Cannabis has long been used for its medicinal and psychoactive properties. With the relatively new adoption of formal medicinal cannabis regulations worldwide, the study of cannabinoids, both endogenous and exogenous, has similarly flourished in more recent decades. In particular, research investigating the role of cannabinoids in regeneration and neurodevelopment has yielded promising results in vertebrate models. However, regeneration-competent vertebrates are few, whereas a myriad of invertebrate species have been established as superb models for regeneration. As such, this review aims to provide a comprehensive summary of the endocannabinoid system, with a focus on current advances in the area of endocannabinoid system contributions to invertebrate neurodevelopment and regeneration.

Addressing escalating energy demands and greenhouse gas emissions in the oil and gas industry has driven extensive efforts in carbon capture and utilization (CCU), focusing on power plants and industrial facilities. Utilizing CO2 as a primary feedstock for industrial fuels and petrochemical materials offers a favorable alternative to sequestration, with byproducts substituting traditional chemical feedstocks. This comprehensive review explores the current landscape of CO2 capture technologies, examining opportunities, economic viability, and efficiency challenges. It provides a detailed analysis of various CO2 utilization methods and the combined process of capture and utilization. The review highlights primary obstacles in planning, production, and widespread implementation, emphasizing the need for strategic integration of materials research, process performance, and cost-effectiveness to advance new technologies.

Background The spread of COVID-19 continues, the mutation of SARS-COV-2 is still difficult to control, and the need for antiviral drugs to treat COVID-19 remains urgent. The use of arbidol in the treatment of COVID-19 is limited and controversial. Methods To clarify the efficacy of arbidol on COVID-19, we collected 25 cases and 178 related studies. We analyzed the treatment information of arbidol based on the obtained cases, expanded the scope of the study, and collected current studies on the treatment of COVID-19 in various databases for in-depth analysis. Results History analysis showed that arbidol was effective (76% cure rate) compared with other drugs. However, compared with other antiviral drugs or standard therapy, the arbidol group had no significant advantage in reducing the time to negative virus transformation, length of hospital stays, or improvement in CT (MD=0.22, 95%CI -0.29-0.73; MD = 0.61, 95% CI 1.46 to 2.67; RR=1.15, 95%CI 0.88-1.50); Analysis of adverse events showed no significant difference between the arbidol group and the other groups (RR=0.82, 95%CI 0.25-2.71). Conclusion Our study showed that arbidol had no significant effect on COVID-19, but showed a slight advantage in CT improvement and adverse events. Our study objectively evaluated the efficacy of arbidol in the treatment of COVID-19 and provided some guidance for arbidol in the treatment of COVID-19.

Abstract: (1) Background: After the COVID-19 pandemic, there is increasing concern regarding the immunity of population to SARS-CoV-2 variants, particularly the Omi-cron variant and its sub-lineages. (2) Methods: The study involved analyzing the im-mune response and symptomatology of 27 vaccinated individuals who were subse-quently infected by Omicron sub-lineages. Blood samples were collected for serological analysis, including the detection of IgG antibodies reactive to the Nucleocapsid (N) and Spike (S) antigens of SARS-CoV-2. Additionally, participants were interviewed to assess the intensity of symptoms during the infection. (3) Results: Despite the high levels of anti-Spike IgG observed after vaccination, all participants were infected by Omicron sub-lineages. The most common symptoms reported by participants were fever or chills, sore throat, and cough. Surprisingly, the levels of anti-Spike IgG found prior to infection did not correlate with symptom severity post-infection. However, it was observed that high post-infection anti-Nucleocapsid IgG levels correlates with mild symptoms during the course of the disease, suggesting a potential role for anti-N antibodies in disease resolution. (4) Conclusions: The high levels of IgG anti-Spike resulting from vaccination may not provide complete protection against infection by the Omicron variant. Addi-tionally, our data suggest that anti-Nucleocapsid IgG titers are negatively correlated with the intensity of the symptoms during mild infections. These findings underscore the importance of ongoing surveillance of viral variants and continuous adaptation of vaccination strategies to ensure efficacy against SARS-CoV-2 variants.

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.

Patients with COVID-19 have coagulation and platelet disorders, with platelet’s alterations and thrombocytopenia representing negative prognostic parameters, being associated with severe forms of the disease, and increase lethality. Methods: Aim of this study was to study expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation Results: a total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19 +), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS CoV-2 (-) negative lungs (COVID-19 -), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1 positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of dead patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocytes over-expression in the lung. Conclusions: microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

Aim: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from 6 hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. Secondary outcomes were composite adverse outcomes including pregnancy complications, delivery complications, and neonatal complications. Cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1,543 pregnant individuals in the standard screening group and 2,197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs 6.9%, respectively; p

Jingmen viruses are newly described segmented flavi-like viruses that have a worldwide distribution in ticks and have been associated with febrile illnesses in humans. Computational analyses were used to predict that Jingmen flavi-like virus glycoproteins have structural features of class II viral fusion proteins, including an ectodomain consisting of beta-sheets and short alpha-helices, a fusion peptide with interfacial hydrophobicity and a three domain architecture. Jingmen flavi-like virus glycoproteins have a sequence enriched in serine, threonine and proline at the amino terminus, which is a feature of mucin-like domains. Several of the serines and threonines are predicted be modified by the addition of O-linked glycans. Some of the glycoproteins are predicted to have an additional mucin-like domain located prior to the transmembrane anchor, whereas others are predicted to have a stem consisting of two alpha-helices. The flavivirus envelope protein and Jingmen flavi-virus glycoproteins may have diverged from a common class II precursor glycoprotein with a mucin-like domain or domains acquired after divergence.

Delineating chilling and forcing periods is one of the challenging topics in understanding how temperatures drive the timing of budburst and bloom in fruit tree species. Here, we investigated this question on olive trees, using flowering data collected over six years on 331 cultivars in the worldwide collection of Marrakech, Morocco. Using a Partial Least Squares approach on a long-term phenology (29 years) of ‘Picholine Marocaine’ cultivar, we showed that the relevance of delineating the chilling and forcing periods depends more on the variability of inter-annual temperatures than on the long-term datasets. In fact, chilling and forcing periods are similar between those delineated by using datasets of 29 years and those of only 6 years (2014–2019). We demonstrated that the variability of inter-annual temperatures is the main factor explaining this pattern. We then used the datasets of six years to assess the chill and heat requirements of 285 cultivars. We classified Mediterranean olive cultivars into four groups according to their chill requirements. Our results, using the Kriging interpolation method, indicated that flowering dates of most of these cultivars (92%) were governed by both chilling and forcing temperatures. Our investigations provided first insights to select adapted cultivars to global warming.

A large population has been infected by COVID-19 (Coronavirus disease-19) and it has been necessary a rapid and simple diagnostic method to detect the SARS-CoV-2and control its spread. We developed a colorimetric reverse transcription-loop-mediated isothermal amplification (RT-LAMP) kit that allow the detection of SARS-CoV-2 from nasopharyngeal swab samples without the need of RNA extraction. The kit utilizes three sets of LAMP primers targeting two regions of ORF1ab and one region in the E gene. The results are reported using colorimetric change of hydroxynaphthol blue, enabling visual interpretation without the need for expensive instrument. The kit demonstrated sensitivity to detect between 50 and 100 copies of the viral genome per reaction. The kit was authorized by the National Administration of Drugs, Food and Technology (ANMAT) of Argentina after validation using samples previously analyzed by gold standard RT-qPCR. The results showed sensitivity of 90,6 % and specificity of 100%, consistent with conventional RT-qPCR. In silico analysis confirmed the recognition of SARS-CoV-2 Variants of Concern (VOCs) B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.427, B.1.429and lineages of variant Omicron (B.1.1.529) with 100% homology. This rapid, simple, and sensitive RT-LAMP method paves a way for a large screening strategy to be carried out at locations lacking sophisticated-instrumental and trained-staff, as particularly happen at regional hospitals and medical centers from rural areas.

Alexithymia as the inability to describe one's own feelings, is being increasingly researched. According to contemporary psychodynamic theories, negative emotions cannot be adequately named and externalized, but remain trapped in the body. Recent research shows the connection of alexithymia with numerous somatic diseases. Diabetes mellitus type 2 and obesity represent a great challenge in treatment, and the psychological profiles in these diseases are being studied more and more often. Therefore, alexithymia enters the focus of some research as one that could play a significant role namely in these diseases as the factor that makes a difference. The aim of this paper is a review of the literature with the purpose of understanding the current knowledge about the interconnection between alexithymia, obesity and type 2 diabetes mellitus.

The aim of the study was to determine the effect of the application of different organic matter, UGmax soil conditioner and simplifications in potato cultivation on the content of dry matter, starch, sugars in tubers of the medium-early edible cultivar 'Satina' after harvest and after long-term storage. The highest dry matter (173.4 g kg-1) and starch (124.6 g kg-1 f. m.) content was ob-tained with the simultaneous application of a manure with soil conditioner at 100% mineral fer-tilization. In the case of sugars, the withdrawal of the soil conditioner from the crop proved most beneficial, for total sugars on the stubble intercrop (5.06 g kg-1 f. m.) and for reducing sug-ars (1.99 g kg-1 f. m.) on the straw. Each protection reduction applied resulted in a significant re-duction in starch content. In this regard, the withdrawal of herbicides with simultaneous appli-cation of manure and UGmax proved most beneficial. Long-term storage of tubers caused a sig-nificant reduction in their quality in terms of dry matter and starch content (average by -3.6 and -2.3%, respectively) and an increase in total and reducing sugars (average by 11.8 and 9.6%, re-spectively). The decrease in dry matter and starch content was significantly influenced by the 50% reduction in NPK fertilization applied during the growing season, while the application of soil conditioner with full protection contributed to the increase in reducing sugars after storage at 28.9 pts%. Our research is in line with current trends of used potato cultivation technologies focused mainly on environmental protection, so the results of this study can provide a basis for validation for researchers currently engaged in such evaluation.

The genetic engineering of plants often relies on the use of antibiotic or herbicide resistance genes for initial selection of primary transgenic events. Nevertheless, the commercial release of genetically modified crops containing any marker gene encounters several challenges stemming from the lack of consumer acceptance. Development of strategies enabled the generation of marker-free transgenic plants is a possible alternative to deal with public concerns over the safety of biotech crops. Leveraging the high in vitro regeneration and transformation capabilities of potato, this study examined the factors associated with the development of transgenic plants without presence of selective substances in medium. To compare the antibiotic-assisted with the antibiotic-free transformation, nodal explants from five highly regenerative potato cultivars were inoculated with the Agrobacterium strain AGL0 carrying the pBIN-mGFP5-ER (35SGFP/nosNPTII) plasmid. The efficiency of transient expression and the formation of chimeric and completely transgenic shoots were assessed through vital GFP observations. Under non selective conditions, the regeneration efficiency of stable non-chimeric transgenic shoots varied from 0.9 (‘Chicago’) to 2.7% (#12-36-42). In order to streamline transformation protocol, a specific timeline for collecting transgenic plantlets was established for each analyzed cultivar. This timeline strategy was implemented to generate transgenic potato plants, which demonstrated the suppression of homologous SteIF4Es family genes as a result of the successful introduction of the marker-free hpRNAi construct.

The effect of high temperature (HT) stress on nicotine biosynthesis in Nicotiana attenuata was examined. Nicotine content was measured in mature leaves, young sink leaves and in roots from well-watered plants grown at 25 °C as controls and from plants exposed to 38 °C and 43 °C temperatures applied for 24, 48, 72 and 96-hr duration. At 38 °C, all leaf nicotine levels were significantly less than control plants for up to 72-hr exposure but rose sharply thereafter to levels significantly greater than controls with 96-hr exposure. In contrast, plants exposed to 43 °C never exhibited a reduction in leaf nicotine content and showed a significant increase in content with just 48-hr exposure. When radioactive 11CO2 was administered to plants, HT stress significantly reduced fixation. Furthermore, radiocarbon flux analysis revealed that ‘new’ C partitioning (as 11C) into the [11C]-amino acid pool was significantly reduced with HT stress as were yields of [11C]-aspartic acid, an important amino acid in nicotine biosynthesis, and its beta-amido counterpart [11C]-asparagine significantly reduced. In contrast, [12C]-aspartic acid levels appeared unaffected at 38 °C but were significantly elevated at 43 °C relative to controls. Additionally, [12C]-asparagine levels were significantly elevated at both stress temperatures. Finally, leaf total soluble protein (TSP) was reduced 39% with long exposures to both stress temperatures. However, Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) which was 41% TSP appeared unaffected by HT stress. Altogether, these results support the theory that plant proteins other than Rubisco degrade at elevated temperatures freeing up essential amino acids supporting the nicotine biosynthetic machinery, and while feedback might downregulate de novo amino acid synthesis from ‘new’ C resources, more than likely plant C/N rebalancing caused by HT reductions in C input restricted N uptake, which in turn, limited this process.

Estimating the parameters of statistical distributions generally involves solving a system of nonlinear equations or a nonlinear equation, being a technical difficulty in their usual application in hydrology. This article presents improved approximations and, in some cases, new approximations for the estimation with the method of ordinary moments and the method of linear moments, which are useful for the direct calculation of the parameters, because the errors in the approximate estimation are similar to the use of iterative numerical methods. Thirteen statistical distributions of two and three parameters frequently used in hydrology are presented, for which parameter estimation was laborious. Thus, the approximate estimation of the parameters by the two methods is simple but also precise and easily applicable by hydrology researchers. The approximate forms characterized by very small errors are the result of the research conducted within the Faculty of Hydrotechnics to update the romanian normative standards in the hydrotechnical field.

The pomegranate, an ancient plant native to Central Asia, cultivated in different geographical areas including the Mediterranean basin and California, consists of flowers, roots, fruits and leaves. Presently, it is utilized not only for the exterior appearance of its fruit but above all, for the nutritional and health characteristics of the various parts composing this last one (carpellary membranes, arils, seeds and bark). The fruit, the pomegranate, is rich in numerous chemical compounds (flavonoids, ellagitannins, proanthocyanidins, mineral salts, vitamins, lipids, organic acids) of high biological and nutraceutical value that make it the object of study for many research groups, particularly in the pharmaceutical sector. Its interest is mainly addressed to the knowledge of its biological and functional properties and the research of new formulations to apply it in a wide range of diseases such as neoplastic, cardiovascular, viral, inflammatory, metabolic, microbial, intestinal, reproductive and skin diseases. In this review we highlight the health-promoting properties of pomegranate and its bioactive compounds against human diseases.

Background: The rise of new SARS-CoV-2 mutations brought challenges and progress in the global fight against COVID-19. Mutations in spike and accessory genes affect transmission, vaccine efficacy, treatments, testing, and public health strategies. Monitoring emerging variants is crucial to halt virus spread. Methods: 44 nasopharyngeal/oropharyngeal swabs from Kenyan patients were sequenced with the Illumina platform. Galaxy's bioinformatic tools were used for genomic analysis. SARS-CoV-2 genome classification was done using PANGOLIN and mutation annotation with the COVID-19 Annotator tool. Results: The study showed 5 clades to be circulating in the region. 38(86%) were BA.1.1; 2(5%) were BA.1.1.1; 1(2%) was BA.1; 1(2%) was BA.1.14 and 2(5%) were AY.46. These clades had a cumulative of 173 mutations among them with 50 novel mutations. Forty-eight of these novel mutations occurred in a low frequency of 2.3% of the sequences tested while the other two, S:R214R, and NSP2:A555A, were for 43.2% and 18.2% of the cases respectively. Conclusions: The high-frequency novel mutations were synonymous mutations, a phenomenon that was previously viewed as phenotypically silent but recent studies indicate they can affect viral fitness with potential functional associations. These findings add to the understanding of the SARS-CoV-2 virus future evolutionary and immunological dynamics in the region

We report the treatment of a 21-year-old female Covid-19 patient by a novel combination of minocycline and a guanosine-restricted diet. Minocycline is an antibiotic with well documented broad spectrum anti-viral effects, including evidence of activity against SARS-CoV-2. Deprivation of guanosine has been documented as an effective anti-viral modality in vitro and in animal models, and specific in vitro activity against CoV-SARS-2 has been reported. The patient's symptoms resolved rapidly.

Oil spills from offshore drilling and coastal refineries often cause degradation of coastal wetlands that can take a long time to recover. Early oil detection may prevent losses and speed up recovery if monitoring of the initial oil extent, oil impact, and recovery are in place. Satellite imagery data can provide a cost-effective alternative to expensive airborne imagery or labor intensive field campaigns for monitoring effects of oil spills on wetlands. However, these satellite data may be restricted in their ability to detect and map ecosystem recovery post-spill given their spectral measurement properties and temporal frequency. In this study, we assessed whether spatial and spectral resolution, and other sensor characteristics influence the ability to detect and map vegetation stress and die-off due to oil. We compared how well three satellite multispectral sensors: WorldView2, RapidEye and Landsat EMT+, match the ability of the airborne hyperspectral AVIRIS sensor to map oil-induced vegetation stress, recovery, and die-off after the DeepWater Horizon oil spill in the Gulf of Mexico in 2010. We found that finer spatial resolution (3.5m) provided better delineation of the oil-impacted wetlands and better detection of vegetation stress along oiled shorelines in saltmarsh wetland ecosystems. As spatial resolution become coarser (3.5m to 30m) the ability to accurately detect and map stressed vegetation decreased. Spectral resolution did improve the detection and mapping of oil-impacted wetlands but less strongly than spatial resolution, suggesting that broad-band data may be sufficient to detect and map oil-impacted wetlands. AVIRIS narrow-band data performs better detecting vegetation stress, followed by WorldView2, RapidEye and then Landsat 15m (pan sharpened) data. Higher quality sensor optics and higher signal-to-noise ratio (SNR) may also improve detection and mapping of oil-impacted wetlands; we found that resampled coarser resolution AVIRIS data with higher SNR performed better than either of the three satellite sensors. The ability to acquire imagery during certain times (midday, low tide, etc.) or a certain date is also important in these tidal wetlands; WorldView2 imagery captured at high-tide detected a narrower band of shoreline affected by oil likely because some of the impacted wetland was below the tideline. These results suggest that while multispectral data may be sufficient for detecting the extent of oil-impacted wetlands, high spectral and spatial resolution, high-quality sensor characteristics, and the ability to control time of image acquisition may improve assessment and monitoring of vegetation stress and recovery post oil spills.

Coppicing has been neglected in recent decades leaving gaps in knowledge on silvicultural interventions, especially the long-term effects on coppices of South-East Europe. Thus, our work aims to define the long-term effects of thinning in sessile oak (Quercus petraea (Matt.) Liebl.) and European beech (Fagus sylvatica L.) sub-mountainous thermophilic low coppices in the Croatian Dinarides. The experiment includes two localities with thinning plots and control plots. Thinning was done in 2002 with 17.71% of wood volume removed in the European beech coppice and 26.09% in the sessile oak coppice. 1276 trees were marked, measured (DBH, tree height, number of stems per stump) and assessed for vitality, origin and six silvicultural features revealing tree quality. Descriptive statistics for all variables, RMANOVA for DBH and height and for continuous variables mean+-+ standard deviation for categorical frequency and relative frequency variables were carried out. The results show a statistically significant positive long-term effect of thinning on tree growth, stem and crown features and support findings that thinning, by increasing growth and quality, is a necessary intervention in European beech and sessile oak low coppices. The recent economic crisis, the sudden increase in energy prices, and the increased demand for assorted wood products have initiated higher interest in coppices in Croatia.

While vaccines are a well-established method of controlling the spread of infectious diseases, vaccine hesitancy jeopardizes curbing the spread of COVID-19. Through the Vaccine Information Network (VIN), this study explored barriers and motivators to COVID-19 vaccine uptake. We conducted 18 focus group discussions with male and female community members, stratified by country, age group, and—for Zimbabwe only—by HIV status. Participants’ median age across both countries was 40 years (interquartile range of 22–40) and most (65.9%) were female. We conceptualized the key themes within the World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) 3Cs (convenience, confidence, complacency) vaccine hesitancy model. Barriers to vaccine uptake—lack of convenience, low confidence, and high complacency—included inaccessibility of vaccines and vaccination sites, vaccine safety and development concerns, and disbelief in COVID-19’s existence. Motivators to vaccine uptake—convenience, confidence and low complacency—included accessibility of vaccination sites, user-friendly registration processes, trust in governments and vaccines, fear of dying from COVID-19 and knowing someone who had died or become infected with COVID-19. Overall, vaccine hesitancy in South Africa and Zimbabwe was influenced by inconvenience, a lack of confidence, and high complacency around COVID-19 vaccines.

We are proposing, for any interested investigator, a randomized open clinical trial for mild and mild-to-moderate Covid-19 comparing a treatment regimen with standard of care, and eventually with another investigational regimen, if ongoing or will be implemented. The patients could be hospitalized or ambulatory but not requiring admission to intensive care units and mechanical ventilation. The proposed therapeutic regimen consists of doxycycline (an antimicrobial having also anti-inflammatory properties, probable antioxidant and possible some antiviral effects), and pentoxifylline, a hemorheological compound used in occlusive arterial diseases but also having proven anti-inflammatory properties. Doxycycline is included in the WHO’s list of essential medicine being an effective, safe, widely available, and inexpensive medication and widely accessible. It will be administered at a dosage of 100 mg orally twice daily for ten days. Pentoxifylline, in clinical use since 1972, and also widely accessible, will be given at a dosage of 400 mg orally, also twice daily, for ten days. The primary outcome measures are: 1) Progression of disease to a severe form requiring intensive care admission and mechanical ventilation; 2) Fatality rates and 3) Time to clinical recovery.This proposal was presented to the National Directors and Core Leads meeting of the Canadian Trials Network (CTN) on May 6, 2020. The interventional trial template suggested by CTN was used for designing the trial.

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

Rhabdomyolysis is a serious clinical condition, which if left untreated can lead to kidney failure and in extreme cases, to death. It has also been reported in association with SARS COV2 infection and can be its initial presentation. COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), which has many variants that change the characteristics of the disease affecting, among other things, the method of transmission or treatment. Some investigators have implicated excessive immune response in the causes of muscle damage during SARS-CoV-2 infection. Others point to direct damage caused by the virus or involving immune factors. In this study we described cases of COVID-19 infection from 1 June 2022 to 15 July 2022 with elevated muscle enzymes in the blood and hospitalized to the first division of Cotugno hospital in Campania. Of 39 patients with SARS-CoV-2 infection, 15 patients presented also rhabdomyolysis. The most common symptoms were: asthenia, fever, arthomyalgia, lipothymia and syncope. No patient had myocardial infarction and 2 patients had atrial fibrillation. All patients were affected by omicron SARS-CoV-2 variants. Of these patients: 4 patients died (2 due to rhabdomyolysis and 2 due to sepsis) and only one patient presented acute kidney injury.

Optical rotatory dispersion (ORD) is a beautiful analytical technique for the study of chiral molecules and polymers. In this study, ORD was applied successfully to follow the degree of polycondensation of l-(+)-lactic acid toward the formation of poly(lactic acid) oligomers (PLAO) and high molecular weight poly(l-lactic acid) (PLLA) in a simple esterification reaction equipment. PLLA is a biodegradable polymer obtainable from renewable raw materials. The racemization of the intrinsically isotactic PLLA through thermal treatment can be easily followed through the use of ORD spectroscopy. Organic or molecular electronics is a hot topic dealing with the combination of π-conjugated organic compounds and polymers with specific properties (e.g. chirality) which can be exploited to construct optoelectronic devices such as organic light-emitting diodes (OLEDs), organic photovoltaic (OPV) high efficiency cells, switchable chirality devices, organic field-effect transistors (OFETs), and so on. ORD spectroscopy was applied to study either the gigantic optical rotation of PLLA films as well as to detect successfully the excitonic coupling occurring in thin solid PLLA green film loaded with a combination of two dyes: SY96 (a pyrazolone dye) and PB16 (the metal-free phthalocyanine pigment). The latter compound PLLA loaded with SY96 and PB16 shows a really gigantic optical activity in addition to typical ORD signal due to exciton coupling and may be considered as a simple and easily accessible model composite of a chiral polymer matrix combined with π-conjugated dyes for molecular electronics studies.

Background: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2 has posed unprecedented challenges to healthcare systems worldwide. Here, we have identified proteomic and genetic signatures for improved prognosis which is vital for COVID-19 research. Methods: We investigated the proteomic and genomic profile of COVID-19 positive patients (n=400 for proteomics, n=483 for genomics), focusing on differential regulation between hospitalised and non-hospitalised COVID-19 patients. Signatures had their predictive capabilities tested using independent machine learning models such as Support Vector Machine (SVM), Random Forest (RF) and Logistic Regression (LR). Results: This study has identified 224 differentially expressed proteins in hospitalised COVID-19 patients compared to non-hospitalised COVID-19 patients, involved in various inflammatory and immunological pathways. LGALS9 (p-value < 0.001), LAMP3 (p-value < 0.001), PRSS8 (p-value < 0.001) and AGRN (p-value < 0.001), were identified as the most statistically significant proteins. Several hundred rsIDs were queried across the top 10 significant signatures, identifying three significant SNPs on the FSTL3 gene showing correlation with hospitalisation status. Conclusion: Our study has not only identified key signatures of COVID-19 patients with worsened health but has also demonstrated their predictive capabilities as potential biomarkers, which suggests a staple role in the worsened health effects caused by COVID-19.

Mitochondria are classically termed as powerhouse of a mammalian cell. Most of the cellular chemical energy in the form of adenosine tri phosphate (ATP) is generated by mitochondria and dysregulation of mitochondrial functions thus can be potentially fatal of cellular homeostasis and health. Acute respiratory distress has been earlier linked to mitochondrial dysfunction. SARS-CoV-2 infection severity leads to acute respiratory distress syndrome (ARDS) and can be fatal. We tried to investigate possible connection between SARS-CoV-2, ARDS and mitochondria. Here, we report identification of SARS-CoV-2 non-structural proteins (particularly Nsp12 and 13) that have recognition sequence with respect to mitochondrial entry. We also report that these proteins can potentially shuttle between cytoplasm and mitochondria based on the localization signals and help in downstream maintenance of the virus. Their properties to use ATP for enzymatic activities may cause ATP scavenging allowing viral RNA functions in lieu of host cell health.

Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms, while others that infect animals can evolve and become infectious to humans. Three recent examples of this viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19).COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 14 April 2020 show more than 2 million people had been infected with the virus, causing more than 120,000 deaths in over 210 countries worldwide. The large amount of information we receive every day concerning this new disease is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

Long Covid or post-acute sequelae of SARS-CoV-2 infection (PASC) can manifest as long-term symptoms in multiple organ systems, including respiratory, cardiovascular, neurological, and metabolic systems. In patients with severe COVID-19, immune dysregulation is significant, and the relationship between metabolic regulation and immune response is of great interest in determining the pathophysiological mechanisms. We aimed to characterize the metabolomic footprint for recovering severe COVID-19 patients in three consecutive time points and compare metabolite levels to controls. Our findings add proof of dysregulated amino acid metabolism in the acute phase, and dyslipidemia, glycoprotein level alterations, and energy metabolism disturbances in severe COVID-19 patients 3-4 months post hospitalization.

Introduction: The aim of this study is to compare the histopathological findings in the resected tracheal ring of tracheotomized critically ill patients with or without severe SARS-CoV-2 infection. Material and Methods: Prospective case-control study. Data collection period was between May 2020-2022. 80 tracheostomies on patients with long intubation were performed and the resected tracheal ring was examined by standard microscopy. 40 consecutive tracheotomies in COVID-19 patients and 40 in patients without COVID-19 disease were carried out. Results: The mean age was 68.18 years in the COVID group and 56.1 years in the NO COVID group. The male/female ratio was 32/8 versus 29/11 respectively. No relevant histological alterations were found in 82.5% of samples. Chronic subepithelial inflammation was found in 13.8% of cases. Two cases presented vasculitis (2,5%) and one case thrombotic microangiopathy (1,2%), all cases in the COVID group. We found no statistically significant dependence between relevant histologic findings versus no alterations (X2=0.779) no significant indices for measuring association (Rho= 0.1316) and no significant risk indices (RR = 1.8, OR=2.032, PAR= 44%). Conclusion: There is no evidence of increased risk of histopathological findings of the resected tracheal ring in patients with long intubation and COVID-19 disease.

To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease, TMPRSS2, in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. As shown, ACE2 has medium levels of expression in both small airway epithelium and masticatory mucosa, and high levels of expression in nasal epithelium. The expression of ACE2 is low in mucosal associated invariant T (MAIT) cells, and can’t be detected in alveolar macrophages. TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium, and has lower expression in masticatory mucosa. Our results provide the molecular basis that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection and consequently for subsequent droplet transmission and should be the focus for protection against SARS-CoV-2 infection.

COVID-19 pandemic has caused a large-scale havoc in almost every country across the globe, putting major challenges for the healthcare system in many parts of the world. Several of the laboratories are running in the race with undying efforts for developing potential vaccine, drugs or therapeutics to treat or prevent the infection. However, with the limited time window and high rate of infection, the task is very big for humanity to find a cure. With hundreds of genomic data of SARS-CoV-2 virus isolates from humans are being submitted almost every day, it is coming into knowledge that virus is mutating, slower in countries with sporadic cases, but higher in countries experiencing large outbreak. These types of mutations in virus may bring challenges in vaccine or therapeutic development for use in each and every country, as each hotspot region may have their own pattern of mutations in virus with ongoing outbreak. In our current study, we retrieved non-synonymous mutation data of around 12,225 SARS-CoV-2 virus samples isolated from humans globally, and discovered all mutations that are collectively happening in antibody epitope regions of the virus country-wise. We found a few numbers of epitope regions in SARS-CoV-2 that are highly conserved collectively in all variants and may be used for epitope-based vaccine development for whole world. We also found epitope regions that are conserved collectively in SARS-CoV-2 variants country-wise and can be used for customized epitope-based vaccine development in each different country.

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scan and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impact on the functions of the cardiovascular system and the liver. The aim of this study is to stipulate and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, CCAAT/enhancer binding protein α, sterol regulatory ele-ment-binding protein 1c, fatty acid synthase, endothelial lipase, carnitine palmitoyltransferase 1A, and adiponectin receptor 2 in liver tissue; lipoprotein lipase, visceral adipose tissue-derived serine protease inhibitor, and retinol-binding protein 4 in visceral adipose tissue; resistive index of com-mon carotid arteries and aortas, and histopathological changes in CCAs. Obtained outcomes are referred to the results of our previous works. Moreover, our study, to our knowledge, test the in-fluence of Cornus derivative on CPT1A, AdipoR2, RBP4, LIPG, and vaspin for the first time, with a relevant outcome for the first three. Oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and de-creased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigation in atheromatous changes in rabbits’ CCAs was also observed. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.

Ubiquitin-specific protease 2 (USP2) maintains mitochondrial integrity in culture myoblasts. In this study, we investigated molecular mechanisms underlying the protective role of USP2 on mitochondria. Knockout (KO) of the Usp2 gene or chemical inhibition of USP2 induced robust accumulation of mitochondrial reactive oxygen species (ROS), accompanied by defects in mitochondrial membrane potential, in C2C12 myoblasts. ROS removal by N-acetyl-L-cysteine restored the mitochondrial dysfunction induced by USP2 deficiency. Comprehensive RT-qPCR screening and following protein analysis indicated that both genetic and chemical inhibition of USP2 elicited a decrease of uncoupling protein 2 (UCP2) at mRNA and protein levels. Accordingly, the introduction of a Ucp2-expressing construct effectively recovered mitochondrial membrane potentials, entailing an increment of the intracellular ATP level in Usp2KO C2C12 cells. In contrast, USP2 deficiency also decreased peroxisome proliferator-activated receptor  coactivator 1 (PGC1 protein in C2C12 cells, while it upregulated Ppargc1a mRNA. Overexpression studies indicate that USP2 potentially stabilizes PGC1 in an isopeptidase-dependent manner. Given that PGC1 is an inducer of UCP2 in C2C12 cells, USP2 might ameliorate mitochondrial ROS by maintaining the PGC1–UCP2 axis in myoblasts.

A green, fast and selective approach for the synthesis of mono-substituted closo-decaborate derivatives [2-B10H9COR]n– has been established via a nucleophilic addition reaction between the carbonyl derivative of closo-decaborate [2-B10H9CO]– and the corresponding Grignard reagent RMgX, where R is the ethyl, iso-propyl, pentyl, allyl, vinyl, and propynyl groups. This approach is accomplished under mild conditions with 70–80% yields. The significance of these derivative is their ability to constitute building blocks for polymeric integration via the allyl, vinyl and propynyl substituents. All products were characterized by 11B, 1H, and 13C NMR, elemental analysis and mass spectrometry.

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different biopertinent activities specially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,β-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI assay. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05, respectively, demonstrating remarkable apoptosis and mod-erate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold a clinical promise against acute myeloid leukemia.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

Abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with ACE2 receptor located in endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease leading to irreversible tissue damage and death of patients with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated to the interaction of SARS CoV-2 with ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome (ARDS), multiorgan failure and sepsis requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure (HF), coronary heart disease (CHD) and risk factors for atherosclerotic progression, hypertension and diabetes among others.Atherosclerotic progression, as chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic progression may impact on a different degree of severe infection and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic progression due to excessive and aberrant plasmatic concentration of cytokines.

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic affecting approximately 490,000 people and accounting for more than 22,000 deaths and has no generally acceptable cure. Here, the recently resolved 3D structure of SARS-CoV-2 receptor binding domain (RBD) in complex with its receptor-the angiotensin converting enzyme-2 (ACE-2) have provided the basis for screening chemical database for novel entry inhibitors. Methods: Molecular docking protocols have been used to rapidly screen FDA database for high affinity interaction at the SARS-CoV-2-RBD/ACE-2 interface. One of the top candidates, ubrogepant has been selected and further studied using atomistic molecular dynamics simulation method. Results: Molecular docking result showed that ubrogepant (UBR) and darunavir have binding energies of -10.4 kcal/mol. MMPBSA free energy analyses of UBR bound to RBD, ACE-2 and RBD/ACE-2 revealed RBD/ACE-2 > ACE-2 > RBD preference. Network analysis showed that interaction captured in the crystal structure were disrupted in UBR-bound state, hydration of the interface and increased atomic fluctuation within the RBD oligomerization interface and ACE-2 zinc binding site. Conclusions: The ability of ubrogepant to rupture the interaction at the RBD/ACE-2 interface residues of SARS-CoV-2 RBD/ACE-2 complex may result in loss of protein function with direct implication on oligomerization formation in RBD and loss of function in ACE-2 thus, making binding, cellular receptor recognition impossible. General Significance: Ubrogepant represents a new therapeutic candidate in the fight against COVID-19, as it binds with relatively high affinity with free RBD, ACE-2 receptor and SARS-CoV-2 RBD/ACE-2 complex based on binding affinity calculations.

SARS-CoV-2 is constantly evolving leading to new variants. We analysed data from 4,400 SARS-CoV-2-positive samples in order to continue variant surveillance in Italy to evaluate their epidemiological and relative impact on public health in the period April-December 2021. The main circulating strain (76.2%) was Delta followed by Alpha (13.3%), Omicron (5.3%) and Gamma variants (2.9%). B.1.1 lineages, Eta, Beta, Iota, Mu and Kappa variants represented around 1% of cases. Overall, 48.2% of subjects were not vaccinated with a lower median age compared to vaccinated subjects (47 vs. 61 years). An increasing number of infections in vaccinated subjects was observed overtime, with the highest proportion in November (85.2%). Variants correlated with clinical status; the largest proportion of symptomatic patients (59.6%) was observed among Delta variant, while subjects harboring Gamma variant showed the highest proportion of asymptomatics (21.6%), albeit also of deaths (5.4%). The Omicron variant was only found in vac-cinated subjects, of which 47% were hospitalized. Diffusivity and pathogenicity associated with the different SARS-CoV-2 variants are likely to have relevant public health implications, both at national and international level. Our study pro-vides data on the rapid changes in the epidemiological landscape of SARS-CoV-2 variants in Italy.

The COVID-19 pandemic initiated a race to determine the best measures to control the disease and to save as many people as possible. Efforts to implement social distancing, the use of masks, and massive vaccination programs turned out to be essential in reducing the devastating effects of the pandemic. Nevertheless, the high mutation rates of SARS-CoV-2 challenge the vaccination strategy and maintain the threat of new outbreaks due to the risk of infection surges and even lethal variations able to resist the effects of vaccines and upset the balance. Most of the new therapies tested against SARS-CoV-2 came from already available formulations developed to treat other diseases, so they were not specifically developed for SARS-CoV-2. In parallel, the knowledge produced regarding the molecular mechanisms involved in this disease was vast due to massive efforts worldwide. Taking advantage of such a vast molecular understanding of virus genomes and disease mechanisms, a targeted molecular therapy based on siRNA specifically developed to reach exclusive SARS-CoV-2 genomic sequences was tested in a non-transformed human cell model. Since coronavirus can escape from siRNA by producing siRNA inhibitors, a complex strategy to simultaneously strike both the viral infectious mechanism and the capability of evading siRNA therapy was developed. The combined administration of the chosen produced siRNA proved to be highly effective in successfully reducing viral load and keeping virus replication under control, even after many days of treatment, unlike the combinations of siRNAs lacking this anti-anti-siRNA capability. Additionally, the developed therapy did not harm the normal cells, which was demonstrated because, instead of testing the siRNA in nonhuman cells or in transformed human cells, a non-transformed human thyroid cell was specifically chosen for the experiment. The proposed siRNA combination deeply reduced the viral load throughout the experiment and allowed cellular recovery, thus representing a potential innovation, to be considered as an additional weapon for therapy of COVID-19 and even other infectious diseases.

Ferroptosis is a unique variety of non-apoptotic cell death, driven by massive lipid oxidation in an iron-dependent manner. Since Ferroptosis was introduced as a concept in 2012, it was shown it's essential role in the pathogenesis in neurodegenerative diseases and an important role in therapy-resistant cancer cells. Thus, a detailed molecular understanding of both canonical and alternative ferroptosis pathways are required. There is a set of widely used chemical agents to modulate ferroptosis using different pathway targets: Erastin blocks cystine-glutamate antiporter, system xc-; ML210 directly inactivate GPX4; L-buthionine sulfoximine (BSO) inhibits γ-glutamylcysteine synthetase, an essential enzyme for glutathione synthesis de novo. Most studies were focused on lipidomic profiling of model systems undergoing death in a ferroptotic modality.

Angiotensin-converting enzyme 2 (ACE2) is an important player of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II into angiotensin (1-7). While expressed on the surface of human cells, such as lung, heart, kidney, neurons, and endothelial cells (EC), ACE2 is the entry receptor for SARS-CoV-2. Here, we would like to highlight that ACE2 is predominant on the EC membrane. Many of coronavirus disease 2019 (COVID-19) symptoms have been associated with the large recruitment of immune cells, directly affecting EC. Additionally, cytokines, hypoxia, and complement activation can trigger the activation of EC leading to the coagulation cascade. The EC dysfunction plus the inflammation due to SARS-CoV-2 infection may lead to abnormal coagulation, actively participating in thrombo-inflammatory processes resulting in vasculopathy and indicating poor prognosis in patients with COVID-19. Considering the intrinsic relationship between EC and the pathophysiology of SARS-CoV-2, EC-associated therapies such as anticoagulants, fibrinolytic drugs, immunomodulators, and molecular therapies have been proposed. In this review, we will discuss the role of EC in the lung inflammation and edema, in the disseminate coagulation process, ACE2 positive cancer patients, and current and future EC-associated therapies to treat COVID-19.

The novel respiratory disease COVID-19 has reached the status of worldwide pandemic and large efforts are currently being undertaken in molecularly characterizing the virus causing it, SARS-CoV-2. The genomic variability of SARS-CoV-2 specimens scattered across the globe can underly geographically specific etiological effects. In the present study, we gather the 48,635 SARS-CoV-2 complete genomes currently available thanks to the collection endeavor of the GISAID consortium and thousands of contributing laboratories. We analyze and annotate all SARS-CoV-2 mutations compared with the reference Wuhan genome NC_045512.2, observing an average of 7.23 mutations per sample. Our analysis shows the prevalence of single nucleotide transitions as the major mutational type across the world. There exist at least three clades characterized by geographic and genomic specificity. In particular, the clade G, prevalent in Europe, carries a D614G mutation in the Spike protein, which is responsible for the initial interaction of the virus with the host human cell. Our analysis may drive local modulation of antiviral strategies based on the molecular specificities of this novel virus.

A novel coronavirus has been reported as the causative pathogen of the Coronavirus disease 2019 (COVID-19) outbreak Wuhan city, China in December 2019. Due to the rapid spreading of COVID-19 worldwide, it has been announced as a pandemic by the World Health Organization (WHO). Hospitalized patients in Wuhan are associated with the Huanan seafood wholesale market where live animals, such as poultry, bats, snakes, frogs, rabbits, marmots, and hedgehogs are sold in that market which suggests a possible zoonotic infection. Therefore, it is essential to identify the potential animal reservoir, and the possibility of infection for other animal species. This short review aims to provide an overview on the relation between severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection and animals.

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread so rapidly and severely affected the people of almost every country in the world. The highly contagious nature of this virus makes it difficult to take control of the present pandemic situation. With no specific treatment available, the coronavirus disease 2019 (COVID-19) presents a threat to people of all ages including the elderly people and people with other medical complications as a vulnerable group to this disease. Better understanding of viral pathogenesis, appropriate preventive measures, early diagnosis and supportive treatments of the infected patients are now the general solutions to fight against this viral transmission. But, as an emerging disease, most about it remains still poorly understood. This article holds an overview on the origin and structure, pathogenesis, diagnosis and possible therapeutic options for the causative agent, SARS-CoV-2 and disease, COVID-19. However, few therapeutic options, laboratory experiments and other strategies proposed here need to be further clinically tested.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, rheumatoid arthritis or cancer. Inflammation in the brain is marked by the upregulation of the translocator protein (TSPO) in microglia. Moreover, high TSPO levels are found, for example in macrophages during rheumatoid arthritis and in malignant tumor cells compared to its relatively low physiological expression. The same applies for cycloxygenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable to monitor the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases like rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry and the associated function in different T2D -mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. Physiological controls included 5mM glucose with 20mM mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25mM glucose. Further treatments included insulin, palmitate, or both. After short-term (24h) or long-term (96h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. Mitochondrial size and relative frequencies were assessed by morphometric analyses using electron micrographs. C2C12 and H9C2 cells treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D -mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity, and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D -mimicking treatments.Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow studying disease mechanisms, potential new targets, and screen candidate therapeutic compounds.

(1) Background: Since the onset of the SARS-CoV-2 pandemic, seven epidemic waves have been described in Spain. Our objective was to study mortality and severity, and associated factors in our hospitalized patients; (2) Method: Retrospective cohort study was conducted on COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) from the beginning of the pandemic until December 31, 2022; (3) Results: A total of 5,510 admissions for COVID-19 were recorded. First wave accounted for 1,823 (33%) and exhibited the highest proportion of severe patients (lowest mean oxygen saturation, 88.2%; elevated levels of CRP, IL-6, D-dimer and ferri-tin), but a below-average percentage of intubated patients (5% vs. 6.5%). Overall mortality rate was 10.3%, higher during the first wave (11.5%) and the two winter waves (third: 11.3%, sixth: 12%), although the first wave represented 39% of the total. Variables associated with mortality were age (OR 1.08,1.07-1.09), need for high-flow oxygen (OR 6.10,4.94-7.52), oncological disease (OR 1.88,1.53-2.60), dementia (OR 1.82,1.2-2.75), Charlson index (OR 1.38,1.31-1.47), and maxi-mum IL-6 levels (OR 1.001,1.000-1.001); (4) Conclusions: Variables associated with mortality in-cluded age, comorbidity, respiratory failure, and inflammation. Differences on baseline charac-teristics of patients admitted explained differences on mortality in each wave

Background: Continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS) have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). Despite a similar outcome of all device-aided therapies (DATs), some patients switch or combine DATs. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons and their frequency for switching/combining were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale. Non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in total 30 patients (6%), who either switched DAT (N=24: 7 LCIG-to-STN-DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN-DBS, 8 CSAI-to-LCIG, 1 STN-DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN-DBS, and 1 STN-DBS-to-CSAI-to-LCIG) or combined DATs (N=6: 5 STN-DBS+LCIG and 1 STN-DBS+CSAI-to-STN-DBS+LCIG). In most of these patients, inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT related complications.

Introduction: On March 11, 2020, the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) as a pandemic. The spread of the Delta variant of coronavirus started in June 2021 and accounted for the fifth peak of COVID-19 in Iran in July 2021. According to reports from other countries, vaccination protects against severe diseases caused by COVID-19, including the Delta variant. Studies have also shown that vaccination provides strong protection against SARS-CoV-2 infection, COVID-19-related hospitalization, and mortality. This retrospective cohort study was designed based on the medical care monitoring center (MCMC) database of Sayyad Shirazi Hospital.Methods: The following patient data were extracted for this study: demographic characteristics, signs and symptoms, ICU admission, need for aggressive oxygen therapy, including intubation, mortality, and vaccination status. Results: Being vaccinated was associated with a 4.14-fold increase in survival (adjusted OR=4.14; 95% CI: 2.22 to 7.69; P<0.01), and individuals in a younger age group demonstrated a 5.58-fold higher likelihood of surviving (adjusted OR=5.58; 95% CI: 4.25 to 8.14; P<0.01). The risk of severe COVID-19 was significantly lower in vaccinated individuals, showing a 3.12-fold decrease in risk (adjusted OR=3.12; 95% CI: 2.06 to 4.72; P<0.01), and in younger age groups, the risk exhibited a 3.28-fold decrease (adjusted OR=3.28; 95% CI: 2.66 to 4.04; P<0.01).Conclusion: The present results suggest that receiving at least one dose of COVID-19 vaccine had a significant relationship with decreased COVID-19 severity and mortality in vaccinated patients compared to unvaccinated patients.

Recycled wastewater is considered as a sustainable source of irrigation water. Despite commendable safety records, viral contamination of agricultural products has occurred the past causing disease outbreaks. This review examines the apprehension that the novel coronavirus (SARS-CoV-2) may also spread through recycled wastewater irrigation (RWI) industry. The novel SARS-CoV-2 is now perceived as an enteric pathogen, and has been found to remain stable in the wastewater for days. Mounting evidences also suggest that viral particles shed by infected individuals through sewage, and greywater is much higher (up to 10 Log₁₀) than the amount typically removed (6-7 Log₁₀) through the recycled water disinfection processes. Such gap indicated an increased risk of infection through fecal-oral transmission route. This study also identified greywater irrigation schemes posing a higher risk of transmission of SARS-CoV-2. It was recommended that countries putting greywater in the ‘low risk’ category may rewrite the safety guidelines in post COVID-19 times. This review also suggest that the choice of irrigation method could be critical in protecting the farmers, and the consumers from possible infections during the pandemic. In this regard, irrigation methods (i.e. sprinkler) that generate airborne droplet (leading to aerosols) may be operated with caution when public spaces are in the vicinity. The study also indicated that the developing countries should regulate surface irrigation practice that pump water from polluted rivers during the pandemic.

Osteoporosis is a common metabolic bone disease in patients with diabetes, which can develop simultane-ously with Type 2 diabetes (T2D) in postmenopausal women. Bisphosphonate (BP) is administered to pa-tients with both the conditions and may cause medication-related osteonecrosis of the jaws (MRONJ). It affects the differentiation and function of osteoclasts as well as thickness of cortical bone through bone mineralization. Therefore, this study aimed to investigate the effects of T2D on osteoclast differentiation and activity as well as cortical bone formation in postmenopausal patients with MRONJ. Tissue samples were collected from 10 patients diagnosed with T2D and Stage III MRONJ in the experimental group and from 10 patients without T2D in the control group. Histological examination was conducted, and expres-sion of dendritic cell-specific transmembrane protein (DC-STAMP) and tartrate resistant acid phosphatase (TRAP) was assessed. Cortical bone formation was analyzed using CBCT images. The number of TRAP-positive osteoclasts and DC-STAMP-positive mononuclear cells were significantly less in the experi-mental group (p < 0.05). Furthermore, the thickness and ratio of cortical bone were significantly greater in the experimental group (p < 0.05). In conclusion, T2D decreased the differentiation and function of osteo-clasts, and increased cortical bone formation in postmenopausal patients with MRONJ.

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action – to uncover and develop anti-viral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analog prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of its mechanism of action, discovery, and the current studies exploring its clinical effectiveness.

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

Aims: Spironolactone is a steroidal mineralocoricosteroid receptor antagonist (MRA) used for treatment of resistant hypertension, heart failure and edema. It exerts class specific adverse effects that are shared by other MRAs. Additionally, it exerts unique “off target” steroidal effects that include gynecomastia, impotence and loss of libido in males and menstrual irregularity in females. Together, these have led to a poor tolerability and limited use despite positive results in many randomized, controlled clinical trials. We review the off-target effects of spironolactone that may summate with its MRA action to provide an advantageous profile for prevention or treatment of patients with COVID-19. Methods: Literature review using PubMed Central. Results: The blockade by spironolactone of the androgen receptor should diminish the expression of transmembrane protease serine 2 (TMPRSS2) that has an androgen promoter while its MRA action should enhance the expression of protease nexin1 (PN1) that inhibits furin and plasmin. TMPRSS2, furin and plasmin cooperated to process the SARS-CoV-2 spike protein to increase its high affinity binding to the angiotensin converting enzyme 2 (ACE2) and thereby promote viral cell entry. Its actions as an MRA may reduce inflammation and preserve pulmonary, cardiac and vascular functions. Its anti-plasmin action may combat hemostatic dysfunction. Conclusion: The hypothesis that the off-target effects of spironolactone summate with its MRA actions to provide special benefits for COVID-19 is worthy of direct investigation and clinical trial.

Many reports showed a dramatic decrease in the levels of physical activity during the current pandemic of SARS-COV-2. This has substantial immunometabolic implications, especially in those at risk or with metabolic diseases including individuals with obesity and Type 2 diabetes. Here we discuss the route from physical inactivity to immnometabolic aberrancies; focusing on how insulin resistance could represent an adaptive mechanism to the low physical activity levels and/or high energy intake and on how such an adaptive mechanism could derail to be a pathognomonic feature of metabolic diseases creating a vicious circle of immune and metabolic aberrancies. We provide a theoretical framework to the severe immunopathology of COVID-19 in patients with metabolic diseases. We finally discuss the idea of exercise as a potential adjuvant against COVID-19 and emphasize how even interrupting prolonged periods of sitting with short time breaks of very light activity could be a feasible strategy to limit the deleterious effects of sedentary behavior.

The aim of this study was to analyze other possible new markers of severity that can be assessed in patients with type 2 diabetes and SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) infection. Our study included 90 subjects: 45 patients with type 2 diabetes mellitus and infected with the SARS-CoV-2 virus, and 45 healthy persons as control. The serum level of ceruloplasmin at hospital admission was statistically significant directly correlated with the severity of COVID-19 (Coronavirus disease) (p=0.037) and with the serum level of IL-6 (Interleukine 6) (p=0.000). Ceruloplasmin was statistically significant inversely correlated with serum iron level (p=0.000). However, we observed that ACE (Angiotensin converting enzyme) decreased in severe forms of the infection with SARS-CoV-2 virus in patients with type 2 diabetes (p=0.001). Moreover, the decrease in ACE level was correlated with an increase in IL-6 level in these patients (p=0.001). IL-6 increase was statistically significant inversely correlated with serum iron, transferrin and ACE levels. There was a noticed a decreasing tendency of the transferrin depending on the severity of the COVID-19 infection (p=0.000). In addition to the known severity factors in the context of infection with the new coronavirus, decreased concentrations of ceruloplasmin, ACE and transferrin may represent new markers of COVID-19 severity in patients with type 2 diabetes. These parameters analyzed at the hospital admission could show the evolution towards the severe forms of infection with the SARS-CoV-2 virus.

In this study, we investigated the effects of Akebia quinata ethanol extract (AE), Akebia quinata sikhye (AS), and Akebia quinata water extract (AW) on alcohol-induced liver injury in rats. The hepatoprotective, anti-inflammatory, anti-apoptotic, and antioxidant effects of AE, AS, and AW were examined. Experimental animals were randomly divided into five groups: normal, ethanol, AE (10 mL/kg), AS (10 mL/kg), and AW (10 mL/kg). Each group was administered the respective treatment orally once per day for 21 days. CYP2E1 mRNA expression was significantly lower in the AE, AS, and AW groups than that in the ethanol group. Pro-inflammatory cytokines including cyclooxygenase-2, IL-6, and TNF-α increased significantly in the ethanol group but these increases were ameliorated with AE, AS, and AW treatment. Moreover, the expression of the apoptosis-associated proteins Bax, p53, procaspase-3, and PARP decreased after treatment with AE, AS, and AW. The expression of antioxidant enzymes including BCL-2, SOD, and GST slightly decreased in the ethanol group, but AE, AS, and AW treatment augmented their activities. AQ extracts and AS attenuated ethanol-induced increases in the levels of phosphorylated p-AKT, p-ERK, and p-JNK. These results demonstrate that AQ is a competence indicator for inhibiting alcoholic liver injury.

The SARS-CoV-2 Omicron variant and its sublineages continue to cause COVID-19—associated pediatric hospitalizations, severe disease, and death globally. BNT162b2 and CoronaVac are among the top most widely used COVID-19 vaccines. Much less is known on the Wuhan-Hu-1 strain based vaccines in the pediatric population compared to adults. Given the worldwide need for booster vaccinations to stimulate the immune response against new Omicron variants of SARS-CoV-2, we characterized the humoral and cellular immune response against Omicron variant BA.1 in a pediatric population aged 10 to 16 years who received heterologous vaccination based on two doses CoronaVac, two doses CoronaVac (2x) plus one booster doses BNT162b2 [CoronaVac(2x) + BNT162b2 (1x)], two doses CoronaVac plus two booster doses BNT162b2 [CoronaVac(2x) + BNT162b2 (2x)], and three doses BNT162b2. We observed that [CoronaVac(2x) + BNT162b2 (2x)] vaccination showed higher anti-S1 and neutralizing antibody titers and CD4 and CD8 T cell immunity specific to the Omicron variant compared to immunization with two doses CoronaVac alone. Furthermore, from all groups tested, immunity against Omicron was highest in individuals who received three doses BNT162b2. We conclude that booster vaccination with BNT162b2 promotes greater immunity against SARS-CoV-2 in the pediatric population compared to two doses CoronaVac alone.

Our investigation focused on the degradation of perfluorooctanoic acid (PFOA) and 6:2 fluorotelomer sulfonamide alkyl betaine (6:2 FTAB, Capstone B), using UV photolysis under various pH conditions. Initially, we used PFOA as a reference, finding a 90% decomposition after 360 minutes at the original (unadjusted) pH 5.6, with a decomposition rate constant of (1.08 ± 0.30) × 10-4 sec-1 and a half-life of 107 ± 2 minutes. At pH 4 and 7, degradation averaged 85% and 80%, respectively, while at pH 10, it reduced to 57%. For 6:2 FTAB at its natural pH 6.5, almost complete decomposition occurred. The primary UV transformation product was identified as 6:2 fluorotelomer sulfonic acid (6:2 FTSA), occasionally accompanied by shorter-chain perfluoroalkyl acids (PFAA). Interestingly, the overall decomposition percentages were unaffected by pH for 6:2 FTAB, though pH influenced rate constants and half-lives. In PFOA degradation, direct photolysis and reaction with hydrated electrons were presumed mechanisms, excluding the involvement of hydroxyl radicals. The role of superoxide radicals remains uncertain. For 6:2 FTAB, both direct and indirect photolysis were observed, with potential involvement of hydroxyl, superoxide radicals, and/or other reactive oxygen species (ROS). Clarification is needed regarding the role of eaq- in the degradation of 6:2 FTAB.

We have proposed a simple algorithm to retrieve the total ozone column and snow properties (spectral albedo and effective light absorption path) using the high spatial resolution single – view MSI/S-2 measurements over Antarctica.

The aim of this study was the reconstruction of SARS-CoV-2 evolutionary dynamics in time and space in Italy and Europe between February and June 2020. The cluster analysis showed that pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 entered Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, the reconstructed ancestral scenario suggests a central role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 2020.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

Purpose: Pandemic Novel Coronavirus (SARS-CoV-2) has emerger centered from wuhan, China. Structurally homologous spike protein of SARS-CoV-2 receptor is taxonomically homologous with SARS-Cov and SARS associated bat coronavirus. Still now scientists are trying to find out proper vaccine and treatments for this disease. Methods: Systematically we modeled and compared the structure of SARS-CoV-2 spike protein along with Bat Cov, Bat SARS Cov and SARS Cov Urbani. S1 and S2 unit of the coronavirus (SARS-CoV-2) are attached with ACE2 and furin, here we docked 5 Ca+ chelating drugs with these two proteins. Results: Structural comparison with all these spike proteins revealed that less significant but not negligible difference exists among them. Inserted stable nucleotide sequences and corresponding surface exposed peptidal region may be considered as epitope. Docking result with Toxicokinetics and half life of Penicillamine can effectly inhibit the attachment site of spike protein of coronavirus (SARS-CoV-2). Conclusions: Docking summery and the pharmacokinetics with toxicokinetics index recommend that Penicillamine can able to inhibit the infection of SARS-CoV-2.

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.

Best Management Practices (BMPs) are commonly used to control pollution in the river basins. Prioritization of BMPs helps improve the efficiency and effectiveness of pollution reduction, especially in Critical Source Areas (CSAs) that produce the highest pollution loads. Recently, the Dez River in Khuzestan, Iran, has become highly eutrophic from the overuse of fertilizers and pesticides. In this basin, dry and irrigated farming produce 77.34% and 6.3% of the Total Nitrogen (TN) load, and 83.56% and 4.3% of the Total Phosphorus (TP) load, respectively. In addition, residential, pasture, and forest land uses together account for 16.36% of the TN and 12.14% of the TP load in this area. The Soil and Water Assessment Tool (SWAT) was implemented to model the Dez River basin and evaluate the applicability of several BMPs, including point source elimination, filter strips, livestock grazing, and river channel management, in reducing the entry of pollution loads to the river. Sensitivity analysis and calibration/validation of the model was performed using the SUFI-2 algorithm in the SWAT Calibration Uncertainties Program (SWAT-CUP). The CSAs were identified using individual (sediment, TN, TP) and combined indices, based on the amount of pollution produced. Among the BMPs implemented, the 10 m filter strip was most effective in reducing TN load (42.61%), and TP load (39.57%).

Providing simultaneously autotrophic and heterotrophic carbon sources is a promising strategy to overcome the limits of autotrophic syngas fermentations. D-xylose and L-arabinose are particularly interesting as they can be obtained by the hydrolysis of lignocellulosic biomass. The individual conversion of varying initial concentrations of these pentoses and D-fructose as reference was studied with C. autoethanogenum in fully-controlled stirred-tank reactors with a continuous syngas supply. All mixotrophic batch processes showed increased biomass and product formation compared to an autotrophic reference process. Simultaneous CO and D-xylose or L-arabinose conversion was observed in contrast to D-fructose. In the mixotrophic batch processes with Larabinose or D-xylose, the simultaneous CO and sugar conversion resulted in high final alcohol to acid ratios of up to 58 g g-1. L-arabinose was superior as a mixotrophic carbon source because biomass and alcohol concentrations (ethanol and 2,3-butanediol) were highest, and significant amounts of meso-2,3-butanediol (>1 g L-1) in addition to D-2,3-butanediol (>2 g L-1) were solely produced with L-arabinose. Furthermore, C. autoethanogenum could not produce meso-2,3 butanediol under purely heterotrophic conditions. The mixotrophic production of meso-2,3-butanediol from Larabinose and syngas, both available from residual lignocellulosic biomass, is very promising for use as a monomer for bio-based polyurethanes or as an antiseptic agent.

The viability, productivity and survival of higher plants under the adverse factors influence are largely determined by the functional activity of the antioxidant system. The aim of our work was to investigate changes in formation of high-molecular (superoxide dismutase and peroxidase) and low-molecular (phenolics, including flavanols and proanthocyanidins) antioxidants in callus culture of Camellia sinensis under influence of phenolic precursors (L-phenylalanine – 3 mM, trans-cinnamic acid – 1 mM, naringenin – 0.5 mM). According to the data obtained, precursors effect on tea callus cultures did not lead to significant increasing of superoxide dismutase and peroxidase activity in most cases. However, it led to the increased accumulation of the total phenolics content, as well as flavanols and proanthocyanidins contents. For C. sinensis callus cultures, the most promising regulator of phenolic compounds was L-phenylalanine, in the presence of which its content increased almost twice. Thus, the exogenous effect of various precursors is possible to use for the targeted regulation of the certain phenolics classes accumulation in plant cells.

Phenotypic plasticity is widely acknowledged as one of the most common solutions for coping with novel environmental conditions following climate change. However, it is less known wheth-er current amounts of trait plasticity, which is sufficient for matching with contemporary climate, will be adequate when global temperatures exceed historical levels. We addressed this issue by ex-ploring the responses of functional and structural leaf traits in Iris pumila clonal individuals to ex-perimentally increased temperature (~1.5°C), using an open top chamber (OTC) design. We de-termined phenotypic values of specific leaf area, leaf dry matter content, specific leaf water con-tent and leaf thickness in leaves sampled from the same clone inside and outside of the OTC de-ployed on it, over seasons and years within two natural populations. We analyzed the data by a repeated multivariate analysis of variance, which is primarily focused on profiles (reaction norms, RNs) of a variable gathered from the same individual at several different time points. We found that the mean RNs of all analyzed traits were parallel regardless of experienced temperatures, but differed in the level and the shape. The populations RNs were similar as well. Since the amount of plasticity in analyzed leaf trait was adequate for coping with elevated temperatures inside the OTCs, we predict that it will be also sufficient for responding to increased temperatures if they exceed the 1.5°C target.

Methods for cost calculation of Laser-based Additive Manufacturing (LAM) have evolved over the last two decades. Starting from a rapid prototyping manufacturing method, cost calculation over time included more than single part production for small series or mixed batches. New machine developments nowadays aim at large scale production and introduce modular machine designs that give LAM factory operators more decision freedom on machine configurations and expansibility. To leverage this new possibilities, LAM costing methods must be adapted to calculate and visualize the economic consequences of different module configurations.In this work a modelling architecture of L-PBF machines using virtual modules is presented. Using principles of the industry 4.0 communication standard OPC UA, a virtual machine is set up, parametrized and connected to the AM digital process chain. Two different views on the cost information are used, optimized for different use cases.First, the product view allows detailed analysis of cost allocation to parts in mixed batches and the layered geometry of the part. Second, the machine view tracks utilization of all machine modules, divided into the states idle, active, off and maintenance. The theoretical Overall Equipment Effectiveness (OEE) is calculated on a module basis, enabling economic analysis and optimization of module composition as well as module improvements and new modular machine constellations. This allows focusing research and development on most valuable improvements. By calculating different scenarios like spare part production, mass production or rapid prototyping, the part portfolio to be manufactured can be considered.

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are also widespread. To prove the effectiveness and safety of these preventive vaccines and therapeutic drugs, available animal models that faithfully recapitulate clinical hallmarks of COVID-19 are urgently needed. Currently, animal models including mice, golden hamsters, ferrets, nonhuman primates and other susceptible animals have been involved in the study of COVID-19. 92 vaccine candidates have entered clinical trials after the primary evaluation in animal models, of which inactivated vaccines, subunit vaccines, virus-vectored vaccines and mRNA vaccines are promising vaccine candidates. In this review, we summarize the landscape of animal models and advanced vaccines with efficacy range from about 50% to more than 95%. In addition, we point out future directions for animal models and vaccine development, aiming at providing valuable information and accelerating the breakthroughs confronting SARS-CoV-2.

Tea (Camellia sinensis) is one of the most popular beverages worldwide. Many types of tea prod-ucts continuously emerge in an endless stream; so, the classification or verification of tea be-comes more difficult. Aroma is a vital indicator of tea quality. The present study deals with the identification of aroma compounds in 18 different kinds of tea belonging to three typical tea va-rieties, including green tea, oolong tea, and black tea, using GC-IMS and GC×GC-O-MS. More-over, the clustering of all 18 tea samples and the in-depth correlation analysis between sensory evaluation and instrumental data were performed using the PCA and OPLS-DA. The results re-vealed that in all 18 kinds of tea, a total of 85 aroma compounds were detected by GC-IMS, whereas 318 were detected by GC×GC-O-MS. The PCA result revealed that green tea, oolong tea, and black tea could be clearly separated based on their peak areas. The OPLS-DA result showed that a total of 49 aroma compounds with VIP value > 1.0 could be considered as the potential in-dicators to quickly classify or verify tea types. This study not only compared the aroma differ-ences across different types of teas, but also provided ideas for the rapid monitoring of tea qual-ity and variety.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (SARS-CoV and MERS-CoV) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to the some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summaries the possible and logic answers to these questions.

SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.

Saliva is a promising matrix with several purposes. Our aim is to verify if salivary anti-SARS-CoV-2 antibody determination is suitable for monitoring immune response. One-hundred eighty-seven subjects were enrolled at University-Hospital Padova: 105 females (56.1%) and 82 males (43.9%), 95 (50.8%) children and 92 (49.2%) adults. Subjects self-collected saliva using Salivette; nineteen subjects collected three different samples within the day. A serum sample was obtained for all individuals. The N/S anti-SARS-CoV-2 salivary IgG (sal-IgG) and serum anti-SARS-CoV-2 S-RBD IgG (ser-IgG) were used for determining anti-SARS-CoV-2 antibodies. The mean (min-max) of age was 9.0 (1–18) for children and 42.5 (20–61) for adults. Of 187 samples, 63 were negative for sal-IgG (33.7%), while 7 were negative for ser-IgG (3.7%). Spearman’s correlation was 0.56 (p&lt;0.001). Sal-IgG and ser-IgG levels were correlated with age, but not with gender, comorbidities, prolonged therapy, previous SARS-CoV-2 infection or time from last COVID-19 infection/vaccination. The repeatability ranged from 23.8% (7.4kAU/L) to 4.0% (3.77kAU/L). Linearity of the assay missed in 4/6 samples. No significant intra-subject differences were observed in sal-IgG across samples collected at different time points. Sal-IgG have a good agreement with ser-IgG. Non-invasive saliva collection represents an alternative method for antibody measurement, especially in children.

The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. It has been shown that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on way to an endemic form, however the threat of the virus is more for susceptible (older people and immunocompromised) people. The human body has more bacterial cells than its own, thus making us more bacterial than humans. As a consequence, the bacteriomes in the human body heavily influence human health and disease. The bacteriomes in the body and the immune system seem to be in constant association during bacterial and viral infections. In this review, we identify various bacterial spp. in major bacteriomes (oral, nasal, lung, and gut) of the body in healthy humans and compare them with dysbiotic bacteriomes of COVID-19 patients. We try to identify key bacterial spp. that have a positive effect on the functionality of the immune system and human health. These select bacterial spp. could be used as potential probiotics to counter or prevent COVID-19 infections. In addition, we try to identify key metabolites produced by probiotic bacterial spp. that could have potential anti-viral effects against SARS-CoV-2. These metabolites could be subject to future therapeutic trials to determine their anti-viral efficacy.

The novel coronavirus named by WHO and Coronavirus Study Group (CSG) as SARS-COV-2 is the etiological agent of the newly emerged Coronavirus disease (COVID-19). COVID-19 has become a pandemic threat as the WHO declared it a public health emergency of international concern. Early and precise detection of the virus is important for effective diagnosis and treatment. Various testing kits and assays, including real-time reverse Transcriptase PCR, thermal screening guns, ELISA-based immunoassays, and Point-of-Care (POC), have been implemented or are being explored to detect the virus and/or characterise cellular and antibody responses to the infection. However, these approaches have inherent limitations such as non-specificity, high cost, characterize by long turnaround times for test results, and can be labour intensive. Aptamers, which are single-stranded oligonucleotides, generated artificially by SELEX (Evolution of Ligands by Exponential Enrichment) may offer the capacity to generate high affinity bioprobes for monitoring relevant SARS-COV 2 and COVID-19 biomarkers. This article discusses the prospects of implementing aptasensing technologies for rapid point-of-care detection of SARS-COV-2.

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

BA.2, a sublineage of Omicron BA.1, is now prominent in many parts of the world. Early reports indicate that BA.2 is more infectious than BA.1. To gain insight into BA.2 mutation profile and the resulting impact of mutations on interaction with receptor and/or monoclonal antibodies, we analyzed available se-quences, structures of Spike/receptor, and Spike/antibody complexes, and conducted molecular dynamics simulations. The results showed that BA.2 has 50 high-prevalent mutations compared to 48 in BA.1. Seventeen BA.1 mutations are not present in BA.2. Instead, BA.2 has 19 unique mutations and a signature Delta variant mutation (G142D). Intriguingly, the BA.2 has 28 signature mutations in Spike, compared to 30 in BA.1. This is due to two revertant mutations S446G and S496G in the receptor-binding domain (RBD), making BA.2 somewhat similar to Wuhan-Hu-1 (WT), which has G446 and G496. The molecular dynamics simulations showed that the RBD consisting of G446/G496 is more stable than S446/S496 containing RBD. Thus, our analyses suggest that BA.2 has evolved with novel mutations (i) to maintain receptor binding similar to WT, (ii) evade the antibody binding greater than BA.1, and (iii) acquire mutation of the Delta variant that may be associated with the high infectivity.

One of the hallmarks of the SARS-CoV-2 infection has been the inflammatory process that played a role in its pathogenesis, resulting in mortality within susceptible individuals. This uncontrolled inflammatory process leads to severe systemic symptoms via multiple pathways, however, the role of endothelial dysfunction and thrombosis have not been truly explored. This review aims to highlight the pathogenic mechanisms of these inflammatory triggers leading to thrombogenic complications. There are direct and indirect pathogenic pathways of the infection that are examined in detail. We also describe the case of carotid artery thrombosis in a patient following the SARS-CoV-2 infection, while reviewing the literature on the role of ACE2, the endothelium, and the different mechanisms by which SARS-CoV-2 may manifest both acutely and chronically. We also highlight differences from the other coronaviruses that have made this infection pandemic with similarities to the influenza virus.

Knowing the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many places during the first wave of COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain), during “Falles” mass gathering events in March 2020, a cross-sectional study was performed in June 2020 querying public health register. Logistic regression models were used. From a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak by anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), thus an underreporting of 92.3% (95% Confidence Interval [CI] 89.5%-94.6%), 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting were no medical assistance for COVID-19 disease, adjusted odds ratio [aOR] 10.83 (95% CI 2.49-47.11), no chronic illness, aOR=2.81 (95% CI 1.28-6.17), middle and lower social classes, aOR=3.12 (95% CI 1.42-6.85), younger age, aOR=0.97 (95% CI 0.94-0.99), shorter duration of illness, aOR=0.98 (95% CI 0.97-0.99). To improve surveillance, studies of representative population samples are necessary to estimate the magnitude of future epidemics, and novel approaches are recommended.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive sense single stranded RNA genome containing virus which has infected millions of people all over the world particularly China. The virus has been mutating rapidly enough resulting in the emergence of new variants and sub-variants which have reportedly been spread from Wuhan city of China, the epicenter of the virus, to the rest of China and all over the world. The occurrence of mutations in the viral genome especially in the viral spike protein region has resulted in the evolution of multiple variants and sub-variants which gives the virus benefit of host immune evasion and render the modern-day vaccines and therapeutics ineffective. Therefore, there is a continuous need to study the genetic characteristics and evolutionary dynamics of the SARS-CoV-2 variants. Hence, in this study, a total of 833 complete genomes of SARS-CoV-2 variants (including the wild-type or reference sequence) from Taiyuan and Wuhan cities of China were genetically characterized and studies their phylogenetic and evolutionary dynamics using phylogenetics, genetic similarity, and phylogenetic network analysis. Our results show a lot of useful information regarding the evolutionary dynamics of the viral variants, their genetic similarities/dissimilarities, and their phylogenetic relationships. It has been reported in this study that the SARS-CoV-2 variants have nine recombinant events which suggest very important information regarding the viral evolution. In addition, the phylogenetic network analysis shows the number of mutations resulting in emergence and clustering of the viral variants of both cities which reveal significant information regarding the phylodynamics of the virus. This study, to the best of our knowledge, is the first ever genetic comparative study of Taiyuan and Wuhan cities. This study will help better understand the virus, cope with the emergence, and spread of new variants at local level as well as at international level and inform the public health authorities to make better informed decisions in designing new viral vaccines and therapeutics.

The DnaA protein has long been considered to play the key role in the initiation of chromosome replication in modern bacteria. Many questions about this role, however, remain unanswered. Here, we raise these questions within a framework based on the dynamics of hyperstructures alias large assemblies of molecules and macromolecules that perform a function. In this dynamics, hyperstructures can (1) emit and receive signals or (2) fuse and separate from one another. We ask whether the DnaA-based initiation hyperstructure acts as a logic gate receiving information from the membrane, the chromosome and metabolism to trigger replication; we try to phrase some of these questions in terms of DNA supercoiling, strand opening, glycolytic enzymes, SeqA, ribonucleotide reductase, the Macromolecular Synthesis operon, post-translational modifications and metabolic pools. Finally, we ask whether, underpinning the regulation of the cell cycle, there is a physico-chemical clock inherited from the first protocells, and whether this clock emits a single signal that triggers both chromosome replication and cell division.

The objective of this study is to assess the hepatic/renal and splenic/renal echointensity ratios in ultrasonography in patients with and without diabetic nephropathy. This retrospective study included patients with diabetes mellitus who underwent ultrasound examinations at our hospital between January 2023 and May 2023. Ultrasound examinations done with renal cortical echogenicity and cortico-medullary differentiation by using B-mode ultrasonography. The hepatic/renal and splenic/renal echo intensity ratios were compared among study groups (diabetic patients with diabetic nephropathy and without nephropathy). The diabetic nephropathy group exhibited significantly higher right renal echointensity and left renal echointensity compared to the non-nephropathic group. Additionally, the splenic/renal echointensity ratio and hepatic/renal echointensity ratio were significantly lower in the diabetic nephropathy group. Urinary microalbumin levels was significantly correlated with Right renal echointensity (r=0.65, p&lt;0.001) and Left renal echointensity (r=0.69, p&lt;0.001). There was also a significant inverse correlation between urinary albumin and splenic/renal echointensity ratio (r=-0.58, p&lt;0.001). Ultrasonography, specifically the assessment of hepatic/renal and splenic/renal echointensity ratios, shows promise as a non-invasive and cost-effective method for evaluating morphological changes in the kidneys in patients with diabetic nephropathy. These findings suggest that ultrasonography can be a valuable tool for monitoring the progression of diabetic nephropathy and contributing to its early detection and management.

Hypoxia — reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OG dioxyenases in the control of gene expression in response to hypoxia and their relevance to human cancers.

Coronaviruses are positive sense RNA virus belonging to the Coronaviridae family, which are further subdivided into four genera: Alpha, Beta, Gamma, and Delta Coronaviruses. Infectious bronchitis virus and SARS-CoV belong to Beta Coronaviridae family. Infectious bronchitis virus causes respiratory and nephritic signs that includes tracheal rales, urate crystals, lethargy and nasal discharge. In livestock and pets, the Coronavirus infection causes mostly gastrointestinal lesions, which may be prevented through vaccination and biosecurity. Recent infections of SARS-CoV-2 (also known as COVID-19) on farm and pet animals were summarized in this study. Besides, zoo animals were reported with infections in some countries/regions. Although the damage of COVID-19 has not been reported as serious as highly pathogenic avian influenza (HPAI) and African Swine Fever (ASF) on farm animals so far, the transmission mechanism of COVID-19 among group animals/farms and its long-term impacts are still not clear. The impact of Coronavirus on animals and potential prevention strategies, such as vaccine development and farm biosecurity measures, were discussed. Prior to the development of the effective vaccine, the biosecurity measures (e.g., conventional disinfection strategies and innovated technologies) may play roles in preventing potential spread of diseases/viruses.

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

Introduction: IFITM3, an innate immune protein linked to COVID-19 severity, has recently been identified as a novel γ-secretase modulator. Independent research has shown that IFITM3 may facilitate SARS-CoV-2 neurotropism in an ACE2-independent manner. In a previous study, we had detected perturbations in IFITM3 networks in both the CNS and peripheral immune cells donated by AD patients. The purpose of this study is to explore the transcriptomic evidence of the SARS-CoV-2 / IFITM3 / AD interplay, validating previous findings from our group. Methods: Exploratory analyses involved meta-analysis of bulk and single cell RNA data for IFITM3 and FYN differential expression. For confirmatory analyses, we performed gene set enrichment analysis (GSEA) on an AD gene signature from AD Consensus transcriptomics; using the Enrichr platform, we scrutinized COVID-19 datasets for significant, overlapping enriched biological networks. Results: Bulk RNA data analysis revealed that IFITM3 and FYN were differentially expressed in two CNS regions in AD: the temporal cortex (AD vs. Controls, adj.p-value=1.3e^-6) and the parahippocampal cortex (AD vs. controls, adj.p-value=0.012). Correspondingly, single cell RNA analysis of IFITM3 and FYN revealed that it was differentially expressed in neuronal cells donated from AD patients (astrocytes, microglia and oligodendrocyte precursor cells), when compared to controls. Discussion: IFITM3 and by extent FYN were found as interactors within biological networks overlapping between AD and SARS-CoV-2 infection. SARS-CoV-2-mediated FYN/IFITM3 induction would mechanistically result in increased Tau fibrilization and Aβ oligomerization. FYN recruitment by viral processes results in abrogation of both fusion of IFITM3 vesicles with lysosomes; immunoevasion, by FYN-mediated impairment of autophagy would then serve to promote impaired detoxification from Aβ, while propagating Tau pathology in an IFITM3-independent manner.

IntroductionThe aim of this study is to describe the epidemiology of all COVID-19 patients in Vietnam and to describe the measures of disease control and prevention implemented. MethodsData were recovered from Wikipedia regarding the 2020 coronavirus pandemic in Vietnam. The period covered was from 23 January to 20 April 2020. Descriptive analysis was stratified by gender, age, country of origin, travel history, clinical symptoms and outcome. A survey of disease control and prevention measures was conducted at the Centre for Disease Control in the Thai Binh province, which is responsible for screening and isolating individuals at high risk of COVID-19. ResultsAs of 20 April 2020, Vietnam had recorded 268 confirmed COVID-19 patients. 55.2% were female. 67.9% were aged 20-49 years and 82.5% were Vietnamese. 60.4% of cases were imported from outside Vietnam. Other cases were acquired in Vietnam by individuals in close contact with imported cases. Only one patient who had not travelled had had no known contact with a confirmed case. 63.1% of patients were asymptomatic. 75.7% of patients were discharged. No deaths were recorded. The Thai Binh CDC surveyed a total of 2,203 persons at risk of COVID-19. 336 persons (15.2%) were isolated at hospitals and 1,411 (64.0%) in dedicated isolation facilities. 16.4% reported at least one respiratory symptom. No positive cases confirmed by RT-PCR have been reported in the Thai Binh province to date. ConclusionThe effect of the systematic screening and isolation strategy made it possible to limit local transmission in Vietnam. Vietnam needs to reinforce diagnostic capacities, prevention measures and provide the necessary epidemiological data on which to base interventions. The wider use of rapid serological tests is also advisable in order to be able to conduct extensive screening in the community.

The Sentinel-2 satellite mission offers high resolution multispectral time series image data, enabling the production of detailed land cover maps globally. At this scale, the trade-off between processing time and result quality is a central design decision. Currently, this machine learning task is usually performed using pixelwise classification methods. The radical shift of the computer vision field away from hand engineered image features and towards more automation by representation learning comes with many promises, including higher quality results and less engineering effort. In this paper we assess fully convolutional neural networks architectures as replacements for a Random Forest classifier in an operational context for the production of high resolution land cover maps with Sentinel-2 time series at the country scale. Our contributions include a framework for working with Sentinel-2 L2A time series image data, an adaptation of the U-Net model for dealing with sparse annotation data while maintaining high resolution output, and an analysis of those results in the context of operational production of land cover maps.

Background: Signaling by toll like receptors (TLRs) initiates important immune responses against viral infection. The role of TLRs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is not well elucidated. Thus, we investigated the interaction of TLRs agonists and SARS-COV-2 antigens with immune cells in vitro. Material & methods: 30 coronavirus disease 2019 (COVID-19) patients (15 severe and 15 moderate) and 10 age and sex matched control (HC) were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and activated with TLR3, 7, 8 and 9 agonists, the spike protein (SP) of SARS-CoV-2 and the Receptor Binding Domain (RBD) unit of SP. Frequencies of CD3⁺IFN-β⁺ T cells, and CD3⁺IFN-g⁺ T cells was evaluated by flow cytometry. Interferon (IFN)-b gene expression was assessed by qRT-PCR. Results: The frequency of CD3+IFN-β+ T cells was higher in moderate and severe patients at baseline in comparison with HCs. Stimulation of PBMCs from moderate patients with SP and TLR8 agonist significantly upregulated the frequency of CD3+IFN-β+ T cells (P=0.0005 and 0.0024, respectively) when compared to non-stimulated (NS) samples. The greatest increase in CD3⁺IFN-b⁺ T cell frequency in PBMCs from severe patients was seen with TLR8 and TLR7 agonists when compared to NS (P= 0.003 and 0.0167, respectively). TLR stimulation did not significantly enhance the frequency of CD3+IFN-g+ T cells generated from PBMCs from moderate and severe patients compared with unstimulated controls. However, the frequency of CD3+IFN-ɣ+ T cells in PBMCs from moderate patients was upregulated by agonists of TLR3, 8 and 9, SP and RBD when compared with NS samples from HCs. The expression of the IFN-β gene after stimulation of CD3⁺T cells with the TLR8 agonist was also up-regulated in moderate than severe patients (moderate vs. severe: p=0.0006). In addition, stimulation of CD3⁺ T cells with SP, up-regulated the expression of IFN-β gene expression in cells from patients with moderate disease (moderate vs. severe: p=0.01). Conclusion: Stimulation of PBMCs from COVID-19 patients with a TLR8 agonist and with SP enhanced IFN-b protein and gene levels. This may potentiate immune responses against SARS-CoV-2 infection and prevent viral replication and spread.

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, which represents a critical and abundant population in most solid tumours microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

It is highly likely that the wearing of face masks reduces the rate of respiratory infections (e.g. SARS-CoV-2), to protect both the user and those around them. This paper sets out to review the areas that effect the efficacy of masks, the materials, design, hygiene and fit testing, in order to make recommendations as to how to make mask from resources found in most homes for when commercial models are unavailable. This paper finds that a mask constructed with a filter made from high thread count cotton is likely to provide a reasonable level of protection (~70% filtration) and that if a layers of other materials such as chiffon or silk is added the filtration may be much higher (~90%). There is also some promise in less available materials such as vacuum cleaner bags and air conditioner filters. Examples of fabric and rigid designs are reviewed but most are limited by the fit to the users which is hard to determine in a home setting. It would be extremely helpful if a method was devised for people to test or be tested for the fit of home made masks. In the mean time careful thought should be given to whether the user judges a good fit. Users should also be careful to practice other means of hygiene and distancing.

Zinc is mostly extracted from zinc oxide and sulfide minerals, and this process involves flotation as a key step. While it is easier to float the sulfide mineral, its consumption and depletion has led to an increased reliance on zinc oxide minerals, including smithsonite; hence the development of efficient ways of collecting smithsonite by flotation is an important objective. Herein, we describe the use of 2-(hexadecanoylamino)acetic acid (HAA), a novel surfactant, as a collector during smithsonite flotation. The mechanism and flotation performance of HAA during smithsonite flotation were investigated by total organic carbon (TOC) content studies, zeta potential measurements, FTIR spectroscopy, and XPS analyses, combined with micro-flotation experiments. The flotation results revealed that HAA is an excellent collector in pulp over a wide pH range (9–12) and at a relatively low concentration (2 × 10^‒4 mol/L), at which a recovery of close to 90% of the smithsonite mineral was obtained. TOC-content studies reveal that the good flotation recovery is ascribable to large amounts of collector molecule adsorbed on the smithsonite surface, while zeta potential measurements show that the HAA is chemically adsorbed onto the smithsonite. FTIR and XPS analyses reveal that the HAA-collector molecules adsorb onto the smithsonite surface as zinc-HAA complexes involving carboxylate moieties and Zn sites on the smithsonite surface in alkaline solution.

Proper satellite-based crop monitoring applications at the farm-level often require near-daily imagery at medium to high spatial resolution. The synthesizing of ongoing satellite missions by ESA (Sentinel 2) and NASA (Landsat7/8) provides this unprecedented opportunity at a global scale; nonetheless, this is rarely implemented because these procedures are data demanding and computationally intensive. This study developed a complete stream processing in the Google Earth Engine cloud platform to generate harmonized surface reflectance images of Landsat7,8 and Sentinel 2 missions. The harmonized images were generated for two agriculture schemes in Bekaa (Lebanon) and Ninh Thuan (Vietnam) during the period 2018-2019. We evaluated the performance of several pre-processing steps needed for the harmonization including image co-registration, brdf correction, topographic correction, and band adjustment. This study found that the miss-registration between Landsat 8 and Sentinel 2 images, varied from 10 meters in Ninh Thuan, Vietnam to 32 meters in Bekaa, Lebanon, and if not treated, posed a great impact on the quality of the harmonized dataset. Analysis of a pair overlapped L8-S2 images over the Bekaa region showed that after the harmonization, all band-to-band spatial correlations were greatly improved from (0.57, 0.64, 0.67, 0.75, 0.76, 0.75, 0.79) to (0.87, 0.91, 0.92, 0.94, 0.97, 0.97, 0.96) in bands (blue, green, red, nir,swir1,swir2, ndvi) respectively. We demonstrated that dense observation of the harmonized dataset can be very helpful for characterizing cropland in highly dynamic areas. We detected unimodal, bimodal and trimodal shapes in the temporal NDVI patterns (likely cycles of paddy rice) in Ninh Thuan province only during the year 2018. We fitted the temporal signatures of the NDVI time series using harmonic (Fourier) analysis. Derived phase (angle from the starting point to the cycle's peak) and amplitude (the cycle's height) were combined with max-NDVI to generate an R-G-B image. This image highlighted croplands as colored pixels (high phase and amplitude) and other types of land as grey/dark pixels (low phase/amplitude). Generated harmonized datasets that contain surface reflectance images (bands blue, green, red, nir, swir1, swir2, and ndvi at 30 meters) over the two studied sites are provided for public usage and testing.