Miracle-dz/UniFAR-FTUs huggingface dataset:
The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection

Iron is an essential mineral participating in different functions of the organism under physiological conditions. Numerous biological processes, such as oxygen and lipid metabolism, protein production, cellular respiration, and DNA synthesis, require the presence of iron, and mitochondria play an important role in the processes of iron metabolism. In addition to its physiological role, iron may be also involved in the adaptive processes of myocardial “conditioning”. On the other hand, disorders of iron metabolism are involved in the pathological mechanisms of the most common human diseases and include a wide range of them, such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease, and accelerate the development of atherosclerosis. Furthermore, iron also exerts potentially deleterious effects that may be manifested under conditions of ischemia/reperfusion (I/R) injury, myocardial infarction, heart failure, coronary artery angioplasty, or heart transplantation, due to its involvement in reactive oxygen species (ROS) production. Moreover, iron has been recently described to participate in the mechanisms of iron-dependent cell death defined as “ferroptosis”. Ferroptosis is a form of regulated cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been shown to be associated with I/R injury and several other cardiac diseases as a significant form of cell death in cardiomyocytes. In this review, we will discuss the role of iron in cardiovascular diseases, especially in myocardial I/R injury, and protective mechanisms stimulated by different forms of “conditioning” with a special emphasis on the novel targets for cardioprotection.
Synthesis, Characterization and Surface Modification of Titanium and Zinc Oxide Nanostructures for Nanotoxicity, Visible Light Emission and Photocatalytic Studies

Size dependent quantum confinement and differential characteristics of the anisotropic ZnO and TiO2 nanomaterials have attracted huge interest in the quest of new functional materials. In order to synthesize ZnO QD’s for visible light emission applications, surface modulation for stability in dispersions and defect control at the surface is vitally important. Therefore long alkyl chain group (e.g. oleate) and biological molecule cysteine were used as vectors to regulate reactivity of the ZnO QD’s and their visible light emission. Sol-gel chemistry serves as a versatile tool for the fabrication of controlled synthesis of quantum dots and to modify their properties for emission applications such as cell labeling, cell toxicity, solid-state light emission and to understand size/property correlation. High temperature liquid phase synthesis methods, namely heating up and hot injection method were applied toward the synthesis of anisotropic ZnO and TiO2 nanoparticles. Using different ligand concentrations and reaction conditions, semiconductor nanostructures of unusual geometrical shapes were synthesized and characterized. Hexagonal crystal growing habit of ZnO provided unusual geometrically distorted examples of the hexagonal geometry that have not been reported so far in the literature. Furthermore, TiO2 nanostructures with significant absorption in visible range of the solar spectrum were obtained by hot injection method and nitrogen doping. The rapid injection and decomposition of Ti-precursor and amine enabled to produce self assembled ball like and multibranched structures with remarkable visible range absorption. Utilization of different concentrations for the precursors provided the possibility of band gap engineering for the anisotropic TiO2 nanostructures.
Antagonistic Potential of Novel Endophytic Bacillus Strains and Mediation of Plant Defense against Verticillium Wilt in Upland Cotton

Verticillium wilt caused by Verticillium dahliae is a threatening disease of cotton, causing economic loss worldwide. In this study, nine endophytic Bacillus strains isolated from cotton roots exhibited inhibitory activity against V. dahliae strain VD-080 in a dual culture assay. B. altitudinis HNH7 and B. velezensis HNH9 were chosen for further experiments based on their high antagonistic activity. The secondary metabolites of HNH7 and HNH9 also inhibited the growth of VD-080. Genetic marker-assisted detection revealed the presence of bacillibactin, surfactin, bacillomycin and fengycin encoding genes in the genome of HNH7 and HNH9 and their corresponding gene products were validated through LC-MS. Scanning electron microscopy revealed mycelial disintegration, curling and shrinkage of VD-080 hyphae after treatment with methanolic extracts of the isolated endophytes. Furthermore, a significant reduction in verticillium wilt severity was noticed in cotton plants treated with HNH7 and HNH9 as compared to control treatments. Moreover, the expression of defense-linked genes, viz., MPK3, GST, SOD, PAL, PPO and HMGR, was considerably higher in plants treated with endophytic Bacillus strains and inoculated with VD-080 as compared to control.
The Role of Alcohol Metabolism in the Pathology of Alcohol Hangover

The limited number of available studies that examined the pathology of alcohol hangover focused on biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol as potentially important determinants of hangover severity. The available literature on alcohol metabolism and oxidative stress is reviewed in this article. The current body of evidence suggests a direct relationship between blood ethanol concentration and hangover severity, whereas this association is not significant for acetaldehyde. The rate of alcohol metabolism seems to be an important determinant of hangover severity. That is, fast elimination of ethanol is associated with experiencing less severe hangovers. An explanation for this observation may be the fact that ethanol—in contrast to acetaldehyde—is capable of crossing the blood–brain barrier. With slower ethanol metabolism, more ethanol is able to reach the brain and elicit hangover symptoms. Hangover severity was also significantly associated with biomarkers of oxidative stress. More oxidative stress in the first hours after alcohol consumption was associated with less severe next-day hangovers (i.e., a significant negative correlation was found between hangover severity and malondialdehyde). On the contrary, more oxidative stress at a later stage after alcohol consumption was associated with having more severe next-day hangovers (i.e., a significant positive correlation was found between hangover severity and 8-isoprostane). In conclusion, assessment of biomarkers of alcohol metabolism suggests that fast elimination of ethanol is associated with experiencing less severe hangovers. More research is needed to further examine the complex interrelationship between alcohol metabolism, the role of acetaldehyde and oxidative stress and antioxidants, and the pathology of the alcohol hangover.
The Protective Role of Hydrogen Sulfide Against Obesity-Associated Cellular Stress in Blood Glucose Regulation

Circulating palmitic acid (PA) is increased in obesity and causes metabolic stress, leading to diabetes. This includes the impairment of the glucoregulatory hormone glucagon-like peptide-1 (GLP-1) secreted from intestinal L-cells. Recently, the anti-inflammatory gasotransmitter hydrogen sulfide (H2S) has been implicated in the enhancement of GLP-1 secretion. We hypothesized that H2S can reduce the oxidative stress caused by palmitate and play a protective role in L-cell function. This study was conducted on both human and mouse L-cells and a mouse model of Western diet (WD)-induced obesity. PA-induced L-cell stress was assessed using DCF-DA. H2S was delivered using the donor GYY4137. C57BL/6 mice were fed either chow diet or PA-enriched WD for 20 weeks with ongoing measurements of glycemia and GLP-1 secretion. In both L-cell models, we demonstrated that PA caused an increase in reactive oxygen species (ROS). This ROS induction was partially blocked by the H2S administration. In mice, the WD elevated body weight in both sexes and elevated fasting blood glucose and lipid peroxidation in males. Additionally, a single GYY4137 injection improved oral glucose tolerance in WD-fed male mice and also enhanced glucose-stimulated GLP-1 release. To conclude, H2S reduces oxidative stress in GLP-1 cells and can improve glucose clearance in mice.
Serine synthesis influences tamoxifen response in ER+ human breast carcinoma.

Estrogen receptor positive breast cancer (ER+ BC) is the most common form of breast carcinoma accounting for approximately 70% of all diagnoses. Although ER-targeted therapies have improved survival outcomes for this BC subtype, a significant proportion of patients will ultimately develop resistance to these clinical interventions, resulting in disease recurrence. Phosphoserine aminotransferase 1 (PSAT1), an enzyme within the serine synthetic pathway (SSP), has been previously implicated in endocrine resistance. Therefore, we determined whether expression of SSP enzymes, PSAT1 or phosphoglycerate dehydrogenase (PHGDH), affects the response of ER+ BC to 4-hydroxytamoxifen (4-OHT) treatment. To investigate a clinical correlation between PSAT1, PHGDH, and endocrine resistance, we examined microarray data from ER+ patients who received tamoxifen as the sole endocrine therapy. We confirmed that higher PSAT1 and PHGDH expression correlates negatively with poorer outcomes in tamoxifen treated ER+ BC patients. Next, we found that SSP enzyme expression and serine synthesis were elevated in tamoxifen-resistant compared to tamoxifen-sensitive ER+ BC cells in vitro. To determine relevance to endocrine sensitivity, we modified the expression of either PSAT1 or PHGDH in each cell type. Overexpression of PSAT1 in tamoxifen-sensitive MCF-7 cells diminished 4-OHT inhibition on cell proliferation. Conversely, silencing of either PSAT1 or PHGDH resulted in greater sensitivity to 4-OHT treatment in LCC9 tamoxifen-resistant cells. Likewise, the combination of a PHGDH inhibitor with 4-OHT decreased LCC9 cell proliferation. Collectively, these results suggest that overexpression of serine synthetic pathway enzymes contribute to tamoxifen resistance in ER+ BC, which can be targeted as a novel combinatorial treatment option.
Effects of Vacuum Packaging on Enzymatic Browning and Ethylene Response Factor (ERF) Gene Expression of Fresh-cut Lotus Root

Ethylene response factor (ERF) genes have been involved in responses to biotic and abiotic stress, including hypoxia and anaerobic stress. Vacuum packaging (a typical anaerobic stress) is an effective storage method used to delay browning of fresh-cut lotus root (Nelumbo nucifera). In model plants, ERF genes have been identified as responsive to hypoxia. Whether ERF is associated with browning of vacuum-packaged lotus root has not been studied. The effects of vacuum packaging on browning, phenolic content, the enzyme activity of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD), and PPO, PAL, POD, and ERF genes expression in fresh-cut lotus root were studied. Downregulation of NnPAL1, NnPPOA, and NnPOD2/3 attributable to vacuum packaging coincided with increased related enzyme activities and the degree of browning of fresh-cut lotus root. The expression patterns of NnERF4/5 were consistent with the changes in NnPAL1, NnPPOA, and NnPOD2/3 gene expression. It has been proposed that NnERF4/5 could have be important regulators of fresh-cut lotus root browning, and that the relationships of NnERF4/5 and NnPAL1, NnPPOA, and NnPOD2/3 should to be studied further.
Control of Wnt Trans-Synaptic Signaling by Secreted Extracellular Regulators

FM dyes are used to study the synaptic vesicle (SV) cycle. These amphipathic probes have a hydrophilic head and hydrophobic tail, making them water-soluble with the ability to reversibly enter and exit membrane lipid bilayers. These styryl dyes are relatively non-fluorescent in aqueous medium, but insertion into the outer leaflet of the plasma membrane causes a >40X increase in fluorescence. In neuronal synapses, FM dyes are internalized during SV endocytosis, trafficked both within and between SV pools, and released with SV exocytosis, providing a powerful tool to visualize presynaptic stages of neurotransmission. A primary genetic model of glutamatergic synapse development and function is the Drosophila neuromuscular junction (NMJ), where FM dye imaging has been used extensively to quantify SV dynamics in a wide range of mutant conditions. The NMJ synaptic terminal is easily accessible, with a beautiful array of large synaptic boutons ideal for imaging applications. Here, we compare and contrast the three ways to stimulate the Drosophila NMJ to drive activity-dependent FM1-43 dye uptake/release: 1) bath application of high [K] to depolarize neuromuscular tissues, 2) suction electrode motor nerve stimulation to depolarize the presynaptic nerve terminal, and 3) targeted transgenic expression of channelrhodopsin variants for light-stimulated, spatial control of depolarization. Each of these methods has benefits and disadvantages for the study of genetic mutation effects on the SV cycle at the Drosophila NMJ. We will discuss these advantages and disadvantages to assist the selection of the stimulation approach, together with the methodologies specific to each strategy.
Evaluation of Nephrotoxicity among First-Line Antiretroviral Therapy-Experienced Patients at the Yaounde Central Hospital

The withdrawal of stavudine from the first line Antiretroviral Therapy (ART) and the introduction of tenofovir (TDF) since 2010 in sub-Saharan Africa had a direct repercussion on the initiation of many patients on this new molecule. Despite its therapeutic efficiency already proved, TDF seems to induce some side effects such as renal failures. So, it is important to study the variation of early renal marker and immunological response (CD4 cells) of patients on regimen with TDF in order to have an optimal therapeutic follow up.
Safety, Efficacy and Pharcacokinetics of Targeted Therapy with The Liposomal RNA Interference Therapeutic Atu027 Combined with Gemcitabine in Patients with Pancreatic Adenocarcinoma. A Randomized Phase Ib/IIa Study

Simple Summary Pancreatic cancer is still a challenging disease, as chemotherapeutic options are limited. We present the data of a new liposomally formulated short interfering RNA, Atu027, which has antimetastatic activity. In this randomized trial, pharmacokinetics and efficacy were assessed in two different treatment schedules. Both types of treatment were well-tolerated, with the side effects mainly being laboratory abnormalities without clinical importance. The twice-weekly regime compared patients with locally advanced to those with metastatic disease; in the latter group, a significant prolongation of survival without disease progression could be found. Therefore, as Atu027 influences the vascular endothelium, we suggest the further investigation of this compound as it seems to be able to prevent or delay metastases of pancreatic cancer. Abstract Background: Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences the expression of protein kinase N3 (PKN3) in the vascular endothelium. This trial was designed to assess the safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). Methods: In total, 23 patients (pts) with inoperable APC were randomly assigned to gemcitabine combined with two different Atu027 schedules (0.235 mg/kg once weekly vs. 0.235 mg/kg twice weekly). ClinicalTrials.gov Identifier: NCT01808638. Results: The treatment was well-tolerated. There were Grade 3 adverse events (AEs) in 9/11 pts (arm 1) and 11/12 pts (arm 2), while Grade 4 AEs were reported for two pts in each arm. The AEs were mainly laboratory abnormalities without clinical significance. The median progression-free survival reached statistical significance in patients who had metastatic disease (1.6 vs. 2.9 months, p = 0.025). Disease control during treatment was achieved in 4/11 pts (arm 1) and in 7/12 pts (arm 2). Pts in arm 1 experienced stable global health status while pts in arm 2 reported improvement. Conclusions: Combining Atu027 with gemcitabine is safe and well tolerated. In pts with metastatic APC, twice-weekly Atu027 is associated with significantly improved outcomes. Our clinical results support the significant involvement of the vascular endothelium in the spread of cancer, and thus the further investigation of its target role.
Charting shared developmental trajectories of cortical thickness and structural connectivity in childhood and adolescence

The cortex is organised into broadly hierarchical functional systems with distinct neuroanatomical characteristics reflected by macroscopic measures of cortical morphology. Diffusion-weighted MRI allows the delineation of areal connectivity, changes to which reflect the ongoing maturation of white matter tracts. These developmental processes are intrinsically linked with timing coincident with the development of cognitive function. In this study, we use a data-driven multivariate approach, non-negative matrix factorisation, to define cortical regions that co-vary together across a large paediatric cohort (n=456) and are associated with specific subnetworks of cortical connectivity. We find that age between 3 and 21 years is associated with accelerated cortical thinning in fronto-parietal regions, whereas relative thinning of primary motor and sensory regions is slower. Together, the subject-specific weights of the derived set of components can be combined to predict chronological age. Structural connectivity networks reveal a relative increase in strength in connection within, as opposed to between hemispheres that vary in line with cortical changes. We confirm our findings in an independent sample.
Isolation and Structural Elucidation of 15-Nuclear Copper Dihydride Clusters: An Intermediate in the Formation of a Two-Electron Copper Superatom.

Highly reactive copper-dihydride clusters, [Cu15 (H)2 (S2 CNR2 )6 (C2 Ph)6 ](PF6 ) {R = n Bu (1H ), n Pr (2H ), i Bu (3H )}, are isolated during the reaction of [Cu28 H15 {S2 CNn Bu2 }12 ](PF6 ) with ten equivalents of phenylacetylene. They are found to be intermediates in the formation of the earlier reported two-electron superatom [Cu13 (S2 CNR2 )6 (C2 Ph)4 ]+ . Better yields are obtained by reacting dithiocarbamate sodium salts, [Cu(CH3 CN)4 ](PF6 ), BH4 - and phenylacetylene. The presence of two hydrides in the isolated clusters is confirmed by the synthesis and characterization of its deuteride analogue [Cu15 (D)2 (S2 CNR2 )6 (C2 Ph)6 ]+ , and a single-crystal neutron structure of 2H . Structural characterization of 1H reveals a new bicapped icosahedral copper(I) cage encapsulating a linear copper dihydride (CuH2 )- unit. Reaction of 3H with Au(I) salts yields a highly luminescent [AuCu12 (S2 CNi Bu2 )6 (C2 Ph)4 ]+ cluster.
Technology System Evolution: Inertia and Momentum Revisited

In markets with network externalities, the technology that gains a critical mass of users will gain market momentum, and further attract users. Despite this predicted self-reinforcing feedback propelled by “excess inertia”, we observe technologies dethroning established systems in several contexts. Why are some technologies able to sustain momentum over time while others loose it in favor of dethroners? We address this question conceptually, by revisiting the concept of momentum into the inertial and dynamic components, and empirically, by estimating the effects of both components on technology adoption and market performance in a platform technology context. Drawing from Physics, we conceptualize the inertial component of momentum (i.e., mass) as the stock of platform complements, and the dynamic component (i.e., velocity) as the period-by-period change in such stock, or complement novelty. We show that the dynamic component of momentum explains to a larger extent the sustained momentum and performance of a platform technology system, and has a predictability power for estimating the point at which the overall market tips for platforms of next generation technology. This has relevant implications for technology adoption and competitive dynamics, and help explain why latecomers may dethrone incumbents despite network disadvantage.
Control of Biological Hazards in Insect Processing: Application of HACCP Method for Yellow Mealworm (Tenebrio molitor) Powders

Entomophagy has been part of human diets for a long time in a significant part of the world, but insects are considered to be a novel food everywhere else. It would appear to be a strategic alternative in the future of human diet to face the challenge of ensuring food security for a growing world population, using more environmentally sustainable production systems than those required for the rearing of other animals. Tenebrio molitor, called yellow mealworm, is one of the most interesting insect species in view of mass rearing, and can be processed into a powder that ensures a long shelf life for its use in many potential products. When considering insects as food or feed, it is necessary to guarantee their safety. Therefore, manufacturers must implement a Hazard Analysis Critical Control plan (HACCP), to limit risks for consumers’ health. The aim of this case study was to develop a HACCP plan for Tenebrio molitor larvae powders for food in a risk-based approach to support their implementation in industry. Specific purposes were to identify related significant biological hazards and to assess the efficiency of different manufacturing process steps when used as Critical Control Points. Then, combinations of four different processes with four potential uses of powders by consumers in burger, protein shake, baby porridge, and biscuits were analyzed with regard to their safety.