Changes in extreme weather patterns are expected under climate change. In this study, a risk assessment was conducted using 4 building damage history datasets and 33 weather datasets (precipitation, wind speed, snow, and temperature) from 230 regions in South Korea to quantitatively analyze and predict building damage caused by potential future natural disasters. Decision tree analysis was used to evaluate building damage risk in 230 regions. The decision tree model to determine the risk of flood, gale, and typhoon was generated, which excluded gales, with less damage. The weight (variable importance) and limit value (damage limit) of the weather variables ware derived using the decision tree model. Using these two factors, we assessed the building damage risk in 230 regions in South Korea until 2100. The number of regions at risk of flood damage increased by more than 30% in average. Conversely, regions at risk of snowfall damage decreased by more than 90%. The regions at risk of typhoons decreased by 57.5% on average, and the number of regions at high risk of typhoon damage increased by up to 62.5% in RCP 8.5. These results can be used as objective data to minimize future building damage throughout South Korea, representing the first step towards sustainable development in the region with respect to disaster response.

In recent years, online social networks have received important consideration in spatial modelling fields given the critical information that can be extracted from them for events in real time; one of the most latent issues is that regarding various natural disasters such as earthquakes. Although it is possible to retrieve data from these social networks with embedded geographic information provided by GPS, in many cases this is not possible. An alternative solution is to reconstruct specific locations using probabilistic language models, more specifically those based on Name Entity Recognition (NER), which extracts names from a user’s description about an event occurring in a specific place (e.g., a collapsed building on a specific avenue). In this work, we present a methodology to use twitter as a social sensor system for disasters. The methodology scores NER locations with a kernel density estimation function for different subtopics originating from a natural disaster and that maps them into a geographic space is proposed. The proposed methodology is evaluated with tweets related to the 2017 earthquake in Mexico.

The realization of the third-generation artificial intelligence (AI) requires the evolution from perceptual intelligence to cognitive intelligence, where knowledge graphs may not meet the practical needs anymore. Based on the dual channel theory, cognitive graphs are established and developed through coordinating the implicit extraction module and the explicit reasoning module as well as integrating knowledge graphs, cognitive reasoning and logical expressions, which have achieved successes in multi-hop question answering. It is desired for cognitive graphs to be widely used in advanced AI applications such as large-scale knowledge representations and intelligent responses, promoting the development of Al dramatically. This review discusses cognitive graphs systematically and elaborately, including basic concepts, generations, theories and technologies. Moreover, we try to predict the development of cognitive intelligence in the short-term future and further enlighten more researches and studies.

Natural capital is the wealth of nations that give them the economic status they represent. Worldwide, vulnerable people depend on natural capital for employment, salaries, wealth, and livelihoods and, in turn, determine the developmental index of the nation to which they belong. The availability of ecological services is crucial for clean water and air, food and fodder, and agricultural development. In this short commentary, we have tried to sum up the ideas and discussions over natural capital's role in ascribing economic status to countries. We have discussed how the prosperity of humans is intertwined with the services ecosystems provide and how poor natural resource management (NRM) has adversely cost human well-being. The paper concludes that to ensure the current and future human well-being, an in-depth understanding of the services ecosystems provide, is essential.

Based on the geologic conditions of natural gas hydrate (NGH) accumulations in the Shenhu area, northern slope of the South China Sea, this paper used a method of combining reservoir stimulation technique (RST) with depressurization to investigate the conversion efficiency of marine NGH reservoirs in different intrinsic permeability and initial NGH saturation conditions, and analyze the influence of variably-stimulation effect on marine NGH conversion efficiency in different accumulation conditions, provided a reference scheme for improving the NGH conversion efficiency in the Shenhu area. In this work, we performed calculations for the variations in CH4 production rate and cumulative volume of CH4 in different initial NGH saturation, intrinsic permeability and stimulation effect conditions, variance analysis and range analysis methods were used to analyze the significance of these key factors and their interaction, and investigated the sensitivity of stimulation effect on NGH conversion efficiency, respectively. The simulation results showed that stimulation effect have a significant influence on NGH conversion efficiency, and the influence of interaction between these three factors were not obvious. Possibly most important, we clarified an optimum stimulation effect for higher NGH conversion efficiency under different accumulation conditions, especially in low-permeability and high-saturation, which corresponding stimulation effect were different.

A twin prime numbers are two prime numbers which have the difference of 2 exactly. In other words, twin primes is a pair of prime that has a prime gap of two. Sometimes the term twin prime is used for a pair of twin primes; an alternative name for this is prime twin or prime pair. Up to date there is no any valid proof/disproof for twin prime conjecture. Through this research paper, my attempt is to provide a valid disproof for twin prime conjecture.

Distributional word vector representation orword embedding has become an essential ingredient in many natural language processing (NLP) tasks such as machine translation, document classification, information retrieval andquestion answering. Investigation of embedding model helps to reduce the feature space and improves textual semantic as well as syntactic relations.This paper presents three embedding techniques (such as Word2Vec, GloVe, and FastText) with different hyperparameters implemented on a Bengali corpusconsists of180 million words. The performance of the embedding techniques is evaluated with extrinsic and intrinsic ways. Extrinsic performance evaluated by text classification, which achieved a maximum of 96.48% accuracy. Intrinsic performance evaluatedby word similarity (e.g., semantic, syntactic and relatedness) and analogy tasks. The maximum Pearson (ˆr) correlation accuracy of 60.66% (Ssˆr) achieved for semantic similarities and 71.64% (Syˆr) for syntactic similarities whereas the relatedness obtained 79.80% (Rsˆr). The semantic word analogy tasks achieved 44.00% of accuracy while syntactic word analogy tasks obtained 36.00%

There is an increasing interest in revisiting plants for drug discovery proving scientifically their role as remedies. Pistacia lentiscus (PL) is a wild-growing shrub rich in terpenoids, which are pharmacological appealing. The more recurrent components in the oil are represented by α-pinene, terpinene, caryophyllene, limonene, and myrcene. High concentration of polyphenols enriches the extracts. PL-extracts showed in vitro and in animal model strong anti-inflammatory and anti-oxidative activities. The anti-inflammatory activity mainly occurs due to inhibition of NF-kB pathway or directly toward the proinflammatory cytokines, or arachidonic acid cascade against COX-2 and LOX. The antimicrobial activity of PL essential oil and extracts includes among others Staphylococcus aureus, Escherichia coli, periodontal bacteria and Candida sp.. In conclusion, the biological properties, and particularly the anti-inflammatory and anti-microbial capacity, propose PL as a new safe pharmaceutical agent.

Cyanobacteria are photosynthetic microorganisms that colonize diverse environments worldwide, ranging from ocean to freshwaters, soils, and extreme environments. Their adaptation capacities and the diversity of natural products (molecules, metabolites, or compounds) that they synthesize support the cyanobacterial success for the colonization of their respective ecological niches. Although cyanobacteria are well-known for their toxin production and their relative deleterious consequences, they also produce a large variety of molecules that exhibit beneficial properties with high potential for various fields of application (e.g., synthetic analog of the dolastatin 10 used against Hodgkin lymphoma). The present review specially focuses on the beneficial activities of cyanobacterial molecules described so far. Based on an analysis of 670 papers, it appears that more than 90 genera of cyanobacteria have been found to produce compounds with potential beneficial activities, most of them belonging to the orders Oscillatoriales, Nostocales Chroococcales, and Synechococcales. The rest of the cyanobacterial orders (i.e., Pleurocapsales, Chroococcidiopsales, and Gloeobacterales) remain poorly explored in terms of their molecular diversity and relative bioactivity. The diverse cyanobacterial molecules presenting beneficial bioactivities belong to 10 different chemical classes (alkaloids, depsipeptides, lipopeptides, macrolides/lactones, peptides, terpenes, polysaccharides, lipids, polyketides, and others) that exhibit 14 major kinds of bioactivity. However, no direct relation between the chemical class and the bioactivity of these molecules has been demonstrated. We further selected and specifically described 50 molecule families according to their specific bioactivities and their potential uses in pharmacology, cosmetology, agriculture, or other specific fields of interest. This up-to-date review takes advantage of the recent progresses in genome sequencing and biosynthetic pathway elucidation, and presents new perspectives for the rational discovery of new cyanobacterial metabolites with beneficial bioactivity.

Despite increased global interest in the impacts of natural disasters on tourism, less study executes exploring how tourism sensitivity is addressed at the destination level. Generating a link between tourism and natural disaster management is vital in places that rely heavily on tourism and are prone to natural hazards. Ranau, Sabah (Malaysia) is one of the disaster-prone tourists' destination area. Hence, this paper applies the case study of Ranau earthquake 2015 to explore tourism sensitivity towards natural disasters. A qualitative of in-depth interview is applied to acquire information needed from the Ranau tourism entrepreneurs and operators. To analyse the qualitative data, a thematic analysis is conducted. Overall findings show that tourism activity in Ranau are identified to be sensitive towards the 2015 earthquake with a significant percentage of sensitivity level on two elements. These elements are known as Source and Power. The Source element includes tourism products, size of business, development, and natural disasters management with a significant sensitivity compared to the Power element (social capital). This provides insight to the need of specific tourism system adaptation as response to the earthquake and considering the integration of natural disaster management into tourism development to enhance long term sustainability.

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.

Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative and antineoplastic activities. Recently, different studies have shown that flavonoid have the potential to inhibit BET bromodomains. Previous reports suggest that flavonoids are putative inhibitors of the ZA channel due to their orientation and interactions with P86, V87, L92, L94 and N140. Herein, a comprehensive characterization of the binding mode of the biflavonoid amentoflavone and fisetin is discussed. To this end, both compounds were docked with BRD4 using four docking programs. Results were post-processed with protein-ligand interaction fingerprints. To gain further insights into the binding mode of the two natural products, docking results were further analyzed with molecular dynamics. Results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as basis for scaffold optimization and further characterization of flavonoids as BET inhibitors.

One way to increase overall natural gas engine efficiency is to transform exhaust waste heat into useful energy by means of a bottoming cycle. Organic Rankine cycle (ORC) is a promising technology to convert medium and low grade waste heat into mechanical power and electricity. This paper presents an energy and exergy analysis of three ORC-Waste heat recovery configurations by using an intermediate thermal oil circuit: Simple ORC (SORC), ORC with Recuperator (RORC) and ORC with Double Pressure (DORC), and Cyclohexane, Toluene and Acetone have been proposed as working fluids. An energy and exergy thermodynamic model is proposed to evaluate each configuration performance, while available exhaust thermal energy variation under different engine loads was determined through an experimentally validated mathematical model. Additionally, the effect of evaportating pressure on net power output , absolute thermal efficiency increase, absolute specific fuel consumption decrease, overall energy conversion efficiency, and component exergy destruction is also investigated. Results evidence an improvement in operational performance for heat recovery through RORC with Toluene at an evaporation pressure of 3.4 MPa, achieving 146.25 kW of net power output, 11.58% of overall conversion efficiency, 28.4% of ORC thermal efficiency, and an specific fuel consumption reduction of 7.67% at a 1482 rpm engine speed, a 120.2 L/min natural gas Flow, 1.784 lambda, and 1758.77 kW mechanical engine power.

Bone is a dynamic tissue with the capacity of repair and regeneration in specific conditions. Nevertheless, due to the increased incidence of bone disorders, the need of bone grafts has been growing over the past decades and the development of an ideal bone graft with optimal properties remains a clinical challenge. This review addresses the bone properties (morphology, composition and their repair and regeneration capacity) and puts the main focus on the potential strategies for developing bone repair and regeneration materials. It describes the requirements for designing a suitable scaffold material, types of materials (polymers, ceramics and composites) and techniques to obtain the porous structures (additive manufacturing techniques/robocasting or derived from marine skeletons) for bone tissue engineering applications. The main objective of this review is to gather the knowledge on the materials and methods for the production of scaffolds for bone tissue engineering and highlighting the potential of natural porous structures such as marine skeletons as promising alternative bone graft substitute materials without any further mineralogical changes, or after partial or total transformation into calcium phosphate. The suitability of the marine-derived porous bone graft substitutes for the intended applications will be also discussed.

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.

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.

Ongoing COVID-19 Pandemic has resulted into massive damage to various platforms of global economy which has caused disruption to human livelihood. Natural Language Processing has been extensively used in different organizations to categorize sentiments, perform recommendation, summarizing information and topic modelling. This research aims to understand the non-medical impact of COVID-19 on global economy by leveraging the natural language processing methodology. This methodology comprises of text classification which includes topic modelling on unstructured COVID-19 media articles dataset provided by Anacode. Like other Natural Language Processing algorithms, Latent Dirichlet allocation (LDA) and Non-negative matrix factorization (NMF) has been proposed to classify the media articles dataset in order to analyze COVID-19 pandemic impacts in the different sectors of global economy. Model Accuracy was examined based on the coherence and perplexity score which came out to be 0.51 and -10.90 using LDA algorithm. Both the LDA and NMF algorithm identified similar prevalent topics that was impacted by COVID-19 pandemic in multiple sectors of economy. Through intertopic distance map visualization produced by LDA algorithm, it can be reciprocated that general industries which includes children schooling, parental care, and family gatherings had the major impact followed by business sector and the financial industry.

In order to assess the human exposure risks from the release of contaminants from water pipes made of polyvinyl chloride (PVC), experiments were carried out by subjecting the PVC pipe material to burning and leaching conditions followed by analysis of the emission and leachate samples. The emissions of burning pipes were analyzed by both infrared spectrometry and gas chromatography-mass spectrometry (GC-MS). The emission results indicate the presence of chlorinated components including chlorine dioxide, methyl chloride, methylene chloride, allyl chloride, vinyl chloride, ethyl chloride, 1-chlorobutane, tetrachloroethylene, chlorobenzene, and hydrogen chloride were detected in the emissions of burning PVC pipes. Furthermore, the concentrations of benzene, 1,3-butadiene, methyl methacrylate, carbon monoxide, acrolein, and formaldehyde were found at levels capable of affecting human health adversely. The analysis of PVC pipe leachates using GC-MS shows that there are 40-60 tentatively identified compounds, mostly long-chain hydrocarbons such as tetradecane, hexadecane, octadecane, and docosane, were released when the burned PVC materials were soaked in deionized water for one week. Quantitative analysis shows that 2-butoxyethanol, 2-ethyl-1-hexanol, and diethyl phthalate were found in the burned PVC polymer at the average levels of 2.7, 14.0, and 3.1 micrograms per gram (g/g) of pipe material. This study has significant implications for understanding the benzene contamination of drinking water in the aftermath of wildfires that burned polymer pipes in California.

Calcium (Ca) is an essential element constituting sedimentary carbonate in subducting sediments. Ca isotopic characteristics of subduction-related rocks could provide insight into the behavior and budget of carbonate and carbon cycles in subduction zones, due to the distinctive δ^44/40Ca ranges of sedimentary carbonate with respect to the mantle. Here, we studied the Ca isotopic compositions of arc magmas from the Northern Luzon arc (NLA), which are evolved from a depleted mantle metasomatized by slab-derived fluids and sediment melts. The δ^44/40Ca values range from 0.76 ± 0.04‰ to 1.01 ± 0.03‰ and cover the typical ranges for bulk silica earth (BSE, ~ 0.94‰) and fresh mid-ocean ridge basalt (MORB, ~ 0.83‰). The Ca isotopes of NLA volcanics are not dominantly determined by the effects of mantle partial melting or fractional crystallization, nor significantly modified by secondary alteration. Instead, the δ^44/40Ca values of NLA volcanics are controlled by the subduction-related metasomatism. The metasomatism by slab-derived fluids (mainly expelled from altered oceanic crust, AOC) dramatically elevated the contents of fluid-mobile elements (e.g., Ba and Pb) with respect to fluid-immobile elements (e.g., Ce). This process, however, rarely modified the Ca isotopes, possibly ascribed to the δ^44/40Ca similarity between AOC and the depleted mantle. The δ^44/40Ca values significantly correlated with subduction indicators (e.g., Sr-Nd isotopes, Ba/Nb, Ce/Pb, and Nb/La), demonstrating the Ca isotopes of NLA volcanics are mainly controlled by the metasomatism of sediment melts subducting from the South China Sea (SCS). Based on the thermal structures and chemical compositions of sediments subducting into global trenches, we propose that carbonate Ca isotopic signals can only be observed in the arcs with high sedimentary Ca fluxes and temperature-pressure conditions well beyond the solidus of H₂O-saturated sediment melting, e.g., NLA, Nicaragua, Guatemala, Colombia, Peru, South Chile, North Vanuatu, New Zealand, and Kermadec. The absence of such signals in other arcs suggests either limited sedimentary fluxes or much of the subducting sedimentary carbonate has been survived during plate subduction to enter the deep mantle.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

To sustain water-dependent economic and socio-ecological systems, natural capital and its interactions with other capitals is gaining attention, but a clear understanding of how to manage natural capital sustainably and how to make decisions relevant to water-related ecosystem services is yet to be achieved. In this study, we extended the framing of water-related ecosystem service flows as a cycle, integrating water quantity and quality and capturing the flows of ecosystem services (i.e., green phase) and ecosystem disservices (i.e., red phase), and connecting natural capital, built capital, and beneficiaries. We applied this framework to the Jiulong River watershed in China, using hydrological models to model water quantity and quality based on historical observations and experimental data. Our results showed that, during the green phase, the interactions of natural capital and built capital significantly improved water quality in downstream areas with higher flows. During the red phase, built capital reduced ecosystem disservices by ~10% while natural capital further reduced it by over one half. Our framework can provide information for natural capital management, eco-compensation, and pollutant management relevant to water-related ecosystem services.

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.

The sentiment of a word varies based on its context of usage: the words used around it and the part-of-speech it is used as. This paper proposes a technique to suggest the sentiment of a word by combining its part-of-speech and the semantic similarities of its co-occurrences with both context-specific and pre-trained embeddings to achieve powerful and fast results. A study was conducted across domains and sub-domains to measure variance of sentiment by switching domains and switching context within the same domain. Re-scoring a commonly used polarity lexicon showed that 10% of words changed scores while switching domains and 8% changed scores within domains while switching context. Part of Speech analysis on 65,353 commonly used sentiment lexicons showed that 81% of sentiment bearing (non-neutral) lexicons were of the tags NN (Common Noun), JJ (Adjective) or NNS (Proper Noun).

Formation of Fe- and Mg-rich smectite and zeolite under alkaline conditions is concerned as secondary minerals after alkaline alteration of bentonite in a repository of radioactive wastes. It might be crucial for safety assessment whether smectite will be formed or not as secondary minerals after alkaline alteration of bentonite. In present paper, Fe- and Mg-rich smectite which are currently interacting with hyperalkaline groundwater was found at Narra in Palawan, Philippines. Mineralogical and geochemical investigation was conducted to understand formation process of smectite and factors determined secondary mineral species. Our study revealed a certain amount of smectite may have been produced under hyperalkaline conditions, altered from amorphous or poorly crystalline material such as M-S-H and F-S-H. Key factor which decides smectite or zeolite as secondary minerals after alkaline alteration of bentonite might be whether nuclei of M-S-H and/or F-S-H will be formed or not. This might be decided by the presence of dissolved Mg2+ and Fe2+ in the system. Our suggested formation process of smectite under alkaline conditions is analogue with generally-accepted model of smectite formation that might have been occurred on early Mars.

Aiming to improve the flame retardancy performance of natural rubber (NR), we developed a novel flame retardant synergistic agent through grafting of MCM-41 to graphene oxide (GO)，named as GO-NH-MCM-41，as an assistant of intumescent flame retardants (IFR). The structure of GO-NH-MCM-41 was characterized by FTIR, TEM and SEM tests, which confirmed that a fine grafting had been applied between GO and MCM-41. The flame retardancy of NR/IFR/GO-NH-MCM-41 composites was evaluated by limited oxygen index (LOI), UL-94 and cone calorimeter test. The LOI value of NR/IFR/GO-NH-MCM-41 reached to 26.3%; the UL-94 ratings improved to V-0 rating. Moreover, the addition of GO-NH-MCM-41 obviously decreased the peak heat release rate (PHRR) and the total heat release (THR) of the natural rubber composites. And the addition of GO-NH-MCM-41 increased the thickness of char residue. The images of SEM indicated the char residue were more compact and continuous. The degradation of GO-NH-MCM-41 based NR composites completed with a mass loss of 35.57% at 600 ℃. The tensile strength and the elongation at break of NR/IFR/GO-NH-MCM-41 composites were 13.9 MPa and 496.7%, respectively. The results of rubber process analyzer (RPA) reached the maximum value, probably due to a better network of the fillers in the matrix.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer’s disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect possibly can increase over time, there is still a need for alternative treatments that will improve the cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed neuroprotective effect against amyloid-beta or energy-deprivation induced neurotoxicity, and increased the levels of brain derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase of BDNF in the brains of 21-months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

Kenya’s natural resource base has dwindled over years. The existence of many natural resource policies, some that are incompatible, has resulted in complex rangeland management regimes, giving rise to fragmented interventions and inadequate natural resource policies in relation to pastoralism. The majority of pastoral land resources held under a controlled access system by the national government that regulates management and utilization of resources. Pastoralists in Kenya have become among the most marginalized and disadvantaged minority groups. This is due to limited or under investment by government and other actors, and access to, or ownership of land, water and other resources, which are fundamental for pastoralism. This study examines significant obstacles for the establishment of a more inclusive ‘governance’ approach to natural resource management in northern Kenya, that characterize the customary Boran knowledge such as Deedha’s (traditional grazing unit) and formal institutions and seeks to address the tension between them through a legal framework that accommodates both. The results of the study established existence of the traditional structures and institutions in governance of natural resources within the pastoralist communities in Isiolo County. These institutions have evolved to cope with changing dynamics brought about by formalization of the natural resources governance. The resulted showed that various formal institutions from national government agencies to county government department were involved in management of the natural resources. However, the study established various operational divergence and links between informal and formal institutions involved in natural resources management. The study concluded that both informal institution such as Deedha and formal institutions constituted by national and county government did governance of natural resources among pastoralist communities in Isiolo County. The communities however have more trust in the informal structures and institutions because of their flexibility and inclusiveness.

Social media gives researchers an invaluable opportunity to gain insight into different facets of human life.Researchers put a great emphasis on categorizing the socioeconomic status (SES) of individuals to help predict various findings of interest. Forum uses, hashtags and so on are common tools of conversations grouping. On the other hand, crowdsourcing is a concept that involves gathering intelligence to group online user community based on common interest. This paper provides a mechanism to look at writings on social media and group them based on their academic background. We build upon earlier work where we analyzed online forum posts from various geographical regions in the USA and Canada and characterized the readability scores of such users. Specifically, we collected 1000 tweets from the members of the US Senate and computed the Flesch-Kincaid readability score for the Senators. Comparing the Senators’ tweets to the ones from average citizens, we note the following. 1) US Senators’ readability based on their tweets rate is much higher affirming the gap between the academic performance of US Senators and their average citizen, and 2) the immense difference among average citizen’s score compared to those of US Senators is attributed to the wide spectrum of academic attainment.

Computational Fluid Dynamics (CFD) is utilized to study entropy generation for the rarefied steady state laminar 2-D flow of air-Al2O3 nanofluid in square cavity equipped with two solid fins at the hot wall. Such flows are of great importance in industrial applications, such cooling of the electronic equipment’s and nuclear reactors. In the current study, effects of Knudsen number (Kn), Rayleigh number (Ra) and the nano solid particles volume fraction (ϕ) on the entropy generation are investigated. The values of parameters considered in this work are as follows: 0≤Kn≤0.1, 〖10〗^3≤Ra≤〖10〗^6,0≤ϕ≤0.2. Length of the fins (LF) is considered to be fixed and equals to 0.5 m, whereas the location of the fins with respect to the lower wall (HF) is set to 0.25 and 0.75 m. Simulations demonstrate that there is an inverse direct effect of Kn on the entropy generation. Moreover, it is found that when Ra is less than 104, the entropy generation, due to the flow, increases as ϕ increases. In addition, the entropy generation due to the flow will decrease at Ra greater than 104 as ϕ increases. Moreover, the entropy generation due to heat will increase as both the ϕ and Ra increase. In addition, a correlation model of the total entropy generation as a function of all of the investigated parameters in this study is proposed. Finally, an optimization technique is adapted to find out the conditions at which the total entropy generation is minimized

The current energy policy recommends the idea of energy efficiency over fossil energy as a primary matter for the coming years. The kingdom of Morocco requires restructuring of its power equipment by increasing the percentage of renewable energy supplies, optimizing their systems and power storage. Therefore, increasing energy efficiency is an as important obligation as reducing the overall energy consumption. The purpose of this research is to present the energy transition in Morocco towards renewable energies and to assess the diversity of available marine natural resources. Recent research in conversion of ocean thermal energy, wave energy, tidal energy, offshore wind energy, and osmotic energy into power supply has started to encourage different technologies. This research has led to commercial deployment in some cases such as our 550 km long Mediterranean coast and 3000 km long Atlantic. This does not only result in fossil energies independency but also provides advantages like less cost and no pollution.

The deep neural network - BERT model (Bidirectional Encoder Representations from Transformers) and the stocks cumulative abnormal return is used in this article to analyze the sentiment of financial texts. The proposed approach, unlike those used so far, does not require the creation of dictionaries, takes into account the broad context of words and their meaning in financial texts, eliminates the problem of ambiguity of words in various contexts, does not require manual labelling of data and is free from the subjective assessment of the researcher. The sentiment of financial texts in the meaning presented in this paper is directly related to the market reaction to the information contained in these texts. For texts belonging to one of the two classes (positive or negative) with the highest probability the BERT model gives the results of predictions with a precision level of 62.38% for the positive class and 55% for the negative class. The results at this level can be used in event study, market efficiency research, investment strategy development or support of investment analysts using fundamental analysis.

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

Streptomyces, being one of the most promising genera due to its ability to synthesize a variety of bioactive secondary metabolites of pharmaceutical interest, here studied in relation to its genomic and metabolomic potential. Coinciding with the increase in sequenced data, mining of bacterial genomes for biosynthetic gene clusters (BGCs) has become a routine component of natural product discovery. Herein, we describe the isolation and characterization of a Streptomyces tendae VITAKN with quorum sensing inhibitory activity (QSI) that was isolated from southern coastal parts of India. The nearly complete genome consists of 8,621,231bp with a GC content of 72.2%. Utilizing the BiG-SCAPE-CORASON platform, a sequence similarity network predicted from this strain was evaluated through sequence similarity analysis with the MIBiG database and existing 3,365 BGCs predicted by antiSMASH analysis of publicly available complete Streptomyces genomes. Crude extract analyzed on LC-HRMS/MS and Global Natural Product Social Molecular Networking (GNPS) online workflow using dereplication resulted in the identification of cyclic dipeptides (2,5-diketopiperazines, DKPs) in the extract, which are known to possess QSI activity. Our results highlight the potential use of genomic mining coupled with LC-HRMS/MS and bionformatic tools (GNPS) as a potent approach for metabolome studies in discovering novel QSI lead compounds. This study also provides the biosynthetic diversity of these BGCs and an assessment of the predicted chemical space yet to be discovered.

We discuss further details on the concepts of “drug-likeness”, “lead-likeness”, and “natural product-likeness”. The discussion will first focus on natural products as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semi-synthetic compounds and FDA-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. We end up by presenting a tool for measuring “natural product-likeness” of compounds and a brief presentation of machine learning approaches and a binary quantitative structure-activity relationship (QSAR) for classifying drugs from non-drugs and natural compounds from non-natural ones, respectively.

Crowdsourced Data (CSD) generated by citizens is becoming more popular as its potential utilisation in many applications is increasing due to its currency and availability. However, the quality of CSD, including its relevance, is often questioned as the data is not generated by professionals nor follows standard data collection procedures. The quality of CSD can be assessed according to a range of attributes including its relevance. Information relevance has been explored through using in Geographic Information Retrieval (GIR) techniques to identify relevant information. This research tested a relevance assessment approach for CSD by adapting relevance assessment techniques available in the GIR domain. The thematic and geographic relevance were assessed using the Term Frequency-Inverse Document Frequency (TF-IDF), Vector Space Model (VSM) and Natural Language Processing (NLP) techniques. The thematic and geographic specificities of the queries were calculated as 0.44 and 0.67 respectively, which indicates the queries used were more geographically specific than thematically specific. The Spearman's rho value of 0.62 indicated that the final ranked relevance lists showed reasonable agreement with a manually classified list and confirmed the potential of the approach for CSD relevance assessment for other possible crowdsourced data analysis.

Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct N^ɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed AGEs are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using MG-H1 as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

Development of supervised AI algorithms requires a large amount of labeled images. Image labelling is both time-consuming and expensive. Therefore, we explored the value of e-learning derived annotations for AI algorithm development in medical imaging. Methods We have developed an e-learning platform that involves image-based single click labelling as part of the educational learning process. Ten radiology residents, as part of their residency training, trained the recognition of pneumothorax on 1161 chest X-rays in posterior-anterior projection. Using this data, multiple AI algorithms for detecting pneumothorax were developed. Classification and localization performance of the models was tested on an independent internal testing dataset and on the public NIH ChestX-ray14 dataset. Results The AI models F1 scores on the internal and the NIH dataset were 0.87 and 0.44, respectively. Sensitivity was 0.85 and 0.80 for classification and specificity 0.96 and 0.48 for classification. F1 scores were 0.72 and 0.66, sensitivity 0.72 and 0.72. False positive rate was 0.36 and 0.32 for localisation. Conclusion Our results demonstrated that e-learning derived annotations are a valuable data source for algorithm development. Further work is needed to include additional parameters such as user performance, consensus of diagnosis, and quality control in the development pipeline.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

The recent revival of the study of organic natural products as renewable sources of medicinal drugs, cosmetics, dyes, and materials motivated the creation of general-purpose structural databases. Dereplication, the efficient identification of already reported compounds, relies on the grouping of structural, taxonomic and spectroscopic databases that focus on a particular taxon (species, genus, family, order…). A set of freely available python scripts, CNMRPredict, is proposed for the quick supplementation of taxon-oriented search results from the LOTUS database (lotus.naturalproducts.net) with predicted carbon-13 NMR data from the ACD/Labs (acdlabs.com) CNMR predictor and DB software to provide easily searchable databases. The database construction process is illustrated using Brassica rapa as taxon example.

Patient-derived xenograft (PDX) models are created by engraftment of patients’ tumor tissues into immunocompetent mice. Since PDX model keep the characteristics of primary patient’s tumor such as gene expression profiles and drug sensitivity, it now becomes most reliable in vivo human cancer model. The engraftment rate are increased with the introduction of NOD/Scid based immunocompromised mice, especially, NK cell defective NOD strains such as NOD/Scid/IL2Rγnu (NOG/ NSG) mice and NOD/Scid/Jak3null (NOJ) mice. Success ratio differs from the origin of tumor: Gastrointestinal tumors tend to higher success rate and breast cancer is lower. Subcutaneous transplantation is most popular method to establish PDX, but some tumor needs orthotropic or renal capsule transplantation, and human hormone treatment is needed to establish hormone dependent cancers such as prostate and breast cancer. PDX library with patient’s clinical data, gene-expression patterns, mutational status, drug responsiveness and tumor architecture will be the powerful tool for developing specific biomarker and novel individualized therapy and establishing precision cancer medicine.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

Gastric cancer, also known as stomach cancer, is a cancer which develops from the lining of the stomach. Accumulated evidences and epidemiological studies have been indicated that natural products play an important role in gastric cancer prevention and treatment, although its mechanism of action did not elucidate yet. Particularly, experimental studies have been showed that natural products displayed a protective effect against gastric cancer via numerous molecular mechanisms such as suppression of cell metastasis, anti-angiogenesis, inhibition of cell proliferation, induction of apoptosis, and modulation of autophagy. Although chemotherapy remains the standard treatment for advanced gastric cancer along with surgery, radiation therapy, hormone therapy and immunotherapy, but its adverse side effects including neutropenia, stomatitis, mucositis, diarrhea, nausea, and emesis are well documented. Additionally, intake of naturally occurring phytochemicals could increase the efficacy of gastric chemotherapy and chemotherapeutics resistance. However, natural product structural stability and powerful bioactivity are important to develop novel treatments for gastric cancer that may minimize such adverse effects. Therefore, the purpose of this review is to summarize the potential therapeutic effects of natural products on prevention and treatment of gastric cancer with intensive molecular mechanisms of action, bioavailability, and safety efficacy.

Fusarium graminearum is a dangerous pathogen of the cereals producing mycotoxins (trichothecene and zearalenone) harmful for human and animal health. There were evaluated sixteen winter wheat varieties for their response in conditions of natural infection with F. graminearum in the epidemic year 2019, being well known that accumulation of mycotoxins (DON, ZON and T-2) is induced by different biotic and abiotic factors. Field plot was organized in Latin rectangle randomized with three replicates. For all evaluated wheat varieties were collected field data (incidence, severity and infection degree of the fungus F. graminearum) and laboratory data (mycotoxins concentration in grains) that have been processed using the software JASP (Version 0.14) for descriptive statistics, and exploratory factor analysis (EFA). Microsoft Excel 2019 was used to calculate Pearson’s correlation coefficients. The results showed negative corelation between plants’ density and F. graminearum attack frequency. Positive correlations were found between DON and T-2 and between DON and fungus attack intensity. This work highlights that during a F. graminearum epidemic year some of the most influential factors in the contamination with harmful mycotoxins (DON, ZON and T-2) are: plants density, frequency of the attack on ear, diseased ears and attack intensity on ears.

This research was a study of the effect of addition linear alkylbenzene sulfonates (LAS), NaHCO3, and NaCl and pasteurization on the preservation of natural rubber (NR). The samples were collected from rubber plantations of Chiang Rai province which were added with three surfactants in samples already. Physical and chemical properties were evaluated using pH, deterioration, viscosity, color, and odor. Then, the samples were stored at 28-30°C periods times of 0, 15, 30, 45, and 60 days. The experiment found that the color, viscosity, odor, and texture of NR samples were not spoiled after being preserved for 30 days but after 45 and 60 days found some coagulation of NR. In the case of non-preserved NR was found that spoiled NR in every period time range of 15-60 days. The pH testing found that increasing period times affect decreased pH value and increased viscosity due to salt of sulfate, carbonate, chloride, and thermal treatment of pasteurization which kill microorganisms and evaporated water. It concluded that the reagents were the process of cosurfactants with heat and frozen for increased effectiveness of anti-acid-producing bacteria and can use as short and long-term preservation of NR under the planting area condition of Thailand.

Myxobacteria represent a viable source of chemically diverse and biologically active secondary metabolites. The myxochelins are a well-studied family of catecholate-type siderophores produced by various myxobacterial strains. Here, we report the discovery, isolation and structure elucidation of three new myxochelins N1–N3 from the terrestrial myxobacterium Corallococcus sp. MCy9049, featuring an unusual nicotinic acid moiety. Precursor-directed biosynthesis (PDB) experiments and total synthesis were performed in order to confirm structures, improve access to pure compounds for bioactivity testing and to devise a biosynthesis proposal. The combined evaluation of metabolome and genome data covering myxobacteria supports the notion that the new myxochelin congeners reported here are in fact frequent side products of the known myxochelin A biosynthetic pathway in myxobacteria.

Beer is a fermented beverage with a history as old as human civilization and its productive process has been spread all around the world becoming unique in every country and iconic of entire populations. Ales and lagers are by far the most common beers; however, the combination of raw materials, manufacture techniques and aroma profiles are almost infinite, so it is not surprising to notice that there is a large amount of different beer styles, each of them with unique characteristics. Nowadays, diversification is becoming increasingly important in the brewing market and the brewers are continuously interested in improving and extending the already wide range of products, especially in craft brewery. One of the major components that can have a deep impact on the final product is yeast, since it is able to convert carbohydrates in wort, especially maltose and maltotriose, into ethanol, carbon dioxide and other minor aroma-active compounds. Saccharomyces cerevisiae (top‐fermenting yeasts used to produce ales) and Saccharomyces pastorianus (cryotolerant bottom‐fermenting hybrids between S. cerevisiae and Saccharomyces eubayanus responsible for the fermentation of lagers) are most used in breweries. However, an increasing number of different yeast starter cultures are commercially available, to improve the production efficiency also at relative low temperatures and to obtain desirable and diversified aroma profiles avoiding undesired compounds. Four main genetic engineering-free trends are becoming popular in craft brewing yeast development: 1) the research for novel reservoirs as source of new performant S. cerevisiae yeasts; 2) the creation of synthetic hybrids between S. cerevisiae and Saccharomyces non-cerevisiae in order to mimic lager yeasts by expanding their genetic background; 3) the exploitation of evolutionary engineering approaches; 4) the usage of non-Saccharomyces yeasts either in co-coculture or in sequential fermentation with S. cerevisiae. In the present work we summarized pro and contra of these approaches and provided an overview on the most recent advances on how brewing yeast genome evolved and domestication took place. Finally, we delineated how the correlations maps between genotypes and relevant brewing phenotypes can assist and further improve the search for novel craft beer starter yeasts.

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naïve mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, introduction of genes encoding immunomodulatory functions into a candidate LAIV that can serve as natural adjuvants to improve overall vaccine safety and efficacy.

Recommender systems have been applied in a wide range of domains such as e-commerce, media, banking, and utilities. This kind of system provides personalized suggestions based on large amounts of data in order to increase user satisfaction. These suggestions help client select products, while organizations can increase the consumption of a product. In the case of social data, sentiment analysis can help gain better understanding of a user’s attitudes, opinions and emotions, which is beneficial to integrate in recommender systems for achieving higher recommendation reliability. On the one hand, this information can be used to complement explicit ratings given to products by users. On the other hand, sentiment analysis of items that can be derived from online news services, blogs, social media or even from the recommender systems themselves is seen as capable of providing better recommendations to users. In this study, we present and evaluate a recommendation approach that integrates sentiment analysis into collaborative filtering methods. The recommender system proposal is based on an adaptive architecture, which includes improved techniques for feature extraction and deep learning models based on sentiment analysis. The results of the empirical study performed with two popular datasets show that sentiment–based deep learning models and collaborative filtering methods can significantly improve the recommender system’s performance.

The Loess Plateau is an important region for vegetation restoration in China, however, changes in soil organic carbon (SOC), soil nutrients, and stoichiometry after restoration in this vulnerable ecoregion are not well understood. Typical restoration types, including orchardland (OL), grassland (GL), shrubland (SL), and forestland (FL) were chosen to examine changes in the stocks and stoichiometry of SOC, soil total nitrogen (TN), and soil total phosphorus (TP) at different soil depths and recovery times. Results showed that SOC stocks first increased and then stabilized in OL, GL, and SL at 0–30 cm depth, while in FL, stocks gradually increased. Soil TN stocks first increased and then decreased in OL, SL, and FL with vegetation age at 0–30 cm depth, while soil TP stocks showed little variation between restoration types. In the later stages of restoration, the stocks of SOC and soil TN at 0–30 cm soil depth were still lower than those in natural grassland (NG) and natural forest (NF). The overall C:N, C:P, and N:P ratios increased with vegetation age. Additionally, the SOC, soil TN and soil TP stocks, and C:N, C:P, and N:P ratios decreased with soil depth. The FL had the highest rate of change in SOC and soil TN stocks, at 0-10 cm soil depth. These results indicate a complex response of SOC, soil TN, and soil TP stocks and stoichiometry to vegetation restoration, which could have important implications for understanding C, N, and P changes and nutrient limitations after vegetation restoration.

The violation of privacy, others people or personal, is a very current problem, which concerns not only on the web but also in private life. In the years 1990 it was expected that nowadays, that any routine operation was carried out "manually", and it would be performed through mobile phones or personal computers. The problem pertains the distribution network that allows to share and bring together information and as result the network becomes unsafe, if subjected to attacks. Nowaday we put personal information on web because otherwise we are seen as “weak”. This work aims to measure and analyze how much information are shared by users of a pre-established social network and it is carried out through a set of algorithms techniques of machine learning.

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.

The dominance of social media has added to the channels of bullying to perpetrators. Unfortunately, cyberbullying (CB) is the most prevalent phenomenon in today’s cyber world and is a severe threat to the mental and physical health of citizens. This opens the need to develop a robust system to prevent bullying content from online forums, blogs, and social media platforms to manage the impact in our society. Several machine learning (ML) algorithms have been proposed for this purpose. However, their performances are not consistent due to high class imbalance issue and generalisation. In recent years, large language models (LLM) like BERT and RoBERTa have achieved state of the art (SOTA) results in several natural language processing (NLP) tasks. Unfortunately, the LLMs have not been applied extensively. In our paper, we explored the use of these models for cyberbullying (CB) detection. We have prepared a new dataset (D2) from existing studies (Formspring and Twitter). Our experimental results for dataset D1 and D2 showed RoBERTa outperformed other models.

Numerous goods and services are now offered through online platforms due to the recent growth of online transactions like e-commerce. Users have trouble locating the product that best suits them from the numerous products available in online shopping. Many studies in deep learning-based recommender systems (RSs) have focused on the intricate relationships between the attributes of users and items. Deep learning techniques have used consumer or item-related traits to improve the quality of personalized recommender systems in many areas, such as tourism, news, and e-commerce. Various companies, primarily e-commerce, utilize sentiment analysis to enhance product quality and effectively navigate today's business environment. Customer feedback regarding a product is gathered through sentiment analysis, which uses contextual data to split it into separate polarities. The explosive rise of the e-commerce industry has resulted in a large body of literature on e-commerce from different perspectives. Researchers have made an effort to categorize the recommended future possibilities for e-commerce study as the field has grown. There are several challenges in e-commerce, such as fake reviews, frequency of user reviews, advertisement click fraud, and code-mixing. In this review, we introduce an overview of the preliminary design for e-commerce. Second, the concept of deep learning, e-commerce, and sentiment analysis are discussed. Third, we represent different versions of the commercial dataset. Finally, we explain various difficulties facing RS and future research directions.

Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with myeloid-derived suppressor cells (MDSCs) in tumor microenvironments regulates cancer progression. Immunodeficient mice lacking T cells are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The xenograft tumor microenvironment, comprising human cancer and mouse host cells, exhibits more complex bidirectional signaling and function than a syngeneic tumor microenvironment. Here human and mouse colorectal cancer cells were transplanted into nude mice to elucidate differences in macrophage, DC, and MDSC functions in human xenograft and mouse allograft tumor models. Plasma interferon-γ and interleukin-18 concentrations in the former model after intraperitoneal lipopolysaccharide (LPS) administration were significantly higher than those in the latter model and non-transplanted control group. Splenic MHC class I, II, and CD80 expression increased in CD11b+ and MDSC populations after LPS administration in only the xenograft tumor model. The number of CD80- and MRC1-expressing cells decreased upon LPS administration in only the xenograft tumor. These results suggxest that macrophages and DCs function normally in xenograft tumor models, whereas their functions in response to LPS administration vary in allograft tumor models.

Software engineers from all over the world solve independently a lot of similar problems. In this condition the problem of code or even better architecture reusing becomes an issue of the day. In this paper two phase approach to determining the functional and structural likenesses of software projects is proposed. This approach combines two methods of artificial intelligence: natural language processing techniques with a novel method for comparing software projects based on ontological representation of their architecture automatically obtained from the projects source code. Additionally several similarity metrics are proposed to estimate similarity between projects.

Around the World, the number of compound databases of natural products in the public domain is rising. This is in line with the increasing synergistic combination of natural product research and chemoinformatics. Towards this global endeavor, countries in Latin America are assembling, curating, and analyzing the contents and diversity of natural products available in their geographical regions. In this manuscript we collect and analyze the efforts that countries in Latin America have made so far to build natural product databases. We further encourage the scientific community in particular in Latin America, to continue their efforts to building quality natural product databases and, whenever possible, to make them publicly accessible. It is proposed that all compound collections could be assembled into a unified resource called LANaPD: Latin America Natural Products Database. Opportunities and challenges to build, distribute, and maintain LANaPD are also discussed

Documenting cultural heritage by using artificial intelligence (AI) is crucial for preserving the memory of the past and a key point for future knowledge. However, modern AI technologies make use of statistical learners that lead to self-empiricist logic, which, unlike human minds, use learned non-symbolic representations. Nevertheless, it seems that it is not the right way to progress in AI. If we want to rely on AI for these tasks, it is essential to understand what lies behind these models. Among the ways to discover AI there are the senses and the intellect. We could consider AI as an intelligence. Intelligence has an essence, but we do not know whether it can be considered “something” or “someone”. Important issues in the analysis of AI concern the structure of symbols -operations with which the intellectual solution is carried out- and the search for strategic reference points, aspiring to create models with human-like intelligence. For many years, humans, seeing language as innate, have carried out symbolic theories. Everything seems to have skipped with the advent of Machine Learning. In this paper, after a long analysis of history, the rule-based and the learning-based vision, we propose KERMIT as a unit of investigation for a possible meeting point between the different learning theories. Finally, we propose a new vision of knowledge in AI models based on a combination of rules, learning and human knowledge.

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.

The incidence of gastrointestinal diseases (cancer in particular) has increased progressively with considerable morbidity, mortality, and a high economic impact on the healthcare system. Dietary intake of natural bioactive phytochemicals showed to have cancer-preventing and therapeutic effects. This includes the cruciferous vegetable derivative phenethyl isothiocyanate (PEITC), a bioactive compound from watercress. PEITC antioxidant, anti-inflammatory and anti-cancer properties are of particular importance. This review summarizes the current knowledge on the role of PEITC as a potential natural nutraceutical or an adjuvant against oxidative/inflammatory-related disorders in the gastrointestinal tract. We also discuss the safe and recommended dose of PEITC. Besides, we establish a framework to guide the research and development of sustainable methodologies for obtaining and stabilizing this natural nutraceutical for industrial use. This is a topic that still needs more scientific development, but with the potential to lead to a viable strategy in the prevention of cancer and other associated diseases of the gastrointestinal tract.

Acquired Immunodeficiency Syndrome (AIDS) which is chiefly originated by a retrovirus named Human Immunodeficiency Virus (HIV), has influenced about 70 million populations worldwide. Even though several advancements have been invented in the field of antiretroviral combination therapy, still HIV has become the dominant reason for death in South Africa, for example. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. In the present day, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate the drugs obtained from natural plants as well as the synthetic derivatives that have been derived from the natural compounds by various chemical reactions. Several plants such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity showing more potent anti-HIV activity along with their structures, SARs & important key findings.

The main restriction of the Semantic Web is the difficult of the SPARQL language, that is necessary to extract information from the Knowledge Representation also known as ontology. Making the Semantic Web accessible for people who do not know SPARQL, is essential the use of friendlier interfaces and a good alternative is Natural Language. This paper shows the implementation of a friendly prototype interface to query and retrieve, by voice, information from website building with the Semantic Web tools. In that way, the end users avoid the complicated SPARQL language. To achieve this, the interface recognizes a speech query and converts it into text, it processes the text through a java program and identifies keywords, generates a SPARQL query, extracts the information from the website and read it in voice, for the user. In our work Google Cloud Speech API makes Speech-to-Text conversions and Text-to Speech conversions are made with SVOX Pico. As results, we have measured three variables: The success rate in queries, the response time of query and a usability survey. The values of the variables allows the evaluation of our prototype. Finally the interface proposed provides us a new approach in the problem, using the Cloud like a Service, reducing barriers of access to the Semantic Web for people without technical knowledge of Semantic Web technologies.

A global revolution in information and communication technologies (ICT) has occurred over the past few decades, emerging first in industrialized countries and then in developing countries. While researchers have examined many facets of the ICT revolution, relatively little work has systematically examined the degree to which ICT has reduced natural disaster vulnerability. In this article we use cross-country data over the 1980-2013 period to estimate the relationship between newly-emerging cell phone access/use and disaster-induced fatalities. Our estimates suggest that a one-standard-deviation increase in cell phone usage reduces disaster fatalities by nearly one half. The estimated effect increases to almost three quarters for geologic events where people are typically afflicted without warning. The largest marginal benefit from cell phones in terms of saving lives come from events where there is typically no warning, thus many are caught by surprise; cell phones are used to call for help and coordinate assistance.

Abstract: The promotion of sustainable packaging is part of the European Green Deal and plays a key role in the EU’s social and political strategy. One option is the use of renewable resources and biomass waste as raw materials for polymer production. Lignocellulose biomass from annual and perennial industrial crops and agricultural residues are a major source of polysaccharides, proteins, and lignin, and can also be used to obtain plant-based extracts and essential oils. Therefore, these biomasses are considered as potential substitute for fossil-based resources. Here, the status quo of bio-based polymers is discussed and evaluated in terms of properties related to packaging applications such as gas and water vapor permeability as well as mechanical properties. So far, their practical use is still restricted due to lower performance in fundamental packaging functions that directly influence food quality and safety, the length of shelf life and thus the amount of food waste. Besides bio-based polymers, this review focuses on plant extracts as active packaging agents. Incorporating extracts of herbs, flowers, trees, and their fruits is inevitable to achieve desired material properties that are capable to prolong the food shelf life. Finally, the adoption potential of packaging based on polymers from renewable resources is discussed from a bioeconomy perspective.

In this review, we discuss novel natural products discovered within the last decade that are reported to have antifungal activity against pathogenic species. Nearly a hundred natural products were identified that originate from bacteria, alga, fungi, sponges and plants. Fungi were the most prolific source of antifungal compounds discovered during the period of review. The structural diversity of these antifungal leads encompasses all the major classes of natural products including polyketides, shikimate metabolites, terpenoids, alkaloids and peptides.

The concept of green energy is now at the forefront of development discourse, with the United Nations Sustainable Development Goals (SDGs) 7, 11, and 12 all aimed at promoting green energy consumption to combat the three planetary crises: climate change, biodiversity loss, and pollution. Similarly, issues regarding Africa’s natural resource curse have caused a stir in the growth and development literature for some time now and there is no sign that it will die out. This study, the first of its kind, simultaneously assesses the impact of green energy consumption and Africa’s natural resources rents on economic growth by applying the Feasible Generalized Least Square (FGLS) estimator and the dynamic panel models of the Pooled Mean Group (PMG) and Mean Group (MG) estimators on data from 1990 to 2020 for 24 selected African countries. The results show that green energy consumption has a short-run growth-limiting effect and a long-run growth-enhancing effect in Africa. The study also found evidence of the natural resource curse phenomenon in Africa. The study, therefore, calls for the advancement and usage of green energy for both domestic and industrial production in Africa. The study further calls for a revamp in the global tax policy to curb illicit financial activities and strengthening institutional quality for transparency and accountability in the entire value chain of natural resource management in Africa.

Through the half-unit circle area computation using the integration of the corresponding curve power series representation, we deduce a slow converging positive infinite series to $\pi$. However, by studying the remainder of that series we establish sufficiently close inequalities with equivalent lower and upper bound terms allowing us to estimate, more precisely, how the series approaches $\pi$. We use the obtained inequalities to compute up to four-digit denominator, what are in this sense, the best rational numbers that can replace $\pi$. It turns out that the well-known convergents of the continued fraction of $\pi$, $22/7$ and $355/113$ called, respectively, Yuel\"{u} and Mil\"{u} in China are the only ones found. Thus we apply a similar process to find rational estimations to $\pi+e$ where $e$ is taken as the power series of the exponential function evaluated at $1$. For rational numbers with denominators less than $2000$, the convergent $920/157$ of the continued fraction of $\pi+e$ turns out to be the only rational number of this type.

This review examines the categorization of Essentially Derived Varieties (EDV) introduced in the 1991 revision of the Convention of the Union internationale pour la protection des obtentions végétales (UPOV). Challenges in the implementation of the concept and progress made on a crop-by-crop basis to provide greater clarity and more efficient implementation are reviewed. The current approach to EDV remains valid provided i) clarity on thresholds can be achieved including through resource intensive research on an individual crop species basis and ii) that threshold clarity does not lead to perverse incentives to avoid detection of essential derivation. However, technological advances leading to new varieties resulting from the simultaneous introduction or change in expression of more than “a few” genes will so challenge the concept to require a new Convention. Revision could include deletion of the concept of essential derivation and revision on a crop-by-crop basis of the breeder exception. Countries that allow utility patents for individual plant varieties per se should consider removing that possibility unless plant breeders utilize those encouragements for risk taking and investment to broaden the germplasm base upon which the long-term sustainability of plant breeding resides.

Fire behavior of natural rubber latex foam under different thickness conditions(d=1,2and 5cm)were explored though a little of experiments by using the self-built small scale experimental platform. It can be shown that the flame spread law of thermally thin and thermally thickness are different. Natural rubber latex foam with thickness of 2cm show higher fire risk, which value of flame spread rate, maximum flame height, maximum mass loss rate and maximum temperature is 0.00293m/s, 851.875mm, 1.83g/s, 948K,repectively.That may because the thickness of residue formed of thermally thick materials is larger than the thin one, obstructing the contact of the natural rubber latex foam with fresh air .In addition, a special phenomenon is noticed that during the second stage, the bottom unburned zone located in the four edges(thermally thin material) and middle player(thermally thick material).

One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists either in blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-Epigallocatechin-3-gallate, Quercetin, and Rosmarinic acid) with the amyloid-β(1-40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulate the double-layered structure stability.

Effective biomarkers are essential to the early diagnosis of non-small cell lung cancer (NSCLC). Herein, a retrospective study of 49 newly diagnosed and recurrent NSCLC patients, 31 patients with benign pulmonary disease and 24 healthy volunteers was conducted, to evaluate the diagnostic value of circulating rare cells for NSCLC. The expression of circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in peripheral blood were measured by subtraction enrichment-immunostaining-fluorescence in situ hybridization (SE-iFISH). The level of CTCs (P＜0.001) and CTECs (P＜0.001) was significantly higher in NSCLC group than that in benign pulmonary disease group. The proportion of small CTCs (P＜0.001) and CTECs (P＜0.0001) significantly increased from benign lung disease individuals to NSCLC patients. The AUC of ROC curves of total CTCs and CTECs were 0.815 (95%CI: 0.722~0.907), 0.739 (95%CI: 0.618~0.860), respectively. The cut-off values for discriminating NSCLC with benign lung disease patients were total CTCs 11.5 units/6ml and total CTECs 10.5 units/6ml, with sensitivity and specificity being 67.3% and 83.9%, 77.6% and 77.4%, respectively. When CTCs and CTECs were combined, predictive value significantly increased to 82.6% as measured by the area under the curve. Small CTCs and triploid CTCs had high positive predictive value (PPV) and positive likelihood ratio (LR+) of the diagnosis of NSCLC in early stage. CTCs and CTECs can not only be used as new biomarkers for the diagnosis of NSCLC, but can also improve diagnostic performance of the early stage NSCLC. Moreover, the combined examination of CTCs and CTECs is be superior to the single.

Recently natural gas (NG) global market attracted much attention in case it is cleaner than oil, and simultaneously in most regions is cheaper than renewable energy sources. However, price fluctuations, environmental concerns, technological development, emerging unconventional resources, energy security challenges, and shipment are some of the forces that made the NG market more dynamic and complex. From a policy-making perspective, it is vital to uncover demand-side future trends. This paper proposed an intelligent forecasting model to forecast NG global demand, however investigating a multi-dimensional purified input vector. The model starts with a data mining (DM) step to purify input features, identify the best time lags, and to pre-process selected input vector. Then a hybrid artificial neural network (ANN) which equipped with genetic optimizer is applied to set up ANN’s characteristics. Among 13 available input features, six features (e.g. Alternative and Nuclear Energy, CO2 Emissions, GDP per Capita, Urban Population, Natural Gas Production, Oil Consumption) selected as the most critical feature via the DM step. Then, the hybrid prediction model is designed to extrapolate the consumption of future trends. The proposed model overcomes competitive models refer to different error based evaluation statistics. Besides, as the model proposed the best input feature set, results compared to the model which used the raw input set, with no DM purification process.

The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will discuss about the biogenesis and function of small non-coding RNAs derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs), and their potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences—because of their overabundance—from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because we could not believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit the Mpro at low micromolar concentrations. It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease's catalytic Cys145 site. Selected potent molecules also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for COVID-19 research.

In the recent years, tissue engineering researchers have exploited a variety of biomaterials that can potentially mimic extracellular matrix (ECM) for tissue regeneration. Natural cellulose, mainly obtained from bacterial (BC) and plant-based (PC) sources, can serve as a high potential scaffold material for different regenerative purposes. Natural cellulose has drawn the attention of researchers due to its advantage over synthetic cellulose in terms of availability, cost-effectiveness, perfusablility, biocompatibility, negligible toxicity, mild immune response and due to imitating native tissues. In this article, we will review the recent in vivo and in vitro studies aimed to assess the potentials of natural cellulose for the purpose of soft (skin, heart, veins, nerve, among others) and hard (bone and tooth) tissue engineering.

This data descriptor summarizes the process applied and data gathered from 50 publications/papers reporting on the use of photography generated by tourists, tour operators and members of the public, with a particular focus on the crowdsourcing of photographs through online platforms and social networking sites (SNSs) as a method of research for wildlife conservation and ecotourism. The papers were collected in a systematic literature review to inform a pilot study of the feasibility of using SNSs to crowdsource georeferenced photographs of endangered Bornean Pygmy Elephants (Elephas maximus borneensis) taken by ecotourists along the Lower Kinabatangan River region of Sabah, Malaysia. Papers were sourced using the Murdoch University Findit online-search tool to search over 100 databases, including Proquest, Scopus and Web of Science. The criteria for a paper to be included in the review (and shared via the dataset attached to this this data descriptor) were that it was peer-reviewed, published in English, between 1997 and the 31 December 2017, had the full text accessible online and reported on a study or studies that utilized photographs that tourists, tour operators and/or members of the public generated and shared via SNSs or online platforms.

Neutrophils are the most abundant immune cells and make up about 70% of white blood cells in human blood and play a critical role as the first line of defense in the innate immune response. They also help regulate the inflammatory environment to promote tissue repair. However, in cancer, neutrophils can be manipulated by tumors to either promote or hinder tumor growth depending on the cytokine pool. Studies have shown that tumor-bearing mice have increased levels of neutrophils in peripheral circulation, and that neutrophil-derived exosomes can deliver various cargos, including lncRNA and miRNA, which contribute to tumor growth and degradation of extracellular matrix. Exosomes derived from immune cells generally possess anti-tumor activities and induce tumor-cell apoptosis by delivering cytotoxic proteins, ROS generation, H2O2 or activation of Fas-mediated apoptosis in target cells. Engineered exosome-like nanovesicles have been developed to deliver chemotherapeutic drugs precisely to tumor cells. However, tumor-derived exosomes can aggravate cancer-associated thrombosis through the formation of neutrophil extracellular traps. Despite the advancements in neutrophil-related research, a detailed understanding of tumor-neutrophil crosstalk is still lacking and remains a major barrier in developing neutrophil-based or targeted therapy. This review will focus on the communication pathways between tumors and neutrophils, and the role of neutrophil-derived exosomes (NDEs) in tumor growth. Additionally, potential strategies to manipulate NDEs for therapeutic purposes will be discussed.

Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. It is described that the immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless the route of administration used, the inflammation conditions and the MHC context. These observations arise the question as to whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect. To address this, we examined the biodistribution and the efficacy of intraperitoneal luciferase-expressing human expanded adipose derived stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were stratified according to their response to the Luci-eASC treatment. According to the stratification criteria, there was a tendency to increase the bioluminescence signal in the intestine at the expense of a decrease in the bioluminescence signal in the liver in the `responder´ mice. These data thus suggest that the accumulation of the eASCs to the inflamed tissues is beneficial to achieve an optimal modulation of inflammation.

Different alcoholic beverages can have different effects on blood alcohol concentrations (BAC) and neurotoxicity even if equalized for alcohol content by volume. Anecdotal evidence suggested that natural wine is metabolized differently from conventional wines. This triple-blind study compared the BAC of 55 healthy male subjects after consuming the equivalent of 2 units of alcohol of a natural or conventional wine over 3 mins in two separate sessions one week apart. BAC was measured using a professional breathalyzer every 20 mins after consumption for 2 hrs. The BAC curves in response to the two wines diverged significantly at twenty minutes, at forty minutes and also at their maximum concentrations (peaks), with the natural wine inducing a lower BAC than the conventional wine (T20 0.40 vs. 0.46 [p<0.0002], T40 0.49 vs. 0.53 [p<0.0015], peak 0.52 vs. 0.56 [p<0.0002]). These differences are likely related to the development of different amino acids and antioxidants in the two wines during their production. This in turn may affect the kinetics of alcohol absorption and metabolism. Other contributing factors may also include pesticide residues, differences in dry extract content and the use of indigenous or selected yeasts. Further studies are needed to fully understand why natural wines are metabolized differently from conventional wines.

A revitalized practice of natural philosophy can help people to live a better life and promote a flourishing ecosystem. Such a philosophy is natural in two senses. First, it is natural by seeking to understand the whole of nature, including mental phenomena, In particular, a comprehensive natural philosophy should address the phenomena of sentience by embracing first- and second-person methods of investigation. Moreover, to expand our understanding of the world, natural philosophy should embrace a full panoply of explanations, similar to Aristotle’s four causes. Second, such a philosophy is natural by being grounded in human nature, taking full account of human capacities and limitations. Future natural philosophers should also make use of all human capacities, including emotion and intuition as well as reason and perception, to investigate nature. Finally, since the majority of our brain's activities are unconscious, natural philosophy should explore the unconscious mind with the aim of deepening our relation to the rest of nature and enhancing well-being.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

It has become practically impossible to survey the literature on cells derived from adipose tissue with the aim to apply them in regenerative medicine. The aim of this review is to provide a jump start to understanding the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) in regenerative medicine. We show that serious and adequate clinical research demonstrates that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither 'fat stem cells' nor could they exclusively be isolated from adipose tissue, as ADRCs contain the same adult (depending on the definition) pluripotent or multipotent stem cells that are ubiquitously present in the walls of small blood vessels. Of note, the specific isolation procedure used has significant impact on the number and viability of the cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to further separate adipose-derived stem cells (ASCs) from ADRCs if the latter were adequately isolated from adipose tissue. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for manipulating, stimulating and/or (genetically) reprogramming the cells for this purpose. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use.

This study evaluated the antimicrobial activity of Leptospermum scoparium (Mānuka) and Cryptomeria japonica (Sugi) essential oils and assessed the effect of seasonal chemical variation on the oils’ antimicrobial efficacies. Plate based assays were conducted to elucidate the oils’ spectrum of in vitro antimicrobial activity and to determine the oils’ minimum inhibitory concentrations (MIC) as a measure of antimicrobial efficacy. Gas chromatography – mass spectrometry was adopted to chemically profile oils distilled in different seasons. The resultant compositional information in conjunction with MIC data was used to evaluate the effect of seasonal variation on the oils’ antimicrobial efficacy. Both Mānuka and Sugi essential oils were active against all classes of target microorganisms. However, limited activity was observed against Gram-negative bacteria. The oils displayed consistent chemotypic characteristics regardless of the time of distillation. Nonetheless, there were quantitative differences in compound abundance in both essential oils. Significant differences in the MIC of Sugi essential oil was observed against target microorganisms as a result of seasonal variation in constituent abundances while Mānuka essential oil’s antimicrobial efficacy was unaffected. This study demonstrates that seasonal chemical variation is an important quality assurance parameter to consider for future application of essential oils as antimicrobial agents in consumer products.

This article presents and discusses analytical data on the scientific publication record from 1910 to 2020 on two topics: "climate" and "climate change/global warming/climate emergency". The goal is to visualize how the publication record on these two topics has evolved over time, from different classification perspectives (year, country, source and organization). Three hypotheses are tested using data collected from Web of Science and various graphical representations of the data. It is found that research output related to the Earth’s contemporary changing climate overtook that of general climate research in 2011, and the publication ratio has been expanding in the last decade. There are significant differences in the publication countries and sources between the two topics, and conversely less significant differences in terms of organizations publishing these works. Differentiation factors that affect the level of research output and engagement on the climate challenge include: island versus landlocked nations, specialized versus general scientific journals, academic versus institutional organizations. The future of the publication records is discussed, such as the emergence of new terms to refer to the climate challenge, such as “climate emergency”.

The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered. It is currently known that AMH introgressed with archaic hominins once they left the African continent. Current out of African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.

Most Acinetobacter baumannii strains are naturally competent. Although some information is available about factors that enhance or reduce the frequency of transformation of this bacterium, the regulatory elements and mechanisms are barely understood. In this article, we describe studies on the role of H-NS in the regulation of expression of genes related to natural competency and the ability to uptake foreign DNA. The expression levels of the natural transformation-related genes pilA, pilT, pilQ, comEA, comEC, comF, and drpA were significantly increased in a Δhns derivative of Acinetobacter baumannii A118. Complementation of the mutant with a recombinant plasmid harboring hns restored expression levels of six of these genes (pilT remained expressed at high levels) to those of the wild-type strain. The transformation frequency of the A. baumannii A118 Δhns strain was significantly higher than that of the wild-type. Similar, albeit not identical, effects occurred when hns was deleted from the hypervirulent A. baumannii AB5075 strain. Reduction of gene expression in a few cases was not as pronounced as to reach wild-type levels, and expression of comEA was enhanced further. In conclusion, the expression of all seven transformation-related genes was enhanced after deleting hns in A. baumannii A118 and AB5075, and these modifications are accompanied by an increase in the cells’ transformability. The results demonstrate a role of H-NS in A. baumannii’s natural competence.

The present work aims to characterize the mechanical behavior of a new composite material for the conservation and development of the vast historical and architectural heritage that is particularly vulnerable to environmental and seismic actions. The new composite consists of natural hydraulic lime (NHL) -based mortar, reinforced by sisal short fibers randomly oriented in the mortar matrix. The NHL-based mortar ensures the chemical-physical compatibility with the original feature of the historical masonry structures (mostly in stone and clay) aiming to pursue both the effectiveness and durability of the intervention. The use of vegetable fibers (i.e. the sisal one) is an exciting challenge for the construction industry since they require a lower degree of industrialization for their processing, and therefore, their costs are also low, as compared to the most common synthetic/metal fibers. Beams of sisal-composite sizing 160x40x40 mm3 with a central notch are tested in three-point bending, aiming to evaluate both their bending strength and fracture energy. Also, tensile tests and compressive tests were performed on the composite samples, while water retention test and slump test were performed on the fresh mix. Finally, the tensile tests on the Sisal strand were carried out to evaluate the tensile strength of both strand and wire. A final comparison with unreinforced mortar specimens shows that the proposed composite ensures great workability and good performances in term of ductility and strength and it can be considered a promising alternative to the classic fiber-reinforcing systems.

The high demand for liquefied natural gas (LNG) requires more LNG carriers (LNGCs) to be in operation. During transportation, there is a high risk due to the required extremely low temperatures and the explosive nature of LNG cargo. Moreover, when there is a lack of experience in operating old LNGCs, there is a serious concern regarding operational accidents. A systematic maintenance strategy, especially for LNG cargo containment systems, is crucial for maintaining safe LNG transportation at sea. The purpose of this study is to develop preventive LNG cargo containment system maintenance models by using LNGC dock specifications from LNGCs of various ages. The dock specifications from a conventional LNGC repairing dock were analyzed using natural language processing techniques in order to develop preventive maintenance models of the LNG cargo containment system. From these results, and by considering the ship’s age, it was found that for young LNGCs the priority for repair should focus on checking routine consumable spare parts by tank inspections, whereas for older LNGCs the focus should be on tank condition maintenance rather than on other facilities. These results are expected to be useful in the development of a maintenance strategy of preventive LNG cargo containment systems in maritime LNG transportation.

This paper aims to review the challenges, toxicity, and routes of synthesis and usage of silver nanoparticles in different applications but also highlighting their sustainability from both medical and environmental issues. Regarding their toxicity, it is known that silver nanoparticles can destroy over 650 microorganisms comparing with antibiotics. Supplementary, will be presented in a comparative manner some conventional synthesis routes (physical and chemical methods) and green synthesis routes using plant extracts. The approach using plant extracts have various advantages comparing with physical, chemical and microbial synthesis methods because there is no need to use chemicals, wasteful purifications and high energy requirements. The paper presents an overview on “green nanotechnology” focused on using either biological micro-organisms or plant extracts as an alternative to the classical chemical and physical methods. An important issue discussed in the paper is an overview of the synthesis routes of silver nanoparticles, some expected applications of silver based active agents and their toxicity and challenges that must be overcome. Also, it needs to focus our attention on the dismissal of silver nanoparticles into the environment and especially in water systems, fact which suggests that this issue must be fully understood and applied the law.

Bread wheat (Triticum aestivum L.) is staple of Pakistani people. However, its yield at farmer field is low as compared with its genetic potential. Integration of various crop and soil management strategies might be an option to enhance wheat productivity at farmer field. This 2-year experiment was conducted to check the influence of combine application of natural plant water extracts and biochar on the productvity of wheat during the winter season of 2015-16. The experiment consisted of seven treatment viz. (1) control (2) application of biochar (0.18 kg pot-1) alone, (3) application of sorghum water extract (SWE) alone, (4) application of moringa water extract (MWE) alone, (5) application of biochar + SWE, (6) application of biochar + MWE, (7) application of biochar + SWE+MWE. The results revealed that application of both crop water extracts in combination with biochar improved the growth and grain yield of wheat. Use of MWE in combination with biochar enhanced the grain weight, grain number and grain yield of wheat by 44, 14, and 24%, respectively than the control treatment. In crux, use of MWE in combination with biochar might be a viable option to improve the productivity of bread wheat.

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.

Thanks to rapid development of artificial intelligence technology in recent years, the current artificial intelligence technology is contributing to many part of society. Education, environment, medical care, military, tourism, economy, politics, etc. are having a very large impact on society as a whole. For example, in the field of education, there is an artificial intelligence tutoring system that automatically assigns tutors based on student's level. In the field of economics, there are quantitative investment methods that automatically analyze large amounts of data to find investment laws to create investment models or predict changes in financial markets. As such, artificial intelligence technology is being used in various fields. So, it is very important to know exactly what factors have an important influence on each field of artificial intelligence technology and how the relationship between each field is connected. Therefore, it is necessary to analyze artificial intelligence technology in each field. In this paper, we analyze patent documents related to artificial intelligence technology. We propose a method for keyword analysis within factors using artificial intelligence patent data sets for artificial intelligence technology analysis. This is a model that relies on feature engineering based on deep learning model named KeyBERT, and using vector space model. A case study of collecting and analyzing artificial intelligence patent data was conducted to show how the proposed model can be applied to real-world problems.

Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active while compound 17, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds.

As an important follow-up report on the latest study of the first author (H.S.) on an off-shell quantum field causing a dressed photon and dark energy, we further discuss a couple of intriguing subjects based on our new theory. One is the dressed photon constant. If we use it, in addition to h¯ and c, as the third component of natural units, then it is defined as the geometric mean of the smallest and the largest lengths: Planck length and that relating to the cosmological constant. Interestingly, this length (≈ 50 nanometers) seems to give a rough measure of the Heisenberg cut for electromagnetic phenomena. The other is a new perspective on cosmology that combines two original notions, i.e., twin universes and conformal cyclic cosmology, proposed respectively by Petit and Penrose, into one novel picture where universes expand self-similarly. We show the possibility that twin universes having a dual structure of [matter with (dark energy &amp; matter)] vs. corresponding anti-entities, separated by an event horizon embedded in the geometric structure of de Sitter space, undergo endless cyclic processes of birth and death, as in the case of the pair creation and annihilation of elementary particles through the intervention of a conformal light field.

The UK Government is committed to reducing greenhouse gas (GHG) emissions by 80% by 2050. Buildings are responsible for 37% of the total GHG emissions in the UK and the need to reduce their emissions has resulted in more stringent building regulations in the recent past. The regulations, energy rating systems and voluntary guidelines — all are primarily aimed at reducing the need for heating and associated energy use by increasing insulation and air-tightness. However, future climates are projected to be warmer than the present day. Internal gains dominated non-domestic buildings will likely overheat, the adaptation to which will require energy-intensive cooling solutions, thus defeating the purpose of heating-focused regulations. This research investigated the effects of warming climate on overheating, and energy use and resulting emissions in representative urban office spaces in London in the present-day and future climates using hourly dynamic thermal simulations. Findings suggest that more airtight and highly—insulated office buildings designed for heating—dominated temperate UK climate will overheat in the 2050s. Heating demand reduces but electricity consumption increases by 121% when hybrid cooling is adopted to ameliorate overheating. Despite the rise, adopting a mixed-mode ventilation strategy was one of the ways of achieving overall energy efficiency while meeting benchmark overheating and carbon emissions target in present and future climatic contradictions. Current heating-focused legislations need to be urgently re-evaluated to account for the effects of climatic variability and overheating risks.

Ultrafast laser 3D lithography based on non-linear light-matter interactions, widely known as multi-photon lithography (MPL), offers unrivaled precision rapid prototyping and flexible additive manufacturing options. 3D printing equipment based on MPL are already commercially available, yet there is still no comprehensive understanding of factors determining spatial resolution, accuracy, fabrication throughput, repeatability, and standardized metrology methods for the accurate characterization of the produced 3D objects and their functionalities. The photoexcitation mechanisms, spatial-control or photo-modified volumes, and the variety of processable materials are topics actively investigated. The complexity of the research field is underlined by limited understanding and fragmented knowledge of light-excitation and material response. Research to date has only provided case-specific findings on photoexcitation, chemical modification, and material characterization of the experimental data. In this review, we aim to provide a consistent and comprehensive summary of the existing literature on photopolymerization mechanisms under highly confined spatial and temporal conditions, where, besides the excitation and cross-linking, parameters such as diffusion, temperature accumulation, and the finite amount of monomer molecules start to become of critical importance. Key parameters such as, photoexcitation, polymerization kinetics, and the properties of the additively manufactured materials at the nanoscale in 3D are examined, whereas, the perspectives for future research and as well as emerging applications are outlined.

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD), the closest animal model available to the human situation, is known to similarly induce long lasting behavioural effects, to cause changes in the HPA axis and to have an impact in the immune system. Even though the immune responses to potential pathogens after early stress have been somehow documented, the mechanisms by which they occur are still not fully understood. Here, we have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after childhood adversity. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. Altogether, these results lead us to conclude that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

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.

Whey is the main by-product of the dairy industry and contains sugars (lactose) and proteins (especially serum proteins and, at lesser extent, residual caseins), which can be valorized by the fermentative action of yeasts. In the present study, we characterized the spoilage yeast fraction inhabiting natural whey starter (NWS), the undefined starter culture of thermophilic lactic acid bacteria used in Parmigiano Reggiano (PR) cheesemaking, and evaluated thermotolerance, mating type, and the aptitude to produce ethanol and bioactive peptides from whey lactose and proteins, respectively, in a selected pool of strains. We found that PR NWS yeast population consists of other species (Saccharomyces cerevisiae, Wickerhamiella pararugosa, and Torulaspora delbrueckii) in addition to the well-documented Kluyveromyces marxianus, with multiple biotypes scored within each species. Haploid and diploid K. marxianus strains were identified through MAT genotyping, while thermotolerance assay allowed the selection of strains suitable to grow up to 48 °C. In whey fermentation assay, one thermotolerant strain was suitable to release ethanol with yield of 86.5%, while another candidate was able to produce the highest amounts of both ethanol and bioactive peptides with potentially anti-hypertensive function. The present work demonstrated that PR NWS is a reservoir of ethanol and bioactive peptides producer yeasts, which can be exploited to valorize whey, in agreement with the principles of circularity and sustainability.