Dengue has long been a serious health burden to the global community, especially for those living in the tropics. In spite of the availability of vaccines, effective treatment for the infection is still needed and currently remained absent. In the present study, antiviral properties of the KSF 103 ME which consisted of a number of potential antiviral compounds were investigated against DENV-2. The effects of this extract against DENV-2 replication were determined using the qRT-PCR. Findings from the study suggested that the KSF 103 ME showed maximum inhibitory properties toward the virus during the virus entry stage at concentrations of more than 12.5 µg/mL. Minimal antiviral activities were observed at other virus replication stages; adsorption (42% reduction at 50 µg/mL), post-adsorption (67.6% reduction at 50 µg/mL), prophylactic treatment (68.4% and 87.7% reductions at 50 µg/mL and 25 µg/mL, respectively) and direct virucidal assay (48% and 56.8% reductions at 50 µg/mL and 25 µg/mL, respectively. The KSF 103 ME inhibited dengue virus repication with an IC50 value of 20.3 µg/mL and SI value of 38.9. The KSF 103 ME showed potent antiviral properties against DENV during the entry stage. Further studies will be needed to deduce the antiviral mechanisms of the KSF 103 ME against DENV.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the COVID-19 pandemic still able to infect the population in many countries. The Omicron strain is the most mutated variant of SARS-CoV-2. The high transmissibility of the strain and the ability to evade immunity require a priority study of its properties in order to quickly create effective means of preventing it. The present work is devoted to the study of in silico interaction of piRNAs with the genome of the SARS-CoV-2 (gRNA) in order to identify endogenous piRNAs and propose synthetic piRNAs with high antiviral activity for drug development. The studies were carried out using proven bioinformatic methods of interaction of the entire SARS-CoV-2 genome with more than eight million piRNAs. Binding sites (BSs) of piRNAs in the 5'UTR were located with overlapping nucleotide sequences called clusters of BSs. Several clusters of BSs were found in the nsp3, nsp7, RNA-dependent RNA polymerase, endoRNAse, S surface glycoprotein, ORF7a and nucleocapsid. 16 synthetic piRNAs have been proposed that interact with gRNA with free binding energy from -170 kJ/mol to -175 kJ/mol, which can be used to create drugs that suppress the reproduction of SARS-CoV-2.

Arf-like protein 2 (ARL2) is a ubiquitously expressed small GTPase with multiple functions. In cell culture, ARL2 participates with tubulin cofactor D (TBCD) in the neogenesis of tubulin αβ-heterodimers, the building blocks of microtubules. To evaluate this function in retina, we conditionally deleted ARL2 in mouse retina at two distinct stages, either during embryonic development (retArl2-/-) or after ciliogenesis specifically in rods (rodArl2-/-). retArl2-/- retina sections displayed distorted nuclear layers and a disrupted microtubule cytoskeleton (MTC) as early as postnatal day 6 (P6). Rod and cone outer segments (OS) did not form. By contrast, rod ARL2 knockouts were stable at postnatal day 35 and revealed normal ERG responses. Cytoplasmic dynein is reduced in retArl2-/- inner segments (IS), suggesting that dynein may be unstable in the absence of a normal MTC. We investigated microtubular stability in the absence of either ARL2 (retARL2-/-) or DYNC1H1 (retDync1h1-/-), the dynein heavy chain, and found that both the retArl2-/- and retDync1h1-/- retinas exhibited reduced microtubules and nuclear layer distortion. The results suggest that ARL2 and dynein depend on each other to generate a functional MTC during early photoreceptor development.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 600 million cases and over 6 million deaths worldwide. Vaccination has been the main strategy used to contain the spread of the virus, and to avoid hospitalizations and deaths. Currently, there are two mRNA-based and one adenovirus vectored vaccines approved and available for use in the U.S. population. The versatility, low cost and rapid-to-manufacture attributes of DNA vaccines are important advantages over other platforms. However, DNA vaccination must meet higher efficiency levels for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been successfully used in the veterinary field. Here we evaluated the safety, immunogenicity and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate for delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. The results demonstrated that the linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects, and was able to elicit neutralizing antibodies and T cell responses using a low dose of the linear DNA construct in prime-boost regimen, and significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model.

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents was not yet available. Given Omicron’s high transmissibility, the ability to assess its impact on admission and hospitalization rates in children’s hospitals is critical for the purpose of understanding the scope of its burden on the German health care system. (2) Methods: From January 24, 2022 to July 31, 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and need for respiratory support were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4–3) per reporting pediatric hospital per day were hospitalized on general wards, whereas a median of 0.1 cases (range 0–0.4 cases) were on intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with need for intensive care treatment and respiratory support due to a symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children’s hospitals.

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing with various household disinfection products (Soap powder, Lysoform®, Hypochlorite sodium and 70% Alcohol), rinse numbers, and exposure times. Afterward, the fabrics were washed in sterile water, viral RNA extracted and amplified using RT-qPCR. Finally, viral replication in cell cultures was examined. Our findings show that all biocidal treatments successfully disinfected the tissue tested. Some products showed less reduction in viral loads, Soap powder (1.60 x 104, 1.04 x 103), Soap powder and Lysoform® (1.60 x 104, 1.04 x 103) and Alcohol 70% (1.02 x 103, 5.91 x 101) respectively. However, when sodium hypochlorite was used, this reduction was significantly increased (viral inactivation in 100% of the washes). After the first wash, the reduction of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51759, p 0.05). In conclusion the sodium hypochlorite role on cloth masks disinfection may also have implications for future health emergencies as well as recommended by WHO.

In this study, we analyzed sequences of SARS-CoV-2 isolates of the Delta variant in Mexico, which completely replaced other previously circulating variants in the country due to its transmission advantage. Among Delta sublineages detected, 81.5 % were classified as AY.20, AY.26, and AY.100. According to publicly available data, these sublineages only reached a world prevalence of less than 1%, suggesting a possible Mexican origin. The signature mutations of these sublineages are described, and phylogenetic analyses and haplotype networks were used to track their spread across the country. Other frequently detected sublineages include AY.3, AY.62, AY.103, and AY.113. Over time, the principal sublineages showed different geographical distributions, with AY.20 predominant in Central Mexico, AY.26 in the North, and AY.100 in the Northwest and South/Southeast. This work describes the circulation, from May to November 2021, of the primary sublineages of the Delta variants associated to the third wave of the COVID-19 pandemic in Mexico and reinforces the importance of SARS-CoV-2 genomic surveillance for timely identification of emerging variants that may impact public health.

The pandemic associated with SARS-CoV-2 is a worldwide public health challenge. The WHO has proposed to achieve 70% COVID-19 vaccination coverage in all countries by mid-2022. Nevertheless, the prevention strategy based on COVID-19 vaccination and other applied prevention measures have not been sufficient to prevent SARS-CoV-2 epidemic waves. The study assessed the vaccination coverage that would be required to establish herd immunity against SARS-CoV-2 by taking into account virus transmissibility (Ro values from 1.1 to 10) and Covid-19 vaccination effectiveness. The study found that Covid-19 vaccination programs could establish herd immunity against SARS-CoV-2 with Ro < 3 with levels of Covid-19 vaccination effectiveness of 10−100% and against viruses with Ro values ranging from 3 to 10 with levels of Covid-19 vaccination effectiveness of 70−100%. Factors reducing Covid-19 vaccination effectiveness (emergent variants, reinfections, high risk individuals) and factors increasing SARS-CoV-2 transmissibility (close settings) increased percentages of vaccination coverage that would be required to establish herd immunity. The vaccination coverage objective of 70% could be adequate against SARS-CoV-2 with Ro values of 1.1−2.5, while percentages of vaccination coverage of 80% and 90% could be more adequate against viruses with Ro values of 2.5−3.5 and >3.5, respectively. On February 2022, the vaccination coverage for complete vaccination was lower than 70% in 73.2% of the countries of the world. Percentages of Covid-19 vaccination coverage must be increased in most countries of the world to increase individual and herd immunity levels in the population.

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.

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

Globally 390 millions of people are at risk of dengue infection; over the past 50 years the virus incidence increased thirty-fold. In Senegal, an unprecedented occurrence of outbreaks and sporadic cases was noticed since 2017. In October 2018 an outbreak of DENV-2 was reported in Rosso area in the north of Senegal at the border with Mauritania. Out of the 187 blood specimen samples collected, 27 were positives by qRT-PCR and 8 were serologically positive for DENV IgM. Serotyping using qRT-PCR reveals that isolates were positive for DENV-2. A subset of DENV-2 positives samples was selected and subjected to full genome sequencing followed by phylogenetic analysis. Analysis of 06 nearly completed genome sequences (n= 6) revealed that isolates belong to the cosmopolitan genotype and are closely related to the Mauritanian strains detected between 2017 and 2018 and those detected in many West African countries such as Burkina Faso or Cote d’Ivoire. Our results suggest a transboundary circulation of the DENV-2 cosmopolitan genotype between Senegal and Mauritania and call for a need of coordinated surveillance of arboviruses between these two countries. Interestingly, high level of homology between West African isolates highlights endemicity and call for a set-up of sub-regional viral genomic surveillance which will lead to a better understanding of viral dynamic, transmission and spread across Africa.

Introduction: The current generation of 3D printers are lighter, cheaper, and smaller, making them more accessible to the chairside digital dentist than ever before. 3D printers in general in the industrial and chairside setting can work with various types of materials including, metals, ceramics, and polymers. Evidence presented in many studies show that an ideal material used for dental restorations is characterised by several properties related to durability, cost-effectiveness, and high performance. This review is the second part in a 3D Printing series that looks at the literature on material science and applications for these materials in 3D printing as well as a discussion on the potential further development and future evolution in 3D printing materials. Conclusions: Current materials in 3D printing provide a wide range of possibilities for providing more predictable workflows as well as improving efficiency through less wasteful additive manufacturing in CAD/CAM procedures. Incorporating a 3D printer and a digital workflow into a dental practice is challenging but the wide range of manufacturing options and materials available mean that the dentist should be well prepared to treat patients with a more predictable and cost effective treatment pathway. As 3D printing continues to become a commonplace addition to chair side dental clinics, the evolution of these materials, in particular reinforced PMMA, resin incorporating zirconia and glass reinforced polymers offer increased speed and improved aesthetics that will likely replace subtractive manufacturing milling machines for most procedures.

Background: The COVID-19 pandemic has hit the Spanish economy hard. The result is an unprecedented economic and social crisis due to uncertainty about the remedy, and due to the socio-economic effects on people’s lives. Methods: We performed a retrospective analysis of the macro-economic impact of COVID-19 in 2020, using the principal indicators of the Spanish economic and productive model. National statistics were examined in the search for impacts or anomalies occurring since the beginning of the pandemic. To estimate the strength of the impact on each of the indicators analysed, we used Bayesian structural time series. Results: In 2020, the cumulative impact on the Gross Domestic Product was of -11.41% [95% credible interval: -13.46; -9.29]. The indicator for Business Turnover fell by -9.37% [-12.71; -6.07]. The reduction in business activity was related to the sharp fall in demand. The Spanish employment market was strongly affected; our estimates showed a cumulative increase of 11.9% [4.27; 19.45] in the rate of unemployment during 2020. The autonomous communities which are economically the most heavily dependent on the services sector were those which recorded the worst indicators. Conclusions: Our estimates portray a dramatic situation in our country, and show all too clearly the fragility of a productive system which has to make the behavioural changes that are necessary to confront the COVID-19 pandemic.

Prevention practices have been extensively used to contain the spread of the SARS-CoV-2 virus. These include social distancing, wearing masks, disinfection of hands, and sanitization of contact surfaces. However, the excessive usage of chemical disinfectants pose long term adverse effects to human health and the environment. Development of effective and environmentally friendly biocides, or virucidal agents, will help mitigate the ill effects of chemical disinfectants. Enzymes are potential candidates for the preparation of biocides against bacteria and viruses. Exploration of the virucidal activity of commercial enzymes, will highlight prospective, readily available sources for research on enzyme based biocides. In this study, the virucidal effect of some com-mercial enzyme preparations has been investigated against the SARS-CoV-2 virus. Vida Defense (2000 µg/ml), Excellacor (1500 µg/ml), and SEBkinase (3000 µg/ml) reduced SARS-CoV-2 viral ti-ters by ≥1 log CCID50 (≥90%). ImmunoSEB (6000µg/ml) and Peptizyme SP (500µg/ml) reduced the SARS-CoV-2 viral titers by 0.8 log CCID50 (84.2%). The study indicates that enzyme prepara-tions offer the potential to be explored further for an anti-viral biocide against SARS‐CoV‐2 for reducing the risk of COVID‐19 transmission. However, further studies are mandated to improve efficacy and establish safety.

With increasing fatalities, the COVID-19 pandemic constitutes a formidable global health challenge. The causative agent, SARS-CoV-2 constantly tests the efficacy of the immune system of its victims. The protective ability of the innate immune system as the first responder largely determines the progression of disease and its clinical prognosis. Evidence suggests that mortalities associated with COVID-19 are largely due to hyperinflammation and a dysregulated immune response. Consequently, the degree of the release of pro-inflammatory cytokines such as IL1, IL-6, and TNF alpha remarkably distinguishes between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for laboratory tests, and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. With respect to the SARS-CoV-2 and the host cell, this literature review focuses on the dynamics of the COVID-19 disease highlighting on the pathogenesis, and the markers of Cytokine Storm. It also proffers solutions by critically looking at the current and potential pharmacological agents that are or can be used to mitigate and manage cytokine storms.

Although rRT-PCR is the gold standard method for SARS-CoV-2 detection, some factors, such as amplification inhibitors presence, lead to false-negative results. Here we describe differences between rRT-PCR results for SARS-CoV-2 infection in normal and diluted samples, simulating the need for dilution due to amplification inhibitors presence. Viral RNA extraction of nasopharyngeal swabs samples from 20 patients previously detected as 'Negative' and 21 patients detected as 'Positive' for SARS-CoV-2 was realized with the EasyExtract DNA-RNA (Interprise®). rRT-PCR was realized with OneStep/COVID-19 (IBMP) kit with normal and diluted (80µl of H₂O RNAse free) samples, totaling 82 tests. The results indicate that there is an average variation (ɑ < 0.05) delaying Cq between the amplification results of internal control (IC), N Gene (NG), and ORF-1ab (OF) of 1.811 Cq, 3.840 Cq, and 3.842 Cq, respectively. The extraction kit does not completely purify the inhibitor compounds, therefore non-amplification by inhibitors may occur. In this study, we obtained a 19.04% false-negative diagnosis after sample dilution, and this process reduces the efficiency of rRT-PCR to 29.80% for detecting SARS-CoV-2. Knowing the rRT-PCR standards of diluted samples can help in the identification of false-negative cases, and consequently avoid a wrong diagnosis.

In regions lacking genomic data, analysis of sequences from the early stages of an outbreak can provide important insights into the diversity of pathogens present. Following the detection of the first imported case of COVID-19 in the Northern sector of Ghana on 13^th March 2020, we have now molecularly characterized and phylogenetically analysed sequences including three (3) complete genomes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from nine (9) patients observed in Ghana. Eight (8) of these patients reported with a recent history of foreign travel and one (1) with no history of foreign travel. We performed high throughput sequencing for 9 samples following the determination of high concentration of viral RNA. In addition, we estimated the potential impact that long distance transportation of samples to testing centres may have on sequencing outcomes. Here, two samples that were closest in terms of viral RNA concentration but transported from sites which are over 400km apart were assessed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Complete genomes were obtained for three (3) sequences and with another near complete genome with a coverage of 95.6%. Sequences with coverage in excess of 80% were found to belong to three lineages namely A, B.1 and B.2. Our sequences clustered in two different clades with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23 which was collected 9km compared with sample TTH6 which was collected and transported over a distance of 400km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be the need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.

Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. In silico analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease (COVID-19).

Since there is no vaccine or regulatory approved therapy available for treatment of SARS-CoV-2 infection, the medical need to prevent the transition of a mild into the severe COVID-19 stage of infection is of outmost importance. Among several drug candidates, Chloroquine (CQN) and Hydroxy-Chloroquine (H-CQN) have been tested most intensively. However, the therapeutic effect of H-CQN and CQN has been discussed controversially in the light of severe side effects. Originally, H-CQN descended from the natural substance Quinine, a medicinal product used since the Middle Ages and is now regulatory approved for various indications. We hypothesized that Quinine also exerts anti-SARS-CoV-2 activity. First, virus production in Vero B4 cells was analyzed by Western blot, showing that Quinine exerts antiviral activity against SARS-CoV-2 that at 10 µM was even stronger than that of H-CQN or CQN. Second, fluorescence end-point and time lapse analysis of SARS-CoV-2-mNeonGreen-infected Caco-2 cells could confirm a similar antiviral effect of Quinine in a human-derived cell line. Thereby, our in vitro studies revealed, that the antiviral effect appears to be specific, since in Vero cells Quinine impacted cell viability at approximately 50-fold higher concentration, while the therapeutic window of H-CQN and CQN was approximately 10-fold lower. In Caco-2 cells no toxic effect was observed while complete block of infection occurred between 50 and 100 µM at high MOIs. In conclusion, our data indicate that Quinine would have the potential of a well tolerable and widely used treatment option for SARS-CoV-2 infections, with a predictable and significantly better toxicological profile when compared to H-CQN or CQN.

Motivated by the definition of the type 2 poly-Bernoulli polynomials introduced by Kim-Kim, in the present paper, we consider a class of new generating function for the Frobenius-Genocchi polynomials, called the type 2 poly-Frobenius-Genocchi polynomials, by means of the polyexponential function. Then, we derive some useful relations and properties. We show that the type 2 poly-Frobenius-Genocchi polynomias equal a linear combination of the classical Frobenius-Genocchi polynomials and Stirling numbers of the first kind. In a special case, we give a relation between the type 2 poly-Frobenius-Genocchi polynomials and Bernoulli polynomials of order k. Moreover, inspired by the definition of the unipoly-Bernoulli polynomials introduced by Kim-Kim, we introduce the unipoly-Frobenius-Genocchi polynomials by means of unipoly function and give multifarious properties including derivative and integral properties. Furthermore, we provide a correlation between the unipoly-Frobenius-Genocchi polynomials and the classical Frobenius-Genocchi polynomials.

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

The outbreak across the globe due to coronavirus disease 2019 (COVID-19) has spread abruptly by infected humans worldwide. The continuous efforts by scientists is on way to understand how pandemic of COVID-19 resembles and differs from serve acute respiratory syndrome coronavirus (SARS-CoV) at transcriptomic and genomic level. The SARS-CoV and COVID-19 exploits the angiotensin converting enzyme 2 (ACE2) receptor to gain entry inside the cells.We analyzed the entry COVID-19 into host cell due to receptor binding domain (RBD) of spike glycoprotein. The proposed simulation data shows similar ternary structures from two viruses shares approximately 80 percent identity in amino acid sequences. Our molecular modeling investigation signifies that angiotensin converting enzyme 2 (ACE2) has stronger interaction with COVID -19 RBD. The Amino acid phenylaniline F486 LOOP plays vital role due to its penetration into hydrophobic pocket in ACE2.The said investigation of S-Glycoprotein RBD of COVID-19 or SARS-CoV-2 via ACE2 provides post genome analysis of protein-protein interaction for rapid assessing transmission of infected patients by deadly CoVID-19. The scientific data extracted implies early guidance to control and viral prevention of CoVID-19.

Recently, the outbreak of coronavirus disease 2019 (COVID-19) is threatening human health globally. There is a dire need to find potential therapeutic agents. Angiotensin converting enzyme 2 (ACE2), as an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered as potential therapeutic target in COVID-19 pandemic. Here, our bioinformatics analysis revealed that the biological function of ACE2 was correlated with regulation of blood pressure and mediation of SARS-CoV-2 entry into host cells. Ten ACE2 cooperative proteins were identified by using STRING with a high score. ACE2 expressed highly in the small intestine, testis, and kidney. The level of ACE2 expression in tumor tissues varies in different types of cancers compared with that in normal tissues. It was worth noting that the expression level of ACE2 in the tumor has no effect on patient survival. MiRNA hsa-miR-942-5p, and three transcription factors (TFs) including Signal transducer and activator of transcription 4 (STAT4), Estrogen related receptor α (ESRRA), and Signal transducer and activator of transcription 3 (STAT3) were selected as novel ACE2 regulators. Moreover, nine potential therapeutic drugs were predicted by two online databases. Thus, our research may expand the overall view of ACE2 in COVID-19 treatment.

This review chronicles the indirect transmission method which seems to be overlooked by most people and makes attempts to clearly document the various transmission ways with a hope that such information may strengthen the knowledge base of researchers towards methods of eradicating the pandemic. Current knowledge of transmission and exposure of SARS-CoV-2 has been explained. Various researchers have put forward different ways of exposure and transmission. Literature does not reveal whether the indirect transmission route is the dominant one. However total lockdown could be a veritable means to reduce both direct and indirect transmission routes. In many countries where the indirect transmission has been reduced, the scourge of the virus is less. The work creates awareness on the need to watch out for those routes of transmissions that may not be popular and suggested key knowledge gaps that needs to filled.

The coronavirus disease 2019 (COVID-19) has spread over the world for more than one year. COVID-19 often develops life-threatening hypoxemia. Endothelial injury caused by the viral infection leads to intravascular coagulation and ventilation-perfusion mismatch. However, besides above pathogenic mechanisms, the role of alveolar edema in the disease progression has not been discussed comprehensively. Since the exudation of pulmonary edema fluid was extremely serious in COVID-19 patients, we bring out a hypothesis that severity of alveolar edema may determine the size of poorly-ventilated area and the blood oxygen content. Treatments to pulmonary edema (alcohol-oxygen vapor therapy and fluid management) may be great helpful for reducing occurrence of severe cases. Given that late mechanical ventilation may cause mucus (edema fluid) to be blown to the deep of the small airways, oxygen therapy should be given at the early stages. The optimal time and SpO₂ threshold for oxygen therapy are also discussed.

We propose a Gauss model (GM), a map from time to the bell-shaped Gauss function to model the deaths per day and country, as a quick and simple model to make predictions on the coronavirus epidemic. Justified by the sigmoidal nature of a pandemic, i.e. initial exponential spread to eventual saturation, we apply the GM to existing data, as of April 2, 2020, from 25 countries during first corona pandemic wave and study the model's predictions. We find that logarithmic daily fatalities caused by Covid-19 are well described by a quadratic function in time. By fitting the data to second order polynomials from a statistical chi2-fit with 95\% confidence, we are able to obtain the characteristic parameters of the GM, i.e. a width, peak height and time of peak, for each country separately, with which we extrapolate to future times to make predictions. We provide evidence that this supposedly oversimplifying model might still have predictive power and use it to forecast the further course of the fatalities caused by Covid-19 per country, including peak number of deaths per day, date of peak, and duration within most deaths occur. While our main goal is to present the general idea of the simple modeling process using GMs, we also describe possible estimates for the number of required respiratory machines and the duration left until the number of infected will be significantly reduced.

The 2019 novel coronavirus (previously 2019-nCoV) or coronavirus infectious disease 2019 (COVID-19) outbreak has been summarized as on March 29, 2020. COVID-19 is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SERS-CoV-2). The disease was first seen during an outbreak in Wuhan, China and continuous spreading from human to human around the sphere. The disease is uncontrolled and increasing the death toll through. The world is facing a global challenge to protect human lives caused by coronavirus outbreak. The number of infected patients is increasing day by day due to COVID-19 as a pandemic. The world health organization (WHO) has declared global public health emergency on January 30, 2020. The disease has been spread around 201 countries with total confirmed cases 634835 and death cases 29891 as on March 29, 2020. The goal of this review to summaries and update the clinical/medical features and suggestions for diagnosis of the COVID-19 as a pandemic. The discussion of the various therapeutic algorithms, risk, prevention and control based on the latest reports has been provided.

At a time when the world faces an emotional breakdown, crushing our dreams if not taking our lives, we realize that together we must fight the war against the COVID-19 outbreak even if almost the majority of the scientific community finds itself confined to home. Every day, like everyone else, we, scientists, listen to the latest news with its promises and announcements. Across the world, a surge of clinical trials trying to cure or slow down the coronavirus pandemic has been launched to bring hope instead of fear and despair. One first proposed clinical trial has drawn worldwide hype to the benefit of chloroquine (CQ), a well-known and broadly used anti-malarial drug, in the treatment of patients infected by the recently emerged deadly coronavirus (SARS-CoV-2). We should consider this information in the light of the long-standing anti-inflammatory and anti-viral properties of CQ-related drugs. Yet, none of the articles promoting the use of CQ in the current pandemic evoked a possible molecular or cellular mechanism of action that could account for any efficacy. Here, given the interaction of viruses with macroautophagy (hereafter referred to as autophagy), a CQ-sensitive anti-viral safeguard pathway, we would like to discuss the pros, but also the cons concerning the current therapeutic options targeting this process.

The recent outbreak of coronavirus disease 2019 caused by the new coronavirus, SARS-CoV-2, has become an international emergency. Since there is no effective therapy for the treatment of this disease, drugs or vaccine that can prevent or cure the SARS-CoV-2 infection are urgently needed. The viral 3-chymotrypsin-like cysteine protease (3CLpro), which plays a key role in the replication of coronavirus, is a potential drug target for the development of anti-SARS-CoV-2 drugs. With the crystal structure of 3CLpro, we performed virtual screening from a small chemical library of a Traditional Chinese Medicine recipe- FuFang Zhenzhu Tiaozhi (FTZ). Five compounds with the best scores were screened and could be considered as potential hit compounds to be investigated further with bioassays for their anti-virus effects.

A novel coronavirus (SARS-CoV-2) that is initially found to trigger human severe respiratory illness in Wuhan City of China in 2019, has killed 2,718 people in China by February 26, 2020, and which has been recognized as a public health emergency of international concern as well. And the virus has spread to more than 38 countries around the world. However, the drug has not yet been officially licensed or approved to treat SARS-Cov-2 infection. NSP12-NSP7-NSP8 complex of SARS-CoV-2, essential for viral replication and transcription, is generally regarded as a potential target to fight against the virus. According to the NSP12-NSP7-NSP8 complex (PDB ID: 6NUR) structure of SARS, two homologous models were established for virtual screening in the present study, namely NSP12-NSP7 interface model and NSP12-NSP8 interface model. Seven compounds (Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir, and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. All seven compounds can combine well with NSP12-NSP7-NSP8 in the homologous model, providing drug candidates for the treatment and prevention of SARS-CoV-2.

This paper reports design of a 2 × 4 hybrid multimode interferometer-Mach-zehnder interferometer (MMI-MZI) configuration and compact thermo-optical switch consisting of slab waveguides on the silicon-on-insulator (SOI), platform. The device consisted of two identical MMIs as power splitters and couplers that are connected with two identical MMI-based phase shifters, and linear tapers at both ends of the MMIs to minimize the power coupling loss. A thin Al pad is used as a heating element, and a trench is created around this pad to prevent heat from spreading and to minimize loss. The calculated average thermo-optical switching power consumption, excess loss, and power imbalance are 1.4 mW, 0.9 dB, and 0.1 dB, respectively. The overall footprint of the device is 6 × 304 μm². The new heating method has advantages of compact size, ease of fabrication on SOI platform with the current CMOS technology, and offers low excess loss and power consumption as demanded by devices based on SOI technology. The device can act as two independent optical switches in one structure.

Angiogenesis mediated by proteins such as Fibroblast Growth Factor – 2 (FGF-2) is a vital component of normal physiological processes and has also been implicated in contributing to disease state associated with various microbial infections. Previous studies by our group and others have shown that Candida albicans, a common agent of candidiasis, induces FGF-2 expression in vitro, and angiogenesis in brains and kidneys during systemic infections. However, the underlying mechanism(s) via which the fungus increases FGF-2 expression and the role(s) that FGF-2/angiogenesis plays in C. albicans disease remain unknown. Here we show, for the first time, that C. albicans hyphae (and not yeast cells) increase the FGF-2 response in human endothelial cells. Moreover, candidalysin, a toxin secreted exclusively by C. albicans in the hyphal state is required to induce this response. Our in vivo studies show that, in the systemic C. albicans infection model, mice treated with FGF-2 exhibit significantly higher mortality rates when compared to untreated mice not given the angiogenic growth factor. Even treatment with fluconazole could not fully rescue infected animals that were administered FGF-2. Our data suggest that the increase of FGF-2 production/angiogenesis induced by candidalysin contributes to the pathogenicity of C. albicans.

Prostanoids modulate the pathogenesis of vascular diseases such as atherosclerosis, in which inflammation has an important role. It is well known that inducible Ciclooxygenase-2 (COX-2) is responsible for prostanoid production associated with inflammation. Angiotensin II may be implicated through the expression of COX-2 in the vascular wall. The purpose of this study was to examine in angiotensin II-stimulated adventitial fibroblasts the anti-inflammatory activity of different food peptides by inhibiting COX-2 expression, and the production of pro-inflammatory prostanoids. Fibroblasts from aorta of Sprague-Dawley rats were incubated with different food derived peptides followed by incubation with Angiotensin II. COX-2 expression was determined by western blot, transcriptional activity by luciferase assays and prostaglandin E2 by enzyme immunoassay. COX-2 expression was inhibited in the presence of Val-Pro-Pro (bovine β-casein 84–86), Arg-Asp-Ile-Leu-Asn-Gln (ovalbumin 84–89) and Tyr-Arg-Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe (ovalbumin 125–134). Angiotensin II-induced prostaglandin E2 production was also reduced by all the above-mentioned sequences. The incubation with ovalbumin-derived peptides displayed a significant reduction of COX-2 promoter activity compared to the stimuli with Angiotensin II in transiently transfected cells. These three sequences could potentially be used as functional food ingredients to reduce inflammation related to cardiovascular diseases.

A compact 2-DOF (two degrees of freedom) piezoelectric-driven platform for 3D cellular bio-assembly systems has been proposed based on “Z-shaped” flexure hinges. Multiple linear motions with high resolution both in x and y directions are achieved. The “Z-shaped” flexure hinges and the parallel-six-connecting-rods structure are utilized to obtain the lowest working stress while compared with other types of flexure hinges. In order to achieve the optimized structure, matrix-based compliance modeling (MCM) method and finite element method (FEM) are used to evaluate both the static and dynamic performances of the proposed 2-DOF piezoelectric-driven platform. Experimental results indicate that the maximum motion displacements for x stage and y stage are lx=17.65 μm and ly=15.45 μm, respectively. The step response time for x stage and y stage are tx=1.7 ms and ty =1.6 ms, respectively.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

Background and Objectives: ACTION-France (Awareness, Care and Treatment In Obesity MaNagement in France) aims to identify the perceptions, attitudes, behaviors, and potential barriers to effective obesity management in France and guide collaborative actions. Methods: ACTION-France is a cross-sectional survey of people with obesity (PwO) and healthcare professionals (HCPs), in France. The PwO and HCP questionnaires ran from 27/09/2022 to 01/02/2023 and from 19/12/2022 to 31/03/2023, respectively. Results: The study, encompassing 1226 PwO and 166 HCPs, reveals a shared recognition of obesity as a chronic condition. However, despite being requested by most PwO, weight-related discussions are surprisingly infrequent, leading to delayed diagnosis and care. PwO and HCPs held different views as to why: HCPs often attributed it to PwO’s lack of motivation or disinterest, whereas PwO avoided them because they felt weight managing was their own responsibility and were uncomfortable discussing it. When weight was discussed, primarily with general practitioners (GPs), discussions mostly focused on physical activity and dietary. However, results identified a strong psychosocial impact of obesity: 42% of respondents reported anxiety-depressive symptoms, and many more hesitated to engage in certain social activities because of their weight. Psychotherapy was only discussed by 55% of HCPs. Pharmaceutical options were also rarely discussed (19.5% of HCPs), though 56.1% of PwO reported they would want to. Conclusions: HCPs’ and PwO’s perceptions differed significantly and need to converge through enhanced communication. A holistic approach, integrating comprehensive training for GPs and psychological comorbidities, would help to bridge perceptual gaps effectively and foster more empathetic and effective patient care.

A well-known result of Posner’s second theorem states that if the commutator of each element in a prime ring and its image under a nonzero derivation is central, then the ring is commutative. In the present paper, we extend this bluestocking theorem to an arbitrary ring with involution involving prime ideals. Further, apart from proving several other interesting and exciting results, we establish *-version of Vukman’s theorem [48, Theorem 1]. Precisely, we describe the structure of quotient ring A/L, where A is an arbitrary ring and L is a prime ideal of A. Further, by taking advantage of the *-version of Vukman’s theorem, we show that if a 2-trosion free semiprime ring A with involution admits a nonzero *-centralizing derivation, then A contains a nonzero central ideal. This result is in a spirit of the classical result due to Bell and Martindale [19, Theorem 3]. As the applications, we extends and unify several classical theorems proved in [6],[25,[42], and [48] . Finally, we conclude our paper with a direction for further research.

The research work explores the impact of temperature on Silicon photovoltaic (PV) panels considering Nigeria as case study. It is found that high solar radiation in Nigeria increases surface temperature of PV panel above 25oC of optimal operating temperature of PV panels. Redundant energy gain from incident solar energy is dissipated at the rear of PV panels as heat, which reduces the efficiency of PV panel. Cooling mechanism is needed to cool the PV panels to increase the efficiency. In this study we demonstrated a unique design of a bifunctional photovoltaic-thermal (PVT) system by employing heat exchanger at the rear of PV panel and water is used as a working fluid that is circulated through the heat exchanger to remove the excess heat. It is observed from the simulation results that Maiduguri peak annual electrical power output gives 1907kWh/kWp which is the highest, because of high solar radiation average of 727W/m2 in a year. And for Makurdi the peak annual electrical power output of 1542kWh/kWp while for Port Harcourt the peak power output of 1355kWh/kWp respectively. Interestingly, Polycrystalline Si-PV surface temperature decrease from 49.25oC to 38.38oC. Electrical power increased from 1526.83W to 1566.82W in a day and efficiency increase from 13.99% to 15.01%.

Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do not fully account for HbF variation. To investigate rare and common variants influencing HbF levels in SCD, we performed targeted next generation sequencing covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1. Results revealed a range of functionally relevant genetic variants. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified frameshift deletion in individuals with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis. This study provides new insights in selecting essential variants associated with extreme HbF levels in SCD.

The main aims of this study were (1) to identify and compare the major biologically active compounds in the metabolome of ligulate and tubular flowers of two C. officinalis cultivars, ‘Golden Sea’ (GS) and ‘Paradise Garden’ (PG), and (2) to investigate the effect of different proportions of ligulate and tubular flowers in the inflorescences on their metabolome. Ultra-performance liquid chromatography with photodiode array detection and a Q Exactive Orbitrap high-resolution mass spectrometer were used to analyse the flower metabolome. Analysis of the metabolomics data revealed that polar lipids showed the most significant differences between flowers. Tubular flowers of PG and GS cultivars contained higher levels of 31 and 34 out of 36 lipids, respectively. Furthermore, tubular flowers of both cultivars contained significantly higher levels of phenolamides and caffeoylquinic acids, but lower levels of triterpenoids. To compare the metabolite content of the two C. officinalis cultivars, we analysed the data for their inflorescences. The study showed that GS inflorescences contained significantly higher levels of phenolic compounds and lipids than PG inflorescences. This GS advantage was due to two factors: firstly, the higher content of these metabolites in tubular flowers and, secondly, the higher proportion of tubular flowers in GS inflorescences.

German chamomile galenic preparations are used to treat mild skin diseases, inflammation and spasms, and they have also reported to have anxiolytic and sedative effects. The medicinal use of chamomile is well-known in ethnomedicine. Since chamomile has shown to have some adverse effects, there is a need to develop new formulations, such as dry extracts, for the present herb. The aims of this study were (1) to develop a novel method for preparing essential oils and dry extracts from German chamomile flowers, (2) to reveal the phytochemical composition of such extracts, and (3) to verify the analgesic and soporific activity of extracts in vivo with a rodent animal model. Furthermore, our study aims to gain knowledge of the ethnomedical status of chamomile in the past and presence. Essential oils and dry extracts were successfully prepared from the tincture and aqueous extracts obtained after hydrodistillation and from a tincture powder. Total 22 phenolic compounds (7 hydroxycinnamic acids, 13 flavonoids and 2 phenolic acids), were found in the dry extracts by using UPLC-MS/MS. Total 9 main terpenoids were identified in the chamomile oil, and these terpenoids represent the chemotype rich in bisabolol oxides A and B. In the highest yield, the ratio of phenolic compounds and extract was in the range of 1:14-1:16 and triple extraction was performed. In in-vivo studies with mice and rats, the extracts showed analgesic activity and improvements in sleep. The highest sedative effect in rodents was found with the extract prepared by using a 70% aqueous ethanol solution for extraction. The administration of such extract at the dose of 50 mg/kg significantly prolonged the sleeping time in rats.

The There are many factors influencing the performance of photovoltaic (PV) systems. Among these factors, temperature and solar radiation are two major parameters that have a large effect on the efficiency of PV systems. The cell temperature of PV panels is related to the ambient temperature while the solar radiation incident on the surface of the PV modules depends on the slope and azimuth of these modules. Furthermore, ground reflectance (albedo) affects the irradiance incident on the PV panel surface, which in turn affects the output of a PV system. Nevertheless, the effects of these factors on the economic performance of the solar PV systems are scarcely reported. This paper presents a complete design of a stand-alone PV/battery system to supply electric power for a mobile base station in Choman, Erbil, Iraq. The effects of different factors on the total electricity produced by PV arrays and its economic performance are simultaneously investigated. HOMER software has been used as a tool for the techno-economic and environmental analysis. As indicated from the simulation results, the PV array capacity and its economic performance are highly affected by the variation of the slope and azimuth. With a base case (albedo of 20% and average annual ambient temperature of 11°C), the best feasible system which is achieved by facing PV due to south with a tilt angle of 40° or 45°, is found to have net present cost (NPC) of 70595 $ and cost of energy (COE) of 0.54 $/kWh. Moreover, the results indicate that increasing the ground reflectance from 10% to 90% results in a 7.2% decrease in the PV array capacity and about 3% decrease in the NPC and COE. On the other hand, increasing the ambient temperature from 0°C to 40°C results in a 19.7% increase in the PV array capacity and an 8.2% increase in the NPC and COE. Furthermore, according to the ambient temperature of Choman, using PV modules with high sensitivity to temperature is found to be an attractive option. Provided simulation performance analysis proves that the studied parameters must be treated well to establish an enabling environment for solar energy development in Iraq.

PM2.5 and PM>2.5 were separately collected in Kanazawa, Japan in every season from the spring of 2017 to the winter of 2018, and nine polycyclic aromatic hydrocarbons (PAHs) and six nitropolycyclic aromatic hydrocarbons (NPAHs) were determined by HPLC with fluorescence and chemiluminescence detections, respectively. Atmospheric concentrations of both PAHs and NPAHs showed seasonal changes (highest in the winter and lowest in the summer), which were different from the variations of TSP and PM2.5 (highest in the spring). Contributions of major sources to combustion-derived particulate (Pc) in PM2.5 were calculated by the NP-method using pyrene and 1-nitropyrene as representative markers of PAHs and NPAHs, respectively. The annual average concentration of Pc accounted for only 2.1% of PM2.5, but showed the same seasonal variation as PAHs. The sources of Pc were automobiles (31%) and coal heating facilities/industries (69%). The source of Pyr was almost entirely coal heating facilities/industries (98%). A backward trajectory analysis showed that automobile-derived Pc was mainly from Kanazawa and its surroundings and that coal heating facilities-derived Pc was transported from city areas in central and northern China in the winter and during the Asian dust event in the spring. These results show that large amounts of PAHs were long-range transported from China in the winter. Even in spring when the coal heating season was over in China, PAHs came over to Japan after Asian dust storms passed through Chinese city areas. The main contributor of NPAHs was automobiles in Kanazawa and its surroundings. The recent Pc concentrations were much lower than those in 1999. This decrease was mostly attributed to the decrease in the contribution of automobiles. Thus, changes of atmospheric concentrations of Pc, PAHs and NPAHs in Kanazawa were strongly affected not only by the local emissions but also long-range transport from China.

The issues mothers face in the academy have been discussed for decades. Routinely, new studies report significant differences between women and men at comparable career stages with respect to salary, service demands, publications, grant submissions, and overall funding rates. The COVID-19 pandemic is further exposing these inequalities as women scientists who are parenting while also engaging in a combination of academic related duties are falling further behind. COVID-19 is shaking the very foundations of our society and laying bare the many inequalities that defined our pre-COVID world. We can solve these inequities by investing strategically in creative solutions, thereby making the most of women’s contributions to scientific endeavors. Here we describe strategies that would make the academy more equitable for working mothers now and into the future. Importantly, while the data are clear that mothers are being disproportionally impacted by COVID-19, many groups could benefit from these same ideas. Now is the time to act. Rather than rebuilding what we once knew, let us be the architects of a new world.

Intraprocedural rupture (IPR) is a severe complication of coil embolization (CE) for intracranial aneurysms, yet the clinical and hemodynamic features of rupture risk areas remain unclear. From January 2013 to December 2023, 435 saccular cerebral aneurysms (316 unruptured, 119 ruptured) underwent CE at our institution. Included were cases where extravasation or coil protrusion occurred during CE. The rupture point was determined from postoperative data, and computational fluid dynamics (CFD) analysis was conducted to assess hemodynamic features. IPR occurred in six aneurysms (1.3%; three ruptured, three unruptured; dome size: 4.7±1.8 mm, D/N: 1.5±0.5, locations: four internal carotid artery [ICA], one anterior cerebral artery, one middle cerebral artery). ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with maximum pressure (Pmax) in five aneurysms (83.3%). Time-averaged wall shear stress (WSS) was locally reduced around this area (1.3±0.7 [Pa]). Hemodynamically unstable areas indicated fragile, thin walls with rupture risk. Microcatheter insertion along the inflow zone, directed towards the caution area, was practiced. The presence of a flow impingement zone with Pmax and low WSS suggests potential aneurysm rupture in CE, particularly with adjunctive techniques. Small aneurysms, especially those with axial misalignment, warrant careful consideration due to the risk of excessive flow impact stress on the aneurysm wall.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.

Radiomics involves the extraction of information from medical images not visible to the human eye. There is evidence these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations namely Matlab toolkit and Pyradiomics when applied on independent datasets of CT scans of patients i) the open access RIDER dataset containing a set of repeat CT scans taken 15 minutes apart for 31 patients (RIDER Scan 1 and Scan 2 respectively) treated for lung cancer and ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV) manually outlined by an experienced observer available on both datasets was used. 43 common radiomics features available on Matlab and Pyradiomics were calculated using 2 intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters and the Spearman’s rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset and vice versa. 29 out of 43 reported stable features were found to be highly reproducible between Matlab and Pyradiomics implementations, having consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs &gt; 0.8). 18/43 reported features were common in RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

The present study evaluates the manufacturing parameters effects on the tensile properties of material composed by polylactic acid (PLA) with wood fibers known as Timberfill. The specimens were built through fused filament fabrication (FFF). The influence of four printing parameters (Layer height, Fill density, Printing velocity, and Orientation) are considered through a L27 Taguchi orthogonal array in order to reduce experimental runs. Tensile test is applied to obtain the response variable used as output results to perform the ANOVA calculations. Fill density is the most influential parameter on the tensile strength, followed by building orientation and layer height, whereas the printing velocity shows no significant influence. The optimal set of parameters and levels is found, being 75% fill density, 0○Z-axis orientation, 0.4 mm layer height, and 40 mm/s velocity as the best combination. Applying this combination showed 9.37 MPa in maximum tension. Lastly, five solid Timberfill specimens manufactured via injection molding technology were also tested and the results compared to the printed samples. The values of the elastic modulus, elastic limit, and maximum tension of the injected samples were almost twofold of those were obtained for the FFF samples, but the maximum elongation of injected specimens was fell sharply.

This study aimed to assess prescription transfer and medicines collection through Wasfaty, an electronic prescription service recently introduced in Saudi Arabia. A link to a cross-sectional online questionnaire was sent to all students and staff at the University of Jeddah, targeting beneficiaries who received e-prescriptions at the University Medical Centre (n = 2067). The questionnaire comprised 20 items under the following sections; demographics, patient perceptions and satisfaction with the Wasfaty service, and the availability of medicines. Of the 217 questionnaires received, the majority were filled by females (n = 125, 57.6%). Most were satisfied with the initial registration process of Wasfaty (n = 183, 84.1%). However, almost one-third of the participants reported that they could not find the prescribed medicines (n = 64, 29.7%), and most of them had to look for another pharmacy to obtain their treatment (n = 138, 63.9%). Respondents voiced their displeasure owing to the lack of access to certain pharmaceuticals, including anti-hypertensives and antidiabetics. This pilot study identified some challenges relating to the use of the Wasfaty service. Further attention to these challenges is required from the service providers, and a large-scale national study is warranted.

Endothall dipotassium salt and monoamine salt are herbicide formulations used for controlling submerged aquatic macrophytes and algae in aquatic ecosystems. Microbial activity is the primary degradation pathway for endothall. To better understand what influences endothall degradation, we conducted a mesocosm experiment to 1) evaluate the effects of different water and sediment sources on degradation, and 2) determine if degradation was faster in the presence of a microbial community previously exposed to endothall. Endothall residues were determined with LC-MS at intervals to 21 days after endothall application. Two endothall isomers were detected. Isomer-1 was abundant in both endothall formulations, while isomer-2 was only abundant in the monoamine endothall formulation and was more persistent. Degradation did not occur in the absence of sediment. In the presence of sediment degradation if isomer-1 began after a lag phase of 5-11 days and was almost complete by 14 days. Onset of degradation occurred 2-4 days sooner when the microbial population was previously exposed to endothall. We provide direct evidence that the presence and characteristics of sediment are of key importance in the degradation of endothall in an aquatic environment, and that monoamine endothall has two separate isomers that have different degradation characteristics.

In electromagnetic ultrasonic testing, it is difficult to recognize small-size bottom cracks by time of flight (ToF), and the lift-off fluctuation of the probe affects the accuracy and consistency of the inspection results. In order to overcome the difficulty, a novel EMAT (electromagnetic acoustic transducer)-PEC (pulse eddy current) composite sensor is designed. We use amplitude of bottom echo recorded by EMAT to identify the tiny bottom crack as well as the amplitude of PEC signals picked up by the integrated symmetric coils to measure the average lift-off of the probe in real time. Firstly, the effects of lift-off and bottom cracks on amplitude of bottom echo are distinguished combining the theoretical analysis and finite element method (FEM). And then an amplitude correction method based on the fusion of EMAT and PEC signals is proposed to reduce the impact of lift-off on the defect signal. The experimental results demonstrate that the designed composite sensor can effectively detect the bottom crack as small as 0.1mm* 0.3mm. The signal fusion method can accurately correct the amplitude of defect signal and the relative error is less than ±8%.

Affinity chromatography on procainamide-Sepharose has been an important step in the purification of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) since its introduction in 1978. The procainamide affinity gel has limitations. In the present report a new affinity gel called Hupresin^® was evaluated for its ability to purify truncated, partly-deglycosylated human butyrylcholinesterase (rHuBChE) expressed in a stably transfected CHO cell line. We present a detailed example of the purification of rHuBChE secreted into 3940 mL of serum-free culture medium. The starting material contained 13,163 units of BChE activity (20.9 mg). rHuBChE was purified to homogeneity in a single step by passage over 82 mL of Hupresin^® and elution with 0.1 M tetramethylammonium bromide in 20 mM TrisCl pH 7.5. The fraction with the highest specific activity of 630 units/mg contained 11 mg of BChE. Hupresin^® is superior to procainamide-Sepharose for purification of BChE, but is not suitable for purifying native AChE because Hupresin^® binds AChE so tightly that AChE is desorbed with denaturing solvents such as 50% acetonitrile or 1% trifluoroacetic acid. Procainamide-Sepharose will continue to be useful for purification of AChE.

We report an unusual transformation where a transient formation of a nitrene moiety initiates a sequence of steps where leading to a remote oxidative C-H functionalization (R-CH3 to R-CH2OC(O)R’) and concomitant reduction of the nitrene into an amino group. No external oxi-dants or reductants are needed for this formal molecular com-proportionation. Detected and iso-lated intermediates and computational analysis suggest that the process occurs with pyrazole ring opening and recyclization.

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.

Bee colonies that belong to the biocenosis are constantly threatened by the bacterial larvae disease called American foulbrood, caused by Paenibacillus larvae. The current state of the law prevents the inclusion of pharmacotherapy in the treatment and the only control is based on physical eradication of infected colonies by order of the Vet. The purpose of this study was to investigate the antimicrobial activity of selected bacteria with proven probiotic potential that could reduce American foulbrood pressure by promoting the development of the larvae microbiome that competes with and blocks the excessive proliferation and production of P. larvae endospores. The antimicrobial activity of inoculants of selected strains was studied: B. pumilus, B. licheniformis, S. narbonensis, L. fusiformis, L. brevis, B. megaterium against P. larvae ATCC 9545 and P. larvae CCUG 48973. Analyses were performed by the well-diffusion method according to EUCAST standards with modifications due to the specificity of the bacteria used. The largest zone of growth inhibition of P. larvae was confirmed with: S. narbonensis, B. licheniformis, B. megaterium, medium activity was observed with L. brevis and B. pumilus. Negligible activity was shown by L. fusiformis. Differences were noticed in the resistance of indicator strains of P. larvae and between the media and carriers used.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

To better understand farmers’ refusal and corresponding negative emotions to pay agricultural water fee under current policy in rural China, this paper applies mental accounting, a behavioral economics framework, to explore how the governmental policies of reform of rural taxes and fees, direct agricultural subsidy programs and agricultural water fee individually influence farmers’ decisions in paying agricultural water fee. Using fieldwork data from 577 farmers and 20 water managers in Sichuan, we explore farmers’ information processing regarding paying agricultural water fee via three sequential mental accounting processes, with the associated underlying principles and measures behind each process. We find that the information processing in three mental accounting scenarios related to the agricultural water fee elucidates farmers’ observed behaviors in rural China. Generally, in the three mental accounting scenarios, two conditional intuitive expectations and nine conditional intuitive preferences are formed, however, the conditions of those expectations or preferences cannot be matched with the facts due to the reform of rural taxes and fees, the direct agricultural subsidy programs and the internal attributes of agricultural water fee, which interpret those negative behaviors in rural China. Additionally, this paper offers a view into how previous policies create negative psychological externalities (such as farmers’ psychological dependence on the government) through mental accounting to negatively influence agents’ subsequent decision making; it highlights the significance of underlying mental factors and information processing of negative behaviors in policymaking for managing or conserving common pool resources.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Coronavirus disease-2019 (COVID-19) was seen as a respiratory disease, however, an increasing number of reports indicated that the spike protein could also be the cause of the long-term post-infectious conditions known as Long-COVID characterized by a group of unresponsive idiopathic severe neuro, cardio-vascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Parkinson's like-disease. Different lines of pieces of evidence confirmed that the spike protein that can be found on the surface of the SARS-CoV-2 virus latches onto angiotensin-converting enzyme 2 (ACE2) receptors located on target cells. The RNA genome of coronaviruses, which, has a median length of 29 kb and is the longest among all RNA viruses, is comprised of six to ten open reading frames (ORFs) that are responsible for encoding both the replicase and structural proteins for the virus. Each of the components of the viral genome is packaged into a helical nucleocapsid that is surrounded by a lipid bilayer. The viral envelope of coronaviruses is typically made up of three proteins that include the membrane protein (M), the envelope protein (E), and the spike protein (S). The spike protein not only facilitates the virus entry into healthy cells, which is the first step in infection but also promote profound damage to different organs and tissues leading to severe impairments and long-term disabilities. Here, we discussed the pervasive mechanism that spikes mRNA adopted to alter multipotent and pluripotent stem cell (SCs) genomes and the acquired disability of generating an infinite number of affected clonal cells. This stance is based on the molecular and evolutionary aspects obtained from retrotransposons-retrotransposition in mammalians and humans that documented the frequent integration of mRNA molecules into genomes and thus into DNA. Retrotransposition is the molecular process in which transcribed and spliced mRNAs are accidentally reverse-transcribed and inserted into new genomic positions to form a retrogene. Sequence-specific traits of mRNA clearly showed long interspersed element-1 (LINE-1 or L1) to confirm the retrotransposition, considered the most abundant autonomously active retrotransposons in the human genome. In mammals, L1 retrotransposons drive retrotransposition and are composed of long terminal repeats (LTRs) and non-LTR retrotransposons (mainly long interspersed nuclear elements or LINEs); specifically, the LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons. In response to retrotransposons transposition, stem cells (SCs) employ a number of silencing mechanisms, such as DNA methylation and histone modification. This manuscript theorizes the expression patterns, functions, and regulation of mRNA Spike protein imprinted by SCs retrotransposons which generate unlimited lines of affected cell progenies and tissues as the main condition of untreatable Spike-related inflammatory conditions.

Introduction: Agricultural practices significantly influence soil microbial populations and physicochemical properties, which are crucial for crop growth and quality. This study aims to investigate the impact of different agrochemical applications on soil microbial dynamics, soil physicochemical properties, as well as yield and proximate properties of maize. Methods: Carefully gathered topsoil samples at depths ranging from 1 to 15 cm, were transported to Jimma University to cultivate maize. Over a period of up to 120 days, soil and maize samples were collected at specified days to analyze various parameters, including soil pH, microbial populations, as well as nutrient content both in soil and plants. The collected data was statistically analyzed using one-way ANOVA, with a significance level of p < 0.05. Results: The soil bacterial and fungal populations were measured on days 5, 10, 20, 40, 80, and 120. The highest total mesophilic bacterial count (TMBC) was measured in the pots containing compost (G) and the lowest in pots that received macronutrient fertilizers and glyphosates (B) (i.e. 91.8 x 105 and 13.13 x 105 cfu/g of soil, respectively). The highest total mesophilic fungal count (TMFC) was observed in pots containing glyphosates and compost (F) (i.e. 67.25 x 104 cfu/g soil) and again the lowest in pot treated with macronutrient fertilizers and glyphosate (B) (i.e. 3.23 x 104 cfu/g soil). Moreover, the pots treated with macronutrient fertilizers and glyphosate (B), macronutrient fertilizers (A), and micronutrient fertilizers (C) exhibited the lowest levels of Fe and Zn. Furthermore, the pots receiving macronutrient fertilizer combined with glyphosate (B), as well as those receiving macronutrient fertilizers (A) alone had the lowest concentrations of Mn and Cu micronutrients. Finally, in maize the lowest protein, fats, and carbohydrates (g/100g) were found in the pots treated with macronutrient fertilizer combined with glyphosate (B, 2.21 ± 0.2), micronutrient fertilizer (C, 8.57 ± 0.25), and glyphosates only (D, 57.34 ± 0.1). Maize treated with compost (G) showed the highest levels of Fe, Cu, and Zn, while macronutrient fertilizer combined with glyphosate (B) resulted in the lowest content of these micronutrients. Additionally, maize receiving micronutrient fertilizer (C) had the highest concentration of Mn, whereas those treated with glyphosates (D) had the lowest. Conclusions: Significant variations in soil’s mesophilic bacterial and fungal populations, micronutrient levels, and nutritional composition were observed, indicating treatment-related changes. Generally, treatment with micromineral fertilizer combined with glyphosate (B) seemed to deplete the soil while compost treatment improved. Compost-treated soils exhibited the highest mesophilic bacterial and fungal count, as well as Fe and Zn micronutrient concentrations. The use of agrochemicals also had a negative effect on maize yield quality. The fluctuations in the soil parameters underscore the multifaceted effects of agrochemical treatments.

Here we report a comparative study of the pyhtochemical profile and a biological activity of the two onion extracts, namely A. cepa L. and A. × cornutum (Clementi ex Visiani 1842). Identification of flavonoids and anthocyanins and their individual quantities were determined by high performance liquid chromatography (HPLC). The potency of both extracts to scavenge free radicals was determined by DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical-scavenging activity and oxygen radical absorbance capacity (ORAC) methods. DNA protective role was further tested by single-cell gel electrophoresis (COMET) assay and by Fenton’s reagent causing double strand brakes on pUC19 plasmid. In the presence of both extracts, a significant decrease in the DNA damage was observed, which indicates a protective role of A. cepa and A. × cornutum on the DNA strand brakes. Additionally, cytotoxicity was tested on glioblastoma and breast cancer cell lines. The results showed that both extracts had antiproliferative effect, but the most prominent decrease in cellular growth was observed with glioblastoma cells

Hoechst 33342 (H33342) is a fluorescent probe that is commonly used to stain DNA of living cells. To do so, it needs to interact with and permeate through cell membranes. The pH of biological media may vary quite significantly and this influences H33342 ionization state, and may change its rate of permeation through biomembranes. In this work, we address the effect of pH in the association of H33342 with lipid bilayers using a combined experimental and computational approach. The partition of H33342 to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid membranes was experimentally quantified using fluorescence spectroscopy and isothermal titration calorimetry (ITC) measurements. Quantum chemical calculations were performed to select the most stable isomer of H33342 for the overall charges 0, +1, and +2, expected to predominate across the 5 &lt; pH &lt; 10 range. The interaction of these isomers with POPC bilayers was then studied by both unrestrained and umbrella sampling molecular dynamics simulations. While probe insertion occurs for all ionization states, with similar overall equilibrium location, orientation was found to depend on the probe charge, with the neutral form lying mostly parallel and the doubly charged displaying a significant tilt relative to the membrane plane. Both experimental results and computational free energy profiles indicate that the partition coefficient of H33342 displays a small variation over a wide pH range, not exceeding one order of magnitude. The enthalpy of interaction is negative and is larger at lower pH values. This suggests efficient hydrogen bonding between the probe and the lipid, namely for the protonated +2 form. The relatively high lipophilicity obtained for the charged species contrasts with the decrease in their general hydrophobicity as estimated from water and octanol partition. This highlights the distinction between lipophilicity and hydrophobicity, and the importance of considering association with lipid bilayers when predicting the affinity for biomembranes.

Polyvinyl Alcohol (PVA)/ Graphene Quantum Dots (GQDs) polymer nanocomposite films have been prepared, and the relationship between their structural, thermal and nanoscale morphologi-cal properties, and their photoluminescent response, has been investigated. Although according to X-ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR) and Differential Thermal Analysis (DTA) the incorporation of GQDs does not significantly affect the percentage crystallinity of the PVA matrix, for a range of added GQD concentrations, Atomic Force Micros-copy (AFM) showed the formation of islands with apparent crystalline morphology on the surface of the PVA/GQD films, with GQD presumably acting as a nucleating agent for island growth. The incorporation of GQD also led to the formation of characteristic surface pores with increased stiffness and frictional contrast, according to Ultrasonic Force Microscopy (UFM) and Frictional Force Microscopy (FFM) data. The photoluminescence (PL) spectra of the films were found to de-pend both on the amount of GQD incorporated and on the film morphology. For GQD loads > 1,2wt%, a GQD-related band was observed at ~ 1650 cm-1 in FT-IR, along with an increase in the PL band at lower energy. For a load of ~2wt% GQD, the surface morphology was characterized by extended cluster aggregates with lower stiffness and friction than the surrounding matrix, and the PL signal decreased.

This paper explores the role of agroforestry in mitigating climate change by sequestering atmospheric carbon in the tropics and subtropics, specifically in the Madhupur Sal forest of Bangladesh. Agroforestry, combining trees with crops on agricultural lands, is recognized for its potential to act as carbon sinks and enhance productivity. The study assesses various agroforestry practices, including Acacia-Pineapple-Turmeric-Papaya, Acacia-Pineapple-Zinger-Banana, and Sal-Pineapple-Aroid combinations. The research reveals improved farm productivity in these agroforestry systems, with different tree species sequestering varying amounts of carbon. Acacia species, ranging from 12 to 25ft in height, sequestered an average of 23.35 lbs/year, while Sal species (Shorea robusta), with trees 45 to 61ft tall, sequestered 49.80 lbs/year on average. Factors such as tree height, diameter at breast height (DBH), number of leaves, and branches influence carbon sequestration. The paper suggests integrating the carbon trading system of the Clean Development Mechanism (CDM) with Carbon Sequestration (CS) potential to leverage agroforestry for greenhouse gas emission reduction in Bangladesh. By emphasizing the profitability of these practices alongside carbon sequestration, the study encourages the adoption of agroforestry as a sustainable and economically viable strategy for climate change mitigation.

Food packaging plays an imperative role in the food processing sector by safeguarding foods from their point of harvesting until the moment of consumption. In recent years, biopolymers have attracted the attention of the scientific community as an alternative to conventional packaging materials, reducing the negative environmental impact. Among the available biopolymer sources, a lot of focus has been directed toward polysaccharides due to their superior barrier qualities against gases, oil, and odour and their processing versatility. Moreover, there is a growing interest in aliphatic polyesters as a potential replacement for petrochemical-based synthetic plastics. Both polysaccharides and aliphatic polyesters have gained popularity in sustainable food packaging due to their unique characteristics, including low cost, readily available, biodegradability, gas and moisture barrier qualities, film-forming capabilities, excellent heat resistance, and ability to be processed into films, trays, and coatings. This review highlights the structural features, properties and recent advancements of several vital polysaccharides, namely starch, chitosan, cellulose, alginate, pectin, carrageenan, and aliphatic polyesters, including polylactic acid (PLA) and polyhydroxybutyrate (PHB) for developing packaging materials and their applications in the food industry. Conventional packaging and future perspectives of biopolymer-based food packaging are also comprehensively covered in this review.

Among the different ways to reduce the secondary effects of antineoplastic drugs in cancer treatment, the use of nanoparticles has demonstrated good results due to the protection of the drug and the possibility of releasing compounds to a specific therapeutic target. The α-isoform of folate receptor (FR) is overexpressed on a significant number of human cancers; therefore, folate-targeted crosslinked nanoparticles based on BSA and alginate mixtures and loaded with paclitaxel (PTX) have been prepared to maximizing the proven antineoplastic activity of the drug against solid tumors. Nanometric-range sized particles (169 ± 28nm - 296 ± 57nm), with negative Z-potential values (between -0.12 ± 0.04 and -94.1± 0.4), were synthesized. The loaded PTX (2.63±0.19 - 3.56 ±0.13 µg PTX/mg Np) was sustainably released along 23 and 27h. Three cell lines (MCF-7, MDA-MB-231 and HeLa) were selected to test the efficacy of the folate-targeted PTX-loaded BSA/ALG nanocarriers. The presence of FR on cell membrane led to a significant larger uptake of BSA/ALG-Fol nanoparticles regarding to the equivalent nanoparticles without folic acid on its surface. The cell viability results demonstrated a cytocompatibility of unloaded nanoparticle-Fol and a gradual decrease in cell viability after treatment with PTX-loaded nanoparticles-Fol due to the sustainable PTX release.

Tussilago farfara L. is a traditional medicinal plant valued for its potentially health-promoting metabolites. Its herbal raw material has been recognized and used since ancient times and continues to be widely used in traditional medicine. Introducing these plants to in vitro cultivation is a challenging task, but once the protocol is developed, such cultures can provide an abundant and inexhaustible source of plant material. In this study, we report the successful induction and growth of vigorous T. farfara L. callus in vitro. Callus induction was achieved on solid media in darkness, whereas it appeared inefficient under light conditions and in suspension culture. We present a detailed description of callus growth kinetics, morphological analysis, photosynthetic activity and biochemical parameters (including protein content and photosynthetic pigments) supported by histological studies. Furthermore, we observed potential for organogenesis and somatic embryogenesis. This method for in vitro propagation of T. farfara, along with callus culture maintenance, offers a wide range of applications in pharmacy and could benefit the environment by minimizing the depletion of natural populations of this species.

In this study we used a recently developed ex vivo-in vitro model to assess the effect of feeding older adults a casein protein hydrolysate (CPH) compared with non-bioactive non-essential amino acid (NEAA) supplement on Muscle Protein Synthesis (MPS) and Breakdown (MPB). Serum from six healthy older males following overnight fast and 60 min postprandial ingestion of CPH or NEAA (0.33 g.kg^-1 body mass) was used to condition C2C12 myotube media. CPH-fed serum significantly increased MPS compared to fasted serum. In addition, CPH-fed serum induced myotube growth and markedly suppressed atrogin-1, but not MuRF1, expression. Comparatively, no change in MPS, myotube growth and gene expression was observed following NEAA-fed serum treatment. CPH-fed serum from older adults stimulated de novo MPS, suppressed markers of protein breakdown and resulted in myotube growth, indicating a potential role for CPH as a dietary protein source to prevent age-related sarcopenia.

Surgical site infections (SSIs) are a major concern in public healthcare, leading to increased morbidity, pro-longed hospital stays length, and significant economic costs. Understanding the epidemiology and risk fac-tors of SSIs is crucial for developing effective prevention and management strategies. In the last century, CDC ‘s HICPAC improved a bundle for prevention of HAIs based on the use of aseptic procedures, disin-fection of the skin and correct use of antibiotics for SSIs. In our country, Gelli-Bianco law introduced the national health guidelines system that include the prophylaxis antibiotic therapy pre- and post-surgery. The aim of our study is to evaluate adherence and appropriateness of the use of antibiotic-preoperative prophylaxis in a province of southern Italy and to identify risk factors that may influence the development of an SSI. The study found many statistically significant associations among the factors examined, i.e. the timing of administration adherent to guidelines, with 47% of the analyzed files administering antibiotics within 60 min before the intervention and 62.7% using intravenous administration.

In this study, we surveyed over 600 participants to determine: a) major causes to mental stress during the pandemic and its future impacts, and b) diversity in public perception and acceptance (specifically for children) of Covid-19 vaccination. Statistical results and intelligent clustering outcomes indicate significant relationships between sociodemographic diversity, mental stress causes, vaccination perception, and Covid-19 infections. For instance, statistical results indicate significant dependence between mental stress due to Covid-19 and gender (p = 1.7e-05). Over 25% of males indicated work related stress comparing 35% in females however, females indicated more stressed (17%) due to relationships comparing to males (12%). Around 30% of Asian/Arabic participants don’t feel vaccination being safe as compared to 8% of white-British and 22% of white-European indicating significant dependence (p = 1.8e-08) with ethnicity. More specifically, vaccination acceptance for children is significantly dependent to ethnicity (p = 3.7e-05) where only 47% participants show willingness towards children’s vaccination. Primary dataset in this study along with experimental outcomes identifying sociodemographic information diversity with respect to public perception and acceptance of vaccination to children and potential stress factors might be useful for public and policy makers to be better prepared for future epidemics as well as working globally to combat mental health issues and running more effective vaccination campaigns.

Abstract: Comparing outcrop data to laboratory results is important to verify and validate experiments of analogue and reservoir materials especially regarding conditions for deformation experiments. This is important better understand highly complex carbonate reservoir strata and their response to changes in subsurface conditions, reducing subsurface uncertainty. This study develops methods to allow for a more straightforward comparison of outcrop data (m-scale) with experimentally created fracture arrays developed in cylindrical samples (cm-scale). The main objective is to assess usefulness of experimentally-produced fracture networks as analogues for subsurface structures, typically at the meter and above scale by developing new techniques to use the lab deformation. It analyses key characteristics of laboratory-induced fracture networks by adapting scanline methods to use with x-ray tomography (XRT) images to allow for comparison with outcrop and field data. To test and verify these new methods two low permeability carbonate samples were used for deformation testing and analysis. Applying the different scanline methods we show that they can be used to analyse lab induced fractures (mm to cm-scale) identified in XRT images for comparison with outcrop data (m-scale). In addition, these methods also allow for quantification of fracture network attributes e.g. fracture spacing, fracture apertures, orientation. This new data bridges the gap between micro-scanlines using thin sections and outcrop scanlines.

During the COVID-19 pandemic, the circulation of non–SARS-CoV-2 respiratory viruses changed throughout the world. This study aimed to analyze the effect of respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus (RV), and parainfluenza (PIV)-3 single infection, dual co-infection, and viral load on cytokine and chemokine expression in 300 Mexican patients with ARIs negative for SARS-CoV-2. Molecular detection and viral load were performed by RT-qPCR. Cytokine and chemokine expression was determined in samples positive for single RSV, MPV, RV, or PIV-3 infection, and in the most frequent dual co-infections, by a cytokine panel using a magnetic-bead-based multiplex immunoassay. Of the patients positive for viral infection, 91.7% had a single infection and 8.3% had dual co-infections. In this study, RSV was the respiratory virus with the highest prevalence, and the most common dual co-infection was RV+RSV. On the other hand, RV infections had the highest viral loads compared to the other viruses detected. FGF basic, MIP-1α IL-8, IP-10, MCP-1, IFN-γ, and RANTES showed differential expression between single infections and dual co-infections compared to healthy patients. We report, for the first time, the circulation of non-SARS-CoV-2 viruses in the south of Mexico and the cytokine and chemokine profiles associated with these viruses.

C-reactive protein to lymphocyte ratio (CLR) has been shown to be associated with diseases characterized by chronic, low-grade inflammation. Since type 2 diabetes (T2DM) is also associated with inflammation, we aimed to study the association between CLR and T2DM. Patients with T2DM who presented to internal medicine outpatient clinics of our institution were divided into 2 groups according to their glycosylated hemoglobin (HbA1c) levels as well-controlled (HbA1c&lt;7%) and poorly controlled (HbA1c≥7%) T2DM groups. Subjects assigned as healthy in routine check-up were included as control group. CLR values of the well and poorly controlled diabetics and control cases were compared. CLR of T2DM group (3.51 (0.03-21.78)) was significantly higher than that of the controls (0.65 (0.02-2.92)) (p&lt;0.001). CLR was found to have a sensitivity of 63.2% and a specificity of 97.3% in predicting T2DM. The CLR value of patients with poor diabetic control was 4.76 (0.06-21.78), while the CLR value of patients with well controlled disease was 2.53 (0.03-12.07) (p&lt;0.001). The sensitivity and specificity of the CLR in demonstrating poor diabetic control was 41.2% and the 86.1%, respectively. In conclusion, elevated CLR in T2DM patients and even more increased levels in poorly controlled diabetics suggest that CLR could be a useful additional diagnostic tool in treatment follow-up of the T2DM population.

Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

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

Obesity, type 2 diabetes, and different forms of cancers are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches. Diabetes and cancer are among the most frequent and complex diseases and based on epidemiological evidence and study it can be concluded that the patients suffering from diabetes are considered to be significantly at higher risk for a number of cancer types. Both these diseases are among the highly complex and heterogeneous in nature. There are a number of evidences which support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of both these diseases type 2 diabetes and different types of cancers. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic. With so many known challenges, it is critical to understand the relationships and the common shared causes between type 2 diabetes and cancer which is difficult to unravel and understand. Furthermore, the real complexity arises during diagnosis from contended corroborations that specific drug(s) (individually or in combination) during diagnosis process of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidences from the studies where the origin, biological background, correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. we have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases diabetes and cancer.

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

SARS-CoV-2 or COVID-19, a new seventh human corona virus, has out-broken in Wuhan, China since 31^st December 2019, and quickly escalated to take the form of pandemic which killed many human beings throughout almost all countries across continents. The rapidity of its transmission from human to human is far greater than all previous human corona viruses which came into existence like SARS-CoV, MERS-CoV, etc. The nucleotide sequence of SARS-CoV-2 (isolates Wuhan-Hu-1) is 29,875 bp in ss-RNA. Symptoms of SARS-CoV-2 infected pneumonia include from asymptomatic to high fever and/or respiratory illnesses. Coronavirus virion (spherical/round /elliptical in shape) consists of three parts- outer membrane or envelope, nucleocapsid and genome (RNA). SARS-CoV-2 was shown to use receptor, angiotensin converting enzyme 2 (ACE2) for attachment to the cells through its surface spike (S) protein (S1), and the virion enters into the host cell through two routes- direct membrane fusion and endocytotic pathway. The RNA of SARS-CoV acts directly as mRNA and here minus(-) 1 programmed ribosomal frameshift (-1PRF) is being operated by slippery sequence and pseudoknot, so it translates 16 nonstructural proteins including RNA dependent RNA replicase. Then genomic RNA replicated continuously on – strand RNA template and subgenomic RNA transcribed discontinuously on –RNA template to sgmRNA. Subgenomic RNAs/sgmRNAs synthesize all structural proteins. This article takes into consideration the details of established theories of viral structure, viral attachment, mode of entry into human cells, different models of replication and transcription of virus genome proposed by eminent scientists over the years, and makes an in depth examination highlighting meaningful points or important target cites of viral propagation or synthesis, which are conserved, for prompt development of potent drugs or vaccine to counter COVID-19 for which human race is anxiously and eagerly waiting.

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). Overall, severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 10²-10⁵ gc/ml) and feces (ca. 10²-10⁷ gc/ml) is much lower than in nasopharyngeal fluids (ca. 10⁵-10¹¹ gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the GI tract and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that over eight million global cases of COVID-19 have occurred, but exposure to feces or wastewater has never been implicated as a transmission vector.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

Corona viruses hijack human enzymes to assembly sugar coat on Spike glycoproteins. The mechanism that human antibodies may uncover the antigenic viral peptide epitopes hidden by sugar coat are unknown. In this study, we analyzed recombinant SARS-CoV-2 Spike protein secreted from BTI-Tn-5B1-4 cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired MS/MS spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of Spike proteins according to Cryo-EM and homolog-modeled structures, and available antibodies that bind to SARS-CoV-1. The results showed that all 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose type of N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the Spike receptor binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains included those located on Central Helix, between amino acids 967 and 1016 of SARS-CoV-1, and 985 to 1034 of SARS-CoV-2 Spike protein. As the majority of antibody paratopes bind to peptide portion with or without sugar modification, we propose a snake-catcher model that a minimal length of peptide is first clamped by a paratope, and the binding is either strengthened by sugars close to peptide, or not interfered by sugar modification.

The effect of prostaglandin E1 (PGE1) encapsulated in nanoparticles (Nano PGE1) on motor dysfunction and muscle atrophy induced by sciatic nerve injury (SNI) was investigated in rats, and was compared with PGE1 encapsulated in lipid microspheres (Lipo PGE1) or PGE1 clathrated in cyclodextrin (PGE1-CD). The hind limb muscle weight ratio decreased until 2 weeks after SNI. All 3 PGE1 formulations significantly improved SNI-induced motor dysfunction. Nano PGE1 significantly promoted recovery from muscle atrophy at 2 and 3 weeks after SNI. Lipo PGE1 was also effective, but multiple doses were required. Compared with the SNI control group, the Nano PGE1 group showed upregulation of vascular endothelial growth factor (VEGF) and agrin expression in the injured sciatic nerve and atrophic muscles. Nano PGE1 accumulated prominently at the site of nerve injury and persisted for longer than Lipo PGE1 or PGE1-CD. Expression of all EP receptors was detected in the normal sciatic nerve, and EP2 expression increased after SNI. Finally, Nano PGE1 promoted ERK1/2 and Akt phosphorylation. These findings suggest that PGE1 released from nanoparticles accumulates at sites of nerve injury and increases VEGF production by augmenting ERK1/2 phosphorylation via EP receptor signaling, thus promoting tissue repair and regeneration.

We examine the mass balance of the glaciers in the Novaya Zemlya Archipelago, located in the Russian High Arctic using time series of time-variable gravity from the NASA/DLR Gravity Recovery and Climate Experiment (GRACE) mission, laser altimetry data from the NASA Ice Cloud and land Elevation Satellite (ICESat) mission, and radar altimetry data from the ESA CryoSat-2 mission. We present a new algorithm for detecting changes in glacier elevation from these satellite altimetry data and evaluate its performance in the case Novaya Zemlya by comparing the results with GRACE. We find that the mass loss of Novaya Zemlya increased from 10±5 Gt/yr over 2003-2009 to 14±4 Gt/yr over 2010-2016, with a brief period of near mass balance between 2009 and 2011. The results are consistent across the gravimetric and altimetric methods. Furthermore, the analysis of elevation change from CryoSat-2 indicates that 60\% of the mass loss occurs at low elevation, where thinning rates are highest. We also find that marine-terminating glaciers in Novaya Zemlya are thinning significantly faster than land-terminating glaciers, which indicates an important role of ice dynamics of marine-terminating glaciers. We posit that the glacier changes have been caused by changes in atmospheric and ocean temperatures. We find that the increase in mass loss after 2010 is associated with a warming in air temperatures, which increased the surface melt rates. There is no enough information on the ocean temperature at the front of the glaciers to conclude on the role of the ocean, but we posit that the temperature of subsurface ocean waters must have increased during the observation period.

Mutations of PKD1 coding for polycystin-1 (PC1) account for most of the autosomal dominant polycystic kidney disease (ADPKD). The extracellular region of PC1 contains many evolutionarily conserved domains for ligand interactions. Among these is the leucine-rich repeats (LRR) in the far N-terminus of PC1. Using zebrafish (Danio rerio) as an in vivo model system, we explored the role of LRR in the function of PC1. Zebrafish expresses two human PKD1 paralogs, pkd1a and pkd1b. Knockdown of both genes in zebrafish by morpholino antisense oligonucleotides produced phenotypes of dorsal axis curvature and pronephric cyst formation. We found that overexpression of LRR suppressed both phenotypes in pkd1-morphant zebrafish. Purified recombinant LRR domain inhibited proliferation of HEK cells in culture and interacted with the heterotrimeric basement membrane protein laminin-511 (α5β1γ1) in vitro. Mutations of amino acid residues in LRR structurally predicted to bind laminin-511 disrupted LRR-laminin interaction in vitro and neutralized the ability of LRR to inhibit cell proliferation and cystogenesis. Our data support the hypothesis that the extracellular region of PC1 plays a role in modulating PC1 interaction with the extracellular matrix and contributes to cystogenesis of PC1-deficiency.

Background: Breast cancer is a commonly diagnosed cancer worldwide. Human MutT homolog 1 (MTH1) is found to be elevated in breast tumors and cancer cells are addicted to MTH1 for sur-vival. Pharmacological inhibition of MTH1 may be potentially beneficial in the treatment of breast cancer. Methods: MA-24 was screened by malachite green colorimetric assay from MTH1 inhibitors and the kinetic characteristics of MA-24 was assessed. Binding features of MA-24 with MTH1 was as-certained through molecular docking, and cytotoxic activity of MA-24 was validated in vitro and in vivo. Target engagement assays, comet assay and western blot confirmed that the intracellular target and mechanism of MA-24. Results: MA-24 with potent antitumor bioactivity both in vitro and in vivo. MA-24 competitively inhibited the MTH1 and further induce DNA strand breaks, leading to increased apoptosis of cancer cells depending on upregulation of cleaved-caspase 3 – cleaved-PARP axis. Especially, MA-24 exhibited a powerful efficacy and safety in vivo (tumor growth inhibition rate: 61.8%). Conclusions: MA-24 possesses a broad spectrum of breast cancer cytotoxicity and offered valuable insights for overcoming the challenges of chemotherapy-related toxicity, which holds great po-tential for further development MA-24 as an anti-cancer drug.

Human pulmonary paragonimiasis, an emerging concern in North East India, frequently masquerades as pulmonary tuberculosis due to clinical and radiological similarities, leading to diagnostic challenges. This research was aimed to harness the immunoblotting technique to discern immunodiagnostic protein antigens from both adult worm and excretory-secretory (ES) extracts of the prevalent Paragonimus westermani type 1 in Arunachal Pradesh, North East India. We studied the time kinetics of immunoreactive patterns in relation to the duration of infection in rodent models. Immunoblot analyses were also conducted using sera from ELISA positive patients confirmed with paragonimiasis, facilitating the selection of antigenic extracts with diagnostic potential. Further, ES proteins antigens were subjected to 2D- immunoblot analysis and immunoreactive protein spots identified by MALDI-TOF MS. Immunoreactivity patterns of ES antigens with sera of paragonimiasis positive patients were detailed, and specific immunoreactive protein antigens were pinpointed using peptide mass fingerprinting (MALDI-TOF). This work underscores the enhanced diagnostic accuracy when combining ELISA with immunoblotting for pulmonary paragonimiasis in regions like North East India, marked by co-existing helminth infections.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02-restricted CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope exclusively restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, we extensively discussed about bioprinting endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed.

Monitoring snowmelt dynamics in mountains is crucial to understand water releases downstream. Sentinel-1 (S-1) synthetic aperture radar (SAR) has become one of the most widely used techniques to achieve this aim due to its high frequency of acquisitions and all-weather capability. This work aims to understand the possibilities of S-1 SAR imagery to capture snowmelt dynamics and related changes in streamflow response in semiarid mountains. The results proved that S-1 SAR imagery was able not only to capture the final spring melting but also all melting cycles that commonly appear throughout the year in these types of environments. The general change detection approach to identify wet snow was adapted for these regions using as reference the average S-1 SAR image from the previous summer, and a threshold of -3.00 dB. In addition, four different type of melting runoff onsets depending on physical snow condition were identified. When translating that at the catchment scale, distributed melting runoff onset maps were defined to better understand the spatiotemporal evolution of melting dynamics. Finally, a linear connection between melting dynamics and streamflow was found for long-lasting melting cycles, with a determination coefficient (R2) ranging from 0.62 to 0.83 and an average delay between the melting onset and streamflow peak of about 21 days.

Prevention and management of cytomegalovirus (CMV) reactivation is important to improve outcome of allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The aim of this study was to analyze real-world data for incidence and characteristics of CMV infections until 1-year after allo-HCT under 100-day letermovir prophylaxis. A single-center retrospective study was conducted between November 2020 and October 2021. During the study period, 358 patients underwent allo-HCT, 306 of whom received letermovir prophylaxis. Cumulative incidence of clinically significant CMV infection (CS-CMVi) was 11.4%, 31.7%, and 36.9% at 14-weeks, 24-weeks, and 1-year post-HCT, respectively. In multivariate analysis, risk of CS-CMVi increased with graft-versus-host disease (GVHD) ≥ grade 2 (adjusted odds ratio 3.640 [2.036–6.510]; P &lt; 0.001). One-year non-relapse mortality was significantly higher in letermovir breakthrough CS-CMVi patients than those with subclinical CMV reactivation who continued letermovir (P = 0.002). There were 18 (15.9%) refractory CMV infection in this study population. In summary, letermovir prophylaxis is effective in preventing CS-CMVi until day 100, which increased after cessation of letermovir. GVHD is still a significant risk factor in letermovir prophylaxis era. Further research is needed to establish individualized management strategies especially in patients with significant GVHD or letermovir breakthrough CS-CMVi.

The reef manta ray (Mobula alfredi) is a highly mobile and plankton-feeding species, classified vulnerable to extinction on the IUCN Red List for Threatened Species. Knowledge on their spatial ecology and the extent of their dispersal remain incomplete, especially within island-fragmented habitats as found in New Caledonia. Satellite telemetry was used to investigate the horizontal movement ecology of reef manta rays in New Caledonia. A total of 21 manta rays were tagged with pop-up satellite archival transmitting tags (21 Fastloc and 2 MiniPAT) that remained deployed for a duration ranging from 3 to 180 days (mean ± SE = 76.7 ± 50.3). Rays presented a strong site fidelity and an important affinity for coastal waters. Long-distance migrations (> 300 km) were also observed, mainly through coastal and shallow water paths. Horizontal movements were compared to a home range area and classified into four distinct patterns: Fidelity, Excursion, Fidelity + Relocation and Relocation. The most dominant pattern was Fidelity where manta rays remained within their home range for the whole duration of the tag deployment. Our findings may assist the design of more appropriate management strategies for the species in New Caledonia and other regions worldwide.

Aim: Sca-1+CD31− cells were shown to be endothelial stem/progenitor cells, found in many mammalian tissues, including heart, were able to differentiate into cardiomyocytes in vitro and in vivo. Our previous work indicated that heart derived Sca-1+CD31− cells increased Nr1d1 mRNA level and decreased cells plasticity with aging. However, little is known about how NR1D1 affects Sca-1+CD31− cells plasticity. Methods: Lentiviral vector was used to stably overexpress Nr1d1 in young Sca-1+CD31− cells and to knockdown Nr1d1 in aged Sca-1+CD31− cells. Cell differentiation, proliferation, apoptosis, and cell cycle were evaluated. Results and Conclusions: The overexpression of Nr1d1 in young Sca-1+CD31− cells inhibited cell proliferation and promoted apoptosis. Knockdown of Nr1d1 in aged Sca-1+CD31− cells promoted cell proliferation and inhib-ited apoptosis. Using mouse cardiac myocytes cell line, confirmed the effect of Nr1d1 and indi-cated that Nr1d1 induce Serpina3 expression via Nr1d1 interaction with Nr4a3. Nr1d1 may there-fore be identified as a potent anti-aging receptor and be a therapeutic target for aging relative diseases.

African swine fever (ASF) is one of the most important and devastating viral diseases in wild boar and domestic pigs worldwide. In the absence of vaccines or treatment options, early clinical detection is key and requires sound knowledge of disease characteristics. To provide practitioners and state veterinarians with detailed information, the objective of the present study was to characterize the ASF virus (ASFV) isolate “Belgium 2018/1” in subadult and weaning domestic pigs. To this end, two animal trials were performed. Trial A included eight subadult domestic pigs and trial B five weaner pigs. In general, clinical signs and pathological lesions were in line with previous studies utilizing highly virulent ASF genotype II viruses. However, in trial A, four subadult domestic pigs survived and recovered pointing to an age dependent outcome. The long-term fate of those survivors remains under discussion and would need further investigations.

Novel mechanism of ccRCC progression is essential, including PBRM1, BAP1, and SETD2 in histone-modifying and chromatin remodeling genes. The study aimed to investigate VHL, PD-1, PD-L1, PD-L2. BAP1, PBRM1, SETD2 expression in ccRCC primary cancers and metastatic tissues associated with the cancer dissemination. A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level of VHL, PD-1, PD-L1, PD-L2. PCR in real-time performed BAP1, PBRM1, SETD2 with the previous RNA isolation. Western Blotting analysis was used for detecting the p-VHL protein content in tissues. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. ccRCC progression in VHL overexpression is associated with the decrease in BAP1 gene expression. It is revealed the heterogeneity in molecular markers in primary tumors and metastases. The low mRNA level of BAP1, PBRM1, SETD2, PD-1, PD-L1, PD-L2 in metastases compared with primary tumors were found. We show a novel mechanism for VHL tumor progression and present a new instrument and factor targeting tumor-related pathologies with p-VHL/HIF altered function.

Aim: To establish, through molecular modelling, safe and clinically acceptable putative antagonists of E571K-mutated exportin-1 among the bioactive compounds in various parts of Juglans mandshurica. Methods: The bioactive compounds were subjected to compendium of druglikeness and lead-likeness filter workflows prior to docking of the resultant compounds into E571K exportin-1 active site using PyRx AutoDock vina to establish their binding affinity and interaction profile. The evolutionary algorithm of Osiris property explorer DataWarrior software as well as lead-likeness filter were employed for generation of novel non-promiscuous analogues of the lead compound with better putative selectivity and clinical acceptability as E571K Exportin-1 antagonists.Results: The findings of this study present taxifolin as the putatively effective and lead-like E571K Exportin-1 inhibitor with high potential of qualifying for clinical evaluation but is associated with high promiscuity tendency in high throughput screening. The evolutionary derivation of novel analogues of the compound, however, results in the generation of putatively non-promiscuous, non-toxic, and lead-like E571K Exportin-1 antagonists with high synthetic accessibility and clinical developability for evaluation in the strategy for treatment of drug-resistant KRAS-mutant lung adenocarcinoma condition.

Acute myeloid leukemia (AML) is an incurable hematological malignancy. To treat the disease successfully, new therapeutic strategies are urgently needed. One of these strategies can be the use of neurokinin-1 receptor (NK-1R) antagonists (e.g., aprepitant), because the substance P (SP)/NK-1R system is involved in cancer progression, including AML. AML patients show an up-regulation of the NK-1R mRNA expression; human AML cell lines show immunoreactivity for both SP and the NK-1R (it is overexpressed: the truncated isoform is more expressed than the full-length form) and, via this receptor, SP and NK-1R antagonists (aprepitant, in a concentration-dependent manner) respectively exert a proliferative action or an antileukemic effect (apoptotic mechanisms are triggered by promoting oxidative stress via mitochondrial Ca++ overload). Aprepitant inhibits the formation of AML cell colonies and, in combination with chemotherapeutic drugs, is more effective in inducing cytotoxic effects and AML cell growth blockade. NK-1R antagonists also exert an antinociceptive effect in myeloid leukemia-induced bone pain. The antitumor effect of aprepitant is diminished when the NF-κB pathway is overactivated and the damage induced by aprepitant in cancer cells is higher than that exerted in non-cancer cells. Thus, the SP/NK-1R system is involved in AML and aprepitant is a promising antitumor strategy against this hematological malignancy. In this review, the involvement of this system in solid and non-solid tumors (in particular in AML) is up-dated and the use of aprepitant as an anti-leukemic strategy for the treatment of AML is also mentioned (a dose of aprepitant (> 20 mg/kg/day) for a period of time according to the response to treatment is suggested).

For voltage-gated Ca2+ channel (VGCC), its α2δ subunits are traditionally considered to be auxiliary subunits that regulates VGCC trafficking to the plasma membrane. The antiepileptic, antinociceptive and anxiolytic gabapentin (GBP) has previously been shown to bind the VGCC α2δ subunits with high affinity to disrupt VGCC trafficking. Yet, the interaction between GBP and α2δ still remains poorly understood from a structural point of view. For instance, it is not clear yet what the structural implication is of α2δ-1-bound GBP against VGCC trafficking. With a set of experimental data-driven structural analysis of the VGCC α2δ-1 and its ligand GBP, this article postulates for the first time that: 1), α2δ-1 bound GBP stabilizes the α2δ-1-GBP complex structure; 2), α2δ-1 bound GBP restrains the conformational flexibility of α2δ-1; 3), α2δ-1-bound GBP establishes an electrostatic axis consisting of Q535 (Gln535)-R241 (Arg241)-GBP (gabapentin)-D452 (Asp452), which constitutes an energetically favourable contribution towards the structural stability of the α2δ-1-GBP complex and helps restrains the conformational flexibility and local structural rigidification of α2δ-1; and 4), GBP-induced local conformational inflexibility and structural rigidification of α2δ-1 is one key step in the pharmacological disruption of VGCC trafficking by GBP.

A novel and simple method to improve the corrosion resistance of copper by constructing a 3D 1-dodecanethiol self-assembled monolayers (SAMs) in 3.5% NaCl solution is reported in this study. Several drops of 1% H3PO4 solution are thinly and uniformly distributed on copper surface to form a 3D nanostructure constituted by Cu3(PO4)2 nanoflowers. The anticorrosion properties of 1-dodecanethiol SAMs on copper surface and on copper surface treated with H3PO4 solution were evaluated. Results demonstrated that 1-dodecanethiol SAMs on bare copper surface exhibit good protection capacity, whereas a copper surface pretreated with H3PO4 solution can substantially enhance the corrosion resistance of 1-dodecanethiol SAMs.