The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

The saphenous vein is the conduit of choice for bypass grafting. Unfortunately, the hemodynamic stress associated with the arterial environment of the bypass vein graft leads to the development of intimal hyperplasia (IH), an excessive cellular growth and collagen deposition that results in restenosis and secondary graft occlusion. Hydrogen sulfide (H2S) is a ubiquitous redox-modifying gasotransmitter that inhibits IH. H2S is produced via the reverse trans-sulfuration pathway by 3 enzymes: cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). However, the expression and regulation of these enzymes in the human vasculature remains unclear. Here, we investigated the expression of CSE, CBS and 3-MST in segments of native human saphenous vein and large arteries. Furthermore, we evaluated the regulation of these enzymes in vein segments cultured under static, venous (7 mmHg pressure) or arterial (100 mmHg pressure) pressure. CSE was expressed in the media, neointima and intima of the vessels and was negatively regulated by arterial shear stress. Adenoviral-mediated CSE overexpression or RNA interference-mediated CSE knock-down revealed that CSE inhibited primary human VSMC migration but not proliferation. We propose that high shear stress in arteriovenous bypass grafts inhibits CSE expression in both the media and endothelium, which may contribute to increased VSMC migration in the context of IH.

The successive steps of the oxidation mechanism of crocin, major compound of saffron, by the free OH• radical are investigated by the pulse radiolysis, steady-state (gamma) radiolysis methods and molecular simulations. The optical absorption properties of the transient species and their reaction rate constants are determined. The absorption spectrum of the oxidized radical of crocin resulting from the H-abstraction presents a maximum at 678 nm and a band at 441 nm, almost as intense as that of crocin. The spectrum of the covalent dimer of this radical contains an intense band at 441 nm and a weaker one at 330 nm. The final oxidized crocin, issued from radical disproportionation, absorbs weaker with a maximum at 330 nm. The molecular simulation results suggest that the OH• radical is electrostatically attracted by the terminal sugar and is scavenged predominantly by the neighbor methyl site of the polyene chain as in a sugar-driven mechanism. Based on detailed experimental and theoretical investigations, the antioxidant properties of crocin are highlighted.

Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from PGC-1α-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. Upon achieving a cellular confluence of 70-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vivo mouse models. In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to control-secretome (Ctrl-Sec). In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum pro-inflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, OPA1 (a mitochondrial function marker), and PPARα (an anti-fibrogenic marker) in the PGC-Sec-treated group, along with reduced Collagen 1A expression (a pro-fibrogenic marker). These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine’s anticancer activity together with that of three other bisindoles - conophylline, leucophyllidine and bipleiophylline against human-derived carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (as observed in MDA-MB-468 breast cancer cells) or senescence (as detected in HT-29 colorectal carcinoma cells). Annexin V-FITC/PI, caspase activation and PARP cleavage confirmed the former while positive β-gal staining corroborated the latter. Evident cell cycle perturbations were observed comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed induction of aberrant mitotic phenotypes - multi-nucleation, membrane blebbing and DNA-fragmentation. The DNA integrity assessment of HCT-116 and MDA-MB-468 showed irreparable damage identified by increased fluorescent γ-H2AX during the G1 cell cycle phase. Furthermore, γ-H2AX foci were visually validated in HCT-116 and MDA-MB-468 cells using confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by NQO1 expression. Collectively, we present conofolidine as a potential anticancer candidate capable of inducing heterogeneous modes of cancer cell death in vitro, encouraging further preclinical evaluation of this natural product.

Like all RNA viruses, SARS-CoV-2 shows high mutation rate, which has led to the emergence of new variants. Among them, Gamma and Delta developed at the turn of 2020-2021 in Amazonas and India, two ecoregions characterized by hot-humid weather, very similar to that of the summer season due to climate change in Italy, the first Western country to have been hit hard by COVID-19 and to experience lockdown restrictions in a democratic framework of 58,85 million people. Methods: during the state of national health emergency and the Draghi government, the Civil Defense Department daily released the aggregate data coming from the Ministry of Health, the Higher Institute of Health, the Independent Provinces and the Italian Regions, in order to inform about the pandemic situation in Italy. Among these data there were the number of deaths, hospitalizations in intensive care units (ICU), non-ICU patients, contagions, and performed swabs. By means of a team effort, we have collected and elaborated all these data, comparing COVID-19 pandemic in Italy during the summers 2020 (following the nationwide lockdown), 2021 and 2022. Results: from summer 2020 (before mass vaccination) to summers 2021 (after primary mass vaccination) and 2022 (after booster mass vaccination) all pandemic trend indicators have showed a sharp worsening in Italy. COVID-19 deaths increased by ≈298% and ≈834%, ICU hospitalizations by ≈386% and ≈310%, non-ICU hospitalizations by ≈224% and ≈600%, contagions by ≈627% and ≈6.850% (i.e. ≈68,50 times), swabs by ≈354% and ≈370%, and the mean positivity rate passed from ≈1% to ≈2% and ≈20%, respectively. Conclusions: SARS-CoV-2 can be transmitted in any climate, including areas with hot and humid weather, and the emergence of variants adapted to hot-humid climate may result in summer COVID-19 outbreaks, even in neither tropical nor subtropical countries. Although COVID-19 vaccines can confer cross-protection against newly emerging variants, this cross-immunity is obviously not absolute but limited, also taking into account that vaccine protection wanes considerably after 6 months. It follows that a subject vaccinated at the beginning of winter will not be completely covered in the height of summer, without forgetting the unvaccinated. As a final remark, the long nationwide lockdown made it possible to flatten SARS-CoV-2 circulation and, therefore, its negative impact on Italy during summer 2020.

This article describes a novel topical composition constituted by gamma-amino butyric acid (GABA) and microbial chondroitin sulfate. This composition, formulated by the author and manufactured in a certified facility in the United States of America, exhibits potential for non-invasive intervention in anxiety management, sleep quality enhancement, and promotion of brain-related functions like meditation and nonlocal consciousness. The core component comprises GABA, a key inhibitory neurotransmitter within the central nervous system, complexed with a suitable carrier molecule, microbial chondroitin sulfate. This complexation aims to enhance transdermal absorption and optimize delivery of GABA to target tissues. The proposed mechanism of action involves modulation of GABAergic signal transduction pathways. Application of the topical composition allows GABA penetration into the skin and potentially deeper tissues, where it interacts with GABA receptors. This interaction leads to mental calmness and relaxation as assessed by electroencephalography. The influence of GABAergic signaling on brain circuits demonstrated in this article, when associated with meditation and nonlocal consciousness, suggests potential for the composition to support these practices. The advantage of such an approach consists in avoiding the potential systemic side effects associated with oral or injectable administration of GABA, anxiolytics or hypnotics. Furthermore, the combination of GABA and microbial chondroitin sulfate may offer synergistic benefits, potentially enhancing the overall biological effects. In conclusion, this article presents a novel topical approach for managing anxiety, enhancing sleep quality, and potentially facilitating meditation and nonlocal consciousness through modulation of GABAergic signaling pathways. While further research is necessary, the potential for a non-invasive and potentially side-effect-free intervention in these areas is promising.

The adaptation of plants to biotic and abiotic stress depends on their abilities to sense their surroundings and to generate and transmit corresponding signals to different parts of their body that can evoke changes necessary for optimizing growth and defense. Light has been shown to be one of the key environmental factors that modulate the physiology of both plants and animals via the diverse photoreceptors found in them. Both plants and animals contain a large repertoire of intra- and intercellular signals molecules that include organic and inorganic. One such molecule is a neurotransmitter, γ-aminobutyric acid (GABA), a non-protein amino acid, that rapidly accumulates in plant tissues in response to biotic and abiotic stress and regulates plant growth. Lots of research has been done on GABA in plants for slightly more than half a century now: Its discovery in plant tissues was immediately followed by physiological and biochemical studies. Thereafter molecular-genetics era of cloning the genes encoding the GABA shunt enzymes and transporters, and recombinant expression and purification of the enzymes in vitro to elucidate their regulatory properties and substrate specificity was established. Recently the discovery of the first bona fide GABA target proteins in plants, the ALMTs suggest that GABA indeed could be one of the signaling molecules in plants. All this research did not address in detail the relationship between light and GABA. To better understand the role of GABA in relation to light we set up six light conditions to investigate the changes in the hypocotyl and root growth in Arabidopsis thaliana under different light conditions, including total light, total dark, light blocker, gradient light, shoot dark, shoot dark with blocker. We treated the seedlings with 3-MPA, a GABA inhibitor, using different concentrations grown under different light conditions between 24 to 96 h. Our results show that both the root and hypocotyl are modulated by GABA when grown under different light conditions. These results clearly suggest a link in the signaling pathway of GABA with photoreceptor signaling pathways.

This study aims to reveal the revolutionary Gamma Distribution Manifold (GDM) info-geometric analysis combined with potential Gamma distribution (GD) applications to advance Satellite Earth Observations (SEOs). An exposition of the GDM Fisher Information Matrix (FIM) was undertaken, together with the analytic investigation of the existence of FIM’s inverse. The derivation of GDM’s Geodesic Equations (GEs) is undertaken. The solution of the obtained Geodesic Equations is optimally complicated, and it provides more extensions to numerous open problems. Notably, the current paper provides a first-time unification between three multi-interdisciplinary fields, namely, information geometry theory, probability theory, and Satellite earth observations. Looking at the other side of the coin, the provided revolutionary approach in this current work reports the significant impact of info-geometric analysis on the probabilistic dynamics as well as the influential role of information geometry on satellite and space industry. This poses numerous open issues that initiates a new form of contemporary unification between these inter-disciplinaries to discover another visionary thinking out of traditional statistical frames. In other words, refraining ourselves from using classical statistical frames of thinking and delving into a new info-geometric vision of statistical distributions as well as examining real life applications of information geometry to advance satellite earth observations. The curtain is drawn on this paper by providing several challenging open problems in combination with a concluding remark and the next phase of research.

(1) Background: Until December 2021, French Guiana (FG), located in South America, faced four consecutive COVID-19 epidemic waves. This study sought to analyze the mortality trend of severe COVID-19 patients admitted to the referral ICU of FG. (2) Methods: We conducted a prospective, observational, and non-interventional study in ICU at Cayenne Hospital. We included 383 patients older than 18 admitted with SARS-CoV-2-related pneumonia hospitalized from May 2020 to December 2021. The study covers three periods. Period 1 (Waves 1 and 2, original variant), period 2 (Wave 3, gamma variant), and period 3 (Wave 4, delta variant). (3) Results: The median age was 63 years (52-70). Frailty was diagnosed in 36 patients over 70 (32.4%). Only 4.8% of patients were vaccinated. The median ICU LOS was 10 days (6-19). Hospital mortality was 37.3%. It was 30.9% in period 1, 36.6% in period 2 (p=0.329 vs. period 1), and 47.1% in period 3 (0.015 vs. period 1). In multivariate analysis, independent factors associated with hospital mortality were age more than 40 years (]40-60 years] OR=5.2, 95%CI: 1.4-19.5; (]60-70 years] OR=8.5 95%CI: 2.2-32; (]70+ years] OR=17.9, 95%CI: 4.5-70.9), frailty (OR=5.6, 95%CI: 2.2-17.2), immunosuppression (OR=2.6, 95%CI: 1.05-6.7), and MV use (OR=11, 95%CI: 6.1-19.9). This model had an overall sensitivity of 72%, a specificity of 80.4%, a positive predictive value of 68.7%, and a negative predictive value of 82.8%. (4) Conclusions: The mortality of severe COVID-19 patients in French Amazonia was higher during the delta variant wave. This over-death is explained by the virulence of the responsible SARS-CoV-2 variant and the under-vaccination coverage of the studied population.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare genetic cause of cholestasis. It is considered as part of inherited intrahepatic cholestasis syndromes, such as progressive familial intrahepatic cholestasis (PFIC), and intrahepatic cholestasis of pregnancy. BRIC is presented in infancy or in early adulthood. It is characterized by exacerbations and remissions of jaundice with accompanying intense itching, lasting from weeks to years throughout lifetime. Normal gamma-glutamyl transferase (GGT) is a characteristic laboratory finding. Contrary to PFIC, which may progress to cirrhosis, BRIC does not progress to chronic liver disease or cirrhosis. However, incessant episodes of cholestasis result in marked reduction in quality of life and distinct mutations increase the risk of hepatobiliary malignancy. In intervals between the exacerbations, the histological findings of centrilobular cholestasis together with the abnormal laboratory parameters return to normal. In this context, liver biopsy might be avoided. In this review, we will focus on the genetic aspects of BRIC, its pathophysiology, clinical presentation, and prognosis of this autosomal recessive genetically determined cholestatic disorder. Moreover, triggering factors as well as treatment options will be further elucidated.

The details of the solar flare production mechanisms are not yet completely understood. One of the standing questions is the anisotropy of the X-ray flux, especially in strong flares. It can be studied indirectly by analysing the characteristics of flares at different positions on the visible disc. In this paper, the durations, peak and integral fluxes of strong (X-class) solar flares from cycles 22--25 are considered with respect to their apparent position on the Sun. It is found that there exists a significant north--south asymmetry in all three parameters, which also varies depending on the phase of the solar cycle (with general predominance of the south). This confirms the results of previous studies. A weaker and less significant east--west asymmetry is found as well, partly supported by literature. A previously undetected centre-to-limb asymmetry is reported (in favour of the limb) in all three parameters. All three asymmetries are enhanced during the solar minimum, which could hint at their connection to the large scale magnetic structuring of the Sun. The prevalence of strong solar flares near the limb at the solar minimum has clear space weather warning implications.

Peripapillary intrachoroidal cavitation (PICC) is a yellow-orange lesion, located at the outer border of the myopic conus. First described as a localized detachment of the retinal pigment epithelium, its intrachoroidal location was later disclosed, justifying its current name. PICC is related to other myopic complications like posterior staphyloma, but its pathogenesis is not clear to date. Although it has been considered a benign condition, most eyes with PICC show visual field defects, leading to diagnostic uncertainty as these deficits resemble those observed in glaucoma. Furthermore, eyes with PICC can develop macular detachment with retinoschisis. Finally, misdiagnosis of PICC as a metastatic choroidal tumor may lead to unnecessary and anxiety-provoking investigation. Advances in optical coherence tomography (OCT) imaging have improved the visualization of ocular structures, contributing to the understanding of PICC. Recently high optic nerve sheaths traction forces during eye movements in highly myopic eyes have been suggested as promoters of PICC, renewing interest around this condition. However, a review of PICC is still lacking. Therefore, we aimed to provide a concise yet comprehensive overview of the current state of the art, focusing on OCT documentation, pathophysiology and potential future perspectives based on biomechanics of the optic nerve.

The PAX8/PPARγ rearrangement, producing the PAX8–PPARγ fusion protein (PPFP), is thought to play an essential role in the oncogenesis of thyroid follicular tumors. To identify PPFP-targeted drug candidates and establish an early standard of care for thyroid tumors, we performed ensemble docking-based compound screening. Specifically, we investigated which pocket structure should be adopted to search for a promising ligand compound for the PPFP; the position of the ligand binding pocket on the PPARγ side of the PPFP is common to that of PPARγ; however, the shape is slightly different between them due to environmental factors. We developed a method for selecting a PPFP structure with a relevant pocket and high prediction accuracy for ligand binding. This method was validated using PPARγ, whose structure and activity values are known for many compounds. Then, we performed docking calculations to PPFP for 97 drug or drug-like compounds with a thiazolidine backbone, which is one of the characteristics of ligands that bind well to PPARγ, registered in the DrugBank database. Furthermore, the binding affinities of promising ligand candidates were estimated more reliably using the molecular mechanics-Poisson–Boltzmann surface area method. Thus, we propose promising drug candidates for the PPFP with a thiazolidine backbone.

In this work, the nearest neighbor distances and Voronoi cell features of the Cu-Ag deposits were analyzed and fitted with Lognormal, Weibull, and Gamma distributions. The nearest neighbor distance distributions of the samples were compared with those of complete spatially random points, showing spatial inhomogenity due to the nucleation exclusion effect. The radial distribution function was calculated, showing both influences from the grain size and the nucleation exclusion effect. Voronoi cells were generated based on the shape of the grains. The size, occupancy, and coordination of the Voronoi cells were examined and fitted. The results show that despite the Cu-Ag deposits seem to be governed by instantaneous nucleation mode, the spatial distribution of the nuclei is more impacted by the nucleation exclusion effect than the Cu-only samples. This behavior is also justified by the grain size distribution generated with Voronoi cell size and occupancy distributions.

Heat-stressed lactating dairy cattle exhibit unique metabolic symptoms; many of which are undoubtedly involved in heat-induced subfertility. Because of its known systemic effects, we hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of insulin and progesterone during heat stress. Multiparous lactating Holstein cows (n=6) were studied during four experimental periods: 1) thermoneutral (TN; d 1-5), 2) TN + hyperinsulinemic-hypoglycemic clamp (d 6-10), 3) heat stress (HS; d 16-20), and 4) HS + euglycemic clamp (d 21-25). Blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Analysis of GABA concentrations from all four treatment periods yielded no differences. In direct comparison to TN concentrations, plasma GABA tended to be decreased during HS (16.57±2.64 vs 13.87±2.28 ng/ml, respectively, P = 0.06). Both milk production and plasma insulin were moderately correlated with plasma GABA (r=0.35, P<0.01; r = -0.32, P<0.01). Plasma progesterone was correlated with plasma GABA concentrations during TN but not HS. These results are the first to indicate that peripheral GABA could be involved in regulating aspects of production and reproduction during heat stress. More research is needed to determine its precise role(s).

Monometallic (Ni, Co, Cu) and bimetallic (Ni-Co, Ni-Cu) 10-20 wt. % metal containing catalysts supported on fly ash zeolite were prepared by post-synthesis impregnation method. The catalysts were characterized by X-ray powder diffraction, N2 physisorption, XPS and H2-TPR methods. Finely dispersed metal oxides and mixed oxides were detected after the decomposition of impregnating salt on the relevant zeolite support. By reduction intermetallic, NiCo and NiCu phases were identified in the bimetallic catalysts. Hydrogeoxygenation of lignocellulosic biomass-derived levulinic acid to γ-valerolactone (GVL) was studied. Bimetallic, 10 wt. % Ni, 10 wt. % Cu or Co containing fly ash zeolite catalyst showed higher catalytic activity than monometallic ones. Their selectivity to GVL reached 70-85 % at 100 % conversion. The reaction proceeds through formation of 4-hydroxy pentanoic acid, as the only intermediate compound.

Our aim was to determine the secondary antibody deficiency profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%; chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG <400 mg/dL in 60.0%, IgA <40 mg/dL in 55.0%, and CD19 <20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 1.9% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (P=0.0001). Most patients progressed to hypo-γ-globulinemia and secondary antibody deficiency after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases, therefore monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement

This study explores the dynamics of liquid holdup in a lab-scale co-current two-phase upflow moving packed bed reactor, specifically examining how superficial gas velocity influences the line average external liquid holdup at a fixed superficial liquid velocity. Utilizing Gamma-ray Densitometry (GRD) for precise measurements, this research extends to determining line average internal porosity within catalyst particles and the overall external bed porosity. Conducted with an air-water system within a bed packed with 3 mm extrudate porous particles, the study presents a novel methodology to calculate liquid holdup, grounded in Beer–Lambert's law. Findings reveal a decrease in liquid holdup corresponding with increased superficial gas velocity across axial and radial locations, with a notable transition from bubbly to pulse flow regime at a critical velocity of 3.8 cm/sec. Additionally, the lower sections of the packed bed exhibited higher external liquid holdup compared to the middle sections at varied gas velocities. The liquid holdup distribution appeared uniform at lower flow rates, whereas higher flow rates favored the middle sections.

Aquaculture is an important source of food for the growing global population. To meet the increasing demand for fish, intensive aquaculture methods are commonly used. However, these methods can lead to stress and disease in fish, which can result in significant economic losses. Gamma-aminobutyric acid (GABA) is a non-protein amino acid that is found in the brain and central nervous system of animals as inhibitory neurotransmitter. It has been shown to have a variety of physiological functions, including stress reduction and immune enhancement. This study investigated the effects of dietary supplementation of GABA on growth, serum biochemistry, innate immunity and disease resistance in juvenile olive flounder (Paralichthys olivaceus) challenged with Edwardsiella tarda under high stocking density. A control diet and three experimental diets were prepared, with 150 mg/kg (GABA150), 200 mg/kg (GABA200), and 250 mg/kg (GABA250) of GABA added to each diet, respectively. The actual GABA content of the experimental diets was analyzed and found to be 63.9 mg/kg (CON), 231.3 mg/kg (GABA150), 291.6 mg/kg (GABA200), and 323.9 mg/kg (GABA250). Each experimental diet was fed to olive flounder with an initial weight of 12.75 g ± 0.3 g in 40 L tanks at two stocking densities: normal density (20 fish/tank) and high density (40 fish/tank). The experiment was conducted in triplicate for each diet and stocking density. The water temperature was maintained at 17.5 ± 1℃ and the salinity at 33 ± 1 ppt. After 8 weeks of feeding trial, growth, feed utilization, whole-body proximate composition, blood analysis, non-specific immune response, and challenge test were performed. There were no significant difference in weight gain and specific growth rate among the GABA concentrations and density × GABA concentration interaction groups. However, the low-density groups showed significantly higher values than the high-density groups (P &lt; 0.05). There was no significant difference in feed efficiency and protein efficiency ratio among all groups. Moreover, there was no significant difference in the whole-body general composition analysis (P &gt; 0.05). In the hematological analysis, there was no significant difference in cortisol in terms of diet and density × GABA concentration interaction, but the high-density experimental group showed a significantly higher value. Blood GABA significantly increased in proportion to the addition amount regardless of the density group (P&lt;0.05). Superoxide dismutase activity in the non-specific immune response showed that the GABA-added experimental group had a significantly higher value than the control group, but there was no significant effect of the density densities or density × GABA concentration interaction (P&lt;0.05). Myeloperoxidase activities in fish fed the GABA200 and GABA250 diets showed significantly higher values, and a density × GABA concentration interaction effect was observed (P&lt;0.05). Lysozyme activity was significantly higher in the GABA150 group than in the CON, GABA200, and GABA250 groups (P &lt; 0.05). After 15 days of challenge test by intraperitoneal injection of Edwardsiella tarda, the cumulative survival rates of the GABA150, GABA200, and GABA250 groups were significantly higher than that of the CON group (P &lt; 0.05). The results suggested that the optimal dietary GABA level for juvenile olive flounder culture is 150 mg/kg, regardless of rearing density, to enhance growth, immune function and disease resistance.

We investigate the impact of incoming nuclear data on the predictions of the neutron star (NS) stripping model for short gamma-ray bursts. The main area to which we pay attention is the NS crust. We show that the uncertain properties of the NS equation of state can significantly influence the stripping time tstr, the main dynamical parameter of the model. Based on the known time delay (tstr≈1.7s) between the peak of the gravitational wave signal GW170817 and the detection of gamma photons from GRB170817A, we obtain new restrictions on the nuclear matter parameters, in particular, the symmetry energy slope parameter: L&lt;114.5MeV. In addition, we study the process of nucleosynthesis in the outer and inner crusts of a low-mass NS. We show that the nucleosynthesis is strongly influenced by both the incoming nuclear data and the equation of state of the NS matter.

Some current systematized reviews of macroalgae are concise and descriptive, but it is important to conduct these of a larger number of taxa to facilitate visualizations of the types of primordial research, relevant methods, and areas of opportunity. The aim was to elaborate the state of the art in the taxonomic knowledge of Dictyota based on a systematized review of the generated information since its original description (1809 to 2023). We conducted a search for names and literature in different databases, followed by a temporal analysis (by century and bidecadal). To date, a total of 313 names have been registered for Dictyota; 108 are accepted names. The largest number of registered taxonomic names (207) was found for the 19th century, derived from large expeditions. Our analysis of literature involved 318 publications, 89 of which corresponded to alpha taxonomy, 187 to beta, and 42 to gamma. We determined that the trend in taxonomic works is integrative in nature because they include other disciplines to explain aspects that go beyond taxonomic description. Our analysis suggests that extensive reviews and monographic approaches are still required to achieve a better understanding of the genus. The effort in integrative taxonomy must be intensified, which allow improve the systematic of Dictyota.

Ultra-low radioactive titanium alloy is a promising material for the manufacture of low-background detectors, which are being developed for experiments in astroparticle physics and neutrino astrophysics. Structural titanium is manufactured on an industrial scale from titanium-sponge. The ultra-low-background titanium-sponge can be produced on an industrial scale with a contamination level of less than 1 mBq/kg of uranium and thorium isotopes. The pathways of contaminants during the industrial production of structural titanium have been analyzed. The measurements have been carried out using two methods: inductively coupled plasma spectroscopy (ICP-MS) and gamma-spectroscopy using high-purity germanium detectors (HPGe). It has been shown that the level of contamination with radioactive impurities does not increase during remelting of titanium-sponge and mechanical processing. We examined titanium-alloys samples obtained at different stages of titanium production, namely, an electrode compaction, a vacuum arc remelting with a consumable electrode (VAR), and a cold rolling of titanium-sheets. It has been found out that all studied samples will be a source of uranium and thorium contamination of the final titanium-alloys. It has been established that the only product allowed obtaining ultra-low-background titanium was the VT1-00 which is manufactured without master alloys addition..

The mechanism of immune activation and de-activation is very important. Host should trigger effective immunity against pathogen infection. And, host cannot trigger immunity against self-antigens that will lead to detrimental autoimmune disorders. Spleen and liver have opposite roles in mediating immune responses. Spleen is the organ involving in immune activation, and liver is the organ involving in immune de-activation. Sympathetic nerve system and parasympathetic nerve system have opposite roles in mediating immune responses. Sympathetic nerve system is involving in pro-inflammatory, and parasympathetic nerve system is involving in anti-inflammatory. ACTH and glucocorticosteroid have opposite roles in mediating immune responses. ACTH is involving in activating adaptive immunity with inhibiting innate immunity, and glucocorticosteroid is involving in activating innate immunity with inhibiting adaptive immunity. The molecular chaperons, heat shock proteins, which are induced by fever, have the vital roles in immune activation. On the contrary, IgD B cells and gamma-delta T cells are causing immune de-activation via the mechanism of clonal anergy. These mechanism can help us the know the work of immunological pathways better for better control of infectious diseases and autoimmune disorders.

Hubble diagrams are examined for SN1a supernovae in the redshift range z = 0.01–1.3 and for gamma ray bursts in the range z = 0.034–8.1. It is shown that in the low redshift range, the Hubble diagram shows an innate equivocality between the ΛCDM and the tired light model. This means that the strong agreement between the z/µ data, calculated with the parameters of the ΛCDM model, and the experimentally measured z/µ values cannot be considered as definite evidence for the expansion hypothesis. The exponential function , which is characteristic of the tired light redshift mechanism, fits the data with similarly high accuracy. Hence, on the premise of low redshift data, a decision for or against either model is completely arbitrary. The Hubble diagram for high redshift gamma ray bursts shows poor agreement with the ΛCDM model, but concurs with the exponential energy decay following from the tired light redshift hypothesis.

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant com-pound, on osteoporotic bone loss remains largely unknown. Here, we show that the administra-tion of LYC to OVX rats reduces body weight gain, improves lipid metabolism and preserves bone quality. In addition, LYC treatment inhibits ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and pro-moting osteogenesis during bone remodeling. Mechanically, LYC may improve bone quality via an increase in the expressions of FoxO1 and Runx2, and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regula-tion of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for os-teoporosis management.

The MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) Florian Goebel telescopes are a system of two Cherenkov telescopes located on the Canary island of La Palma (Spain), at the Roque de Los Muchachos Observatory, and operating in stereo mode since 2009. Their low energy threshold (reaching 15 GeV) allows the study of Active Galactic Nuclei (AGNs) in the very-high-energy gamma ray range with an impressive sensitivity up to the redshift limit of the existing IACT systems. MAGIC has collected many discoveries and comprehensive studies of different kinds of galaxies and their AGNs, also in a multi-wavelength context, expanding the knowledge of our Universe. Here we report the highlights which have been achieved by the MAGIC collaboration since the beginning of the operations.

Recently, Shehata et al. [37] introduced the r+1Rs(B;C; z) matrix function and established some properties. The aim of this study established to devote and derive certain basic properties including analytic properties, recurrence matrix relations, dierential properties, new integral representations, k- Beta transform, Laplace transform, fractional k-Fourier transform, fractional integral properties, the k-Riemann{Liouville and k-Weyl fractional integral and derivative operators an extended version of r+1Rs;k matrix function. We establish its relationships with other well known special matrix functions which have some particular cases in the context of three parametric Mittag-Leer matrix function, k- Konhauser and k-Laguerre matrix polynomials. Finally, some special cases of the established formulas are also discussed.

We show succinctly a natural origin of the beautiful Gamma function in light of the WJ distribution, linking to quite distinct fields.

In this work, we studied light-output properties, efficiency function as well as PSD capability of p-Terphenyl scintillator. The selected solid cylindrical scintillation detector has a size of (45 x 45) mm with PSD properties. Recently presented studies of light-output functions have been measured only for low neutron energies. Our motivation has been to determine more accurate the light output function for p-Terphenyl scintillator over a wider neutron energy range.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulate NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased secretion of various cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.

This study assesses the predictive performance of six machine learning models in forecasting tumor dynamics within three months following Gamma Knife Radiosurgery (GKRS) in 77 brain metastasis (BM) patients. The analysis meticulously evaluates each model before and after hyperparameter tuning, utilizing accuracy, AUC and other metrics derived from confusion matrices. Initial findings highlighted that XGBoost significantly outperformed other models with an accuracy of 0.95 and an AUC of 0.95 before tuning. Post-tuning, the Support Vector Machine (SVM) demonstrated the most substantial improvement, achieving an accuracy of 0.98 and an AUC of 0.98. Conversely, XGBoost showed a decline in performance after tuning, indicating potential overfitting. The study also explores feature importance across models, noting that features like “control at one year”, “age of the patient”, and “beam on time for volume V1 treated”, were consistently influential across various models, albeit their impacts were interpreted differently depending on the model’s underlying mechanics. This comprehensive evaluation not only underscores the importance of model selection and hyperparameter tuning but also highlights the practical implications in medical diagnostic scenarios, where the accuracy of positive predictions can be crucial.

In this paper, we study the effect of decreasing aperture diameter on signal transmission from the scintillator to the PMT. The apertures have been inserted directly between the scintillator and the photomultiplier. Three different aperture diameters have been used over a wide energy range.A newly developed fast digital spectrometer has been utilised for experimental measurement in the radial channel of the VR-1 research reactor. The detector signals with and without inserted apertures have been measured and evaluated. The aim of our research was to determine the effect of the apertures on the spectral quality, energy range and the evaluated physical quantities.