVYO in mixed infections. To deter-mine this, we investigated interactions between PVYO and three recombinant PVY strains com-mon in North America: PVYNTN, PVYN-Wi, and PVYN:O. Overall, our study showed that these inter-actions are tissue dependent. Specifically, PVYNTN, the main causal agent of potato tuber necrotic ringspot disease (PTNRD), was found to be more adaptable than PVYO, especially in potato leaves due, at least in part, to the Ny gene that confers hypersensitive resistance (HR) to PVYO. Further-more, PVYN-Wi was found to repress PVYO in potato tubers but act synergistically in potato leaves. The PVYO-induced foliage necrosis in cultivar ‘Ranger Russet’ was observed to be more severe in plants co-infected by PVYN-Wi and PVYN:O, respectively, resulting in plant death. Strikingly, this PVYO -induced necrosis was suppressed by PVYNTN in doubly infected plants. These interactions may, at least partially, explain the decreasing incidence of PVYO in United States potato produc-tion regions, especially given that many cultivars contain the Ny gene, which likely limits PVYO enabling PVYNTN and PVYN-Wi to outcompete. We also found that replication and cell-to-cell movement of these PVY strains in tubers at 4C was similar to levels at ambient temperature.

We introduce a magnetic bead-based sample preparation scheme for enabling a Raman spectroscopic differentiation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) positive and negative samples. The beads were functionalized with the angiotensin-converting enzyme 2 (ACE2) receptor protein, which is used as recognition element to selectively enrich SARS-CoV-2 on the surface of the magnetic beads. Subsequent Raman measurements directly enable discriminating SARS-CoV-2 positive and negative samples. The proposed approach is applicable for other virus species, too, when the specific recognition element is exchanged. Series of Raman spectra were measured on three types of samples, namely SARS-CoV-2, Influenza A H1N1 virus and a negative control. For each sample type, eight independent replicates were considered. All spectra are dominated by the magnetic bead substrate and no obvious differences between sample types are apparent. In order to address the subtle differences in the spectra, we calculated different correlation coefficients, namely the Pearson coefficient and the Normalized Cross Correlation coefficient. By comparing the correlation with the negative control differentiating between SARS-CoV-2 and Influenza A virus is possible. This study provides a first step towards the detection and potential classification of different viruses with the use of conventional Raman spectroscopy.

Background: COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being described. Objective: To describe the findings of a current systematic review of the long-term effects related to post-COVID-19 sequelae. Design: A systematic review was carried out in which cohort studies, case series, clinical case reports were included, and the PubMed, Scielo, SCOPUS and Web of Science databases were ex-tracted. Information published 2020 to June 1, 2022, was sought. Results: We reviewed 300 manuscripts during the first step of the literature review process. Then 260 abstracts were analyzed. In the end, we included 32 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 9 for neurological and psychiatric, and 8 for cutaneous sequelae. Conclusion: Studies show that the most common sequelae are those linked to the lungs, followed by skin, cutaneous and psychiatric alterations. Women report a higher incidence of the sequelae, as well as those with comorbidities and severer COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its apparition but has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems and further burden healthcare systems around the world.

Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR confirmed SARS-CoV-2 infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.

An experiment was carried out at Nabogram Khamarbari, near the Manannogor, Sadar Upazila, Noakhali District, Noakhali-3814, Bangladesh during the period from 12th January 2018 to 17th April 2018, with two varieties of tomatillo (Physalis ixocarpa Brot.) SAU tomatillo-1 and SAU tomatillo-2. It was laid out in RCBD method having three replications and was conducted to observe the influence of staking and non-staking on tomatillo cultivation in coastal areas. For the study, growth indicating characters like no. of leaves plant^-1, size of leaf plant^-1, height of each plant, no. of branches plant^-1 and yield attributing parameters such as days to first flowering, days to 50% flowering, no. of fruits branch^-1, fruit weight and yield were obtained from the plants with the treatments of staking and non-staking. A wide variation was observed between two varieties of tomatillo with the effect of these treatments. According to the results highest no. of leaves branch^-1, maximum size of leaves branch^-1, tallest height of each plant, uppermost no. of branches plant^-1, highest no. of fruits branch^-1, maximum weight of each fruit and yield were obtained in the staking treatment over the non-staking treatment of SAU tomatillo-1 and in case of SAU tomatillo-2, with the same parameters the result indicated significantly upper in the staking treatment over non-staking treatment. Considering the two varieties of tomatillo, the outcome were significantly superior with staking treatment for the similar parameters. The findings of the experiment indicated that the best yield (21 tha¹) and highest financial benefit could be obtained by SAU tomatillo-1 and the best tomatillo production in saline soil of coastal areas is possible by cultivating SAU tomatillo-1.

Home Security Systems are very important features of modern residential and office setups. This system is used to keep home safe from harmful gases, fire and intruders. It must be affordable, reliable and effective. In this paper, a GSM based home security system has been designed and implemented. The system consists of a GSM Module, MQ-2 smoke detector, Ultrasonic sonar sensor, LM35 temperature sensor, Arduino Uno and relay module. The MQ-2 smoke detector is used to detect harmful gases i.e. LPG, CH4, CO, Alcohol, Smoke or Propane. Any of the harmful gases stated above is detected it will warn the owner by activating the buzzer and displaying a warning message on the LCD display. It will also send a SMS to the owner. Our system can also measure temperate and if the temperature is increased above a certain range it will compensate it by activating Air Conditioner through the relay module. The system will also send a SMS to the owner. It can also detect intruders using Ultrasonic sensor and warn us through buzzer, SMS and displaying message on the LCD. Our system is reliable as it has very fast response and cost effective and it has been developed using our own technologies.

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained through an extensive review of the literature, and additionally included target genes identified by the COVID-19 Host Genetic Initiative, as well as the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with severe COVID-19 outcome.

Forest biomass is one of the most significant renewable energy sources in the Czech Republic. Recently, Czech forests have been under attack by spruce bark beetles, threatening the stability of biomass supply also for energy purposes. The goal of this paper is to uncover the impact of four different biomass development scenarios and three policies on the energy system and to evaluate the contribution of biomass to decarbonization efforts. We use the TIMES-CZ energy system optimization model to perform the analyses. We provide a crucial extension of this model by regionalizing it into NUTS3 +1 regions. Our main findings are that under the expected price of various types of biomass and their transportation cost, energy system would still exploit available biomass almost entirely throughout the period under review; subsidizing the production cost of the most expensive type of biomass for households would help utilize the full potential of biomass; and power and heat sector and industry would compete for biomass consumption against the residential sector.

Accurate seasonal weather forecasts are vital across a broad spectrum of applications, bearing significant environmental and socioeconomic implications. This importance renders the subject a matter of primary interest to a wide range of stakeholders, including the general public, agricultural sector, emergency responders, financial institutions, and policy strategists. The need for precision in long-term predictive models necessitates the development of innovative methodologies. These methodologies should be capable of deciphering atmospheric patterns and mechanisms with detail, especially at a local level, without the resource constraints that dynamical downscaling imposes. In response to this expanding demand, this study presents a novel solution, combining a stochastic deep learning methodology, specifically Generative Adversarial Networks (GANs), with a Digital Elevation Model (DEM). The cornerstone of the proposed model is the enhancement of gridded temperature fields from seasonal forecasts. The area of focus was the Hellenic region, wherein the spatial resolution is amplified from a coarse 1° x 1° grid to an impressively detailed 0.1° x 0.1° grid. This offers a transformative perspective for interpreting and employing this crucial meteorological data. The results suggest that the downscaled fields adequately approximate the actual spatial distribution, although the predicted values tend to slightly overestimate and in some cases underestimate the original ones. This study underlines the potential of this approach to significantly enhance the resolution and utility of weather forecasts, thereby contributing to a variety of sectors dependent on reliable meteorological data.

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin-6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are similar to those of other hyperinflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal-oral transmission. Increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options.

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while other show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA form fish oil in combination with GLA form blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period from autumn, winter, and spring avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing specific blend of omega-3 and omega-6 fatty acids or placebo. Primary outcomes were change in severity of AD measured using SCORing Atopic Dermatitis (SCORAD) patient oriented SCORAD (PO-SCORAD) and the difference in TCS use. Secondary outcomes were change in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving active product intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and use of topical corticosteroids (from median 30 to 10 mg/day, p < 0.001) but also significant improvement in itch, sleep quality and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D has a great beneficial effect in treatment of atopic dermatitis in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that can significantly reduce the severity of AD in pediatric patients.

Biological nanoparticles (NPs), such as extracellular vesicles (EVs), exosome-mimetic nanovesicles (EMNVs) and nanoghosts (NGs), are perspective non-viral delivery vehicles for all types of therapeutic cargo. Biological NPs are renowned for their exceptional biocompatibility and safety, alongside their ease of functionalization, but a significant challenge arises when attempting to load therapeutic payloads, such as nucleic acids (NAs). One effective strategy involves fusing biological NPs with liposomes loaded with NAs, resulting in hybrid carriers that offer the benefits of both biological NPs and the capacity for high cargo loads. Despite their unique parameters, one of the major issues of virtually any nanoformulation is the ability to escape degradation in the compartment of endosomes and lysosomes which determines the overall efficiency of nanotherapeutics. In this study, we fabricated all major types of biological and hybrid NPs and studied their response to acidic environment observed in endolysosomal compartment. In this study, we show that EMNVs display increased protonation and swelling relative to EVs and NGs in an acidic environment. Furthermore, the hybrid NPs exhibit an even greater response compared to EMNVs. Short-term incubation of EMNVs in acidic pH corresponding to late endosomes and lysosomes again induces protonation and swelling, whereas hybrid NPs are ruptured, resulting in the decline of their quantities. Our findings demonstrate that in an acidic environment, there is enhanced rupture and release of vesicular cargo observed in hybrid EMNVs that are fused with liposomes compared to EMNVs alone. This was confirmed through PAGE electrophoresis analysis of mCherry protein loaded into nanoparticles. In vitro analysis of NPs colocalization with lysosomes in HepG2 cells demonstrated that EMNVs mostly avoid endolysosomal compartment whereas hybrid NPs escape it over time. To conclude, (1) hybrid biological NPs fused with liposomes appear more efficient in the endolysosomal escape via the mechanism of proton sponge associated with scavenging of protons by NPs, influx of counterions and water, and rupture of endo/lysosomes, but (2) EMNVs are much more efficient than hybrid NPs in actually avoiding endolysosomal compartment in human cells. These results reveal biochemical differences across four major types of biological and hybrid NPs, and indicate that EMNVs are more efficient in escaping or avoiding endolysosomal compartment.

This work presents the results regarding the synthesis of tungsten nanoparticles (W NPs) by magnetron sputtering combined with gas aggregation (MSGA) when H2 mixed with Ar is used as working gas, the amount of H2 being increased up to 82%. The results show that up to 40% H2 in discharge the synthesis rate increases over 60 times, rapidly decreasing for over 50% H2 in discharge. The W dust is still produced in H2 dominated discharge (82%), the deposition rate being small but not negligible (20 mg/hour). The obtained WNPs are isolated, with the diameter decreasing from 50 nm to 15 nm when the amount of H2 in discharge is smaller than 41%. Over this value, the particles tend to agglomerate, forming structures similar to film-like deposits. Also, the diameter of the deposited spots on substrates is dependent on the H2 content in discharge. This allows the efficient coating of substrates with dimensions up to 26 mm by translating them in front of the MSGA cluster source exit aperture. Supplementary, for 41% H2 in discharge, the influence of synthetic air leaks (0-5%) in discharge was investigated. The deposition rate decreases rapidly (ceasing for around 4% air in discharge) and the obtained nanoparticles tend to agglomerate (at 2% air content, the dust deposit has the aspect of a near continuous film). Chemical composition investigations show a pronounced tendency of oxidation, nitridation and oxynitride formation in the presence of air leaks.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

SARS-CoV-2 Omicron variants contain many mutations in its spike receptor binding domain, the target of all authorized monoclonal antibodies (mAbs). Determining the extent to which Omicron variants reduced mAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated February 22, 2022, of the in vitro activity of authorized mAbs against the Omicron variants. Thirty-three studies were eligible including 33 containing Omicron BA.1 susceptibility data and five that also contained Omicron BA.2 susceptibility data. The first two authorized mAb combinations, bamlanivimab/etesevimab and casirivimab/imdevimab, were inactive against the Omicron BA.1 and BA.2 variants. In 24 studies, sotrovimab (third authorized mAb) displayed a median 4.1-fold (IQR: 2.4-7.6) reduced activity against Omicron BA.1 and, in four studies, a median 26-fold (IQR:16-35) reduced activity against Omicron BA.2. In 18 studies, cilgavimab and tixagevimab independently displayed median reductions in activity of >300-fold against Omicron BA.1, while in ten studies, the cilgavimab/tixagevimab combination (fourth authorized mAb preparation) displayed a median 63-fold (IQR: 26-145) reduced activity against Omicron BA.1. In two studies, cilgavimab was approximately 100-fold more susceptible to BA.2 than to BA.1. In two studies, bebtelovimab, the most recently authorized mAb, was fully active against both the Omicron variants. Disparate results between assays were common as evidenced by a median 42-fold range (IQR: 25-625) in IC50 between assays for the eight authorized individual mAbs and three authorized mAb combinations. Highly disparate results between published assays indicates a need for improved mAb susceptibility test standardization or inter-assay calibration.

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b compared to IgG1. Furthermore, we found that immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicates that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

There is a relatively high risk of virus transmission in dental procedures and oropharyngeal examinations. We investigated the effects of mouthwashes on covid-19 viral load reduction during dental practices and oro-pharyngeal assessments. We performed a systematic search in PubMed, EMBASE, Scopus, Web of Science, Cochrane library for relevant studies up to February 2021. Papers evaluating patients with covid-19 infection (patients) who rinse mouthwashes (intervention) compared to patients who don’t rinse them (comparison) for reducing covid-19 viral load or reducing cross-infection of covid-19 (outcome) in the randomized and non-randomized clinical trial and quasi-experimental studies (study) were included due to PICOS question. Three independent authors conducted literature screening and data extraction. We extracted the most relevant data and we evaluated the risk of bias from the included studies. Out of 344 potentially eligible articles, six studies were included in this systematic review. Regarding viral load and negative cycle threshold (ct) values, 1% PVP_I and Listerine mouthwash were effective. 0.12% CHX mouthwash was effective 0-2 hours post rinsing, but it was not effective after 2 hours. A mixture solution of 0.2% Chlorhexidine gluconate and 6% Hydrogen peroxide was effective on day 5 of intervention. Gargling 1% hydrogen peroxide, 0.075% Cetylpiridinum Chloride (CPC), 0.5%PVP-I and 0.2% CHX mouthwashes was not effective on SARS-COV-2. It cannot be guaranteed that rinsing a specific kind of mouthwash prevents cross-infection of covid-19; however, the viral load of SARS-COV-2 in saliva will be decreased after rinsing mouthwashes containing 1%PVP-I and Listerine.

Part of philosophy is to subject assertions to critical scrutiny, clarifying exactly what the assertion is saying, its implications, and thus its direct plausibility. The goal is to ensure clarity, logical consistency, and rational argumentation in order to arrive at reasoned conclusions. A common problem is that arguments have missing implied premises that, unless explicitly stated, are mistakenly assumed to be true. Here we subject conclusions made regarding the SARS-CoV-2 pandemic to critical scrutiny, revealing their implied premises so that these premises can be explicitly examined and refuted. Specifically, we refute the conclusions that “no one is protected until everyone is protected” and “population lockdowns are required to protect those at high risk of adverse outcomes.” In the end, we argue for the conclusion that “an Emergency Management principles based response to the pandemic, compared to population-wide lockdowns, offers a way to prevent more adverse outcomes from COVID-19, better prevent overwhelmed healthcare, and prevent most of the collateral damage to the wellbeing of the population that has resulted from the lockdowns.”

Based on comprehensible non-parametric methods, estimates of crucial parameters that characterise the COVID-19 pandemic with a focus on the German epidemic are presented. Where appropriate, the estimates for Germany are compared with the results for seven other countries (FR, IT, US, UK, ES, CH, BR) to get an idea of the breadth of applicability and a relational understanding. Thereby, only prevalence data of daily reported new counts of diagnosed cases and fatalities provided by the Johns Hopkins University are used. Drawing on uncertain a priori knowledge is avoided. Specifically, we present estimates resulting from delay-time correlations for the duration from diagnosis to death being 13 days for Germany and Switzerland. The delay-time correlation applied to time series from other countries exhibit less pronounced peaks suggesting high variabilities for the corresponding time-to-death durations. With respect to the German data, the two time series of new cases and fatalities exhibit a strong coherence within the frequency range of interest, which backs our findings. Furthermore, based on the knowledge of this time lag between diagnoses and deaths, properly delayed asymptotic as well as instantaneous fatality-case ratios are calculated having superiority compared to the commonly published case-fatality rate. The temporal median of the instantaneous fatality-case ratio with proper delay of 13-days between cases and deaths for Germany turns out to be 0.02. Time courses of asymptotic fatality-case ratios are presented for other countries which substantially differ during the first half of the pandemic, however, converge to a narrow range with standard deviation 0.57% and mean 2.4%. Additionally, the time courses of instantaneous fatality-case ratios with optimal delay for the 8 exemplarily chosen countries are calculated and compared by means of the temporal medians. Similarly to the asymptotic fatality-case ratios, the differences are much smaller than expected from mass media reports. The basic reproduction number, R₀, for Germany is estimated to be between 2.4 and 3.4. The uncertainty stems from uncertain knowledge of the generation time. A delay autocorrelation shows resonances at about 4 days and 7 days, where the latter resonance is at least partially attributable to the sampling process with weekly periodicity. The calculation of the basic reproduction number is based on an evaluation of cumulative numbers of cases yielding time-dependent doubling times as an intermediate step. This allows to infer to the reproduction number during the early phase of onset of the epidemic. In a second approach, the instantaneous reproduction number is derived from the incident (counts of new) cases and allows, in contrast to the first version, to infer to the temporal behaviour of the reproduction number during the later epidemic course. The time course of the reproduction number is compared to an alternative control measure given by the per capita growth, which largely confirms the conclusions drawn from the reproduction number. To conclude, by avoiding complicated parametric models we provide insights into basic features of the COVID-19 epidemic in an utmost transparent and comprehensible way. The perhaps most striking insight is that the fatality-case ratios do not differ between countries as much as previously suspected.