Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Atypical Cannabinoid Ligands O-1602 and O-1918 on Skeletal Muscle Homeostasis with a Focus on Obesity

O-1602 and O-1918 are atypical cannabinoid ligands for GPR55 and GPR18, which may be novel pharmaceuticals for the treatment of obesity by targeting energy homeostasis regulation in skeletal muscle. This study aimed to determine the effect of O-1602 or O-1918 on markers of oxidative capacity and fatty acid metabolism in the skeletal muscle. Diet-induced obese (DIO) male Sprague Dawley rats were administered a daily intraperitoneal injection of O-1602, O-1918 or vehicle for 6 weeks. C2C12 myotubes were treated with O-1602 or O-1918 and human primary myotubes were treated with O-1918. GPR18 mRNA was expressed in the skeletal muscle of DIO rats and was up-regulated in red gastrocnemius when compared with white gastrocnemius. O-1602 had no effect on mRNA expression on selected markers for oxidative capacity, fatty acid metabolism or adiponectin signalling in gastrocnemius from DIO rats or in C2C12 myotubes, while APPL2 mRNA was up-regulated in white gastrocnemius in DIO rats treated with O-1918. In C2C12 myotubes treated with O-1918, PGC1α, NFATc1 and PDK4 mRNA were up-regulated. There were no effects of O-1918 on mRNA expression in human primary myotubes derived from obese and obese T2DM individuals. In conclusion, O-1602 does not alter mRNA expression of key pathways important for skeletal muscle energy homeostasis in obesity. In contrast, O-1918 appears to alter markers of oxidative capacity and fatty acid metabolism in C2C12 myotubes only. GPR18 is expressed in DIO rat skeletal muscle and future work could focus on selectively modulating GPR18 in a tissue-specific manner, which may be beneficial for obesity-targeted therapies.
Aggregation patterns of pelagic predators and their principal prey, Antarctic krill, near South Georgia

We examined the spatial distributions of pelagic seabirds and fur seals near South Georgia, and asked to what extent the distributions of these predators were influenced by the spatial distribution of their principal prey, Antarctic krill Euphausia superba Dana. One novel aspect of our analysis is an explicit consideration of the separation in space between swarms of krill and aggregations of predators that feed upon krill. Our data were collected in February 1986, during a systematic shipboard survey of the waters surrounding Bird Island, South Georgia. Predator abundance was estimated visually using strip transects, and krill abundance was simultaneously estimated using a hull-mounted echosounder
Early-life nutrition and metabolic disorders in later life: a new perspective on energy metabolism

Abstract Type 2 diabetes mellitus and metabolic disorders have become an epidemic globally. However, the pathogenesis remains largely unclear and the prevention and treatment are still limited. In addition to environmental factors during adulthood, early life is the critical developmental window with high tissue plasticity, which might be modified by external environmental cues. Substantial evidence has demonstrated the vital role of early-life nutrition in programming the metabolic disorders in later life. In this review, we aim to overview the concepts of fetal programming and investigate the effects of early-life nutrition on energy metabolism in later life and the potential epigenetic mechanism. The related studies published on PubMed database up to March 2020 were included. The results showed that both maternal overnutrition and undernutrition increased the riskes of metabolic disorders in offspring and epigenetic modifications, including DNA methylation, miRNAs, and histone modification, might be the vital mediators. The beneficial effects of early-life lifestyle modifications as well as dietary and nutritional interventions on these deleterious metabolic remolding were initially observed. Overall, characterizing the early-life malnutrition that reshapes metabolic disease trajectories may yield novel targets for early prevention and intervention and provide a new point of view to the energy metabolism.
The Age of Cyclic Dinucleotide Vaccine Adjuvants

As prophylactic vaccine adjuvants for infectious diseases, cyclic dinucleotides (CDNs) induce safe, potent, long-lasting humoral and cellular memory responses in the systemic and mucosal compartments. As therapeutic cancer vaccine adjuvants, CDNs induce potent anti-tumor immunity, including cytotoxic T cells and NK cells activation that achieve durable regression in multiple mouse models of tumors. Clinical trials are ongoing to fulfill the promise of CDNs (ClinicalTrials.gov: NCT02675439, NCT03010176, NCT03172936, and NCT03937141). However, in October 2018, the first clinical data with Merck’s CDN MK-1454 showed zero activity as a monotherapy in patients with solid tumors or lymphomas (NCT03010176). Lately, the clinical trial from Aduro’s CDN ADU-S100 monotherapy was also disappointing (NCT03172936). The emerging hurdle in CDN vaccine development calls for a timely re-evaluation of our understanding on CDN vaccine adjuvants. Here, we review the status of CDN vaccine adjuvant research, including their superior adjuvant activities, in vivo mode of action, and confounding factors that affect their efficacy in humans. Lastly, we discuss the strategies to overcome the hurdle and advance promising CDN adjuvants in humans.
Health and Nutritional Beliefs and Practices among Rural Elderly Population: An Ethnographic Study in Western Spain

Background: Demographic transition is causing an increasingly aged society, which has a significant impact on public health strategies. Increases in the size of the elderly cohort create a wider stratification and pose specific challenges. Nutrition and diet are one key issue. This study aims to describe food-related practices, beliefs, and representations of non-institutionalized older adults in rural communities in Extremadura (Western Spain). Method: The ethnographic-based fieldwork was conducted from January to July 2019. Empirical material was collected through different research relationships (semi-structured interviews and informal conversations) and direct observation in various locations in Extremadura―involving a variety of agents associated with different aspects of the nutritional process. Results: Data analysis revealed four major themes: (1) Limitations on choice and quality of food available; (2) food preferences and cooking methods; (3) the role of nostalgia in the construction of taste preferences; and (4) perceptions of what “healthy” food is and how respondents relate to the advice provided by health professionals. Conclusions: Nutritional choices among the group studied presented significant differences from medical advice―which was seen as a series of “bans” that did not carry enough authority to alter the symbolic value attached to their traditions.
Oxidant-Induced Alterations in the Adipocyte Transcriptome: Role of the Na,K-ATPase Oxidant Amplification Loop

(1) Background: Recently we have noted that adipocyte specific expression of the peptide, NaKtide, which was developed to attenuate the Na,K-ATPase oxidant amplification loop, could ameliorate the phenotypical features of uremic cardiomyopathy. We performed this study to better characterize the cellular transcriptomes that are involved in various biological pathways associated with adipocyte function occurring with renal failure. (2) Methods: RNAseq was performed on the visceral adipose tissue of animals subjected to partial nephrectomy. Specific expression of NaKtide in adipocytes was achieved using an adiponectin promoter. To better understand the cause of gene expression changes in vivo, 3T3L1 adipocytes were exposed to indoxyl sulfate (IS) or oxidized low density lipoprotein (oxLDL), with and without pNaKtide (the cell permeant form of NaKtide). RNAseq was also performed on these samples. (3) Results: We noted a large number of adipocyte genes were altered in experimental renal failure. Adipocyte specific NaKtide expression reversed most of these abnormalities. High correlation with some cardiac specific phenotypical features was noted amongst groups of these genes. In the murine adipocytes, both IS and oxLDL induced similar pathway changes as were noted in vivo, and pNaKtide appeared to reverse these changes. Network analysis demonstrated tremendous similarities between the network revealed by gene expression analysis with IS compared with oxLDL, and the combined in vitro dataset was noted to also have considerable similarity to that seen in vivo with experimental renal failure. (4) Conclusions: This study suggests that the myriad of phenotypical features seen with experimental renal failure may be fundamentally linked to oxidant stress within adipocytes.
Evaluation of the Insecticidal Activities of α-Pinene and 3-Carene on Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae)

Simple Summary In order to assure food security, proven postharvest pest management tools are needed to secure grains and processed food from insect infestations. Plants and plant products have over the years been proven to possess great insecticidal properties. Farmers in Cameroon use cypress leaves (Cupressus sempervirens) as pesticide against the maize weevil (Sitophilus zeamais). Two pure compounds (α-Pinene and 3-Carene) from cypress were tested against the maize weevil for contact and fumigant toxicities. Both compounds demonstrated efficacies against both adult and immature weevils. These compounds did not change the color of the treated stored maize and could be exploited as novel maize insecticides. Abstract Pest management in most sub-Saharan subsistence agriculture involves mainly the use of botanicals that are either applied as powders, solvent extracts, ash or essential oils. Two hydrogenated monoterpenes (α-pinene and 3-carene) from Cupressus sempervirens were tested against Sitophilus zeamais in the laboratory to evaluate the contact and fumigation effects on the mortality of adult and immature weevils, progeny production, and grain damage. Contact toxicity of the terpenes was investigated at these concentrations: 0.08, 4, 8 and 12 ppm (terpene/maize), while fumigant action was studied at the following doses: 1, 2, 3, and 4 ppm. The results indicate that insecticidal effects were concentration-dependent since mortality increased with dosage and exposure periods. After a 14-day exposure period at the concentration of 12 ppm of α-pinene and 3-carene/grain, more than 98% mortality of the mature weevils was observed at concentrations of 4.1333 and 1.642 ppm respectively and progeny production was reduced by 98% and 100%, respectively. When α-pinene and 3-carene were applied as fumigants, LC50s (lethal concentrations that generate 50% mortality) of 1.402 and 0.610 ppm were obtained after 24 h of exposure, respectively. At concentrations above 3 ppm, both monoterpenes acted as repellents to weevils and reduced grain damage by 80%. Both monoterpenes inhibited the development of immature stages of the weevil and reduced progeny by up to 94%. These compounds are very promising and effective and could be exploited as novel phytoinsecticides against the maize weevil.
Superhard Boron-Rich Boron Carbide with Controlled Degree of Crystallinity

Superhard boron-rich boron carbide coatings were deposited on silicon substrates by microwave plasma chemical vapor deposition (MPCVD) under controlled conditions, which led to either a disordered or crystalline structure, as measured by X-ray diffraction. The control of either disordered or crystalline structures was achieved solely by the choice of the sample being placed either directly on top of the sample holder or within an inset of the sample holder, respectively. The carbon content in the B-C bonded disordered and crystalline coatings was 6.1 at. % and 4.5 at. %, respectively, as measured by X-ray photoelectron spectroscopy. X-ray diffraction analysis of the crystalline coating provided a good match with a B50C2-type structure in which two carbon atoms replaced boron in the α-tetragonal B52 structure, or in which the carbon atoms occupied different interstitial sites. Density functional theory predictions were used to evaluate the dynamical stability of the potential B50C2 structural forms and were consistent with the measurements. The measured nanoindentation hardness of the coatings was as high as 64 GPa, well above the 40 GPa threshold for superhardness.
Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

Significance The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, a major pandemic that threatens millions of human lives and the global economy. We identified a large number of mammals that can potentially be infected by SARS-CoV-2 via their ACE2 proteins. This can assist the identification of intermediate hosts for SARS-CoV-2 and hence reduce the opportunity for a future outbreak of COVID-19. Among the species we found with the highest risk for SARS-CoV-2 infection are wildlife and endangered species. These species represent an opportunity for spillover of SARS-CoV-2 from humans to other susceptible animals. Given the limited infectivity data for the species studied, we urge caution not to overinterpret the predictions of the present study. The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.
Breakfast Characteristics and Their Association with Energy, Macronutrients, and Food Intake in Children and Adolescents: A Systematic Review and Meta-Analysis

Breakfast plays an important role in health because it has been associated with overall health, which includes a high daily nutrient intake and a low risk of chronic diseases. For this reason, we investigated the associations between breakfast consumption and daily energy, macronutrients, and food and beverage consumption. We systematically searched peer-reviewed articles in three datasets (Pubmed, Scopus, and Cochrane). Two independent reviewers evaluated 3188 studies against the inclusion criteria using the Appraisal tool for Cross-Sectional Studies (AXIS) critical appraisal and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodologies. The meta-analysis was performed by comparing results based on type of breakfast consumed (ready to eat cereal breakfasts or other types of breakfasts). Ultimately, 38 studies were included in the review and 7 of them in the energy and macronutrients intake meta-analysis. In the Systematic Review, breakfast consumers had higher energy intake (EI), fibre intake, and higher consumption of fruits and vegetables and lower consumption of soft drinks than breakfast skippers. In the Meta-Analysis, breakfast consumers had a higher carbohydrates intake (MD, −8.21; 95%CI: −11.37, −5.05) and fibre intake (MD, −8.43; 95%CI: −12.63, −4.23) than breakfast skippers. However, breakfast consumers had a lower fat intake (MD, 4.59; 95%CI: 2.04, 7.15). Our review suggests that breakfast consumption is associated with better macronutrient intake and healthier food and beverage consumption.
Evaluation of the Individual and Combined Toxicity of Fumonisin Mycotoxins in Human Gastric Epithelial Cells

Fumonisin contaminates food and feed extensively throughout the world, causing chronic and acute toxicity in human and animals. Currently, studies on the toxicology of fumonisins mainly focus on fumonisin B1 (FB1). Considering that FB1, fumonisin B2 (FB2) and fumonisin B3 (FB3) could coexist in food and feed, a study regarding a single toxin, FB1, may not completely reflect the toxicity of fumonisin. The gastrointestinal tract is usually exposed to these dietary toxins. In our study, the human gastric epithelial cell line (GES-1) was used as in vitro model to evaluate the toxicity of fumonisin. Firstly, we found that they could cause a decrease in cell viability, and increase in membrane leakage, cell death and the induction of expression of markers for endoplasmic reticulum (ER) stress. Their toxicity potency rank is FB1 > FB2 >> FB3. The results also showed that the synergistic effect appeared in the combinations of FB1 + FB2 and FB1 + FB3. Nevertheless, the combinations of FB2 + FB3 and FB1 + FB2 + FB3 showed a synergistic effect at low concentration and an antagonistic effect at high concentration. We also found that myriocin (ISP-1) could alleviate the cytotoxicity induced by fumonisin in GES-1 cells. Finally, this study may help to determine or optimize the legal limits and risk assessment method of mycotoxins in food and feed and provide a potential method to block the fumonisin toxicity.
Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?

Limited reports exist on the relationships between regulation of oxygen homeostasis and circadian clock genes in type 2 diabetes. We examined whether the expression of Hypoxia-Inducible Factor-1α (HIF-1α) and HIF-2α relates to changes in the expression of clock genes (Period homolog proteins (PER)1, PER2, PER3, Retinoid-related orphan receptor alpha (RORA), Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), Circadian locomotor output cycles kaput (CLOCK), and Cryptochrome proteins (CRY) 1 and CRY2) in patients with type 2 diabetes. A total of 129 subjects were evaluated in this cross-sectional study (48% with diabetes). The gene expression was measured by polymerase chain reaction. The lactate and pyruvate levels were used as surrogate of the hypoxia induced anaerobic glycolysis activity. Patients with diabetes showed an increased plasma concentration of both lactate (2102.1 ± 688.2 vs. 1730.4 ± 694.4 uM/L, p = 0.013) and pyruvate (61.9 ± 25.6 vs. 50.3 ± 23.1 uM/L, p = 0.026) in comparison to controls. However, this finding was accompanied by a blunted HIF-1α expression (1.1 (0.2 to 5.0) vs. 1.7 (0.4 to 9.2) arbitrary units (AU), p ≤ 0.001). Patients with diabetes also showed a significant reduction of all assessed clock genes’ expression. Univariate analysis showed that HIF-1α and almost all clock genes were significantly and negatively correlated with HbA1c concentration. In addition, positive correlations between HIF-1α and the clock genes were observed. The stepwise multivariate regression analysis showed that HbA1c and clock genes independently predicted the expression of HIF-1α. Type 2 diabetes modifies the expression of HIF-1α and clock genes, which correlates with the degree of metabolic control.
Oligonucleotides and microRNAs Targeting Telomerase Subunits in Cancer Therapy

Telomerase provides cancer cells with replicative immortality, and its overexpression serves as a near-universal marker of cancer. Anti-cancer therapeutics targeting telomerase have garnered interest as possible alternatives to chemotherapy and radiotherapy. Oligonucleotide-based therapies that inhibit telomerase through direct or indirect modulation of its subunits, human telomerase reverse transcriptase (hTERT) and human telomerase RNA gene (hTERC), are a unique and diverse subclass of telomerase inhibitors which hold clinical promise. MicroRNAs that play a role in the upregulation or downregulation of hTERT and respective progression or attenuation of cancer development have been effectively targeted to reduce telomerase activity in various cancer types. Tumor suppressor miRNAs, such as miRNA-512-5p, miRNA-138, and miRNA-128, and oncogenic miRNAs, such as miRNA-19b, miRNA-346, and miRNA-21, have displayed preclinical promise as potential hTERT-based therapeutic targets. Antisense oligonucleotides like GRN163L and T-oligos have also been shown to uniquely target the telomerase subunits and have become popular in the design of novel cancer therapies. Finally, studies suggest that G-quadruplex stabilizers, such as Telomestatin, preserve telomeric oligonucleotide architecture, thus inhibiting hTERC binding to the telomere. This review aims to provide an adept understanding of the conceptual foundation and current state of therapeutics utilizing oligonucleotides to target the telomerase subunits, including the advantages and drawbacks of each of these approaches.
Beta-Glucans as Immunomodulators in Poultry: Use and Potential Applications

Escalating consumer concerns have placed the poultry industry under mounting pressure to reduce the use of chemotherapeutic agents as feed additives. One possible alternative receiving increased attention is the use of immunomodulators such as β-glucan. Beta-glucans belong to a group of physiologically active compounds termed biological response modifiers due to their ability to stimulate the immune system. Beta-glucans are structural components of the cell wall of many bacteria, fungi, algae and yeast as well as cereal grains. The effects of β-glucans as active immunomodulators in mammals have been well noted; however, research concerning their impact in poultry has only recently been published. This review will begin with an “avian immunology primer”, and will then discuss various effects on performance and immune responses elicited by β-glucans in poultry and their potential implications to the industry.