Miracle-dz/UniFAR-FTUs huggingface dataset:
Co-Regulated Genes and Gene Clusters

There are many co-regulated genes in eukaryotic cells. The coordinated activation or repression of such genes occurs at specific stages of differentiation, or under the influence of external stimuli. As a rule, co-regulated genes are dispersed in the genome. However, there are also gene clusters, which contain paralogous genes that encode proteins with similar functions. In this aspect, they differ significantly from bacterial operons containing functionally linked genes that are not paralogs. In this review, we discuss the reasons for the existence of gene clusters in vertebrate cells and propose that clustering is necessary to ensure the possibility of selective activation of one of several similar genes.
Zinc and the Innovative Zinc-α2-Glycoprotein Adipokine Play an Important Role in Lipid Metabolism: A Critical Review

Numerous studies indicate that zinc and the new zinc-related adipokine, zinc-α2-glycoprotein (ZAG), are involved in lipid metabolism. Excess body fat lowers blood concentrations of Zn and ZAG, leading not only to the development of obesity but also to other components of the metabolic syndrome. Zinc homeostasis disorders in the body negatively affect the lipid profile and cytokine secretion. Zinc appears to be a very important ZAG homeostasis regulator. The physiological effects of ZAG are related to lipid metabolism, but studies show that ZAG also affects glucose metabolism and is linked to insulin resistance. ZAG has a zinc binding site in its structure, which may indicate that ZAG mediates the effect of zinc on lipid metabolism. The review aimed to verify the available studies on the effects of zinc and ZAG on lipid metabolism. A literature review within the scope of this research area was conducted using articles available in PubMed (including MEDLINE), Web of Science and Cochrane Library databases. An analysis of available studies has shown that zinc improves hepatic lipid metabolism and has an impact on the lipid profile. Numerous studies have found that zinc supplementation in overweight individuals significantly reduced blood levels of total cholesterol, LDL (Low-density lipoprotein)cholesterol and triglycerides, potentially reducing cardiovascular morbidity and mortality. Some results also indicate that it increases HDL-C (High-density lipoprotein) cholesterol levels. ZAG has been shown to play a significant role in reducing obesity and improving insulin sensitivity, both in experimental animal model studies and in human studies. Furthermore, ZAG at physiologically relevant concentrations increases the release of adiponectin from human adipocytes. In addition, ZAG has been shown to inhibit in vitro leptin production. Further studies are needed to provide more data on the role of zinc and zinc-α2-glycoprotein.
Altitudinal Visual Field Defects Following Diagnostic Transfemoral Cerebral Angiography

Transfemoral cerebral angiography (TFCA) has been increasingly used as diagnostic method for the evaluation of cerebral vessels. Ophthalmologic complication after TFCA has rarely been reported, and most complications are associated with an intraoperative thrombo-embolic event. We reported a patient who developed a superior altitudinal visual field defect one day after diagnostic TFCA. The ophthalmic exam revealed a prominent inferior optic disc edema, and the fluorescein angiographic showed the non-perfusion of the corresponding inferior sectoral optic disc. Diffusion-weighted MRI on the day following cerebral angiography revealed multiple focal scattered acute infarctions. Even one month after steroid pulse therapy, the superior nasal field defect remained with minimal improvement. We believe this case was consistent with an acute anterior ischemic optic neuropathy (AION) due to thrombo-embolism after TFCA. Ophthalmic examinations and a visual field test should be performed before and immediately after the TFCA, particularly in the case with a high risk of thromboembolic events.
Histological Heterogeneity of Primary Liver Cancers: Clinical Relevance, Diagnostic Pitfalls and the Pathologist’s Role

Simple Summary Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined (c)HCC-CCA. Both small duct types iCCA (a subtype pf iCCA) and cHCC-CCA are known to be tumors with histological heterogeneity. Understanding key tumor heterogeneity is crucial as it reflects tumor aggressiveness, patient outcome, treatment choice, and is predictive of treatment efficacy. In addition, PLCs often present with multiple liver tumors, which can be a combination of different types of PLCs or HCCs (intrahepatic metastasis or multicentric occurrence), and the pathological interpretation plays an important role in these cases. The aim of this review is to clarify the pathological features of HCC, iCCA, and cHCC-CCA, including their diagnostic pitfalls, molecular profiles, and the correlation between tumor subtypes and treatment choice. Abstract Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and cHCC-CCA. Combined HCC-CCA and small duct type iCCA show similar clinical presentations, and their histological features are more complex than seen in HCC. Therefore, while their treatment strategy differs, it is difficult to properly diagnose these tumors. Currently, HCC is the only tumor that can be treated by liver transplantation. In addition, small duct type iCCA harbors IDH1/2 mutations and FGFR2 fusions, which can be used for targeted therapy. Thus, improving diagnostic accuracy is crucial. A further point to note is that PLCs often present as multiple liver tumors, and they can be a combination of different types of PLCs or HCCs. In the case of HCCs, two different scenarios are possible, namely intrahepatic metastasis, or multicentric occurrence. Therefore, it is essential to characterize the type of multiple liver tumors. This review aims to clarify the pathological features of HCC, iCCA and cHCC-CCA, including their diagnostic pitfalls and clinical relevance. It is designed to be of use to clinicians who are dealing with PLCs, to provide a better understanding of the pathology of these tumors, and to enable a more accurate diagnosis and optimal treatment choice.
Enhancement of Luminescence Efficiency of Y2O3 Nanophosphor via Core/Shell Structure

We successfully fabricated Y2O3:RE3+ (RE = Eu, Tb, and Dy) core and core–shell nanophosphors by the molten salt method and sol–gel processes with Y2O3 core size of the order of 100~150 nm. The structural and morphological studies of the RE3+-doped Y2O3 nanophosphors are analyzed by using XRD, SEM and TEM techniques, respectively. The concentration and annealing temperature dependent structural and luminescence characteristics were studied for Y2O3:RE3+ core and core–shell nanophosphors. It is observed that the XRD peaks became narrower as annealing temperature increased in the core–shell nanophosphor. This indicates that annealing at higher temperature improves the crystallinity which in turn enhances the average crystallite size. The emission intensity and quantum yield of the Eu3+-doped Y2O3 core and core–shell nanoparticles increased significantly when annealing temperature is varied from 450 to 550 °C. No considerable variation was noticed in the case of Y2O3:Tb3+ and Y2O3:Dy3+ core and core–shell nanophosphors.
Vanadium‐Ion Redox Reactions in a Three‐Dimensional Network of Reduced Graphite Oxide

A three-dimensional (3D) fine network structure of thin carbon microflakes inside a loosely entangled carbon-fiber matrix was formed by applying an ice-template method to a graphite oxide (GO) dispersion in the matrix and thermal reduction of the GO. Vanadium-ion redox reactions were investigated in the network of reduced GO (RGO) for potential application as electrodes in vanadium redox flow batteries (VRFB). The development of the fineness, the degree of graphitization, the structural disorder, and the surface composition were characterized. The interaction between the carbon surface species and the vanadium ions was implied by the X-ray absorption fine structure (XAFS). The structure of the 3D RGO network was clearly correlated to the activity for the VRFB positive electrode reactions, and the development of the fine network structure effectively enhanced the reactions due to increased exposure of the edge planes and sufficient dispersion of the active sites.
Loss of WTAP Impairs Early Parthenogenetic Embryo Development

Simple Summary Wilms’ tumor 1-associating protein (WTAP) is a key subunit of the N6-methyl-adenosine (m6A) methyltransferase complex during porcine early embryo development. However, the role of WTAP in embryonic development is still unclear. In this study, we demonstrate that WTAP plays an indispensable role in embryonic development, and the loss of WTAP will promote the apoptosis of embryonic cells, and reduce the rate and quality of embryonic development. Abstract m6A is one of the most common and abundant modifications of RNA molecules present in eukaryotes. The methyltransferase complex, consisting of methyltransferase-like 3 (METTL3), METTL14, and WTAP, is responsible for the m6A modification of RNA. WTAP was identified as an mRNA splicing regulator. Its role as a regulatory subunit of the m6A methyltransferase complex in embryonic development remains largely unknown. To investigate the role of WTAP in porcine early embryonic development, si-WTAP was microinjected into porcine parthenogenetic zygotes. WTAP knockdown significantly reduced the blastocyst rate and global m6A levels, but did not affect the cleavage rate. Betaine was supplemented into the in vitro culture (IVC) to increase the m6A levels. Betaine significantly increased the global m6A levels but did not affect the blastocyst rate. Furthermore, the pluripotency genes, including OCT4, SOX2, and NANOG, were downregulated following WTAP knockdown. The apoptotic genes BAX and CASPASE 3 were upregulated, while the anti-apoptotic gene BCL2 was downregulated in WTAP knockdown blastocysts. TUNEL staining revealed that the number of apoptotic cells was significantly increased following WTAP knockdown. Our study indicated that WTAP has an indispensable role in porcine early embryonic development.
Analytical Assessment and Nutritional Adequacy of School Lunches in Sintra’s Public Primary Schools

School meals present several cost benefits overtime at the short, medium, and long term for individuals and society. This cross-sectional study aims to analyse the nutritional composition and evaluate the adequacy of school lunches. One hundred and fifty-eight samples were collected and analysed from 10 primary schools in Sintra’s municipality, served during one week. On average, energy (27.7% daily energetic requirements) and carbohydrate (48.1%) contents did not reach the reference values, and the content of protein (19.5%) exceeded the reference value (p < 0.05). The mean total fat (28.8%) and saturated fatty acids (5.4%) content complied with the recommendations. The mean salt (1.7 g) and dietary fibre (8.3 g) content exceeded the reference value but did not differ significantly from the recommendations. Addressing school canteens is crucial, not only in a nutritional approach, but also as an opportunity to achieve healthier, sustainable, and accessible food systems, aligned with the Sustainable Development Goals 2030. We highlighted the importance of evaluating evidence-based practices and disseminated practice-based evidence regarding the adequacy of school lunches.
Current Status of Rabies and Its Eradication in Eastern and Southeastern Europe

The objective of this paper is to provide an overview of the current status of rabies in Europe, with special emphasis on Croatia and Southeast and East Europe. Due to the systematic implementation of a rabies eradication program by oral vaccination of wild animals, by the end of the 20th century, most West and Central European countries were rabies-free. The EU goal was to eradicate rabies in wildlife and domestic animals by 2020. No matter how achievable the goal seemed to be, the disease is still present in the eastern part of the EU, as was notified in 2020 by two member states—Poland and Romania. Croatia has been rabies-free for the last seven years but given that it borders a non-EU country in which a case of rabies was confirmed in 2020, it will continue to contribute to the maintenance of the rabies-free region. A rabies-free EU can only be achieved by continuous oral vaccination, coordination and a regional approach. The prevention of reintroductions from bordering countries in which rabies has not been eradicated yet, and the support for the eradication efforts made by these countries, are goals still pending.
Genome-Wide Association Analysis for Stem Cross Section Properties, Height and Heading Date in a Collection of Spanish Durum Wheat Landraces

Durum wheat landraces have a high potential for breeding but they remain underexploited due to several factors, including the insufficient evaluation of these plant materials and the lack of efficient selection tools for transferring target traits into elite backgrounds. In this work, we characterized 150 accessions of the Spanish durum wheat collection for stem cross section, height and heading date. Continuous variation and high heritabilities were recorded for the stem area, pith area, pith diameter, culm wall thickness, height and heading date. The accessions were genotyped with DArTSeq markers, which were aligned to the durum wheat ‘Svevo’ genome. The markers corresponding to genes, with a minor allele frequency above 5% and less than 10% of missing data, were used for genome-wide association scan analysis. Twenty-nine marker-trait associations (MTAs) were identified and compared with the positions of previously known QTLs. MTAs for height and heading date co-localized with the QTLs for these traits. In addition, all the MTAs for stem traits in chromosome 2B were located in the corresponding synteny regions of the markers associated with lodging in bread wheat. Finally, several MTAs for stem traits co-located with the QTL for wheat stem sawfly (WSS) resistance. The results presented herein reveal the same genomic regions in chromosome 2B are involved in the genetic control of stem traits and lodging tolerance in both durum and bread wheat. In addition, these results suggest the importance of stem traits for WSS resistance and the potential of these landraces as donors for lodging tolerance and WSS resistance enhancement. In this context, the MTAs for stem-related traits identified in this work can serve as a reference for further development of markers for the introgression of target traits into elite material.
Protective Effect of Lusianthridin on Hemin-Induced Low-Density Lipoprotein Oxidation

Oxidation of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin that can be found in thalassemia patients. Hemin is a strong oxidant that can cause LDL oxidation and contributes to atherosclerosis in thalassemia patients. Lusianthridin from Dendrobium venustrum is a phenolic compound that possesses antioxidant activity. Hence, lusianthridin could be a promising compound to be used against hemin-induced oxidative stress. The major goal of this study is to evaluate the protective effect of lusianthridin on hemin-induced low-density lipoprotein oxidation (he-oxLDL). Here, various concentrations of lusianthridin (0.25, 0.5, 1, and 2 µM) were preincubated with LDL for 30 min, then 5 µM of hemin was added to initiate the oxidation, and oxidative parameters were measured at various times of incubation (0, 1, 3, 6, 12, 24 h). Lipid peroxidation of LDL was measured by thiobarbituric reactive substance (TBARs) assay and relative electrophoretic mobility (REM). The lipid composition of LDL was analyzed by using reverse-phase HPLC. Foam cell formation with he-oxLDL in RAW 264.7 macrophage cells was detected by Oil Red O staining. The results indicated that lusianthridin could inhibit TBARs formation, decrease REM, decrease oxidized lipid products, as well as preserve the level of cholesteryl arachidonate and cholesteryl linoleate. Moreover, He-oxLDL incubated with lusianthridin for 24 h can reduce the foam cell formation in RAW 264.7 macrophage cells. Taken together, lusianthridin could be a potential agent to be used to prevent atherosclerosis in thalassemia patients.
Physiological and Behavioral Mechanisms of Thermoregulation in Mammals

Simple Summary The study of the hypothalamic neuromodulation of thermoregulation offers broad areas of opportunity with practical applications that are currently being strengthened by the availability of efficacious tools like infrared thermography (IRT). This review analyzes the effect of climate change on behavior and productivity; and the effects of exercise on animals involved in sporting activities; identifies the microvascular changes that occur in response to fear, pleasure, pain, and other situations that induce stress in animals; and examines thermoregulating behaviors. Abstract This review analyzes the main anatomical structures and neural pathways that allow the generation of autonomous and behavioral mechanisms that regulate body heat in mammals. The study of the hypothalamic neuromodulation of thermoregulation offers broad areas of opportunity with practical applications that are currently being strengthened by the availability of efficacious tools like infrared thermography (IRT). These areas could include the following: understanding the effect of climate change on behavior and productivity; analyzing the effects of exercise on animals involved in sporting activities; identifying the microvascular changes that occur in response to fear, pleasure, pain, and other situations that induce stress in animals; and examining thermoregulating behaviors. This research could contribute substantially to understanding the drastic modification of environments that have severe consequences for animals, such as loss of appetite, low productivity, neonatal hypothermia, and thermal shock, among others. Current knowledge of these physiological processes and complex anatomical structures, like the nervous systems and their close relation to mechanisms of thermoregulation, is still limited. The results of studies in fields like evolutionary neuroscience of thermoregulation show that we cannot yet objectively explain even processes that on the surface seem simple, including behavioral changes and the pathways and connections that trigger mechanisms like vasodilatation and panting. In addition, there is a need to clarify the connection between emotions and thermoregulation that increases the chances of survival of some organisms. An increasingly precise understanding of thermoregulation will allow us to design and apply practical methods in fields like animal science and clinical medicine without compromising levels of animal welfare. The results obtained should not only increase the chances of survival but also improve quality of life and animal production.
Asthmatic Eosinophils Promote Contractility and Migration of Airway Smooth Muscle Cells and Pulmonary Fibroblasts In Vitro

Enhanced contractility and migration of airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF) are part of airway remodeling in asthma. Eosinophils are the central inflammatory cells that participate in airway inflammation. However, the role of asthmatic eosinophils in ASMC and PF contractility, migration, and differentiation to contractile phenotype has not yet been precisely described. A total of 38 individuals were included in this study: 13 steroid-free non-severe allergic asthma (AA) patients, 11 severe non-allergic eosinophilic asthma (SNEA) patients, and 14 healthy subjects (HS). For AA patients and HS groups, a bronchial allergen challenge with D. pteronyssinus was performed. Individual combined cell cultures were prepared from isolated peripheral blood eosinophils and immortalized ASMC or commercial PF cell lines separately. The migration of ASMC and PF was evaluated using wound healing assay and contractility using collagen gel assay. Gene expression of contractile apparatus proteins, COL1A1, COL5A1, and FN, in ASMC and PF was evaluated using qRT-PCR. We found that contractility and migration of ASMC and PF significantly increased after incubation with asthmatic eosinophils compared to HS eosinophils, p < 0.05, and SNEA eosinophils demonstrated the highest effect on contractility of ASMC and migration of both cell lines, p < 0.05. AA and SNEA eosinophils significantly increased gene expression of contractile apparatus proteins, COL1A1 and FN, in both cell lines, p < 0.05. Furthermore, the allergen-activated AA eosinophils significantly increased the contractility of ASMC, and migration and gene expression in ASMC and PF, p < 0.05. Thus, asthmatic eosinophils change ASMC and PF behavior by increasing their contractility and migration, contributing to airway remodeling.
Histoplasmosis Diagnosed in Europe and Israel: A Case Report and Systematic Review of the Literature from 2005 to 2020

Human histoplasmosis is a mycosis caused by two distinct varieties of a dimorphic fungus: Histoplasma capsulatum var. capsulatum and H. capsulatum var. duboisii. In Europe, it is usually imported by migrants and travellers, although there have been some autochthonous cases, especially in Italy; however, most European physicians are unfamiliar with its clinical and pathological picture, particularly among immunocompromised patients without HIV infection. This systematic review of all the cases of histoplasmosis reported in Europe and Israel between 2005 and 2020 identified 728 cases diagnosed in 17 European countries and Israel described in 133 articles. The vast majority were imported (mainly from Central and South America), but there were also seven autochthonous cases (six in Europe and one in Israel). The patients were prevalently males (60.4%), and their ages ranged from 2 to 86 years. The time between leaving an endemic region and the diagnosis of histoplasmosis varied from a few weeks to more than 40 years. Progressive disseminated histoplasmosis was the most frequent clinical picture among people living with HIV infection (89.5%) or a different immunocompromising condition (57.1%), but it was also recorded in 6.2% of immunocompetent patients. Twenty-eight cases were caused by Histoplasma duboisii. Immunocompromised patients without HIV infection had the worst outcomes, with a mortality rate of 32%.
New Perspectives in the Antimicrobial Activity of the Amphibian Temporin B: Peptide Analogs Are Effective Inhibitors of Candida albicans Growth

Temporin B (TB) is a short, positively charged peptide secreted by the granular glands of the European frog Rana temporaria. While the antibacterial and antiviral efficacy of TB and some of its improved analogs are well documented, nothing is known about their antifungal potency so far. We dedicated this study to characterize the antifungal potential of the TB analog TB_KKG6K and the newly designed D-Lys_TB_KKG6K, the latter having the L-lysines replaced by the chiral counterpart D-lysines to improve its proteolytic stability. Both peptides inhibited the growth of opportunistic human pathogenic yeasts and killed planktonic and sessile cells of the most prevalent human pathogen, Candida albicans. The anti-yeast efficacy of the peptides coincided with the induction of intracellular reactive oxygen species. Their thermal, cation, pH and serum tolerance were similar, while the proteolytic stability of D-Lys_TB_KKG6K was superior to that of its template peptide. Importantly, both peptides lacked hemolytic activity and showed minimal in vitro cytotoxicity in primary human keratinocytes. The tolerance of both peptides in a reconstructed human epidermis model further supports their potential for topical application. Our results open up an exciting field of research for new anti-Candida therapeutic options based on amphibian TB analogs.