Miracle-dz/UniFAR-FTUs huggingface dataset:
Visual Symptoms, Vegetative Growth, and Mineral Concentration in Fig Tree (Ficus carica L.) Under Macronutrient Deficiencies

The common fig is an edible fruit which is appreciated for its organoleptic characteristics and high commercial value. Several factors, including mineral nutrition, affect fig production. Macronutrients fulfill specific functions in the metabolism of plants, affecting some functions when they are at low levels. So, in the present investigation, the visual symptoms of nitrogen, phosphorus, potassium, calcium, and magnesium deficiencies were identified and characterized, as well as their effects on vegetative growth and the concentration of minerals in fig tree tissues, using the missing element technique in a controlled hydroponic system. N was the element that most affected vegetative growth, causing smaller stem diameter, leaf area, and dry weight. Treatments without P and K followed. In addition, significant differences were found in the mineral concentration in leaf, stem, and root, with various interactions of antagonism and synergism observed according to the absence of each element.
In Vivo Hepatoprotective Effects of a Peptide Fraction from Krill Protein Hydrolysates against Alcohol-Induced Oxidative Damage

Background: Krill (Euphausia superba) represent the largest animal biomass on earth, and are a rich source of high-quality protein with essential amino acids. Krill-derived peptides are renowned for their antioxidant activities. Hence, these peptides may have protective effects against oxidative stress. Alcoholic liver disease is a prevalent cause of death worldwide. The present study explores the hepatoprotective effects of krill peptide hydrolysate fractions against ethanol-induced liver damage in BALB/c mice. Methods: Hydrolysis was carried out by mimicking the gastrointestinal digestion environment and the filtrate was fractionated based on molecular weight (<1 kDa, 1–3 kDa, and >3 kDa). The 1–3 kDa fraction (KPF), which indicated the highest antioxidant effect, was further investigated for its effect on weight and survival rate increase in mice and its influence on serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and liver cholesterol levels. Moreover, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels were measured, followed by Nrf2 and HO-1 expression. Histopathology studies were conducted to assess hepatic tissue damage. Results: KPF enhanced the weight and survival rate of mice while reducing serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and liver cholesterol levels. Moreover, KPF upregulated SOD, CAT, and GPx in liver tissues, while downregulating tumor necrosis factor α and interleukin-6 mRNA expression. KPF further increased Nrf2 and HO-1 expression and suppressed ethanol-induced apoptotic proteins in the liver. Histopathology of KPF-treated mice showed less hepatic tissue damage compared to ethanol-treated mice. Conclusions: Hydrolysates and bioactive peptides prepared from krill can be employed as functional foods to enhance liver function and health. Further investigations of KPF could lead to the development of functional foods.
GREEN AT HOME. GREEN ON THE ROAD? AN EXAMINATION OF WHETHER INDIVIDUALS WHO PRACTICE ECO-SUSTAINABLE BEHAVIOURS IN THEIR DAILY LIVES MAINTAIN THESE HABITS

Recent data indicates eco-sustainable tourism accounts for an increasing percentage of total worldwide tourism receipts. The economic influence, leveraged with the positive environmental implications associated with sustainability practices, has resulted in the emergence of eco-sustainability as an up and coming area of study. This study aims to examine whether tourists who employ eco-sustainable practices in their daily routines maintain these practices while traveling. This research will essentially bridge the gap between conflicting research which indicates a willingness to pay more, and studies which exhibit price sensitivity in relation to travelers’ green tendencies. Furthermore, this study will help to ascertain whether tourists seek out environmentally-friendly properties, or whether these entities are viewed as simply a convenience while travelling. This research is unique in its approach, since it examines which traits consumers are looking for in a green hospitality business and whether these firms benefit financially from increased demand if environmentally conscious policies are adopted.
Identification of Drug Resistance Determinants in a Clinical Isolate of Pseudomonas aeruginosa by High-Density Transposon Mutagenesis

With the aim to identify potential new targets to restore antimicrobial susceptibility of multidrug-resistant (MDR) Pseudomonas aeruginosa isolates, we generated a high-density transposon (Tn) insertion mutant library in an MDR P. aeruginosa bloodstream isolate (isolate ID40). The depletion of Tn insertion mutants upon exposure to cefepime or meropenem was measured in order to determine the common resistome for these clinically important antipseudomonal β-lactam antibiotics. ABSTRACT With the aim to identify potential new targets to restore antimicrobial susceptibility of multidrug-resistant (MDR) Pseudomonas aeruginosa isolates, we generated a high-density transposon (Tn) insertion mutant library in an MDR P. aeruginosa bloodstream isolate (isolate ID40). The depletion of Tn insertion mutants upon exposure to cefepime or meropenem was measured in order to determine the common resistome for these clinically important antipseudomonal β-lactam antibiotics. The approach was validated by clean deletions of genes involved in peptidoglycan synthesis/recycling, such as the genes for the lytic transglycosylase MltG, the murein (Mur) endopeptidase MepM1, the MurNAc/GlcNAc kinase AmgK, and the uncharacterized protein YgfB, all of which were identified in our screen as playing a decisive role in survival after treatment with cefepime or meropenem. We found that the antibiotic resistance of P. aeruginosa can be overcome by targeting usually nonessential genes that turn essential in the presence of therapeutic concentrations of antibiotics. For all validated genes, we demonstrated that their deletion leads to the reduction of ampC expression, resulting in a significant decrease in β-lactamase activity, and consequently, these mutants partly or completely lost resistance against cephalosporins, carbapenems, and acylaminopenicillins. In summary, the determined resistome may comprise promising targets for the development of drugs that may be used to restore sensitivity to existing antibiotics, specifically in MDR strains of P. aeruginosa.
Dry Coupling of Ultrasonic Transducer Components for High Temperature Applications

The viability for dry coupling of piezoelectric ultrasonic transducer components was investigated, using a thin foil of annealed silver as a filler material/coupling agent at each component interface. Criteria used for room temperature evaluation were centered on signal-to-noise ratio (SNR) and echo bandwidth, for a Li-Nb based transducer operating in pulse-echo mode. A normal clamping stress of only 25 MPa, applied repeatedly over three loading cycles on a precisely-aligned transducer stack, was sufficient to yield backwall echoes with a SNR greater than 25 dB, and a 3 dB bandwidth of approximately 65%. This compares to a SNR of 32 dB and a 3 dB bandwidth of 65%, achievable when all transducer interfaces were coupled with ultrasonic gel. The respective roles of a soft filler material, alignment of transducer components, cyclic clamping, component roughness, and component flatness were evaluated in achieving this high efficiency dry coupling, with transducer clamping forces far lower than previously reported. Preliminary high temperature tests indicate that this coupling method is suitable for high temperature and achieves signal quality comparable to that at room temperature with ultrasonic gel.
Psychometric Evaluation of the Nasal Obstruction Symptom Evaluation Scale for Pediatric Patients

Objective To evaluate the psychometric properties of the nasal obstruction symptom scale within a sample of pediatric patients undergoing septoplasty or functional septorhinoplasty. Study Design This was a prospective study with nasal obstruction symptom scale evaluations conducted pre- and postoperatively. Setting A tertiary care pediatric hospital. Subjects and Methods Pediatric patients underwent septoplasty or functional septorhinoplasty (FSR) from January 2013 to January 2017. Reliability of the scale was assessed through measures of internal consistency. In addition, item response models of each item were evaluated to assess how well each item captured individuals with varying levels of nasal obstruction. Study authors assessed face validity, and construct validity was assessed by correlation measures between items and exploratory factor analysis. Results A total of 136 patients, ages 8 to 18 years with a mean age of 15.7 ± 2.1 years, completed pre- and postoperative evaluations. Internal consistency of the scale was high (Cronbach’s α = 0.83). Predominantly a unidimensional scale resulted from exploratory factor analyses. Item response models indicate questions capture low to moderate levels of nasal obstruction within this population. Additional analyses show the scale functions similarly between septoplasty and FSR patients. Conclusion The Nasal Obstruction Symptom Evaluation scale is a robust tool that may be incorporated as a subjective evaluation of severity of nasal obstruction among pediatric patients undergoing a septoplasty or functional septorhinoplasty.
MuTraff: A Smart-City Multi-Map Traffic Routing Framework

Urban traffic routing is deemed to be a significant challenge in intelligent transportation systems. Existing implementations suffer from several intrinsic issues such as scalability in centralized systems, unnecessary complexity of mechanisms and communication in distributed systems, and lack of privacy. These imply force intensive computational tasks in the traffic control center, continuous communication in real-time with involved stakeholders which require drivers to reveal their location, origin, and destination of their trips. In this paper we present an innovative urban traffic routing framework and reference architecture (multimap traffic control architecture, MuTraff), which is based on the strategical generation and distribution of a set of traffic network maps (traffic weighted multimaps, TWM) to vehicle categories or fleets. Each map in a TWM map set has the same topology but a different distribution of link weights, which are computed by considering policies and constraints that may apply to different vehicle groups. MuTraff delivers a traffic management system (TMS), where a traffic control center generates and distributes maps, while routing computation is performed at the vehicles. We show how this balance between generation, distribution, and routing computation improves scalability, eases communication complexities, and solves former privacy issues. Our study presents case studies in a real city environment for (a) global congestion management using random maps; (b) congestion control on road incidents; and c) emergency fleets routing. We show that MuTraff is a promising foundation framework that is easy to deploy, and is compatible with other existing TMS frameworks.
CXCR4/TGF-β1 mediated self-differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and promoted colorectal carcinoma development

ABSTRACT Background: Tumor microenvironment (TME) is a crucial part of tumor hallmarks. Mesenchymal stem cells (MSCs), important components of TME, are the main source of Carcinoma-associated fibroblasts (CAFs), but the mechanism of transformation regulation is still unclear. Transforming growth factor-β1 (TGF-β1), chemokine Stromal cell-derived factor-1 (SDF-1) and its endogenous receptor CXCR4 may play important roles during this process. Methods: Co-culture technique was used to explore the effects of MSCs on the proliferation, migration and invasion of colorectal carcinoma (CRC) cells and how they induced MSCs to differentiate into CAFs. The expression of α-SMA, Vimentin, S100A4 and FAP were detected as CAFs markers. Inhibitors AMD3100 and cyclophosphamide (Cy) were pre-treated in MSCs to verify the functions of CXCR4/TGF-β1. Finally, the xenograft models in nude mice were generated to further verify this process in vivo. Results: MSCs promoted the CRCs proliferation, invasion and migration, and induced SDF-1 expression and secretion, which dramatically up-regulated CXCR4 and TGF-β1 expression in MSCs. The levels of CAFs markers elevated in MSCs, indicating CAFs differentiation occurred in MSCs. AMD3100 and Cy treatment significantly blocked this differentiation process of MSCs by suppressing CXCR4 expression and TGF-β1 secretion. In vivo xenograft experiments also demonstrated that MSCs promoted differentiation into CAFs through CXCR4/TGF-β1 signaling in either primary tumor tissues or hepatic metastatic tissues of CRC. Conclusion: Our studies have revealed the essential role of CXCR4/TGF-β1 axis playing in the transformation of tumor microenvironment by mediating MSCs differentiation into CAFs, promoting CRCs growth and metastasis.
Ethyl Rosmarinate Prevents the Impairment of Vascular Function and Morphological Changes in L-NAME-Induced Hypertensive Rats

Background and Objectives: The potent, endothelium-independent, vasorelaxant effect of ethyl rosmarinate, an ester derivative of rosmarinic acid, makes it of interest as an alternative therapeutic agent for use in hypertension. This study was designed to investigate the effect of ethyl rosmarinate on Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Materials and Methods: L-NAME was given orally to male Wistar rats for 6 weeks to induce hypertension concurrently with treatment of ethyl rosmarinate at 5, 15, or 30 mg/kgor enalapril at 10 mg/kg Systolic blood pressure (SBP), heart rate, and body weight of all experimental groups were recorded weekly, while the vascular sensitivity and histological changes of the aorta were evaluated at the end of the experiment. Results: For all treatment groups, the data indicated that ethyl rosmarinate significantly attenuated the SBP in hypertensive rats induced by L-NAME, with no significant differences in heart rate and body weight. In addition, the response of vascular sensitivity to acetylcholine (ACh) was improved but there was no significant difference in the response to sodium nitroprusside (SNP). Furthermore, the sensitivity of the aorta to phenylephrine (PE) was significantly decreased. The thickness of the aortic wall did not differ between groups but the expression of endothelial nitric oxide synthase (eNOS) was increased in ethyl rosmarinate- and enalapril-treated groups compared with the hypertensive group. Conclusions: Ethyl rosmarinate is an interesting candidate as an alternative treatment for hypertension due to its ability to improve vascular function and to increase the expression of eNOS similar to enalapril which is a drug commonly used in hypertension.
Molecular Analysis of UV-C Induced Resveratrol Accumulation in Polygonum cuspidatum Leaves

Resveratrol is one of the most studied plant secondary metabolites owing to its numerous health benefits. It is accumulated in some plants following biotic and abiotic stress pressures, including UV-C irradiation. Polygonum cuspidatum represents the major natural source of concentrated resveratrol but the underlying mechanisms as well as the effects of UV-C irradiation on resveratrol content have not yet been documented. Herein, we found that UV-C irradiation significantly increased by 2.6-fold and 1.6-fold the resveratrol content in irradiated leaf samples followed by a dark incubation for 6 h and 12 h, respectively, compared to the untreated samples. De novo transcriptome sequencing and assembly resulted into 165,013 unigenes with 98 unigenes mapped to the resveratrol biosynthetic pathway. Differential expression analysis showed that P. cuspidatum strongly induced the genes directly involved in the resveratrol synthesis, including phenylalanine ammonia-lyase, cinnamic acid 4-hydroxylase, 4-coumarate-CoA ligase and stilbene synthase (STS) genes, while strongly decreased the chalcone synthase (CHS) genes after exposure to UV-C. Since CHS and STS share the same substrate, P. cuspidatum tends to preferentially divert the substrate to the resveratrol synthesis pathway under UV-C treatment. We identified several members of the MYB, bHLH and ERF families as potential regulators of the resveratrol biosynthesis genes.
A patent review of BRD4 inhibitors (2013-2019)

ABSTRACT Introduction: The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal (BET) family, functions as an ‘epigenetic reader’ that binds to acetylated lysine (KAc) residues on histone tails sophisticatedly regulating chromatin structure and gene expression. Recently, emerging evidence demonstrates that BRD4 plays a significant role in the occurrence and progression of several malignant human diseases especially cancers, making it a hot target in cancer therapy. Areas covered: This review mainly summarizes the patents of BRD4 inhibitors that have been authorized from 2013 to 2019. The patents are mostly described in terms of chemical structures, molecular mechanisms of action, pharmacological activities and potential clinical applications, including combination therapies. The development of BRD4 inhibitors in the clinical phase has been highlighted. Prospects for further development of more selective BRD4 inhibitors are provided. Expert opinion: In 2013–2019, several previously known chemical scaffolds have been further developed and disclosed. Although many small molecule BRD4 inhibitors with high potency and diverse scaffolds have been developed, the selectivity of most BRD4 inhibitors still needs to be improved. Therefore, the development of more selective small molecule inhibitors or combined use of drugs such as immunotherapy may provide new ideas for drug development.
Optimizing Water-Based Extraction of Bioactive Principles of Hawthorn: From Experimental Laboratory Research to Homemade Preparations

Hawthorn (Crataegus) is used for its cardiotonic, hypotensive, vasodilative, sedative, antiatherosclerotic, and antihyperlipidemic properties. One of the main goals of this work was to find a well-defined optimized extraction protocol usable by each of us that would lead to repeatable, controlled, and quantified daily uptake of active components from hawthorn at a drinkable temperature (below 60 °C). A thorough investigation of the extraction mode in water (infusion, maceration, percolation, ultrasounds, microwaves) on the yield of extraction and the amount of phenolic compounds, flavonoids, and proanthocyanidin oligomers as well as on the Ultra High Performance Liquid Chromatography (UHPLC) profiles of the extracted compounds was carried out. High-resolution Fourier transform ion cyclotron resonance mass spectrometry was also implemented to discriminate the different samples and conditions of extraction. The quantitative and qualitative aspects of the extraction as well as the kinetics of extraction were studied, not only according to the part (flowers or leaves), the state (fresh or dried), and the granulometry of the dry plant, but also the stirring speed, the temperature, the extraction time, the volume of the container (cup, mug or bowl) and the use of infusion bags.
RASSF10 Is a TGFβ-Target That Regulates ASPP2 and E-Cadherin Expression and Acts as Tumor Suppressor That Is Epigenetically Downregulated in Advanced Cancer

The Ras Association Domain Family (RASSF) encodes members of tumor suppressor genes which are frequently inactivated in human cancers. Here, the function and the regulation of RASSF10, that contains a RA (Ras-association) and two coiled domains, was investigated. We utilized mass spectrometry and immuno-precipitation to identify interaction partners of RASSF10. Additionally, we analyzed the up- and downstream pathways of RASSF10 that are involved in its tumor suppressive function. We report that RASSF10 binds ASPP1 (Apoptosis-stimulating protein of p53) and ASPP2 through its coiled-coils. Induction of RASSF10 leads to increased protein levels of ASPP2 and acts negatively on cell cycle progression. Interestingly, we found that RASSF10 is a target of the EMT (epithelial mesenchymal transition) driver TGFβ (Transforming growth factor beta) and that negatively associated genes of RASSF10 are significantly over-represented in an EMT gene set collection. We observed a positive correlation of RASSF10 expression and E-cadherin that prevents EMT. Depletion of RASSF10 by CRISPR/Cas9 technology induces the ability of lung cancer cells to proliferate and to invade an extracellular matrix after TGFβ treatment. Additionally, knockdown of RASSF10 or ASPP2 induced constitutive phosphorylation of SMAD2 (Smad family member 2). Moreover, we found that epigenetic reduction of RASSF10 levels correlates with tumor progression and poor survival in human cancers. Our study indicates that RASSF10 acts a TGFβ target gene and negatively regulates cell growth and invasion through ASPP2. This data suggests that epigenetic loss of RASSF10 contributes to tumorigenesis by promoting EMT induced by TGFβ.
Plasma Homocysteine and Polymorphisms of Genes Involved in Folate Metabolism Correlate with DNMT1 Gene Methylation Levels

DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of DNA methylation patterns during cell division. Several human diseases are characterized by impaired DNMT1 gene methylation, but less is known about the factors that regulate DNMT1 promoter methylation levels. Dietary folates and related B-vitamins are essential micronutrients for DNA methylation processes, and we performed the present study to investigate the contribution of circulating folate, vitamin B12, homocysteine, and common polymorphisms in folate pathway genes to the DNMT1 gene methylation levels. We investigated DNMT1 gene methylation levels in peripheral blood DNA samples from 215 healthy individuals. All the DNA samples were genotyped for MTHFR 677C > T (rs1801133) and 1298A > C (rs1801131), MTRR 66A > G (rs1801394), MTR 2756A > G (rs1805087), SLC19A1 (RFC1) 80G > A (rs1051266), TYMS 28-bp tandem repeats (rs34743033) and 1494 6-bp insertion/deletion (indel) (rs34489327), DNMT3A -448A > G (rs1550117), and DNMT3B -149C > T (rs2424913) polymorphisms. Circulating homocysteine, folate, and vitamin B12 levels were available from 158 of the recruited individuals. We observed an inverse correlation between plasma homocysteine and DNMT1 methylation levels. Furthermore, both MTR rs1805087 and TYMS rs34743033 polymorphisms showed a statistically significant effect on DNMT1 methylation levels. The present study revealed several correlations between the folate metabolic pathway and DNMT1 promoter methylation that could be of relevance for those disorders characterized by altered DNA methylation.