Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis, Antitumor and Antiviral In Vitro Activities of New Benzotriazole-Dicarboxamide Derivatives

Cancer and viral infections continue to threaten humankind causing death worldwide. Hence, the discovery of new anticancer and antiviral agents still represents a major scientific goal. Heterocycles designed to mimic the chemical structure of natural pyrimidines and purines have been designed over the years, exerting their activity acting as false substrates on several different targets. We reported a series of bis-benzotriazole-dicarboxamide derivatives which inhibit viral helicase of poliovirus, and hence we planned structure modifications to obtain different series of new dicarboxamides. Here, the synthesis and characterization of 56 new compounds: 31 bis-benzotriazole dicarboxamides and 25 mono-substituted acidic derivatives are reported. The synthesized compounds were tested for their antiviral and antitumor activity. Mostly, compounds 4a, 4c and 4d showed antiviral activity against tested Picornaviruses, Coxsackievirus B5 and Poliovirus-1. Likewise, four derivatives (3b, 3d, 4d, 9b) showed notable antiproliferative activity inhibiting cell growth in two distinct antitumor screenings. Compound 3b was selected as the antitumor lead compound for the wide range of activity and the potency proved. The lead compound was proved to induce apoptosis in SK-MES1 tumor cells, in a dose-dependent manner.
The Zinc Nutritional Immunity of Epinephelus coioides Contributes to the Importance of znuC During Pseudomonas plecoglossicida Infection

Previously, the dual RNA-seq was carried out in a Pseudomonas plecoglossicida- Epinephelus coioides infection model to investigate the dynamics of pathogen-host interplay in vivo. ZnuC, a member of ZnuCBA Zn importer, was found transcriptionally up-regulated during infection. Thus, this study aimed to assess its role during the trade-off for Zn between host and P. plecoglossicida. ICP-MS analysis and fluorescent staining showed that Zn was withheld from serum and accumulated in the spleen, with increased Zn uptake in the Golgi apparatus of macrophages after infection. Additionally, growth assay, macrophage infection and animal infection after gene knockout / silencing revealed that znuC was necessary for growth in Zn-limiting conditions, colonization, intracellular viability, immune escape and virulence of P. plecoglossicida. Further analysis with dual RNA-seq revealed associations of host’s Zn nutritional immunity genes with bacterial Zn assimilation genes. IL6 and ZIP4 played key roles in this network, and markedly affected znuB expression, intracellular viability and immune escape, as revealed by gene silencing. Moreover, EMSA and GFP reporter gene analysis showed that Fur sensed changes in Fe concentration to regulate znuCBA in P. plecoglossicida. Jointly, these findings suggest a trade-off for Zn between host and P. plecoglossicida, while ZnuC is important for P. plecoglossicida Zn acquisition.
MiR-19a-3p Suppresses M1 Macrophage Polarization by Inhibiting STAT1/IRF1 Pathway

Macrophages, an important type of immune cells, are generally polarized to classically activated macrophage (M1) or alternatively activated macrophage (M2) to respond to environmental stimuli. Signal transducer and activator of transcription 1 (STAT1), a very important transcription factor, can promote M1 macrophage polarization. However, the mechanisms of regulating STAT1 in macrophage polarization remain unclear. In the present study, STAT1 was markedly elevated, however, miR-19a-3p was down-regulated in interferon (IFN)-γ and lipopolysaccharide (LPS) treated RAW264.7 cells, and dual-luciferase reporter assay identified that miR-19a-3p directly targeted STAT1 by binding to its 3′UTR. Up-regulated miR-19a-3p inhibited M1 polarization by targeting STAT1/interferon regulatory factor 1 (IRF1) and vice versa in vitro. Consistently, overexpression of miR-19a-3p in LPS treated mice by systemically administering agomiR-19a-3p effectively reduced the inflammation in mouse lung tissues, and inhibited M1 macrophage polarization via suppressing STAT1/IRF1 pathway. In summary, our study confirmed that miR-19a-3p, as a direct regulator of STAT1, inhibited M1 macrophages polarization. The miR-19a-3p/STAT1/IRF1 pathway can potentially be used to design novel immunotherapy for modulating macrophage polarization.
Managing Teachers' Job Attitudes: The Potential Benefits of Being a Happy and Emotional Intelligent Teacher

According to the broaden-and-build theory of positive emotions, the frequency of positive emotions is associated with the development of positive attitudes, cognitions, and behaviors in organizational contexts. However, positive and negative attitudes at work might also be influenced by different personal and job resources. While emotional intelligence has been significantly associated with positive job attitudes and personal well-being, no studies have yet examined the joint role of teacher happiness and emotional intelligence in key teacher job attitudes. The present study assesses whether emotional intelligence interacts with levels of teacher happiness to jointly explain important teacher job attitudes (i.e., job satisfaction and turnover intention). A total sample of 685 teaching professionals (431 female) filled out a battery of scales including subjective happiness, emotional intelligence, job satisfaction, and turnover intention. Our results revealed that subjective happiness was significantly associated with both higher job satisfaction and lower turnover intention. Likewise, emotional intelligence was positively related to happiness and job satisfaction, and negatively related to turnover intention. Finally, interaction analysis showed the main effects of happiness and emotional intelligence in explaining teacher job attitudes. Beyond the main effects, the interaction effects of happiness and emotional intelligence were significant in predicting all teachers' job attitude indicators, even controlling for the effects of their sociodemographic variables. This work expands our knowledge about the role of teachers' positive emotions in the development of positive work attitudes, and also supports the inclusion of emotional skills in future teacher preparation programs as resources to facilitate work-related well-being.
Self-Related Stimuli Decoding With Auditory and Visual Modalities Using Stereo-Electroencephalography

Name recognition plays important role in self-related cognitive processes and also contributes to a variety of clinical applications, such as autism spectrum disorder diagnosis and consciousness disorder analysis. However, most previous name-related studies usually adopted noninvasive EEG or fMRI recordings, which were limited by low spatial resolution and temporal resolution, respectively, and thus millisecond-level response latencies in precise brain regions could not be measured using these noninvasive recordings. By invasive stereo-electroencephalography (SEEG) recordings that have high resolution in both the spatial and temporal domain, the current study distinguished the neural response to one's own name or a stranger's name, and explored common active brain regions in both auditory and visual modalities. The neural activities were classified using spatiotemporal features of high-gamma, beta, and alpha band. Results showed that different names could be decoded using multi-region SEEG signals, and the best classification performance was achieved at high gamma (60–145 Hz) band. In this case, auditory and visual modality-based name classification accuracies were 84.5 ± 8.3 and 79.9 ± 4.6%, respectively. Additionally, some single regions such as the supramarginal gyrus, middle temporal gyrus, and insula could also achieve remarkable accuracies for both modalities, supporting their roles in the processing of self-related information. The average latency of the difference between the two responses in these precise regions was 354 ± 63 and 285 ± 59 ms in the auditory and visual modality, respectively. This study suggested that name recognition was attributed to a distributed brain network, and the subsets with decoding capabilities might be potential implanted regions for awareness detection and cognition evaluation.
Three-Dimensional in vitro Models of Healthy and Tumor Brain Microvasculature for Drug and Toxicity Screening

Tissue vascularization is essential for its oxygenation and the homogenous diffusion of nutrients. Cutting-edge studies are focusing on the vascularization of three-dimensional (3D) in vitro models of human tissues. The reproduction of the brain vasculature is particularly challenging as numerous cell types are involved. Moreover, the blood-brain barrier, which acts as a selective filter between the vascular system and the brain, is a complex structure to replicate. Nevertheless, tremendous advances have been made in recent years, and several works have proposed promising 3D in vitro models of the brain microvasculature. They incorporate cell co-cultures organized in 3D scaffolds, often consisting of components of the native extracellular matrix (ECM), to obtain a micro-environment similar to the in vivo physiological state. These models are particularly useful for studying adverse effects on the healthy brain vasculature. They provide insights into the molecular and cellular events involved in the pathological evolutions of this vasculature, such as those supporting the appearance of brain cancers. Glioblastoma multiform (GBM) is the most common form of brain cancer and one of the most vascularized solid tumors. It is characterized by a high aggressiveness and therapy resistance. Current conventional therapies are unable to prevent the high risk of recurrence of the disease. Most of the new drug candidates fail to pass clinical trials, despite the promising results shown in vitro. The conventional in vitro models are unable to efficiently reproduce the specific features of GBM tumors. Recent studies have indeed suggested a high heterogeneity of the tumor brain vasculature, with the coexistence of intact and leaky regions resulting from the constant remodeling of the ECM by glioma cells. In this review paper, after summarizing the advances in 3D in vitro brain vasculature models, we focus on the latest achievements in vascularized GBM modeling, and the potential applications for both healthy and pathological models as platforms for drug screening and toxicological assays. Particular attention will be paid to discuss the relevance of these models in terms of cell-cell, cell-ECM interactions, vascularization and permeability properties, which are crucial parameters for improving in vitro testing accuracy.
Atrophy Resistant vs. Atrophy Susceptible Skeletal Muscles: “aRaS” as a Novel Experimental Paradigm to Study the Mechanisms of Human Disuse Atrophy

Objective Disuse atrophy (DA) describes inactivity-induced skeletal muscle loss, through incompletely defined mechanisms. An intriguing observation is that individual muscles exhibit differing degrees of atrophy, despite exhibiting similar anatomical function/locations. We aimed to develop an innovative experimental paradigm to investigate Atrophy Resistant tibialis anterior (TA) and Atrophy Susceptible medial gastrocnemius (MG) muscles (aRaS) with a future view of uncovering central mechanisms. Method Seven healthy young men (22 ± 1 year) underwent 15 days unilateral leg immobilisation (ULI). Participants had a single leg immobilised using a knee brace and air-boot to fix the leg (75° knee flexion) and ankle in place. Dual-energy X-ray absorptiometry (DXA), MRI and ultrasound scans of the lower leg were taken before and after the immobilisation period to determine changes in muscle mass. Techniques were developed for conchotome and microneedle TA/MG muscle biopsies following immobilisation (both limbs), and preliminary fibre typing analyses was conducted. Results TA/MG muscles displayed comparable fibre type distribution of predominantly type I fibres (TA 67 ± 7%, MG 63 ± 5%). Following 15 days immobilisation, MG muscle volume (–2.8 ± 1.4%, p < 0.05) and muscle thickness decreased (−12.9 ± 1.6%, p < 0.01), with a positive correlation between changes in muscle volume and thickness (R2 = 0.31, p = 0.038). Importantly, both TA muscle volume and thickness remained unchanged. Conclusion The use of this unique “aRaS” paradigm provides an effective and convenient means by which to study the mechanistic basis of divergent DA susceptibility in humans, which may facilitate new mechanistic insights, and by extension, mitigation of skeletal muscle atrophy during human DA.
Mental Health Applications for Primary and Secondary Prevention of Common Mental Disorders: Attitudes of German Employees

Background: Web-based and mobile mental health applications for the prevention and treatment of common mental disorders (CMDs) are on the rise. Under certain circumstances they have proved to be effective for a range of conditions (e.g., depression). Objective: There is not sufficient evidence regarding the benefits and barriers especially for mobile phone apps and for programs in the field of primary prevention. Studies on the acceptance of potential users of mental health apps yielded mixed outcomes. In a large survey we investigated the attitudes of employees toward mental health apps and various traditional mental health services. Our main research question in this contribution focuses on the acceptance of apps compared to other measures and the moderating influence of individual characteristics. Methods: The standardized survey was completed by members of an online access panel with different job types. A set of 33 self-developed items, including three questions on e-health, captured the perceived relevance of prevention at the (A) occupational, (B) individual, and (C) societal level. On the basis of an exploratory factor analysis, mean scores for mapping seven (sub-)dimensions were constructed and compared using the Wilcoxon test. The influence of potential predictors was analyzed in linear regression models. Results: The data of 610 respondents were analyzed (response rate 75%). Support from mental health applications was rated significantly less important compared to all other dimensions at the levels (A) to (C). Respondents were more likely to use mental health apps if they felt literate with electronic devices, perceived a high relevance of work-related demands as causal factors for CMDs, stated they would be ashamed of having a CMD, and would be willing to begin psychotherapy if recommended. Discussion and Conclusions: The results confirm the critical attitudes of potential mental health app users found in other studies. Since users with a negative attitude toward e-health might have a higher risk for dropout and non-adherence as well as lower intervention effects, well-designed educational strategies should be carried out beforehand.
Ecofriendly synthesis of novel antifungal (thio)barbituric acid derivatives

An expeditious solventless synthesis of novel Mannich bases of thiobarbiturates and barbiturates using montmorillonite clay under microwaves are herein described. This methodology eliminates the use of excess of solvent during the course of reaction. The reaction time is brought down from hours to minutes along with yield enhancement. The rate enhancement and high yield is attributed to the coupling of MWS with solventless conditions. Further, the role of montmorillonite K-10 clay is studied in the reaction and it is concluded that microwave assisted montmorillonite clay catalyzed reaction is the best in terms of catalysis as well as reaction and yield. All the compounds synthesized were screened for their antifungal activity against A. niger and A. flavus and found to possess good activity.
Chinese Herbal Medicine for Chemotherapy-Induced Leukopenia: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials

Aim: We conducted a systematic review of high-quality randomized controlled trials (RCTs) to assess the efficacy and safety of Chinese herbal medicine (CHM) for the treatment of chemotherapy-induced leukopenia (CIL). Methods: Eight electronic databases were searched from the date of inception to November 4, 2020 for high-quality RCTs that met the requirements of at least four key domains of the Cochrane risk of bias (RoB) tool. RevMan 5.3 was applied for the meta-analysis. Results: Fourteen RCTs involving 1,053 patients were included. The pooled results showed that CHM + chemotherapy exerted greater beneficial effects on white blood cell (WBC), neutrophil (NEU), hemoglobin (Hb), and platelet (PLT) counts in addition to the Karnofsky performance scale (KPS) score, but showed no significant difference on granulocyte colony-stimulating factor (G-CSF) dosage compared with chemotherapy alone. Placebo (PBO) + chemotherapy and CHM + chemotherapy groups showed no significant differences in terms of reduction of the incidence of neutropenia. CHM + chemotherapy was superior to Western medicine (WM) + chemotherapy in improving the WBC count, KPS, infection amount, G-CSF use rate, and incidence of leukopenia. In addition, no severe adverse events were observed in the 14 RCTs. Conclusion: CHM in combination with chemotherapy could effectively improve the clinical symptoms of CIL when compared with chemotherapy alone or Western medicine + chemotherapy, except when comparing with PBO + chemotherapy. While CHMs were generally safe for clinical use and exerted no severe side effects in the 14 RCTs, high-quality RCTs with larger sample sizes are essential to reduce study heterogeneity.
Genomic Characterization of the Fruity Aroma Gene, FaFAD1, Reveals a Gene Dosage Effect on γ-Decalactone Production in Strawberry (Fragaria × ananassa)

Strawberries produce numerous volatile compounds that contribute to the unique flavors of fruits. Among the many volatiles, γ-decalactone (γ-D) has the greatest contribution to the characteristic fruity aroma in strawberry fruit. The presence or absence of γ-D is controlled by a single locus, FaFAD1. However, this locus has not yet been systematically characterized in the octoploid strawberry genome. It has also been reported that the volatile content greatly varies among the strawberry varieties possessing FaFAD1, suggesting that another genetic factor could be responsible for the different levels of γ-D in fruit. In this study, we explored the genomic structure of FaFAD1 and determined the allele dosage of FaFAD1 that regulates variations of γ-D production in cultivated octoploid strawberry. The genome-wide association studies confirmed the major locus FaFAD1 that regulates the γ-D production in cultivated strawberry. With the hybrid capture-based next-generation sequencing analysis, a major presence–absence variation of FaFAD1 was discovered among γ-D producers and non-producers. To explore the genomic structure of FaFAD1 in the octoploid strawberry, three bacterial artificial chromosome (BAC) libraries were developed. A deletion of 8,262 bp was consistently found in the FaFAD1 region of γ-D non-producing varieties. With the newly developed InDel-based codominant marker genotyping, along with γ-D metabolite profiling data, we revealed the impact of gene dosage effect for the production of γ-D in the octoploid strawberry varieties. Altogether, this study provides systematic information of the prominent role of FaFAD1 presence and absence polymorphism in producing γ-D and proposes that both alleles of FaFAD1 are required to produce the highest content of fruity aroma in strawberry fruit.
Impact of Grazing Intensity on Soil Properties in Teltele Rangeland, Ethiopia

Grazing intensity (GI) is a major determining factor that controls the functioning of rangelands and the overall nutrient cycle. The Teltele rangeland is used for communal grazing area by the local pastorals; however, to date, there is no documented study data about the impact of GI. The objective of this study was to evaluate the impacts of grazing intensity on selected soil properties in the Teltele rangeland, Ethiopia. Soil samples were collected from different GI sites using different elevation gradient and soil depth from both open grazing and bush-encroached grazing land sand-assessed soil properties. Grazing intensity, elevation, and soil depth significantly (p < 0.05) affected both soils’ physical and chemical properties but rangeland types had no significant effect. The correlation analysis of soil characteristics with the principal component analysis axes showed significant variation. The highly weighted and correlated properties under principal component 1 (PC1) were electrical conductivity, organic carbon, total nitrogen, available phosphorus, and potassium, and under principal component 2, sand and bulk density with equal loaded value (r = −0.998), clay and silt, with silt (0.962) a more loaded one. Soil pH (0.743) demonstrated a significant (p < 0.05) positive correlation with sodium (−0.960) at PC1 (r = 0.610). Based on our results, we recommend further model-based studies on spatial–temporal change of soil properties due to impact of grazing intensity, combined with GIS and remote sensing data to be developed for sustainable rangeland management.
Identity, Digital Learning Environments and Academic Success

: A student’s identity significantly influences their attitude and behavior towards academics regardless of abilities. This paper proposes a framework for the design and evaluation of digital learning environments (DLEs) that explicitly promote identity construction related to academic success. Subsequent research can address three questions: (1) How does one’s identity affect how they interact with DLEs? (2) Which aspects of DLEs best promote identity construction? and (3) How does exploring issues around identity affect learning outcomes?
Concordia: Distributed Shared Memory with In-Network Cache Coherence

Distributed shared memory (DSM) is experiencing a resurgence with emerging fast network stacks. Caching, which is still needed for reducing frequent remote access and balancing load, can incur high coherence overhead. In this paper, we propose CONCORDIA, a DSM with fast in-network cache coherence backed by programmable switches. At the core of CONCORDIA is FLOWCC, a hybrid cache coherence protocol, enabled by a collaborative effort from switches and servers. Moreover, to overcome limitations of programmable switches, we also introduce two techniques: (i) an ownership migration mechanism to address the problem of limited memory capacity on switches and (ii) idempotent operations to handle packet loss in the case that switches are stateful. To demonstrate CONCORDIA’s practical benefits, we build a distributed key-value store and a distributed graph engine on it, and port a distributed transaction processing system to it. Evaluation shows that CONCORDIA obtains up to 4.2×, 2.3× and 2× speedup over state-of-the-art DSMs on key-value store, graph engine and transaction processing workloads, respectively.
Social Media Adoption by Health Professionals: A TAM-Based Study

This research identifies the underlying drivers impacting on healthcare professionals’ social media usage behaviours using the technology acceptance model (TAM) as the theoretical lens. A self-administered survey questionnaire was developed and administered to 219 healthcare professionals. Data are analysed applying the structural equation modelling (SEM) technique. The SEM model demonstrated an acceptable model fit (χ2 = 534.241; df, 239, χ2/df = 2.235, RMSEA = 0.06, IFI = 0.92, TLI = 0.93, and CFI = 0.92) and indicates content quality, perceived risk, perceived credibility, peer influence, confirmation of expectations, supporting conditions, and perceived cost significantly influence the notion of perceived social media usefulness. Furthermore, perceived social media usefulness positively affects social media usage behaviour of healthcare professionals. This research generates important insights into what drives the adoption of social media by healthcare professionals. These insights could help develop social media guidelines and strategies to improve the state of professional interactions between health professionals and their clients.