Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of Trace Elements on Neurodegenerative Diseases of The Eye—The Glaucoma Model

Glaucoma is a heterogeneous group of chronic neurodegenerative disorders characterized by a relatively selective, progressive damage to the retinal ganglion cells (RGCs) and their axons, which leads to axon loss and visual field alterations. To date, many studies have shown the role of various elements, mainly metals, in maintaining the balance of prooxidative and antioxidative processes, regulation of fluid and ion flow through cell membranes of the ocular tissues. Based on the earlier and current research results, their relationship with the development and progression of glaucoma seems obvious and is increasingly appreciated. In this review, we aimed to summarize the current evidence on the role of trace elements in the pathogenesis and prevention of glaucomatous diseases. Special attention is also paid to the genetic background associated with glaucoma-related abnormalities of physiological processes that regulate or involve the ions of elements considered as trace elements necessary for the functioning of the cells.
The Protein Interactome of Glycolysis in Escherichia coli

Glycolysis is regulated by numerous mechanisms including allosteric regulation, post-translational modification or protein-protein interactions (PPI). While glycolytic enzymes have been found to interact with hundreds of proteins, the impact of only some of these PPIs on glycolysis is well understood. Here we investigate which of these interactions may affect glycolysis in E. coli and possibly across numerous other bacteria, based on the stoichiometry of interacting protein pairs (from proteomic studies) and their conservation across bacteria. We present a list of 339 protein-protein interactions involving glycolytic enzymes but predict that ~70% of glycolytic interactors are not present in adequate amounts to have a significant impact on glycolysis. Finally, we identify a conserved but uncharacterized subset of interactions that are likely to affect glycolysis and deserve further study.
Combination of Talazoparib and Palbociclib as a Potent Treatment Strategy in Bladder Cancer

The use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors represents a potent strategy for cancer therapy. Due to the complex molecular network that regulates cell cycle progression, cancer cells often acquire resistance mechanisms against these inhibitors. Previously, our group identified molecular factors conferring resistance to CDK4/6 inhibition in bladder cancer (BLCA) that also included components within the DNA repair pathway. In this study, we validated whether a combinatory treatment approach of the CDK4/6 inhibitor Palbociclib with Poly-(ADP-Ribose) Polymerase (PARP) inhibitors improves therapy response in BLCA. First, a comparison of PARP inhibitors Talazoparib and Olaparib showed superior efficacy of Talazoparib in vitro and displayed high antitumor activity in xenografts in the chicken chorioallantoic membrane (CAM) model. Moreover, the combination of Talazoparib and the CDK4/6 inhibitor Palbociclib synergistically reduced tumor growth in Retinoblastoma protein (RB)-positive BLCA in vitro and in a CAM model, an effect that relies on Palbociclib-induced cell cycle arrest in G0/G1-phase complemented by a G2 arrest induced by Talazoparib. Interestingly, Talazoparib-induced apoptosis was reduced by Palbociclib. The combination of Palbociclib and Talazoparib effectively enhances BLCA therapy, and RB is a molecular biomarker of response to this treatment regimen.
Hemagglutinin Stability and Its Impact on Influenza A Virus Infectivity, Pathogenicity, and Transmissibility in Avians, Mice, Swine, Seals, Ferrets, and Humans

Genetically diverse influenza A viruses (IAVs) circulate in wild aquatic birds. From this reservoir, IAVs sporadically cause outbreaks, epidemics, and pandemics in wild and domestic avians, wild land and sea mammals, horses, canines, felines, swine, humans, and other species. One molecular trait shown to modulate IAV host range is the stability of the hemagglutinin (HA) surface glycoprotein. The HA protein is the major antigen and during virus entry, this trimeric envelope glycoprotein binds sialic acid-containing receptors before being triggered by endosomal low pH to undergo irreversible structural changes that cause membrane fusion. The HA proteins from different IAV isolates can vary in the pH at which HA protein structural changes are triggered, the protein causes membrane fusion, or outside the cell the virion becomes inactivated. HA activation pH values generally range from pH 4.8 to 6.2. Human-adapted HA proteins tend to have relatively stable HA proteins activated at pH 5.5 or below. Here, studies are reviewed that report HA stability values and investigate the biological impact of variations in HA stability on replication, pathogenicity, and transmissibility in experimental animal models. Overall, a stabilized HA protein appears to be necessary for human pandemic potential and should be considered when assessing human pandemic risk.
Food Dishes for Sustainable Development: A Swedish Food Retail Perspective

Current dietary patterns contribute negatively to greenhouse gas emissions and to the increased prevalence of non-communicable diseases. Earlier research on sustainable food consumption mainly focuses on diets, rather than single meals. Diets are difficult to measure, which is usually executed through self-reporting. This paper aims to identify frequently prepared dishes in a home setting through sales statistics, and how they can be altered to reduce climate impact and increase nutritional value. Commonly prepared food dishes in a home setting among customers of a major food retailer in Sweden were identified through sales statistics. The dishes were altered to reach nutritional and climate impact guidelines. Commonly prepared food dishes exceeded goals for climate boundaries by more than threefold and were not in line with nutritional guidelines. The content of fat, including saturated fat, was too high. Vegetables, fruits, wholegrains and fiber need to be increased. To reduce climate impact and increase nutritional value, the amount of animal-based product need to be reduced and/or exchanged to plant-based alternatives. This research contributes empirically to understandings of how portfolio management decisions influence food consumption based on sales statistics and how nutritional and climate impact guidelines can be applied from a single meal perspective.
Electrochemical and Spectroelectrochemical Studies on the Reactivity of Perimidine–Carbazole–Thiophene Monomers towards the Formation of Multidimensional Macromolecules versus Stable π-Dimeric States

During research on cross-linked conducting polymers, double-functionalized monomers were synthesized. Two subunits potentially able to undergo oxidative coupling were used—perimidine and, respectively, carbazole, 3,6-di(hexylthiophene)carbazole or 3,6-di(decyloxythiophene)carbazole; alkyl and alkoxy chains as groups supporting molecular ordering and 14H-benzo[4,5]isoquinone[2,1-a]perimidin-14-one segment promoting CH⋯O interactions and π–π stacking. Electrochemical, spectroelectrochemical, and density functional theory (DFT) studies have shown that potential-controlled oxidation enables polarization of a specific monomer subunit, thus allowing for simultaneous coupling via perimidine and/or carbazole, but mainly leading to dimer formation. The reason for this was the considerable stability of the dicationic and tetracationic π-dimers over covalent bonding. In the case of perimidine-3,6-di(hexylthiophene)carbazole, the polymer was not obtained due to the steric hindrance of the alkyl substituents preventing the coupling of the monomer radical cations. The only linear π-conjugated polymer was obtained through di(decyloxythiophene)carbazole segment from perimidine-di(decyloxythiophene)-carbazole precursor. Due to the significant difference in potentials between subsequent oxidation states of monomer, it was impossible to polarize the entire molecule, so that both directions of coupling could be equally favored. Subsequent oxidation of this polymer to polarize the side perimidine groups did not allow further crosslinking, because rather the π–π interactions between these perimidine segments dominate in the solid product.
The Heterogeneity of Skewness in T2W-Based Radiomics Predicts the Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Our study aimed to investigate whether radiomics on MRI sequences can differentiate responder (R) and non-responder (NR) patients based on the tumour regression grade (TRG) assigned after surgical resection in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT). Eighty-five patients undergoing primary staging with MRI were retrospectively evaluated, and 40 patients were finally selected. The ROIs were manually outlined in the tumour site on T2w sequences in the oblique-axial plane. Based on the TRG, patients were grouped as having either a complete or a partial response (TRG = (0,1), n = 15). NR patients had a minimal or poor nCRT response (TRG = (2,3), n = 25). Eighty-four local first-order radiomic features (RFs) were extracted from tumour ROIs. Only single RFs were investigated. Each feature was selected using univariate analysis guided by a one-tailed Wilcoxon rank-sum. ROC curve analysis was performed, using AUC computation and the Youden index (YI) for sensitivity and specificity. The RF measuring the heterogeneity of local skewness of T2w values from tumour ROIs differentiated Rs and NRs with a p-value ≈ 10−5; AUC = 0.90 (95%CI, 0.73–0.96); and YI = 0.68, corresponding to 80% sensitivity and 88% specificity. In conclusion, higher heterogeneity in skewness maps of the baseline tumour correlated with a greater benefit from nCRT.
Ligand-free rutile and anatase TiO2 nanocrystals as electron extraction layers for high performance inverted polymer solar cells

Ligand-free rutile and anatase TiO2 nanocrystals have been synthesized through a hydrolytic sol–gel reaction. The morphology, crystal structure, elemental composition and band structure of the obtained nanocrystals are characterized by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy and UV-visible absorption spectroscopy. These two kinds of nanocrystals could serve as electron extraction layers for improving the performance in inverted polymer solar cells. Compared with the device fabricated by using amorphous TiO2 (6.11%) and rutile TiO2 (6.93%), the device based on anatase TiO2 shows a significant enhancement in power conversion efficiency (7.85%). Meanwhile, the ideal current–voltage model for a single heterojunction solar cell is applied to clarify the junction property of the cell. The model demonstrates that the device based on anatase TiO2 has effective electron extraction and hole-blocking properties.
Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells

Simple Summary Cancer extracellular vesicles (EVs) are implicated in various processes of cancer development, with most of the EV-induced changes attributed to EV proteins and microRNAs. However, the knowledge about the cancer EV-mRNAs remains limited. Here, we have assessed the mRNAs of 61 diverse oncogenes and found half of them, including VEGFA and SNAIL1/2, are abundant in cancer EVs while absent in non-tumorigenic cell-derived EVs. Fluorescent trafficking shows the EV VEGFA mRNAs are translatable after being internalized by the recipient cell. Concomitantly, the cancer EVs induced VEGFA-dependent angiogenesis and upregulated epithelial-mesenchymal transition-related genes. Our findings reveal that the EV-mRNA profile can reflect the cell malignancy, and the intercellular transfer of these mRNAs can contribute toward tumor angiogenesis. Abstract Cancer-derived extracellular vesicles (EVs) have been demonstrated to be implicated in various processes of cancer development, with most of the EV-induced changes attributed to EV-proteins and EV-microRNAs. However, the knowledge about the abundance of cancer EV-mRNAs and their contribution to cancer development remain elusive. Here, we show that mRNAs prevail in cancer EVs as compared with normal EVs, and cancer EVs that carry abundant angiogenic mRNAs activate angiogenesis in human umbilical vein endothelial cells (HUVECs). Specifically, of a gene panel comprising 61 hypoxia-targeted oncogenes, a larger proportion is harbored by cancer EVs (>40%) than normal EVs (14.8%). Fluorescent trafficking indicates cancer EVs deliver translatable mRNAs such as VEGFA to HUVECs, contributing to the activation of VEGFR-dependent angiogenesis and the upregulation of epithelial-mesenchymal transition-related and metabolism-related genes. Overall, our findings provide novel insights into EV-mRNAs and their role in angiogenesis, and has potential for diagnostic and therapeutic applications.
Increased Compulsivity in Adulthood after Early Adolescence Immune Activation: Preclinical Evidence

Immune activation during early developmental stages has been proposed as a contributing factor in the pathogenesis of neuropsychiatric conditions such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and autism in both human and animal studies. However, its relationship with the vulnerability to inhibitory control deficit, which is a shared feature among those conditions, remains unclear. The present work studied whether postnatal immune activation during early adolescence, combined with exposure to early-life adverse events, could lead to adult vulnerability to impulsive and/or compulsive behaviors. Male Wistar rats were exposed to lipopolysaccharide (LPS) in early adolescence at postnatal day 26 (PND26). During peripuberal period, half of the animals were exposed to a mild stress protocol. In adulthood, behavioral assessment was performed with the aid of the sustained attentional 5-choice serial reaction time (5-CSRT) task, schedule-induced polydipsia (SIP), and open-field locomotor activity and novelty reactivity. Rats exposed to LPS showed more compulsive responses than their control counterparts on 5-CSRT task, although no differences were observed in SIP or locomotor responses. Our study contributes to the knowledge of the relationship between immune activation and inhibitory control deficit. Future studies should aim to disentangle how, and to what extent, immune activation impacts behavior, and to understand the role of early life mild stress.
Vinpocetine alleviates lung inflammation via macrophage inflammatory protein-1β inhibition in an ovalbumin-induced allergic asthma model

Asthma is a well-known bronchial disease that causes bronchial inflammation, narrowing of the bronchial tubes, and bronchial mucus secretion, leading to bronchial blockade. In this study, we investigated the association between phosphodiesterase (PDE), specifically PDE1, and asthma using 3-isobutyl-1-methylxanthine (IBMX; a non-specific PDE inhibitor) and vinpocetine (Vinp; a PDE1 inhibitor). Balb/c mice were randomized to five treatment groups: control, ovalbumin (OVA), OVA + IBMX, OVA + Vinp, and OVA + dexamethasone (Dex). All mice were sensitized and challenged with OVA, except for the control group. IBMX, Vinp, or Dex was intraperitoneally administered 1 h before the challenge. Vinp treatment significantly inhibited the increase in airway hyper-responsiveness (P<0.001) and reduced the number of inflammatory cells, particularly eosinophils, in the lungs (P<0.01). It also ameliorated the damage to the bronchi and alveoli and decreased the OVA-specific IgE levels in serum, an indicator of allergic inflammation increased by OVA (P<0.05). Furthermore, the increase in interleukin-13, a known Th2 cytokine, was significantly decreased by Vinp (P<0.05), and Vinp regulated the release and mRNA expression of macrophage inflammatory protein-1β (MIP-1β) increased by OVA (P<0.05). Taken together, these results suggest that PDE1 is associated with allergic lung inflammation induced by OVA. Thus, PDE1 inhibitors can be a promising therapeutic target for the treatment of asthma.
Glucocorticoid Receptor: A Multifaceted Actor in Breast Cancer

Breast cancer (BC) is one of the most common cancers in women worldwide. Even though the role of estrogen receptor alpha (ERα) is extensively documented in the development of breast tumors, other members of the nuclear receptor family have emerged as important players. Synthetic glucocorticoids (GCs) such as dexamethasone (dex) are commonly used in BC for their antiemetic, anti-inflammatory, as well as energy and appetite stimulating properties, and to manage the side effects of chemotherapy. However, dex triggers different effects depending on the BC subtype. The glucocorticoid receptor (GR) is also an important marker in BC, as high GR expression is correlated with a poor and good prognosis in ERα-negative and ERα-positive BCs, respectively. Indeed, though it drives the expression of pro-tumorigenic genes in ERα-negative BCs and is involved in resistance to chemotherapy and metastasis formation, dex inhibits estrogen-mediated cell proliferation in ERα-positive BCs. Recently, a new natural ligand for GR called OCDO was identified. OCDO is a cholesterol metabolite with oncogenic properties, triggering mammary cell proliferation in vitro and in vivo. In this review, we summarize recent data on GR signaling and its involvement in tumoral breast tissue, via its different ligands.
A Review on Health-Promoting, Biological, and Functional Aspects of Bioactive Peptides in Food Applications

Food-derived bioactive peptides are being used as important functional ingredients for health-promoting foods and nutraceuticals in recent times in order to prevent and manage several diseases thanks to their biological activities. Bioactive peptides are specific protein fractions, which show broad applications in cosmetics, food additives, nutraceuticals, and pharmaceuticals as antimicrobial, antioxidant, antithrombotic, and angiotensin-I-converting enzyme (ACE)-inhibitory ingredients. These peptides can preserve consumer health by retarding chronic diseases owing to modulation or improvement of the physiological functions of human body. They can also affect functional characteristics of different foods such as dairy products, fermented beverages, and plant and marine proteins. This manuscript reviews different aspects of bioactive peptides concerning their biological (antihypertensive, antioxidative, antiobesity, and hypocholesterolemic) and functional (water holding capacity, solubility, emulsifying, and foaming) properties. Moreover, the properties of several bioactive peptides extracted from different foods as potential ingredients to formulate health promoting foods are described. Thus, multifunctional properties of bioactive peptides provide the possibility to formulate or develop novel healthy food products.
Extracellular Vesicle Release Promotes Viral Replication during Persistent HCV Infection

Hepatitis C virus (HCV) infection promotes autophagic degradation of viral replicative intermediates for sustaining replication and spread. The excessive activation of autophagy can induce cell death and terminate infection without proper regulation. A prior publication from this laboratory showed that an adaptive cellular response to HCV microbial stress inhibits autophagy through beclin 1 degradation. The mechanisms of how secretory and degradative autophagy are regulated during persistent HCV infection is unknown. This study was performed to understand the mechanisms of viral persistence in the absence of degradative autophagy, which is essential for virus survival. Using HCV infection of a CD63-green fluorescence protein (CD63-GFP), labeled stable transfected Huh-7.5 cell, we found that autophagy induction at the early stage of HCV infection increased the degradation of CD63-GFP that favored virus replication. However, the late-stage of persistent HCV infection showed impaired autophagic degradation, leading to the accumulation of CD63-GFP. We found that impaired autophagic degradation promoted the release of extracellular vesicles and exosomes. The impact of blocking the release of extracellular vesicles (EVs) on virus survival was investigated in persistently infected cells and sub-genomic replicon cells. Our study illustrates that blocking EV and exosome release severely suppresses virus replication without effecting host cell viability. Furthermore, we found that blocking EV release triggers interferon lambda 1 secretion. These findings suggest that the release of EVs is an innate immune escape mechanism that promotes persistent HCV infection. We propose that inhibition of extracellular vesicle release can be explored as a potential antiviral strategy for the treatment of HCV and other emerging RNA viruses.
A Highlight on the Inhibition of Fungal Carbonic Anhydrases as Drug Targets for the Antifungal Armamentarium

Carbon dioxide (CO2), a vital molecule of the carbon cycle, is a critical component in living organisms’ metabolism, performing functions that lead to the building of compounds fundamental for the life cycle. In all living organisms, the CO2/bicarbonate (HCO3−) balancing is governed by a superfamily of enzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the pivotal physiological reaction, consisting of the reversible hydration of the CO2 to HCO3− and protons. Opportunistic and pathogenic fungi can sense the environmental CO2 levels, which influence their virulence or environmental subsistence traits. The fungal CO2-sensing is directly stimulated by HCO3− produced in a CA-dependent manner, which directly activates adenylyl cyclase (AC) involved in the fungal spore formation. The interference with CA activity may impair fungal growth and virulence, making this approach interesting for designing antifungal drugs with a novel mechanism of action: the inhibition of CAs linked to the CO2/HCO3−/pH chemosensing and signaling. This review reports that sulfonamides and their bioisosteres as well as inorganic anions can inhibit in vitro the β- and α-CAs from the fungi, suggesting how CAs may be considered as a novel “pathogen protein” target of many opportunistic, pathogenic fungi.
Vapor Phase Fabrication of Nanoheterostructures Based on ZnO for Photoelectrochemical Water Splitting

Nanoheterostructures based on metal oxide semiconductors have emerged as promising materials for the conversion of sunlight into chemical energy. In the present study, ZnO‐based nanocomposites have been developed by a hybrid vapor phase route, consisting in the chemical vapor deposition of ZnO systems on fluorine‐doped tin oxide substrates, followed by the functionalization with Fe2O3 or WO3via radio frequency‐sputtering. The target systems are subjected to thermal treatment in air both prior and after sputtering, and their properties, including structure, chemical composition, morphology, and optical absorption, are investigated by a variety of characterization methods. The obtained results evidence the formation of highly porous ZnO nanocrystal arrays, conformally covered by an ultrathin Fe2O3 or WO3 overlayer. Photocurrent density measurements for solar‐triggered water splitting reveal in both cases a performance improvement with respect to bare zinc oxide, that is mainly traced back to an enhanced separation of photogenerated charge carriers thanks to the intimate contact between the two oxides. This achievement can be regarded as a valuable result in view of future optimization of similar nanoheterostructured photoanodes.