SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It produces severe acute respiratory disease (COVID-19), which is fatal in many cases, characterised by cytokine release syndrome (CRS). According to the World Health Organization (WHO), those who smoke are likely to be more vulnerable to infection. Here, in order to clarify the epidemiologic relationship between smoking and COVID-19, we present a systematic literature review until 28 April 2020 and a meta-analysis. It includes 18 recent COVID-19 clinical and epidemiological studies based on smoking patient status from 720 initial studies in China, USA, and Italy. The percentage of hospitalised current smokers was 7.7% (95%CI: 6.9-8.4) in China, 2.3% (95%CI: 1.7-2.9) in the USA and 7.6% (95%CI: 4.2-11.0) in Italy. These percentages were compared to the smoking prevalence of each country and statistically significant differences were found in them all (p <0.0001). By means of the meta-analysis, we offer epidemiological evidence showing that smokers were statistically less likely to be hospitalised (OR=0.18, 95%CI: 0.14-0.23, p<0.01). CRS and exacerbated inflammatory response are associated with aggravation of hospitalise patients. In this scenario, we hypothesise that nicotine, not smoking, could ameliorate the cytokine storm and severe related inflammatory response through the cholinergic-mediated anti-inflammatory pathway.

SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an outbreak of COVID-19 disease in humans with the aid of spike protein. It consists of a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2). The aim of this study was to examine the mutational effect of spike protein on the sequence through an interaction study of the mutant spike protein and the human ACE2 protein at the structural level. A total of 17,227 spike proteins from Asia, Africa, Europe, Oceania, South America, and North America were compared to the Wuhan spike protein reference sequence (Wuhan-Hu-1). The structural and stability implications of D614G, N501Y, and S477N mutations were evaluated. The binding affinity between mutated RBD and human ACE2 protein was also studied. The D614G mutation may have originated in Germany, Europe based on the date of the first sample collection report. It is now widely circulated all over the world with most occurrences in North America. The mutations N501Y and S477N may have originated from Oceania based on the date of the first sample collection report and also have the highest occurrences in Oceania. Based on the computational analysis of mutational effects, the D614G, N501Y, and S477N mutations decreased stability and were tolerated. For disease propensity prediction, N501Y was more prone to disease compared to D614G, while S477N was not prone to disease. The mutation of D to G at position 614 and S to N at position 477 for secondary structure prediction shows no changes in secondary structure while remaining in the coil region, whereas the mutation of N to Y at position 501 changes from coil structure to extended strand. N501Y mutation has a higher affinity to human ACE2 protein compared to D614G and S477N based on a docking study. D614G spike mutation was identified to exist between the two hosts based on a comparison of SARS-CoV-2 derived between the mink and human. Further research is needed on the link between the mink mutation N501T and the mutation N501Y in humans, which has evolved as a separate variant.

COVID 19, a pandemic spread without any solid anti-viral antidote. Researchers worldwide are currently giving their best to make antidote for this virus with all available literatures and knowledge. Research carried out indicates sulfated polysaccharides (carrageenan) are selective inhibitors of several enveloped and non-enveloped viruses and act predominantly by inhibiting the binding or internalization of virus into the host cells. Polysaccharides produced from Porphyridium sp. are sulfated polysaccharides which are promising antiviral agents against respiratory viruses from the family of coronavirus. These biocompatible compounds can be used as a coating material on the sanitary items for COVID-19 prevention.

ABSTRACT. In this paper, we run for all INDIA mutations and variants a biomathematical numerical method for analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions (Perez, 2021). In this study, we limit ourselves to the analysis of whole genomes, all coming from the mutations and variants of SARS-CoV2 sequenced in India in 2020 and 2021. We then demonstrate - both on actual genomes of patients and on variants combining the most frequent mutations to the SARS-CoV2 Wuhan genomes and then to the B.1.617 variant - that the numerical Fibonacci AU / CG metastructures increase considerably in all cases analyzed in ratios of up to 8 times. We can affirm that this property contributes to a greater stability and lifespan of messenger RNAs, therefore, possibly also to a greater INFECTUOSITY of these variant genomes. Out of a total of 108 genomes analyzed: - None ("NONE") of them contained a number of metastructures LOWER than those of the reference SARS-CoV2 Wuhan genome. - Eleven (11) among them contained the same number of metastructures as the reference genome. - 97 of them contained a GREATER number of metastructures than the reference genome, ie 89.81% of cases. The average increase in the number of metastructures for the 97 cases studied is 4.35 times the number of SARS-CoV2 UA/CG 17711 Fibonacci metastructures. Finally, we put a focus on B.1.617.2 crucial exponential growth Indian variant. Then, we demonstrate, by analyzing the main worldwide 19 variants, both at the level of spikes and of whole genomes, how and why these UA / CG metastuctures increase overall in the variants compared to the 2 reference strains SARS-CoV2 Wuhan and D614G.

Utility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of ≥ 70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.

Prothrombotic thrombocytopathy mimicking heparin-induced thrombocytopenia has been observed in patients with severe COVID-19 and after immunisation with the Vaxzevria vaccine. Herein, we discuss the possible pathogenesis of this disorder focusing on the possible involvement of anti-platelet factor 4 (PFA) autoantibodies.

While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, bonds between autologous carbohydrates and foreign peptides, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

The storage of biochemical information, which is a prerequisite for the development of the first cell, is an unsolved problem affecting all concepts of the origin of life. However, if the protected environment in the continental crust is taken into account, completely new possibilities emerge for identifying processes that may have been crucial for the formation of the first cell. Under this background, we can hypothesize that cellular life began, with a self-sustaining cycle of molecular reaction steps and information storage of peptide sequences in RNA in a crustal depth of approximately 1000 m. This cycle was made possible in an open system bound to gas-permeable tectonic fracture zones with a high proportion of CO₂ and/or N₂. It can be assumed that a large number of RNA-like molecular strands formed in the crustal environment, from which a special RNA was selected by flotation processes, which formed the basis of a proto-tRNA. The formation of peptides and vesicles in supercritical CO₂ and the chemical evolution of peptides have already been proven at conditions of the upper continental crust. The behavior of individual amino acids in connection with vesicle formation deserves special interest. Hydrophobic amino acids accumulate in the vesicle membrane, with their position in the membrane depending on the degree of hydrophobicity. Selection of a proto-tRNA with an acceptor arm ending with the bases CCA resulted in a distinctive property. The position of adenine at the tip of the acceptor arm permitted it to penetrate the membrane, allowing it to be linked to an amino acid at the 3'-OH position of the terminal ribose. The penetration depth was controlled by the hydrophobicity of the opposite anti-codon, with adenine always occupying the middle position for the hydrothermally formed hydrophobic amino acids. When the vesicle membrane was closely occupied by proto-tRNAs, the anti-codons acted as templates and stored the sequence of the peptides that form. In the cases of hydrophilic anti-codons, the acceptor arm does not reach far enough into the membrane. This allowed hydrophilic amino acids to be linked to 2´-OH.

Relationships between the Farey sequence and the Riemann hypothesis other than the Franel-Landau theorem are discussed. Whether a function similar to Chebyshev’s second function is square-root close to a line having a slope different from 1 is discussed. The nontrivial zeros of the Riemann zeta function can be used to approximate many functions in analytic number theory. For example, it could be said that the nontrival zeta function zeros and the Möbius function generate in essence the same function - the Mertens function. A different approach is to start with a sequence that is analogous to the nontrivial zeros of the zeta function and follow the same procedure with both this sequence and the nontrivial zeros of the zeta function to generate in essence the same function. A procedure for generating such a function is given.

Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose has the capacity to neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)].56 su bjects with IBD and 12 healthy subjects were recruited. 90% of patients with IBD (49/56) were receiving biologics and/or immunomodulatory therapy. 24 subjects with IBD did not develop effective neutralizing capability against the Omicron variant. 70% (17/24) of those subjects were receiving anti-Tumor Necrosis Factor therapy [10= adalimumab, 7= infliximab], two of them had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and larger studies are needed to evaluate optimal immunity.

The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC₅₀ values below 4 µM and inhibitory constant (Ki) <3 µM.

The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a natural remedy, which has gained international recognition for its anti-anemic effect and energy boosting qualities in debilitating diseases. The widespread use of traditional medicine in the region usually confirms its safety, but not its efficacy or deep assessment of their pharmacological properties. The other major issue for herbal-based treatments is the lack of definite and complete information about the composition of the extracts. Despite limitations, efforts have been made in isolation and characterisation of active compounds in this specie of sorghum showing various subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and potential fungal growth inhibitor, which accounts for 84% of the total extract. Non-clinical in vitro and in vivo studies support previous indications that this variety of Sorghum bicolor possesses several biologically active compounds with potent antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical studies show that SBLS has the ability to boost hemoglobin concentrations in anemic conditions and most remarkably to increase CD4 count in HIV-positive patients. The multiple effects and high safety profiles of this extract may encourage its development as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or in the symptomatic management of HIV infections. This review describes the potential therapeutic aspects of SBLS extract and its potential benefits.

Using recent developments in econometrics and computational statistics we consider the estimation of the instantaneous rate of asset return process when the underlying Data Generating Mechanism (DGM) is an Ornstein-Uhlenbeck process, driven by fractional noise, and sampled at fixed intervals of length h. To address the problem we adopt throughout the paper an exact discretization approach. This enable us to exploit the fact that a flow sampling scheme arises naturally when observing the DGM. For, while the instantaneous rate of return process is unobservable at points in time, its time integral over successive observations is observable since it equals the increment of log-prices. Exact discretization delivers an ARIMA(1,1,1) model for log-prices with a fractional driving noise. Building on the resulting exact discretization formulae and covariance function, a new Markov Chain Monte Carlo (MCMC) scheme is proposed and we examine the properties of both the time and frequency domain likelihoods / posteriors through Monte Carlo. For the exact discrete model we adopt a general sampling interval of length h. This allow us to determine the optimal choice of h independent of the sample size. An empirical application using high frequency stock price data is presented showing the relevance of aggregation over time issues in modelling asset prices.

Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional medicine with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A₁ receptor. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin could inhibit prolactin secretion in GH₃ cells via upregulating the expression of adenosine A₁ receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A₁ receptor.

The separation of sister chromatids during anaphase is the culmination of mitosis and one of the most strikingly beautiful examples of cellular movement. It consists of two distinct processes: Anaphase A, the movement of chromosomes toward spindle poles via shortening of the connecting fibers, and anaphase B, separation of the two poles from one another via spindle elongation. I focus here on anaphase A chromosome-to-pole movement. The chapter begins by summarizing classical observations of chromosome movements, which support the current understanding of anaphase mechanisms. Live cell fluorescence microscopy studies showed that poleward chromosome movement is associated with disassembly, or ‘melting’ of the kinetochore-attached microtubule fibers that link chromosomes to poles. Microtubule-marking techniques established that kinetochore-fiber disassembly often occurs through a ‘pac-man’ mechanism, where tubulin subunits are lost from kinetochore-attached plus ends and the kinetochore appears to consume its microtubule track as it moves poleward. In addition, kinetochore-fiber disassembly in many cells occurs partly through ‘flux’, where the microtubules flow continuously toward the poles and tubulin subunits are lost from minus ends. Molecular mechanistic models for how load-bearing attachments are maintained to disassembling microtubule ends, and how the forces are generated to drive pac-man and flux-based movements, are discussed.

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

Intelligent fault diagnosis techniques have replaced the time-consuming and unreliable human analysis, increasing the efficiency of fault diagnosis. Deep learning model can improve the accuracy of intelligent fault diagnosis with the help of its multilayer nonlinear mapping ability. This paper has proposed a novel method named Deep Convolutional Neural Networks with Wide First-layer Kernels (WDCNN). The proposed method uses raw vibration signals as input (data augmentation is used to generate more inputs), and uses the wide kernels in first convolutional layer for extracting feature and suppressing high frequency noise. Small convolutional kernels in the preceding layers are used for multilayer nonlinear mapping. AdaBN is implemented to improve the domain adaptation ability of the model. The proposed model addresses the problem that currently, the accuracy of CNN applied to fault diagnosis is not very high. WDCNN can not only achieve 100% classification accuracy on normal signals, but also outperform state of the art DNN model which is based on frequency features under different working load and noisy environment.

Saikosaponin (SS) a is a compound with various pharmacological properties and easily degraded into SSb1 and SSg in acid condition. In present work another two new degradation products of SSa formed under acid hydrolytic condition were detected and isolated by analytical and semi-preparative liquid chromatography technology, furthermore their structures were characterized as hydroxyl-saikosaponin a and SSb2 by spectral analysis, which is not only essential in stability-indicating method development and validation but also could be used as a worst case to assess the analytical method performance of SSa. Moreover their structural transformation pathways were also proposed.

The aim of this work is to compare two softwares (MAUD and TOPAS) based on the Rietveld algorithm and to test the concept of tolerance factor using the dissolution at high temperature of yttrium into BaTiO₃. In general, both softwares give up different values of the crystalline parameters however the trends are similar in most cases but the analysis of the strain and crystallite size in the BaTiO₃ crystals suggests that, in this particular case, MAUD offered results more consistent with the expected behavior. Using the crystalline parameters calculated by Rietveld, the tolerance factor values were obtained and these data suggest even better stability in the crystalline structure than that expected using theoretical parameters. Tolerance factor concept also indicates that Ti⁴⁺ should be preferred.

BACKGROUND: Chronic hepatitis B infected with Hepatitis B virus remains a major health concern worldwide. Despite standard interferon-α and nucleotide analogues have been shown to reduce the deterioration of liver disease among chronic hepatitis B patients, covalently closed circular DNA was still difficult to eradicate. METHODS: A literature search of Pubmed and Web of science was performed with the following key words: ‘CRISPR’, ‘CRISPR/Cas9’, ‘hepatitis B’, ‘HBV’, ‘chronic hepatitis B’ and ‘HBV cccDNA’. The information about CRISPR/Cas9 for the treatment of HBV cccDNA or hepatitis B was reviewed. RESULTS: CRISPR/Cas9 could treat hepatitis B through suppressing or clearing HBV cccDNA with different gRNAs. CONCLUSION: With the emergence of CRISPR/Cas9 (the RNA-guided clustered regulatory interspaced short palindromic repeats, CRISPR) editing technology, clearance of hepatitis B virus and better prevention of liver carcinoma seemed to be possible.

Tea (Camellia sinenesis) is a health beneficial beverage and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of hetero-polysaccharides bounded with proteins. There were tests showing that TPS had various bioactivities, such as antioxidant, antitumors, antihyperglycemia, anti-inflammation and improving immunity. However, inconsistent results concerning chemical composition and bioactivity of TPS were published in recent years. The advances in chemical composition and bioactivities of TPS were reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS were also discussed.

1) Landsat operational land imager (OLI) data and consequent laboratory measurements were used to predict Chlorophyll-a (Chl-a) concentration and the trophic states for an inland lake within the East Kolkata Wetland, India; 2) The most suitable band ratio was identified by performing Pearson correlation analysis between Chl-a concentrations and possible OLI band and band ratios from the study points; 3) The results showed highest correlation coefficient from the band ratio OLI5/OLI4 with an R value of 0.85. The prediction model was then developed by applying regression analysis between the band ratio OLI5/OLI4 and Chl-a concentration of the study points. The reflectance ratios of the validation points were given as input on the prediction model and the model output was considered as predicted Chl-a values of the validation points to check the efficiency of the prediction model. The regression model between laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points revealed a high correlation with an R² value of 0.78. Trophic State Index (TSI) of the lake was also calculated from laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points. The study presented a high correlation of TSI determined from predicted data with TSI from laboratory reference data (R = 0.88). The TSI values of the lake ranged from 65 to 75 which indicate that the lake is appeared to be eutrophic to hypereutrophic conditions. 4) This empirical study showed that Landsat 8 OLI imagery can be effectively applied to estimate Chl-a levels and trophic states for inland lakes.

The COVID-19 pandemic affects all parameters, especially health care professionals, drugs and medical supplies. The KERRA is a mixed medicinal plant capsule that is used for the treatment of patients with high fever with food and drug administration approved by FDA Thailand. Recently, KERRA showed quicker recovery for COVID-19 patients. Therefore, it is possible that some ingredients in KERRA could inhibit SARS-CoV-2. In this study, two important replication-related enzymes in SARS-CoV-2, a main protease and an RNA-dependent RNA polymerase (RdRp), were used to study the effect of KERRA. The results showed that KERRA inhibited the SARS-CoV-2 main protease and SARS-CoV-2 RdRp with IC50 values of 49.91 ± 1.75 ng/mL and 36.23 ± 5.23 µg/mL, respectively. KERRA displayed no cytotoxic activity on macrophage cells at concentrations lower than 1 mg/mL and exhibited anti-inflammatory activity. Additionally, KERRA was against a feline coronavirus (feline infectious peritonitis [FIP]) infection with an EC50 value of 134.3 g/mL. This study supports the potential use of KERRA as a candidate drug for COVID-19.

The outbreak of the 2019 Novel Coronavirus (2019-nCoV) has rapidly spread from Wuhan, China to multiple countries, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of 2019-nCoV is lacking, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development. In this study, we predicted the potential of all the 2019-nCoV viral proteins to induce class I and II MHC presentation and form linear antibody epitopes. We showed that the enrichment for T cell and B cell epitopes is not uniform on the viral genome, with several focused regions that generate abundant epitopes and may be more targetable. We showed that genetic variations in 2019-nCoV, though fewer for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus, which should be considered in the development of therapies. We create an online database to broadly share our research outcome. Overall, we present an immunological resource for 2019-nCoV that could significantly promote both therapeutic development and mechanistic research.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

Recently, design of electric scooters (ESs) has commonly adopted brushless DC motors (BLDCMs) in place of brushed DC motors. This invention develops a new anti-lock braking system (ABS), based on a slip-ratio estimator, for ES utilizing the braking force generated by the BLDCM when electrical energy releases to the load yielding an analogous effect of ABS control in gas-engine vehicles. Comparing to mechanical ABS, the design possesses the advantages of rapid torque responses due to fast actuating response. The electrical ABS is realized by associating with kinematic and Short-circuit braking. A current controller is used to adjust the braking force, while the sliding mode control strategy is adopted to regulate the slip ratio for best road adhesion while braking. Real-world experiments have been conducted for functional and performance verification.

HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl₂, Bcl_x/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

Huperzine A is an herbal reversible inhibitor of Acetylcholinesterase (AChE). A molecular docking analysis on Huperzine A molecule has been carried out to understand its structure, conformational flexibility, intermolecular interaction and the binding affinity in the active site of AChE enzyme. Further, the charge density distribution of huperzine A molecule (lifted from the active site of AChE) was determined from the high level quantum chemical calculations coupled with charge density analysis. The binding affinity of Huperzine A towards AChE was calculated from the molecular docking; the lowest docked energy is -8.46 kcal/mol. In the active site, huperzine A molecule interacts with acyl binding pocket-Phe330 of AChE, that is, the bicyclo ring group of huperzine A forms an intermolecular interaction with the oxygen atom of main chain of the amino acid residue Phe330 at the distances 3.02 and 3.25 Å respectively. On the other hand, a gas phase study on huperzine A molecule also performed using HF and DFT (B3LYP) methods with the basis set 6-311G**. The molecular structure, conformation, and the charge density distribution of huperzine A molecule in the gas phase have determined using quantum chemical calculations and the charge density analysis. The comparative studies between the gas phase and the active site forms of huperzine A molecule, explicitly reveals the degree of conformational modification and the charge density redistribution of huperzine A when present in the active site. The dipole moment of the molecule in the active site is 6.85 D, which is slightly higher than its gas phase value (5.91 D). The electrostatic potential (ESP) surface of active site molecule clearly shows the strong electronegative and positive ESP regions of the molecule, which are the expected strong reactive locations of the molecule.

Development of the self-cleaning and anti-fogging superhydrophobic coating for aluminum surfaces which is durable in the aggressive conditions has raised tremendous interest in materials science. In this work, by employing chemical etching technique with mixture of hydrochloric and nitric acid, followed by passivation with lauric acid, superhydrophobic aluminum surface was synthesized. The surface morphology analysis reveals the presence of rough microstructures on coated aluminium surface. Superhydrophobicity with water contact angle of 170 ± 3.9° and sliding angle of 4 ± 0.5° is achieved. Surface bounces off the high speed water jet, indicating excellent water-repellent nature of coating. It is also continuously floated on water surface for several weeks, showing excellent buoyancy nature. Additionally, coating maintains its superhydrophobicity after undergoing 100 cycles of adhesive tape peeling test. Its superhydrophobic nature withstands 90° and 180° bending, and repeated folding and de-folding. Coating exhibits the excellent self-cleaning property. In low temperature condensation test, almost no accumulation of water drops on the surface, showing the excellent anti-fogging property of coating. This approach can be applied to any size and shape of aluminium surface and hence has great industrial applications.

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydoxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by significant decrease in non enzymatic antioxidants and TAS concentrations. 8-OHdG and cell proliferation level were negatively correlated with non enzymatic antioxidants viz., Vitamin A, Vitamin C, vitamin E level and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity amongst the malignant, benign and controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. Among the oxidative stress markers and cell proliferation index, decreased level of vitamin A, vitamin C, vitamin E, TAS and increased level of 8-OHdG, cell proliferation index emerged as best predicted biomarkers for subjects with malignancy and benign breast disease.

This article develops duality principles and numerical results for a large class of non-convex variational models. The main results are based on fundamental tools of convex analysis, duality theory and calculus of variations. More specifically the approach is established for a class of non-convex functionals similar as those found in some models in phase transition. Finally, in the last section we present a concerning numerical example and the respective software.

We summarize structural instabilities exhibited by the one dimensional (1D) (arene)2X family of organic conductors in relation with their electronic and magnetic properties. With a charge transfer of one electron to each anion X these salts exhibit a quarter-filled (hole) conduction band located on the donor stacks. Compounds built with donors such as fluorenthene and perylene derivatives and anions X such PF6 or AsF6 exhibit a high temperature (TP~170K) conventional Peierls transition which is announced by a sizeable regime of 1D 2kF charge density wave fluctuations (kF is the Fermi wave vector of the 1D electron gas located on Per stacks). Surprisingly, and probably because of the presence of a multi-sheet warped Fermi surface, the Peierls transition is considerably reduced in the perylene series α-(Per)2[M(mnt)2] where X is the dithiolate molecule with M=Au, Cu, Co and Fe. A special attention is devoted in this paper to physical properties of α-(Per)2[M(mnt)2] salts which with M=Pt, Pd and Ni incorporate segregated S=1/2 1D antiferromagnetic (AF) dithiolate stacks with 1D metallic Per stacks. We analyse conjointly the structural and magnetic properties of these salts in relation with the 1D spin-Peierls (SP) instability located on the dithiolate stacks. We show that the SP instability of the Pd and Ni derivatives occurs in the classical (adiabatic limit) while the SP instability of the Pt derivative occurs in the quantum (anti-adiabatic limit). Furthermore we show that in the Pd and Ni derivatives frustrated 1st neighbour direct and 2nd neighbour indirect (through a fine tuning with the mediated 2kF RKKY coupling interaction on Per stacks) AF interactions add their contribution to the SP instability to open a singlet-triplet gap. Our analysis of the data show unambiguously that magnetic α-(Per)2[M(mnt)2] salts are a typical realization of the physics predicted for two chain 1D Kondo lattices.

A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other symptoms or signs related to the male reproductive system. The analysis of 2019-nCoV RNA in semen included 17 patients with fertility needs. Among these patients, 9 (52.9%) remained positive for 2019-nCoV according to throat swab analysis, and 8 (47.1%) became negative. In the semen 2019-nCoV analysis, all 17 patients were negative for the N gene and ORF1ab gene. In view of the potential impairment, long-term follow-up for male COVID-19 patients with fertility needs is of great significance.

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.

Quantifying the landscape pattern change can effectively demonstrate the ecological progresses and the consequences of urbanization. Based on remotely sensed land cover data in 1994, 2000, 2006 and a gradient analysis with landscape metrics at landscape- and class- level, we attempted to characterize the individual and entire landscape patterns of Shanghai metropolitan during the rapid urbanization. We highlighted that a roadscape transect approach that combined the buffer zone method and the transect-based approach was introduced to describe the urban-rural patterns of agricultural, residential, green, industrial, and public facilities land along the railway route. Our results of landscape metrics showed significant spatiotemporal patterns and gradient variations along the transect. The urban growth pattern in two time spans conform to the hypothesis for diffusion–coalescence processes, implying that the railway is adaptive as a gradient element to analyze the landscape patterns with urbanization. As the natural landscape was replaced by urban landscape gradually, the urban fringe expanded radically. The results also showed that the desakota region expanded its extent widely. Satellite towns witnessed the continual transformation from the predominantly rural landscape to peri-urban landscape. Furthermore, the gap between urban and rural areas remained large especially in public service. More reasonable urban plans and land use policies should push to make more of an effort to transition from the urban-rural separation to coordinated urban-rural development. This study is a meaningful trial in demonstrating a new form of urban–rural transects to study the landscape change of large cities from a strategic viewpoint. By combining gradient analysis with landscape metrics, we addressed the process of urbanization both spatially and temporally, and provided a more quantitative approach to urban studies.

Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of HER2 amplified breast cancers has increased meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed .

Oligonol is a low-molecular-weight polyphenol derived from lychee fruit. This study was conducted to examine whether oligonol has an ameliorative effect on diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and changes in serum glucose, C-peptide, insulin, reactive oxygen species (ROS), and thiobarbituric acid-reactive substance (TBARS) levels as well as body weight and food and water consumption were assessed. Furthermore, rat pancreases were analyzed for weight, ROS generation, TBARS level, insulin content, and protein expressions of phosphor (p)-p38, p-extracellular-signal regulated kinase 1/2, p-inhibitor of nuclear factor kappa Bα, nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Markers of diabetes were shown to be decreased by oligonol administration and histological damage in the pancreas was also ameliorated. These results indicate that oligonol exerts antidiabetic activities, which may be mediated via antioxidative, stress-related, anti-inflammatory signaling.

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

A novel approach has been suggested to use isoelectric points of viral and human proteins to quickly identify proteins that are effective in not allowing virus particles to attach to human receptor cells by virtue of their electrical charge. The method has been applied to SARS CoV-2 to suggest potentially important human proteins that can be suitable for making anti-viral drugs.

The proposed research methodology aims to design a generally implementable framework for providing a house owner/member with the immediate notification of an on-going theft (unauthorized access to their premises). For this purpose, a rigorous analysis of existing systems was undertaken to identify research gaps. The problems found with existing systems were that they can only identify the intruder after the theft, or cannot distinguish between human and non-human objects. Wireless Sensors Networks (WSNs) combined with the use of Internet of Things (IoT), Cognitive Internet of Things, Internet of Medical Things, and Cloud Computing are expanding smart home concepts and solutions, and their applications. The primary objective of the present research work was to design and develop IoT and cloud computing based smart home solutions. In addition, we also propose a novel smart home anti-theft system that can detect an intruder, even if they have partially/fully hidden their face using clothing, leather, fiber, or plastic materials. The proposed system can also detect an intruder in the dark using a CCTV camera without night vision facility. The fundamental idea was to design a cost-effective and efficient system for an individual to be able to detect any kind of theft in real-time and provide instant notification of the theft to the house owner. The system also promises to implement home security with large video data handling in real-time.

A plenty of theories on the origin of genetic codes have been proposed so far, yet all ignored the energetic driving force, its relation to the biochemical system, and most importantly, the missing “matchmaker” between proteins and nucleic acids. Here, a new hypothesis is proposed, according to which ATP is at the origin of the primordial genetic code by driving the coevolution of the genetic code with the pristine biochemical system. This hypothesis aims to show how the genetic code was produced e.g. by photochemical reactions in a protocell that derived from a lipid vesicle enclosing various life’s building blocks (e.g. nucleotides and peptides). At extant cell, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the biochemical systems. ATP could energetically form and elongate chains of both polynucleotides and polypeptides, thus acting a “matchmaker” between these two bio-polymers and eventually mediating precellular biochemical innovation from energy transformation to informatization. ATP was not the only one that could drive the formation of polynucleotides and polypeptides, but favored by precellular selection. The protocell innovated a photosynthesis system to produce ATP efficiently and regularly with the aids of proteins and RNA/DNA. The completion of permanently recording the genetic information by DNA marked the dawn of cellular life operated by Darwinian evolution. The ATP hypothesis assumes or supports the photochemical origin of life, shedding light on the origins of both photosynthetic and biochemical systems, which remains largely unknown thus far. Based on ATP hypothesis, virus (like the new coronavirus) could not be the earliest life on Earth, as it has neither biochemical systems nor lipid bilayer membrane that provided relatively isolated environment for the development of protobiochemical reactions, although it owns the genetic code of a cellular life. Virus could not be a bridge between life and non-life, but is an anti-life substance, as it depletes cellular material for its own replication, and then spreads by destroying the host cells. It can be imagined that if cellular life are completely wiped out by the virus, the complete destruction of life on Earth would be inevitable.

A pump station is a very important flood control facility for mitigating inundation of urban lowland areas. It is not easy to secure a site to increase the capacity of a pump station in an urban area because of various limitations or to maximize the discharge capacity of the pump sump. Adding a facility to improve the pump capacity of a pump station may affect the flow characteristics, such as unexpected increases in the flow velocity and vorticity, and cause severe problems with operating the pump station. To solve those problems, anti-vortex devices (AVDs) have been developed and adopted for appropriate design standards. The Korean design criteria for AVDs are based on experience and foreign standards because not enough data on the AVD are available. In this study, the flow in the sump was numerically simulated at various AVD heights to collect information on improving the design and efficiency of a pump station. Consequently, an appropriate height for the AVD and changes in the flow pattern and vortex in the pump sump were determined and compared with 12 cases of inflow conditions with respect to the vertical location.

SARS-CoV2 RNA depended RNA polymerase is an essential enzyme for the survival of the virus in hosts as it helps in the replication of viral RNA. There are no human polymerases that share either sequence or structural homology with viral RNA depended RNA polymerase. These make it a good target for inhibitor discovery, as a specific inhibitor cannot cross-react with the human polymerases. We have used virtual screening, docking, binding energy calculation and simulation to show that valproic acid Co-A, a metabolite from prodrug valproic acid, forms stable interaction with nsP12 of CoV. Our results suggest valproic acid Co-A could be a potential inhibitor of nsP12 of SARS-CoV2.

In order to overcome the limitation of the traditional adaptive Unscented Kalman Filtering (UKF) algorithm in noise covariance estimation for statement and measurement, we propose a hybrid adaptive UKF algorithm based on combining Maximum a posteriori (MAP) criterion and Maximum likelihood (ML) criterion, in this paper. First, to prevent the actual noise covariance deviating from the true value which can lead to the state estimation error and arouse the filtering divergence, a real-time covariance matrices estimation algorithm based on hybrid MAP and ML is proposed for obtaining the statement and measurement noises covariance, respectively; and then, a balance equation the two kinds of covariance matrix is structured in this proposed to minimize the statement estimation error. Compared with the UFK based MAP and based ML, the proposed algorithm provides better convergence and stability.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

We propose a new theory beyond the standard model of elementary-particle physics. Employing the concept of a quantized spacetime, our theory demonstrates that the zero-point energy of the vacuum alone is sufficient to create all the fields, including gravity, the static electromagnetic field, and the weak and strong interactions. No serious undetermined parameters are assumed. Furthermore, the relations between the forces at the quantum-mechanics level is made clear. Using these relations, we quantize Einstein’s gravitational equation and explain the Dark Energy in our universe. Beginning with the zero-point energy of the vacuum, and after quantizing Newtonian gravity, we combine the energies of a static electromagnetic field and gravity in a quantum spacetime. Applying these results to the Einstein gravity equation, we substitute the energy density derived from the zero-point energy in addition to redefining differentials in a quantized spacetime. We thus derive the quantized Einstein gravitational equation without assuming the existence of macroscopic masses. This also explains the existence of the Dark Energy in the universe. For the weak interaction, by considering plane-wave electron and the zero-point energy, we obtain a wavefunction that represents a β collapse. In this process, from a different point of view than Weinberg-Salam theory, we derive the masses of the W and Z bosons and the neutrino, and we calculate the radius of the neutron. For the strong interaction, we previously reported an analytical theory for calculating the mass of a proton by considering a specific linear attractive potential obtained from the zero-point energy, which agrees well with the measurements. In the present study, we calculate the strong interaction between two nucleons, i.e., the mass of the pi-meson. The resulting calculated quantities agree with the measurements, which verifies our proposed theory.

Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. They dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.

Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, Oleanolic Acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized.A549 and SGC-7901 cells were used to screen the antitumor activity in vitro through the standard MTT method. The compounds, II₃, III₅ and Ⅳ_4, exhibited more potent cytotoxicity than positive drugs.

An ultra-low anti-reflection optical coating on both surfaces of a plastic cover slip was studied for use in confocal image measurement. The optical reflectance at a wavelength of 632.8 nm was less than 0.1% when the coated sample was placed in a liquid having a refractive index of 1.34 close to the aqueous solution of the biomaterial. The high- and low-index coating films, Substance-2 (PrTiO3) and silicon dioxide (SiO2), were measured by an ellipsometer to determine their optical refraction indices and extinction coefficients. Theoretically, when the two layer thicknesses are designed using the optical admittance diagram of the cover slip to approach the equivalent index of 1.34, a reflectance of 1.6×10-5% in the liquid could be obtained. Experimentally, the reflectance of the sample deposited on the two faces of the cover slip was 4.223±0.145% as measured in the air; and 0.050±0.002% as measured by a He-Ne laser in the liquid.

Background: Early identification and prevention of hypoxic ischemic encephalopathy (HIE) may reduce neonatal mortality and morbidity. Objective: We aimed to correlate between urinary Activin-A and MRI (conventional and Diffusion-weighted) and the severity of HIE in full-term neonates. Methods: Forty-five full-term neonates with HIE admitted to NICU and 15 normal neonates were enrolled into the study. The concentration of urinary Activin-A was determined using enzyme immunoassay kits and MRI were done. Correlations between urinary Activin-A and MRI with the degree of HIE were done. Results: Urinary Activin-A levels were significantly higher in neonates with HIE than controls (P<0.001). It was positively correlated with the clinical grading of HIE and a cutoff value of 0.08µg/l on day-1 after birth had a sensitivity of 98.6% and specificity of 97.1% for prediction of HIE. DW-MRI detected HIE with a high sensitivity (85%) compared to the low sensitivity of conventional MRI (35%). An ADC value of ≤ 0.8 was the best sensitivity-specificity cutoff point for detecting severe ischemic injury. DW-MRI imaging was positively correlated with Urinary Activin-A and both of them were positively correlated with the clinical grades of HIE (P < 0.001). Conclusions: DW-MRI imaging is correlated well with urinary Activin-A in full-term neonates with HIE and both of them are correlated with the degree of HIE. Early determination of urinary Activin-A combined with DW-MRI imaging can early detect HIE and its severity in full-term neonates with HIE.

In the present study, we derive a new B-spline technique namely trigonometric B-spline collocation algorithm to solve some initial boundary value problems for the nonlinear Klein-Gordon equation. In order to carry out the time integration with Crank-Nicolson implicit method, the order of the equation is reduced to give a coupled system of nonlinear partial differential equations. The collocation approximation based on trigonometric cubic B-splines for spatial discretization is followed by the linearization of the nonlinear term. The efficiency and accuracy of the present method are validated by measuring the error between the numerical and analytical solutions when exist. The conservation laws representing momentum and energy are also computed for all problems.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

MEMS (Micro-electromechanical Systems) becomes important increasingly due to the smarter and smaller fuze used in OICW (Objective Individual Combat Weapon). MEMS Safety and Arming (S&A) device is employed in different platforms and regions for small caliber projectile. Therefore, it is necessary to make a parametric study of the MEMS S&A device in different apply environments and explore the main sensitive factors of the MEMS S&A device to provide reference for designs. In this paper, based on the MEMS S&A device designed by our term, theory and finite element models are established, and the centrifugal insurance mechanism of the MEMS S&A device is parametric studied under the different speeds, temperature and thickness of the model by nonlinear dynamic method. By comparing the experimental and predicted results, the established FEM model is verified, and the conclusion is that the temperature and the centrifugal force are the main sensitive factors in the centrifugal insurance mechanism. In summary, we can suggest that the application environment, which the MEMS S&A device is suitable for, is the temperature equal to or slightly greater than normal temperature and the rotating speed higher than35000r/min of small caliber projectile.

The purpose of this study was to evaluate the bioactivity and cell response of a well-characterized Nurse´s A-phase (7CaO•P2O5•2SiO2) ceramic and his effect compared to a control (tissue culture polystyrene-TCPS) on the adhesion, viability, proliferation and osteogenic differentiation of ahMSCs in vitro. Cell proliferation (Alamar Blue Assay), Alizarin Red-S (AR-s) staining, alkaline phosphatase (ALP) activity, osteocalcin (OCN) and collagen I (Col I) were evaluated. Also, field emission scanning electron microscopy (FESEM) images were acquired in order to visualise the cells and the topography of the material. The proliferation of cells growing in a direct contact with the material was slower at early stages of the study because of the new environmental conditions. However, the entire surface was colonized after 28 days of culture in growth medium (GM). Osteoblastic differentiation markers were significantly enhanced in cells growing on Nurse´s A phase ceramic and cultured with osteogenic medium (OM), probably due to the role of silica to stimulate the differentiation of ahMSCs. Moreover, calcium nodules were formed under the influence of ceramic material. Therefore, it is predicted that Nurse´s A-phase ceramic would present high biocompatibility and osteoinductive properties being a good candidate to be used as a biomaterial for bone tissue engineering.

The development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For understanding the mechanism, a series of experiments had been employed based on computational methods and cell experiments. The insulin secretion significantly increased with the incubation of 0.01μM loureirin B for 4 hours. The viability of Ins-1 cells showed no significant difference with the treatment of loureirin B. Through computational methods, we hypothesized that loureirin B could interacts with K_ATP channels to promote insulin secretion. In cell experiments, it could be found that the current of K_ATP channel of Ins-1 cells was inhibited by the effect of loureirin B. After then, the voltage-dependent calcium channels were activated, the increase of Cx43 protein expression might mediate the Ca²⁺ to the intracellular. In summary, it could be concluded that loureirin B promoted insulin secretion mainly through inhibiting K_ATP current, the influx of Ca²⁺ to the Intracellular and the expression of Cx43.

In order to meet the military requirements of the fuze, such as precision strike, efficient mutilates ability and low collateral damages, the microminiaturization is an inevitable trend of secure system. Based on the silicon-based MEMS S&A device designed by our term, the design principles of each module and fabrication process are introduced. The average fracture strength and Young's modulus of the silicon are 726 MPa and 175 GPa from the tensile test, respectively. From Hopkinson impact experiment, we can get the threshold-value judging mechanism being safety under the impact overload of 20526 g, and this value is much more than the standard of the drop overload 12000g; the arming value under the centrifugal overload obtained from theory, simulation and experiment is at the range of 28200 g and 32000 g, it shows that the threshold-value judging mechanism can be arming compared with the value 35951g of design principle. Therefore, the threshold-value judging mechanism can meet the design requirements of overload. Furthermore, the relationship of fracture threshold-values obtained by different theories is found out through parametric design method, as shown in Figure 14, it provides the theory evidence to the follow parametric design.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

Enzymatic degradation of organic pollutants is a new and promising remediation approach. Peroxidases are one of the most commonly used classes of enzymes to degrade organic pollutants. However, it is generally assumed that all peroxidases behave similarly and produce similar degradation products. In this study, we conducted detailed studies of the degradation of a model aromatic pollutant, Sulforhodamine B dye (SRB dye), using two peroxidases—soybean peroxidase (SBP) and chloroperoxidase (CPO). Our results show that these two related enzymes had different optimum conditions (pH, temperature, H₂O₂ concentration...etc.) for efficiently degrading SRB dye. High-performance liquid chromatography and LC-mass spectrometry analyses confirmed that both SBP and CPO transformed the SRB dye into low molecular weight intermediates. While most of the intermediates produced by the two enzymes were the same, the CPO treatment produced at least one different intermediate. Furthermore, toxicological evaluation using lettuce (Lactuca sativa) seeds demonstrated that the SBP-based treatment was able to eliminate the phytotoxicity of SRB dye, but the CPO-based treatment did not. Our results show, for the first time, that while both of these related enzymes can be used to efficiently degrade organic pollutants, they have different optimum reaction conditions and may not be equally efficient in detoxification of organic pollutants.

In the paper, by virtue of the Fa`a di Bruno formula, some properties of the Bell polynomials of the second kind, and the inversion formulas of binomial numbers and the Stirling numbers of the first and second kinds, the authors simplify meaningfully and significantly coefficients in two families of ordinary differential equations associated with higher order Frobenius–Euler numbers.

The aim of this study was to investigate the effect of β-Hydroxy-β-methylbutyrate (HMB) supplementation on anti-inflammatory cytokines including IL-4, IL-10 and TGF-β during an acute bout of resistance exercise (RE) in young resistance trained men. Ten resistance-trained men in a randomized, double-blind, placebo-controlled and crossover study, were administered a 7-day HMB supplementation (3×1 g.d-1 of HMB) and placebo (3×1 g.d-1 of Maltodextrin) with a 7 days washout period. After supplementation periods, subjects performed three sets of bench press, lat pull down, leg extension, leg curl, biceps curl, triceps curl and shoulder press to failure with 85% of one repetition to maximum (1RM). Blood samples were obtained before- (Pre), immediately post- (IP) and 1 hour-post RE (1h P) to assess serum concentrations of IL-4, IL-10 and TGF-β1. The data were analyzed using 2 (treatment: HMB and PL) × 3 (time points: Pre, IP and 1hP) repeated measures analysis of variance (ANOVA) followed by the Bonferroni post hoc test with a significant level of p<0.05. Serum IL-4 was significantly higher at IP resistance exercise in HMB compared to placebo. Circulating IL-4 and TGF-β1 were significantly raised at IP compared to Pre in both HMB and placebo treatments. No significant differences between treatments were observed for IL-10 and TGF-β1at any time points. In conclusion, HMB supplementation increased the circulating level of IL-4 during RE in resistance-trained men, which may attenuate inflammation and facilitate adaptation to RE.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

The synthesis of metal nanoparticles using plant extracts is a very promising method in green synthesis. The medicinal value of Moringa oleifera leaves and the anti-microbial activity of metallic copper were combined in the present study to synthesize copper nanoparticles having a desirable added-value inorganic material. The use of a hydroalcoholic extract of M. oleifera leaves for the green synthesis of copper nanoparticles is an attractive method as it leads to the production of harmless chemicals and reduces waste. The total phenolic content in the M. oleifera leaves extract was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The M. oleifera leaves extract was treated with a copper sulphate solution. A color change from brown to black indicates the formation of copper nanoparticles. Characterization of the synthesized copper nanoparticles was performed using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized copper nanoparticles have an amorphous nature and particle size of 35.8-49.2 nm. We demonstrate that the M. oleifera leaves extract and the synthesized copper nanoparticles display considerable antioxidant activity. Moreover, the M. oleifera leaves extract and the synthesized copper nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 μg/mL; MIC values for the cooper nanoparticles: 500, 500, 500, and 250 μg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized copper nanoparticles exert relatively more potent anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 μg/mL; MIC values for the cooper nanoparticles: 125, 125, 62.5, and 31.2 μg/mL, respectively). Our study reveals that the green synthesis of copper nanoparticles using a hydroalcoholic extract of M. oleifera leaves was successful. In addition, the synthesized copper nanoparticles can be potentially employed in the treatment of various microbial infections due to their potent antioxidant, anti-bacterial, and anti-fungal activities.

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of broken bones. Previous studies have demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing the osteoblast differentiation. A bioactive compound, Kukoamine B (KB), was identified from a fractionation of LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. For the in vivo experiments, KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.

Many academics are critical of the current publishing system, but it is difficult to create a better alternative. This review relates to the Sciences and Social Sciences, and discusses the primary purpose of academic journals as providing a seal of approval for perceived quality, impact, significance, and importance. The key issues considered include the role of anonymous refereeing, continuous rather than discrete frequency of publications, avoidance of time wasting, and seeking adventure. Here we give recommendations about the organization of journal articles, the roles of associate editors and referees, measuring the time frame for refereeing submitted articles in days and weeks rather than months and years, encouraging open access internet publishing, emphasizing the continuity of publishing online, academic publishing as a continuous dynamic process, and how to improve research after publication. Citations and functions thereof, such as the journal impact factor and h-index, are the benchmark for evaluating the importance and impact of academic journals and published articles. Even in the very top journals, a high proportion of published articles are never cited, not even by the authors themselves. Top journal publications do not guarantee that published articles will make significant contributions, or that they will ever be highly cited. The COVID-19 world should encourage academics worldwide not only to rethink academic teaching, but also to re-evaluate key issues associated with academic journal publishing in the future.

In this study, we describe quark confinement in terms of linear interaction potentials and solve the problem of the net spin of a proton. The three quarks in a proton are assumed to revolve around a common center, and their masses are determined assuming they are Dirac particles. On the basis of these assumptions, the magnetic moment of a proton can be derived. Moreover, the rotation of the quarks is considered, in which an electrical current induces a magnetic field. Thus, the scalar product of the magnetic moment and field describes the linear interaction potential between the quarks, and the mass of the proton can be obtained. The proton mass predicted by this physical model is consistent with experimental values, and no numerical or fitting calculations are required. Furthermore, using the newly derived spins and angular momentum of the three quarks, we derived the net spin of a proton. Additionally, we predicted the mass of a pi-meson from the same model, which agrees with the experimental values.

Vitamin A and E are important during pregnancy, the neonatal period, and childhood. The objective of this study was to assess whether maternal RRR-a-tocopherol supplementation affects serum and breast milk retinol. Serum was collected at baseline and twenty days later, and breast milk, at baseline, and on days 1, 7, and 20 after delivery. After the baseline serum collection, the supplemented group (n=16) received a single 400 IU of RRR-α-tocopherol. The control group (n=18) was only performed collections. Retinol and alpha tocopherol levels were determined by liquid chromatography. Serum retinol and alpha tocopherol at baseline and 20 days after delivery indicated proper vitamin A (> 20 µg/dL) and E (> 516 μg/dL) statuses in the control and supplemented groups (p > 0.05). Colostrum retinol levels on days 1 and 7 after delivery were significantly higher in the supplemented group (p = 0.018 and p = 0.012, respectively). Maternal vitamin E supplementation increased colostrum retinol by 52.23% and 111.2%, 24 hours and 7 days, respectively. However, retinol in mature milk did not differ between the groups (p > 0.05). In conclusion, the supplementation with 400 IU of RRR-α-tocopherol improved vitamin A bioavailability in breast milk.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Due to the fact that abrasive media can deform flexibly in abrasive flow machining (AFM) making this method easily to polish the complex holes and the curved surface of the hard machining shapes. Although abrasive media dominate the polishing behavior in AFM process, the mechanism of the abrasive media are not easy to understand because of the high viscous gels, therefore, many finishing works need lots of time to design AFM process. Power laws of the abrasive gels is studied here to evaluate the non-Newtonian flow of abrasive gels in complex holes polishing firstly, at the mean time different abrasive gels are utilized to finish the complex holes to follow the results by non-Newtonian flow calculation. Moreover, traditional AFM has difficulty to achieve a uniform roughness of radial distribution in the complex holes polishing because of the non-uniform abrasive forces. So a helical passageway is proposed to create a multiple motion of abrasive medium and to obtain the even surface of the complex holes in AFM process.

This study aimed to investigate the healing effect of advanced platelet-rich fibrin (A-PRF) clot membranes in the reduction of palatal wounds resulting from free gingival graft (FGG) harvesting, in the re-epithelization rate and in the pain experience after surgery. Twenty-five patients requiring soft tissue augmentation (gingival recession coverage or keratinized gingiva augmentation) participated in this prospective randomized clinical study. After FGG harvesting, the test group (n=14) received A-PRF clot membranes at the palatal wound and the control group (n=11) a gelatin sponge. Epithelialization rate of the palatal wound, wound healing area, correspondent percentage of reduction and post-surgical pain experience were assessed. The follow-up period was 90 days. There was a significantly higher reduction of the palatal wound area in the A-PRF group vs. the control group, at 7 (p<0.001), 14 (p=0.009) and 30 days (p<0.001) follow-up. The maximum difference between groups was attained at 30 days (91.5% for A-PRF vs. 59.0% for the control group). At 14 days a significant difference in the proportion of patients showing total epithelization was found: 64.3% for A-PRF vs. 9.1% for the control group (p=0.012). At 90 days, both groups showed total recovery. Overall, the control group experienced a higher level of pain and discomfort until the 14th day, being significantly higher on the second day (p=0.013). The results suggest that A-PRF membranes haste the healing process by promoting a greater reduction along the recovery period and an apparent less painful postoperative period.

The anti-money laundering (AML) process has failed both in identifying suspicious cases in due time as in assisting the AML analysts in decision making. Starting from a new generic anti-fraud approach, this article presents the main aspects related to the development of a multi-agent system that goes beyond the capture of suspicious transactions, seeking to assist the human expert in the analysis of suspicious behaviour. First, a transactional behavioural profile of clients is obtained in a data mining process. A set of rules, obtained through data mining over a real database, in conjunction with specific rules based on legal aspects and in the expertise of the AML analysts make up the agents' knowledge base. The cases for which the system was unable to suggest a decision are flagged as requiring more detailed analysis. The system analysed 6 months of real transactions and indicated several suspicious profiles, a set of these suspects was investigated by the AML analysts who proved the suspicion of several cases, including some that had not been identified by the systems in execution.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

Total 219 countries and territories globally suffering from the recent pandemic COVID-19 is now in its second wave with more brutality, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . It has several symptoms like as persistent fever; respiratory illnesses; cough; fatigue; shortness of breath; loss of appetite; persistent pain or pressure in the chest; dysgeusia; acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19 in both peoples who had died of due to acute respiratory distress syndrome (ARDS) or those who survived. Due to COVID-19, dysregulated immune response and wound repair mainly in elderly patients causes this secondary pulmonary fibrosis. Thus using anti-fibrotic agents could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article you will get to know about the lung fibrosis generation due to COVID-19 infection, about anti-fibrotic agents and the currents challenges of this field.

More than a decade ago, a new mitochondrial Open Reading Frame (mtORF) was discovered in corals of the family Pocilloporidae, which turn out to be an effective barcode gene for these corals. However, its function remains unknown. Recently, this gene revealed the existence of a hybrid Stylophora lineage (RS_LinA) inhabiting in sympatry along the environmental gradient of the Red Sea (18.5°C to 33.9°C) with its parental species (RS_LinB). Furthermore, in RS_LinB, the mtORF uncovered phylogeographic patterns that were strongly correlated with environmental variations. This was similar to the patterns unraveled by hsp70, suggesting that mtORF too might be involved in thermal adaptation. Here we used computational approaches to characterize the mtORF and to identify its potential role. Results showed that this gene encodes a transmembrane protein (0.97<P< 1.00) involved in transport (0.80<P< 0.87), regulation of metabolic processes (0.70<P<0.85), and likely in the cell-surface receptor signaling pathway (0.56<P<0.80). Predicted protein functions differed among Stylophora lineages and interestingly, in RS_LinB only, the protein was intrinsically disordered and displayed domains involved in cellular complexes and stress response (0.0001< P <0.001). These characteristics, exclusive of an endemic lineage adapted to extreme environmental fluctuations, support a role of the mtORF in stress response, speciation and adaptation.

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.

Hydrophilic coatings have recently emerged as a new approach to avoid the adhesion of (bio)organisms on surfaces immersed in water. In these coatings the hydrophilic character is crucial for the anti-fouling (AF) performance. However, this property can be rapidly lost due to the inevitable damages which occur at the surface, reducing the long-term effectiveness of the AF functionality. We report hydrophilic polycarbonate-mPEG polyurethane coatings with tunable hydrophilic properties as well as an excellent and long-term stability in water. The coatings exhibit low protein adhesion values and are able to self-replenish their hydrophilicity after damage, due to the existence of a reservoir of hydrophilic dangling chains incorporated in the bulk. The combination of low T_g and sufficient mobility of the mPEG dangling chains (enabled by chains with higher molecular weight) proved to be crucial to ensure autonomous surface hydrophilicity recovery when the coatings were immersed in water. This coatings and design approach offer new possibilities towards high performance AF coatings with an extended service life-time which can be used in several major applications areas, such as marine and biomedical coatings, with major economic and environmental benefits.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

The alkylation of 1,1,2-trimethyl-1H-benzo[e]indole with 2-chloroacetamide, followed by work-up of the reaction mixture with a base and the subsequent treatment of a crude product with acetic acid gives 10a,11,11-trimethyl-10a,11-dihydro-8H-benzo[e]imidazo[1,2-a]indol-9(10H)-one. The structure assignments were based on data from ¹H, ¹³C and ¹⁵N NMR spectroscopy. The optical properties of the obtained compound were studied by UV-vis and fluorescence spectroscopy.

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.

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

An in vitro medium-throughput screen using M. tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. From this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than 50% at a 50 µM concentration. This prompted further exploration of all the 7-substituted coumarins in our library, nineteen in total, as potential antimycobacterial agents. Four derivatives showed promising antimycobacterial activity with MIC₉₉ values of 8.31 – 29.70 µM and 44.15 – 57.17 µM on M. tuberculosis H37Rv in independent assays using Gaste-Fe and 7H9 + OADC media, respectively. These compounds were found to bind to albumin which may explain the variations in MIC between the two assays. Preliminary antimycobacterial evaluation of moxifloxacin resistant M. tuberculosis show that these compounds are able to maintain their activity in fluoroquinolone resistant mycobacteria. Analysis of structure activity relationships for antimycobacterial versus neuronal enzyme inhibitory activity indicate that structural modification on position 4 and/or 7 of the coumarin scaffold may be utilized to improve selectivity towards either inhibition of neuronal enzymes or antimycobacterial effect. Cytotoxicity evaluations of the compounds indicate moderate cytotoxicity with slight selectivity towards mycobacteria. Further neuroprotective assays on SH-SY5Y human neuroblastoma cells indicate significant neuroprotection for selected compounds irrespective of their neuronal enzyme inhibitory properties. These coumarin molecules are thus interesting lead compounds that may provide insight into the design of new antimicrobacterial and/or neuroprotective agents.

In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: Section one addresses the relationship between the anti-inflammatory bioactivities of different phospholipids in relation to their structures and compositions. Sections two and three are dedicated to the structures, functions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option due to its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.

In this study, diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into 3 different study and control groups according to the duration of the OTA administration. Rats received 45 μg OTA daily in their feed for 6, 9 and 24 weeks study groups. Three control groups without any treatment were also used in the same periods. Blood and pancreatic tissue samples were collected during the necropsy at the end of 6, 9 and 24 weeks. Plasma values of insulin, glucagon and glucose in study and control groups were determined. Pancreatic lesions were evaluated by histopathological examination; then insulin and glucagon expression in these lesions were determined by immunohistochemical methods. Statistically significant decrease in insulin levels in contrast to increases in glucagon and glucose levels in blood were observed. Slight degeneration in Langerhans islet cells were observed at the histopathological examination in all OTA treated groups. Immunohistochemistry of pancreatic tissue revealed decreased insulin and increased glucagon expression. This study demonstrated that OTA may cause pancreatic damage in Langerhans islet and predispose rats to DM.

The rapid development of multicopters has led to many security problems. In order to prevent multicopters from invading restricted areas or famous buildings, an Anti-UAV Defense System (AUDS) has been developed and become a research topic of interest. Topics under research in relation to this include electromagnetic interference guns for unmanned aerial vehicles (UAVs), high-energy laser guns, US military net warheads, and AUDSs with net guns. However, these AUDSs use either manual aiming or expensive radar to track UAVs. This paper proposes a dual-axis rotary platform with UAV automatic tracking. The tracking platform uses visual image processing technology to track and lock the dynamic displacement of a UAV. When a target UAV is locked, the system uses a nine-axis attitude meter and laser rangefinders to measure its flight altitude and calculates its longitude and latitude coordinates through sphere coordinates to provide UAV monitoring for further defense or attack missions. Tracking tests of UAV flights in the air were carried out using a DJI MAVIC UAV at a height of 30 meters to 100 meters. It was set up for UAV image capture and visual recognition for tracking under various weather conditions by a thermal imager and a full-color camera respectively. When there was no cloud during the daytime, the images captured by the thermal imager and full-color camera provide a high-quality image recognition result. However, under dark weather, black clouds will emit radiant energy and seriously affect the capture of images by a thermal imager. When there is no cloud at night, the thermal imager performs well in UAV image capture. When the UAV is tracked and locked, the system can effectively obtain the flight altitude and longitude and latitude coordinate values.

Torenia Concolor Lindley var. formosama Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent a manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286) and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor) and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (a NOS inhibitor). Collectively, our findings suggest that TCEE confers protection from endothelial dysfunction by activating the Akt/CaMKII/AMPK/eNOS/NO signaling pathway.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

Flavonoids, compounds present in many dietary supplements, affect growth of different bacterial species when tested as purified or synthetic substances. Here, we asked if soy isoflavone extracts, commonly used in many products sold as anti-menopausal dietary supplements, influence bacterial growth similarly to synthetic isoflavone, genistein. Four commercially available products were tested in amounts corresponding to genistein concentrations causing inhibition of growth of Vibrio harveyi (a model bacterium sensitive to this isoflavone) and Escherichia coli (a model bacterium resistant to genistein). Differential effects of various extracts on V. harveyi and E. coli growth, from stimulation, through no changes, to inhibition, were observed. Moreover, contrary to genistein, tested extracts caused a decrease (to different extends) in viability of human dermal fibroblasts. These results indicate that effects of various soy isoflavone extracts on bacterial growth and viability of human cells are different, despite similar declared composition of the commercially available products.

Micronutrient deficiencies are a major public health problem. Beans are an important plant-based source of iron, zinc and copper, but their absorption is reduced in the presence of anti-nutrients such as phytates, polyphenols and tannins. Soaking and discarding the soaking water before cooking is unanimously recommended, but this can result in mineral loss. Data on the consequences for mineral bioaccessibility is still limited. This study aimed to evaluate iron, zinc and copper bioaccessibility in black beans cooked (regular pan, pressure cooker) with and without the soaking water. Minerals were quantified by ICP-MS, myo-inositol phosphates (InsP₅, InsP₆) by HPLC ion-pair chromatography, total polyphenols using Folin-Denis reagent and condensed tannins using Vanillin assay. Mineral bioaccessibility was determined by in vitro digestion and dialysis. All treatments resulted in a statistically significant reduction of total polyphenols (30%) and condensed tannins (20%). Only when discarding the soaking water a loss of iron (6%) and copper (30%) was observed, and InsP₆ was slightly decreased (7%) in one treatment. Bioaccessibility of iron and zinc were low (about 0.2% iron and 35% zinc), but copper presented high bioaccessibility (about 70%). Cooking beans under pressure without discarding the soaking water resulted in the highest bioaccessibility levels among all household procedures. Discarding the soaking water before cooking did not improve the nutritional quality of the beans.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

The new pandemic coronavirus disease 2019 (COVID-19) is a worldwide threatening health issue. Early progression of this disease starts in the lung airways with an exaggerated inflammation, triggered by the viral infection and characterized by a “cytokine storm” that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs, Thalidomide, a historically emblematic controversial molecule that harbors an FDA approval for treating Erythema Nodosum Leprosum (ENL) and multiple myeloma (MM). Based on only one-case report of positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Conversely, the absence of any substantial, promising evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases might cause a significant obstacle for carrying on clinical studies. In this review, we will discuss the theoretical effectiveness of this drug in attenuating inflammatory complications that are encountered in patients with COVID-19 while pinpointing the lack of evidence that is needed to move forward with this drug.

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

Aurora kinase A (AURKA) is a normal cell proliferation-inducing enzyme encoded by AURKA gene, with over-expression observed in different types of malignancies. Hence, the goal is to find potential inhibitors against AURKA. In this study, molecular docking, Standard Precision and Extra Precision methods were employed. After the docking study, the ligands showed an extremely low binding score which suggested very high binding affinity of the ligands. Furthermore, Quantum polarized ligand docking (QPLD) was performed to predict the binding status of the molecules. Based on the binding affinity, the top four compounds were chosen for further analysis. The docked complexes were further analyzed in explicit water conditions using 100 ns molecular dynamics simulations and binding free energy calculation. Then, density functional theory (DFT) calculation was used to calculate the molecular properties of the molecules. Finally, systems biology experiments validated the molecular docking and molecular dynamics simulation studies and indicated that quercetin, kaempferol, luteolin and rutin could inhibit the AURKA. The results show that, these four molecules have high binding affinity to the AURKA and significant interactions (LEU139, GLU211and ALA213) were also identified with the hinge region of Aurora kinase A. Thus, LEU139, GLU211, and ALA213 were identified as the crucial protein mechanisms.

Owing to fascinating applications of ZnO in modern devices, it is interesting to explore its more features for future devices. Hence, herein, we have synthesized the high quality ZnO spherical nanoparticles (SNPs) through a facile green synthesis route and robust structural and biomedical studies are carried out. Hexagonal phase with 93.2% crystallinity was confirmed through XRD analysis. ZnO nanoparticles were tested for their bioactivities both in vivo (acute cytotoxicity test) and in vitro (Anti-cancer activities on liver (HepG2) and cervical (Hela) cancer cell lines, stimulatory/inhibitory effects on normal rat splenic cells and hemolytic effects on red blood cells). Results showed that ZnO SNPs has no cytotoxic effects on vital organ like liver and has no hemolytic action on red blood cells. ZnO SNPs showed inhibitory consequence on normal rat splenic cells growth at all tested concentrations. ZnO nanoparticles showed an inhibitory effect on HepG2 cell line. While showed stimulatory effect on Hela cell line. Current study presents the synthesized ZnO SNPs as highly applicable in bio-optoelectronics.

After proving, in a purely categorial way, that the inclusion functor InAlg(Σ) from Alg(Σ), the category of many-sorted Σ-algebras, to PAlg(Σ), the category of many-sorted partial Σ-algebras, has a left adjoint FΣ, the (absolutely) free completion functor, we recall, in connection with the functor FΣ, the generalized recursion theorem of Schmidt, which we will also call the Schmidt construction. Next we define a category Cmpl(Σ), of Σ-completions, and prove that FΣ, labeled with its domain category and the unit of the adjunction of which it is a part, is a weakly initial object in it. Following this we associate to an ordered pair (α,f), where α=(K,γ,α) is a morphism of Σ-completions from F=(C,F,η) to G=(D,G,ρ) and f a homomorphism in D from the partial Σ-algebra A to the partial Σ-algebra B, a homomorphism ΥαG,0(f):Schα(f)B. We then prove that there exists an endofunctor, ΥαG,0, of Mortw(D), the twisted morphism category of D, thus showing the naturalness of the previous construction. Afterwards we prove that, for every Σ-completion G=(D,G,ρ), there exists a functor ΥG from the comma category (Cmpl(Σ)↓G) to End(Mortw(D)), the category of endofunctors of Mortw(D), such that ΥG,0, the object mapping of ΥG, sends a morphism of Σ-completion in Cmpl(Σ) with codomain G, to the endofunctor ΥαG,0.