Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive Virtual Screening of the Antiviral Potentialities of Marine Polycyclic Guanidine Alkaloids against SARS-CoV-2 (COVID-19)

The huge global expansion of the COVID-19 pandemic caused by the novel SARS-corona virus-2 is an extraordinary public health emergency. The unavailability of specific treatment against SARS-CoV-2 infection necessitates the focus of all scientists in this direction. The reported antiviral activities of guanidine alkaloids encouraged us to run a comprehensive in silico binding affinity of fifteen guanidine alkaloids against five different proteins of SARS-CoV-2, which we investigated. The investigated proteins are COVID-19 main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and a non-structural protein (nsp10) (PDB ID: 6W4H). The binding energies for all tested compounds indicated promising binding affinities. A noticeable superiority for the pentacyclic alkaloids particularly, crambescidin 786 (5) and crambescidin 826 (13) has been observed. Compound 5 exhibited very good binding affinities against Mpro (ΔG = −8.05 kcal/mol), nucleocapsid phosphoprotein (ΔG = −6.49 kcal/mol), and nsp10 (ΔG = −9.06 kcal/mol). Compound 13 showed promising binding affinities against Mpro (ΔG = −7.99 kcal/mol), spike glycoproteins (ΔG = −6.95 kcal/mol), and nucleocapsid phosphoprotein (ΔG = −8.01 kcal/mol). Such promising activities might be attributed to the long ω-fatty acid chain, which may play a vital role in binding within the active sites. The correlation of c Log P with free binding energies has been calculated. Furthermore, the SAR of the active compounds has been clarified. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies were carried out in silico for the 15 compounds; most examined compounds showed optimal to good range levels of ADMET aqueous solubility, intestinal absorption and being unable to pass blood brain barrier (BBB), non-inhibitors of CYP2D6, non-hepatotoxic, and bind plasma protein with a percentage less than 90%. The toxicity of the tested compounds was screened in silico against five models (FDA rodent carcinogenicity, carcinogenic potency TD50, rat maximum tolerated dose, rat oral LD50, and rat chronic lowest observed adverse effect level (LOAEL)). All compounds showed expected low toxicity against the tested models. Molecular dynamic (MD) simulations were also carried out to confirm the stable binding interactions of the most promising compounds, 5 and 13, with their targets. In conclusion, the examined 15 alkaloids specially 5 and 13 showed promising docking, ADMET, toxicity and MD results which open the door for further investigations for them against SARS-CoV-2.
Skeletal Muscle in ALS: An Unappreciated Therapeutic Opportunity?

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective degeneration of upper and lower motor neurons and by the progressive weakness and paralysis of voluntary muscles. Despite intense research efforts and numerous clinical trials, it is still an incurable disease. ALS had long been considered a pure motor neuron disease; however, recent studies have shown that motor neuron protection is not sufficient to prevent the course of the disease since the dismantlement of neuromuscular junctions occurs before motor neuron degeneration. Skeletal muscle alterations have been described in the early stages of the disease, and they seem to be mainly involved in the “dying back” phenomenon of motor neurons and metabolic dysfunctions. In recent years, skeletal muscles have been considered crucial not only for the etiology of ALS but also for its treatment. Here, we review clinical and preclinical studies that targeted skeletal muscles and discuss the different approaches, including pharmacological interventions, supplements or diets, genetic modifications, and training programs.
Crystal structure of acridine(pyridine-2,6-dicarboxylato- k3N,O,O')platinum(II), Pt(C7H3NO4)(C13H9N)

C20H12N2O4Pt, monoclinic, C12/c1 (no. 15), a = 25.342(2) Å, b = 9.1951(8) Å, c = 13.932(1) Å, * = 94.280(2)°, V = 3237.5 Å, Z = 8, Rgt(F) = 0.035, wRref(F ) = 0.080, T = 200 K.
Convenient Synthesis of Functionalized Unsymmetrical Vinyl Disulfides and Their Inverse Electron-Demand Hetero-Diels-Alder Reaction

The simple, convenient, and efficient methods for the preparation of unsymmetrical vinyl disulfides with additional functional groups under mild conditions with moderate to high yields were designed. The developed methods include the reaction of S-vinyl phosphorodithioate with thiotosylates or S-vinyl thiotosylate with thiols. The designed methods allow for the synthesis of unsymmetrical vinyl disulfides with additional functionalities such as hydroxy, carboxy, protected amino, or ester groups. Vinyl disulfides reacted with the generated transient o-iminothioquinones in an inverse electron-demand [4+2] cycloaddition to produce benzo[b][1,4]thiazine derivatives.
Latest Insights into Mechanisms behind Atrial Cardiomyopathy: It Is Not always about Ventricular Function

Atrial cardiomyopathy (ACM) represents a constantly evolving concept, with increasing importance in contemporary research and clinical practice. A better understanding of the mechanisms involved in atrial remodeling and its clinical correlations especially with atrial fibrillation (AF) and other cardiometabolic comorbidities may induce a significant impact on the diagnosis, prognosis, and therapeutic approach of ACM-related comorbidities. Although initially described several decades ago, investigators have only recently highlighted that several renal, metabolic, and cardiovascular diseases are determining factors for atrial remodeling and subsequent ACM. Based on data from multiple recent studies, our research emphasizes the correlations between ACM and other coexisting pathologies including cardiovascular, respiratory, or metabolic diseases, with fibrosis being the most incriminated pathophysiological mechanism. In addition to the usual tests, the paraclinical assessment of ACM is increasingly based on the use of various cardiac biomarkers, while the cardiac magnetic resonance (CMR) has become an increasingly tempting diagnostic too for describing morphofunctional aspects of the heart chambers, with the gadolinium contrast enhanced CMR (LGE-CMR) emerging as a commonly used technique aiming to identify and quantify the precise extent of atrial fibrosis. Further research should be conducted in order to clarify our knowledge regarding atrial remodeling and, therefore, to develop new and improved therapeutic approaches in these patients.
New Insights into the Metabolism of the Flavanones Eriocitrin and Hesperidin: A Comparative Human Pharmacokinetic Study

The intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individual variability (high vs. low-producers) that prevents consistent health-related evidence. Contrarily, the human metabolism of (lemon) eriocitrin is hardly known. We hypothesize that the higher solubility of (lemon) eriocitrin vs. (orange) hesperidin might yield more bioavailable metabolites than hesperidin. A randomized-crossover human pharmacokinetic study (n = 16) compared the bioavailability and metabolism of flavanones from lemon and orange extracts and postprandial changes in oxidative, inflammatory, and metabolic markers after a high-fat-high-sugars meal. A total of 17 phase-II flavanone-derived metabolites were identified. No significant biomarker changes were observed. Plasma and urinary concentrations of all metabolites, including hesperetin metabolites, were higher after lemon extract intake. Total plasma metabolites showed significantly mean lower Tmax (6.0 ± 0.4 vs. 8.0 ± 0.5 h) and higher Cmax and AUC values after lemon extract intake. We provide new insights on hesperetin-eriodictyol interconversion and naringenin formation from hesperidin in humans. Our results suggest that regular consumption of a soluble and eco-friendly eriocitrin-rich lemon extract could provide a circulating concentration metabolites threshold to exert health benefits, even in the so-called low-producers.
Hybrid Deep Learning Models with Sparse Enhancement Technique for Detection of Newly Grown Tree Leaves

The life cycle of leaves, from sprout to senescence, is the phenomenon of regular changes such as budding, branching, leaf spreading, flowering, fruiting, leaf fall, and dormancy due to seasonal climate changes. It is the effect of temperature and moisture in the life cycle on physiological changes, so the detection of newly grown leaves (NGL) is helpful for the estimation of tree growth and even climate change. This study focused on the detection of NGL based on deep learning convolutional neural network (CNN) models with sparse enhancement (SE). As the NGL areas found in forest images have similar sparse characteristics, we used a sparse image to enhance the signal of the NGL. The difference between the NGL and the background could be further improved. We then proposed hybrid CNN models that combined U-net and SegNet features to perform image segmentation. As the NGL in the image were relatively small and tiny targets, in terms of data characteristics, they also belonged to the problem of imbalanced data. Therefore, this paper further proposed 3-Layer SegNet, 3-Layer U-SegNet, 2-Layer U-SegNet, and 2-Layer Conv-U-SegNet architectures to reduce the pooling degree of traditional semantic segmentation models, and used a loss function to increase the weight of the NGL. According to the experimental results, our proposed algorithms were indeed helpful for the image segmentation of NGL and could achieve better kappa results by 0.743.
Toxicity of Terahertz-Based Functional Mineral Water (Plant-Derived) to Immature Stages of Mosquito Vectors

Simple Summary In light of the shortcomings of using insecticides, there is an urgent need to explore alternative compounds that are effective for mosquito control with minimal adverse effects. The terahertz-based functional mineral water used in the current study exhibited concentration-dependent toxicity to mosquito larvae, pupae and larvivorous predatory copepods and could be a potential biodegradable and eco-friendly bioinsecticide. Abstract Functional mineral water and related products are popular in some Asian countries as health drinks and, recently, have been employed in agricultural crop production as well as pest control. This study aimed to investigate the survival of mosquito vectors exposed to plant-derived functional mineral water produced by terahertz technology. The terahertz-based functional mineral water used in the current study not only decreased the hatching of Culex quinquefasciatus (Say) larvae but also showed concentration-dependent toxicity to the 3rd instar larvae and pupae of the three mosquito species tested. Aedes albopictus (Skuse) and Cx. quinquefasciatus pupae were more susceptible to terahertz-based functional mineral water than the larval stage, as indicated by their lower LC50. Lower concentrations (<100 ppm) of terahertz-based functional mineral water were not lethal to the pupae; however, these low concentrations still resulted in a reduced adult emergence. Although terahertz-based functional mineral water did not significantly affect Aedes aegypti (Linnaeus) hatching, it could potentially be used for vector control at the larvae and pupae stages. The larvicidal and pupicidal activity of diluted terahertz-based functional mineral water gradually diminished after 24 h, indicating that it is a biodegradable and eco-friendly bioinsecticide. However, as the terahertz-based functional mineral water is also toxic to larvivorous predatory-copepods, it should not be utilized in aquatic environments where predatory-based mosquito control programs are employed.
Community Composition and Spatial Distribution of N-Removing Microorganisms Optimized by Fe-Modified Biochar in a Constructed Wetland

Microbial nitrogen (N) removal capability can be significantly enhanced in a horizontal subsurface flow constructed wetland (HSCW) amended by Fe-modified biochar (FeB). To further explore the microbiological mechanism of FeB enhancing N removal, nirS- and nirK-denitrifier community diversities, as well as spatial distributions of denitrifiers and anaerobic ammonium oxidation (anammox) bacteria, were investigated in HSCWs (C-HSCW: without biochar and FeB; B-HSCW: amended by biochar; FeB-HSCW: amended by FeB) treating tailwater from a wastewater treatment plant, with C-HSCW without biochar and FeB and B-HSCW amended by biochar as control. The community structures of nirS- and nirK-denitrifiers in FeB-HSCW were significantly optimized for improved N removal compared with the two other HSCWs, although no significant differences in their richness and diversity were detected among the HSCWs. The spatial distributions of the relative abundance of genes involved in denitrification and anammox were more heterogeneous and complex in FeB-HSCW than those in other HSCWs. More and larger high-value patches were observed in FeB-HSCW. These revealed that FeB provides more appropriate habitats for N-removing microorganisms, which can prompt the bacteria to use the habitats more differentially, without competitive exclusion. Overall, the Fe-modified biochar enhancement of the microbial N-removal capability of HSCWs was a result of optimized microbial community structures, higher functional gene abundance, and improved spatial distribution of N-removing microorganisms.
Every Detail Matters. That Is, How the Interaction between Gα Proteins and Membrane Affects Their Function

In highly organized multicellular organisms such as humans, the functions of an individual cell are dependent on signal transduction through G protein-coupled receptors (GPCRs) and subsequently heterotrimeric G proteins. As most of the elements belonging to the signal transduction system are bound to lipid membranes, researchers are showing increasing interest in studying the accompanying protein–lipid interactions, which have been demonstrated to not only provide the environment but also regulate proper and efficient signal transduction. The mode of interaction between the cell membrane and G proteins is well known. Despite this, the recognition mechanisms at the molecular level and how the individual G protein-membrane attachment signals are interrelated in the process of the complex control of membrane targeting of G proteins remain unelucidated. This review focuses on the mechanisms by which mammalian Gα subunits of G proteins interact with lipids and the factors responsible for the specificity of membrane association. We summarize recent data on how these signaling proteins are precisely targeted to a specific site in the membrane region by introducing well-defined modifications as well as through the presence of polybasic regions within these proteins and interactions with other components of the heterocomplex.
The Integral Role of Organisational Governance in Promoting Interprofessional Education in Rural Settings

One of the key challenges with implementing and sustaining interprofessional education initiatives is the lack of governance structures and processes to guide them. This case study presents a process evaluation of an intersectoral advisory group that facilitated a novel interprofessional clinical education model in rural health settings in the state of Queensland, Australia. The group consisted of health and academic partners to guide the implementation and promote sustainability of this new model. The advisory group process was evaluated mid-way and at conclusion of the group functions, using focus group discussions. The focus group audio recordings were transcribed verbatim and subjected to inductive content analysis. Categories were developed for reporting. Three broad categories were identified: Characteristics of the group, functions of the group and multifaceted communication within the group and between sectors. By identifying and mapping the processes used by a strategic, high-level intersectoral advisory group consisting of members from the health and academic fields, key recommendations have been formulated to guide similar work in the future.
Cholesterol Content, Fatty Acid Profile and Health Lipid Indices in the Egg Yolk of Eggs from Hens at the End of the Laying Cycle, Following Alpha-Ketoglutarate Supplementation

The current study aimed to assess the effects of dietary alpha-ketoglutarate (AKG) supplementation to laying hens on the fatty acid (FA) profile and cholesterol levels of the egg yolk at the end of production cycle. The experiment was performed on forty-eight Bovans Brown laying hens randomly assigned to either a control group (CONT) or a group supplemented with AKG. The CONT group was fed the basal diet, and the AKG group was fed the basal diet plus 1.0% AKG from the 31st until the 60th week of age, when FA profile, fat and cholesterol content of the egg yolks were determined. No significant changes in the cholesterol and total fat content of the egg yolks were observed. However, there were positive (the decrease in n-6 FA and the increase in MUFA), and negative (decrease in PUFA and n-3 FA, increase in TI and n-6/n-3 ratio) changes in FA profile following AKG supplementation. In conclusion, it was shown that dietary AKG after a 30-week long supplementation influence FA profile in egg yolk and its nutritional value.
Determination of the components of plant cuticles

Quantitative methods are described for the determination of waxy substances and cutin in plant cuticles. Surface waxy materials are obtained by immersing leaves or fruits in chloroform at room temperature; waxy substances embedded within the cuticles of fruits are recovered by further extraction of the skin after surface washing. Acidic materials are removed from the extract, and true wax and “oil” fractions are obtained by partition between n-heptane and methanol. The cuticular membranes are then separated by treatment with ammonium oxalate-oxalic acid solution, and the cutin in the membranes is determined by saponification. Work by other investigators on the nature and determination of components of plant cuticles is reviewed.
Lipids and Antiplatelet Therapy: Important Considerations and Future Perspectives

Lipids play an essential role in platelet functions. It is known that polyunsaturated fatty acids play a role in increasing platelet reactivity and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases’ incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies discontinuation of clopidogrel in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed “on-demand” in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.
Effect of a Simulated Heat Wave on Physiological Strain and Labour Productivity

Background: The aim of the study was to investigate the effect of a simulated heat-wave on the labour productivity and physiological strain experienced by workers. Methods: Seven males were confined for ten days in controlled ambient conditions. A familiarisation day was followed by three (pre, during, and post-heat-wave) 3-day periods. During each day volunteers participated in a simulated work-shift incorporating two physical activity sessions each followed by a session of assembly line task. Conditions were hot (work: 35.4 °C; rest: 26.3 °C) during, and temperate (work: 25.4 °C; rest: 22.3 °C) pre and post the simulated heat-wave. Physiological, biological, behavioural, and subjective data were collected throughout the study. Results: The simulated heat-wave undermined human capacity for work by increasing the number of mistakes committed, time spent on unplanned breaks, and the physiological strain experienced by the participants. Early adaptations were able to mitigate the observed implications on the second and third days of the heat-wave, as well as impacting positively on the post-heat-wave period. Conclusions: Here, we show for first time that a controlled simulated heat-wave increases workers’ physiological strain and reduces labour productivity on the first day, but it promotes adaptations mitigating the observed implications during the subsequent days.
Nanomaterials as Novel Cardiovascular Theranostics

Cardiovascular diseases (CVDs) are a group of conditions associated with heart and blood vessels and are considered the leading cause of death globally. Coronary heart disease, atherosclerosis, myocardial infarction represents the CVDs. Since CVDs are associated with a series of pathophysiological conditions with an alarming mortality and morbidity rate, early diagnosis and appropriate therapeutic approaches are critical for saving patients’ lives. Conventionally, diagnostic tools are employed to detect disease conditions, whereas therapeutic drug candidates are administered to mitigate diseases. However, the advent of nanotechnological platforms has revolutionized the current understanding of pathophysiology and therapeutic measures. The concept of combinatorial therapy using both diagnosis and therapeutics through a single platform is known as theranostics. Nano-based theranostics are widely used in cancer detection and treatment, as evident from pre-clinical and clinical studies. Nanotheranostics have gained considerable attention for the efficient management of CVDs. The differential physicochemical properties of engineered nanoparticles have been exploited for early diagnosis and therapy of atherosclerosis, myocardial infarction and aneurysms. Herein, we provided the information on the evolution of nano-based theranostics to detect and treat CVDs such as atherosclerosis, myocardial infarction, and angiogenesis. The review also aims to provide novel avenues on how nanotherapeutics’ trending concept could transform our conventional diagnostic and therapeutic tools in the near future.
Physical and Chemical Methods for Reduction in Aflatoxin Content of Feed and Food

Aflatoxins (AFs) are among the most harmful fungal secondary metabolites imposing serious health risks on both household animals and humans. The more frequent occurrence of aflatoxins in the feed and food chain is clearly foreseeable as a consequence of the extreme weather conditions recorded most recently worldwide. Furthermore, production parameters, such as unadjusted variety use and improper cultural practices, can also increase the incidence of contamination. In current aflatoxin control measures, emphasis is put on prevention including a plethora of pre-harvest methods, introduced to control Aspergillus infestations and to avoid the deleterious effects of aflatoxins on public health. Nevertheless, the continuous evaluation and improvement of post-harvest methods to combat these hazardous secondary metabolites are also required. Already in-use and emerging physical methods, such as pulsed electric fields and other nonthermal treatments as well as interventions with chemical agents such as acids, enzymes, gases, and absorbents in animal husbandry have been demonstrated as effective in reducing mycotoxins in feed and food. Although most of them have no disadvantageous effect either on nutritional properties or food safety, further research is needed to ensure the expected efficacy. Nevertheless, we can envisage the rapid spread of these easy-to-use, cost-effective, and safe post-harvest tools during storage and food processing.