Although the phenomenon of serial killers has received great attention from media, governments, and public, very little information is known about them and very few theories are presented by researchers specifically their definition and motives for killing. Through cross tabulation analysis of top ninety-eight serial killers, this present study poses six questions that investigate the correlations between, offender's gender, offender's level of education, time span of killing, killing severity, number of victims, killer's type of abuse, motives for killing, and victim's profile. Findings show that males kill more than females and for longer time, less educated serial killers kill more horribly, female serial killers consider their family members easy target, and finally males kill most for enjoyment and sex and females kill for financial gains.

A review of the concept of "fitness" as it is used in evolutionary theory.

New class of biologically active and non-active compounds can be synthesized via transition metal mediated Suzuki cross coupling reaction that has a great impact on the advancement of organic chemistry. These resulted products can lend a helping hand in pharmaceutical and polymer chemistry for the betterment of mankind. Suzuki-Miyaura cross coupling reaction is one of the best tools through which many natural and non-natural compounds can be synthesized.

The market of natural and organic cosmetics has been growing in last decades. The increase in interest in this type of product is a consequence of the concern that consumers have been presenting in relation to the environment and health. In addition to the appreciation the use of sustainable ingredients in cosmetic formulations, the consumers are also concerned about pollution caused by the use of plastics, which leads industries to reinvent themselves and rethink about the composition of packaging. The factor that most drives the purchase of natural and organic cosmetics is the fact that the consumer, in addition to contributing to the preservation of the environment, is also using a sustainable product. The growing demand for natural and organic cosmetics results in a concern of the brands with the organic issue, with the decreased use of animal derived ingredients and with the updating the parameters required for certification of a cosmetic as natural or organic. Due to the few studies available in this area, the importance of clarifying the definitions and concepts of natural and organic cosmetics is evident, in order to contribute with accurate information for the cosmetic sector.

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) pioneered by Katalin Karikó and Drew Weissman at the University of Pennsylvania are a promising new vaccine platform used by two of the leading vaccine candidates against coronavirus disease in 2019 (COVID-19). However, there are many questions regarding their mechanism of action in humans that remain unanswered. Here we consider the immunological features of LNP components and off-target effects of the mRNA, both of which could increase the risk of side effects. We suggest ways to mitigate these potential risks by harnessing dendritic cell (DC) biology.

A multi-tool analytical practice was used for characterization of 16^th century carpet manufactured in Cairo. Mild extraction method with hydrofluoric acid enabled isolation of intact flavonoids and their glycosides, anthraquinones, tannins and indigoids from fibre samples. High-performance liquid chromatography coupled to spectroscopic and mass spectrometric detectors was used for identification of natural dyes present in the historical samples. Weld, young fustic and brazilwood were identified as the dye sources in yellow thread samples. Red fibres have been colored with lac dye, whereas green fibre shades were obtained with indigo and weld. Tannin-containing plant material in combination with indigo and weld were used to obtain brown hue of thread. Four uncommon and thus-far unknown dye components were also found in the historical samples. These compounds probably represent unique fingerprint of dyed threads from this region. Scanning electron microscopy with energy-dispersive X-ray detector (SEM-EDS) and Fourier transformation infrared spectroscopy (FT-IR) were used for identification and characterization of substrates and mordants present in the historical carpet. Carbon and oxygen were detected in large quantities as a part of the wool protein. The presence of aluminum, iron and calcium indicated their usage as mordants. FT-IR analysis showed bands characteristic to woolen fibres and SEM micrographs definite structure of wool.

Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.

The paper examines design and operating data of current concentrated solar power (CSP) solar tower (ST) plants. The study includes CSP with or without boost by combustion of natural gas (NG), and with or without thermal energy storage (TES). The latest, actual specific costs per installed capacity are very high, 6085 $/kW for Ivanpah Solar Electric Generating System (ISEGS) with no TES, and 9227 $/kW for Crescent Dunes with TES. The actual production of electricity is very low and much less than the expected. The actual capacity factors are 22% for ISEGS, despite combustion of a significant amount of NG largely exceeding the planned values, and 13% for Crescent Dunes. The design values were 33% and 52%. The study then reviews the proposed technology updates to produce better ratio of solar field power to electric power, better capacity factor, better matching of production and demand, lower plant’s cost, improved reliability and increased life span of plant’s components. The key areas of progress are found in materials and manufacturing processes, design of solar field and receiver, receiver and power block fluids, power cycle parameters, optimal management of daily and seasonal operation of the plant, new TES concepts, integration of solar plant with thermal desalination, integration of solar plant with combined cycle gas turbine (CCGT) installations and finally, specialization and regionalization of the project specification.

LC–NMR combines the advantage of the outstanding separation power of liquid chromatography (LC) and the superior structural elucidating capability of nuclear magnetic resonance (NMR). NMR has proved that it is a standout detector for LC by providing maximum structural information about plant originated extracts particularly in its isolating ability of isomeric (same molecular formula) and/or isobaric (same molecular weight) compounds as compared to other detectors. The present review provides an overview of the LC–NMR developmental trends and its application in natural products analysis. The different LC–NMR operational modes are described, as well as how technical improvements assist in establishing this powerful technique as an important analytical tool in the analysis of complex plant-derived compounds. On-flow, stop-flow and loop-storage modes, as well as the new offline mode LC–SPE–NMR and capLC-NMR configurations that avoid the ingestion of expensive deuterated solvents throughout the experiment are mentioned. Utilization of cryogenic probe and microprobe technologies which are the other important promising approaches for guaranteeing the sensitivity issues are also described. Concluding remarks and future outlooks are also discussed.

The aim of this study was to determine the effect of Pandanus (Pandanus amaryllifolius 20 Roxb.) and Neem (Azadirachta indica) leaves powder on the repellency, mortality, and weight loss 21 of grains due to Sitophilus oryzae. The methodes of this study used a completely randomized design 22 (CRD) with 7 treatments and 4 replications. The results of this study indicate that the best treat- 23 ment in terms of causing repellency was the treatment of 10 grams of pandanus with a percentage 24 of 87.5%, while the best treatment in terms of causing pest mortality and was also able to reduce 25 the risk of rice weight loss due to Sitophilus oryzae was treatment 10 gram of neem with a mortality 26 percentage of 76.25% and weight loss of rice 3.14%. This research showed that neem leaf com- 27 pounds are better in terms of causing mortality, while Pandanus compounds are better in terms of 28 causing mortality of Sitophilus oryzae.

Sourced so far mostly from beet root juice, betanin is a red-violet natural colorant increasingly used by the food, beverage and nutraceutical industries. We provide an updated bioeconomy perspective into a valued betacyanin whose supply and applications, we argue in this study, will rapidly expand.

CONTEXT– Energy is widely involved in human activity and corresponding emissions of SOX, NOX and CO2 from energy generation processes affect global climate change. Clean fuels are desired by society because of their reduced greenhouse gas emissions. Hydrogen is once such candidate fuel. Much hydrogen is produced from fossil fuel, with biomass being an alternative process. OBJECTIVE– The project compared the environmental impact of hydrogen production by natural gas steam reforming vs. biomass gasification. METHOD–Environmental impact was calculated from the input and output data from life cycle inventory analysis. The impact assessment was focused on greenhouse gas emission, acidification, and eutrophication. Models of the two processes were developed and analysed in OpenLCA. The agribalyse database was used to connect inventory flow data to environmental impacts. FINDINGS– For all three metrics, biomass gasification had lower impacts than natural gas steam reforming, sometimes by large margins. For biomass gasification the silica sand production contributes most to all three impact categories, whereas for natural gas steam reforming it is the LPG extraction.

The development and optimization of an effective non-viral gene delivery method for genetic manipulation of primary human T cells is a major challenge in clinical immunotherapy researches. According to the low transfection efficiency of conventional methods in human primary T cells, there is an effort in order to increase the transfection rate in these cells. Protamine is an FDA-approved compound with a documented safety profile that enhances DNA condensation for gene delivery. In this study, the effect of protamine on the transfection efficiency of standard transfection reagents, TurboFect, and Lipofectamine 2000 was evaluated in order to transfect primary human T cells. Results demonstrated that protamine condenses DNA and increases the positive charge of DNA/Cargo complex efficiently without any cytotoxic effect on the primary human T cells. The results also revealed that the DNA/Protamine/Cargo complexes effectively transfect human primary T cells.

Increasing environmental concern and consumer demand for natural, sustainable and eco-friendly products have prompted the replacement of synthetic surfactants with their natural plant-based alternatives. Saponins are the plant based natural surfactants characterized by their foam forming properties in aqueous solution. Their natural origin makes them eco-friendly, bio-degradable and non-toxic. Further, they possess better physicochemical properties than the syn-thetic ones. They are also reported to exhibit a lot of useful biological activities such as anti-cancer, antifungal, anti-inflammatory, antimicrobial, antioxidant and cholesterol-lowering properties. Because of their excellent surface activity, biological activities and wide distribution in nature, saponin rich plants deserve deeper insight as a sustainable source of natural surfactants as they possess the potential to replace toxic synthetic surfactants abundant today. This review article is intended to provide a brief overview on the saponins with a special notion on their surface-active properties. It encourages further studies on development of commercial formulations based on saponins for the complete replacement of the synthetic counter parts, making better use of plants sources thereby contributing to global agenda of green environment.

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

The transition from the Peptide/RNA world to the Protein/RNA world in the hydrothermal vent environment was a major event in the history of life. The advent of proteins utterly changed the conditions of emerging life, representing a watershed in its development. During subsequent translation various protein enzymes emerged driving protocells into a more complex and interconnected system. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Four major events followed after availability of various kinds of protein molecules during prebiotic synthesis. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) the beginnings of the virus world; and (4) the advent of DNA. The first innovation mediated by proteins was the improvement of the cell membrane. The phospholipid membrane was initially evolved in a vent environment from the gradual modification of a fatty acid membrane via an intermediate phosphatidate acid by non-enzymatic reactions. The phospholipid is then synthesized from phosphatidate acid by a series of enzymes. To make the phospholipid membrane more permeable, various protein molecules interacted with the cell membrane. Proteins not only stabilized the wall membrane, but also acted as pumps, preventing some molecules from the protocells from crossing the membrane barriers, while permitting other selected molecules and ions to enter and leave the protocell. The second modification led by proteins is the gradual conversion of the interior of the protocell from a water-like medium into a gel-like cytoplasm, which became the storehouse of a wide range of biomolecules including amino acids, proteins, nucleic acids, ribosomes, as well as salt and water. The third innovation utilizing the newly synthesized proteins was the emergence of the ancient virus world. In the milieu of different kinds of mRNAs in the prebiotic soup, jelly-roll capsid genes originated de novo within genomes of nonviral mRNAs by overprinting. These fragile capsid genes were possibly coated by proteins on the mineral substrate for stability and durability, transforming them into ancient viral particles. These protein coats were random and were not encoded by encased genes. Some protocells might have engulfed these viral particles, when the capsid genes utilized the ribosomes of the host to translate into the appropriate capsid proteins. These capsid proteins then coated the viral genes to make new copies of primordial viruses inside the protocell. Since then, viruses became capsid-encoding organisms. These primordial mRNA viruses parasitized RNA-based protocells, manipulating them to make new copies of themselves. This was the beginning of a relentless war between viruses and their protocellular hosts. The next stage in viral evolution was the emergence of a primitive retrovirus (pre-retrovirus) with a new kind of replicative strategy in a sense that it could turn its RNA into DNA using its own reverse transcriptase enzyme. This is the beginning of the Retro world that facilitated the transition from RNA to DNA genomes. The infection of RNA protocells with pre-retroviruses progressively transferred the RNA genome to a viral DNA genome by retro-transcription. The advent of DNA by the pre-retrovirus marks the fourth innovation, when a number of enzymes had already developed and were utilized by pre-retroviruses. With continued infection, DNA viruses slowly transferred not only their core replication enzymes, such as helicase, primase, and DNA polymerase, to RNA protocells, but also to their DNAs as well. Thus, began the DNA world, when DNA replaced RNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. The new protocell with the DNA genome will diversify into large populations of DNA protocells that will outcompete populations of RNA protocells. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. It was carried out by a set of enzymes that formed a Z-ring at the site of replication. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification. These primordial hyperthermophiles, presumably the first life, obtained food and energy directly from the vent environment. However, such a situation was self-limiting, so the early cells evolved their own mechanisms for generating metabolic energy and synthesizing the molecules necessary for their reproduction. The earliest fossil record (≥ 3.5 Ga) of biotic activity is preserved in the Archean hydrothermal and sedimentary rocks of the Nuvvuagittuq Craton of Canada, the Isua Craton of Greenland, the Pilbara Craton of Australia, the Kaapvaal Craton of South Africa, and the Singhbhum Craton of India in the form of the carbonaceous remains of microbial cells, cellular microfossils, and stromatolites. These microscopic fossils provide crucial evidence of the origin and early evolution of prokaryotic cells, beginning with hyperthermophiles. Molecular phylogenetic analysis suggests that both domains of life ¬– Bacteria and Archaea probably split from the last universal common ancestor (LUCA), a hyperthermophilic organism. In the younger sequences of these Archean cratons, two kinds of photosynthetic bacteria, anoxygenic green sulfur bacteria, and oxygenic cyanobacteria, appeared in quick succession from the thermophilic ancestor, indicating a shift of niche from a benthic to a planktonic, with reduced thermotolerance. The development of anoxygenic and oxygenic photosynthesis would have allowed life to escape the hydrothermal setting and invade a newly evolved habitat—broad continental shelves to tap solar energy. Cyanobacteria invaded the global ocean, turned it into blue and green, produced oxygen for the first time, and left their signatures in the carbonates and stromatolites.

“You should know the words by the company they keep!” has been one of the most famous slogans attributed to John Rubert Firth, 1957. This has ignited a whole school in linguistic research known as the British empiricist contextualism. Sixty years later, many un- or semi-supervised machine learning algorithms have been successfully designed and implemented aiming at extracting word meaning from within the context of a text corpus. These algorithms treat words, more or less, as vectors of real numbers representing frequencies of word occurrences within context and word meaning as positions of words in a high-dimensional vector space model. Word associations, in turn, are treated as calculated distances among them. With the rise of Deep Learning (DL) and other artificial neural networks based architectures, learning the positioning of words and extracting word associations as measured by their distances has further improved. In this paper, however, we revisited the main stream of algorithmic approaches and set the stage for a partly cross-disciplinary evaluation framework to judge about the nature of the extracted word associations by state-of-the-art machine learning algorithms. Our preliminary results are based on word associations extracted from the application of DL framework on a Google News text corpus, as well as on comparisons with human created word association lists such as word collocation dictionaries and psycholinguistic experiments. The results and conclusions provide some insights into the inherited limitations in interpreting the type of word associations and underpinning relations between words with inevitable consequences in other areas, such as extraction of knowledge graphs or image understanding.

Google play store allow the user to download a mobile application (app) and user get inspired by the rating and reviews of the mobile app. A recent study analyzes that user preferences, user opinion for improvement, user sentiment about particular feature and detail with descriptions of experiences are very useful for an application developer. However, many application reviews are very large and difficult to process manually. Star rating is given of the whole application and the developer cannot analyze the single feature. In this research, we have scrapped 282,231 user reviews through different data scraping techniques. We have applied the text classification on these user reviews. We have applied different algorithms and find the precision, accuracy, F1 score and recall. In evaluated results, we have to also find the best algorithm.

The interaction between spinors and gravity is the most complicated and subtle interaction in the universe, which involves the basic problem to unified quantum theory and general relativity. By means of Clifford Algebra, a unified language and tool to describe the rules of nature, this paper systematically discusses the dynamics and properties of spinor fields in curved space-time, such as the decomposition of the spinor connection, the classical approximation of Dirac equation, the energy momentum tensor of spinors and so on. To split spinor connection into Keller connection $\Upsilon_\mu\in\Lambda^1$ and pseudo-vector potential $\Omega_\mu\in\Lambda^3$ by Clifford algebra not only makes the calculation simpler, but also highlights their different physical meanings. The representation of the new spinor connection is dependent only on the metric, but not on the Dirac matrix. Keller connection only corresponds to geometric calculations, but the potential $\Omega_\mu$ has dynamical effects, which couples with the spin of a spinor and may be the origin of the celestial magnetic field. Only in the new form of connection can we clearly define the classical concepts for the spinor field and then derive its complete classical dynamics, that is, Newton's second law of particles. To study the interaction between space-time and fermion, we need an explicit form of the energy-momentum tensor of spinor fields. However, the energy-momentum tensor is closely related to the tetrad, and the tetrad cannot be uniquely determined by the metric. This uncertainty increases the difficulty of deriving rigorous expression. In this paper, through a specific representation of tetrad, we derive the concrete energy-momentum tensor and its classical approximation. In the derivation of energy-momentum tensor, we obtain a spinor coefficient table $S^{\mu\nu}_{ab}$, which plays an important role in the interaction between spinor and gravity. From this paper we find that, Clifford algebra has irreplaceable advantages in the study of geometry and physics.

Electronic health records (EHRs) are becoming a vital source of data for healthcare quality improvement, research, and operations. However, much of the most valuable information contained in EHRs remains buried in unstructured text. The field of clinical text mining has advanced rapidly in recent years, transitioning from rule-based approaches to machine learning and, more recently, deep learning. With new methods come new challenges, however, especially for those new to the field. This review provides an overview of clinical text mining for those who are encountering it for the first time (e.g. physician researchers, operational analytics teams, machine learning scientists from other domains). While not a comprehensive survey, it describes the state of the art, with a particular focus on new tasks and methods developed over the past few years. It also identifies key barriers between these remarkable technical advances and the practical realities of implementation at health systems and in industry.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

Parasitic diseases continue represent a threat on a global scale, particularly among the poorest countries in the world. This is particularly because of the absence of vaccines, and in some cases, resistance against available drugs, currently being used for their treatment. In this review emphasis is laid on natural products and scaffolds from African medicinal plants (AMPs) for lead drug discovery and possible further development of drugs for the treatment of parasitic diseases. In the discussion, emphasis has been laid on alkaloids, terpenoids, quinones, flavonoids and narrower compound classes of compounds with micromolar range activities against Schistosoma, Trypanosoma and Leishmania species. Suggestions for future drug development from African medicinal plants have also been provided.

There is a marked momentum towards the use of clean hydrogen energy as an alternative for fossil fuels. Renewable energies such as solar and wind are being used to generate hydrogen from the water hydrolysis process. Indeed, this approach stores renewable energies in the form of combustible hydrogen for other energy uses. The other alternative that could be economically more cost-effective at the current technology stage is to explore the natural “Hydrogen System” where the natural hydrogen is generated and accumulated within the earth system, the same that stands for a “Petroleum System”. The Discovery of a large accumulation of relatively pure natural hydrogen (H2) in Mali has triggered the opportunity of searching for natural hydrogen accumulations in other countries. The generation of hydrogen from a circular depression in Mali and some other countries is linked to the presence of geologically very old iron-rich basement rocks. Solid-liquid redox reactions between iron-rich minerals and groundwater that split water are a possible source of H2 in deep basement rocks. It is believed that the hydrogen degassing may be detected by surface topographic circular to sub-circular shallow depressions. Chemical processes such as dissolution by hydrogen are considered to play the main role in the formation of the circular depressions through preferential vertical hydrogen migration channel. Archean iron-rich Yilgarn Craton that covers a vast area of Western Australia (WA) contains abundant iron-rich mafic-ultramafic rocks. The craton reveals many surficial circular depressions visible through satellite images. The area has abundant fault systems and is blanketed with Eocene sedimentary rocks containing high-quality reservoir rocks. All these characteristics seem to provide most of the required elements, such as hydrogen source, migration pathway, and reservoir rock for a “Hydrogen System” in this area.

This article presents a dataset of tweets in the Urdu language. There are 1,140,824 tweets in the dataset, collected from Twitter for September and October 2020. This large-scale corpus of tweets is generated by performing pre-processing which includes removing columns containing user information, retweet’s count, followers information, duplicate tweets, removing unnecessary punctuation, links, symbols, and spaces, and finally extracting emojis if present in the tweet text. In the final dataset each tweet record contains columns for tweet id, text, and emoji extracted from the text with a sentiment score. Emojis are extracted to validate Machine Learning models used for the multilingual sentiment and behavior analysis. These are extracted using a Python script that searches for an emoji from the list of 751 most frequently used emojis. If an emoji is present in the text, a column with the emoji description and sentiment score is added.

The current emergency due to the worldwide spread of the COVID-19 caused by the new SARS-CoV-2 is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness was not yet assessed. The main protease (Mpro) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent Mpro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed to highlight some crucial aspects. Seventeen potential SARS-CoV-2 Mpro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

The synthesis of four samples of new polyurethanes was evaluated by changing the ratio of the diol monomers used, poly(propylene glycol) (PPG) and D-isosorbide, in the presence of aliphatic isocyanates such as the isophorone diisocyanate (IPDI) and 4,4′-methylenebis(cyclohexyl isocyanate) (HMDI). The thermal properties of the four polymers obtained were determined by DSC, exhibiting Tg values in the range 55-70 ºC, and their molecular structure characterized by FTIR, 1H and 13C NMR spectroscopies. The diffusion coefficients of these polymers in solution were measured by the Pulse Gradient Spin Echo (PGSE) NMR method, enabling the calculation of the corresponding hydrodynamic radii in diluted solution (1.62–2.65 nm). The molecular weights were determined by GPC/SEC and compared with the values determined by quantitative 13C NMR analysis. Finally, the biocompatibility of the polyurethanes was assessed using the HaCaT keratinocyte cell line by the MTT reduction assay method showing values superior to 70% cell viability.

Artificial intelligence (AI) tools, such as OpenAI's Chat Generative Pre-trained Transformer (ChatGPT), have great potential in various fields, such as healthcare, education, and industry. This review highlights the applications and challenges of the ChatGPT versions 3.5 and 4.0 in radiology. ChatGPT can process medical texts, analyze medical images, and generate reports and summaries for different audiences. ChatGPT can also answer patients' questions and translate complex medical information into a plain language. ChatGPT has shown impressive results in medical tests and quizzes, indicating its potential to enhance diagnostic accuracy and medical education. These models show promise for reducing diagnosis times and healthcare costs. However, ChatGPT also faces challenges and limitations, such as a lack of visual content, ethical and legal issues, data quality, and error detection. This review highlights the benefits and future directions of ChatGPT and artificial intelligence (AI) in radiology.

Natural gas hydrate, also known as combustible ice and mainly composed of methane, it is identified as the potential clean energy in the 21th century. Due to its large reserves, gas hydrate can ease problems caused by energy resource shortage and has gained attention around the world. In this paper, we focus on the exploration and development of gas hydrate as well as discussing its status and future development trend in China and abroad, then we analyze its opportunities and challenges in China from four aspects: resource, technology, economy and police with five forces model and PEST method. The results show, China has abundance gas hydrate resource; however the backward technologies and inadequate investment has seriously hindered the future development of gas hydrate, so China should establish relevant cooperation framework and intuitional arrangement to attract more investment as well as breaking through technical difficulties to make gas hydrate commercialization as soon as possible.

Cervical cancer screening systems aim to detect established HPV infections early. However, if there are no high-grade lesions, the intervention choice is basically limited to observational follow-up with recommendations on life habits like diet, to favor infection control. Therefore, it is important to establish specific feeding guidelines that provide clear evidence about the benefit they may bring against HPV infections. The present study evaluates the benefits of nutritional supplementation with a casein hydrolysate-based formula in patients with HR-HPV infection, compared with a non-supplemented control group. A total of 118 patients completed 6 months of follow-up. Significant differences between supplemented and control groups were observed for total or partial HR-HPV clearance at 6 months (74.6% vs 35.6%). Supplemented patients also suffered a lower occurrence of new intracervical lesions (0% vs 28.6%), a significantly greater resolution (67.4% vs 41.9%) and less progression of pre-existing lesions (4.7% vs 9.7%) at 6 months. An increase in the effectors of cellular immunity that could be responsible for their effect was also observed in supplemented patients. We conclude that nutritional supplementation with this casein hydrolysate-based formula could improve the outcomes of observational management of HPV infection.

Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. The risk of these cancers is increased even in people who have only one alcoholic drink per day. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect has been overlooked probably because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of endogenous and exogenous DNA-damaging agents (e.g., reactive oxygen species, acetaldehyde and tobacco carcinogens). Alcohol consumption probably increases the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Because the cytotoxic activity of ethanol is concentration-dependent, the risk of these cancers will not only increase with increasing amounts of ethanol, but also with increasing concentrations; an ounce of whisky is probably more carcinogenic when taken undiluted than when taken mixed with non-alcoholic beverages. The local cytotoxic effect of ethanol can also explain the known synergistic effect of alcohol and tobacco use on the risk of these cancers. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.

The emergence of proteins in the prebiotic world was a watershed event at the origin of life. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Five major biochemical innovations followed in succession after availability of various kinds of protein molecules during decoding and translation of mRNAs. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) primitive gene regulation; (4) the beginnings of the virus world; and (5) the advent of DNA. The creative role of viruses during prebiotic synthesis led to the origin of the DNA world, when DNA replaced mRNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification by mutation. The habitat of the earliest fossil record (≥ 3.5 Ga) from the Archean sedimentary rocks of Canada, Greenland, Australia, South Africa, and India offers a new window on the early radiation of microbial life. The development of anoxygenic and then oxygenic photosynthesis from early hyperthermophiles would have allowed life to escape the hydrothermal setting to the mesophilic global ocean.

Transient analysis of gas flow in pipeline was studied. Finite Element Method based on ANSYS FLOTRAN was used to account for changes in pressure, temperature and flow rate. Compressibility factor function of temperature and pressure was considered. For non-isothermal transient results, the pressure and the flowrate gave wave propagation as a result of slow transients created by demand condition at the outlet end of custody transfer. Results obtained were in agreement with the demand restrictions at the outlet end of custody transfer indicating that the predictions are accurate and reliable. The results demonstrated that the Finite Element Method gave accurate prediction of pressure, temperature and flowrate in transient gas studies. For steady state non-isothermal model, results showed that the magnitude of the average pressure drop was higher when pressure was predicted with constant compressibility factor, but the same average pressure drop was reduced when the pressure was predicted with variable compressibility factor, z. Since compressibility factor is a function of temperature and pressure, the above findings signifies that in the case when gas temperature does not stabilize, the prediction of pressure with isothermal model and constant compressibility factor will lead to significant errors.

Coronavirus, also known as COVID-19, has been declared a pandemic by the World Health Organization (WHO). At the time of conducting this study, it had recorded over 1.6 million cases while more than 105,000 have died due to it, with these figures rising on a daily basis across the globe. The burden of this highly contagious respiratory disease is that it presents itself in both symptomatic and asymptomatic patterns in those already infected, thereby leading to an exponential rise in the number of contractions of the disease and fatalities. It is therefore crucial to expedite the process of early detection and diagnosis of the disease across the world. The case-based reasoning (CBR) model is an effective paradigm that allows for the utilization of cases’ specific knowledge previously experienced, concrete problem situations or specific patient cases for solving new cases. This study therefore aims to leverage the very rich database of cases of COVID-19 to solve new cases. The approach adopted in this study employs the use of an improved CBR model for state-of-the-art reasoning task in classification of suspected cases of Covid19. The CBR model leverages on a novel feature selection and semantic-based mathematical model proposed in this study for case similarity computation. An initial population of the archive was achieved with 68 cases obtained from the Italian Society of Medical and Interventional Radiology (SIRM) repository. Results obtained revealed that the proposed approach in this study successfully classified suspected cases into their categories at an accuracy of 97.10%. The study found that the proposed model can support physicians to easily diagnose suspected cases of Covid19 base on their medical records without subjecting the specimen to laboratory test. As a result, there will be a global minimization of contagion rate occasioned by slow testing and as well reduce false positive rates of diagnosed cases as observed in some parts of the globe.

Despite the implementation of control strategies, the invasive parasitic mite Varroa destructor remains one of the principal causes of honey bee (Apis mellifera) colony losses in numerous countries. For this reason, the parasite represents a serious threat to beekeeping and to agro-ecosystems that benefit from the pollination services provided by honey bees. Numerous selection programmes have been initiated over the last three decades with the aim of promoting the establishment of balance in the host–parasite relationship and, thus, helping European honey bees to survive in the presence of the parasite without the need for acaricide treatments. Such programmes have focused on either selective breeding for putative resistance traits or natural selection. To date, no clear overview of these attempts has been available, which has prevented building on past successes or failures and, therefore, hindered the development of a sustainable strategy for solving the V. destructor problem. In the present study, we review past and current selection strategies, report on their outcomes and discuss their limitations. Based on this state-of-the-art knowledge, we propose a strategy for increasing response to selection and colony survival against V. destructor infestations. Developing in-depth knowledge regarding the selected traits, optimising selection programmes and communicating their outcomes are all crucial to our efforts to establish a balanced relationship between the invasive parasite and its new host.

Personality is the most critical feature that tells us about an individual. It is the collection of the individual’s thoughts, opinions, emotions and more. Personality detection is an emerging field in research and Deep Learning models have only recently started being developed. There is a need for a larger dataset that is unbiased as the current dataset that is used is in the form of questionnaires that the individuals themselves answer, hence increasing the chance of unconscious bias. We have used the famous stream-of-consciousness essays collated by James Pennbaker and Laura King. We have used the Big Five Model often known as the five-factor model or OCEAN model. Document-level feature extraction has been performed using Google’s word2vec embeddings and Mairesse features. The processed data has been fed into a deep convolutional network and a binary classifier has been used to classify the presence or absence of the personality trait. Hold- out method has been used to evaluate the model, and the F1 score has been used as the performance metric.

Background: SARS-CoV-2 that are the causal agent of a current pandemic are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly and pathogenicity. The ~33.8KDa M^pro protease of SARS-CoV-2 is a non-human homologue and highly conserved among several coronaviruses indicating M^pro could be a potential drug target for Coronaviruses.Methods: Here we performed computational ligand screening of four pharmacophores (OEW, Remdesivir, Hydroxycholoquine and N3) that are presumed to have positive effects against SARS-CoV-2 M^pro protease (6LU7) and also screened 50,000 molecules from the ZINC Database dataset against this protease target.Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 10 best selected ligands namely, ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as β-carboline, Alkaloids and Polyflavonoids, and all of them displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as with other known ligands.Conclusion: Our results suggest that these 10 molecules could be effective against SARS-CoV-2 protease and may be tested in vitro and in vivo to develop novel drugs against this virus.

The choice associated with words is a fundamental property of natural languages. It lies at the heart of quantitative linguistics, computational linguistics, and language sciences more generally. Information-theory gives us tools at hand to measure precisely the average amount of choice associated with words—the word entropy. Here we use three parallel corpora—encompassing ca. 450 million words in 1916 texts and 1259 languages—to tackle some of the major conceptual and practical problems of word entropy estimation: dependence on text size, register, style and estimation method, as well as non-independence of words in co-text. We present three main results: 1) a text size of 50K tokens is sufficient for word entropies to stabilize throughout the text, 2) across languages of the world, word entropies display a unimodal distribution that is skewed to the right. This suggests that there is a trade-off between the learnability and expressivity of words across languages of the world. 3) There is a strong linear relationship between unigram entropies and entropy rates, suggesting that they are inherently linked. We discuss the implications of these results for studying the diversity and evolution of languages from an information-theoretic point of view.

In humankind’s endeavor to explore beyond our planet and travel further into space, we are now at the threshold of an era in which it is possible to move to and from low Earth orbit (LEO) with increasing ease and reduced cost. Through the International Space Station (ISS) U.S. National Laboratory, investigators from industry, academia, and government can easily access the unique LEO environment on the ISS to conduct research and development (R&D) activities in ways not possible on Earth. A key advantage of the LEO environment for life sciences research is the ability to conduct experiments in sustained microgravity conditions. The ability to conduct long-term research in microgravity enables opportunities for novel, fundamental studies in tissue engineering and regenerative medicine, including research on stem cell proliferation and differentiation, biofabrication, and disease modeling using microphysiological systems (MPS) that build on prior research using simulated microgravity conditions (Grimm, D., et al. 2018). Over the last decade, space-based research has demonstrated that microgravity informs our knowledge of fundamental biology and accelerates advancements in health care and medical technologies (International Space Station 2019). The benefits provided by conducting biomedical research in LEO may lead to breakthroughs not achievable on Earth. We are now at a transition point, in which nations are changing their approach to space-based R&D. The focus is shifting from government-funded fundamental science toward the expansion of privately funded R&D with terrestrial application and economic value that will drive a robust marketplace for innovation and manufacturing in LEO. Making this long-term transition requires public-private participation and near-term funding to support critical R&D to leverage the benefits of the LEO environment and de-risk space-based research. Studies conducted on the ISS over the past several years have indicated that one area with potential significant economic value and benefit to life on Earth is space-based biomanufacturing, or the use of biological and nonbiological materials to produce commercially relevant biomolecules and biomaterials for use in preclinical, clinical, and therapeutic applications. We must take advantage of the remaining lifetime of the ISS as a valuable LEO platform to demonstrate this economic value and Earth benefit. By facilitating access to the space station, the ISS National Lab is uniquely positioned to enable the R&D necessary to bridge the gap between the initial discovery phase of space-based biomedical research and the development of a sustainable, investment-worthy biomanufacturing market in LEO supported by future commercial platforms. Through a joint effort, the Center for the Advancement of Science in Space (CASIS), which manages the ISS National Lab, and the University of Pittsburgh’s McGowan Institute for Regenerative Medicine brought together thought leaders from around the U.S. for a Biomanufacturing in Space Symposium that consisted of a series of working sessions to review data from past space-based tissue engineering and regenerative medicine research, discuss relevant current space-based R&D in this area, and consider potential future markets to address the questions: What are the most promising opportunities to leverage the ISS to advance space-based biomanufacturing moving forward? What are the current gaps or barriers that, if overcome, could clear pathways toward private investment in LEO as a valued site for research, development, and production activity? And, most importantly: For which opportunities do the most compelling value propositions exist? The goal of the Biomanufacturing in Space Symposium was to help identify the specific areas in which government and industry investment would be most likely to stimulate advancements that overcome barriers. This would lead to a more investment-ready landscape for private interests to enter the market and fuel exponential growth. The symposium was meant to serve as the first step in developing a roadmap to a sustainable market for biomanufacturing in space. The symposium identified and prioritized multiple key R&D opportunities to advance space-based biomanufacturing. These opportunities fall in the areas of disease modeling, stem cells and stem-cell-derived products, and biofabrication. Additionally, symposium participants highlighted the critical need for additional data to help validate and de-risk these opportunities and concluded that approaches such as automation, artificial intelligence (AI), and machine learning will be needed to produce and capture the required data. Symposium participants also came to a consensus that public-private partnerships and funding will be needed to advance the opportunities toward a biomanufacturing marketplace in LEO. This paper will summarize the current state of the science and technology on the ISS and in the fields of tissue engineering and regenerative medicine; provide an overview of biomanufacturing R&D in space to date; review the goals of the Biomanufacturing in Space Symposium; highlight the key commercial opportunities and gaps identified during the symposium; provide information on potential market sizes; and briefly discuss the next steps in developing a roadmap to biomanufacturing in space.

Now when the whole world is still under COVID-19 pandemic, many schools have transferred the teaching from physical classroom to online platforms. It is highly important for schools and online learning platforms to investigate the feedback to get valuable insights about online teaching process so that both platforms and teachers are able to learn which aspect they can improve to achieve better teaching performance. But handling reviews expressed by students would be a pretty laborious work if they were handled manually as well as it is unrealistic to handle large-scale feedback from e-learning platform. In order to address this problem, both machine learning algorithms and deep learning models are used in recent research to automatically process students' review getting the opinion, sentiment and attitudes expressed by the students. Such studies may play a crucial role in improving various interactive online learning platforms by incorporating automatic analysis of feedback. Therefore, we conduct an overview study of sentiment analysis in educational field presented in recent research, to help people grasp an overall understanding of the sentiment analysis research. Besides, according to the literature review, we identify three future directions that researchers can focus on in automatically feedback processing: high-level entity extraction, multi-lingual sentiment analysis, and handling of figurative language.

Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in the developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literatures from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.

A Natural gas is increasingly being sought after as a vital source of energy, given that its production is very cheap and does not cause the same environmental harms that other resources, such as coal combustion, do. Understanding and characterizing the behavior of natural gas is essential in hydrocarbon reservoir engineering, natural gas transport, and process. Natural gas compressibility factor, as a critical parameter, defines the compression and expansion characteristics of natural gas under different conditions. In this study, a simple second-order polynomial model based on the group method of data handling (GMDH) is presented to determine the compressibility factor of different natural gases at different conditions, using corresponding state principles. The accuracy of the model evaluated through graphical and statistical analyses. The results show that the model is capable of predicting natural gas compressibility with an average absolute error of only 2.88%, a root means square of 0.03, and a regression coefficient of 0.92. The performance of the developed model compared to widely known, previously published equations of state (EOSs) and correlations, and the precision of the results demonstrates its superiority over all other correlations and EOSs.

Circulating tumor cells (CTC) have shown to be prognostic in advanced colorectal cancer (advCRC), but their value for predicting response to treatment or as a source of molecular data is debated. We compared CellSearch® (Janssen Diagnostics, LLC) and IsoFlux^TM (Fluxion Biosciences Inc, South San Francisco, CA) systems for the enumeration of CTC in patients with newly diagnosed advCRC (group 1; n=34). Using castPCR^TM we studied KRAS status in CTC isolated with IsoFlux^TM and compared it with that of the primary tumor in patients from group 1 and in KRAS wild-type (KRAS^WT) patients with progressive disease (group 2; n=22). Median number of CTC detected with CellSearch® (groups 1 and 2) was 1 (range: 0-78) and with IsoFlux^TM (group 1) was 8 (range: 0-419), showing a modest correlation (r=0.345, P=0.036), which improved if lung metastases (r=0.805, P=0.016) or if lung and liver metastases were present (r=0.812, P=0.05). A Bland-Altman plot showed that the higher the number of CTC detected the larger the difference between both methods in favor of IsoFlux^TM. After a median follow-up since CTC collection of 16 months (range: 1-30) CellSearch® ≥ 3 CTC (HR 2.77, 95% CI 0.77-9.95) and IsoFlux^TM ≥ 11 CTC (HR 4.14, 95% CI 1.05-16.19) were established as the best cutoff points for predicting survival. Using castPCR^TM we found KRAS mutations in CTC in 4 out of 8 patients from group 1 and in 2 out of 3 patients from group 2. None of these mutations were found in the primary tumor using standard methods, possibly reflecting intratumor heterogeneity or treatment selection pressure. We conclude that IsoFlux^TM is more efficient than CellSearch® in the isolation of CTC in patients with advCRC, achieving, in a majority of cases, the established minimum of CTC for castPCR^TM-based genetic analyses.

Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible using oral cell lines. Normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines were exposed to different tobacco product preparations (TPPs) including cigarette smoke total particulate matter (TPM), whole-smoke conditioned media (WS-CM), smokeless tobacco extract in complete artificial saliva (STE), or nicotine (NIC) alone. We performed microarray-based gene expression profiling and found 3456 probe sets from 101A, 1432 probe sets from 101B, and 2717 probe sets from HGEC to be differentially expressed. Gene Set Enrichment Analysis (GSEA) revealed xenobiotic metabolism and steroid biosynthesis were the top two pathways that were upregulated by combustible but not by non-combustible TPPs. Notably, aldo-keto reductase genes, AKR1C1 and AKR1C2, were the core genes in the top enriched pathways and were statistically upregulated more than 8 fold by combustible TPPs. Our qRT-PCR results statistically support AKR1C1 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products.

Planck’s constant and the gravitational constant are comprised of more fundamental quantities of length, mass, and time. Reformulating traditional equations in terms of these fundamental units offers a more granular view of the physical transformations encoded in the equations of physics. The composite structure of h and G conceals a simple model in which maximum unit potentials are reduced by dimensionless proportionality operators. Natural symmetries correlate the three unit dimensions, yielding predictable quantities of physical dynamics. Insights are organized into a New Foundations Model of physics that reformulates traditional constants and equations in elementary form. The New Foundations Model offers a common language for describing quantum mechanical, gravitational, and electromagnetic phenomena.

Implementation of the German Climate change Strategy in the Federal State of Saxony-Anhalt is discussed in this paper. It shares the requirement and importance of sustainable development. An overview of strategy, The DAS Indicator System is provided with results of a portion of work being done for the ministry of agriculture by Deutscher Wetterdienst (DWD). Applicability of the indicator system is also shown by evaluation of results for specific indicators from 1961-2015.

COVID-19 has affected 212 countries around the world, killing nearly 300,000 and infecting more than 4.4 million by May 14, 2020. Bangladesh, a South Asian low-middle-income economy, has experienced a demographic and epidemiological transition with rapid urbanization and a gradual increase in life expectancy. It is the seventh most populous country in the world and population of the country is expected to be nearly double by 2050. The increasing burden of communicable diseases in Bangladesh can be attributable to rapid urbanization and nearly 50% of all slum dwellers of the country live in Dhaka division. In 2017, National Rapid Response Team of IEDCR investigated 26 incidents of disease outbreak. The joint survey of the Power and Participation Research Centre and BRAC Institute of Governance and Development reveals that per capita daily income of urban slum and rural poor drops by 80% due to present countrywide shutdown enforced by the government to halt the spread of Covid-19. 40%-50% of these population took loans to meet the daily expenses. However, the country has just 127,000 hospital beds, 91,000 of them in government-run hospitals. Researchers say, the country’s economy is economy is losing BDT 33 billion every day from its service and agriculture sectors during the nationwide shutdown.

Dengue virus (DENV) and chikungunya virus (CHIKV) are reemergent arboviruses that are transmitted by mosquitoes of the Aedes genus. During the last several decades, these viruses have been responsible for millions of cases of infection and thousands of deaths worldwide. Therefore, several investigations were conducted over the past few years to find antiviral compounds for the treatment of DENV and CHIKV infections. One attractive strategy is the screening of compounds that target enzymes involved in the replication of both DENV and CHIKV. In this review, we describe advances in the evaluation of natural products targeting the enzymes involved in the replication of these viruses.

Forest ecosystems make a greater contribution to carbon (C) stocks than any other terrestrial ecosystem. To understand the role of regional forest ecosystems in global climate change and carbon exchange, forest C stock and its spatial distribution within the small (2,300 km2) Liuxihe River basin were analyzed to determine the different contributors to the C stock. Forest C stocks were quantified by measuring the biomass of trees, understory vegetation, litter and roots, as well as soil organic C, using data from field samples and laboratory experiments. The results showed that forests stored 38.04 Tg C in the entire basin, with secondary and planted forests accounting for 89.82% and 10.18%, respectively, of the stored C. Five types of forests, a subtropical evergreen broad-leaved forest, a subtropical coniferous and broad-leaved mixed forest, a subtropical coniferous forest, a timber forest, and a non-wood forest, stored 257.55 ± 15.01, 218.92 ± 9.59, 195.24 ± 18.29, 177.42 ± 17.55, and 117.86 ± 6.04 Mg C ha−1, respectively. In the forest ecosystem C stocks of the basin, soils averagely contribute about 73.78%, not including root underground biomass. It provides a comprehensive method for forest ecosystem carbon investigation and forest management in small basin scale.

Microbial electrochemical technologies (MET) rely on the presence of the metabolic activity of electroactive bacteria for the use of solid-state electrodes for oxidizing different kind of compound, that could lead to the synthesis of chemicals, bioremediation of polluted matrices, the treatment of contaminants of interest, as well as the recovery of energy. Keeping in mind those possibilities, since the beginning of the present century, there has been a growing interest in the use of electrochemical technologies for wastewater treatment, and if possible with simultaneous power generation. In the last years, there has been a growing interest to explore the possibility of merging MET with constructed wetlands, to offer a new option of intensified wetland system that could keep a high performance with a lower footprint. Based on that interest, this paper explains the general principles of MET, and the different known extracellular electron transfer mechanisms ruling the interaction between electroactive bacteria and potential solid-state electron acceptors. Also, the adoption of those principles for the development of MET set-ups for simultaneous wastewater treatment and power generation, and the challenges that the technology face. Ultimately, the most recent developments in set-ups that merges MET with constructed wetlands are presented and discussed.

An abundance of natural resources is both an opportunity and a challenge for developing countries. Several resource-rich, low-income countries receive amounts of foreign aid that are similar to or larger than their actual or potential revenues from natural resources. In such countries, the donors may have an opportunity to help a government to use its resource revenues productively and minimize the magnitude of risks created by resource rents. Development of aid instruments tailored for such purposes might be helped by model-based analysis of the effects of foreign aid on resource-rich, low-income economies and its interactions with the flows of natural resource revenues. This paper develops a growth model à la Barro in which the government receives windfalls (from natural resources and foreign aid) and rent-seeking agents contest for public funds. The key conclusion is that making aid countercyclical helps to achieve higher economic growth, and so does conditioning disbursements on enhancement of public capital. Introducing elements of insurance in the design of both aid products financing investments in infrastructure and social services and supporting policy and institutional reforms may help to achieve both of these objectives.

Renewable resources gain increasing interest as source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014–2018). Special focus is drawn on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.

Background: In spinal cord injury, radical treatment is still a persistent hope for patients and clinicians. Our study aimed to determine the different histological changes in central, cranial and caudal sites of compressed spinal cord as a result of neuroectodermal stem cells (NESCs) transplantation in rats. Material and methods: For extraction of NESCs, future brains were extracted from mice embryos (10-days old) and cultured. Eighty, male rats were divided randomly into control, sham (20 rats each); while 40 rats were subjected to compressed spinal cord injury (CSCI). Seven days after spinal cord injury, rats were subdivided into 2 groups (20 rats each); an untreated and treated with NESCs injected cranial and caudal to the site of the spinal cord injury. Rats were sacrificed 4 weeks after transplantations of NESCs and specimens from the spinal cord at the central, cranial and caudal to site of spinal cord injury were proceeded to be stained with haematoxylin & eosin, osmic acid and Immunohistochemistry of glial fibrillary acidic protein (GFAP). Results: Sections of CSCI revealed areas of hemorrhages, necrosis and cavitation limited by reactive astrocytosis, with upregulation of GFAP expression. Evidence of remyelination and mitigation of histopathological features, reactive astrocytosis in CSCI sections were more pronounced in cranial than in caudal region. Conclusions: NESCs transplantation ameliorated the pathological changes, promoted remyelination.

Plant species with anti-inflammatory properties might play an essential role in combatting COVID-19 via reducing cytokine storms. We aimed to review the extant evidence of the potential therapeutic efficacy of natural products against cytokine storms by inhibiting interleukin-6 (IL-6) as a major pathological mediator. Data were collected following an electronic search in major databases (Pubmed, Scopus, Web of Science, Google Scholar) and also preprint articles on preprint and medRxiv servers by using a combination of relevant keywords. Seventeen active compounds and medicinal plants were found and reviewed in the present review. Results of both in-vivo and in-vitro experiments conducted on these compounds showed that Phillyrin, SMFM, Qiangzhi decoction, curcumin, Shen-Fu, Forsythia, and Alpha-Mangostin inhibit the production of IL-6. Andrographolide and Liu Shen Wan have an inhibitory effect on releasing this agent, while Ilex Asprella and Deoxy-11,12-didehydroandrographolide and naringin reduce the expression of IL-6. Theaflavin and Cholorogenic acid inhibit the secretion of IL-6, Xuebijing, and Chai-Hu-Gui-Zi-Gan-Jiang-Tang and Lipanpaidu prescription can reduce the serum level of IL-6. These agents also effectively improve infected lungs, increase survival rates, and minimize tissue damage. Medicinal plants and their phytochemical ingredients with down-regulatory effects on the expression of IL-6 have a potential influence on the inhibition of cytokine storms during viral infection caused by COVID-19. Therefore, phytochemicals could be regarded as promising candidates for managing cytokine storm inflammatory responses due to COVID-19 infection.

The question of the relevance of human and natural capital, as well as the potential adverse effect of natural capital on economic growth, has gained increased attention in development economics. The aim of this paper is to theoretically and empirically assess the relevance of several forms of capital on economic growth in small economies that are dependent upon tourism or natural resources. The empirical framework is based on Impulse Response Functions obtained from Vector Autoregressive models in which we focus on the model where economic growth is the dependent variable for ten small economies that are dependent upon either tourism or natural resources. We find that there is evidence of the ‘’natural resource curse’’, especially in the economies that have a strong dependence on resources that are easily substitutable and whose prices constantly fluctuate. We further find that in the majority of observed cases the type of capital these small economies are most dependent on for their economic growth causes negative impulses in the majority of the observed periods. The main policy recommendation should be to assure that even these small economies should strive towards further diversification and avoid dependence on only one segment of their economy.

Understanding brain function is one of the most important problems in human history. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain's capacities, including motor control, functional states, language, and thinking. Brain function is managed by a well-defined response (R) process that is generally similar to the process underlying the immune system. The R process is strongly reflected in the brain's anatomy, physiology, and external interactions. Different R process stages are supported by distinct excitatory networks located in different cortical layers, hippocampal fields, and bagal ganglia paths, by distinct coordination networks comprised of GABAergic interneurons, and by distinct molecular agents. The roles of norepinephrine, serotonin, dopamine and acetylcholine is to promote the alert, planning, goal-setting and execution R process modes, respectively. Opioids and oxytocin promote termination by success, failure, fight or run, while glucocorticoids and cannabinoids suppress acute responses to protect cells. The R process has two instances occurring at different time scales. The millisecond-scale Quax process implements the execution of hierarchical sequences of movements and thoughts, in which the selection of the next action is determined via interaction between top-down predictions and sensory inputs. The slower Need process controls the satisfaction of internal and external needs. The theory differs from the existing standard accounts in many of the major topics (e.g., the basal ganglia, dopamine, language), and shows how cognition results from biological processes.

Aims: To study the effects of pyridoxal phosphate (PLP) on oxidative stress in isolated pancreatic acinar cells. We have previously shown that PLP has cytoprotective and insulinotropic effects on mice islet cells in vivo and in vitro studies. Main methods: Acinar cells were isolated from three months old WNIN male rats and were cultured in vitro for a period of 24 h in CO₂ incubator. Later the cells were divided into four groups as untreated (group 1), H₂O₂ treatment (group 2)_, PLP treatment (group 3) and PLP followed by H₂O₂ treatment (group 4). Cell viability was confirmed using MTT assays, oxidative stress levels were measured with ROS assay, change in different protein levels were recorded by flow cytometry. The acinar cells insulin secretion assay was performed with ELISA. The amylase protein expression was assessed using confocal microscopy. Key findings: The cell viability of acinar cell in group 1 was considered as 100%, while in group 2 it was reduced to 82% due to H₂O₂ effect, and in group 3 (99.8%) and group 4 (99.5%) were near to group 1 due to the cytoprotective effect of PLP. The ROS levels were increased by 1.47 folds in group 2, while PLP decreased to 1.02 fold in group 4, which was comparable with the changes in group 1. Beneficial effects of PLP were also observed from the increased expression levels of acinar cells are amylase -2.01, neurogenin-3-9.51, PDX-1- 23.6 and insulin-13.5 in group 3 compared to group 1. The specificity of PLP’s response was confirmed by amino oxy acetic acid (AOAA), a specific PLP inhibitor. The increased amylase protein localization with PLP was confirmed by confocal microscopy. Insulin secretion efficiency of acinar cells was observed to be 6.13 folds higher at basal and 24.63 fold higher at stimulated levels in group3 compared to group1. Significance: Our results advocate the antioxidant and cytoprotective effects of PLP on the pancreatic acinar cell along with increased pancreatic marker expressions of amylase,PDX-1, neurogenin-3 and insulin proteins.

Photovoltaic is one of the promising renewable sources of power to meet the future challenge of energy need. Organic and perovskite thin film solar cells are an emerging cost-effective photovoltaic technology because of low-cost manufacturing processing and a light-weight. The main barrier of commercial use of organic and perovskite solar cells is the poor stability of devices. Encapsulation of these photovoltaic devices is one of the best ways to address this stability issue and enhance the device lifetime by employing materials and structures that possess high barrier performance for oxygen and moisture. The aim of this review paper is to find different encapsulation materials and techniques for perovskite and organic solar cells according to the present understanding of reliability issues. It discusses the available encapsulate materials and their utility in limiting chemicals such as water vapour, oxygen penetration. It also covers the mechanisms of mechanical degradation within the individual layers and solar cell as a whole, and possible obstacles to their application in both organic and perovskite solar cells. The contemporary understanding of these degradation mechanisms, their interplay and their initiating factors (both internal and external) are also discussed.

This study presents an exact solution to the free vibration analysis of a uniform Timoshenko beam using an analytical approach, a harmonic vibration being assumed. The Timoshenko beam theory covers cases associated with small deflections based on shear deformation and rotary inertia considerations. In this paper, a moment-shear force-circular frequency-curvature relationship was presented. The complete study was based on this relationship and closed-form expressions of efforts and deformations were derived. The free vibration response of single-span systems, as well as that of spring-mass systems, was analyzed; closed-form formulations of matrices expressing the boundary conditions were presented and the natural frequencies were determined by solving the eigenvalue problem. Systems with intermediate mass, spring, or spring-mass system were also analyzed. Furthermore, first-order dynamic stiffness matrices in local coordinates were derived. Finally, second-order analysis of beams resting on an elastic Winkler foundation was conducted. The results obtained in this paper were in good agreement with those of other studies.

In the second half of the 19th century new methods for quarrying and processing natural stone are developed. In the Nordic countries Sweden, Norway and Finland this technological pro­gress goes hand in hand with a systematic geological mapping and large-scale exploitation of natural stone deposits. As a result, new constructions are developed—changing the building practice in these countries. With the end of historicism a new architecture arises that particularly in Norway and Finland acquires a national-romantic character. This paper examines the interaction between geological exploration, commercial development, technical inventions and the development of a national-romantic architecture.

During the last two years the COVID-19 pandemic has affected the world population in several ways. An important increase in mental health problems is a consequence of this pandemic that is ubiquitous worldwide. In this work we study the effect of the pandemic on the mental health of a population of teenagers and youth based on the analysis of natural language processing, machine learning algorithms and expert knowledge. The data analysed was obtained from a chat helpline called Safe time from theIt Get’s Better Foundation in Chile. The data consists of 10,986 conversations gathered from 2018 until 2020 between volunteers from the foundation and users of the platform. We compared the conversationsbefore and during the pandemic in terms of their thematic content. Our analysis found: a significantdecrease in self-image appreciation during the pandemic; a significant decrease in the quality of personalrelationships during the pandemic, and a significant increase of performance appreciation.

This paper proposes a new approach to investigation into the aesthetics. Specifically, it argues that it is possible to explain the aesthetic and its underlying dynamic relations with axiomatic structure (the octahedral axiom derived category) based on contemporary mathematics – namely, category theory – and through this argument suggests the possibility for discussion about the mathematical structure of the aesthetic. If there was a way to describe the structure of aesthetics with the language of mathematical structures and mathematical axioms – a language completely devoid of arbitrariness – then we would make possible a synthetical argument about the essential human activity of “the aesthetics”, and we would also gain a new method and viewpoint on the philosophy and meaning of the act of creating a work of art and artistic activities. This paper presents one hypothesis as a first step in constructing the science of dynamic generative aesthetics based on axiomatic functionalism, which is in turn based on a new interdisciplinary investigation into the functional structure of aesthetics.

Forest managers are often required to restore forest stands following natural disturbances, a situation that may become more common and more challenging under global change. In parts of Central Europe, particularly in mountain regions dominated by mixed temperate forests, the use of relatively low intensity, uneven-aged silviculture is a common management approach. Because this type of management is based on mimicking less intense disturbances, the restoration of more severe disturbance patches within forested landscapes has received little attention within the context of uneven-aged silviculture in the region. The goal of this paper is to synthesize research on the restoration of forests damaged by disturbances in temperate forests of Slovenia and neighbouring regions of Central Europe, where uneven-aged silviculture is practiced. We place particular emphasis on the most important biotic and abiotic drivers of post-disturbance regeneration, and use this information to inform silvicultural decisions about applying natural or artificial regeneration in disturbed areas. We conclude with guidelines for restoration silviculture in uneven-aged forest landscapes.

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90 % of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Here, we investigate the effects of CBFA2T2 on CSCs regulation in RCC, as well as to elucidate the possible mechanisms. We showed that CBFA2T2 expression can significantly predict the survival of RCC patients. Functional assays showed that knocking-down of CBFA2T2 can inhibit cell migration and invasion in 786-O and A-498 cells in vitro, and reduce ALDH^high CSCs populations. Furthermore, CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines. Collectively, our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of “stemness” through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

Microbial Fuel Cells (MFCs) representing a promising technology for the extract of energy and resources through wastewater and it also offer an economic solution to the problem of environment effluent and energy crisis in near future. The advance device is rather appealing, due its potential benefits, its practical application is, however hindered by several drawbacks, such an internally competing microbial reaction, and low power generation. This report is an endeavor to address various design connected to the MFCs application to wastewater treatment, in particular cost effective bioelectricity from waste water are reviewed and discussed with a multidisciplinary approach. The conclusions drawn herein can be of practical interest to all new researchers dealing with effluent wastewater treatment using MFCs.

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.

One of the most used markers of cancer stem cells in several cancers, including colorectal cancer and breast cancer, is CD44. CD44 is a glycoprotein that traverses the cell membrane and binds to many ligands including hyaluronan resulting in activation of signaling cascades. Several reports have shown conflicting data on the expression of CD44 and that the expression depends on modes of investigations and subtypes of cancers. In addition, the correlation between CD44 expression and drug resistance, immune infiltration, EMT, metastasis and patients prognosis in several cancer types remains unclear. This study investigated CD44 expression in several cancers and explored its relationship with tumorigenesis using various publicly available databases, including The Cancer Genome Atlas, GEPIA, Oncomine, Genomics of Drug Sensitivity in Cancer and Tumor Immune Estimation Resource. Our analysis reveals that CD44 is differentially expressed in different cancers. CD44 expression is significantly associated with cancer patients’ survival in gastric, pancreatic and colorectal cancers. In addition, CD44 expression is closely linked with immune infiltration and immune suppressive features in pancreatic, colon adenocarcinoma and stomach cancer. High CD44 expression was significantly correlated with the expression of drug resistance-, EMT- and metastasis- linked genes. Tumors expressing high CD44 have higher mutation burden and afflict older patients than tumors expressing low CD44. Cell lines expressing high CD44 are more resistant to anti-cancer drugs compared to those expressing low CD44. Protein-protein interaction investigations and functional enrichment analysis showed that CD44 interacts with gene products related to cell-substrate adhesion, migration, platelet activation, and cellular response to stress. KEGG pathway analysis revealed that these genes play key roles in biological adhesion, cell component organization, locomotion, G-α-signaling and the response to stimulus. Overall, this investigation reveals that CD44 play significant roles in tumorigenesis, can be used as a prognostic biomarker in several cancers and can be therapeutically targeted in cancer therapy.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

Zucchini (Cucurbita pepo subsp. pepo) is a seasonal vegetable with high nutritional and medical value. Many useful properties of this fruit are attributed to its bioactive compounds. Zucchini fruits (“Yellow” and “Light Green” varieties) and four distinctive components (lutein, β-carotene, zeaxanthin and dehydroascorbic acid)were selected. Firstly it was determinated the lutein, β-carotene, zeaxanthin and dehydroascorbic acid content in these fruits and then, in order to measure the safety and suitability of their use different assays were carried out: (i) Genotoxicity and antigenotoxicity tests to determine the safety and DNA-protection against hydrogen peroxide; (ii) cytotoxicity and (iii) DNA fragmentation assay to evaluate the proapoptotic effect. Results showed that: (i) all the substances were non-genotoxic, (ii) all the substances were antigenotoxic except the highest concentration of lutein, (iii) “Yellow” Zucchini epicarp and mesocarp exhibited the highest cytotoxic activity (IC₅₀ > 0.1 mg/mL and 0.2 mg/mL, respectively) and iv) “Light Green” Zucchini skin and pulp induced internucleosomal DNA fragmentation . To sump up, Zucchini fruit could play a positive role in human health and nutrition due to this fruit and its components were safe, able to inhibit significantly the H₂O₂-induced damage and exhibit antiproliferative and pro-apoptotic properties toward HL60 tumour cells. The information generated from this research should take into account to select potential accessions for breeding programs purposes.

The corona (COVID-19) pandemic offers an opportunity for dealing with persistent problems, through a transformative recovery process. It is a crisis that offers opportunities for dealing with three interrelated crises: the ecological crisis (climate change, loss of biodiversity, resource depletion, pollution and ecosystem destruction), the confidence crisis (people losing trust in government, politics, companies, regular news channels, science, each other and the future), and the inequality crisis (the widening of the gap between rich and poor). Our argument is that sustainability transitions will not succeed without a different economy and another social contract with the associated rights and duties of care (for the environment and the well-being of others, including future generations). A different social contract is not only desirable from the point of view of sustainability and fairness, justice and equality, but is also necessary to restore citizens' trust in politics, government, companies and each other. In the paper we discuss mechanisms towards a Natural Social Contract, systemic leverage points for system transformations and possibilities for co-evolutionary governance by actor coalitions interested in transformative change. The combination of those three elements helps to synchronize different agendas and reduce the chance that they will work against each other.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the SARS-CoV-2 virus causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top- ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

The literature on the causation of multiple sclerosis (MS), both genetic and environmental, extends over hundreds of years, with no firm conclusions on the exact role of autoimmunity and lifestyle. The epidemiology of MS was the basis for this review, but with a new, extensive examination of genes pertaining to each disorder, and disease of first, and second, degree relatives of those with MS. The author’s motivation was to discover some relationship between MS, and notable familial conditions, as the heredity of MS is concluded to be 30%, and the disorders had a chronic and/or idiopathic nature. This investigation hoped to further understand the randomness of MS- who acquires it, and what symptoms develop- after the author’s decades of observing several incidences of multiple members developing MS in a single family. Online databases for the human genome were used to link genes to MS, and symptoms, including excessive depression, fatigue and suicide rates, in coordination with linking genes for specific familial conditions including seizures, stroke, mental illness, bowel disorders, and thyroid conditions. Interesting associations were found, notably a cluster of Th2 cytokines, known to cure the animal model of MS, important receptors for neurotransmitters and hormones, a gene specific to Epstein Barr Virus, and potential genes for mitochondrial dysfunction. The results surprised the author, showing polygenic regions of chromosome 2 and 5, especially a cluster at loci 5q31-q33, may be dysregulated. The conclusion agrees with past hypotheses MS results not from a single gene, but from various genes, including those expressed in glial cells. The individual theories to the causation of MS, starting with Charcot may be explained by multiple pathways converging into a single disease outcome. In coordination with a sunlight factor, chromosome 2 appears to mediate the immune system, and inflammation, through ultraviolet radiation producing vitamin D3 in the skin, but additionally through peptides formed in the melanocyte stimulating and concentrating hormone class. The impact of stress in MS could be primary, given the loci of several stress-related and stress-modulated genes on these chromosomes, and calls for more appreciation of, and greater care for, the MS patients’ state of mind.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. Herein, we used real-time PCR, western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the Nrf2 function. Surprisingly, we demonstrated that with up-regulated ROS and MDA levels, the effect of oxidative stress was obvious under H2O2 treatment. Anti-oxidative molecules were changed after the H2O2 exposure, whereby the anti-oxidative signaling of Nrf2 was activated with the increase of its downstream effectors, HO-1, NQO1 and γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress and changes in the caspase-9, caspase-3, Bax and c-Fos levels, but not with caspase-8 and down-regulated Bcl-2. The enhanced antioxidant effect could not resist the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, et al, but not that of caspase-8. By contrast, silencing the expression Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on anti-oxidative and anti-intrinsic apoptosis by the activation of anti-oxidative enzymes.

We examine the extensions of the basic arithmetical operations of addition and multiplication on the natural numbers into higher-rank hyper-operations also on the natural numbers. We go on to define the concepts of prime and composite numbers under these hyper-operations and derive some results about factorisation, resulting in fundamental theorems analogous to the Fundamental Theorem of Arithmetic.

The Abnormal increase in the mass of adipose tissue during adipogenesis results in obesity. Obesity is a predominant disorder and its widespread has become a critical concern worldwide. This is due to the burden of its associated co-morbidities like cancer, cardiovascular diseases and diabetes. Over-nutrition and the sedentary lifestyle are considered as the most significant causes of abnormal adipose tissue development. Appropriate lifestyle and behavioural interventions are the corner stones of successful weight loss, but to maintain such a lifestyle is highly challenging. Accordingly, natural products from plants either as crude extracts or purified phytochemicals have shown to have anti-obesogenic properties and are generally non-toxic and cost-effective. In this review, we discuss the comparative analysis of molecular mechanisms involved in adipogenesis and the recently reported anti-obesogenic effects of various plant products. We will provide a common platform for understanding obesity and adipogenesis, and a possible mechanism of action for anti-obesogenic plant products through AMP-activated protein kinase (AMPK), which will support the scientific development of traditional herbal medicine.

The intracellular calcium dynamics in vascular endothelial cells (VECs) in response to wall shear stress (WSS) and/or adenosine triphosphate (ATP) have been commonly regarded as an important factor in regulating VEC function and behavior including proliferation, migration and apoptosis. However, the effects of time-varying ATP signals have been usually neglected in the past investigations in the field of VEC mechanobiology. In order to investigate the combined effects of WSS and dynamic ATP signals on the intracellular calcium dynamic in VECs, a Y-shaped microfluidic device, which can provide the cultured cells on the bottom of its mixing micro-channel with stimuli of WSS signal alone and different combinations of WSS and ATP signals in one single micro-channel, is proposed. Both numerical simulation and experimental studies verify the feasibility of its application. Cellular experimental results also suggest that a combination of WSS and ATP signals rather than a WSS signal alone might play a more significant role in VEC Ca²⁺ signal transduction induced by blood flow.

G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.

Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and anti-inflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

This paper investigates existing mathematical morphology based techniques applied for performing malaria parasites detection and identification in both Giemsa and Leishman stained blood smears images. Malaria is an epidemic health disease and a rapid, accurate diagnosis is necessary for proper intervention. Generally, pathologists visually examine blood stained slides for malaria diagnosis; this kind of visual inspection is subjective, errorprone and time consuming. In order to cope with such issues, computer-aided methods have been increasingly evolved for abnormal erythrocyte and/or parasites detection, segmentation and semi/fully automated classification. The aim of this paper is to present a review of recent mathematical morphology based methods for malaria parasite detection.

Oxidative stress is an elevated intracellular level of free oxygen radicals that cause lipid peroxidation, protein denaturation, DNA hydroxylation, and apoptosis, ultimately negotiating cells viability. Antioxidants can scavenge such free radicals, thus reducing the oxidative stress and eventually prevent cellular damage. Medicinal plants, fruits, and spices remain the prioritized sources of antioxidants and antimicrobial properties since the time immemorial, but in contrast to plants, microorganisms can be grown at a faster rate under controlled conditions. They are non-toxic, non-carcinogenic, and biodegradable as compared to synthetic antioxidants. Microorganisms including actinomycetes, archaea, bacteria, protozoa, yeast, and fungi are auspicious source of vital bioactive compounds. The list comprises ample of bioactive components from microorganisms. One of them is bacteriocins, which are ribosomally synthesized antimicrobial peptides product of Eurotium sp., Streptomyces parvulus, S. thermophiles, Lactococcus lactis, etc. It has a great potential as next-generation antibiotics targeting the multiple-drug resistant pathogens. Pneumocandins are antifungal lipohexapeptides derived from the fungus Glarea lozoyensis, and inhibit 1,3-β-glucan synthase of the fungal cell wall and act as a precursor for the synthesis of caspofungin. It is widely used against invasive fungal infections and has been recently approved by the FDA. Taxol (paclitaxel), a chemotherapeutic drug derived from the bark of Taxus brevifolia can also be produced by endophytic fungi Taxomyces andreanae and Nodulisporium sylviforme. It is known to inhibit several fungi such as Pythium, Aphanomyces and Phytophthora. Hispidin and its derivate isolated from P. hispidus, reduce inducible nitric oxide synthase (iNOS) expression, obstruct the transcriptional activity of NF-κB, and also decrease the production of reactive oxygen species (ROS) in macrophages. Astaxanthin, known as an “aquatic” carotenoid produced by H. pluvialis, also has excellent ROS quenching activity. This study mainly focuses on fascinating antioxidant and antimicrobial compounds that have been scarcely investigated in microorganisms and discuss the promise and challenges of microorganisms as providers of health benefits.

Oxidative stress negatively affects folliculogenesis and embryo development. However, a reliable and biologically accurate indicator of oxidative stress does not yet exist. On these bases, the aim of this study was to assess -and compare- blood and follicular fluid (FF) redox status in 45 infertile subjects (and 45 age-matched controls) undergoing in vitro fertilization (IVF) and to establish its connection with the outcome of IVF. Blood and FF were obtained at the time of egg retrieval and immediately analyzed. Firstly, ROS production in blood leukocytes and in granulosa cells was assessed. Oxidative stress markers in blood and in granulosa cells resulted significantly (p<0.001) increased in infertile patients compared to controls. Then, a redox index was obtained in plasma and in FF of patients and controls. The main findings emerging from our study in infertile women are: i) blood oxidative stress reflects FF oxidative stress as demonstrated by the significant correlation between blood redox markers and FF redox markers; ii) a significant correlation between oxidative stress parameters and the considered IVF outcomes is present. We suggest the strict monitoring of the redox parameters for the improvement of assisted reproductive techniques success rate and infertility management.

The utilization for water resource has been of great concern to human life. To assess the natural water system in Kangding County, the integrated methods of hydrochemcial analysis, multivariate statistics and geochemical modelling were conducted on surface water, groundwater and thermal water samples. Surface water and groundwater were dominated by Ca-HCO₃ type, while thermal water belonged to Ca-HCO₃ and Na-Cl type. The analyzing results concluded the driving factors that affect hydrochemical components. Following the results of the combined assessments, hydrochemcial process was controlled by the dissolution of carbonate and silicate minerals with slight influence from anthropogenic activity. The mixing model of groundwater and thermal water was calculated using silica-enthalpy method, yielding cold-water fraction of 0.56-0.79 and estimated reservoir temperature of 130-199 ^oC, respectively. δD and δ¹⁸O isotopes suggested surface water, groundwater and thermal springs were of meteoric origin. Thermal water should have deep circulation through the Xianshuihe fault zone, while groundwater flows through secondary fractures where it recharges with thermal water. Those analytical results were used to construct a hydrological conceptual model, providing a better understanding of the natural water system in Kangding County.

This paper aims to build up a preference function to evaluate the public benefits of the type of agricultural farming, biodiversity, water provisions, land use type, ecotourism modes, and a monetary attribute (environmental trust fund and willingness to contribute) associated with an ecosystem service and land use program in a forest park. This study used the choice experiments to build a random utility model, analyze the average preference for the above land use attributes based on the conditional logit and used a latent class model to test the resident’s heterogeneous preferences for land use planning in the forest park. We also estimated the welfare derived from various land use programs. The empirical result had shown that: (1) increasing organic farming area, maintaining the status quo of species biodiversity, increasing the surface water provision, increasing the area of custom flora, increasing the wetland area, and setting up an integrated framework for ecotourism increase the public’s preference for the land use program; (2) we found that farmer and non-farmer haven’t the same land use preferences; (3) the ecotourism development program incorporating biodiversity, organic farming, ethnobotany, and wetland area with integrated ecotourism are more preferred than other land use program scenarios.

This paper proposes a method based on genetic algorithm (GA) for the security-constrained optimal dispatch of integrated natural gas and electricity networks, considering operating scenarios in both energy systems. The mathematical formulation of the optimization problem consists of a multi-objective function which aims to minimize both cost of thermal generation (diesel and natural gas) as well as the production and transportation of natural gas. The joint gas-electricity system is modeled by two separate groups of nonlinear equation, which are solved by the combination of Newton's method with the GA. The applicability of the proposed method is tested in the Belgian gas network integrated with the IEEE 14-bus test system and a 15-node natural gas network integrated with the IEEE 118-bus test system. The results demonstrate that the proposed method provides efficient and secure solutions for different operating scenarios in both energy systems.

The provision requirement of 10% openings of the total floor area stated in the Uniform Building by Law 1984 Malaysia has been practiced by designers for building plan submission approval. However, the effectiveness of thermal performance in landed residential buildings, despite the imposition by the by-law, has never been empirically measured and proven. Although terraced houses in Malaysia have dominated 40.9% of the total property transaction in 2019, such mass production with typical designs hardly provides its occupants with thermal comfort due to the static outdoor air condition and lack of external windows, where the conventional ventilation technique does not work well, even for houses with an air well system. Consequently, the occupants need to rely on mechanical cooling, which is a high energy-consuming component contributing to outdoor heat dissipation and therefore urban heat island effect. Thus, encouraging more effective natural ventilation to eliminate excessive heat from the indoor environment is critical. Since most of the research focuses on simulation modelling lacking sufficient empirical validation, this paper drawing on field measurement investigates natural ventilation performance in terraced housing with an air well system. More importantly, the key concern as to what extent the current air well system serving as a ventilator is effective to provide better thermal performance in the single storey terraced house is to be addressed. By adopting an existing single storey air welled terrace house, the existing indoor environmental conditions and thermal performance were monitored and measured using scientific equipment, namely HOBO U12 air temperature and air humidity, the HOBO U12 anemometer and the Delta Ohm HD32.3 Wet Bulb Globe Temperature meter for a six-month duration. The findings show that the air temperature of the air well ranged from 27.48°C to 30.92°C, while the mean relative humidity were from 72.67% to 79.25%. The mean air temperature for a test room (single sided ventilation room) ranged from 28.04°C to 30.92°C with a relative humidity of 70.16% to 76%. These empirical findings are of importance, offering novel policy insights and suggestions to potentially revising the existing building code standard and by laws; since the minimum provision of 10% openings has been revealed to be less effective to provide a desired thermal performance and comfort, mandatory compliance with, and the necessity for, the bylaw requirement should be revisited and further studied.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

Abstract: Understanding social media networks and group interactions are crucial to the ad-vancement of linguistic and cultural behaviour. This includes the manner in which people ac-cessed advice on health, especially during the global lockdown periods. Some people turned to social media to access information on health where most activities were curtailed with isolation rules, especially for older generations. Facebook public pages, groups and verified profiles, using "senior citizen health", "older generations", and "healthy living" keywords were analysed over a 12-month period to analyse the engagement promoting good mental health. CrowdTangle was used to source English language status updates, photo and video sharing information which resulted in an initial 116,321 posts and 6,462,065 interactions Data analysis and visualisation were used to explore large datasets, including natural language processing for “Message” content discovery, word frequency and correlational analysis and co-word clustering. Preliminary results indicate strong links to healthy aging information shared on social media which showed correla-tions to global daily confirmed case and daily death totals. The results can be used to identify public concerns early on and address mental health issues in the senior generation on Facebook.

Many inflammatory mechanisms are involved in the pathophysiology of COVID-19 infection. COVID-19 inhibits IFN antiviral responses, so we should expect an out-of-control viral replication. “Cytokine storms” occur due to the over-production of pro-inflammatory cytokines after an influx of neutrophils and monocytes/macrophages and may be responsible for the immunopathology of the lung involvement. Several cascades have been reported in the activation process of NF-κB. In this paper, to find new therapeutic options for COVID-19 infection, we reviewed some natural products that could potentially inhibit the NF-κB pathway. We found that sevoflurane, quercetin, resveratrol, curcumin, KIOM-C, bergenin, garcinia kola, shenfu, piperlongumine, wogonin, oroxylin, plantamajoside, naringin, ginseng, kaempferol, allium sativum L, illicium henryi, isoliquiritigenin, lianhua qingwen, magnoflorine, and ma Huang Tang might be effective in inhibiting the NF-KB pathway. These natural products could be helpful in the control of COVID-19 infections. However, larger clinical trials are needed to ascertain the efficacy of these products fully.

Following our previous success in identifying new steroid-based anticancer agents, we herein disclosed the structural requirements for retaining high potency against cancer cells and associated modes of action. The structurally novel steroidal dimer by001 inhibited growth of different esophageal cancer cells and colony formation at low micromolar levels, elevated cellular ROS levels and caused mitochondrial dysfunction. Mechanistic studies showed that by001 induced cell death through the mitochondria and death receptor-mediated apoptotic pathways and autophagy induction, as well as inhibited migration.

P2Y2 and P2Y4 receptors are physiologically activated by UTP and are widely expressed in many cell types in humans. They promote an increase in intracellular calcium via PLCβ/ IP3 and act on ion flux and water secretion. P2Y2 plays an important role in inflammation and proliferation of tumor cells, which could be attenuated with the use of antagonists. However, little is known about the physiological functions related to P2Y4 due to the lack of selective ligands for these receptors, which can be solved through the search of novel compounds with antagonistic activity. In the present study, we have applied a methodology of calcium measurement to identify new antagonist candidates for these receptors. Firstly, we established optimal conditions for calcium assay using J774.G8, a murine macrophage cell line, which expresses functional P2Y2 and P2Y4 receptors. J774.G8 cells were loaded with 2 μM of Fluo-4 to test its sensitivity in responding calcium stimuli. ATP and ionomycin, known as inductors of intracellular calcium rise, were used to stimulate cells. The EC50 obtained were 11 μM and 103 nM, respectively. Subsequently, investigation of P2Y2 and P2Y4 expression was performed. These cells responded with EC50 of 1.021 μM to the UTP stimulation. Screening assays were performed and a total of 100 extracts from Brazilian natural products were tested. JA2, RA3, and RB3 extracts stood out for their ability to inhibit UTP-induced responses without causing cytotoxicity and presented IC50 of 32.32 μg/mL, 14.99 μg/mL, and 12.98 μg/mL, respectively. Collectively, our results point to the discovery of potential antagonists candidates from natural products for UTP-activated receptors.

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

As our understanding of the thalamocortical system deepens, the questions we face become more complex. Their investigation requires the adoption of novel experimental approaches complemented with increasingly sophisticated computational modeling. In this review, we take stock of current data and knowledge about the circuitry of the somatosensory thalamocortical loop in rodents, discussing common principles across modalities and species whenever appropriate. We review the different levels of organization, including the cells, synapses, neuroanatomy, and network connectivity. We provide a complete overview of this system that should be accessible for newcomers to this field while nevertheless being comprehensive enough to serve as a reference for seasoned neuroscientists and computational modelers studying the thalamocortical system. We further highlight key gaps in data and knowledge that constitute pressing targets for future experimental work. Filling these gaps would provide invaluable information for systematically unveiling how this system supports behavioral and cognitive processes.

The integral extraction via microwave-assisted hydrodiffusion and hydrodistillation of water-soluble bioproducts contained in the peel of Opuntia ficus-indica white and red cultivars harvested in Sicily, affords red and stable aqueous extracts mostly containing valued betanin, pectin and biophenols. Potentially useful as nutraceutical products, these aqueous extracts are a source of valued ingredients in high demand for a number of important food, cosmetic, beverage and nutraceutical applications.

The interpretation of the local microenvironment of extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (PLLA and PCL) and collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter of (Nuclear/Cytoplasm) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity (IC₅₀) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

Paraphrase Generation is one of the most important and challenging tasks in the field of Natural Language Generation. The paraphrasing techniques help to identify or to extract/generate phrases/sentences conveying the similar meaning. The paraphrasing task can be bifurcated into two sub-tasks namely, Paraphrase Identification (PI) and Paraphrase Generation (PG). Most of the existing proposed state-of-the-art systems have the potential to solve only one problem at a time. This paper proposes a light-weight unified model that can simultaneously classify whether given pair of sentences are paraphrases of each other and the model can also generate multiple paraphrases given an input sentence. Paraphrase Generation module aims to generate fluent and semantically similar paraphrases and the Paraphrase Identification systemaims to classify whether sentences pair are paraphrases of each other or not. The proposed approach uses an amalgamation of data sampling or data variety with a granular fine-tuned Text-To-Text Transfer Transformer (T5) model. This paper proposes a unified approach which aims to solve the problems of Paraphrase Identification and generation by using carefully selected data-points and a fine-tuned T5 model. The highlight of this study is that the same light-weight model trained by keeping the objective of Paraphrase Generation can also be used for solving the Paraphrase Identification task. Hence, the proposed system is light-weight in terms of the model’s size along with the data used to train the model which facilitates the quick learning of the model without having to compromise with the results. The proposed system is then evaluated against the popular evaluation metrics like BLEU (BiLingual Evaluation Understudy):, ROUGE (Recall-Oriented Understudy for Gisting Evaluation), METEOR, WER (Word Error Rate), and GLEU (Google-BLEU) for Paraphrase Generation and classification metrics like accuracy, precision, recall and F1-score for Paraphrase Identification system. The proposed model achieves state-of-the-art results on both the tasks of Paraphrase Identification and paraphrase Generation.

In this investigation dyeing of alginate fiber was carried out after cationic treatment of EPTAC (2, 3-Epoxypropyl Trimethyl Ammonium Chloride). Optimum dyeing process and parameter show good dyeing performance when alginate fiber dyed with rhubarb dye. In addition to cationic treatment is taken into account for alginate fiber to improve fastness, color strength, breaking strength. Later in dyeing for fixation ferrous sulfate, copper sulphate was considered as mordents. Moreover using pre-mordanting methods conveyed the dyeing of alginate fiber with the stave of metallic mordant and without metallic salt mordents. The evaluation of each color dyed material was done through following two terms for instance CIELAB (L*, a*, and b*) and K/S values. According to AATCC test methods color fastness to washing of the dyed fiber was determined whereas according to the ASTM D3822M standard the breaking strength of alginate fiber was estimated and tested. When dyeing was carried out on alginate fiber through considering optimum parameter like 80◦C for 90 min, M: L 1:40 and at pH 7 which showed optimum results. In addition to mostly very good wash fastness was obtained while there was no fading of the color, whereas the moderate level of color fastness to crocking was achieved. Later after dyeing the evaluations of SEM of the cationized alginate fiber and FTIR of powder from the rhubarb dye were observed. The results suggested that the surface of cationized alginate fiber was smoother than the raw alginate fiber.

This review seeks to explain four features of viral respiratory illnesses that have perplexed generations of virologists: (1) the seasonal timing of respiratory illness; (2) the common viruses causing respiratory illness worldwide, including year-round disease in the Tropics; (3) the rapid response of outbreaks to weather, specifically temperature; (4) the rapid arrival and termination of epidemics caused by influenza and other viruses. The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called Temperature Dependent Viral Tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ-specific viral tropism within the human body, whereby they replicate most rapidly at temperatures below body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. Biochemical and tissue-culture studies show that “wild” respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the existence of respiratory illness in the Tropics year-round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. The TDVT hypothesis has important practical implications for preventing and treating respiratory illness including Covid-19. TVDT is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.

Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as Sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of Sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds.

Solid tumors display complex biology and most therapies including chemotherapy cannot prevent therapy resistance and relapse. Most therapeutics target cancer cells, but recent data suggest the presence of cancer stem cells as cells with self-renewal and tumorigenic abilities. Cancer stem cell markers have been suggested to have prognostic value and can be targeted during cancer treatment and in resistant disease. CSCs have been postulated to play significant contextual roles in tumor initiation, progression, therapy resistance and metastasis. CSCs have thus been targeted by new generation cancer drugs. The transcriptional expression of several CSC markers in different cancers was evaluated by searching publicly available The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We report here new findings on expression and prognostic significance of CSC markers in several cancers by examining the expression of CSCs markers in tumor tissues versus the adjacent normal tissues. We found that CSC markers were mostly highly expressed various tumors such as colon, lung, pancreatic and esophageal cancers. No CSC marker is expressed in the same pattern in all cancers and individual CSC marker expression was not linked to patient survival. This analysis calls for continued research on CSCs and clinical evaluation of the CSC markers in relation to prognosis of cancers in large population samples. Novel cancer drugs ought to target CSCs, cancer cells and tumor microenvironment variations.

Separation and interpretation of rebellious Circulating Tumor Cells (CTCs) originating from the primary tumor or cancer tissue plays a significant role in diagnostics, cancer progression analyses, suitable medicine exploration, and treatment proficiency examination. Cancer metastasis occurs when CTCs spread throughout the body and invade healthy tissues, leading to new tumors in that area. Although a dramatic rate of deaths begins from spreading CTCs around the body, valuable measures have been made to control their development. However, the first step is separating these harmful cells from the bloodstream and investigating their features. Having examined the characteristics of CTCs as cancer’s main strength, researchers can introduce complementary treatments that can affect cancerous cells without damaging the healthy cells. Therefore, according to their unique characteristics, numerous techniques have been established for continuous and fast separation and sorting of CTCs. Nevertheless, few separators enjoy the efficient performance and appropriate accuracy and can be produced in mass numbers due to the available fabrication equipment. Microfabrication advancements enable separators to combine the advantages of active and passive methods in a small-scale platform for probing individual cells and separation purposes. Reduction in reagents, sample volume, analysis time, and less harmfulness to patients are some of the motivations that encourage researchers to employ microfluidic instruments for CTCs separation from other blood cells over the last two decades. However, microfabrication limitations mean effective separators, and the diagnostic option they provide, are not readily available. Addressing these limitations requires optimizing the design and fabrication of separators such that they are reduced in their size and fabrication cost, while also maintaining high-throughput separating capability. The emergence of the Lab-On-a-Chip (LOC) and then Lab-On-a-CD (LOCD) technologies, having more inherent benefits than conventional microfluidic devices, has created new opportunities and become increasingly widespread in recent years. Evidence suggests that employing single methodologies or integrating approaches without sufficient understanding of potential outcomes is unlikely to result in successful diagnostic results. This paper contributes an extensive review of several separation systems, including fundamental theories and experimental details, and describes detailed operating principles and device performance.