The presence of the mite, Varroa destructor, requires the use of acaricide treatments in most honeybee colonies. Amitraz is one of the most common acaricide substances used by beekeepers. Some Varroa mite populations have developed resistance to amitraz leading to a loss of efficacy of amitraz-based treatments. Two products, Apivar and Supatraz were applied in the same apiary. Both treatments are amitraz-based but have a different galenics. Thanks to field data, a dynamic model was used to simulate the action of Apivar and Supatraz on the mite population. We consider two parameters to compare the products: daily mortality rate and treatment duration. In the field, the percentage of efficacy between the two products was not significantly different but Supatraz kills mite faster and decreases 90% of the mite infestation in 28.4 days compared to 50.9 days for Apivar. Thanks to modelling, we showed the daily impact of the two different products on mite population. Supatraz has a higher daily mortality rate during the first two weeks than Apivar. Supatraz requires a lower efficacy to stabilize the varroa mite population due to its faster release of active ingredient than Apivar, needing a shorter period to achieve the same result. Depending on the model, Supatraz conserve a good efficacy for low resistant mites but not for high resistant mites. These results show that the comparison of the efficacy of two products with different characteristics (duration of treatment and daily mortality rate) should be analyzed with caution.

We present an overview over eight brightly luminescent Cu(I) dimers of the type Cu2X2(PN)3 with X = Cl, Br, I and P^N = 2-diphenylphosphino-pyridine (Ph2Ppy), 2-diphenylphosphino-pyrimidine (Ph2Ppym), 1-diphenylphosphino-isoquinoline (Ph2Piqn) including three new crystal structures (Cu2Br2(Ph2Ppy)3, 1-Br, Cu2I2(Ph2Ppym)3, 2-I, and Cu2I2(Ph2Piqn)3, 3-I). However, we mainly focus on their photo-luminescence properties. All compounds exhibit combined thermally activated delayed fluorescence (TADF) and phosphorescence at ambient temperature. Emission color, decay time, and quantum yield varies over large ranges. For deeper characterization, we select Cu2I2(Ph2Ppy)3, 1-I, showing a quantum yield of 81 %. DFT and SOC-TDDFT calculations provide insight into the electronic structures of the singlet S1 and triplet T1 states. Both stem from metal+iodide-to-ligand charge transfer transitions. Evaluation of the emission decay dynamics, measured from 1.2 ≤ T ≤ 300 K, gives ∆E(S1-T1) = 380 cm-1 (47 meV), a transition rate of k(S1→S0) = 2.25×106 s-1 (445 ns), T1 zero-field splittings, transition rates from the triplet substates, and spin-lattice relaxation times. We also discuss the interplay of S1-TADF and T1-phosphorescence. The combined emission paths shorten the overall decay time. For OLED applications, utilization of both singlet and triplet harvesting can be highly favorable for improvement of the device performance.

Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Certain aspects of the 5-HT signaling framework hint at its potential role as a modulator of activity-dependent synaptic changes within the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). Therefore, 5-HT could play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic modulation of the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction of the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking LTD at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.

Lung cancer remains the leading cause of cancer-related death worldwide. The involvement of lymph nodes by the tumor has a strong impact on survival of patients. For this reason, lymphadenectomy plays a crucial role in the staging and prognosis of NSCLC, to define the most appropriate therapeutic strategies concerning the stage of the disease. To date, the benefit, in terms of survival, of the different extents of lymphadenectomy remains controversial in the scientific community. It is recognized that metastatic involvement of mediastinal lymph nodes in lung cancer is one of the most significant prognostic factors, in terms of survival, and it is therefore mandatory to identify patients with lymph node metastases who may benefit from adjuvant therapies, to prevent distant disease and local recurrences. The purpose of this review is to evaluate, the role of lymphadenectomy in early-stage NSCLC in terms of efficacy and accuracy, comparing systematic, sampling and lobe-specific lymph node dissection and analyzing the existing critical issue, through a search of the most relevant articles published in the last decades.

Glyphosate　(GLYP)　is a broad-spectrum, non-selective, organic phosphine post emergence herbicide registered for use on many food and non-food field. Herein, we developed a biosensor (Mbs@dsDNA) based on carboxylated modified magnetic beads incubated with NH2-polyA and then hybridized with polyT-glyphosate aptamer and complementary DNA. Afterward, a quantitative detection method based on qPCR was established.　When the glyphosate aptamer on Mbs@dsDNA specifically recognized glyphosate, a complementary DNA is released and then enters the qPCR signal amplification process. The linear range of the method was 0.1-5 μg/mL, and the detection limit was set at 0.1 μg/mL. The recoveries in tap water were ranged from 103.4 ~ 104.9%, and the relative standard deviations (RSDs) were < 1%. The aptamer proposed in this study has a good potential for recognizing glyphosate. The detection method combined with qPCR might have a good application prospect in detecting and supervising other pesticide residues.

Predators are dependent on the capture of prey to meet their energetic and nutritive requirements, imposing a regime of predation risk. Consequently, prey experience both consumptive and non-consumptive effects. Non-consumptive effects may manifest through altered growth and ontogenetic trajectories of prey species, a dynamic modulated by olfactory or other sensory cues from predators. Bactrocera dorsalis Hendel represents a great invasive threat to global horticulture. While earlier research has primarily centered on the consumptive interactions between B. dorsalis and its natural enemies, the potential consequences of non-consumptive interactions on the development of B. dorsalis have been overlooked. In this study, we investigated the impact of predation risk effects, induced by both visual exposure to the predatory mantis Hierodula patellifera Serville and its associated odor, on the life history traits of B. dorsalis. Female B. dorsalis demonstrated reduced development time in the presence of isolated H. patellifera or H. patellifera odor, yet evidenced significantly increased fecundity. Conversely, males displayed no significant change in development time. Additionally, neither female nor male body weight at death was significantly influenced by predation risk from isolated predators or predator odor. These results indicated adaptive developmental strategies of B. dorsalis when faced with risks from predators and highlight the important role of predator odor, which has the potential to lay the groundwork for improving biological control efforts and innovative approaches within pest control.

From grape cultivation to ripening and harvest timing to processing, each step can be a critical point when it comes to wine quality and phenolic composition. In this study, the influence of winemaking technology on resveratrol and quercetin content, as well as other polyphenolic compounds, was investigated. Resveratrol is a non-flavonoid polyphenolic stilbene synthesized by grape skin when damaged by infectious diseases or ionizing radiation. Quercetin is a phenol found in grape skins and stems and is produced to protect grapes from UV light damage. Trans-resveratrol and quercetin are known to act as antioxidants, reduce the risk of atherosclerosis and type 2 diabetes, inhibit the growth of cancer cells, and prevent the release of allergic and inflammatory molecules. However, the question was whether red wine could be enriched with these phenols using an innovative winemaking technology. The innovative idea was to completely replace the cold maceration process with maceration with the addition of wild yeast (Torulaspora delbrueckii, Td). Maceration with the addition of wild yeast (Td) offers the following advantages over traditional cold maceration: (1) higher concentrations of trans-resveratrol (>35-40%) and quercetin (>35-40%) in the final wine, (2) the new wine has a higher potential for human health, (3) the wine has a better aroma and stability due to the higher mannoprotein content, and (4) the better energy efficiency in the production process. The study of stability during storage and aging also included derivatives of benzoic acid and hydroxycinnamic acid, piceid, catechin, naringenin, rutin, kaempherol, hesperetin, and anthocyanins. The study found that younger wines had higher phenolic content, while storage of the wine resulted in a decrease in total phenolic content, especially monomeric stilbenes and quercetin.

In proteomics, it is essential to quantify proteins in absolute terms if we wish compare results among studies and integrate high-throughput biological data into genome-scale metabolic models. While labeling target peptides with stable isotopes allows protein abundance to be accurately quantified, the utility of this technique is constrained by the low number of quantifiable proteins that it yields. Recently, label-free shotgun proteomics has become the “gold standard” for carrying out global assessments of biological samples containing thousands of proteins. However, this tool must be further improved if we wish to accurately quantify absolute levels of proteins. Here, we used different label-free quantification techniques to estimate absolute protein abundance in the model yeast Saccharomyces cerevisiae. More specifically, we evaluated the performance of seven different quantification methods, based either on spectral counting (SC) or extracted-ion chromatogram (XIC), which were applied to samples from five different proteome backgrounds. We also compared the accuracy and reproducibility of two strategies for transforming relative abundance into absolute abundance: a UPS2-based strategy and the total protein approach (TPA). This study mentions technical challenges related to UPS2 use and proposes ways of addressing them, including utilizing a smaller, more highly optimized amount of UPS2. Overall, three SC-based methods (PAI, SAF, and NSAF) yielded the best results because they struck a good balance between experimental performance and protein quantification.

A bottom-up route towards predicting evolution relies on deep understanding of the complex network proteins form inside cells. In a rapidly expanding panorama of experimental possibilities, the most difficult question is how to conceptually approach the disentangling of such complex networks. These can exhibit varying degrees of hierarchy and modularity, which obfuscate certain protein functions that may prove pivotal for adaptation. Using the well-established polarity network in budding yeast as a case study, we first organize current literature to highlight protein entrenchments inside polarity. Following three examples, we see how alternating between experimental novelties and subsequent emerging design strategies can construct a layered understanding, potent enough to reveal evolutionary targets. We show that if you want to understand a cell’s evolutionary capacity, such as possible future evolutionary paths, seemingly unimportant proteins need to be mapped and studied. Finally, we generalize this research structure to be applicable to other systems of interest.

The [PSI⁺] nonsense-suppressor determinant of Saccharomyces cerevisiae is related to formation of heritable amyloids of the Sup35 (eRF3) translation termination factor. [PSI⁺] amyloids have variants in amyloid structure and in the strength of suppressor phenotype. Appearance of [PSI⁺], its propagation and manifestation depend primarily on chaperones. Besides chaperones, the Upf1/2/3, Siw14 and Arg82 proteins restrict [PSI⁺] formation, while Sla2 can prevent the [PSI⁺] toxicity. Here, we identify two more non-chaperone proteins involved in [PSI⁺] detoxification. We show that simultaneous lack of the Pub1 and Upf1 proteins causes lethality of [PSI⁺] cells with a strong, but not with weak suppressor phenotype. This lethality results from excessive depletion of the Sup45 (eRF1) termination factor due to its sequestration into Sup35 polymers. We also show that Pub1 acts to restrict excessive Sup35 prion polymerization, while Upf1 interferes with Sup45 binding to Sup35 polymers. These data allow considering the Pub1 and Upf1 proteins as a novel [PSI⁺] detoxification system.

ntroduction: Respiratory tract Infections are the greatest cause of death worldwide. Since its outbreak in 2019, the coronavirus pandemic (COVID-19) has been a challenge to humans in terms of treatment and prevention of this respiratory viral infection. The re-emergence of respiratory viral infections like influenza, pose a serious hazard to global public health because they occur seasonally. Creating broad-spectrum antiviral compounds for rapid action in the case of an outbreak crisis, as well as bioweapon defences, is critical. Human galectin-3 is found in high concentrations in activated T lymphocytes, epithelial and endothelial cells, and fibroblasts. ProLectin -I and ProLectin -M are both galectin antagonists. Blocking viral entry with a complex polysaccharide component "ProLectin-M" has downstream effects on viral reproduction enabling it to be used as a therapeutic tool and a safe alternative to conventional anti-viral medicines. Methods: In total, 3 cell based assays have been conducted to evaluate antiviral efficacy of ProLectin–I and ProLectin-M against SARS-CoV-2 virus, Influenza-A (H1N1), and human respiratory syncytial virus (hRSV) strain A2. ProLectin-M and ProLectin-I were evaluated for their anti-viral potency using SARS-CoV2 virus strain by viral RNA Extraction and qRT-PCR assays. The plaque assays were carried out to determine the antiviral activity of the test products (ProLectin-I and ProLectin-M) against ‘Influenza-A (H1N1)-A/PR/8/34 (TC adapted)’ and ‘Human respiratory syncytial virus (hRSV) strain A2’ in a cell based in vitro setting. As eference standard, "Oseltamivir Phosphate" and "Remdesivir" were used to determine antiviral activity of test products against H1N1 and hRSV strains respectively.Results: The IC_{50 of} ProLectin-M and ProLectin-I against SARS-CoV-2 virus was found to be 6248 ng/ml (6.2µg/ml) and 4207 ng/ml (4.2μg/ml) respectively. The CC₅₀ value was similar in both the test products i.e. >100 µg/ml. Against Influenza A (H1N1) strain, ProLectin-M exhibited 95 % reduction in the viral load at the test concentration of 21.8 µg/mL with an IC₅₀ value of 5.4 µg/mL whereas, ProLectin-I did not show any cytotoxicity till 250 µg/mL concentration. Against 'human respiratory syncytial virus (hRSV) strain A2, ProLectin-M exhibited 65 % reduction in the viral load at the test concentration of 43.75 µg/mL with an IC₅₀ value of 27.41 µg/mL whereas, ProLectin- I did not show any cytotoxicity till 250 µg/mL concentration. Conclusion: Both ProLectin-I and ProLectin-M have been reported to exhibit broad-spectrum antiviral activity in ‘in-vitro’ setting. ProLectin-M reducing influenza-A virus by 95% and hRSC strain A2 by 65%. To better understand broad spectrum antiviral activity of ProLectin-I and ProLectin-M, further pre-clinical research is warranted.

Fourteen (14) rack-mounted polycrystalline modules installed on the concrete roof of the solar energy applications laboratory at the Kwame Nkrumah University of Science and Technology (KNUST) in Ghana, a hot humid environment were assessed after 19 years of continuous outdoor expodure. The physical state of the modules was documented using a visual inspection checklist. They were further assessed by current-voltage (I-V) characterization and thermal imaging. The modules were found to be in good physical state, except some bubbles on front side and minor discolouration/corrosion at edge of the cells. Compared with reference values, the performance decline of the modules observed over the exposure period was: nominal power (P_nom), 21% to 35%; short circuit current (I_sc), 5.8% to 11.7%; open circuit voltage (V_oc) 3.6% to 5.6% and 11.9% to 25.7% for fill factor (FF). It is hoped that this study will provide some helpful information to project developers, manufacturers and the research community on the long-term performance of PV modules in Ghana.

A twelve-week feeding trial was conducted to investigate the effect of dietary supplementation of a functional immunostimulant mixture (FIM; nucleotides, β-glucan and vitamins C and E) on growth, feed utilization, innate immunity, digestive enzyme activity, hematological parameters, intestinal morphology and inflammatory gene expression of olive flounder, Paralichthys olivaceus. A fish meal-based basal diet (control) was formulated and three other diets were prepared by incorporating 0.5, 1.0 and 1.5% FIM into the basal diet (HB0.5, HB1.0 and HB1.5, respectively). Five replicate groups of fish (26.3 ± 0.1 g) were fed one of the experimental diets. Inclusion of 1.5% FIM in the diet significantly enhanced growth and feed utilization. Significantly higher plasma hemoglobin, hematocrit, total protein levels and lower plasma glucose level were observed in HB1.5 group. Total immunoglobulin content, lysozyme, nitroblue tetrazolium, myeloperoxidase, superoxide dismutase, glutathione peroxidase and catalase activities and immune-related gene expressions of toll-like receptor and perforin were significantly increased at highest inclusion level. FIM supplementation significantly increased villus height and goblet cell counts. Anti-inflammatory gene expression was significantly upregulated at a 1.5% level. Dietary supplementation of 1.5% of FIM could improve growth and feed utilization, immune, hematological and histomorphological parameters of olive flounder.

Bioethanol has many environmental and practical benefits as a transportation fuel. It is one of the best alternatives to replace fossil fuels due to its liquid nature which is similar to petrol and diesel fuels traditionally used in transportation. In addition, bioethanol production technology has the capacity for negative carbon emissions which is vital for solving the current global warming dilemma. However, conventional bioethanol production takes place based on an inland site and relies on freshwater and edible crops (or land suitable for edible crop production) for production, which has led to the food vs fuel debate. Establishing a coastal marine biorefinery (CMB) system for bioethanol production that is based on coastal sites and relies on marine resources (seawater, marine biomass and marine yeast) could be the ultimate solution. In this paper, we aim to evaluate the environmental impact of using seawater for bioethanol production at coastal locations as a step towards the evaluation of a CMB system. Hence, a life cycle assessment for bioethanol production was conducted using the proposed scenario named Coastal-Seawater and compared to the conventional scenario, named Inland-Freshwater (IF). The impact of each scenario in relation to climate change, water depletion, land use and fossil depletion was studied for comparison. The coastal-seawater scenario demonstrated an improvement upon the conventional scenario in all the selected impact categories. In particular, the use of seawater in the process had a significant effect on water depletion showing an impact reduction of 31.2%. Furthermore, reductions are demonstrated in natural land transformation, climate change and fossil depletion of 5.5%, 3.5% and 4.2% respectively. This indicates the positive impact of using seawater and coastal locations for bioethanol production and encourages research to investigate the CMB system.

The use of interspecific hybrids during the industrial fermentation process has been well established, positioning the frontier of advancement in brewing to capitalize on the potential of Saccharomyces hybridization. Interspecific yeast hybrids used in modern monoculture inoculations benefit from a wide range of volatile metabolites that broaden the organoleptic complexity. This is the first report of sake brewing by Saccharomyces arboricola and its hybrids. S. arboricola x S. cerevisiae direct-mating generated cryotolerant interspecific hybrids which increased yields of ethanol and ethyl hexanoate compared to parental strains, important flavor attributes of fine Japanese ginjo sake rice wine. We used hierarchical clustering heatmapping with principal component analysis for metabolic profiling and found that the low levels of endogenous amino/organic acids clustered S. arboricola apart from the S. cerevisiae industrial strains. In sake fermentations, hybrid strains showed a mosaic profile of parental strains, while metabolic analysis suggested S. arboricola had a lower amino acid net uptake than S. cerevisiae. Additionally, we found an increase in ethanolic fermentation from pyruvate and increased sulfur metabolism. Together, our results suggest S. arboricola is poised for in-depth metabolomic exploration in sake fermentation.

The nematode Angiostrongylus cantonensis has been reported worldwide, however, some basic questions remain unanswered about the presence of A. cantonensis in Ecua-dor: 1) Was the invasion of A. cantonensis in Ecuador unique, or did it occur in different waves? 2) Was this invasion as recent as historical records suggest? 3) Did this inva-sion come from other regions of South America or elsewhere? To address these issues, we assessed the genetic diversity of MT-CO1 gene sequences from isolates obtained in eleven of Ecuador's 24 provinces. Our Bayesian inference phylogenetic tree recovered A. cantonensis as a well-supported monophyletic group. All eleven sequences from Ec-uador were identical and identified as AC17a. The haplotype AC17a, found in Ecuador and the USA, formed a cluster with AC17b (USA); AC13 (Thailand); and AC12a-b (Cambodia). It is notable that all the samples, obtained in different geographic and climatic regions of different Ecuadorian provinces, had no genetic difference between them. Despite the lack of genetic information on A. cantonensis in Latin America, ex-cept in Brazil, our finding differs from previous studies by its absence of genetic diver-sity in Ecuador. We concluded that the invasion of A. cantonensis in Ecuador may have occurred: 1) as a one-time event, 2) recently, and 3) from Asia via the USA. Further re-search should include samples from countries neighboring Ecuador to delve deeper in-to this.

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation and we discuss the mechanisms by which exosomes could be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

36 years after the publication of the important article by Busa and Nuccitelli on the variability of intracellular pH (pH_i) and the interdependence of pH_i and intracellular Ca²⁺ concentration ([Ca²⁺]_i), little research has been carried out on pH_i and calcium signaling. Moreover, the results appear to be contradictory. Some authors claim that the increase in [Ca²⁺]_i is due to a reduction in pH_i, others that it is caused by an increase in pH_i. The reasons for these conflicting results have not yet been discussed and clarified in an exhaustive manner. Variations in pH_i have a significant impact on the increase in [Ca²⁺]_i and hence on some of the basic biochemical mechanisms of calcium signaling. This paper focuses on the possible triggering role of protons, highlighting the mechanisms potentially involved and the open issues that could be clarified by research.

Between a vineyard and the foliage wall of an adjacent forest, 25 traps containing different Drosophila attractants were applied on three occasions in autumn after the grape harvest. The attractant liquid was Pinot Blanc grape juice to which pure Saccharomyces cerevisiae yeast had been added to initiate fermentation. The five test variants differed in only one characteristic, namely the fermentation time, which was changed in two-day steps. Nine species of the genus Drosophila were captured, but only two were abundant enough to allow statistical analysis of variant differences in capture frequencies. Both species, D. suzukii and D. simulans, can affect the quality of the berries and ultimately the wine even before the harvest and are therefore considered pests. The studies showed that fermenting grape juice is significantly more attractive to both species than unfermented grape juice and that the attractiveness of the attractant liquid is maximised for D. simulans males with a fermentation time of seven to eight days.Parallel to this experiment, an analysis of the aroma spectrum of the fermenting grape juice was carried out with a temporal resolution of one day for the first twenty days. This made it possible to identify the aroma substances that had the highest concentrations in the time frame in which the attractant was particularly attractive and whose attractant effect should therefore be investigated further.

In eukaryotes, the Dph1•Dph2 dimer is a non-canonical radical SAM enzyme. Using iron-sulfur (FeS) clusters, it cleaves the cosubstrate S-adenosyl-methionine (SAM) to form a 3-amino-3-carboxy-propyl (ACP) radical for synthesis of diphthamide. The latter decorates a histidine residue on elongation factor 2 (EF2) conserved from archaea to yeast and humans and is important for accurate mRNA translation and protein synthesis. Guided by evidence from archaeal orthologues, we searched for a putative SAM binding pocket in Dph1•Dph2 from Saccharomyces cerevisiae. We predict a SAM binding pocket near the FeS cluster domain that is conserved across eukaryotes in Dph1 but not Dph2. Site-directed DPH1 mutagenesis and functional characterization by assays diagnostic for loss of diphthamide reveal the SAM pocket is essential for synthesis of the décor on EF2 in vivo. Further evidence from structural modeling suggests particularly critical residues close to the methionine moiety of SAM. Presumably, they facilitate a geometry specific for SAM cleavage and ACP radical formation that distinguishes Dph1•Dph2 from classical radical SAM enzymes, which generate canonical 5′-deoxyadenosyl (dAdo) radicals.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

In the last years, advances in materials engineering based on adaptive electronics have found a new paradigm to optimize drawbacks in signal processing. A two-layer MnO/ZnO:Zn heterostructure envisioned for frequency adaptive electronic signal processing is synthesized by sputtering where the use of internal states allows reconfigurability to obtain new operating modes at different frequency input signals. An X-Ray Diffraction (XRD) is performed on each layer, MnO:Mn had a cubic and ZnO:Zn a hexagonal structure with preferential growth in [111] and [002] directions respectively. It is determined that the coupling in this heterojunction is compatible with a mismatch less 1 % due texture in each layer which implies a low number of defects. An electrical characterisation with an oscilloscope and signal generator was carried out to obtain the time-response signals and current-voltage (I-V) curves where no degradation is detected when changing from a range of frequencies (100 Hz – 1 MHz). An equivalent circuit is proposed to explain the effects in the interface. Finally, the MnO/ZnO:Zn heterojunction delivers states that are stable, repeatable, and reproducible and it demonstrates how the interaction of the materials can be used in adaptive device applications applying frequencies and internal states as to create new and innovative design schematics, reducing the numbers of components/connections in a system for future sustainable electronics.

A Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by a complex interplay of genetic, molecular, and cellular factors. It is considered a multifactorial disorder influenced by genetic susceptibility, environmental triggers, and dysregulated immune responses. Understanding the molecular and cellular mechanisms driving SLE pathogenesis has been instrumental in developing targeted therapies to manage the disease and improve patient outcomes. In this essay, we will delve into the intricate molecular and cellular processes underlying SLE and examine the key lessons learned from human therapies.

Treatment of the [AuCl(tetrahydrothiophene)] complex with 4-chloro-2-iodo-1-isocyanobenzene furnished the gold(I) compound [AuCl(CNC6H3-4-Cl-2-I)] (1). In the crystal structure of 1, the linear C–Au–Cl group is subject to the solid-state head-to-tail pairing which is determined by the aurophilic Au···Au and the rare π-holeCN···Cl interactions. These two types of structure-determining interactions are complementary to each other and the system of Au···Au and CCN···Cl contacts accomplishes 2D extended ladder-type architecture. In addition, the terminal I-atoms are involved in the three-center halogen bonding. Density functional theory calculations, employing a set of computational tools, verified the role of Au···Au and π-holeCN···Cl noncovalent bonds in the spectrum of noncovalent forces.

The role of innate immunity in neutralization of viral infections (including COVID-19) and forming long-lasting and specific immune memory is considered. It is assumed that antiviral protection is generated by the mechanism of RNA interference (RNAi) and is based on the presence of specific viral patterns in the DNA library of the host cells.

In this paper, we have used magnetron sputtering to grow the high-quality GeSn layer on Ge (100) with Sn compositin up to 7%. The crystallinity of the GeSn layer is pretty good, and the strain relaxation degree of the GeSn layer is evaluated to be approximately 50%. The root mean square (RMS) value is 0.8 nm, and the averaged TDDs in the GeSn layer is 8.7×109 cm-2, which is obtained from the rocking curve of GeSn layer along (004) plane. PL measurement result shows the significant optical emission from the deposited high-quality GeSn layer, which also means that magnetron sputtering is an optional way to achieve the higher Sn composition GeSn luminescent material. To verify whether our deposited GeSn can used for optoelectronic devices, we fabricate the simple vertical p-i-n diode, and the room temperature current-voltage (I-V) characteristic was obtained. This result paves the way for future sputtered-GeSn optimization, which is critical for the optoelectronic application.

In this paper, we introduce and study the notion of rough I₂-lacunary statistical convergence of double sequences in normed linear spaces. We also introduce the notion of rough I₂-lacunary statistical limit set of a double sequence and discuss about some properties of this set.

Non-alcoholic beer (NAB) or low alcoholic beer (LAB) are taking over the market with a growing sale. Sus-tainable recycling and valorization of exhausted brewer’s spent grains (BSG) coming from craft beer is a relevant issue in brewing process. In this work, recycled BSG and BSG+GJ (supplemented with 10% grape juice) were used as wort-substrate to inoculate already selected non-conventional yeasts to produce NABLAB craft beer. Results showed that wort composed by only recycled BSG produced appreciate NAB beers (ethanol from 0.12% to 0.54 % v/v) while the addition of 10% of grape juice made LAB beers (ethanol from 0.82 to 1.66 % v/v). As expected, volatile compounds production was highest with the addition of grape juice. Lachancea thermotolerans confirmed the lactic acid production and, as Saccharomyces cerevisiae, is characterized by (in both worts) ethyl butyrate and isoamyl acetate, while Torulaspora delbrueckii produced relevant amounts of exanol, phenylethyl acetate and β-phenyl ethanol (wort added with grape juice). Wickeramhomyces anomalus and Pichia kluyvery showed consistent volatile production but only in wort with grape juice addition where a fermentation activity was exhibited. The overall results indicated that reused BSGs, non-conventional yeasts and grape juice is a suitable strategy for specialty NABLAB beer.

Saccharomyces cerevisiae are a phenotypically diverse species that adapt to a wide variety of environments by exploiting standing genetic diversity and selecting for advantageous mutations. Glyphosate and copper-based herbicides/ fungicides affect non-target organisms, these incidental exposures can impact microbial populations. In this study, glyphosate resistance was found in the historical collection of yeast which was collected over the last century, but only in yeast isolated after the introduction of glyphosate. The highest glyphosate-resistant yeasts were isolated from agricultural sites. However, herbicide application at these sites was not recorded. In an effort to assess glyphosate resistance and impact on non-target microorganisms, yeast were harvested from 15 areas with known herbicidal histories, including an organic farm, conventional farm, remediated coal mine, suburban locations, state park, and a national forest. Yeast representing 23 genera were isolated from 237 samples of plant, soil, spontaneous fermentation, nut, flower, fruit, feces, and tree material samples. Saccharomyces, Candida, Metschnikowia, Klyveromyces, Hanseniaspora, and Pichia were other genera commonly found across our sampled environments. Managed areas had less species diversity and at the brewery, only Saccharomyces and Pichia were isolated. A conventional farm growing RoundUp Ready™ corn had the lowest phylogenetic diversity and the highest glyphosate resistance. The mine was sprayed with multiple herbicides including a commercial formulation of glyphosate; however, the yeast did not have elevated glyphosate resistance. In contrast to the conventional farm, the mine was exposed to glyphosate only one year prior to sample isolation. Glyphosate resistance is an example of the anthropogenic selection of nontarget organisms.

The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study mRNA turnover since the beginnings of molecular biology. Here we summarize the main methods to measure RNA half-life: transcription inhibition, gene control and metabolic labelling. These methods were used to detect the cellular activity of the mRNAs degradation machinery, including the exo-ribonuclease Xrn1 and the exosome. Less progress has been made in the study of the differential stability of mature RNAs because the different methods have often yielded inconsistent results so that an mRNA considered to be stable can be classified as unstable by another method. Recent advances in the systematic comparison of different method variants in yeast have permitted the identification of the least invasive methodologies that reflect half-lives the most faithfully, which is expected to open the way for a consistent quantitative analysis of the determinants of mRNA stability.

It has been reported that prostaglandin I2, such as epoprostenol, develops Grave's disease. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she started complaining of neck swelling and was diagnosed with Grave’s disease. Thyroid function was controlled by thiamazole and levothyroxine. Nevertheless, her thyroid gland enlargement worsened as epoprostenol dose was titrated. After 23 years of treatment with epoprostenol, she suddenly experienced respiratory failure with a giant goiter leading to airway stenosis and passed away. The autopsy confirmed a giant goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

Infection with Ebola virus (EBOV) is responsible for haemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluc-based protein complementation assay (NPCA) and isolated two compounds disrupting the interaction of the EBOV protein fragment VP35IID with the N terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, we support further testing of the compounds in other species, as well as against further negative sense RNA viruses.

This research investigated the antihypertensive effects of tamarind products and compared their potentials based on their animal model’s data verified by molecular docking, multitarget interactions in network pharmacology, and dynamic simulation assays. The GC-MS characterized tamarind products were administered to the cholesterol-induced hypertensive Wistar albino rat models. Two-week-intervened animals were dissected to collect serum and organs which were respectively subjected to the analyses of hypertension-linked markers and tissue architectures. Lead biometabolites of tamarinds interacted with eight target receptors in molecular docking and dynamic simulation studies and they were tested for multitarget interactions using network pharmacological analyses. Results showed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), Troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour over the sweet tamarind flesh extracts, but seed extracts had a smaller influence. Among the tamarind’s biometabolites, Gamma-sitosterol (ϒ-sitosterol) was found to be the best ligand in managing hypertension via the possible ligand-receptor interactions with the guanylate cyclase which displayed the best drug-likeliness through the highest binding energy -9.3 Kcal. Multitargeted interactions-based degree algorithm and phylogenetic tree of pathways showed 14 targeted genes, of which NR3C1, REN, PPARG, and CYP11B1 hub genes, were consistently modulated by the ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol-guanylate cyclase were stable between 75.00 to 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be supplemented to be a more prospective antihypertensive target or nutraceuticals affirming through advanced preclinical and clinical studies.

Manufacturers of photovoltaic modules do not provide all the information necessary to predict their performance under different climatic conditions. This forces the development of mathematical models of behavior and the application of mathematical methods for the calculation of their associated parameters. A toolbox called PVMSim implemented in MATLAB/GUI is proposed in this paper. PVMSIm provides models allowing the simulation of photovoltaic modules. A two-diode model is used to represent the effect of irradiance and temperature on the V-I and V-P characteristic curves. The accuracy of PVMSim has been vaildated by applying the models to two mono-crystalline and multi-crystalline solar modules of different power ratings and manufacturers. The model PVMSim model accuracy was verified against the manufacturer’s datasheet. This paper shows that this tool is useful for designers and professionals who require an intuitive graphical interface for fast and accurate modeling, simulation and sizing of photovoltaic systems.

Soybean is a highly nutritious legume grown globally as a food and feed crop. An examination of a collection of 10 cultivated and 6 wild Korean soybean varieties showed that there is phenotypic variability notable in different soybeans. Therefore, to develop a list of biomarker candidates useful for growing soybeans of better quality and quantity, the genes of 16 Korean soybean varieties were compared with those of the reference Glycine max var. Williams 82. The comparison was made through gene sequencing to facilitate selection of nsSNPs. The objective of the study was to find out the structural and functional variations caused by nsSNPs and discuss whether the collection of Korean soybean varieties qualifies as biomarkers based on their phenotypic traits. Analysis of the data collected was done using four software: SIFT, Polyphen, PANTHER, and I-mutant 2.0, which are designed to detect the rate of functional and structural variations caused by the nsSNPs in cultivated and wild soybean varieties. Genotypic information obtained in the analysis was used to develop a core collection of biomarkers based on whether nsSNP content was found in more than half of the 16 samples. Therefore, the list of biomarker candidates developed from this study showed that Korean soybean could provide valuable information needed in both future crop genetic research and identification of biomarkers.

Natural Gas (NG) processing is a prominent industrial separation process. Among the available techniques, the innovative membrane process shows potential for efficient removal of impurities, including carbon dioxide (CO₂). This study focuses on utilizing breakthroughs in membrane separation to drive sustainable CO₂ extraction from natural gas. Through comprehensive research and analysis, we explore the effectiveness and feasibility of membrane-based systems in removing CO₂ impurities from NG, thus promoting greener and more sustainable industrial practices. Our findings underscore the transformative nature of membrane separation technology, presenting new possibilities for a more environmentally-friendly and sustainable approach to CO₂ extraction from natural gas.Natural Gas (NG) processing utilizes various techniques for impurity removal, with the membrane process emerging as a promising option for efficient carbon dioxide (CO₂) extraction. This research proposes the integration of a simple mathematical model into ASPEN HYSYS to design a membrane system for CO₂/CH₄ separation. The study also investigates parameter sensitivities by altering operating conditions, such as feed composition and pressure, as well as membrane properties, including selectivity. By analyzing these variables, we aim to optimize the performance and efficiency of the membrane system, facilitating the sustainable extraction of CO₂ from NG. The findings contribute to advancing the design and operation of membrane-based processes for CO₂ separation, paving the way for greener and more sustainable industrial practices. In addition, this study explores various configurations for optimizing the design of the membrane system, including single-stage with and without recycling as well as double-stage configurations. The investigation demonstrates that methane recovery can be enhanced through the recycling of the permeate stream and by implementing a double stage membrane system. These findings highlight the potential for improving the efficiency and performance of the membrane system, enabling higher methane recovery rates. By considering different configurations, this research contributes to the development of more effective and sustainable CO₂ extraction processes from natural gas.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

Milroy's disease (MD), also known as hereditary lymphedema type I, is a rare autosomal dominantly inherited primary lymphedema. It accounts for approximately twenty percent of all primary lymphedemas. MD typically presents clinically with bilateral lower extremity lymphedema. Our case report is about a rare case of MD presenting with unilateral lymphedema in both upper and lower extremities in a patient admitted to our clinic. A 24-year-old woman who had been under observation for lymphedema since she was 8 years old was diagnosed with MD by physical examination, venous Doppler ultrasound, whole body lymphoscintigraphy, and molecular genetic testing in our clinic, and partial improvement was achieved with Complete Decongestive Therapy, the gold standard treatment for lymphedema. Genetic counseling services may be especially useful for the patient and family. Although MD is rarely seen in the literature, many more studies are needed to identify carrier variants in the community.

Obesity and overweight are associated with many metabolic diseases, such as hypertension, diabetes, and dyslipidemia, which are closely related to a sedentary lifestyle and lack of exercise. Aerobic exercise effectively increases the high-density lipoproteins-cholesterol (HDL-C) levels and decreases the triglyceride (TG) levels. The consumption of Cuban policosanol (Raydel®) is also effective in enhancing the HDL-C quantity and HDL functionality to treat dyslipidemia and hypertension. On the other hand, no study has examined the effects of a combination of high-intensity exercise and policosanol consumption in obese subjects to improve metabolic disorders. In the current study, 17 obese subjects (average BMI 30.0±1.1 kg/m2, eight male and nine female) were recruited to participate in a program combining exercise and policosanol (20 mg) consumption for 12 weeks. After completion, their BMI, waist circumference, total fat mass, systolic blood pressure (SBP), and diastolic blood pressure (DBP) decreased by approximately 15% (p=0.022), 12.7% (p=0.008), 33% (p=0.006), 11% (p<0.046), and 13% (p=0.007), respectively. In the serum lipid profile, at week 12, they showed a remarkable decrease in the total cholesterol (TC) and triglyceride (TG) levels, up to 17% (p<0.019) and 54% (p<0.002) from the baseline, respectively. Although the serum HDL-C was increased by approximately +12% from the baseline, the percentage of HDL-C in TC, HDL-C/TC (%), was increased by up to +32% (p=0.007) at week 12. The serum coenzyme Q10 (CoQ10) level was increased 1.2-fold in all participants at week 12 from the baseline. In particular, the male participants showed a 1.4-fold increase (p=0.027) from the baseline. The larger increase in serum CoQ10 was correlated with the larger increase in the serum HDL-C during 12 weeks. The hepatic function parameters were improved; the serum -glutamyl transferase decreased at week 12 by up to 55% (p<0.007), while the aspartate aminotransferase and alanine transaminase levels decreased within the normal range. In the lipoprotein level, the extent of oxidation and glycation were reduced significantly in VLDL and LDL, with a remarkable decrease in the TG content in particles. The antioxidant abilities of HDL2 and HDL3, such as paraoxonase (PON) and ferric ion reduction ability (FRA), were enhanced significantly by up to 1.8-fold (p<0.001) and 1.6-fold (p<0.001) at week 12. The particle size and number of HDL2 were increased up to +10% during the 12 weeks with a remarkable decrease in the TG content, glycation extent, oxidation up to 32% (p=0.032), 18% (p=0.043), and 11% (p=0.023), respectively. The particle number and diameter of HDL3 were increased by up to +9% with a remarkable increase in the PON activity, FRA activity, and TC content of +82% (p<0.001), +56% (p<0.001), and +32% (p=0.009), respectively. Expression of apolipoproteinA-I in HDL2 and HDL3 were significantly elevated more in both gender around 30~48% with more distinct band intensity and less glycation at week 12. These improvements in HDL quality and functionality were linked to the higher survivability of adult zebrafish and their embryos. Under the co-presence of carboxymethyllysine (CML), a microinjection of HDL2 to zebrafish embryo from week 0 resulted in approximately 47% survivability with developmental defects and attenuated speed. On the other hand, the HDL2 microinjection from week 12 resulted in remarkably higher survivability (~ 70%). In conclusion, 12 weeks of Cuban policosanol (Raydel®, 20 mg) consumption with high-intensity exercise showed significant improvement in blood pressure, body fat mass, blood lipid profile without liver damage, CoQ10 metabolism, and renal impairment. At week 12, all participants showed a remarkable decrease in oxidation and glycation extent in the VLDL and LDL with a decrease in the TC and TG content. Significant enhancement of the qualities and functionalities in HDL2 and HDL3 by the policosanol consumption were also detected: increase in apoA-I content, TC content, particle size, and particle numbers along with antioxidant abilities, such as PON and FRA.

The intensive care unit is characterized by the critical care of the infants and children who access it, as well as the high complexity of care. This implies and requires optimal integration among the various professionals working there and their ability to work as a team. The purpose of the study was to describe how nurses perceive clinical risk and how they relate to it and to identify adverse events and related risk factors. Nine nurses, two moderators and one external observer partici-pated in the focus group. In the qualitative analysis, 9 themes describing the perception of clinical risk in PICU were identified, including teamwork, specific training, time management, team communication, management, individual errors, structural criticality, patient fac-tors/characteristics, and standardization. Safety culture can be fostered by hospital management to involve PICU nurses in promoting patient safety, which could improve breaking down barriers that prevent nurses from fulfilling their roles.

Apoptosis under severe hypoxia is induced through p53 phosphorylation and HIF-1α-dependent p53 accumulation via ATR activation by DNA damage response (DDR) activation through replication stress. We previously demonstrated that the topoisomerase I catalytic inhibitor, 3EZ, 20Ac-ingenol, specifically induced apoptosis in Jeko-1 and Panc-1 cells, both of which are cell lines that show cyclin D1 overexpression. After progression to the S phase facilitated by nuclear cyclin D1, in the presence of 3EZ, 20Ac-ingenol, an intra S phase checkpoint was induced in ATR activation as part of replication stress-induced DDR. In this study, we examined whether 3EE, 20Ac-ingenol induces a higher degree of p53 phosphorylation and additional HIF-1α and p53 accumulation in response to replication stress-induced DDR activation under the hypoxic condition than under the normoxic condition by controlling ATR activation. 3EE, 20Ac-ingenol induced p53 activation and HIF-1α-dependent p53 accumulation through cooperative ATR activation via induced DDR with the hypoxia in Panc-1 cells. The Jeko-1 cells showed slight HIF-1α accumulation under hypoxia, but this was not decreased by 3EE, 20Ac-ingenol, so that the cells remained resistant to hypoxia. 3EE, 20Ac-ingenol induces an intricate interplay between p53 and HIF-1α accumulation via ATR activations that results in high p53 accumulation, which advanced transient expression and early disappearance of HIF-1?. The strong p53 accumulation and consequent PTEN activation also decreased HIF-1α accumulation and PD-L1 expression, which resulted in intense apoptosis.

Hydraulic fracturing for oil-gas and geothermal reservoir stimulation is closely related to the generation and propagation of Mode I crack. Nonlinear deformation due to rock heterogeneity occurs at such crack tip, which causes the fracture process zone (FPZ) to form before the crack propagates unsteadily. However, the relationship between the FPZ characteristics and rock heterogeneity still remain elusive. We used three rock types common in reservoir for experimental investigation, and each of them includes two subtypes with different heterogeneity due to grain size or microstructural characteristics. Drawing on the experiment results, we calculated the FPZ size in each cracked chevron notched Brazilian disk, and we reproduced the formation process of the FPZ in marble by discrete element method. We showed that strong heterogeneity is favorable to large FPZ size, can enhance the ability of crack generation and complicate crack morphology. Coupling the Weibull distribution with fracture mechanics, the dependence of the FPZ size on heterogeneity degree can be theoretically explained, which suggests that inherent heterogeneity of rocks set physical foundation for formation of FPZ. These findings can improve our recognition to formation mechanism of the Mode I crack and provide useful guidelines for evaluating reservoir fracability.

Electronic structure calculations have been carried out to examine the effect of protonation and water molecules on the heme group of peroxidases in different redox (ferric, ferrous, compounds I and II) and spin states. Shared geometries, spectroscopic properties at Soret region, and thermodynamics of peroxidases are discussed. B3LYP and M06-2X density functionals with different basis sets were employed on a common molecular model of the active site (Fe-centred porphine and proximal imidazole). Computed Gibbs free energies indicate that the corresponding aquo complexes are not thermodynamically stable, supporting the five-coordinate Fe(III) centre in native ferric peroxidases, with a water molecule located at a non-bonding distance. Protonation of the ferryl oxygen of compound II is discussed in terms of thermodynamics, Fe–O bond distances, and redox properties. It is demonstrated that this protonation is necessary to account for the experimental data and computed Gibbs free energies that reveal pKa values of compound II about 8.5 – 9.0. Computation suggests that the origin of the general oxidative properties of peroxidase species, as well as their reactivity towards water and protons and Soret spectral properties, mostly resides on the iron porphyrin and its proximal ligand histidine.

Mesenchymal stem cells (MSCs) are involved in the process of extracellular matrix (ECM) remodeling where collagens play a pivotal role. We recently demonstrated that the remodeling of adsorbed collagen type I might be disordered upon oxidation following its fate in the presence of human adipose-derived MSC (ADMSCs). With the present study, we intended to learn more about the effect of polyphenolic antioxidant Epigallocatechin gallate (EGCG) attempting to mimic the conditions of oxidative stress in vivo and its putative prevention by antioxidants. Collagen Type I was isolated from mouse tail tendon (MTC) and labeled with FITC before oxidizing according to Fe2+/H2O2 protocol. FITC-collagen remodeling by ADMSC was assessed morphologically before and after EGCG pretreatment and confirmed via detailed morphometry analysis measuring the anisotropy index (AI) and fluorescence intensity (FI) in selected regions of interest (ROI), namely: outside the cells; over the cells and central (nuclear perinuclear) region, whereas the pericellular proteolytic activity was measured by de-quenching of fluorescent collagen probes (FRET effect). Here we provide morphological evidence that MTC undergoes significant reorganization by the adhering ADMSC along with the substantial activation of pericellular proteolysis, and further confirm that both processes are suppressed upon collagen oxidation. An important observation was that this abrogated remodeling cannot be prevented by the EGCG pretreatment. Conversely, the detailed morphometry analysis showed that oxidized FITC-collagen rather tends to accumulate beneath the cells and around the cell’s nuclei suggesting the activation of alternative routes for its removal, such as internalization and/or transcytosis. Morphometry analysis also revealed that both processes are supported by EGCG pretreatment.

We obtain exact solutions to the field equations for 5 dimensional LRS Bianchi type-I spacetime in $f(R,T)$ theory of gravity where specifically the following three cases are considered: (i) $f(R,T)=\mu(R+T)$, (ii) $f(R,T)=R \mu + R T \mu^2$ and (iii) $f(R,T)=R+\mu R^2+\mu T$ where $R$ and $T$ respectively the Ricci scalar and trace of the energy-momentum tensor. It is found that the equation of state (EOS) parameter $w$ is governed by the parameter $\mu$ involved in the $f(R,T)$ expressions. We fine-tune the parameter $\mu$ to obtain effect of phantom energy in the model, however we also restrict this parameter to obtain a stable model of the universe. It is noted that the model isotropizes at finite cosmic time.

Mitochondria play key roles in cellular energy metabolism in eukaryotes. Mitochondria of most organisms contain their own genome and specific transcription and translation machineries. The expression of angiosperm mtDNA involves extensive RNA-processing steps, such as RNA trimming, editing, and the splicing of numerous group II-type introns. Pentatricopeptide repeat (PPR) proteins are key players of plant organelle gene expression and RNA metabolism. In the present analysis, we reveal the function of the MITOCHONDRIAL SPLICING FACTOR 2 gene (MISF2, AT3G22670) and show that it encodes a mitochondria-localized PPR protein that is crucial for early embryo-development in Arabidopsis. Molecular characterization of embryo-rescued misf2 plantlets indicates that the splicing of nad2 intron 1 and thus respiratory complex I biogenesis are strongly compromised. Moreover, the molecular function seems conserved between MISF2 protein in Arabidopsis and its orthologous gene (EMP10) in maize, suggesting that the ancestor of MISF2/EMP10 was recruited to function in nad2 processing before the monocot-dicot divergence, ~200 million years ago. These data provide new insights into the function of nuclear-encoded factors in mitochondrial gene expression and respiratory chain biogenesis during plant embryo development.

Japanese encephalitis (JE) is a vaccine preventable disease caused by the Japanese encephalitis virus (JEV), which is primarily prevalent in Asia. JEV is a Flavivirus, classified into a single serotype with five genetically distinct genotypes (I, II, III, IV, and V). JEV genotype III (GIII) had been the most dominant strain and caused numerous out breaks in the JEV endemic countries until 1990. However, recent data shows the emergence of genotype I (GI) as a dominant genotype and it is gradually displacing GIII. The exact mechanism of this genotype displacement is still unclear. The virus can replicate in mosquito vectors and vertebrate hosts to maintain its zoonotic life cycle; pigs and aquatic wading birds act as an amplifying/reservoir hosts, and humans and equines are the dead end hosts. The important role of pigs as an amplifying host for JEV is well known. However, the influence of other domestic animals especially birds that live in high abundance and close proximity to human is not well studied. Here, we strive to briefly highlight the role of birds in JEV zoonotic transmission, discovery of birds as a natural reservoirs and amplifying host for JEV, species of birds susceptible to JEV infection, and the proposed effect of JEV on poultry industry in future perspective which have been neglected for a long times. We also discussed the recent in vitro and in vivo studies which show that the newly emerged GI viruses replicated more efficiently in bird-derived cells and ducklings/chicks than GIII, and an important role of birds in the JEV genotype shift from GIII to GI.

Indoor dusts are collectively formed from anthropogenic and atmospheric activities. Particle matter 10 (PM10) is inhalable and causes significant inflammation by interaction with the pulmonary epithelial barrier. The mediators involved in bronchial epithelial cells response to dust are remined unknown. The air-liquid interface of our lung on chip model was exposed to indoor dust collected from highly polluted houses in Delhi, India. The media were collected after 4 days and cytokine levels were measured. We found that the concentration of IFN, IFNγ, Interleukin-6 (IL-6), IL1b, TNFa, and Granulocyte monocyte colony stimulating factor (GM-CSF) were significantly increased after exposure to indoor dust. IFN type I pathways were a major response from dust exposure. Further investigation is needed to determine the mechanism of action and targets of dust in bronchial epithelial cells.

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.

Nucleoli are emerging as key sensors of cellular stress and regulators of the downstream consequences on proliferation, metabolism, senescence and apoptosis. NF-kB signalling is activated in response to a similar plethora of stresses, which leads to modulation of cell growth and death programs. Although these pathways are distinct, it is increasingly apparent that they converge at multiple levels. Exposure of cells to certain insults causes a specific type of nucleolar stress that is characterised by degradation of the PolI complex component, TIF-IA, and increased nucleolar size. Recent studies have shown that this atypical nucleolar stress lies upstream of cytosolic IkB degradation and NF-kB nuclear translocation. Under these stress conditions, the RelA component of NF-kB accumulates within functionally altered nucleoli to trigger a nucleophosmin dependent, apoptotic pathway. In this review, we will discuss these points of crosstalk and their relevance to the anti-tumour mechanism of aspirin and small molecule CDK4 inhibitors. We will also briefly discuss how NF-kB-nucleoli crosstalk may be more broadly relevant to the regulation of cellular homeostasis and how it may be exploited for therapeutic purpose.

The activity of prioritizing software requirements should be done as efficiently as possible. Selecting the most stable requirements for the most important customers for the development company can be a positive factor when we consider that the available resource does not always encompass the implementation of all requirements. Quantitative methods for reaching software prioritization in releases are many in the field of Search-Based Software Engineering (SBSE). However, we show that it is possible to use qualitative Verbal Decision Analysis (VDA) methods to solve this same type of problem. Moreover, we will use the ZAPROS III-i methods to prioritize requirements considering the opinion of the decision-maker, who will participate in this process. Finally, the results obtained in the VDA structured methods were quite satisfactory when compared to the methods using SBSE. A comparison of results between quantitative and qualitative methods will be made and discussed later.

The fine structure of Apricot pectin polysaccharides is discussed from both literature and recent work we have performed. Structural characterization utilized 1D and 2D homo- and hetero-nuclear NMR spectroscopy including results from High Performance Size Exclusion Chromatography (HP-SEC), HP Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD) and FTIR spectroscopy. The purified pectin fraction (F1AP) was found to be composed of D-galacturonic acid, L-rhamnose, D-arabinose and D-galactose in a 1.0 : 0.1 : 0.36 : 0.12 molar ratio, respectively, which is consistent with a pectin RG-1 branched with arabinogalactan side chain polysaccharides, and has a weight-average molecular weight of approximately 1588.2 kDa. The slope of the hydrodynamic radius versus the molar mass was 0.57, indicating the presence of coil conformations. The results from HPAEC-PAD, HPSEC and NMR spectroscopy (1H, 13C, zTOCSY, HSQC, HSQCTOXY and HMBC) demonstrated that F1AP fine fraction F1AP1, derived from original F1AP, has a backbone of (1→4)-linked -D-galacturonic acid and -L-rhamnopyranosyl residues branched with arabinogalactan of multiply glycosidic linkages of T- α-Araf, 3-α-Araf, 5-α-Araf, T- α -Arap, 2- α-Arap side chains, having methyl and acetylated groups, and has high molecular weights (1945 kDa). While the other F1A6 fraction consists predominately of an HG region of pectin polysaccharides with low molecular weights (117.5 kDa), less aggregated. The F1AP1 polysaccharide was highly viscous and its hydrodynamic radius was 64,3 nm. The exponent b of Rh-Mw (conformation plot) was determined to be 0.48, indicating a compact flexible coil conformation of the macromolecule in solution. However, the F1AP6 fraction of apricot fruits belong to backbone of repeats units of [-(1→4)-α-D-GalpA-1]n – both HG and partly contents RG-II polysaccharides, bearing heterosugar sidechains, including α-Ara, α -Rha and β-Gal residues and adopt more stiffness rod like conformation.

The growth of plant and process of yield formation in crops are moderated by surrounding conditions as well as interaction of genetic background of plants and environment. In the last two decades significant changes in climate can be observed generating unfavorable and harmful impact on plant development. Drought stress can be considered as one of the most dangerous environmental factor influencing plant life cycle and decreasing production of biomass and finally the yield. Plants can react to water deficit in a wide degree what is dependent on the species, the genetic variability within the species, the phase of the plant ontogenesis, the intensity of stress, and other potential stress factors. In plants there can be observed hybrids between distinct taxa which exhibit certain traits adopted to tolerate stress conditions better than parental plants. Oat × maize addition (OMA) plants are good example of fertile hybrids with retained maize chromosomes as addition to complete oat genome. Hybrids generated via wide crossing can exhibit morphological, physiological and biochemical variations implemented by the occurrence of extra chromosomes of maize, as well as interaction of maize and oat chromatin. The molecular analysis indicated 12.5% OMA lines among all tested descendants of wide oat-maize crossing. On the fourteenth day of the drought, a significant effect of stress on the content of soluble sugars and phenolic compounds was observed, soil drought significantly reduced plant biomass above ground and several yield components. Less water lost revealed by results of the excised leaf water loss test was correlated with high yield of OMA lines. Phenolic compounds content might be used as biochemical indicator of plant drought tolerance since there were significant correlation with high kernel yields of plants subjected to drought stress.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be largely explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif locates next to another, ill-defined cysteine that we show in-here is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCM) suggests a candidate Fe-S cluster ligand role. Hence, we generated by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

We are all similar, but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly and yeast panels with insightful applications for translational research.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

High incidence of epithelial malignancies in HIV-1 infection is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), most often HPV16. A collaboration between HIV-1 and HR HPVs in the malignant transformation of epithelial cells exposed to both viruses have long been anticipated. Here, we delineated the effects on in vitro and in vivo properties of HPV16-infected cervical cancer cells of HIV-1 reverse transcriptase. Epidermoid carcinoma Ca Ski cells were made to express RT of HIV-1 clade A (RT_A) or Green Fluorescence Protein (GFP) by lentiviral transduction, subclones with one or six copies of RT_A and six copies of GFP DNA were generated. Expression by subclones of GFP was assessed by flow cytometry, and of RT_A, by Western blotting. Cells were assessed for the levels of mRNA of the RT_A, E6 and its isoforms, and cellular factors characterizing oxidative stress, and EMT by the real-time PCR. Parameters of glycolysis and mitochondrial respiration were assessed by Seahorse technology. Subclones were surveyed for the changes in cell cycle, doubling time, migration capacity, clonogenic activity and for the capacity to form tumors in nude mice. Ca Ski RT_A produced 20-55 fg of RT_A per cell. Expression of RT_A caused a proportional increase in the expression of E6*I isoform. In Ca Ski, RT_A suppressed mitochondrial respiration and oxygen consumption, and increased glycolysis. Compared to parental cells and GFP control, transcription in Ca Ski RT_A of epithelial (E-CADHERIN) state marker was increased, and of mesenchymal (VIMENTIN) decreased, indicating acquisition by cells of the hybrid epithelial/mesenchymal (E/M) phenotype. While Ca Ski GFP and Ca Ski RT_A with one gene insert had reduced migration rate, decreased clonogenic activity in vitro, and diminished capacity to form tumors in nude mice, increase in RT_A copicity/expression mitigated these effects. Altogether, expression of HIV-1 RT_A gave Ca Ski cells the plasticity required to overcome negative effects of lentiviral transduction and potentially increased their tumorigenicity.

This study aimed to detect picobirnavirus (PBV) in the fecal samples of wild and domestic animals from 2014 to 2016 in the Amazon biome. Fecal samples from different animals, including birds (n=41) and mammals (n=217) were used. The PAGE test showed negativity for PBV. However, 32 samples (12.4%, 32/258) showed positive results in RT-PCR analyses. Among the positive sam-ples, pigs and cats, both with 28.12% (9/32), registered the highest frequencies. In phylogenetic analysis, eight sequences from positive samples grouped in the Genogroup 1 of PBV (PBV GI). PBV occurrence was significantly related to cats and pigs, but not other mammals or birds, in-dependently of their geographical origin. Nucleotide analysis demonstrated similarity among the feline group, but the absence of a defined structure between the clades. PBVs are highly wide-spread viruses that can affect the most diverse types of hosts in the Amazon biome, including humans.

A locally-rotationally-symmetric Bianchi-I model filled with strange quark matter (SQM) is explored in f(R, T) gravity. We take f(R, T) = R + 2 f(T) = R + 2λT, where R is the Ricci scalar, T is the trace of energy-momentum tensor and λ is an arbitrary constant. Exact solutions are obtained by assuming that the expansion scalar is proportional to the shear scalar. This yields a constant value for the deceleration parameter, q = 2, which corresponds to the decelerated phase of the universe. The model is found to be physically viable for λ < −1. SQM during early evolution mimics ultra-relativistic radiation whereas at late times, it behaves as dust, quintessence or even the cosmological constant depending on the value of λ. The effective matter acts as a stiff fluid irrespective of the matter content and of the f(R, T) terms. The model is shear free at late times but remains anisotropic throughout the evolution. In the absence of the f(R, T) terms, SQM accelerates the universe. In the specific case when SQM vanishes at late times, the effect of f(R, T) is to accelerate the universe. The model admits the possibility that SQM could be an alternative to dark energy.

Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase (“NTR 2.0”) for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from Vibrio vulnificus. We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

Glutamate excitotoxicity is implicated in the pathogenesis of many disorders, including stroke, traumatic brain injury, and Alzheimer’s disease, for which central insulin resistance is a comorbid condition. Massive glutamate release primarily through ionotropic N-methyl-D-aspartate receptors (NMDARs) causes a sustained rise in [Ca2+]i, followed by mitochondrial depolarization and an increase in intracellular O2• (superoxide) production. Recently, we found that insulin protected neurons against excitotoxicity by diminishing the delayed calcium deregulation (DCD), However, a role of insulin in superoxide production in excitotoxicity still needs to be clarified. The present study is aimed to investigate the effects of insulin on glutamate-evoked superoxide generation and DCD using the fluorescent indicators dihydroethidium, MitoSOX Red, and Fura-FF in rats cultured cortical neurons. We found that insulin significantly diminished both the intracellular and mitochondrial superoxide production in neurons exposed to glutamate and there was a strong linear correlation between [Ca2+]i and intracellular superoxide. MK 801, an inhibitor of NMDAR-gated Ca2+ influx, completely abrogated the glutamate effects in both the presence and absence of insulin. In experiments on sister cultures, insulin diminishes neuronal death. Thus, collectively, data obtained suggest that insulin diminishes glutamate-induced superoxide production in neurons via fall of [Ca2+]i increased and thereby improves viability of neurons

There is high confidence that climate change has increased the probability of concurrent temperature-precipitation extremes, changed their spatial-temporal variations, and affected the relationships between drivers of such natural hazards. However, the extent of such changes has been less investigated in Australia. Daily weather data (131 years, 1889-2019) at 700 grid cells (1◦ × 1◦) across Australia was obtained to calculate annual and seasonal mean daily maximum temperature (MMT) and total precipitation (TPR). A nonparametric multivariate copula framework was adopted to estimate the return period of compound hot-dry (CHD) events based on an ‘And’ hazard scenario (hotter than a threshold ‘And’ drier than a threshold). CHD extremes were defined as years with joint return periods of larger than 25 years. Mann-Kendall nonparametric tests was used to analyse trends in MMT and TPR as well as in the frequency of univariate and CHD extremes. A general cooling-wetting trend was observed over 1889-1989. Significant increasing trends were detected over 1990-2019 in the frequency and severity of hot extremes across the country while trends in dry extremes were mostly insignificant (and decreasing). Results showed a significant increase in the association between temperature and precipitation at various temporal scales. The frequency of CHD extremes was mostly stable over 1889-1989, but significantly increased between 1990 and 2019 at 44% of studied grid cells, mostly located in the north, south-east and south-west. Spatial homogeneity (i.e. connectedness) and propagation of extreme events from one grid cell to its neighbouring cells was investigated across Australia. It can be concluded that this connectedness has not significantly changed since 1889.

Geopolymer cement has been popularly studied nowadays compared to ordinary Portland cement because it demonstrated superior environmental advantages due to its lower carbon emissions and waste material utilization. This paper focuses on the formulation of geopolymer cement from nickel-laterite mine waste (NMW) and coal fly ash (CFA) as geopolymer precursors, and sodium hydroxide (SH) and sodium silicate (SS) as alkali activators. Different mix formulations of raw materials are synthesized to produce a geopolymer based from an I-optimal design and obtained different compressive strengths. A mixed formulation of 50% NMW and 50% CFA, SH-to-SS ratio of 0.5, and an activator-to-precursor ratio of 0.429 yielded the highest 28-day unconfined compressive strength (UCS) of 22.10 ± 5.40 MPa. Furthermore, using an optimized formulation of 50.12% NMW, SH-to-SS ratio of 0.516, and an activator-to-precursor ratio of 0.428, a UCS value of 36.30 ± 3.60 MPa was obtained. The result implies that the synthesized geopolymer material can be potentially used for concrete structures and pavers, pedestrian pavers, light traffic pavers, and plain concrete.

Chinese divination of I Ching has a history of thousands of years. The six lines changes in 64 hexagrams have exceeded one billion scenarios, and the inherent laws among them have not been well revealed to this day. By using big data's technology and coin toss method, this paper simulates the change of 64 hexagrams, and explores the probability and proportion of each hexagram during the change from the perspective of quantification, as well as the maximum and minimum conversion rate of hexagram change. This paper summarizes the basic characteristics and the basic law of hexagram change, and accordingly constructs the spatial form of hexagram change, and reveals the hidden secrets of the ancient Book of changes (I Ching). To achieve this goal, we randomly toss three coins 600 million times to generate 100 million hexagrams. According to the basic rules of hexagram divination, we calculate the hexagram changes. The results showed that: (1) Changes of things are mostly simple changes. The probability of 1 billion randomly generated hexagrams from one to three dynamic lines is close to 80%. (2) About 17% of the 64 hexagrams have no dynamic lines, which means that a significant proportion of the 64 hexagrams are invariant. (3) Small probability changing hexagram certainty and large probability changing hexagram uncertainty. (4) After generating one billion hexagrams at random, the topographic map with the probability of changing hexagrams has axial symmetry and fractal geometric characteristics, and the fractal characteristics are mainly manifested in that the changes on both sides of the symmetry are presented based on the triangle background. These results reflect the obvious characteristics and internal regularity of the changes in the 64 hexagrams of the I Ching. This article provides new ideas for scientific exploration of the internal laws of the 64 hexagrams in the I Ching.

Although many policosanols from different sources, such as sugar cane, rice bran, and insects, have been marketed worldwide, there has been no comparative study of the in vivo efficacy using a hyperlipidemic animal model. This study compared the efficacy of treating dyslipidemia with four different policosanols, including one sugar cane wax alcohol from Cuba (Raydel®) and three policosanols from China (Xi’an Natural sugar cane, Xi’an Realin sugar cane, and Shaanxi rice bran) in hyperlipidemic zebrafish. After 12 weeks of consumption of each policosanol (final 0.1% in diet, wt/wt) and high cholesterol diet (HCD, final 4%, wt/wt) in a tetrabit, the Raydel policosanol group and Xi’an Natural policosanol group showed the highest survivability of approximately 81%, whereas the Xi’an Realin policosanol group and Shaanxi policosanol group showed 57% and 67% survivability, respectively. Among five HCD groups, the Raydel policosanol group showed the lowest serum total cholesterol (TC, p<0.001 versus HCD control) and triglyceride (TG, p<0.001 versus HCD control) with the highest percentage of high-density lipoproteins (HDL)-C in TC. The Raydel policosanol group also showed the lowest serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels with the least infiltration of inflammatory cells and interleukin-6 production in hepatocytes. In the ovary, the Raydel policosanol group also showed the highest contents of mature vitellogenic oocytes with the lowest production of reactive oxygen species and cellular apoptosis in ovarian cells. In the testis, the Raydel policosanol group also showed the healthiest morphology for spermatogenesis with the least interstitial area and reactive oxygen species (ROS) production in testicular cells. In conclusion, 12 weeks of Raydel policosanol consumption resulted in remarkable improvement of the blood lipid profile, amelioration of inflammation in the liver, and enhancement of the cell morphology in the ovary and testis with the highest survivability under the HCD.

The inositol triphosphate associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins, which regulate intracellular Ca2+. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, that is associated with the intracellular Ca2+ channel IP3R-I and the PKGIβ and inhibits IP3R-I upon PKGIβ-mediated phosphorylation. IRAG2 is a 75 kDa membrane protein homologue of IRAG1 and was recently also determined as a PKGI substrate protein. Several (patho-)physiological functions of IRAG1 and IRAG2 were meanwhile and recently elucidated in a variety of human and murine tissues, e.g. of IRAG1 in various smooth muscles, heart, platelets and other blood cells, of IRAG2 in pancreas, heart, platelets and taste cells. Hence, lack of IRAG1 or IRAG2 leads to diverse phenotypes in these organs, e.g. smooth muscle and platelet disorders or secretory deficiency, respectively. This review aims to highlight the recent research regarding these both regulatory proteins to envision its molecular and (patho-)physiological tasks and to unravel its functional interplay as possible (patho-)physiological counterparts.

Should our planet be visited by an extraterrestrial civilization, the prevailing assumption would undoubtedly be that the extraterrestrial civilization is Type I i.e. its capacity for interstellar travel results from its technological development. This assumption is dangerous for it unnecessarily leads to the Extraterrestrial Tandem Hypothesis (ETH): the belief than an extraterrestrial civilization technologically capable of interstellar travel must also be technologically compatible with the inexorably rapid annihilation of life on Earth. Such a state of things would compromise the planet’s capacity to stage a confident defense should the extraterrestrials prove belligerent. The presumption of Type I extraterrestrials (on the premise of the capacity for interstellar travel alone) is unfounded as extraterrestrials may be Type II i.e. capable of interstellar travel by virtue of natural intrinsic or extrinsic factors. This paper advances, most importantly, that the fundamental policy of first contact should be the employment of various strategies toward the evaluation of the technological capacity of visiting extraterrestrials. This evaluation must be particularly devoted to the detection of Type II extraterrestrials masquerading as Type I (using concealment and Wizard of Oz strategies). Integral to this detection are the concepts of the precedence relation and The Extraterrestrial Exclusion Principle (EEP). A precedence relation is a qualitative relation expressing the relative difficulty of producing a technological action. The Extraterrestrial Exclusion Principle states that a Type I extraterrestrial life form is excluded from certain actions. Such actions are lower in precedence than interstellar travel and may be described as in violation of the EEP or EEP forbidden. EEP actions reveal extraterrestrials to be Type II. As an example, the value of the Hawking Warning is subjected to EEP analysis. Furthermore, a hypothetical conundrum in linguistics termed the Kryptonian Linguistic Paradox (KLP) is discussed as a case of an EEP forbidden act. Finally, the paper explores the limitations of the stated fundamental policy of first contact.

In this paper, we concentrate on the study of the properties of residual Tsallis entropy for order statistics. Order statistics have an important role in reliability structural engineering for example for modelling lifetimes of series and parallel systems. The residual Tsallis entropy of ith order statistic from a continuous distribution function and its deviation from the residual Tsallis entropy of ith order statistics from a uniform distribution is investigated. In a mathematical framework, a method to express the residual Tsallis entropy of the ith order statistic from a continuous distribution in terms of the residual Tsallis entropy of the ith order statistic from a uniform distribution is provided. This approach may provide insight into the behavior and properties of the residual Tsallis entropy for order statistics. Further, we study the monotonicity properties of the residual Tsallis entropy of order statistics under dierent conditions. By studying these properties, deeper understanding of the relationship between the position of order statistics and the resulting residual Tsallis entropy is gained.

The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5’ region that in normal, healthy individuals contains 20-44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55-199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines (LCLs, or lymphoblasts) of premutation carriers have elevated mitochondrial respiratory activities. In the carriers, especially those not clinically affected with FXTAS, AMPK activity was shown to be elevated. In the FXTAS patients, however, it was negatively correlated with brain white matter lesions, suggesting a protective role in the molecular mechanisms. Here we report an enlarged and extended study of mitochondrial function and associated cellular stress-signalling pathways in lymphoblasts isolated from male and female premutation carriers, regardless of their clinical status, and healthy controls. The results confirmed the elevation of AMPK and mitochondrial respiratory activities and reduction of reactive O2 species (ROS) levels in premutation cells and revealed for the first time that TORC1 activities are reduced. Extensive correlation, multiple regression and Principal Components analysis revealed the best fitting statistical explanations of these changes in terms of the other variables measured. These suggested which variables might be the most “proximal” regulators of the others in the extensive network of known causal interactions amongst the measured parameters of mitochondrial function and cellular stress signalling. In the resulting model, the premutation alleles activate AMPK and inhibit both TORC1 and ROS production, the reduced TORC1 activity contributes to activation of AMPK activation and of nonmitochondrial metabolism, and the higher AMPK activity results in elevated catabolic metabolism, mitochondrial respiration and ATP steady state levels. In addition the results suggest a separate CGG repeat number-dependent elevation of TORC1 activity that is insufficient to overcome the inhibition of TORC1 in premutation cells, but may presage the previously reported activation of TORC1 in FXS cells.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.

A series of precise data consisting of zircon U–Pb ages, whole-rock geochemistry and Sr–Nd–Hf isotope compositions from the Huhetaoergai granitic pluton was collected in this study and combined with data from the western Huhetaoergai, Zhuxiaogubuhe and Yagan granitic plutons to constrain the petrogenesis and tectonic setting of granitic plutons in the northern Ya-Gan fault zone, North Alxa, China. The Huhetaoergai pluton is composed of hornblende diorite, medium- to coarse-grained biotite adamellite and coarse-grained biotite adamellite with K-feldspar megacrysts. The U–Pb zircon ages of biotite adamellite are 220.5 ± 1.9 Ma and 226.5 ± 2.4 Ma. These granitoids are I-type granites with highly radiogenic initial ⁸⁷Sr/⁸⁶Sr of 0.708085–0.735470, negative eNd(t) average values of −2.98–3.23 and high eHf(t) of 9–11.05. These features indicate the granitoids were formed from magmas generated from juvenile crust. We speculate that the granitoids of the Huhetaoergai pluton were emplaced during an episode of intense intraplate orogenic movement evolution in an extrusional setting after a period of extensional postcollisional intraplate evolution.

This review describes the positive effects of growth hormone on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on the vascular endothelium improving its dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease inducing the generation of new collateral vessels able to bypass a major artery occlusion. We include some preliminary data from a trial in which GH or placebo is given to elder people suffering from critical limb ischemia, showing the effects of the hormone on plasma markers of inflammation, and stating that the administration of GH in short periods of time is safe and effective even in diabetic patients. We also analyze how Klotho may have strong relationships with GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH to repair the damaged tissue. Lastly, we show how GH induces wound healing by increasing the blood flow to the ischemic tissue. In summary, we postulate that short-time GH administration is useful for treating cardiovascular diseases.

Prolylcarboxypeptidase (PRCP, PCP, Lysosomal Pro-X-carboxypeptidase, Angiotensinase C) controls angiotensin - and kinin- induced cell signaling. Elevation of PRCP appear to be activated in chronic inflammatory diseases (cardiovascular disease (CVD), diabetes) in proportion to severity. Vascular endothelial cell senescence and mitochondrial dysfunction have consistently been shown in models of CVD in aging. The cellular senescence, a driver of age-related dysfunction, can differentially alter the expression of lysosomal enzymes due to lysosomal membrane permeability. There is a lack of data demostrating the effect of age-related dysfunction on the expression and function of PRCP. To explore the changes in PRCP, PRCP-dependent prekallikrein (PK) pathway was charcterized in early – and late-passage human pulmonary artery endothelial cells (HPAECs). Detailed kinetic analysis of cells treated with high molecular weight kininogen (HK), a precursor of bradykinin (BK), and PK revealed a mechansim by which senescent HPAECs activate the generation of kallikrein upon the assembly of the HK-PK complex on HPAECs in parallel with an upregulation of PRCP and endothelial nitric oxide (NO) synthase (eNOS) and NO formation. The NO production and expression of both PRCP and eNOS increased in early-passage HPAECs while decreased in late-passage HPAECs. Low activity of PRCP in late passage HPAECs was associated with rapid decreased telomerase reverse transcriptase mRNA levels. We also found that, with an increase in the passage number of HPAECs, reduced PRCP altered respiration rate. These results indicated that aging dysregulates PRCP protein expression, and further studies will shed light into the complexity of PRCP-dependent signling pathway in aging.

Against the backdrop of global climate change, the frequency of drought events is increasing, leading to significant impacts on human society and development. Therefore, it is crucial to study the propagation patterns and trends of drought characteristics over a long-time scale. The main objective of this study is to delineate the dynamics of drought characteristics by examining their propagation patterns in China from 1951 to 2020. In this study, precipitation data from meteorological stations across mainland China were used. A comprehensive dataset consisting of 700 stations over the past 70 years was collected and analyzed. To ensure data accuracy, the GPCC database was employed for data correction and gap filling. Long-term drought evolution was assessed using both the SPI-12 and SPEI-12 indices to detect drought characteristics. Two Moran indices were applied to identify propagation patterns, and the MK analysis method along with the Theil-Sen slope estimator were utilized to track historical trends of these indices. The findings of this study reveal the following key results: (i) Based on the SPI-12, the main areas of China that are prone to drought are mostly concentrated around the Hu Huanyong Line. Indicating a tendency towards drying based on the decadal change analysis. (ii) The distribution of drought-prone areas in China, as indicated by the SPEI-12, is extensive and broadly distributed, with a correlation to urbanization and population density. These drought-prone areas are gradually expanding. (iii) Between 2010 and 2011, China experienced the most severe drought event in nearly 70 years, affecting nearly 50% of the country's area with a high degree of severity. This event may be attributed to atmospheric circulation variability, exacerbated by the impact of urbanization on precipitation and drought. (iv) The frequency of drought occurrence in China gradually decreases from south to north, with the northeast and northern regions being less affected. However, areas with less frequent droughts experience longer and more severe drought durations. In conclusion, this study provides valuable insights into the characteristics and propagation patterns of drought in China, offering essential information for the development of effective strategies to mitigate the impacts of drought events.

The practice of quantified-self sleep tracking is increasingly common nowadays among healthy individuals as well as patients with sleep problems. However, existing sleep-tracking technologies only support simple data collection and visualization, and are incapable of providing actionable recommendations that are tailored to users' physical, behavioral and environmental context. Here we coined the term context-aware sleep health recommender system (CASHRS) as an emerging multidisciplinary research field that bridges ubiquitous sleep computing and context-aware recommender systems. In this paper, we presented a narrative review to analyze the type of contextual information, the recommendation algorithms, the context filtering techniques, the behavior change techniques, the system evaluation, and the challenges in peer-reviewed publications that meet the characteristics of CASHRS. Analysis results identified current research trends, the knowledge gap, and future research opportunities in CASHRS.

The development of multidrug resistance by pathogenic bacteria and yeast is a significant medical problem that needs to be addressed. One possible answer could be the combined use of antibiotics and silver nanoparticles, which have different mechanisms of antimicrobial action. Nanoparticles can be combined with antifungal agents in the same way. Biogenic silver nanoparticles synthesized using environmentally friendly technology using extracts of biologically active plants are an effective nanomaterial that needs to be comprehensively investigated for implementation into medical practice. In this study, the synergistic effects arising from their combined use with antibiotics and fungicides against various bacteria and yeasts, included in the ESKAPE list, were studied. Effective concentrations of substances were established, recommendations for the studied pathogenic species were presented and the effect of destruction of the bacterial membrane was illustrated. The most significant synergistic effect was manifested in pathogenic candida and brewer's yeast.

The SARS-CoV-2 pandemic continues to pose a global threat. While its virulence has subsided, it has persisted due to the continual emergence of new mutations. Although many high-risk conditions related to COVID-19 have been identified, the understanding of protective factors remains limited. Intriguingly, epidemiological evidence suggests a low incidence of the COVID-19-infected CD patients. The present study explores whether their genetic background, namely the associated HLA-DQs, offers protection against severe COVID-19 outcomes. We hypothesize that the HLA-DQ 2/8 alleles may shield CD patients from SARS-CoV-2 and its subsequent effects, possibly due to memory CD4 T cells primed by previous exposure to human-associated common cold coronaviruses (CCC) and higher affinity to those allele's groove. In this context, we examined potential cross-reactivity between SARS-CoV-2 epitopes and human-associated CCC and assessed the binding affinity (BA) of these epitopes to HLA-DQ 2/8. Using computational methods, we analyzed sequence similarity between SARS-CoV-2 and four distinct CCC. Of 924 unique immunodominant 15-mer epitopes with at least 67% identity, 37 exhibited significant BA to HLA-DQ 2/8, suggesting a protective effect. We present various mechanisms that might explain the protective role of HLA-DQ2/8 in COVID-19-afflicted CD patients. If substantiated, these insights could enhance our understanding of gene-environment enigma and viral-host relationship, guiding potential therapeutic innovations against the ongoing SARS-CoV-2 pandemic.

The average age of in-service bridges has increased in recent years in the United States. To address this issue, structural health monitoring and damage identification approaches can be employed to prioritize maintenance/replacement of aging bridges. Among the damage identification and operational health monitoring approaches, finite element (FE) model updating methods can offer a solution to evaluate the mechanics-based characteristics of bridges. However, in a real-world setting, unidentifiability and mutual dependency between model parameters, modeling errors, especially due to boundary conditions, as well as ill-conditioning of updating algorithms can pose challenges to the application of FE model updating methods. To address these challenges, this study presents a two-step FE model updating approach. In the first step, modal-based model updating is used to estimate linear model parameters mainly related to the stiffness of boundary conditions and material properties. In the second step, in order to refine parameter estimation accounting for nonlinear response behavior of the bridge, a time-domain model updating is carried out. In this step, boundary conditions are fixed at their final estimates using modal-based model updating. To prevent the convergence of updating algorithm to local solutions, the initial estimates for nonlinear material properties are selected based on their corresponding final estimates in the modal-based model updating. To validate the applicability of the two-step FE model updating approach, a series of forced-vibration experiments are designed and carried out on a pair of decommissioned and deteriorated prestressed bridge I-girders. After carrying out the two-step FE model updating, the final estimates of concrete compressive strength are shown to provide reasonable assessment of the damage extent in the girders.

Endothelial cells form a powerful interface between tissues and immune cells. In fact, one of the underappreciated roles of endothelial cells is to orchestrate immune attention to specific sites. Tumor endothelial cells have a unique ability to dampen the immune responses and thereby maintain an immunosuppressive microenvironment. Recent approaches to trigger immune responses in cancers have focused on activating nucleic acid sensors such as cGAS/STING in combination with immunotherapies. In this review, we present a case for targeting nucleic acid sensing pathways within the tumor vasculature to invigorate tumor immune responses. We introduce two specific nucleic acid sensors, the DNA sensor TREX1 and the RNA sensor RIG-I and discuss their functional roles in the vasculature. Finally, we present perspectives on how these nucleic acid sensors in the tumor endothelium can be targeted in an antiangiogenic and immune activation context. We believe understanding the role of nucleic acid sensing in the tumor vasculature can enhance our ability to design more effective therapies targeting the tumor microenvironment.

As shown in former papers, the nonadiabatic Heisenberg model presents a novel mechanism of Cooper pair formation generated by the strongly correlated atomic-like motion of the electrons in narrow, roughly half-filled "superconducting bands". These are energy bands represented by optimally localized spin-dependent Wannier functions adapted to the symmetry of the material under consideration. The formation of Cooper pairs is not the result of an attractive electron-electron interaction but can be described in terms of quantum mechanical constraining forces constraining the electrons to form Cooper pairs. There is theoretical and experimental evidence that only this nonadiabatic mechanism operating in superconducting bands may produce eigenstates in which the electrons form Cooper pairs. These constraining forces stabilize the Cooper pairs in any superconductor, whether conventional or unconventional. Here we report evidence that also the experimentally found superconducting state in bismuth at ambient as well as at high pressure is connected with a narrow, roughly half-filled superconducting band in the respective band structure. This observation corroborates once more the significance of constraining forces in the theory of superconductivity.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

In this paper, a study of modeling PV cell (solar cell), PV module (solar modules) and PV array solar array) using Matlab/Simulink software is presented. This study is focused on the study to design photovoltaic cell, photovoltaic modules, photovoltaic panels and PV array (solar array) and to analyze the change in PV performance according to changes in different parameters such temperature, solar irradiation, reverse saturation current, series resistance and shunt resistance. This study shows the PV and IV characteristics curve for each model from which MPP (maximum power point) is determined. In this study, different PV and IV characteristic curves are gained for varying temperatures with specified solar irradiation conditions,s and then the MPP is tracked. The highest power output is also compared between the designed PV module and the selected PV module (MX Solar USA MX60-245)

The Mediterranean diet (MED) is highly recommended. Medical nutrition therapy is the cornerstone of diabetes treatment. We assessed adherence to the MED, and resultant micronutrient intake and glycemic control in youth with type 1 diabetes. Twenty adolescents, median age 18 years (interquartile range: 15.5-21), median diabetes duration 9 years (7-14), using continuous glucose monitoring devices, received personalized diet regimes based on MED. At 6 months post-intervention, the caloric intake remained unchanged; however, the carbohydrate proportion was lower (p=0.058) and the intakes of some monounsaturated fats increased (p=0.049). Sodium intake exceeded the recommended daily allowance by 250% (p=0.653), before and after the intervention. For blood glucose, the percent time-in-range 70-180 mg/dL improved from 52% (38-60) to 63% (47-71) (p=0.047). The total insulin dose decreased marginally, from 0.76 u/kg (0.64-0.97) to 0.72u/kg (0.61-0.89) (p=0.067). BMI z-score and waist circumference did not change (p=0.316 and p=0.161, respectively). Diastolic blood pressure percentile decreased from 73% (68-88) to 69% (50-79) (p=0.028), and LDL cholesterol from 114mg/ dl (105-134) to 104mg/dl (96-124) (p=0.059). The Israeli Mediterranean diet screener score increased, from 8 (7-11) to 13 points (12-14) (p=<0.001). The MED-based intervention demonstrated feasibility and improvements in glycemic outcomes and in certain nutritional parameters.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.

Nicastrin (NICT) is a transmembrane protein physically associated with the polytypical aspartyl protease presenilin that plays a vital role in the correct localization and stabilization of presenilin to the membrane-bound γ-secretase complex. This complex is involved in the regulation of a wide range of cellular events including cell signaling and the regulation of endocytosed membrane proteins for their trafficking and protein processing. Mehtods: In Trypanosoma cruzi, the causal agent of the Chagas disease, an NICT-like protein (Tc/NICT) was identified with a short C-terminus orthologous to the human protein, a large ectodomain (ECD) with numerous glycosylation sites and a single core transmembrane domain containing a putative TM-domain (457GSVGA461) important for the γ-secretase complex activity. Results: Using the Spot-synthesis strategy with Chagasic patient sera, five extracellular epitopes were identified and synthetic forms were used to generate rabbit anti-Tc/NICT polyclonal serum that recognized a ~72-kDa molecule in immunoblots of T. cruzi epimastigote extracts. Confocal microscopy suggests that Tc/NICT is localized in the flagellar pocket, which is consistent with data from our previous studies with a T. cruzi presenilin-like protein. Phylogenetically, Tc/NICT was localized within a subgroup with the T. rangeli protein that are clearly detached from the other Trypanosomatidae such as T. brucei. These results, together with a comparative analysis of the selected peptide sequence regions between the T. cruzi and mammalian proteins suggest a divergence from the human NICT that might be relevant to Chagas disease pathology. As a whole, our data show that an NICT-like protein is expressed in the infective and replicative stages of T. cruzi and may be considered further evidence for a γ-secretase complex in trypanosomatids.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

In the last two decades, the development of high-throughput diagnostic methods and availabil-ity of effective treatments has increased interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry dis-ease, Gaucher disease), using enzyme activity assay by tandem mass spectrometry, and bi-omarker quantification as second tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive pre-dictive value 40%), with an overall incidence of 1:4,874. Of these, 3 infantile-onset Pompe dis-ease, 2 neonatal-onset Gaucher disease and 4 mucopolysaccharidosis type I patients were imme-diately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrated the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient out-comes. Challenges such as false positive rates, the diagnosis of variants of uncertain significance or late-onset forms, and the lack of treatment for neuronopathic forms, should be addressed.

To further understand the role of phosphorylation in ISGF3- and STAT2/IRF9-mediated constitutive and long-term IFN-I-stimulated transcriptional responses, we performed RNA-Seq and ChIP-Seq, in combination with phosphorylation inhibition and anti-viral experiments. First, we identified a group of ISRE-containing ISGs that were commonly regulated in IFNα treated WT and STAT1-KO cells. Thus, in 2fTGH and Huh7.5 WT cells IFNα-inducible transcription and anti-viral activity relied on the recruitment of the ISGF3 components STAT1, STAT2 and IRF9 in a phosphorylation- and time-dependent manner. Likewise, in ST2-U3C and Huh-STAT1KO cells lacking STAT1, ISG expression correlated with DNA-binding of phosphorylated STAT2/IRF9. This pointed to a dominant role of classical ISGF3 and STAT2/IRF9, and not U-ISGF3 or U-STAT2/IRF9, in the regulation of early and prolonged ISG expression and viral protection, in WT and STAT1-KO cells. In addition, comparative experiments in U3C (STAT1-KO) cells overexpressing all ISGF3 components (ST1-ST2-IRF9-U3C), revealed a threshold-dependent role of U-ISFG3, and potentially U-STAT2/IRF9, in the regulation of constitutive and possibly long-term IFNα-treated ISG expression and anti-viral activity.

This survey reports on the DNA identification and occurrence of Culex torrentium and Cx. pipiens s.s. in Belgium. These native disease vector mosquito species are morphologically difficult to separate and the biotypes of Cx. pipiens s.s. are morphologically indistinguishable. Culex torrentium and Cx. pipiens s.s. were identified using the COI and ACE2 loci. We recorded 1,248 Cx. pipiens s.s. and 401 Cx. torrentium specimens from 24 locations in Belgium (collected between 2017 and 2019). Culex pipiens biotypes pipiens and molestus, and their hybrids, were differentiated by fragment size analysis of the CQ11 locus (956 pipiens and 227 molestus biotype specimens, 29 hybrids). Hybrids were observed at 13 out of 16 sympatric sites. These results confirm that both species are widespread in Belgium, but while Cx. torrentium revealed many COI haplotypes, Cx. pipiens s.s. showed only one abundant haplotype. This latter observation may either reflect a recent population-wide demographic or range expansion, or a recent bottleneck, possibly linked to a Wolbachia infection. Finally, new evidence is provided for the asymmetric but limited introgression of the molestus biotype into the pipiens biotype.

Pericentromeric regions of chromosomes enriched in tandemly repeated satellite DNA although representing a significant part of eukaryotic genomes are still understudied mainly due to interdisciplinary knowledge gaps. Recent studies suggest their important role in genome regulation, karyotype stability and evolution. Thus, the idea of satellite DNA as a junk part of the genome was refuted. Integration of data about molecular composition, chromosome behaviour and details of in situ organization of pericentromeric regions is of great interest. The objective of this work was a cytogenetic analysis of the interactions of pericentromeric regions non-homologous chromosomes in mouse spermatocytes using immuno-FISH. We analysed two events: the associations between cerntomeric regions of X chromosome and autosomes, and associations between centromeric regions of autosomal bivalents forming chromocenters. We conclude that X chromosome form temporary synaptic associations with different autosomes in early meiotic prophase I which normally can be found at pachytene-diplotene without signs of pachytene arrest. These associations are formed between the satellite DNA-enriched centomeric regions of X chromosome and different autosomes but not involve the satellite-poor centromeric region of Y-chromosome. We suggest the mechanism of X chromosome competitive replacement from such associations during synaptic correction. We showed that centromeric region of the X chromosome remains free of γH2Ax-dependent chromatin inactivation, while Y chromosome is completely inactivated. This findings highlights the predominant role of associations between satellite DNA-enriched regions of different chromosomes including X. We assume that X-autosome temporary associations is a manifestation of an additional synaptic disorders checkpoint. These associations are normally corrected before the late diplotene. We revealed that the intense spreading conditions applied to the spermatocytes I nuclei did not lead to destruction of stretched chromatin fibers i.e. elongated chromocenters enriched in satellite DNA. Revealed by us tight associations between pericentromeric regions of different autosomal bivalents and X chromosome may represent the basis for repeat stability maintenance in autosomes an X chromosome. The consequences of our findings are discussed. We obtained the preparations of mouse spermatocytes nuclei in the meiotic prophase I using two approaches: standard and extremely intense surface spread techniques. Using immuno-FISH we visualized tandemly repeated mouse Major and Minor satellite DNA located in the pericentromeric regions of chromosomes and performed a morphological comparison of the standard- and intensely spreaded meiotic nuclei. Based on our results, we assume the remarkable strength of the chromocenter-mediated associations, “chromatin “bridges”, between different bivalents at the pachytene and diplotene stages. We have demonstrated that the chromocenter “bridges” between the centromeric ends of meiotic bivalents are enriched in both tandemly repeated Major and Minor satellite DNA. Association of centromeric regions of autosomal bivalents and X-chromosome but not with Y-chromosome correlates with the absence of Major and Minor satellites on Y-chromosome. We suggest that revealed tight associations between pericentromeric regions of bivalents may represent the network-like system providing dynamic stability of chromosomal territories, as well as add new data for the hypothesis of ectopic recombination in these regions which supports sequence homogeneity between non-homologous chromosomes and does not contradict the meiotic restrictions imposed by the crossing-over interference near centromeres. We conclude that nuclear architecture in meio-sis may play an essential role in contacts between the non-homologous chromosomes providing the specific characteristics of pericentromeric DNA.

The prim objective of commenced article is to determine q-sumudu transforms of a product of unified family of q-polynomials with basic (or q-) analogue of fox’s H-function and q-analog of I-functions. Specialized cases of the leading outcome are further evaluated as q-sumudu transform of general class of q-polynomials and q-sumudu transforms of the basic analogues of Fox’s H-function and I-functions.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

A large body of evidence, replicated in many mouse models of Alzheimer Disease (AD), demonstrated the therapeutic efficacy of oral rapamycin. Administration of m-TOR inhibitors (mTOR-Is), early after the clinical onset, greatly diminished cognitive impairment, amyloid angiopathy, intracellular beta Amyloid and neurofibrillary tangles load. The daily intake of rapamycin has always been 2.24g/Kg/24h. In humans the maximal tolerated oral dose is a few milligrams/day, and at this dosage patients are severely immunosuppressed. Thanks to rapalogs’ scarce CNS-related side effects, we administered intracerebroventricularly (ICV) high doses of the mTOR-I everolimus in a mouse model of AD (3xTg-AD) without significant systemic effects. The instability of the liquid formulation at body temperature (BT) made the treatment very short. Nevertheless, the efficacy of the treatment was high and much longer lasting than expected. In order to set up a thermostable, translational liquid formulation of mTOR-Is, we loaded everolimus in distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles by the thin layer method. The formulation we obtained maintained over 95% of activity after 14 days at BT. We can envision short, potentially periodic ICV treatments in AD patients which replicate results obtained on animal models. The treatment could benefit also Tuberous Sclerosis and Multiple Sclerosis patients.

A novel cytoplasmic dye decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds and general peroxidase substrates like ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN^- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H₂O₂ during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-i in T1D HF management, alongside the emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk, through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests SGLT2-i significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-i into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-i and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim at clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.