Miracle-dz/UniFAR-FTUs huggingface dataset:
The Pharmacokinetics of Doxycycline in Channel Catfish (Ictalurus punctatus) Following Intravenous and Oral Administrations

The objective of this study was to investigate the bioavailability (BA) and pharmacokinetics (PK) of doxycycline (DC) in channel catfish (Ictalurus punctatus) following a single intravenous injection at 5 mg/kg and a single oral administration at 50 mg/kg at 24°C. The calculation of PK parameters was based on the software 3P97. The plasma samples were determined using ultra-performance liquid chromatography. Following oral administration, the multiple-peak phenomenon presented in concentration vs. time curve of DC at 2 h (107.01 mg/L), 8 h (55.07 mg/L), and 72 h (15.10 mg/L), respectively. The compartmental model cannot simulate the oral concentration vs. time profile beside a non-compartmental model. The calculated parameters of the elimination rate constant (λz), the elimination half-life (t1/2λz), and the area under the concentration vs. time curve (AUC0-144) were 0.037 1/h, 18.91 h, and 2255.45 μg. h/mL, respectively. After intravenous administration, the concentration vs. time profile of DC was best described by a two-compartmental open model without absorption. The parameters of the distribution rate constant (α), the distribution half-life (t1/2α), the elimination rate constant (β), the elimination half-life (t1/2β), the apparent distribution volume at steady state (Vss), the total clearance (Cl) and the area under the concentration vs. time curve (AUC0-∞) were 2.79 1/h, 0.25 h, 0.042 1/h, 16.51 h, 300.00 mL/kg, 14.00 mL/h/kg, and 364.99 μg. h/mL, respectively. For the calculation of BA values at the same condition, the data obtained from intravenous injection were also iterated based on a non-compartmental model, and the corresponding parameters of λz, t1/2λz, Vz, Cl, and AUC0-144 were 0.019 1/h, 36.26 h, 480.00 mL/kg, 9.10 mL/h/kg, and 514.45 μg. h/mL, respectively. However, there was a considerable difference in the same parameter when calculated by compartmental and non-compartmental approaches. Finally, the medium BA value of DC was evaluated to be 43.84%. This study provides future studies with a framework for determining the BA of DC in the development of a new formulation and provides information on the appropriate use of DC in aquaculture.
Exosomes in the Pathogenesis and Treatment of Multiple Myeloma in the Context of the Bone Marrow Microenvironment

Multiple myeloma (MM), the second most common hematological malignancy, is an incurable cancer of plasma cells. MM cells diffusely involves the bone marrow (BM) and establish a close interaction with the BM niche that in turn supports MM survival, proliferation, dissemination and drug resistance. In spite of remarkable progress in understanding MM biology and developing drugs targeting MM in the context of the BM niche, acquisition of multi-class drug resistance is almost universally inevitable. Exosomes are small, secreted vesicles that have been shown to mediate bidirectional transfer of proteins, lipids, and nucleic acids between BM microenvironment and MM, supporting MM pathogenesis by promoting angiogenesis, osteolysis, and drug resistance. Exosome content has been shown to differ between MM patients and healthy donors and could potentially serve as both cancer biomarker and target for novel therapies. Furthermore, the natural nanostructure and modifiable surface properties of exosomes make them good candidates for drug delivery or novel immunomodulatory therapy. In this review we will discuss the current knowledge regarding exosome’s role in MM pathogenesis and its potential role as a novel biomarker and therapeutic tool in MM.
The Role of Small Extracellular Vesicles in Viral-Protozoan Symbiosis: Lessons From Trichomonasvirus in an Isogenic Host Parasite Model

The protozoan parasite Trichomonas vaginalis (TV), exclusively adapted to the human genital tract, is one of the most common sexually transmitted pathogens. Adding to the complexity of the host-pathogen interactions, the parasite harbors TV-specific endosymbiont viruses (Trichomonasvirus, TVV). It was reported that small extracellular vesicles (sEVs) released by TV play a role in host immunity; however, the role of the viral endosymbiosis in this process remained unknown. We hypothesized that the virus may offer evolutionary benefit to its protozoan host at least in part by altering the immunomodulatory properties of sEVs spreading from the site of infection to non-infected immune effector cells. We infected human vaginal epithelial cells, the natural host of the parasite, with TV natively harboring TVV and an isogenic derivative of the parasite cured from the viral infection. sEVs were isolated from vaginal cell culture 24 h post TV infection and from medium where the isogenic TV strains were cultured in the absence of the human host. sEVs from TVV-negative but not TVV-positive parasites cultured alone caused NF-κB activation and increase of IL-8 and RANTES expression by uterine endocervical cells, which provide innate immune defense at the gate to the upper reproductive tract. Similarly, mononuclear leukocytes increased their IL-8, IL-6 and TNF-α output in response to sEVs from virus-negative, but not isogenic virus-positive parasites, the latter exosomes being immunosuppressive in comparison to TV medium control. The same phenomenon of suppressed immunity induced by the TVV-positive compared to TVV-negative phenotype was seen when stimulating the leukocytes with sEVs originating from infected vaginal cultures. In addition, the sEVs from the TVV-positive infection phenotype suppressed immune signaling of a toll-like receptor ligand derived from mycoplasma, another frequent TV symbiont. Quantitative comparative proteome analysis of the secreted sEVs from virus-positive versus virus-negative TV revealed differential expression of two functionally uncharacterized proteins and five proteins involved in Zn binding, protein binding, electron transfer, transferase and catalytic activities. These data support the concept that symbiosis with viruses may provide benefit to the protozoan parasite by exploiting sEVs as a vehicle for inter-cellular communications and modifying their protein cargo to suppress host immune activation.
Comparing Objective and Subjective Measures of Parkinson's Disease Using the Parkinson's KinetiGraph

Background: Parkinson's disease (PD) is a neurodegenerative disease that can lead to impaired motor function and execution of activities of daily living (ADL). Since clinicians typically can only observe patients' symptoms during visits, prescribed medication schedules may not reflect the full range of symptoms experienced throughout the day. Therefore, objective tools are needed to provide comprehensive symptom data to optimize treatment. One such tool is the Parkinson's KinetiGraph® (PKG), a wearable sensor that measures motor symptoms of Parkinson's disease. Objective: To build a mathematical model to determine if PKG data measuring Parkinson's patients' motor symptoms can predict patients' ADL impairment. Methods: Thirty-four patients with PD wore the PKG device for 6 days while performing their ADL. Patients' PKG scores for bradykinesia and dyskinesia, as well as their responses to a questionnaire asking if their ADL-level had been impacted by various motor symptoms, were used to build a multiple regression model predicting the patients' Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II scores. Results: Calculation of bradykinesia score response to medication showed that using a dosage response time of 30 min yielded a greater bradykinesia response than when the response time was set to 40, 50, 60, 70, 80, or 90 min. The overall multiple regression model predicting MDS-UPDRS part II score was significant (R2 = 0.546, p < 0.001). Conclusion: The PKG's ability to provide motor symptom data that correlates with clinical measures of ADL impairment suggests that it has strong potential as a tool for the assessment and management of Parkinson's disease motor symptoms.
Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features

The combination of cardiomyocytes (CM) and non-myocyte cardiac populations, such as endothelial cells (EC), and mesenchymal cells (MC), has been shown to be critical for recapitulation of the human heart tissue for in vitro cell-based modeling. However, most of the current engineered cardiac microtissues still rely on either (i) murine/human limited primary cell sources, (ii) animal-derived and undefined hydrogels/matrices with batch-to-batch variability, or (iii) culture systems with low compliance with pharmacological high-throughput screenings. In this work, we explored a culture platform based on alginate microencapsulation and suspension culture systems to develop three-dimensional (3D) human cardiac microtissues, which entails the co-culture of human induced pluripotent stem cell (hiPSC) cardiac derivatives including aggregates of hiPSC–CM and single cells of hiPSC–derived EC and MC (hiPSC–EC+MC). We demonstrate that the 3D human cardiac microtissues can be cultured for 15 days in dynamic conditions while maintaining the viability and phenotype of all cell populations. Noteworthy, we show that hiPSC–EC+MC survival was promoted by the co-culture with hiPSC–CM as compared to the control single-cell culture. Additionally, the presence of the hiPSC–EC+MC induced changes in the physical properties of the biomaterial, as observed by an increase in the elastic modulus of the cardiac microtissue when compared to the hiPSC–CM control culture. Detailed characterization of the 3D cardiac microtissues revealed that the crosstalk between hiPSC–CM, hiPSC–EC+MC, and extracellular matrix induced the maturation of hiPSC–CM. The cardiac microtissues displayed functional calcium signaling and respond to known cardiotoxins in a dose-dependent manner. This study is a step forward on the development of novel 3D cardiac microtissues that recapitulate features of the human cardiac microenvironment and is compliant with the larger numbers needed in preclinical research for toxicity assessment and disease modeling.
Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

Alzheimer’s disease (AD) is an incurable neurodegenerative disease. Numerous studies have demonstrated a critical role for dysregulated glucose metabolism in its pathogenesis. In this review, we summarize metabolic alterations in aging brain and AD-related metabolic deficits associated with glucose metabolism dysregulation, glycolysis dysfunction, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) deficits, and pentose phosphate pathway impairment. Additionally, we discuss recent treatment strategies targeting metabolic defects in AD, including their limitations, in an effort to encourage the development of novel therapeutic strategies.
Prevalence and Patterns of Multimorbidity Among Rural Elderly: Findings of the AHSETS Study

Introduction: In India, the proportion of older population is projected to increase from 8% in 2015 to 19% in 2050 and a third of the country's population will be older adults by end of the century. Multimorbidity is common among the elderly and the prevalence increases with age. Chronic conditions are most often present as clusters and it's critical to explore the prevalent pattern of clustering for better public health strategies. Method: A cross-sectional study was conducted among 725 rural older adults (>60 years) in Tigiria block of Odisha, India. Multimorbidity status was assessed using the prior validated MAQ-PC tool. Survey was conducted using android tablets installed with open data kit software. While Euclidean distances using K-means clustering algorithm were used to estimate the similarity or dissimilarity of observations. The optimum numbers of clusters were determined using silhouette method. Data were analyzed using multiple open source packages of R statistical programming software ver-3.6. 3. Result: The overall prevalence of multimorbidity was 48.8% of which dyads (25%) were the most common form, followed by triads (15.2%). The prevalence of multimorbidity was higher in females (50.4%) than males (47.4%). The optimal number of clusters was found to be 3. While arthritis alone was a separate cluster, hypertension and acid peptic disease were in another cluster and all the rest conditions were included in the third cluster. Conclusion: The cluster analysis to measure of proximity suggested arthritis, hypertension, and acid peptic disease are the diseases that occur mostly in isolation with the other chronic conditions in the rural elderly.
Tomato and Melon Meloidogyne Resistant Rootstocks Improve Crop Yield but Melon Fruit Quality Is Influenced by the Cropping Season

Four rotation sequences consisting of ungrafted tomato cv. Durinta – melon cv. Paloma or tomato grafted onto the resistant rootstock ‘Aligator’ – melon grafted onto the resistant Cucumis metuliferus accession BGV11135, and in reverse order, were conducted from 2015 to 2017 in a plastic greenhouse infested or not with Meloidogyne incognita to determine the plant tolerance (T), the minimum relative crop yield (m) and fruit quality. The relationship between M. incognita densities in soil at transplanting (Pi) of each crop and the crop yield was assessed and T and m were estimated by the Seinhorst’s damage model. In addition, the volume and the number of nuclei of single giant cells and the number of giant cells, its volume and the number of nuclei per feeding site in susceptible tomato and melon were compared to those in the resistant tomato and C. metuliferus 15 days after nematode inoculation in pot test. The relationship between the Pi and the relative crop yield fitted the Seinhorst’s damage model in both ungrafted and grafted tomato and melon, but not for all years and cropping seasons. The estimated T for ungrafted and grafted tomato did not differ but m was lower in the former (34%) than the latter (67%). Sodium concentration in fruits from ungrafted but not from grafted tomato increased with nematode densities in spring 2015 and 2016. The estimated ungrafted melon T did not differ from the grafted melon cultivated in spring, but it did when it was cultivated in summer. The relative crop yield of ungrafted melon was lower (2%) than the grafted cultivated in spring (62%) and summer (20%). Sodium concentration in melon fruits from ungrafted plants increased with nematode densities. No variations in fruit quality from grafted melon cultivated in spring were found, although less dry matter and soluble solid content at highest nematode densities were registered when it was cultivated in summer. Lower number of giant cells per feeding site was observed in both susceptible tomato germplasms compared to the resistant ones but they were more voluminous and held higher number of nuclei per giant cell and per feeding site.
Selenium Biofortification and Interaction With Other Elements in Plants: A Review

Selenium (Se) is an essential element for humans and animals and its deficiency in the diet is a global problem. Crop plants are the main source of Se for consumers. Therefore, there is much interest in understanding the factors that govern the accumulation and distribution of Se in the tissues of crop plants and the mechanisms of interaction of Se absorption and accumulation with other elements, especially with a view toward optimizing Se biofortification. An ideal crop for human consumption is rich in essential nutrient elements such as Se, while showing reduced accumulation of toxic elements in its edible parts. This review focuses on (a) summarizing the nutritional functions of Se and the current understanding of Se uptake by plant roots, translocation of Se from roots to shoots, and accumulation of Se in grains; and (b) discussing the influence of nitrogen (N), phosphorus (P), and sulfur (S) on the biofortification of Se. In addition, we discuss interactions of Se with major toxicant metals (Hg, As, and Cd) frequently present in soil. We highlight key challenges in the quest to improve Se biofortification, with a focus on both agronomic practice and human health.
Nitrogen-Fertilized Systems of Maize Intercropped With Tropical Grasses for Enhanced Yields and Estimated Land Use and Meat Production

Intercropping grain with forage crops bridges the gap between agriculture and sustainability. In tropical regions, forage grasses are increasingly being adopted as winter pasture intercropped and in rotation with maize to maximize food production. However, current recommendations for nitrogen (N) fertilizer application are based on monocropped maize (Zea mays), and the best N management approach for intercropping systems remains unclear. A field experiment was carried out in three growing seasons with three intercropping systems [monoculture maize, intercropped with palisadegrass (Urochloa brizantha), and intercropped with guineagrass (Megathyrus maximus)] combined with six different split applications of N to maize (0–0, 100–0, 70–30, 50–50, 30–70, and 0–100 kg N ha−1 at seeding-sidedressing) with four replicates. We measured dry matter (DM) and accumulated N in maize and forage grasses, as well as maize production components and yields. Additionally, land equivalent ratio, relative crowding coefficient, aggressivity of maize with forage grasses, forage crude protein (CP) concentration, estimated animal stocking rate, and estimated meat production and economic outcomes. Greatest maize yield was 8.7 Mg ha−1 for monocropped maize. However, favorable maize yield was also obtained in intercropping systems. Although no difference was observed between intercropping systems, applying all N at sidedressing of maize negatively affected maize and forage yields and, consequently, land use and economic evaluation. For both intercropping systems, estimated meat and land use were 114 and 10% higher when N fertilizer was applied than the control (0–0 kg N ha−1), on average. Maize-forage grass intercropping is a viable alternative production system for improving yields and land use. In addition, estimated meat production and revenue can be enhanced with palisadegrass or guineagrass. At least half of the N fertilizer must be applied early in the growing season of maize to maximize production of the entire system.
Drug Response Associated With and Prognostic lncRNAs Mediated by DNA Methylation and Transcription Factors in Colon Cancer

Colon cancer is the most commonly diagnosed malignancy and the leading cause of cancer deaths worldwide. As well as lifestyle, genetic and epigenetic changes are key factors that influence the risk of colon cancer. However, the impact of epigenetic alterations in non-coding RNAs and their consequences in colon cancer have not been fully characterized. We detected differential methylation sites (DMSs) in long non-coding RNA (lncRNA) promoters and identified lncRNA expression quantitative trait methylations (lncQTMs) by association tests. To investigate how transcription factor (TF) binding was affected by DNA methylation, we characterized the occurrence of known TFs among DMSs collected from the MEME suite. We further combined methylome and transcriptome data to construct TF–methylation–lncRNA relationships. To study the role of lncRNAs in drug response, we used pharmacological and lncRNA profiles from the Cancer Cell Line Encyclopedia (CCLE) and investigated the association between lncRNAs and drug activity. We also used combinations of TF–methylation–lncRNA relationships to stratify patient survival using a risk model. DNA methylation sites displayed global hyper-methylation in lncRNA promoters and tended to have negative relationships with the corresponding lncRNAs. Negative lncQTMs located near transcription start sites (TSSs) had more significant correlations with the corresponding lncRNAs. Some lncRNAs found to be mediated by the interplay between DNA methylation and TFs were previously identified as markers for colon cancer. We also found that the ELF1-cg05372727- LINC00460 relationship were prognostic signatures for colon cancer. These findings suggest that lncRNAs mediated by the interplay between DNA methylation and TFs are promising predictors of drug response, and that combined TF–methylation–lncRNA can serve as a prognostic signature for colon cancer.
Auxin Directly Upregulates GhRAC13 Expression to Promote the Onset of Secondary Cell Wall Deposition in Cotton Fibers

Cotton fibers are single cells that show a relatively independent developmental process of cell differentiation, elongation, and secondary wall deposition. Auxin promotes fiber cell protrusion from the surface of the ovule. However, the role of auxin at other stages of cotton fiber development remains largely unknown. To gain a deeper insight into this aspect, we measured indoleacetic acid (IAA) content in developing fibers. Results showed an increase in IAA content at the transition stage from elongation to secondary cell wall deposition. Subsequently, we investigated the differences between two transgenic cottons that show upregulated and downregulated fiber auxin levels, respectively. In planta analysis revealed that, in addition to promoting cell elongation, auxin regulated the time of initiation of reactive oxygen species (ROS) production and secondary wall deposition in cotton fibers. This was closely correlated with the upregulated expression of GhRAC13, which regulates ROS-triggered cellulose synthesis. We found multiple putative auxin-responsive elements existed within the promoter region of GhRAC13, and IAA could induce proGhRAC13 activity. The dual-luciferase reporter assay further proved the activation of proGhRAC13 by GhARF5, an auxin-signaling activator. Altogether, our results suggest a role of auxin in promoting the onset of secondary growth by directly upregulating GhRAC13 expression in cotton fibers.
General Cognitive Ability Predicts Survival-Readiness in Genetically Heterogeneous Laboratory Mice

Although genetically heterogeneous laboratory mice express individual differences in general cognitive ability (c.f., “intelligence”), it is unknown whether these differences are translated into behaviors that would promote survival. Here, genetically heterogeneous laboratory CD-1 mice were administered a series of cognitive tests from which their aggregate general cognitive ability was estimated. Subsequently, all animals were tested on nine (unlearned) tasks designed to assess behaviors that could contribute to survival in the wild. These tests included nest building (in the home and a novel environment), exploration, several indices of food finding, retrieval, and preference, and predator avoidance. Like general cognitive ability, a principal component analysis of these measures of survival-related behaviors (survival-readiness) yielded a general factor that accounted for ∼25% of the variance of mice across all of the tasks. An aggregate metric of general cognitive ability predicted an aggregate metric of general survival-readiness (r = 0.64), suggesting that more intelligent animals would be more suited for survival in natural environments. The nature of the pattern of correlations between general cognitive ability and performance on individual tests of survival-readiness (where tests conducted in previously unexplored contexts were more closely related to general cognitive ability) suggests the possibility that heightened attention (which is taxed in a novel environment) may be the common mediator of both of these classes of abilities, although other potential mediators are discussed. In total, these results suggest that performance on tasks that are explicitly intended to assess the likelihood of survival can be impacted by cognitive abilities.
A Randomized Controlled Trial of Ovarian Suppression in Premenopausal Women: No Change in Free‐Living Energy Expenditure

The purpose of this study was to determine whether suppression of ovarian function (gonadotropin‐releasing hormone agonist [GnRHAG]) for 24 weeks in premenopausal women approaching menopause causes changes in body composition and a decline in free‐living physical activity energy expenditure (PAEE) and whether endurance exercise training attenuates the changes.