Miracle-dz/UniFAR-FTUs huggingface dataset:
Cy3-RgIA-5727 Labels and Inhibits α9-Containing nAChRs of Cochlear Hair Cells

Efferent cholinergic neurons inhibit sensory hair cells of the vertebrate inner ear through the combined action of calcium-permeable α9α10-containing nicotinic acetylcholine receptors (nAChRs) and associated calcium-dependent potassium channels. The venom of cone snails is a rich repository of bioactive peptides, many with channel blocking activities. The conopeptide analog, RgIA-5474, is a specific and potent antagonist of α9α10-containing nAChRs. We added an alkyl functional group to the N-terminus of the RgIA-5474, to enable click chemistry addition of the fluorescent cyanine dye, Cy3. The resulting peptide, Cy3-RgIA-5727, potently blocked mouse α9α10 nAChRs expressed in Xenopus oocytes (IC50 23 pM), with 290-fold less activity on α7 nAChRs and 40,000-fold less activity on all other tested nAChR subtypes. The tight binding of Cy3-RgIA-5727 provided robust visualization of hair cell nAChRs juxtaposed to cholinergic efferent terminals in excised, unfixed cochlear tissue from mice. Presumptive postsynaptic sites on outer hair cells (OHCs) were labeled, but absent from inner hair cells (IHCs) and from OHCs in cochlear tissue from α9-null mice and in cochlear tissue pre-incubated with non-Cy3-conjugated RgIA-5474. In cochlear tissue from younger (postnatal day 10) mice, Cy3-RgIA-5727 also labeled IHCs, corresponding to transient efferent innervation at that age. Cy3 puncta in Kölliker’s organ remained in the α9-null tissue. Pre-exposure with non-Cy3-conjugated RgIA-5474 or bovine serum albumin reduced this non-specific labeling to variable extents in different preparations. Cy3-RgIA-5727 and RgIA-5474 blocked the native hair cell nAChRs, within the constraints of application to the excised cochlear tissue. Cy3-RgIA-5727 or RgIA-5474 block of efferent synaptic currents in young IHCs was not relieved after 50 min washing, so effectively irreversible.
Oregano Essential Oil Micro- and Nanoencapsulation With Bioactive Properties for Biotechnological and Biomedical Applications

Due to the preservative, antioxidant, antimicrobial, and therapeutic properties of oregano essential oil (OEO), it has received an emerging interest for biotechnological and biomedical applications. However, stability and bioactivity can be compromised by its natural volatile and hydrophobic nature, and by external factors including light, heat, or oxygen. Therefore, micro- and nanoencapsulation are being employed to guarantee oregano oil protection from outside aggressions and to maximize its potential. Oregano oil encapsulation is an interesting strategy used to increase its stability, enhance its bioactivity, and decrease its volatility. At the same time, the versatility that micro- and nanocarriers offer, allows to prepare tailored systems that can provide a controlled and targeted release of the encapsulated principle, influence its bioactive activities, or even provide additional properties. Most common materials used to prepare these carriers are based on lipids and cyclodextrins, due to their hydrophobic nature, polymers due to their versatility in composition, and hybrid lipid-polymer systems. In this context, recently developed micro- and nanocarriers encapsulating oregano oil with applications in the biotechnological and biomedical fields will be discussed.
Modulation of the Hypothalamic Nutrient Sensing Pathways by Sex and Early-Life Stress

There are sex differences in metabolic disease risk, and early-life stress (ES) increases the risk to develop such diseases, potentially in a sex-specific manner. It remains to be understood, however, how sex and ES affect such metabolic vulnerability. The hypothalamus regulates food intake and energy expenditure by sensing the organism’s energy state via metabolic hormones (leptin, insulin, ghrelin) and nutrients (glucose, fatty acids). Here, we investigated if and how sex and ES alter hypothalamic nutrient sensing short and long-term. ES was induced in mice by limiting the bedding and nesting material from postnatal day (P)2-P9, and the expression of genes critical for hypothalamic nutrient sensing were studied in male and female offspring, both at P9 and in adulthood (P180). At P9, we observed a sex difference in both Ppargc1a and Lepr expression, while the latter was also increased in ES-exposed animals relative to controls. In adulthood, we found sex differences in Acacb, Agrp, and Npy expression, whereas ES did not affect the expression of genes involved in hypothalamic nutrient sensing. Thus, we observe a pervasive sex difference in nutrient sensing pathways and a targeted modulation of this pathway by ES early in life. Future research is needed to address if the modulation of these pathways by sex and ES is involved in the differential vulnerability to metabolic diseases.
Influence of Estuarine Water on the Microbial Community Structure of Patagonian Fjords

Fjords are sensitive areas affected by climate change and can act as a natural laboratory to study microbial ecological processes. The Chilean Patagonian fjords (41–56°S), belonging to the Subantarctic ecosystem (46–60°S), make up one of the world’s largest fjord systems. In this region, Estuarine Water (EW) strongly influences oceanographic conditions, generating sharp gradients of oxygen, salinity and nutrients, the effects of which on the microbial community structure are poorly understood. During the spring of 2017 we studied the ecological patterns (dispersal and oceanographic factors) underlying the microbial community distribution in a linear span of 450 km along the estuarine-influenced Chilean Patagonian fjords. Our results show that widespread microbial dispersion existed along the fjords where bacterioplankton exhibited dependence on the eukaryotic phytoplankton community composition. This dependence was particularly observed under the low chlorophyll-a conditions of the Baker Channel area, in which a significant relationship was revealed between SAR11 Clade III and the eukaryotic families Pyrenomonadaceae (Cryptophyte) and Coccomyxaceae (Chlorophyta). Furthermore, dissolved oxygen and salinity were revealed as the main drivers influencing the surface marine microbial communities in these fjords. A strong salinity gradient resulted in the segregation of the Baker Channel prokaryotic communities from the rest of the Patagonian fjords. Likewise, Microbacteriaceae, Burkholderiaceae and SAR11 Clade III, commonly found in freshwater, were strongly associated with EW conditions in these fjords. The direct effect of EW on the microbial community structure and diversity of the fjords exemplifies the significance that climate change and, in particular, deglaciation have on this marine region and its productivity.
Relationship Between the COVID-19 Pandemic and Ecological, Economic, and Social Conditions

The COVID-19 pandemic had huge impacts on the global world, with both a negative impact on society and economy but a positive one on nature. But this universal effect resulted in different infection rates from country to country. We analyzed the relationship between the pandemic and ecological, economic, and social conditions. All of these data were collected in 140 countries at six time points. Correlations were studied using univariate and multivariate regression models. The world was interpreted as a single global ecosystem consisting of ecosystem units representing countries. We first studied 140 countries around the world together, and infection rates were related to per capita GDP, Ecological Footprint, median age, urban population, and Biological Capacity, globally. We then ranked the 140 countries according to infection rates. We created four groups with 35 countries each. In the first group of countries, the infection rate was very high and correlated with the Ecological Footprint (consumption) and GDP per capita (production). This group is dominated by developed countries, and their ecological conditions have proved to be particularly significant. In country groups 2, 3, and 4, infection rates were high, medium, and low, respectively, and were mainly related to median age and urban population. In the scientific discussion, we have interpreted why infection rates are very high in developed countries. Sustainable ecosystems are balanced, unlike the ecosystems of developed countries. The resilience and the health of both natural ecosystems and humans are closely linked to the world of microbial communities, the microbiomes of the biosphere. It is clear that both the economy and society need to be in harmony with nature, creating sustainable ecosystems in developed countries as well.
The Role of Geographical Area and Entrepreneurs' Personality

This study proposed a line of research on entrepreneurship based on the analysis of personality traits and geographical area. Its objective is to identify whether certain personality traits or sociocultural variables typical of a particular geographical area influence those who have already started an entrepreneurial activity to keep it up, in other words, to maintain their entrepreneurial intention. The research results reach a sample of 479 entrepreneurs from two Iberian Peninsula geographical areas. The analyse of the psychometric properties on the Entrepreneurial Orientation Questionnaire (EOQ) identified five dimensions of the enterprising personality. They also evidence that geographical location is a factor that contributes to the development of the entrepreneurial intentions that determine the business profile. The results show that entrepreneurs in the northern area tend to maintain their business than those in the central zone.
Abscisic Acid Mediates Drought-Enhanced Rhizosheath Formation in Tomato

The rhizosheath, commonly defined as soil adhering to the root surface, may confer drought tolerance in various crop species by enhancing access to water and nutrients under drying stress conditions. Since the role of phytohormones in establishing this trait remains largely unexplored, we investigated the role of ABA in rhizosheath formation of wild-type (WT) and ABA-deficient (notabilis, not) tomatoes. Both genotypes had similar rhizosheath weight, root length, and root ABA concentration in well-watered soil. Drying stress treatment decreased root length similarly in both genotypes, but substantially increased root ABA concentration and rhizosheath weight of WT plants, indicating an important role for ABA in rhizosheath formation. Neither genotype nor drying stress treatment affected root hair length, but drying stress treatment decreased root hair density of not. Under drying stress conditions, root hair length was positively correlated with rhizosheath weight in both genotypes, while root hair density was positively correlated with rhizosheath weight in well-watered not plants. Root transcriptome analysis revealed that drought stress increased the expression of ABA-responsive transcription factors, such as AP2-like ER TF, alongside other drought-regulatory genes associated with ABA (ABA 8′-hydroxylase and protein phosphatase 2C). Thus, root ABA status modulated the expression of specific gene expression pathways. Taken together, drought-induced rhizosheath enhancement was ABA-dependent, but independent of root hair length.
Poultry Response to Heat Stress: Its Physiological, Metabolic, and Genetic Implications on Meat Production and Quality Including Strategies to Improve Broiler Production in a Warming World

The continuous increase in poultry production over the last decades to meet the high growing demand and provide food security has attracted much concern due to the recent negative impacts of the most challenging environmental stressor, heat stress (HS), on birds. The poultry industry has responded by adopting different environmental strategies such as the use of environmentally controlled sheds and modern ventilation systems. However, such strategies are not long-term solutions and it cost so much for farmers to practice. The detrimental effects of HS include the reduction in growth, deterioration of meat quality as it reduces water-holding capacity, pH and increases drip loss in meat consequently changing the normal color, taste and texture of chicken meat. HS causes poor meat quality by impairing protein synthesis and augmenting undesirable fat in meat. Studies previously conducted show that HS negatively affects the skeletal muscle growth and development by changing its effects on myogenic regulatory factors, insulin growth factor-1, and heat-shock proteins. The focus of this article is in 3-fold: (1) to identify the mechanism of heat stress that causes meat production and quality loss in chicken; (2) to discuss the physiological, metabolic and genetic changes triggered by HS causing setback to the world poultry industry; (3) to identify the research gaps to be addressed in future studies.
Prediction of EGFR Mutation Status Based on 18F-FDG PET/CT Imaging Using Deep Learning-Based Model in Lung Adenocarcinoma

Objective The purpose of this study was to develop a deep learning-based system to automatically predict epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Methods Three hundred and one lung adenocarcinoma patients with EGFR mutation status were enrolled in this study. Two deep learning models (SECT and SEPET) were developed with Squeeze-and-Excitation Residual Network (SE-ResNet) module for the prediction of EGFR mutation with CT and PET images, respectively. The deep learning models were trained with a training data set of 198 patients and tested with a testing data set of 103 patients. Stacked generalization was used to integrate the results of SECT and SEPET. Results The AUCs of the SECT and SEPET were 0.72 (95% CI, 0.62–0.80) and 0.74 (95% CI, 0.65–0.82) in the testing data set, respectively. After integrating SECT and SEPET with stacked generalization, the AUC was further improved to 0.84 (95% CI, 0.75–0.90), significantly higher than SECT (p<0.05). Conclusion The stacking model based on 18F-FDG PET/CT images is capable to predict EGFR mutation status of patients with lung adenocarcinoma automatically and non-invasively. The proposed model in this study showed the potential to help clinicians identify suitable advanced patients with lung adenocarcinoma for EGFR‐targeted therapy.
Miltefosine Against Scedosporium and Lomentospora Species: Antifungal Activity and Its Effects on Fungal Cells

Scedosporium and Lomentospora species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the in vitro antifungal activity of miltefosine against Scedosporium and Lomentospora species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different Scedosporium and Lomentospora species at 2–4 µg/ml and reduced biofilm formation. The loss of membrane integrity in Scedosporium aurantiacum caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and Scedosporium and Lomentospora cells, highlighting its potential use as new antifungal drug in the future.
Restoration of Proresolution Pathway with Exogenous Resolvin D1 Prevents Sevoflurane-Induced Cognitive Decline by Attenuating Neuroinflammation in the Hippocampus in Rats with Type 2 Diabetes Mellitus

Sevoflurane (SEV), a commonly used volatile anesthetic, has been shown to cause cognitive decline in diabetic rats by aggregating neuroinflammation in the hippocampus, but the underlying mechanisms are unknown. Recent evidence suggests that neuroinflammation could be a consequence of failure to resolve inflammation by specialized pro-resolving lipid mediators including resolvin D1 (RvD1). Here we first examined whether type 2 diabetes mellitus (DM) alters RvD1 proresolution pathway. Diabetic Goto-Kakizaki (GK) rats and non-diabetic Wistar rats received control or 2.6% SEV exposure for 4 h. Seven days after exposure, GK control rats, compared with Wistar control rats, had significantly lower RvD1 levels in plasma and CSF and decreased RvD1 receptor FPR2 expression in the hippocampus. SEV increased RvD1 levels in plasma and CSF and FPR2 expression in the hippocampus in Wistar rats but not in GK rats. We next examined whether RvD1 treatment of GK rats can prevent SEV-induced neuroinflammation and cognitive decline. GK rats received control, SEV or SEV and once-daily treatment with exogenous RvD1 (0.2 ug/kg, ip) for 7 days. RvD1 administration markedly increased RvD1 levels in plasma and CSF and FPR2 expression in the hippocampus in GK rats received SEV. Compared with GK control rats, GK rats received SEV exhibited shorter freezing times in trace fear conditioning task, which was accompanied by increased microglia activity and pro-inflammatory cytokine expression in the hippocampus. RvD1 administration attenuated SEV-induced increases in microglia activity and pro-inflammatory cytokine expression in the hippocampus, preventing cognitive decline in GK rats. Notably, neither SEV nor RvD1 altered metabolic parameters in GK rats. The results suggest that RvD1 proresolution pathway is impaired in the brain of diabetic GK rats. which may enhance the susceptibility to SEV, contributing to neuroinflammation and cognitive decline. Restoration of RvD1 proresolution pathway in diabetic GK rats with exogenous RvD1 can prevent SEV-induced cognitive decline by attenuating neuroinflammation in the hippocampus.
Effects of Chronic Alcohol Use Disorder on the Visual Tilt Illusion

Rationale: Among the serious consequences of alcohol use disorder (AUD) is the reduced ability to process visual information. It is also generally agreed that AUD tends to occur with disturbed excitation–inhibition (EI) balance in the central nervous system. Thus, a specific visual behavioral probe could directly qualify the EI dysfunction in patients with AUD. The tilt illusion (TI) is a paradigmatic example of contextual influences on perception of central target. The phenomenon shows a characteristic dependence on the angle between the inducing surround stimulus and the central target test. For small angles, there is a repulsion effect; for larger angles, there is a smaller attraction effect. The center-surround inhibition in tilt repulsion is considered to come from spatial orientational interactions between orientation-tuned neurons in the primary visual cortex (V1), and tilt attraction is from higher-level effects of orientation processing in the visual information processing. Objectives: The present study focuses on visual spatial information processing and explores whether chronic AUD patients in abstinence period exhibited abnormal TI compared with healthy controls. Methods: The participants are 30 male volunteers (20–46 years old) divided into two groups: the study group consists of 15 clinically diagnosed AUD patients undergoing abstinence from alcohol, and the control group consists of 15 healthy volunteers. The TI consists of a center target surround with an annulus (both target and annulus are sinusoidal grating with spatial frequency = 2 cycles per degree). The visual angle between center and surround is a variable restricted to 0°, ±15°, ±30°, or ±75°. For measuring the TI, participants have to report whether the center target grating orientation tilted clockwise or counterclockwise from the internal vertical orientation by pressing corresponding keys on the computer keyboard. No feedback is provided regarding response correctness. Results: The results reveal significantly weaker tilt repulsion effect under surround orientation ±15° (p < 0.05) and higher lapse rate (attention limitation index) under all tested surround orientations (all ps < 0.05) in patients with chronic AUD compared with health controls. Conclusions: These results provide psychophysical evidence that visual perception of center-contextual stimuli is different between AUD and healthy control groups.
Extracellular Vesicles: A Novel Opportunity for Precision Medicine in Respiratory Diseases

Extracellular vesicles are membrane-bound nanoparticles secreted by cells which play a well-known role in cell to cell communication. The most update to date nomenclature categorizes extracellular vesicles based on their relative size, protein markers, and/or the cell type of origin. Extracellular vesicles can be isolated from biological fluids using a variety of methods, including but not limited to, ultrafiltration, size-exclusion chromatography, differential ultracentrifugation, density gradient centrifugation, precipitation-based methods, and immunoaffinity capture. These nanovesicles carry distinct “cargo,” made up of biomolecules such as nucleic acids, lipids, and protein, which is delivered to nearby target cells. The “cargo” profile carried by extracellular vesicles is critical in their role of communication and resembles the physiological status of the cell they originated from. For the purpose of this review, we will focus on the miRNA cargo. Extracellular vesicle-miRNA profiles hold the potential to be used in diagnostic panels for a variety of diseases through a novel method known as “liquid biopsy. ” In addition to this, extracellular vesicles may serve as a potential method to deliver drugs to specific cells within the body. This mini-review provides background into what extracellular vesicles are, methods of isolating these nanoparticles, their potential use as a biomarker and drug delivery system for precision medicine, and a summary of the current literature covering the role of some extracellular vesicle-cargo's in various pulmonary diseases.
A Systematic Review of Anogenital Distance and Gynecological Disorders: Endometriosis and Polycystic Ovary Syndrome

Background and Aim Anogenital distance (AGD) can serve as a life-long indicator of androgen action in gestational weeks 8–14. AGD has been used as an important tool to investigate the exposure to endocrine-disrupting compounds in newborns and in individuals with male reproductive disorder. Endometriosis and polycystic ovary syndrome (PCOS) are two common gynecological disorders and both are related to prenatal androgen levels. Therefore, we performed a systematic review to evaluate the relationships of AGD with these gynecological disorders. Methods PubMed, Web of Science, and Embase were searched for published studies up to January 25, 2021. No language restriction was implemented. Results Ten studies were included in this review. Five focused on women with endometriosis, and six investigated women with PCOS. According to these studies, PCOS patients had longer AGD than controls, while endometriosis patients had shorter AGD than controls. In conclusion, this study provides a detailed and accurate review of the associations of AGD with endometriosis and PCOS. Conclusion The current findings indicate the longer AGD was related to PCOS and shorter AGD was related to endometriosis. However, further well-designed studies are needed to corroborate the current findings.