Miracle-dz/UniFAR-FTUs huggingface dataset:
Tribbles Pseudokinase 3 Regulation and Contribution to Cancer

Simple Summary Accumulating evidence supports a key function for Tribbles proteins in oncogenesis, both in leukemia and solid tumors. However, the exact role of these proteins is hard to define since in a context-dependent manner they can function as both oncogenes and tumor suppressors. Their complex role arises from the capacity to interact with a wide range of target molecules thereby acting as molecular scaffolds and signaling regulators of multiple pathways. This review focuses on one particular Tribbles family member, namely, TRIB3, addressing its gene and protein expression, as well as its role in cancer development and progression. Abstract The first Tribbles protein was identified as critical for the coordination of morphogenesis in Drosophila melanogaster. Three mammalian homologs were subsequently identified, with a structure similar to classic serine/threonine kinases, but lacking crucial amino acids for the catalytic activity. Thereby, the very weak ATP affinity classifies TRIB proteins as pseudokinases. In this review, we provide an overview of the regulation of TRIB3 gene expression at both transcriptional and post-translational levels. Despite the absence of kinase activity, TRIB3 interferes with a broad range of cellular processes through protein–protein interactions. In fact, TRIB3 acts as an adaptor/scaffold protein for many other proteins such as kinase-dependent proteins, transcription factors, ubiquitin ligases, or even components of the spliceosome machinery. We then state the contribution of TRIB3 to cancer development, progression, and metastasis. TRIB3 dysregulation can be associated with good or bad prognosis. Indeed, as TRIB3 interacts with and regulates the activity of many key signaling components, it can act as a tumor-suppressor or oncogene in a context-dependent manner.
Development of Epirubicin-Loaded Biocompatible Polymer PLA–PEG–PLA Nanoparticles: Synthesis, Characterization, Stability, and In Vitro Anticancerous Assessment

Epirubicin (EPI) is an anti-cancerous chemotherapeutic drug that is an effective epimer of doxorubicin with less cardiotoxicity. Although EPI has fewer side effects than its analog, doxorubicin, this study aims to develop EPI nanoparticles as an improved formula of the conventional treatment of EPI in its free form. Methods: In this study, EPI-loaded polymeric nanoparticles (EPI-NPs) were prepared by the double emulsion method using a biocompatible poly (lactide) poly (ethylene glycol) poly(lactide) (PLA–PEG–PLA) polymer. The physicochemical properties of the EPI-NPs were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), entrapment efficiency and stability studies. The effect of EPI-NPs on cancer cells was determined by high throughput imaging and flow cytometry. Results: The synthesis process resulted in monodisperse EPI-NPs with a size of 166.93 ± 1.40 nm and an elevated encapsulation efficiency (EE) of 88.3%. In addition, TEM images revealed the spherical uniformness of EPI-NPs with no aggregation, while the cellular studies presented the effect of EPI-NPs on MCF-7 cells’ viability; after 96 h of treatment, the MCF-7 cells presented considerable apoptotic activity. The stability study showed that the EPI-NPs remained stable at room temperature at physiological pH for over 30 days. Conclusion: EPI-NPs were successfully encapsulated within a highly stable biocompatible polymer with minimal loss of the drug. The used polymer has low cytotoxicity and EPI-NPs induced apoptosis in estrogen-positive cell line, making them a promising, safe treatment for cancer with less adverse side effects.
Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC50 = 45.3 µM), Ebola pseudotype viruses (IC50 = 0.12 µM), and authentic EBOV (IC50 = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC50 = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.
Functionalization and Characterization of Silicon Nanowires for Sensing Applications: A Review

Silicon nanowires are attractive materials from the point of view of their electrical properties or high surface-to-volume ratio, which makes them interesting for sensing applications. However, they can achieve a better performance by adjusting their surface properties with organic/inorganic compounds. This review gives an overview of the main techniques used to modify silicon nanowire surfaces as well as characterization techniques. A comparison was performed with the functionalization method developed, and some applications of modified silicon nanowires and their advantages on those non-modified are subsequently presented. In the final words, the future opportunities of functionalized silicon nanowires for chipless tag radio frequency identification (RFID) have been depicted.
Optimization-Based Online Initialization and Calibration of Monocular Visual-Inertial Odometry Considering Spatial-Temporal Constraints

The online system state initialization and simultaneous spatial-temporal calibration are critical for monocular Visual-Inertial Odometry (VIO) since these parameters are either not well provided or even unknown. Although impressive performance has been achieved, most of the existing methods are designed for filter-based VIOs. For the optimization-based VIOs, there is not much online spatial-temporal calibration method in the literature. In this paper, we propose an optimization-based online initialization and spatial-temporal calibration method for VIO. The method does not need any prior knowledge about spatial and temporal configurations. It estimates the initial states of metric-scale, velocity, gravity, Inertial Measurement Unit (IMU) biases, and calibrates the coordinate transformation and time offsets between the camera and IMU sensors. The work routine of the method is as follows. First, it uses a time offset model and two short-term motion interpolation algorithms to align and interpolate the camera and IMU measurement data. Then, the aligned and interpolated results are sent to an incremental estimator to estimate the initial states and the spatial–temporal parameters. After that, a bundle adjustment is additionally included to improve the accuracy of the estimated results. Experiments using both synthetic and public datasets are performed to examine the performance of the proposed method. The results show that both the initial states and the spatial-temporal parameters can be well estimated. The method outperforms other contemporary methods used for comparison.
TP63 Is Significantly Upregulated in Diabetic Kidney

The role of tumor protein 63 (TP63) in regulating insulin receptor substrate 1 (IRS-1) and other downstream signal proteins in diabetes has not been characterized. RNAs extracted from kidneys of diabetic mice (db/db) were sequenced to identify genes that are involved in kidney complications. RNA sequence analysis showed more than 4- to 6-fold increases in TP63 expression in the diabetic mice’s kidneys, compared to wild-type mice at age 10 and 12 months old. In addition, the kidneys from diabetic mice showed significant increases in TP63 mRNA and protein expression compared to WT mice. Mouse proximal tubular cells exposed to high glucose (HG) for 48 h showed significant decreases in IRS-1 expression and increases in TP63, compared to cells grown in normal glucose (NG). When TP63 was downregulated by siRNA, significant increases in IRS-1 and activation of AMP-activated protein kinase (AMPK (p-AMPK-Th172)) occurred under NG and HG conditions. Moreover, activation of AMPK by pretreating the cells with AICAR resulted in significant downregulation of TP63 and increased IRS-1 expression. Ad-cDNA-mediated over-expression of tuberin resulted in significantly decreased TP63 levels and upregulation of IRS-1 expression. Furthermore, TP63 knockdown resulted in increased glucose uptake, whereas IRS-1 knockdown resulted in a decrease in the glucose uptake. Altogether, animal and cell culture data showed a potential role of TP63 as a new candidate gene involved in regulating IRS-1 that may be used as a new therapeutic target to prevent kidney complications in diabetes.
Presence of Antibiotic Residues and Antibiotic Resistant Bacteria in Cattle Manure Intended for Fertilization of Agricultural Fields: A One Health Perspective

Antibiotic resistant bacteria and antibiotic residues can enter the environment when using animal manure as fertilizer. Twenty-five mixed beef cattle farmyard manure samples and 9 mixed fattening calf slurry samples from different farms across Belgium were investigated for the presence of 69 antibiotic residues, antibiotic resistant Escherichia coli and Salmonella spp. Doxycycline, oxytetracycline, ciprofloxacin, enrofloxacin, flumequine and lincomycin were detected in all fattening calf slurry samples with mean concentrations of 2776, 4078, 48, 31, 536 and 36 µg/kg manure, respectively. Sulfadiazine was detected at a mean concentration of 10,895 µg/kg. Further, antibiotic residues were found in only 4 of the 25 beef cattle farmyard manure samples. Oxytetracycline was detected twice below 500 µg/kg. Paromomycin, ciprofloxacin and enrofloxacin were detected in a concentration below 100 µg/kg. Of E. coli isolates, 88% and 23% from fattening calf slurry and beef cattle farmyard manure, respectively, were resistant to at least one of the antibiotics tested. Multi-drug resistance was observed at a maximum of 10 and 7 antibiotics, respectively. The occurrence of antibiotic resistant E. coli and antibiotic residues is shown to be higher in fattening calf slurry than in beef cattle farmyard manure used for agricultural field fertilization.
Platoon Merging Approach Based on Hybrid Trajectory Planning and CACC Strategies

Currently, the increase of transport demands along with the limited capacity of the road network have increased traffic congestion in urban and highway scenarios. Technologies such as Cooperative Adaptive Cruise Control (CACC) emerge as efficient solutions. However, a higher level of cooperation among multiple vehicle platoons is needed to improve, effectively, the traffic flow. In this paper, a global solution to merge two platoons is presented. This approach combines: (i) a longitudinal controller based on a feed-back/feed-forward architecture focusing on providing CACC capacities and (ii) hybrid trajectory planning to merge platooning on straight paths. Experiments were performed using Tecnalia’s previous basis. These are the AUDRIC modular architecture for automated driving and the highly reliable simulation environment DYNACAR. A simulation test case was conducted using five vehicles, two of them executing the merging and three opening the gap to the upcoming vehicles. The results showed the good performance of both domains, longitudinal and lateral, merging multiple vehicles while ensuring safety and comfort and without propagating speed changes.
Grafting Enhances Pepper Water Stress Tolerance by Improving Photosynthesis and Antioxidant Defense Systems

Currently, limited water supply is a major problem in many parts of the world. Grafting peppers onto adequate rootstocks is a sustainable technique used to cope with water scarcity in plants. For 1 month, this work compared grafted peppers by employing two rootstocks (H92 and H90), with different sensitivities to water stress, and ungrafted plants in biomass, photosynthesis, and antioxidant response terms to identify physiological–antioxidant pathways of water stress tolerance. Water stress significantly stunted growth in all the plant types, although tolerant grafted plants (variety grafted onto H92, Var/H92) had higher leaf area and fresh weight values. Var/H92 showed photosynthesis and stomata conductance maintenance, compared to sensitive grafted plants (Var/H90) and ungrafted plants under water stress, linked with greater instantaneous water use efficiency. The antioxidant system was effective in removing reactive oxygen species (ROS) that could damage photosynthesis; a significant positive and negative linear correlation was observed between the rate of CO2 uptake and ascorbic acid (AsA)/total AsA (AsAt) and proline, respectively. Moreover, in Var/H92 under water stress, both higher proline and ascorbate concentration were observed. Consequently, less membrane lipid peroxidation was quantified in Var/H92.
Remarkable Population Resilience in a North African Endemic Damselfly in the Face of Rapid Agricultural Transformation

Simple Summary There has been a rapid expansion of agricultural area worldwide, resulting in a substantial change in the physical structure, biodiversity, and ecosystem functioning of various natural habitats. In North Africa, many natural habitats have been transformed into agricultural lands, especially in the North, where biodiversity is the highest, to meet the food security and economic development of a rapidly growing population. We estimated the agricultural expansion in North African region between the 1990s and 2000s and found that the percentage of agriculture-free area within the species range declined from 79.5% to 26.2%. Knowing that agroecosystems near lotic environments simplify the structural complexity of habitats (from heterogeneous to homogenous ecological communities) of amphibiotic species such as odonates, we estimated the geographic range of an endemic damselfly and quantified the temporal change in the overlap between agriculture and species occurrence. Our results showed the overlap more than tripled between 1992 and 2005, suggesting that the species experienced a radical change in its terrestrial habitats. We conducted capture–mark–recapture to confirm that the species survives by frequently using croplands and grasslands. Abstract Agriculture can be pervasive in its effect on wild nature, affecting various types of natural habitats, including lotic ecosystems. Here, we assess the extent of agricultural expansion on lotic systems in Northern Africa (Algeria, Tunisia, and Morocco) and document its overlap with the distribution of an endemic damselfly, Platycnemis subdilatata Selys, using species distribution modeling. We found that agricultural land cover increased by 321% in the region between 1992 and 2005, and, in particular, the main watercourses experienced an increase in agricultural land cover from 21.4% in 1992 to 78.1% in 2005, together with an increase in the intensity of 226% in agricultural practices. We used capture–mark–recapture (CMR) surveys in terrestrial habitats surrounding a stream bordered by grassland and cropland in northeastern Algeria to determine demographic parameters and population size, as well as cropland occupancy. CMR modeling showed that the recapture and survival probabilities had an average of 0.14 (95%CI: 0.14–0.17) and 0.86 (0.85–0.87), respectively. We estimated a relatively large population of P. subdilatata (~1750 individuals) in terrestrial habitats. The occupancy of terrestrial habitats by adults was spatially structured by age. Our data suggest that P. subdilatata has survived agricultural expansion and intensification better than other local odonate species, mainly because it can occupy transformed landscapes, such as croplands and grasslands.
Physiological and Transcriptomic Analysis Provide Insight into Low Temperature Enhancing Hypericin Biosynthesis in Hypericum perforatum

Hypericin (Hyp), well-known as an antidepressant, is mainly extracted from Hypericum perforatum. Although Hyp accumulation and biomass are greater at lower compared to higher temperature, the regulation mechanism has not been reported. Here, the physiological characteristics and transcriptome of H. perforatum grown at 15 and 22 °C were determined and analyzed by HPLC and de novo sequencing. The results showed that the stomatal density and opening percentages were 1.1- and 1.4-fold more, and the Hyp content was 4.5-fold greater at 15 °C compared to 22 °C. A total of 1584 differentially expressed genes (DEGs) were observed at 15 versus 22 °C, with 749 characterized genes, 421 upregulated (UR) and 328 downregulated (DR). Based on biological functions, 150 genes were associated with Hyp biosynthesis, plant growth and the stress response, including photosynthesis, carbohydrate metabolism, fatty acids metabolism, cytochrome P450 (CYPs), morpho-physiological traits, heat shock proteins (HSPs), cold-responsive proteins (CRPs) and transcription factors (TFs). The differential expression levels of the master genes were confirmed by qRT-PCR and almost consistent with their Reads Per kb per Million (RPKM) values. This physiological and transcriptomic analyses provided insight into the regulation mechanisms of low temperature enhancing Hyp biosynthesis in H. perforatum.
The Oxindole Derivatives, New Promising GSK-3β Inhibitors as One of the Potential Treatments for Alzheimer’s Disease—A Molecular Dynamics Approach

Simple Summary Enzymatic overexpression is a determinant of the development of many diseases. Increased activity of the GSK-3β enzyme is a factor that manifests itself in the development of numerous disease entities such as Alzheimer’s disease, schizophrenia, diabetes and cancers. An important medical procedure in such cases is the inhibition of enzyme activity. Based on the comprehensive use of computational chemistry methods, a group of new compounds derived from 2-oxindole was designed. The conducted research allowed the assessment of the conformational properties of the ligand molecules in the GSK-3β active site, the dynamic stability of the obtained complexes and their exact energetic characteristics. Taking into account the obtained data, a narrow group of derivatives showing an affinity for the active site of the GSK-3β enzyme was selected. The comparison of binding properties of selected 2-oxindole derivatives with an inhibitor with confirmed pharmacological activity indicates the high application potential of the newly developed compounds. Abstract The glycogen synthase kinase 3β (GSK-3β) is a protein kinase involved in regulating numerous physiological processes such as embryonic development, transcription, insulin action, cell division cycle and multiple neuronal functions. The overexpression of this enzyme is related to many diseases such as schizophrenia, Alzheimer’s disease, diabetes and cancer. One of the basic methods of treatment in these cases is the usage of ATP-competitive inhibitors. A significant group of such compounds are indirubin and its analogs, e.g., oxindole derivatives. The compounds considered in this work are 112 newly designed oxindole derivatives. In the first stage, such molecular properties of considered compounds as toxicity and LogP were estimated. The preliminary analysis of the binding capabilities of considered compounds towards the GSK-3β active site was conducted with the use of the docking procedure. Based on obtained molecular properties and docking simulations, a selected group of complexes that were analyzed in the molecular dynamics stage was nominated. The proposed procedure allowed for the identification of compounds such as Oxind_4_9 and Oxind_13_10, which create stable complexes with GSK-3β enzyme and are characterized by the highest values of binding affinity. The key interactions responsible for stabilization of considered ligand–protein complexes were identified, and their dynamic stability was also determined. Comparative analysis including analyzed compounds and reference molecule 3a, which is also an oxindole derivative with a confirmed inhibitory potential towards GSK3B protein, clearly indicates that the proposed compounds exhibit an analogous binding mechanism, and the obtained binding enthalpy values indicate a slightly higher binding potential than the reference molecule.
Lichens—A Potential Source for Nanoparticles Fabrication: A Review on Nanoparticles Biosynthesis and Their Prospective Applications

Green synthesis of nanoparticles (NPs) is a safe, eco-friendly, and relatively inexpensive alternative to conventional routes of NPs production. These methods require natural resources such as cyanobacteria, algae, plants, fungi, lichens, and naturally extracted biomolecules such as pigments, vitamins, polysaccharides, proteins, and enzymes to reduce bulk materials (the target metal salts) into a nanoscale product. Synthesis of nanomaterials (NMs) using lichen extracts is a promising eco-friendly, simple, low-cost biological synthesis process. Lichens are groups of organisms including multiple types of fungi and algae that live in symbiosis. Until now, the fabrication of NPs using lichens has remained largely unexplored, although the role of lichens as natural factories for synthesizing NPs has been reported. Lichens have a potential reducible activity to fabricate different types of NMs, including metal and metal oxide NPs and bimetallic alloys and nanocomposites. These NPs exhibit promising catalytic and antidiabetic, antioxidant, and antimicrobial activities. To the best of our knowledge, this review provides, for the first time, an overview of the main published studies concerning the use of lichen for nanofabrication and the applications of these NMs in different sectors. Moreover, the possible mechanisms of biosynthesis are discussed, together with the various optimization factors influencing the biological synthesis and toxicity of NPs.
Advances in Lipid-Based Nanoparticles for Cancer Chemoimmunotherapy

Nanomedicines have shown great potential in cancer therapy; in particular, the combination of chemotherapy and immunotherapy (namely chemoimmunotherapy) that is revolutionizing cancer treatment. Currently, most nanomedicines for chemoimmunotherapy are still in preclinical and clinical trials. Lipid-based nanoparticles, the most widely used nanomedicine platform in cancer therapy, is a promising delivery platform for chemoimmunotherapy. In this review, we introduce the commonly used immunotherapy agents and discuss the opportunities for chemoimmunotherapy mediated by lipid-based nanoparticles. We summarize the clinical trials involving lipid-based nanoparticles for chemoimmunotherapy. We also highlight different chemoimmunotherapy strategies based on lipid-based nanoparticles such as liposomes, nanodiscs, and lipid-based hybrid nanoparticles in preclinical research. Finally, we discuss the challenges that have hindered the clinical translation of lipid-based nanoparticles for chemoimmunotherapy, and their future perspectives.