Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery of New Schiff Bases Tethered Pyrazole Moiety: Design, Synthesis, Biological Evaluation, and Molecular Docking Study as Dual Targeting DHFR/DNA Gyrase Inhibitors with Immunomodulatory Activity

A series of Bis-pyrazole Schiff bases (6a–d and 7a–d) and mono-pyrazole Schiff bases (8a–d and 9a–d) were designed and synthesized through the reaction of 5-aminopyrazoles 1a–d with aldehydes 2–5 using mild reaction condition with a good yield percentage. The chemical structure of newly formed Schiff bases tethered pyrazole core was confirmed based on spectral and experimental data. All the newly formed pyrazole Schiff bases were evaluated against eight pathogens (Gram-positive, Gram-negative, and fungi). The result exhibited that, most of them have good and broad activities. Among those, only six Schiff bases (6b, 7b, 7c, 8a, 8d, and 9b) displayed MIC values (0.97–62.5 µg/mL) compared to Tetracycline (15.62–62.5 µg/mL) and Amphotericin B (15.62–31.25 µg/mL), MBC values (1.94–87.5 µg/mL) and selectivity to tumor cell than normal cells. Immunomodulatory activities showed that the promising Schiff bases increase the immunomodulator effect of defense cell and the Schiff base 8a is the highest one by (Intra. killing activity = 136.5 ± 0.3%) having a pyrazole moiety as well as amide function (O=C-NH2) and piperidinyl core. Furthermore, the most potent one exhibited broad activity depending on both MIC and MBC values. Moreover, to study the mechanism of these pyrazole Schiff bases, two active Schiff bases 8a and 9b from six derivatives were introduced to study the enzyme assay as dihydrofolate reductase (DHFR) on E. coli organism and DNA gyrase with two different organisms, S. aureus and B. subtilis, to determine the inhibitory activities with lower values in the case of DNA gyrase (8a and 9b) or nearly as DHFR compound 9b, while pyrazole 8a showed excellent inhibitory against all enzyme assay. The molecular docking study against dihydrofolate reductase and DNA gyrase were performed to study the binding between active site in the pocket with the two Schiff bases (8a and 9b) that exhibited good binding affinity with different bond types as H-bonding, aren-aren, and arene-cation interaction as well as study the physicochemical and pharmacokinetic properties of the two active Schiff bases 8a and 9b.
T1-11, an adenosine derivative, ameliorates aging-related behavioral physiology and senescence markers in aging mice

Aging is a natural human process. It is uniquely individual, taking into account experiences, lifestyle habits and environmental factors. However, many disorders and syndromes, such as osteoporosis, neurodegenerative disorders, cognitive decline etc., often come with aging. The present study was designed to investigate the possible anti-aging effect of N6-(4-hydroxybenzyl)adenine riboside (T1-11), an adenosine analog isolated from Gastrodia elata, in a mouse model of aging created by D-galactose (D-gal) and the underlying mechanism, as well as explore the role of adenosine signaling in aging. T1-11 activated A2AR and suppressed D-gal- and BeSO4-induced cellular senescence in vitro. In vivo results in mice revealed that T1-11 abated D-gal-induced reactive oxygen species generation and ameliorated cognitive decline by inducing neurogenesis and lowering D-gal-caused neuron death. T1-11 could be a potent agent for postponing senility and preventing aging-related neuroinflammation and neurodegeneration.
Acyl‐Coenzyme A Thioesterase 9 Traffics Mitochondrial Short‐Chain Fatty Acids Toward De Novo Lipogenesis and Glucose Production in the Liver

Obesity‐induced pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is associated with increased de novo lipogenesis (DNL) and hepatic glucose production (HGP) that is due to excess fatty acids. Acyl‐coenzyme A (CoA) thioesterase (Acot) family members control the cellular utilization of fatty acids by hydrolyzing (deactivating) acyl‐CoA into nonesterified fatty acids and CoASH.
Prevalence of Bad Smells in C# Projects

Bad smell can be defined as structures in code that suggest the possibility of refactoring. In object-oriented languages such as C# and Java, Bad Smells are heavily exploited as a way to avoid potential software failures. The presence of a high number of bad smells in a software project makes the system maintenance and evolution hard. So, identifying smells in code and refactoring them helps to improve and maintain software quality. Antipatterns are considered inadequate programming practices, but not an error, they are bad solutions to recurring software problems. In this work, we propose an exploratory study on open source projects written in C# and published in GitHub. We empirically analyzed a total of 25 projects, studying the prevalence of Bad Smells, in a quantitatively and qualitatively manner, and their relationship in order to identify possible anti-patterns. Our results showed that implementation smells are the most common. Besides, some smells occur together, such as Missing Default and Unutilized Abstraction that are perfectly correlated, and ILS and IMN detected by association rules. Thus, the proposed study aims to assist software developers in avoiding future problems during the development of C# projects.
Detection of difficult calvings in the Polish Holstein-Friesian Black-and-White heifers

The aim of this study was to check the effectiveness of classification and regression trees (CART), support vector machines (SVM) and generalized linear model (GLZ) in the detection of difficult calvings in the Polish Holstein-Friesian Black-and-White heifers and to identify the most influential predictors of such calvings with special regard to oestrogen receptor alpha (ERα) and cytochrome P450 (CYP19) aromatase genotypes. A total of 529 calving records containing four continuous and four categorical predictors were analysed. Calving category (difficult vs. easy) was a dependent variable. The most significant predictors were as follows: gestation length, body condition score index and calving age (for CART), as well as ERα genotype (for GLZ). Sensitivity (percentage of correctly diagnosed difficult calvings) and specificity (percentage of correctly diagnosed easy calvings) on a test set were 70.0% and 94.7% (for CART) as well as 50.0% and 99.0% (for SVM and GLZ), respectively. The studied models were characterized by good detection performance and high specificity and reliability of predictions.
Competition between maturation and degradation drives human snRNA 3′ end quality control

Here, Lardelli and Lykke-Andersen investigated the control of cellular RNA fates by studying the balance between polymerases and exonucleases, which act on 3′ ends of nascent RNAs to promote their maturation or degradation. They identified a central role for the human DEDD deadenylase TOE1 in distinguishing the fates of small nuclear (sn)RNAs of the spliceosome from unstable genome-encoded snRNA variants, and their findings provide new mechanistic insights into RNA quality control.
What can developmental defects of enamel reveal about physiological stress in nonhuman primates?

Several different types of developmental defects occur in enamel, 3,4 including opacities, which are changes in enamel translucency; accentuated striae of Retzius, 1 which are dark microscopic bands that can be observed in thin sections of enamel; and enamel hypoplasias, 1 or macroscopic defects appearing on the enamel surface (see Glossary). Opacities are caused by hy-pomineralization. 1,2 The latter two types of defects result from disruptions to enamel-producing cells, known as ameloblasts, as they secrete the enamel matrix (Box 1). Periods of malnutrition, 2,5,6 systemic illness, 2,7–10 and even, as new evidence suggests, psychologically stressful situations 11 can disrupt ameloblast function. Because enamel does not remodel once a tooth has formed, accentuated striae of Retzius and enamel hypoplasias provide indeli-ble markers of such disturbances. 2 Anthropological interest in accentuated striae of Retzius and enamel hypo-plasias has traditionally concentrated on humans. Because nutritional and disease stress are common causes of enamel hypoplasias, and because these defects can be easily observed on the surfaces of teeth, the prevalence of enamel hypoplasia is often used as an indicator of the health status of human populations. 2 Bioarcheological applications have involved documenting an increase
Controllable Carbonization of Plastic Waste into Three-Dimensional Porous Carbon Nanosheets by Combined Catalyst for High Performance Capacitor

Polyethylene terephthalate (PET) plastic has been extensively used in our social life, but its poor biodegradability has led to serious environmental pollution and aroused worldwide concern. Up to now, various strategies have been proposed to address the issue, yet such strategies remain seriously impeded by many obstacles. Herein, waste PET plastic was selectively carbonized into three-dimensional (3D) porous carbon nanosheets (PCS) with high yield of 36.4 wt%, to be further hybridized with MnO2 nanoflakes to form PCS-MnO2 composites. Due to the introduction of an appropriate amount of MnO2 nanoflakes, the resulting PCS-MnO2 composite exhibited a specific capacitance of 210.5 F g−1 as well as a high areal capacitance of 0.33 F m−2. Furthermore, the PCS-MnO2 composite also showed excellent cycle stability (90.1% capacitance retention over 5000 cycles under a current density of 10 A g−1). The present study paved an avenue for the highly efficient recycling of PET waste into high value-added products (PCSs) for electrochemical energy storage.
Causes of covariation of phenotypic traits among populations

Morphological and life‐history traits often vary among populations of a species. Traits generally do not vary independently, but show patterns of covariation that can arise from genetic and environmental influences on phenotype. Covariance of traits may arise at an among‐population level when genetically influenced traits diverge among populations in a correlated manner. Genetic correlations caused by pleiotropy and/or gene linkage can cause traits to evolve together, but among‐population covariance can also arise among traits that are not genetically correlated. For example, “selective covariance” can arise when natural selection directly causes correlated change in a suite of traits. Similarly, mutation, migration, and drift may also sometimes cause correlated genetic changes among populations. Because covariation of traits among populations can arise by several different processes, the evolution of suites of traits must be interpreted with great caution. We discuss the sources of among‐population covariance and illustrate one approach to identifying the sources' using data on floral traits of Dalechampia scandens (Euphorbiaceae).
Critical Review of Processing and Classification Techniques for Images and Spectra in Microplastic Research

Microplastic research is a rapidly developing field, with urgent needs for high throughput and automated analysis techniques. We conducted a review covering image analysis from optical microscopy, scanning electron microscopy, fluorescence microscopy, and spectral analysis from Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy, pyrolysis gas–chromatography mass–spectrometry, and energy dispersive X-ray spectroscopy. These techniques were commonly used to collect, process, and interpret data from microplastic samples. This review outlined and critiques current approaches for analysis steps in image processing (color, thresholding, particle quantification), spectral processing (background and baseline subtraction, smoothing and noise reduction, data transformation), image classification (reference libraries, morphology, color, and fluorescence intensity), and spectral classification (reference libraries, matching procedures, and best practices for developing in-house reference tools). We highlighted opportunities to advance microplastic data analysis and interpretation by (i) quantifying colors, shapes, sizes, and surface topologies with image analysis software, (ii) identifying threshold values of particle characteristics in images that distinguish plastic particles from other particles, (iii) advancing spectral processing and classification routines, (iv) creating and sharing robust spectral libraries, (v) conducting double blind and negative controls, (vi) sharing raw data and analysis code, and (vii) leveraging readily available data to develop machine learning classification models. We identified analytical needs that we could fill and developed supplementary information for a reference library of plastic images and spectra, a tutorial for basic image analysis, and a code to download images from peer reviewed literature. Our major findings were that research on microplastics was progressing toward the use of multiple analytical methods and increasingly incorporating chemical classification. We suggest that new and repurposed methods need to be developed for high throughput screening using a diversity of approaches and highlight machine learning as one potential avenue toward this capability.
Functionalized Derivatives of Benzocrown Ethers, II. Supramolecular Complexes of L-Amino Acids as Efficient Activators of the Zinc Enzyme Carbonic Anhydrase†

The preparation of a series of supramolecular complexes of the ammonium salt of 2,3,11,12-bis[4-(10-aminodecylcarbonyl)]benzo-18-crown-6 with different natural and non-natural amino acids is reported. In all these ditopic supramolecular complexes, with the exception of the histidine derivative, the ammonium moiety of the amino acid is anchored by means of hydrogen bonds within the macrocyclic cavity of the host, whilst the carboxylate moiety interacts with the ammonium group of the derivatized crown ether. The new complexes act as very efficient activators of the zinc enzyme carbonic anhydrase (isozymes I and II).
Pulse rate variability in cardiovascular health: a review on its applications and relationship with heart rate variability

Heart rate variability has been largely used for the assessment of cardiac autonomic activity, due to the direct relationship between cardiac rhythm and the activity of the sympathetic and parasympathetic nervous system. In recent years, another technique, pulse rate variability, has been used for assessing heart rate variability information from pulse wave signals, especially from photoplethysmography, a non-invasive, non-intrusive, optical technique that measures the blood volume in tissue. The relationship, however, between pulse rate variability and heart rate variability is not entirely understood, and the effects of cardiovascular changes in pulse rate variability have not been thoroughly elucidated. In this review, a comprehensive summary of the applications in which pulse rate variability has been used, with a special focus on cardiovascular health, and of the studies that have compared heart rate variability and pulse rate variability is presented. It was found that the relationship between heart rate variability and pulse rate variability is not entirely understood yet, and that pulse rate variability might be influenced not only due to technical aspects but also by physiological factors that might affect the measurements obtained from pulse-to-pulse time series extracted from pulse waves. Hence, pulse rate variability must not be considered as a valid surrogate of heart rate variability in all scenarios, and care must be taken when using pulse rate variability instead of heart rate variability. Specifically, the way pulse rate variability is affected by cardiovascular changes does not necessarily reflect the same information as heart rate variability, and might contain further valuable information. More research regarding the relationship between cardiovascular changes and pulse rate variability should be performed to evaluate if pulse rate variability might be useful for the assessment of not only cardiac autonomic activity but also for the analysis of mechanical and vascular autonomic responses to these changes.
Incubation and rearing temperature effects on Hsp70 levels and heat stress response in broilers

Incubation temperature (IT) was changed to evaluate if 6-wk-old birds become more tolerant to heat stress. After 13 d of incubation, 470 eggs were submitted to low (36.8°C), normal (37.8°C) and high (38.8°C) temperatures. At day 7 post-hatching, 144 birds were allocated to three rearing temperatures (48 birds/treatment): control/thermoneutral (35–24°C), high (33–30°C) or low (27–18°C) according to the age of the birds. Hsp70 levels in tissues of birds (1 d and 42 d), stress response (42 d) and performance were evaluated. High IT decreased brain (P < 0.01) and liver (P < 0.01) Hsp70 levels, whereas low IT decreased brain (P < 0.01) but increased heart (P < 0.01) Hsp70 levels in 1-d old chicks. Birds incubated at a low temperature had higher (P < 0.05) feed intake (1-42 d). High rearing temperature decreased feed intake (P <0.01) and liveweight (P <0.01). Colonic temperature was lower in birds incubated at a low temperature (P < 0.05) and higher in birds reared in a high temperature (P < 0.05) before heat s.
Forecasting deaths of road traffic injuries in China using an artificial neural network

Abstract Objectives: This study was conducted to estimate road traffic deaths and to forecast short-term road traffic deaths in China using the Elman recurrent neural network (ERNN) model. Methods: An ERNN model was developed using reported police data of road traffic deaths in China from 2000 to 2017. Different numbers of neurons of the hidden layer were tested and different combinations of subgroup datasets have been used to develop the optimal ERNN model after normalization. The mean absolute error (MAE), the root mean square error (RMSE), and the mean absolute percentage error (MAPE) were measures of the deviation between predicted and observed values. Predicted road traffic deaths from the ERNN model and the seasonal autoregressive integrated moving average (SARIMA) model were compared using the MAPE. Results: By comparing the MAE, RMSE and MAPE of different numbers of hidden neurons and different ERNN models, the ERNN model provided the best result when the input neurons were set to 3 and hidden neurons were set to 10. The best validated neural model (3:10:1) was further applied to make predictions for the latest 12 months of deaths (MAPE = 4.83). The best SARIMA (0, 1, 1) (0, 1, 1)12 model was selected from various candidate models (MAPE = 5.04). The fitted road traffic deaths using the two selected models matched closely with the observed deaths from 2000 to 2016. The ERNN models performed better than the SARIMA model in terms of prediction of 2017 deaths. Conclusions: Our results suggest that the ERNN model could be utilized to model and forecast the short-term trends accurately and to evaluate the impact of traffic safety programs when applied to historical road traffic deaths data. Forecasting traffic crash deaths will provide useful information to measure burden of road traffic injuries in China.
Disposition and metabolism of antibacterial agent, triclocarban, in rodents; a species and route comparison

Abstract Triclocarban is a residue-producing antibacterial agent used in a variety of consumer products. These studies investigated the disposition and metabolism of [14C]triclocarban. In male rats following a single gavage administration of 50, 150, and 500 mg/kg, excretion was primarily via feces (feces, 85–86%; urine, 3–6%) with no apparent dose-related effect. In male rats, 29% of the administered dose was excreted in bile suggesting some of the fecal excretion is from the absorbed dose which was excreted to the intestine via bile. The tissue retention of radioactivity was low in male rats (24 h, 3.9%; 72 h, 0.1%). Disposition pattern following gavage administration of 50 mg/kg in female rats and male and female mice were similar to male rats. Plasma elimination half-life of triclocarban in rats following gavage administration was shorter (∼2 h) compared to that based on total radioactivity (≥9 h) which included all products of triclocarban. Absorption following a single dermal application of 1.5 or 3% was low (≤3%) in rodents. Hydroxylated and conjugated metabolites of triclocarban predominated in bile. In hepatocytes, clearance of triclocarban in mouse and human was similar and was faster than in rat.
Direct regulation of WRKY70 by AtMYB44 in plant defense responses

Cross-talk between hormones is required for plant response to developmental cues and environmental stresses. This cross-talk is achieved through several regulators located in convergence point of distinct hormonal signaling. In plant defense responses, salicylic acid and jasmonic acid affect each other in antagonistic manner. In a recent study we showed that AtMYB44 transcription factor positively regulates SA-mediated defense expression and enhanced resistance to Pst DC3000. On the other hand, AtMYB44 negatively regulates expression of JA-mediated defense gene expression and downregulated resistance to Alternaria brassicicola. Effects of AtMYB44 in SA- and JA-mediated defense responses were achieved through direct regulation of WRKY70 expression which acts as an integrator of cross-talk between SA and JA in plant defense responses. Here we provide further evidence that AtMYB44 regulates defense responses by transcriptional activation of downstream gene, WRKY70. This result shows that AtMYB44 is an integrator of cross-talk between SA and JA in plant defense responses.
Genome Sequences of Newcastle Disease Virus Strains from Two Outbreaks in Indonesia

The genomes of two newly emerged Newcastle disease virus strains, chicken/Indonesia/Mega/001WJ/2013 and chicken/Indonesia/Cimanglid/002WJ/2015, from disease outbreaks in chickens in Indonesia are reported. Phylogenetic analysis of different genotypes of Newcastle disease virus using the F gene coding sequences suggests that these two strains belong to genotype VII.2, in class II of avian paramyxoviruses. ABSTRACT The genomes of two newly emerged Newcastle disease virus strains, chicken/Indonesia/Mega/001WJ/2013 and chicken/Indonesia/Cimanglid/002WJ/2015, from disease outbreaks in chickens in Indonesia are reported. Phylogenetic analysis of different genotypes of Newcastle disease virus using the F gene coding sequences suggests that these two strains belong to genotype VII.2, in class II of avian paramyxoviruses.
An Africa-wide genomic evolution of insecticide resistance in the malaria vector Anopheles funestus involves selective sweeps, copy number variations, gene conversion and transposons

Insecticide resistance in malaria vectors threatens to reverse recent gains in malaria control. Deciphering patterns of gene flow and resistance evolution in malaria vectors is crucial to improving control strategies and preventing malaria resurgence. A genome-wide survey of Anopheles funestus genetic diversity Africa-wide revealed evidences of a major division between southern Africa and elsewhere, associated with different population histories. Three genomic regions exhibited strong signatures of selective sweeps, each spanning major resistance loci (CYP6P9a/b, GSTe2 and CYP9K1). However, a sharp regional contrast was observed between populations correlating with gene flow barriers. Signatures of complex molecular evolution of resistance were detected with evidence of copy number variation, transposon insertion and a gene conversion between CYP6P9a/b paralog genes. Temporal analyses of samples before and after bed net scale up suggest that these genomic changes are driven by this control intervention. Multiple independent selective sweeps at the same locus in different parts of Africa suggests that local evolution of resistance in malaria vectors may be a greater threat than trans-regional spread of resistance haplotypes.