Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomic and metabolomic signatures of U87 glioblastoma cells treated with cisplatin and/or paclitaxel

Abstract Background Glioblastoma (GBM) is a primary malignancy of the central nervous system and is classified as a grade IV astrocytoma by the World Health Organization (WHO). Although GBM rarely metastasizes, its prognosis remains poor. Moreover, the standard treatment for GBM, temozolomide (TMZ), is associated with chemoresistance, which is a major factor behind GBM-related deaths. Investigating drugs with repurposing potential in the context of GBM is worthwhile to bypass lengthy bench-to-bedside research. The field of omics has garnered significant interest in scientific research because of its potential to delineate the intricate regulatory network underlying tumor development. In particular, proteomic and metabolomic analyses are powerful approaches for the investigation of metabolic enzymes and intermediate metabolites since they represent the functional end of the cancer phenotype. Methods We chose two of the most widely prescribed anticancer drugs, cisplatin and paclitaxel. To our knowledge, the current literature lacks studies examining their effects on metabolic and proteomic alterations in GBM. We employed the mass spectrometry technological platform ‘UHPLC-Q-TOF-MS/MS’ to examine the changes in the proteome and metabolome profiles of the U87 cell line with defined concentrations of cisplatin and/or paclitaxel via an untargeted approach. Results A total of 1,419 distinct proteins and 90 metabolites were generated, and subsequent analysis was performed. We observed that upon treatment with cisplatin (9.5 μM), U87 cells exhibited apparent efforts to cope with this exogenous stressor, understanding the effect of paclitaxel (5.3 μM) on altering the transport machinery of the cell, and how the combination of cisplatin and/or paclitaxel suggests potential interactions with promising benefits in GBM therapeutics. Conclusion Our research provides a detailed map of alterations in response to cisplatin and paclitaxel treatment, provides crucial insights into the molecular basis of their action, and paves the way for further research to identify molecular targets for this elusive malignancy.
Lactobacillus paracasei JY062 Alleviates Glucolipid Metabolism Disorders via the Adipoinsular Axis and Gut Microbiota

Glycolipid metabolic disorders (GLMD) refer to a series of metabolic disorders caused by abnormal processes of glucose and lipid synthesis, decomposition, and absorption in the body, leading to glucose and lipid excess, insulin resistance, and obesity. Probiotic intervention is a new strategy to alleviate metabolic syndrome. Lactobacillus paracasei JY062 (L. paracasei JY062) was separated from the Tibet-fermented dairy products. The results demonstrated a strong ability to relieve blood glucose disorders, blood lipid disorders, and tissue damage. The LPH group had the best effect, significantly decreasing the total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), leptin, insulin, and free fatty acid (FFA) concentrations and increasing the high-density lipoprotein cholesterol, adiponectin, and GLP-1 level compared to HFD-group mice. L. paracasei JY062 could activate the APN-AMPK pathway, increased AdipoQ, AMPK GLUT-4, and PGC-1α mRNA expression and decreased SREBP-1c, ACC, and FAS mRNA expression. L. paracasei JY062 intervention decreased the relative abundance of harmful bacteria, increased the relative abundance of beneficial bacteria, and restored the imbalance of gut microbiota homeostasis caused by a high-glucose-fat diet. L. paracasei JY062 alleviated glucolipid metabolism disorders via the adipoinsular axis and gut microbiota. This study provided a theoretical basis for probiotics to ameliorate glucolipid metabolism disorders by regulating the adipoinsular axis.
Green Synthesized Polymeric Iodophors with Thyme as Antimicrobial Agents

Antimicrobial resistance (AMR) is a growing concern for the future of mankind. Common antibiotics fail in the treatment of microbial infections at an alarming rate. Morbidity and mortality rates increase, especially among immune-compromised populations. Medicinal plants and their essential oils, as well as iodine could be potential solutions against resistant pathogens. These natural antimicrobials abate microbial proliferation, especially in synergistic combinations. We performed a simple, one-pot synthesis to prepare our formulation with polyvinylpyrrolidone (PVP)-complexed iodine (I2), Thymus Vulgaris L. (Thyme), and Aloe Barbadensis Miller (AV). SEM/EDS, UV-vis, Raman, FTIR, and XRD analyses verified the purity, composition, and morphology of AV-PVP-Thyme-I2. We investigated the inhibitory action of the bio-formulation AV-PVP-Thyme-I2 against 10 selected reference pathogens on impregnated sterile discs, surgical sutures, cotton gauze bandages, surgical face masks, and KN95 masks. The antimicrobial properties of AV-PVP-Thyme-I2 were studied by disc diffusion methods and compared with those of the antibiotics gentamycin and nystatin. The results confirm AV-PVP-Thyme-I2 as a strong antifungal and antibacterial agent against the majority of the tested microorganisms with excellent results on cotton bandages and face masks. After storing AV-PVP-Thyme-I2 for 18 months, the inhibitory action was augmented compared to the fresh formulation. Consequently, we suggest AV-PVP-Thyme-I2 as an antimicrobial agent against wound infections and a spray-on contact killing agent.
Multifunctional Pomegranate Peel Microparticles with Health-Promoting Effects for the Sustainable Development of Novel Nutraceuticals and Pharmaceuticals

Recovering the bioactive components from pomegranate peel (PP) in the fruit-processing industry has attracted great attention in terms of minimizing the waste burden, as well as providing a new source of a multitude of functional compounds. The present study aimed to develop a feasible microencapsulation process of PP extract by using pectin and a pectin/2-hydroxypropyl-β-cyclodextrin (HP-β-CD) blend as coating materials. Microsized powders obtained by a spray drying technique were examined in terms of technological characteristics, exhibiting high powder yield and desirable moisture content, flowability, and cohesive properties. Assuming that the interactions with the used biopolymers occur on the surface hydrophobic domain, their presence significantly improved the thermal stability of the microencapsulated powders up to 200 °C. The health-promoting effects of PP have been associated with its high content in ellagitannins, particularly punicalagin. The obtained PP powders exhibited strong antioxidant and hypoglycemic potential, while an antimicrobial assay revealed their potent activity against Gram-positive bacteria. Additionally, an in vitro release study suggested that the used biopolymers can modify the release of target bioactive compounds, thus establishing a basis for developing an oral-controlled release system. Altogether, biowaste valorization from PP by the production of effective multifunctional microsized powders represents a sustainable way to obtain novel nutraceuticals and/or pharmaceuticals.
Health Promotion with Long-Term Physical Activity Program for Adults with Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) are at higher risk for developing common chronic diseases. Engagement in physical activity (PA) can prevent health issues; however, people with ASD are known to engage in lower levels of PA in comparison to their peers. This study evaluated the effect of a long-term, 12-month PA intervention on the fitness and quality of life of adults with ASD. A quantitative approach was implemented to assess participants’ fitness, functional ability, quality of life, and participation in a range of PA classes at three different time points. Qualitative data were collected via in-depth, semi-structured interviews with three participants with ASD and three staff members. A total of 34 adults with ASD (mean age 39.76 + 7.27) participated in the quantitative part of the study. Approximately 53% of the participants exhibited perseverance and conducted adequate PA each month. Significant improvements were found in one fitness component and two quality-of-life components. Factors revealed for the program’s success were the individuals’ free choice of the PA classes and supporting people and a budget that tailored the project. Policymakers who plan health promotion programs for adults with ASD should consider long-term PA programs, with freedom of choice among PA modalities and schedules.
Deciphering the Immune Microenvironment at the Forefront of Tumor Aggressiveness by Constructing a Regulatory Network with Single-Cell and Spatial Transcriptomic Data

The heterogeneity and intricate cellular architecture of complex cellular ecosystems play a crucial role in the progression and therapeutic response of cancer. Understanding the regulatory relationships of malignant cells at the invasive front of the tumor microenvironment (TME) is important to explore the heterogeneity of the TME and its role in disease progression. In this study, we inferred malignant cells at the invasion front by analyzing single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) data of ER-positive (ER+) breast cancer patients. In addition, we developed a software pipeline for constructing intercellular gene regulatory networks (IGRNs), which help to reduce errors generated by single-cell communication analysis and increase the confidence of selected cell communication signals. Based on the constructed IGRN between malignant cells at the invasive front of the TME and the immune cells of ER+ breast cancer patients, we found that a high expression of the transcription factors FOXA1 and EZH2 played a key role in driving tumor progression. Meanwhile, elevated levels of their downstream target genes (ESR1 and CDKN1A) were associated with poor prognosis of breast cancer patients. This study demonstrates a bioinformatics workflow of combining scRNA-seq and ST data; in addition, the study provides the software pipelines for constructing IGRNs automatically (cIGRN). This strategy will help decipher cancer progression by revealing bidirectional signaling between invasive frontline malignant tumor cells and immune cells, and the selected signaling molecules in the regulatory network may serve as biomarkers for mechanism studies or therapeutic targets.
Immp2l Enhances the Structure and Function of Mitochondrial Gpd2 Dehydrogenase

‘Inner mitochondrial membrane peptidase 2 like’ (IMMP2L) is a nuclear-encoded mitochondrial peptidase that has been conserved through evolutionary history, as has its target enzyme, ‘mitochondrial glycerol phosphate dehydrogenase 2′ (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear-encoded mitochondrial respiratory-related protein, cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory-related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2lKD−/− KO mouse, and in this study, EchoMRI analysis found that the organs of the Immp2lKD−/− KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p < 0.05). Moreover, all organs analysed from the Immp2lKD−/− KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2lKD−/− KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lowest in the kidney of the Immp2lKD−/− KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to the wildtype when glutamate was used as the substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2, we observed ~20% and ~7% respective decreases in respiration in female and male Immp2lKD−/− KO mice over time. Together, these findings indicate that the respiratory-related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues and genders of the Immp2lKD−/− KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial-encoded cytochrome b (Cyb) in Complex III had been altered, as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2lKD−/− KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS), which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2lKD−/− KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2lKD−/− KO mouse displayed a ~27% decrease in total respiration, comprising a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration, where the latter was consistent with the cumulative decreases in substrate-specific mediated mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis.
Biofilm Formation in Campylobacter concisus: The Role of the luxS Gene

Campylobacter concisus is a bacterium that inhabits human oral cavities and is an emerging intestinal tract pathogen known to be a biofilm producer and one of the bacterial species found in dental plaque. In this study, biofilms of oral and intestinal C. concisus isolates were phenotypically characterized. The role of the luxS gene, which is linked to the regulation of biofilm formation in other pathogens, was assessed in relation to the pathogenic potential of this bacterium. Biofilm formation capacity was assessed using phenotypic assays. Oral strains were shown to be the highest producers. A luxS mutant was created by inserting a kanamycin cassette within the luxS gene of the highest biofilm-forming isolate. The loss of the polar flagellum was observed with scanning and transmission electron microscopy (SEM and TEM). Furthermore, the luxS mutant exhibited a significant reduction (p < 0.05) in biofilm formation, motility, and its expression of flaB, in addition to the capability to invade intestinal epithelial cells, compared to the parental strain. The study concluded that C. concisus oral isolates are significantly higher biofilm producers than the intestinal isolates and that LuxS plays a role in biofilm formation, invasion, and motility in this bacterium.
Characterization of slow slip rate faults in humid areas: Cimandiri fault zone, Indonesia

In areas where regional tectonic strain is accommodated by broad zones of short and low slip rate faults, geomorphic and paleoseismic characterization of faults is difficult because of poor surface expression and long earthquake recurrence intervals. In humid areas, faults can be buried by thick sediments or soils; their geomorphic expression subdued and sometimes undetectable until the next earthquake. In Java, active faults are diffused, and their characterization is challenging. Among them is the ENE striking Cimandiri fault zone. Cumulative displacement produces prominent ENE oriented ranges with the southeast side moving relatively upward and to the northeast. The fault zone is expressed in the bedrock by numerous NE, west, and NW trending thrust‐ and strike‐slip faults and folds. However, it is unclear which of these structures are active. We performed a morphometric analysis of the fault zone using 30 m resolution Shuttle Radar Topography Mission digital elevation model. We constructed longitudinal profiles of 601 bedrock rivers along the upthrown ranges along the fault zone, calculated the normalized channel steepness index, identified knickpoints and use their distribution to infer relative magnitudes of rock uplift and locate boundaries that may indicate active fault traces. We compare the rock uplift distribution to surface displacement predicted by elastic dislocation model to determine the plausible fault kinematics. The active Cimandiri fault zone consists of six segments with predominant sense of reverse motion. Our analysis reveals considerable geometric complexity, strongly suggesting segmentation of the fault, and thus smaller maximum earthquakes, consistent with the limited historical record of upper plate earthquakes in Java.
Grape Pomace Rich-Phenolics and Anthocyanins Extract: Production by Pressurized Liquid Extraction in Intermittent Process and Encapsulation by Spray-Drying

A considerable number of grape pomaces are generated annually. It represents a rich source of bioactive compounds, such as phenolic compounds and anthocyanins. Pressurized liquid extraction (PLE) has emerged as a green technology for recovering bioactive compounds from vegetal matrixes. In our study, PLE parameters (temperature, number of cycles, and rinse volume) have been studied to produce grape pomace extracts with high bioactive content using an experimental design. The experimental data obtained were adjusted to linear and quadratic models. The first-order model was better in predicting anthocyanins contents (TA, R2 = 0.94), whereas the second-order model was predictive for total phenolic compounds (TPC, R2 = 0.96). The main process parameter for the recovery of bioactive compounds was temperature, and the results showed opposing behaviors concerning TPC and TA, as it is difficult to optimize conditions for both. The extract containing the higher concentration of TPC (97.4 ± 1.1 mg GAE/g, d.b.) was encapsulated by spray-drying using maltodextrin as wall material. Particles presented with a spherical shape (~7.73 ± 0.95 μm) with a recovery yield of 79%. The results demonstrated that extraction followed by encapsulation of grape pomace extract is a good strategy to simplify future applications, whether for food, cosmetics or pharmaceutical fields.
HPLC-MS/MS Phenolic Characterization of Olive Pomace Extracts Obtained Using an Innovative Mechanical Approach

Olive pomace results from the production of olive oil. Even if olive pomace represents a potential environmental problem, it contains phenolic compounds, which are widely recognized for their beneficial properties for human health. In this study, an innovative and sustainable technological approach to extract phenolic compounds from fresh olive pomace, based on food-grade solvent instead of those usually adopted, is investigated. Characterization and shelf-life evaluation of the hydroalcoholic extracts obtained from the procedure developed for different industrial purposes were also carried out. The phenolic fractions of the different samples were studied with the Folin–Ciocâlteu method to quantify that the total reducing molecules and HPLC-MS/MS analysis was used to define the profile through the identification and quantification of 42 compounds, belonging to five chemical families. Regarding shelf-life, the hydroalcoholic extract showed no significant reduction in phenolic content, for both instrumental evaluations, retaining most of the phenolic compounds present in the raw material; negative attributes were not perceived by sensory evaluation. Thus, these lab-scale results can be the starting point to develop a procedure that is suitable for a real olive mill, representing a valorization strategy in a circular economy and the perspective of new business models.
Exploitation cartographique d'un fichier de terres agricoles

A partir d'un fichier d'analyse de terres agricoles, localisees d'apres la commune du lieu de prelevement et eventuellement par ses coordonnees geographiques, nous avons trace des cartes a l'aide de logiciels specialises. Les informations cartographiees correspondent soit aux donnees brutes contenues dans le fichier, soit au resultat de calculs ou d'interpretations agronomiques effectues a partir de celles-ci. Les cartes sont de trois types: representation par commune (d'apres la mediane des resultats correspondants), point par point et courbes d'isovaleurs
Effects of Vildagliptin, a Dipeptidyl Peptidase-4 Inhibitor, on the Parameters of Glucose Metabolism and the Cardio-Ankle Vascular Index in Individuals with Type 2 Diabetes

DPP-4 inhibitors are frequently used as first-line agents for the treatment of type 2 diabetes in Japan. This study aimed to examine the effects of vildagliptin on glucose metabolism and arterial stiffness. Twenty treatment-naïve patients with type 2 diabetes (8 males and 12 females) received vildagliptin 50 mg twice daily for 6 months. Self-monitored blood glucose measurements and a 75 g OGTT were performed. Arterial stiffness was assessed using the CAVI. After the vildagliptin treatment, a significant decrease in the median HbA1c (from 8.3 to 6.4%) and fasting HOMA-β (from 26.1 to 34.5%), and a marginally significant decrease in the CAVI (from 8.9 to 8.4, p = 0.087) were observed. The glycemic variability parameters also improved, whereas the insulin sensitivity and oxidative stress remained unchanged. Participants with a lower glycemic variability on the 75 g OGTT after vildagliptin treatment showed a significant decrease in their CAVI. The baseline BMI was significantly higher for the participants with a decreased CAVI than in those with no change in their CAVI (24.5 vs. 20.8 kg/m2). After vildagliptin treatment, a decrease in the CAVI was observed, especially in the individuals with improved glycemic variability on the 75 g OGTT. Vildagliptin may be suitable for vascular protection in individuals with high glycemic variability and/or an elevated BMI.
Relationship between home garden ownership and the consumption of fruits and vegetables

Objective: This study assessed the extent to which access to home gardens associate with the frequency of fruit and vegetable (FV) consumption. Setting: The study was carried out in fifty rural communities in Northern Ghana where food insecurity and malnutrition including micronutrient deficiencies are prevalent. Design: A community-based comparative analytical cross-sectional study. Participants: A sample of 847 randomly selected rural households. Results: The proportion of households that consumed FV at least 3 d in a week was 45 %. Members in households who owned a home garden were 1·5 times more likely to consume FV at least 3 d in a week (adjusted OR (AOR) = 1·46 (95 % CI 1·06–2·0)), compared with their counterparts who had no home gardens. Furthermore, households in which mothers had a positive attitude towards FV consumption were 1·6 times more likely to consume FV (AOR = 1·63 (95 % CI 1·17–2·27)) compared with mothers who were less positive. Conclusions: Our results suggest that food and nutrition policy measures that promote home gardens can improve consumption of diversified diets including FV among vulnerable rural households in Northern Ghana. Additionally, households with lower income may benefit from nutrition behaviour change communication campaigns directed towards increasing a positive attitude to FV intake.
Rowhammer Attacks in Dynamic Random-Access Memory and Defense Methods

This paper provides a comprehensive overview of the security vulnerability known as rowhammer in Dynamic Random-Access Memory (DRAM). While DRAM offers many desirable advantages, including low latency, high density, and cost-effectiveness, rowhammer vulnerability, first identified in 2014, poses a significant threat to computing systems. Rowhammer attacks involve repetitive access to specific DRAM rows, which can cause bit flips in neighboring rows, potentially compromising system credentials, integrity, and availability. The paper discusses the various stages of rowhammer attacks, explores existing attack techniques, and examines defense strategies. It also emphasizes the importance of understanding DRAM organization and the associated security challenges.