Our previous studies demonstrated that quercetin (Q) could be ingested and metabolized by macrophages and exerted prophylactic immuno-stimulatory activity and therapeutic anti-inflammatory effects on lipopolysaccharide (LPS)-treated macrophages ex vivo. To further clarify its possible anti-inflammatory mechanism, Q was selected to treat mouse peritoneal macrophages that obtained from female BALB/c mice exposed to LPS i.p. for 12 h. Relative gene expression of pro-/anti-inflammatory (TNF-α/IL-10) cytokines and components of inflammation-related intracellular signaling pathways (TLR2, TLR4, NF-κB, JAK2 and STAT3) was analyzed using two-step reverse transcription (RT) and real-time quantitative polymerase chain reaction (qPCR). STAT3 protein phosphorylation was determined using an in-cell ELISA method. As a result, Q and its metabolite quercetin-3-O-β-D-glucuronide (Q3G) decreased TNF-α gene expression amounts and ratios of pro-/anti-inflammatory (TNF-α/IL-10) cytokine gene expressions, but increased IL-10 gene expression amounts in activated inflammatory macrophages, supporting a substantial anti-inflammatory potential of Q and Q3G treatments. However, Q3G had lower effects than those of Q. Importantly, Q inhibited TLR2 gene expression and phosphorylation of STAT3 protein in the inflamed cells. Our results are the first report to suggest that Q inhibits LPS-induced inflammation ex vivo through suppressing TLR2 gene expression and STAT3 protein phosphorylation in activated inflammatory macrophages. Q has potential to further apply for treating inflammation-associated diseases.

Activated carbons can be produced from biomass in a thermal process either in a direct carbonization-activation process or by first carbonizing the biomass and later on activating the biochars into activated carbons. The properties of the ACs are dependent on the type of process used for production. In this study, the properties of activated carbons produced in a one-stage and a two-stage process are considered. Activated carbons were produced by physical activation of two types of starting materials, bio chars produced from spruce and birch chips in a commercial carbonization plant and from the corresponding raw chips. The activated carbons produced were characterized regarding specific surfaces, pore volumes and pore size distributions. The un-activated bio chars had some degree of surface area 190 and 140 m²g^-1 for spruce and birch and pore volumes of 0.067 and 0.092 cm³g^-1. According to the results obtained, two slightly different types of activated carbons are produced depending if a one-stage or a two-stage carbonization and activation process is used. The ACs produced in the one-stage process had higher specific surface areas compared to the ones produced in a two-stage process (761-940 m²g^-1 vs. 540-650 m²g^-1) . In addition, total pore volumes were higher in one-stage process but development of micropores is greater compared to two-stage process. There was no significant difference in total carbon content between one-stage and two-stage process.

Thrombin (factor IIa) and factor Xa (FXa) are key enzymes at the junction of the intrinsic and extrinsic coagulation pathways and are the most attractive pharmacological targets for the development of novel anticoagulants. Twenty non-amidino N²-thiophencarbonyl- and N²-tosyl anthranilamides 1-20 and six amidino N²-thiophencarbonyl- and N²-tosylanthranilamides 21-26 were synthesized and evaluated prothrombin time (PT) and activated partial thromboplastin time (aPTT) using human plasma at concentration 30 μg/mL in vitro. From these results, compounds 5, 9, and 21-23 were selected to study the further antithrombotic activity. The anticoagulant properties of 5, 9, and 21-23 significantly exhibited a concentration-dependent prolongation of in vitro PT and aPTT, in vivo bleeding time, and ex vivo clotting time. These compounds concentration-dependently inhibited the activities of thrombin and FXa and inhibited the generation of thrombin and FXa in human endothelial cells. In addition, data showed that 5, 9, and 21-23 significantly inhibited thrombin catalyzed fibrin polymerization and mouse platelet aggregation and inhibited platelet aggregation induced U46619 in vitro and ex vivo. N-(3'-Amidinophenyl)-2-((thiophen-2''-yl)carbonyl amino)benzamide (21) was most active.

Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation, C57BL/6 mice on a high-fat diet (HFD) were treated with the dual LXRα/β agonist T0901317 (30 mg/kg per day) for 3 weeks. Differentiated 3T3-L1 was used for analysing the effect of T0901317 on glucose uptake.T0901317 reduced fat mass, accompanied by a massive fatty liver and lower adipokine levels in circulation of HFD mice. Increased adipocyte apoptosis and macrophage infiltration were found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonized PPARγ target genes in epididymal fat and PPARγ-PPRE binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in vehicle-treated HFD mice, the insulin tolerance was significantly decreased in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 by T0901317administration. These findings reveal that LXR activation impairs adipose expansion which contributes to decreased insulin sensitivity.

This study explored the feasibility of fluoride removal from simulated semiconductor industry wastewater and its recovery as calcium fluoride using fluidized bed crystallization. The continuous reactor showed best performance (>90% fluoride removal and >95% crystallization efficiency) at a calcium to fluoride ratio of 0.6 within first 40 days of continuous operation. The resulting particle size increased by more than double during this time along with a 36% increase in the seed bed height indicating deposition of CaF2 onto the silica seed. The SEM-EDX analysis showed the size and shape of the crystals formed along with high amount of Ca-F ions presence. The purity of the CaF2 crystals were determined to be 91.1% though ICP-OES analysis. Following the continuous experiment, different process improvement strategies are explored. The addition of excess amount of calcium resulted in an additional 6% fluoride removal, however, compared to this single stage process, a two-stage approach was found to be better strategy to achieve a low effluent fluoride concentration. The fluoride removal reached 94% with this two-stage approach under optimum condition of 4 + 1 h HRT combinations and a [Ca2+]/[F-] ratio of 0.55 and 0.7 for the two reactors, respectively. CFD simulation showed the impact of inlet diameter, bottom-angle shape and width and height ratio of the reactor on mixing inside reactor and possibility of further improvement in reactor performance by optimizing the FBR configuration.

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

Human RAD51 protein (HsRad51)-promoted DNA strand exchange, a crucial step in homologous recombination, is regulated by proteins and calcium ions. The activator protein Swi5-Sfr1 and Ca2+ ions stimulate different reaction steps and induce a perpendicular orientation of DNA bases in the presynaptic complex. To investigate the importance of base orientation in the strand exchange reaction, we examined the Ca2+ concentration dependence of strand exchange activities and structural changes in the presynaptic complex. Our results show that optimal D-loop formation (strand exchange with closed circular DNA) requires Ca2+ concentrations greater than 5 mM, while 1 mM is sufficient for strand exchange between two oligonucleotides. The structural change, which is evidenced by an increase in fluorescence intensity of poly(dεA) (a poly(dA) analog), reaches a plateau at 1 mM Ca2+. Meanwhile, the linear dichroism signal intensity at 260 nm, which is indicative of rigid perpendicular DNA base orientation, requires >2 mM Ca2+ for saturation and thus correlates with the stimulation of D-loop formation. Therefore, Ca2+ exerts two different effects. Thermal stability measurements suggest that HsRad51 binds two Ca2+ ions with KD values of 0.3 mM and 2.5 mM, implying that one step is stimulated by one Ca2+ bond and the other by two Ca2+ bonds. We further discuss the parallels between Mg2+ activation of RecA and Ca2+ activation of HsRad51.

Ferroptosis is an iron-dependent cell death pathway that involves depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of Glutathione peroxidase 4 (GPx4), a key regulator of lipid peroxidation. The events that occur between GPx4 inhibition and the execution of ferroptotic cell death are currently a matter of active research. Previous work has shown that calcium release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels contributes to ferroptosis-induced cell death in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, which do not express RyR channels, to test if calcium release mediated by the inositol 1,4,5-trisphosphate receptor (IP3R) channel plays a role in this process. We show that inhibition of GPx4 by RAS Selective Lethal Compound 3 (RSL3) generated an increase in reactive oxygen species (ROS), increased cytoplasmic and mitochondrial calcium levels, increased lipid peroxidation and caused cell death. The RSL3-induced calcium signals were inhibited by Xestospongin B, an inhibitor of the ER-resident IP3R calcium channel, by decreasing IP3R levels with carbachol and by IP3R1 knock-down. The intracellular calcium chelator BAPTA-AM inhibited RSL3-induced calcium signals, which were not affected by extracellular calcium depletion. We propose that GPx4 inhibition activates IP3R-mediated calcium release in SH-SY5Y cells, leading to increased cytoplasmic and mitochondrial calcium levels, which in turn stimulate the production of ROS and induce lipid peroxidation and ferroptotic cell death in a noxious positive feedback cycle.

Management of calcium and phosphate in biofluids is key to maintaining physiological mineral homeostasis (i.e., appropriate mineralization of hard tissues and an absence of mineral deposition in soft tissues). This review describes and contrasts the ways vertebrates manage calcium phosphate in two biological fluids (breast milk and serum) and illustrates the benefits of mineral sequestration by proteins. In milk, phosphoprotein-sequestered calcium magnesium phosphates provide nutritional support, whereas in serum, protein-sequestered calcium phosphates control transport and delivery of calcium and phosphate to tissues for biological function or excretion. In addition, subsets of sequestered phosphates in serum have been identified as culprits underlying ectopic deposition of calcium phosphates and toxicity.

Applying of blood biopolymers to regulate the phase composition is promising in designing the hydroxyapatite-based hybrid biomaterials with controllable resorbability. Hybrid materials based on hydroxyapatite and platelet-poor plasma (PPP) were formed in conditions of chemical precipi-tation at pH 11, [Ca2+] / [PO43–] ratio 1.67, PPP volume fraction of 6–24%, maturing time of 4–9 days. Mineral component of the materials was represented as 53% hydroxyapatite / 47% amor-phous calcium phosphate after 4 days of maturation, and 100% hydroxyapatite after 9 days of maturation. Varying PPP content from 6% to 24% provided forming of materials with rather de-fined content of amorphous calcium phosphate and biopolymer component, having desired mor-phology ranging from typical apatitic conglomerates to hybrid apatite-biopolymer fibers. Co-precipitated hybrid materials based on hydroxyapatite and PPP are promising for bone regen-eration in osteoplastic and maxillofacial applications.

The review presents the most developed by date hypotheses on the mechanisms of the influence of low-frequency magnetic fields (LFMF) on organisms. Biophysical models that explain the resonance-like responses of biological systems to LFMF with a specific frequency and amplitude are described. Two groups can be distinguished among these models: one considers ions-cofactors of proteins as the primary targets for the LFMF influence, and the other regards the magnetic moments of particles in biomolecules. Attention is paid to the dependence of resonance-like LFMF effects on the cell type. A radical-pair mechanism of the magnetic field's influence on biochemical processes is described with the example of cryptochrome. Conditions for this mechanism's applicability to explain the biological effects of LFMF are given. A model of the influence of LFMF on radical pairs in biochemical oscillators, which can explain the frequency-amplitude efficiency windows of LFMF, is proposed.

This review article deals with the design of bioactive calcium phosphate coatings deposited on metallic substrates to produce bone implants. The bioceramic coating properties are used to create a strong bonding between the bone implants and the surrounding bone tissue. They provide a fast response after implantation and increase the lifespan of the implant in the body environment. The first part of the article describes the different compounds belonging to the calcium phosphate family and their main properties for applications in biomaterials science. The calcium to phosphorus atomic ratio (Ca/P)at. and the solubility (Ks) of these compounds define their behavior in a physiological environment. Hydroxyapatite is the gold standard among calcium phosphate materials, but other chemical compositions/stoichiometries have also been studied for their interesting properties. The second part reviews the most usual deposition processes to produce bioactive calcium phosphate coatings for bone implant applications. Plasma spraying is the main industrial process, but magnetron sputtering, pulsed laser deposition, electrospray deposition, electrophoretic deposition, and electrodeposition are also widely studied in academic and industrial research. The last part describes the main physicochemical properties of calcium phosphate coatings and their impact on the bioactivity of bone implants in a physiological environment.

Ecological ternary cements (ECP) were perpared with powders of phosphogypsum (PG), fly ash (FA) and portland cement (PC). The evolution mechanism of the hydration product structure was characterized through macro and micro experiments.The thermodynamic characteristics of solid phase, solid solution phase and aqueous solution in process of hydration about phosphogypsum-fly ash-cement ternary cementitious system were studied based on the Gibbs-free-energy C-S-H thermodynamic model and GEM-Selektor software, and compared with experimental results. The results show that in the hydration reaction the thermodynamic interaction between mineral single-phase and hydration products plays an important role in the spatio-temporal distribution of ions in the cementitious system. The values of CaO、SiO2Hand H2Ohyd gradually increased with the increase of Ca/Si ratio, while the values of CaOext and H2OOH showed a positive proportional relationship, and the values of SiO2H and SiO2 showed an inverse proportional relationship. GEM-Selektor is accurate in the simulation calculation of the total amount of AFt and AFm mineral phases which quantitatively analysis the correlation between C-S-H gels formation and C3S with complex decomposition ion groups.

Context: Persea Americana is reported to have medicinal value. Calcium Carbide (CaC2), a fruit-ripening agent, has been shown to be toxic to body organs. Objective: To determine the effect of avocado seed extract (ASE) on CaC2-induced hepatotoxicity in rats. Methodology: Four experimental groups, each of 5 adult wistar rats were fed respectively with normal diets (group A); 250mg/kg ASE (group B); 100mg/kg CaC2 (group C); combination of 100mg/kg CaC2 and 250mg/kg ASE – group D. Changes in the rats’ behaviours, body weights, and liver function were assessed over 21 days. Data were analyzed using SPSS. The cumulated rat weights, rat liver weights and serum liver enzyme levels for groups B, C, and D rats were compared to group A. Results: Abnormal behavior was most observed in group C rats. Rats in group A showed a significant increase in weight before and three weeks following administration of feeds while rats in groups B, C, and D showed significant decrease in weight – more marked in group C rats. Only the mean liver weights of rats in group C showed significant decrease compared to that in group A, p = 0.001. Similarly, only the cumulated liver enzyme levels of rats in group C demonstrated significant increase when compared to group A rats - indicating hepatotoxicity. Conclusion In this study, hepatotoxicity occurred in CaC2-administered rats. However, the combination of CaC2 and ASE showed no liver toxicity indicating a mitigating effect of ASE to CaC2-induced hepatotoxicity.

Reducing the amount of precipitation in summer in the Chernozems area alters soil organic matter (SOM). To compensate for the lack of moisture, farmers are introducing new agricultural technologies such as no-till cultivation. In turn, no-till practices influence the composition of SOM. We examined the impacts of the rise of aridity and no-till technology on the chemical composition of bioavailable and recalcitrant pools of OM. The properties of SOM were assessed using double-shot pyrolysis with gas chromatography/mass spectrometry (GC/MS). The thermolabile substances that are volatilised in the first stage of pyrolysis (300°C) are considered the bioavailable pool. Accordingly, substances are obtained in the second pyrolysis stage (500°C) were attributed to the recalcitrant pool. Identified in both steps of pyrolysis, products were assigned to different chemical groups (lignin-derivative, polysaccharide-fragments, indoles, etc.) and relative abundances were calculated. In work for the separation of substances, a polar column was used for chromatography of the thermolabile fraction. With an increase in aridity in Сhernozems, the content in the bioavailable pool of polysaccharide fragments decreased and the proportion of indoles increased. In the recalcitrant pool, the abundance of six-membered rings with nitrogen and aromatic compounds decreases at the same time the contents of unsubstituted and O-substituted acyclic compounds as well as pyridine increases. The influence of the NT was more noticeable in the recalcitrant OM. The NT practice promotes biological activity and to rich in nitrogen compounds the bioavailable OM; this process contributes to the accumulation of carbon in the recalcitrant OM.

Aquatic animals have unique physiological mechanisms to absorb and retain minerals from their diets and water. Research and development in the area of mineral nutrition of farmed fish and crustaceans have been relatively slow and major gaps exist in the knowledge of trace element requirements, physiological functions and bioavailability from feed ingredients. Quantitative dietary requirements have been reported for three macroelements (calcium, phosphorus and magnesium) and six trace minerals (zinc, iron, copper, manganese, iodine and selenium) for selected fish species. Mineral deficiency signs in fish include reduced bone mineralization, anorexia, lens cataracts (zinc), skeletal deformities (phosphorus, magnesium, zinc), fin erosion (copper, zinc), nephrocalcinosis (magnesium deficiency, selenium toxicity), thyroid hyperplasia (iodine), muscular dystrophy (selenium) and hypochromic microcytic anaemia (iron). An excessive intake of minerals from either diet or gill uptake causes toxicity and therefore a fine balance between mineral deficiency and toxicity is vital for aquatic organisms to maintain their homeostasis either through increased absorption or excretion. Release of minerals from uneaten or undigested feed and from urinary excretion can cause eutrophication of natural waters, which requires additional consideration in feed formulation. The current knowledge in mineral nutrition of fish is briefly reviewed.

Novel molecular pinball machines of the plasma membrane control cytosolic Ca²⁺ levels that regulate plant metabolism. [https://youtu.be/zABg7LiBk88] Essential components involve: 1. an auxin-activated proton pump; 2. arabinogalactan glycoproteins (AGPs); 3. Ca²⁺ channels; 4. auxin-efflux “PIN” proteins. Typical pinball machines release pinballs that trigger various sound and visual effects. However, in plants “proton pinballs” eject Ca²⁺ bound by paired glucuronic acid residues of numerous glycomodules in periplasmic AGP-Ca²⁺. Freed Ca²⁺ ions flow down the electrostatic gradient through open Ca²⁺ channels into the cytosol thus activating numerous Ca²⁺-dependent activities.Clearly cytosolic Ca²⁺ levels depend on activity of the proton pump, the state of Ca²⁺ channels and size of the periplasmic AGP-Ca²⁺ capacitor: Proton pump activation is a major regulatory focal point tightly controlled by the supply of auxin: auxin efflux carriers conveniently known as “PIN” proteins [null mutants are pin-shaped!] pump auxin from cell to cell. Mechanosensitive Ca²⁺ channels and their activation by reactive oxygen species (ROS) are yet another factor regulating cytosolic Ca²⁺.Cell expansion also triggers proton pump/pinball activity by mechanotransduction of wall stress via Hechtian adhesion thus forming a Hechtian oscillator that underlies cycles of wall plasticity and oscillatory growth.Finally, Ca²⁺ homeostasis of plants depends on cell surface external storage as source of dynamic Ca²⁺, unlike the internal ER storage source of animals where the added regulatory complexities ranging from vitamin D to parathormone contrast with the elegant simplicity of plant life. This paper summarises a sixty year Odyssey.

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. To clarify the effect of cAMP and the role of Epac2A in intracellular calcium signals and intercellular coupling, we performed functional multicellular calcium imaging in beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Increased cAMP evoked calcium signals in otherwise sub-stimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and increased cAMP increased the active time via a large increase in oscillation frequency and small decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of increased cAMP in preventing a decline in beta cell functional connectivity with time. Finally, increased cAMP prolonged beta cell activity during deactivation in an Epac2A-independent manner.

Calcium carbonate cements have been synthesized by mixing amorphous calcium carbonate and vaterite powders with water to form a cement paste and study how mechanical strength is created during the setting reaction. In-situ XRD was used to monitor the transformation of ACC and vaterite phases into calcite and a rotational rheometer was used to monitor the strength evolution. There are two characteristic time scales of the strengthening of the cement paste. The short timescale of the order 1 hour is controlled by smoothening of the vaterite grains, allowing closer and therefore adhesive contacts between the grains. The long timescale of the order 10-50 hours is controlled by the phase transformation of vaterite into calcite. This transformation is, unlike in previous studies using stirred reactors, found to be mainly controlled by diffusion in the liquid phase. The evolution of shear strength with solid volume fraction is best explained by a fractal model of the paste structure.

Matrix Metaloproteinase-2 (MMP-2) is an extracellular Zn²⁺ protease specific to type I and IV collagens. Its expression is associated with several inflammatory, degenerative, and malignant diseases. Conformational properties, domain movements, and interactions between MMP-2 and its associated metal ions were characterized using a 1.0 µs molecular dynamics simulation. Dihedral principle component analysis revealed 10 families of conformations with the greatest degree of variability occurring in the link region connecting the catalytic and hemopexin domains. Dynamics cross correlation analysis indicated domain movements corresponding to opening and closing of the hemopexin domain in relation to the fibronectin and catalytic domains facilitated by the link region. Interaction energies were calculated using the MMPBSA-interaction entropy analysis method and revealed strong binding energies for the catalytic Zn²⁺ ion 1, Ca²⁺ ion 1, and Ca²⁺ ion 3 with significant conformational stability at the binding sites of Zn²⁺ ion 1 and Ca²⁺ ion 1. Ca²⁺ ion 2 diffuses freely away from its crystallographically defined binding site. Zn²⁺ ion 2 plays a minor role in conformational stability of the catalytic domain while Ca²⁺ ion 3 is strongly attracted to the highly electronegative sidechains of the Asp residues around the central β-sheet core of the hemopexin domain.

Hypertension is a common and growing medical problem that leads to enormous cardiovascular and kidney disease worldwide. While many drugs exist to treat hypertension, there is large individual variation in how a given individual responds to different agents, which contributes to dismal rates of hypertension control. While demographic factors predict which drugs may work better in certain individuals, a great degree of this variation has a genetic basis. In recent years, genome wide association studies have begun to identify specific gene variants that predict drug response to particular agents. This review identifies the major genetic variants influencing antihypertensive response that have emerged from this growing body of work. For novel genetic variants without a previously known biologic basis in blood pressure, it is crucial to validate initial findings in subsequent studies. This information may eventually lead to a more personalized approach to hypertension management that will improve blood pressure control and patient outcomes. The integration of this large amount of data and its real world application will be highly challenging, but strategies to accomplish this are discussed.

There have been a great number of investigations about the influence of weak magnetic fields on biological systems, such as isolated cells and whole organisms. This is also a subject of considerable medical concern since old epidemiologic observations have indicated a possible tumorigenic effect of these fields. Their mechanism of action, however, is not firmly established. A large number of biological effects of electromagnetic fields have been attributed either to the production of reactive oxygen species (ROS) or to the entrance Ca²⁺ in the cell. A new biochemical pathway is proposed that covers these two possibilities: the primary effect of the magnetic field would be by the mechanism of radical pairs resulting in the production of ROS; these could activate the ion channels TRPM2 producing cellular inflow of Ca²⁺, which would induce the calcium dependent effects. Thus, a large number of biological effects observed up to the present could be explained.

Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the action potential and contraction of the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes via cooperative mechanisms of mechano-calcium-electric feedback are essential to produce the differences in Ca²⁺ transients and contraction profiles and may further enhance transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in afterload than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.

Spent coffee grounds (SCG) have great potential as a useful, value-added biological material. In this context, activated carbon (AC) was prepared from SCG by an activation process using H3PO4 at 600°C in air and used as an adsorbent for the azo dye AO7, a model molecule for dye colorants found in textile industry effluents. X-ray diffraction, SEM and BET revealed that the AC was predominantly amorphous, consisting of a powder of 20-100 µm particles with mesopores averaging 5.5 nm in pore size. Adsorption kinetics followed a pseudo-second-order law, while the Langmuir model best fitted experimental isotherm data (maximum capacity of 119.5 mg AO7 per AC g). Thermodynamic parameters revealed that adsorption was endothermic and spontaneous. All the characterizations indicated that adsorption occurred by physisorption via mainly - interactions. The best experimental removal efficiency optimized by means of a Box-Behnken design and response surface methodology was 98% for an initial AO7 concentration of 20 mg.L-1 at pH 7.5 with a dose of 0.285 g.L-1 of AC and a contact time of 40 min. These results clearly show that activated carbon prepared from SCG can be a useful material for efficiently removing organic matter from aqueous solutions.

Adeno-associated viruses (AAVs) have been used for liver gene therapy. Hemgenix and Roctavian are AAV-based treatments for hemophilia B and A, respectively. They cost $3 million and $2.8 million per dose, respectively. While AAV vectors may eventually be cheaper to mass produce, a bacteria-based DNA delivery system might be much cheaper for patients. Also, “bactofection” would allow for the delivery of much larger DNA packages. Such a bacterial system may now be possible, and a prototype for the liver could possibly be developed immediately.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents. Ethyl acetate fraction(EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-, and di-glycoside of each aglycone. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Flexible energy storage devices, such as solid-state supercapacitors, are becoming increasingly attractive due to their characteristics of high electrochemical performance, reliability, light weight, flexibility, absence of electrolyte leakage, high power density, and long lifetime. For the optimization of the solid-state symmetrical supercapacitor proposed in this work, it was employed in sodium and lithium form Aquivion electrolyte membrane, which serves as the separator and electrolyte. As electrode materials, carbon xerogels, synthesized by microwave-assisted sol-gel methodology, with designed and controlled properties were obtained. Commercial activated carbon (YP-50F, 'Kuraray Europe' GmbH) was used for comparison. Specifically, the developed solid-state symmetrical supercapacitors deliver sufficient high specific capacitances of 105−110 F g−1 at 0.2 A g−1, along with an energy density of 4.5 Wh kg−1 at 300 W kg−1, and in a voltage window of 0-1.2 V in an aqueous environments, also demonstrating excellent cycling stability up to 10,000 charge/discharge cycles. These results can demonstrate the potential applications of carbon xerogel as an active electrode material and cation exchange membrane as the electrolyte in the development of solid-state supercapacitor devices

Cement paste backfill (CPB) is an effective waste management method allowing the storage of fine process tailings into underground mined-out voids. CPB performance generally depends on the sulfur content of the tailings and the type of binder. In recent years, there has been an in-creasing trend on the use of alkali-activated slag (AAS) to improve the performance properties of CPB. This study focuses on the ultrasonic and microstructural investigation of the effect of slag fineness on the mechanical, geochemical and durability properties of CPB made up of AAS (AAS-CPB) over 360 days. In this scope, AAS-CPB samples were prepared at three different fineness (3100-4650-6300 cm2/g). Fineness of slag significantly improved the early age- and long-term strength (~2.3 fold and ~6.6 fold, respectively) of CPB. However, further increase of slag fineness may have adverse effect on CPB microstructure and strength in the long term. Ultrasonic pulse velocity monitoring displayed very high relation with the strength evolution and durability assessment of CPB. Slag fineness at a degree was seen to improve the pore structure evolution of AAS-CPB. Microstructural studies are in good agreement with the geochemical and durability behavior of AAS-CPB. Microstructural and ultrasonic findings suggest that while slag fineness enhances the mechanical properties of AAS-CPB, further increase of the fineness of slag has no additional important technical advantages.

In the last decades, studies on the inflammatory signaling pathways in multiple pathological contexts revealed new targets for novel therapies. Among the family of G-protein-coupled Proteases Activated Receptors, PAR2 was identified as a driver of the inflammatory cascade in many pathologies, ranging from autoimmune disease to cancer metastasis. For this reason, many efforts have been focused on the development of potential antagonists of PAR2 activity. This work focuses on a small molecule, 1-Piperidine Propionic Acid (1-PPA), previously described to be active against inflammatory processes, but whose target is still unknown. Stabilization effects observed by cellular thermal shift assay coupled to in-silico investigations, including molecular docking and Molecular Dynamics simulations, suggested that 1-PPA binds PAR2 in an allosteric pocket of the receptor inactive conformation. In addition, this compound was found able to inhibit platelet aggregation, a process mediated by PAR family members, including PAR2. Since the allosteric pocket binding 1-PPA is highly conserved in all the members of the PAR family, the evidence reported here suggests that 1-PPA could represent a promising new small molecule targeting PARs with antagonistic activity.

(1) Background: Angiotensin II, a major culprit in cardiovascular disease, activates mediators that are also involved in pathological cardiac remodelling. We aimed at investigating the effects of two of them: aldosterone (Ald) and transforming growth factor-beta-1 (TGF-β1 ), on cardiac remodelling in an in vivo model. (2) Methods: Six-week-old male wild-type (WT) and TGF-β1 -overexpressing transgenic (TGF-β1 -TG) mice were infused with subhypertensive doses of Ald for 2 weeks, and/or treated orally with eplerenone from postnatal day 21. Heart’s ventricles were examined: by morphometry, immunoblotting to assess intracellular signalling pathways, RT qPCR to determine hypertrophy and fibrosis marker genes. (3) Results: TGF-β1 -TG mice spontaneously developed cardiac hypertrophy and interstitial fibrosis, exhibited higher baseline phosphorylation of p44/42 and p38 kinases, fibronectin and ANP mRNA expression. Ald induced a comparable increase in ventricular heart weight-to-body-weight ratio and cardiomyocyte diameter in both strains, but less pronounced increase in interstitial fibrosis in transgenic compared to WT mice (23.6% vs 80.9%, p<0.005). Ald increased phosphorylation of p44/42 and p38 in WT but not TGF-β1 -TG mice. While eplerenone-enriched chow partially prevented Ald-induced cardiac hypertrophy in both genotypes and interstitial fibrosis in WT controls, it completely protected from additional fibrosis in transgenic mice. (4) Conclusions: Ald appears to induce cardiac hypertrophy independently of TGF-β1 , while in case of fibrosis downstream signalling pathways of these two factors probably converge

Alkali-activated materials are alternative building binders, where secondary raw materials are processed. Possibility to use landfilled waste materials in their preparation, increases their potential application in construction practice, and therefore they are subject to extensive research, especially in recent years. This paper briefly summarizes interesting results of an experiment aimed at verifying the possibility of applying cement by-pass dust (CBPD) in the preparation of alkali-activated materials. The research work was focused on the possibilities of using these wastes for the preparation of small elements of garden architecture. The paper briefly evaluates in particular the results of X-ray diffraction, which were subjected to three types of binder pastes differing in the amount of used activator. In the experiment, a mixture of blast furnace granulated slag, fly ash and cement by-pass dust was alkali activated with sodium metasilicate.

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.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we performed a mini-meta analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. Mini meta analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling which may be altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we explored whether PAK signaling should be targeted via chemoprevention to reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Systematic literature review provided the effect of anti-diabetic drugs on PAK signaling. Review of clinical studies revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-dependent diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM involves Wnt and G-protein signaling which is altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone is promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

High temperature (HT) geothermal wells can provide green power 24h a day 7 days a week. Harsh environmental and operational conditions, long-term durability requirements of such wells require special cementitious composites for well construction. This paper reports a comprehensive assessment of geothermal cement composites in cyclic pressure function laboratory tests, field exposures in an HT geothermal well (300-350oC) as well as a numerical model to complement the experimental results. Performances of calcium-aluminate-cement (CAC)-based composites and calcium free cement were compared against reference Ordinary Portland Cement (OPC)/silica blend. The stability and degradation of the tested materials was characterized by crystalline composition, thermo-gravimetric, and elemental analyses, morphological studies, water-fillable porosity, and mechanical properties measurements. All CAC-based formulations outperformed the reference blend both in the function and exposure tests. The reference OPC/silica lost its mechanical properties during the 9-month well exposure through extensive HT carbonation, while properties of the CAC-based blends improved over that period. The Modified Cam-Clay (MCC) plasticity parameters of several HT cement formulations were extracted from triaxial and Brazilian tests and verified against the experimental results of function cyclic tests. These parameters can be used in well integrity models to predict field-scale behavior of the cement sheath under geothermal well conditions.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

The regenerated magnesia-calcium brick samples that had added 0, 1.5, 3.0 wt.% aluminium oxide (Al2O3) were prepared by using spent magnesia-calcium bricks, fused magnesia and Al2O3 powder additive as the main raw materials. The phases, microstructures, room temperature and hot flexural strength, resistance to cement clinker corrosion and strength of coating adherence were investigated respectively. It indicated that the addition of Al2O3 increased mainly resulting in the content of tetracalcium aluminoferrite (C4AF) and tricalcium aluminate (C3A) increased in the regenerate samples. The bulk density, the room temperature flexural strength and the strength of coating adherence all increased, while the hot flexural strength and corrosion resistance both deteriorated along with the increase of Al2O3 addition. It was because that on the one hand the low melting point phases of C4AF and C3A improved the sinterability of the regenerated samples during the burning stage, on the other hand they melted or existed in liquid phase during the experimental temperature (1573 K and 1823 K) which degraded hot flexural strength and corrosion resistance, and enhanced the strength of coating adherence as the wettability of the liquid phase. The content of Al2O3 in the regenerated magnesia-calcium brick should not be higher than 1.1 wt.%, considering its room and high-temperature performances for cement rotary kiln.

The role of calcium ions (Ca2+) is extensively documented and comprehensively understood in eukaryotic organisms. Nevertheless, emerging insights, primarily derived from studies on human pathogenic bacteria, suggest that this ion also holds a pivotal role in prokaryotes. In this review, our primary focus will be on unraveling the intricate Ca2+ toolkit within prokaryotic organisms, with particular emphasis on its implications in plant growth promoting rhizobacteria (PGPR). To pinpoint and identify homologues of Ca2+ channels, pumps, exchangers, and Calcium-Binding Proteins (CaBPs) we undertook an in silico exploration in the genomes of four distinct PGPR strains using as query prokaryotic sequences that were experimentally confirmed to play a role in regulating intracellular calcium concentration ([Ca2+]i) or sensing and transducing this essential cation. These investigations were conducted in Pseudomonas chlororaphis subsp. aurantiaca SMMP3, P. donghuensis SVBP6, Pseudomonas sp. BP01, and Methylobacterium sp. 2A. which have been isolated and characterized within our research laboratories. We also present experimental data to evaluate the influence of exogenous Ca2+ concentrations ([Ca2+]ex) on the growth dynamics of these isolated strains

Due to the severe environmental impact of the CO2 emissions associated with the production of Ordinary Portland Cement (OPC) and the increasing demand for this commodity material, the development of alternative products has become a global concern. One alternative to OPC, or alitic-based clinkers, are amorphous-wollastonitic low calcium hydraulic binders (AWLCs). This new class of hydraulic binders, described in the literature for the first time in 2015, may significantly reduce the CO2 emissions associated with its production, resulting from its lower calcium content, but also from the fact that its production technology can be fully electrified. In this paper it is provided a state-of-the-art review, providing a comprehensive description on the latest research, summarizing both the physico-chemical and mechanical characteristics for this type of hydraulic binders, as well as possible routes for its production at an industrial scale.

Aerobic exercise training (AET) has been used in the management of heart disease. AET may, totally or partially, restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis. The objective of this study was to evaluate the effects of AET on calcium handling and cardiac function in rats with heart failure due to aortic stenosis. Wistar rats were distributed into two groups: control (Sham; n= 61) and aortic stenosis (AoS; n= 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. Echocardiogram, isolated papillary muscle, and isolated cardiomyocyte analyzed cardiac function. During isolated papillary muscle assay and isolated cardimyocyte was evaluated Ca2+. The expression of regulatory proteins of diastolic Ca2+ was analyzed via Western Blot. AET attenuated the diastolic dysfunction and benefited the systolic function. AoS-ET animals presented better response to post-rest contraction, and SERCA2a and L-type Ca2+ channels blocked than the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented alteration in the protein expression of the SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity, improved the cellular Ca2+ influx mechanism, and increased myofilament responsiveness to Ca2+, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with aortic stenosis and heart failure.

Transient Receptor Potential Vanilloid 4 (TRPV4) channel is a non-selective cation channel, mostly permeable to calcium (Ca2+), which participates to intracellular Ca2+ handling in cardiac cells. It is widely expressed through the body and is activated by a large spectrum of physico-chemical stimuli, conferring it a role in a variety of sensorial and physiological functions. With-in the cardiovascular system, TRPV4 expression was reported in cardiomyocytes, endothelial cells (ECs) and smooth muscle cells (SMCs) where it modulates mitochondrial activity, Ca2+ ho-meostasis, cardiomyocytes electrical activity and contractility, cardiac embryonic development, fibroblast proliferation but also vascular permeability, dilatation and constriction. On the other hand, TRPV4 channels participate in several cardiac pathological processes such as development of cardiac fibrosis, hypertrophy, ischemia-reperfusion injuries, heart failure, myocardial infarc-tion, and arrhythmia. In this manuscript, we provide an overview of TRPV4 channel implica-tions in cardiac physiology and discuss the potential of TRPV4 channel as therapeutic target against cardiovascular diseases.

Several observational studies have indicated the potential associations between calcium, vitamin D(Vit-D) and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subjected to residual confounding factors and reverse causation. Therefore, we aim to explore the bidirectional causal effects between serum calcium, Vit-D, PTH and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs). The results of the inverse-variance-weighted method did not re-veal any causal relationship shared between genetically predisposed calcium (OR = 0.92, 95% CI: 0.80-1.06, P = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83-1.19, P = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a de-creased level of PTH (beta: -0.19, 95%CI: -0.34 to -0.04, P = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms by which IBS affects serum PTH need to be further investigated.

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play a significant role in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. Here we pro-vide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. The role of magnesium ions in angiogene-sis, an important process associated with osteogenesis, is considered. Finally, the biological properties of magnesium phosphates for bone regeneration are summarized. They show promis-ing results in terms of use as bone replacement material.

The combination of calcium phosphates (CaP) with bioactive glasses (BG) has received an increased interest in the field of bone tissue engineering. In the present work, biphasic calcium phosphates (BCP) obtained by hydrothermal transformation (HT) of cuttlefish bone (CB) were coated with a Sr-, Mg- and Zn-doped sol-gel derived BG. The scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The initial CB structure was maintained after HT and the scaffold functionalization did not jeopardize the internal structure. The results of in vitro bio-mineralization after immersing the BG coated scaffolds in simulated body fluid (SBF) showed extensive formation of bone-like apatite onto the surface of the scaffolds. Overall, the functionalized CB derived BCP scaffolds revealed promising properties for their use in bone tissue engineering field.

The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

The increasing use of energy resources recovered from the subsurface environments and the resulting carbon imbalance in the environment has motivated the need to develop thermodynamically downhill pathways to convert and store CO₂ as water insoluble calcium or magnesium carbonates. While previous studies extensively explored aqueous routes to produce calcium and magnesium carbonates from CO₂, there has been a limited scientific understanding of the phase evolution and textural changes during the direct gas-solid conversion routes to produce calcium carbonate from calcium hydroxide, which is one of the abundant constituents of alkaline industrial residues. With increasing interest in developing integrated pathways for capturing, converting and storing CO₂ from dilute flue gases, understanding the compositions of the product phases as they evolve is essential for evaluating the efficacy of a given processing route. Therefore, in this study, we investigate the phase evolution and the corresponding textural changes as calcium hydroxide is converted to calcium carbonate under the continuous flow of CO₂ at an ambient pressure of 1 atm and on heating continuously from 30 °C to 500 °C using in-operando wide angle X-ray scattering (WAXS), small angle X-ray scattering (SAXS), and ultra-small angle X-ray scattering (USAXS) measurements.

Fiber-rich green river Aonori alga is mass-cultivated in Japan; it has been reported to reduce inflammation and improve metabolic health in humans. Peroxisome proliferation-activated receptor (PPARs) are associated with metabolic disorders such as obesity and type 2 diabetes (T2DM). We evaluated the effects of supplementation with NBF2, a formula made of algal and junos citrus biomaterials, on metabolic markers in obese and diabetic rats. An experimental study was performed using 18 obese and hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats randomly assigned to high dose NBF2 (20mg/kg; n=6), low dose (10mg/kg; n=6) NBF2 drink for 6 weeks, whereas OLETF control rats received similar amount of tap water (vehicle; n=6). LETO rats were used as normal controls (n=8). Biospecimens were taken for ELISA and real-time PCR. Both high dose and low dose NBF2 increased brown adipose tissue (BAT) mass and adiponectin (APN), improved insulin sensitivity, and significantly improved glycemic and lipid (TG, LDL-c) profiles in NBF2-supplemented OLETF rats after a 6-week supplementation with NBF2 (vs. OLETF controls), as well as LDL-c (p<0.05). During the glucose tolerance test (OGTT), both NBF2 groups and LETO rats had normal glycemia by 90-minute time-point (vs. OLETF controls; p<0.01). Furthermore, intake of NBF2 up-regulated PPARa/g-mRNA and Sirt2-mRNA gene expressions in BAT, and improved blood pressure profile in OLETF rats. Findings from this research suggest that intake of NBF2 formula induces dual PPAR-a/g and Sirt2 activation, providing insights on beneficial prophylactic and therapeutic effects of this NB2 formula on dyslipidemia and hyperglycemia in T2DM.

The rapid development of electric vehicles, unmanned aerial vehicles, and wearable electronic devices has led to a high interest in research related to the synthesis of graphene with a high specific surface area for energy applications. However, the problem of graphene synthesis scalability, as well as the lengthy duration and high energy intensity of the activation processes of carbon materials, are significant disadvantages. In this study, a reactor was developed for the green, simple, and scalable electrochemical synthesis of graphene oxide with a low oxygen content of 14.1 %. The resulting material was activated using a fast joule heating method. The processing of mildly oxidized graphene with a high–energy short electrical pulse (32 ms) made it possible to obtain a graphene–based porous carbon material with a specific surface area of up to 1984.5 m2/g. The low energy intensity, simplicity, and use of environmentally friendly chemicals render the proposed method scalable.

This study aimed to elucidate the antibacterial efficacy and unique chemical compositions generated from plasma-activated water (PAW) when utilized a novel vaginal cleansing device. We conducted an analysis of antibacterial activity against probiotics and several chemical compositions including ions under various operational parameters of PAW, including electrical power (12 and 24 V), treatment duration (1, 10, and 20 min), and stay duration (immediate, 30 and 60 min). Our findings revealed that as treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl−concentrations decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW exhibited no antibacterial effects against a type of probiotic, Lactobacillus reuteri that produces lactic acid for vaginal health. This result demonstrated the ability of the vaginal cleaning device to generate ions, primarily HOCl and some cations (Ca2+ and Mg2+), thereby providing vaginal mucosa protecting and cleansing effects with the vaginal environment.

Natural killer cells are associated with the pathogenesis of ulcerative colitis (UC), but their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated genes (ANAGs) in UC. Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, 92 differentially expressed genes (DEGs) were screened out by the “Batch correction” and “Robust rank aggregation” (RRA) methods. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT, which revealed a higher abundance of activated NK cells in noninflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2) and establish an activated NK-associated gene score (ANAG score). The ANAG score demonstrated excellent diagnostic value and was validated in three external datasets. The expression of the 4 key ANAGs was validated in UC patients and healthy controls (HC) samples. Through scRNA-seq data analysis, higher expression levels of SELP, TIMP1, MMP7, and ABCG2 were observed in post-capillary venules, inflammatory fibroblasts, enterocytes, and immature enterocytes. The cell scores based on the ANAGs showed enrichment in endothelial cells and fibroblasts. In conclusion, we established and validated an ANAG score with the ability to precisely diagnose UC. The 4 key ANAGs have the potential to serve as therapeutic targets in UC.

The goal of this work is to develop a sustainable value chain of carbonaceous adsorbents that can be produced from the solid fibrous digestate (SFD) of biogas plants and further applied in integrated desulphurisation-upgrading (CO2/CH4 separation) processes of biogas to yield high purity biomethane. On this purpose, physical and chemical activation of the SFD derived biochar was optimised to afford micro-mesoporous activated carbons (ACs) of high BET surface area (590-2300 m2g−1) and enhanced pore volume (0.57-1.0 cm3g−1). Gas breakthrough experiments from fixed bed columns of the obtained ACs, using real biogas mixture as feedstock, unveiled that the physical and chemical activation conclude to different types of ACs which are sufficient for biogas upgrade and biogas desulphurisation respectively. Performing breakthrough experiments at three temperatures close to ambient it was possible to define the optimum conditions for enhanced H2S/CO2 separation. It was also concluded that the H2S adsorption capacity is significantly affected by restriction to gas diffusion. Hence, the best performance was obtained at 50 oC and the maximum observed in the H2S adsorption capacity vs the temperature is attributed to the counterbalance between adsorption and diffusion processes.

In this paper, mesoporous electrodes consisted of Sb-doped SnO2 deposited onto Ti plates controlled corroded under acidic medium were synthesized by spin-coating method, and morpho structurally characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The electrodes were electrochemical testing in the degradation/mineralization by electrooxidation (EO) of doxorubicin (DOX) as single-component and multi-component together with capecitabine (CCB)-from cytostatic class and humic acid (HA)-from natural organic matter (NOM) class in the absence/the presence of activated carbon (AC) as particulate electrode. The best mineralization efficiency of 67 % was achieved for DOX mineralization using Sb-doped SnO2 deposited onto Ti plate controlled corroded with oxalic acid in electrooxidation process. The presence of AC within the electrolysis process generated a synergy effect of 52.75 % for TOC parameter removal, which is in accordance and quite better than the result reported in the literature. The aspects related to the complex mechanism of DOX degradation and mineralization are discussed. The superiority of AC assisted electrooxidation, as electrochemical filtering (EF), was proved considering simultaneous degradation and mineralization of mixture of doxorubicin, capecitabine and humic acid.

This work aims to investigate the influence of reaction time and catalyst-to-residual fat ratio by catalytic upgrading from pyrolysis vapors of residual fat at 400 °C and 1.0 atmosphere, on the yields of reaction products, physicochemical properties (density, kinematic viscosity, and acid value) and chemical composition of bio-oils, over a catalyst fixed bed reactor of activated carbon pellets impregnated with 10.0 M NaOH, in semi pilot scale. The experiments were carried out at 400 °C and 1.0 atmosphere, using a process schema consisting of a thermal cracking reactor of 2.0 L coupled to a catalyst fixed bed reactor of 53 mL, without catalyst and using 5.0, 7.5, and 10.0% (wt.) activated carbon pellets impregnated with 10.0 M NaOH, in batch mode. Samples of liquid phase products were withdrawn during the course of reaction at 50, 60, 70, 80, 90, 100 and 120 minutes in order to investigate the process kinetics. The physicochemical properties (density, kinematic viscosity, and acid value) of bio-oils were determined by official methods. The chemical composition of bio-oils determined by GC-MS. The thermal catalytic cracking of residual fat show bio-oils yields from 55.55 to 30.22 (wt.%), aqueous phase yields between 2.83 and 3.19 (wt.%), solid phase yields between 13.56 and 9.75 (wt.%), and gas yields from 27.89 to 55.60 (wt.%). The yields of bio-oil decreases from 74.41 to 30.22% (wt.) with increasing catalyst-to-Tallow kernel oil ratio, while that of gaseous phase increases from 12.87 to 55.60% (wt.). For all the thermal and thermal catalytic cracking experiments, the density, kinematic viscosity, and acid value of bio-oils decreases as the reaction time increases varying from 0.9266 to 0.8220 g/cm³, 8.10 to 2.24 mm²/s, and 144.14 to 2.37 mg KOH/g. The GC-MS of liquid reaction products identified the presence of hydrocarbons (alkanes, alkenes, ring-containing alkanes, ring-containing alkenes, and aromatics) and oxygenates (carboxylic acids, ketones, esters, alcohols, and aldehydes). For all the pyrolysis and catalytic cracking experiments, the hydrocarbon selectivity in bio-oil increases with increasing reaction time, while those of oxygenates decrease, reaching concentrations of hydrocarbons up to 95.35% (area.). The best results for the physicochemical properties density, kinematic viscosity, and acid value were 0.8220 g/cm³, 3.03 mm2/s, and 2.37 mg KOH/g, respectively, with a maximum hydrocarbon concentration of 97.194% (area.) and 2.806% ketones (area.) were obtained at 400 °C and 1.0 atmosphere, 80 minutes, without catalyst. For the catalytic cracking experiments, the maximum hydrocarbon content of 75.763% (area.) and 17.041% (area.) carboxylic acids, 4.702% (area.) ketones (area.), and 2.494% (area.) non-identified oxygenates was obtained at 400 °C and 1.0 atmosphere, 90 minutes, using a catalyst fixed bed reactor, with 10.0% (wt.) activated carbon pellets impregnated with 10.0 M NaOH as catalyst.

In this study, the changes in mass, compressive strength and length were analyzed to investigate sulfate resistance according to ground granulated blast furnace slag (GGBFS) blending ratio and type of sulfate solution. All alkali activated mortars showed excellent sulfate resistance when immersed in sodium sulfate (Na₂SO₄) solution. However, when immersed in magnesium sulfate (MgSO₄) solution, different sulfate resistance results were obtained depending on the presence of GGBFS. Alkali activated GGBFS blended mortars showed a tendency to increase mass, increase length and decrease compressive strength when immersed in magnesium sulfate solution, but the alkali activated FA mortars did not show any significant difference depending on the types of sulfate solution. The deterioration of alkali activated GGBFS blended mortars in the immersion of magnesium sulfate solution was confirmed by the decomposition of C-S-H which is the reaction product by magnesium ion and the formation of gypsum (CaSO₄·2H₂O) and brucite (Mg(OH)₂).

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

In 2021 the total world cement production was estimated at 4.1 billion tonnes and the annual CO2 emissions from cement plants reached almost 2.8 billion metric tonnes. In the last years many ef-forts have been made for manufacturing low-CO2 cements. In this regard, a great attention has been paid towards calcium sulfoaluminate (CSA) cements for both their peculiar technical prop-erties and the environmentally friendly features mainly related to their manufacturing process. Moreover, the use of blended cements composed by CSA binders and supplementary cementitious materials (SCMs) could represents a powerful tool for both reducing the CO2 footprint and pro-ducing more durable environmentally friendly materials. In this paper, the possibility of using reservoir sediments (RS), calcined at 830°C, as SCMs in blended-CSA cements was investigated. Four binders were submitted to hydration and physico-mechanical tests for curing periods com-prised in the interval 4 hours-56 days. X-ray fluorescence, X-ray diffraction and differential thermal–thermogravimetric analyses were employed as main characterization techniques. It was found that thermally treated RS are very interesting inasmuch as their utilization allows a CSA clinker dilution, thus implying both a decrease of CO2 emissions and a reduction of costs related to CSA cement production.

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans is still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple of the risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.

In the mid-1950s, a groundbreaking discovery revealed the fascinating presence of caveolae, referred to as flask-shaped invaginations of the plasma membrane, sparking renewed excitement in the field of cell biology. Caveolae are small, flask-shaped invaginations in the cell membrane that play crucial roles in diverse cellular processes, including signal transduction, endocytosis, lipid homeostasis, and signal transduction. The structural stability and functionality of these specialized membrane microdomains are attributed to the coordinated activity of scaffolding proteins, including caveolins and cavins. While caveolae and caveolins have been long appreciated for their integral roles in cellular physiology, the accumulating scientific evidence throughout the years reaffirms their association with a broad spectrum of human disorders. This review article aims to offer a thorough account of the historical advancements in caveolae research, spanning from their initial discovery to the recognition of caveolin family proteins and their intricate contributions to cellular functions. Furthermore, it will examine the consequences of a dysfunctional caveolar network in the development of human diseases.

This study aims to investigate utilizing Precipitated Calcium Carbonate (PCC), a by-product of sugar beet, as a soil stabilizer for addressing settlement issues beneath pavements. Various tests were conducted to assess the engineering properties of PCC-stabilized subgrades using PCC obtained from Amalgamated Sugar Cooperation in Twin Falls, Idaho. Local loess samples, like those found beneath pavements, were collected for testing purposes. Initial tests involved evaluating the unconfined compressive strength of compacted loess samples, followed by tests on samples mixed with different weight percentages of PCC. The results revealed a significant average increase of 10% to 28% in the strength of loess samples stabilized with 5% PCC compared to the strength of the native soil. The chemical composition and microstructure of PCC were further analyzed through X-ray Diffraction (XRD), Energy Dispersive X-ray Spectrometer (EDX), and Scanning Electron Microscopy (SEM) Tests conducted at the Idaho National Laboratory (INL). XRD analysis indicates the presence of calcium carbonate and silica. EDX analysis unveiled a carbon content of 9% by weight in PCC, which could contribute to the carbon footprint when it breaks down. Additionally, SEM images displayed an irregular microstructure and particle shape of PCC. Furthermore, the inclusion of PCC improved the resistance of loess to saturation collapse.

For the replacement of lost contractile elements in the treatment of coronary heart disease, the most promising approaches to obtain cardiomyocytes by cardiac differentiation of pluripotent cells. The aim of this work is to develop a technology for the formation of a functional layer of cardiomyocytes differentiated from iPSCs, capable of generating rhythmic activity and synchronous contractions. To accelerate cardiomyocyte maturation, the renal subcapsular transplantation model was used in SCID mice. After explantation, the formation of cardiomyocyte contractile apparatus was assessed by fluorescence and electron microscopy, and calcium ion oscillation in the cytoplasm was assessed by visualization of the fluorescent calcium binding dye Fluo-8. It was shown that human iPSC-derived cardiomyocyte cell layers transplanted (for up to 6 weeks) under SCID mouse kidney fibrous capsules begin to form an ordered contractile apparatus and retain functional activity and the ability to oscillate calcium ion fluxes after explantation from the body.

In unicellular organisms, intracellular inclusions of amorphous calcium carbonate (ACC) have been initially described in cyanobacteria and, later, in unicellular eukaryotes of Lake Geneva (Switzerland/France). Inclusions in unicellular eukaryotes ‒named micropearls‒ consist of hydrated ACCs, frequently enriched in Sr or Ba, displaying internal oscillatory zonations due to variations in the Ba:Ca or Sr:Ca ratios. The analysis of our database consisting of 1597 micropearl analyses from Lake Geneva and 34 from Lake Titicaca (Bolivia/Peru) has shown that a certain number of Sr and Ba-enriched micropearls from these lakes contain As in amounts measurable by EDXS. A Q-mode statistical analysis has confirmed the existence of five geochemically distinct morpho-chemical groups of As-bearing micropearls, among which a new category identified in Lake Geneva, where As is often associated with Mg. This new type of micropearl is possibly produced in a small (7-12 m size) bi-flagellated organism. Micropearls from Lake Titicaca, which contain Sr, are found in an organism very similar to Tetraselmis cordiformis, observed in Lake Geneva. Lake Titicaca micropearls contain higher As concentrations which can be explained by the high As concentration in the water of this lake. The ubiquity of the biomineralization process observed points to the need for better understanding of the role of amorphous or crystalline calcium carbonates in As cycling in surface waters.

Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

Neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. Analysis of ZIKV epidemic strains showed that glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS.

Plants produce above- and below-ground biomass. However, our understanding of both production and decomposition of below-ground biomass is poor, largely because of the difficulties of accessing study materials. Below-ground organic matter decomposition studies are scanty and especially rare in the tropics. Here, we used a litter bag experiment to quantify the mass loss and nutrients dynamics of decomposing twigs and fine roots from an arbuscular mycorrhizal fungal associated tree, Parashorea chinensis, in a tropical rain forest in Southwest China. Overall, twig litter decomposed 1.9 times faster than fine roots (decay rate (k) twig=0.255, root=0.134). The difference in decomposition rates can be explained by a difference in phosphorus (P) concentration, availability and use by decomposers or C quality. Both materials showed an increase in N concentration, with final measurements still higher than initial levels. This suggests N may not be available due to microbial immobilization. Both carbon and nitrogen dynamics were significantly predicted by mass loss and showed a negative and positive relationship, respectively. Our study results imply that fine roots carbon and nitrogen contribute more to soils organic matter and enlarge the resident time. Therefore, better understanding of carbon cycle requires better understanding of mechanisms governing below ground biomass decomposition.

Reducing CO2 emissions is urgently needed to slow down the impacts of climate change. CO2 capture using an amine solution has been developed and implemented on pilot and commercial scales. However, amine scrubbing, in particular, produces a lot of degraded solvent as waste and is energy intensive. Solid sorbents have been called to overcome those drawbacks. In this work, waste biomass-derived carbon materials were developed and tested for CO2 capture and conversion. Advanced thermal chemical processes i.e. hydrothermal and pyrolysis were applied to produce materials from agri-food waste such as soybean and okara. It was found that the number of functional groups (-C=O and -OH) in activated carbon appears in the synthesized materials, implying the generation of surface oxygenated groups. Preliminary results showed that the synthesized activated carbons are obtained with good yields, and a relatively high surface area, which may be applied as CO2 adsorption materials to solve the CO2 emission problems.

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects by its copper chelating derivatives. Since chronic/persistent borreliosis is characterized by increased amounts of proinflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration and surface marker expression of in vivo activated human monocyte-derived macrophages and dendritic cells with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24h by imaging every 3.5 min. Results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads bearing an electron dense iron core. As a control, phagocytosis was also monitored by visual counting of ingested beads. DSF decreased the phagocytic capacities exhibited by global macrophages and dendritic cells. DSF also impaired the migration of human monocyte-derived macrophages and dendritic cells (hMDMD) and significantly reduced the expression densities of surface antigens CD45 and CD14. In cells consisting of anti-inflammatory M2 macrophages, DSF led to a remarkable cell death and also increased oxidative stress as determined by MitoSox staining. Mitochondrial oxidative stress was a prominent feature in M2 macrophages which were more sensitive to DSF-induced cytotoxicity.

This study deals with the computational analysis of the kinetic processes of a microbial electrolysis cell assisted-anaerobic digestion (MEC-AD) treating raw-waste activated sludge (WAS), comparatively with a conventional AD, as well as the effect of the Organic Loading Rate (OLR) on the system’s performance. The aim was to derive a single kinetic and mathematical model for the study of the MEC-AD, using the ADM1 framework, which can be utilized to extract the effect of an applied potential on the kinetics of AD. The experimental data were obtained from the long-term, continuous operation of two identical reactors (an AD and a MEC-AD), which were operated at different OLRs (1.1, 1.7 and 2.9 gCOD/(L*d)). The results showed that the MEC-AD yielded improved biomass yields, substrate consumption kinetics and 1st order disintegration kinetics, with a predominant contribution to disintegration of complex particulates, comparatively with the AD. Moreover, it enabled operation at higher OLRs (achieving the highest divergence from the AD at the OLR of 4.14 gCOD/(L*d)), therefore accelerating sludge treatment, as well as an improved performance at an increased solids retention time (SRT). These findings can serve as a quantitative guide for the effects of the operating parameters on the raw-WAS-fed MEC-AD performance.

Biomass exploitation is a global trend due to the circular economy and the environmentally friendly spirit. Numerous applications are now based on the use of biomass derived products. Hydrogen sulfide (H2S) is a highly toxic and environmentally hazardous gas, which emitted from various processes. Thus, the efficient removal of this toxic hazardous gas following cost effective processes is an essential requirement. In this study, we present the synthesis and characterization of biomass-derived activated-carbon/zinc-oxide (ZnO@AC) composites from different biomass sources as potential candidates for H2S sorption. The synthesis involved a facile method for activated carbon production via pyrolysis and chemical activation of biomass precursors (spent coffee, Aloe-Vera waste leaves, and corncob). Activated carbon production was followed by the incorporation of zinc oxide nanoparticles into the porous carbon matrix using a simple melt impregnation method. The synthesized ZnO@AC composites were characterized using X-ray diffraction (XRD), infrared spectroscopy (IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and nitrogen porosimetry. The H2S removal performance of the ZnO@AC composites was evaluated through sorption experiments using a handmade apparatus. Our findings demonstrate that the Aloe-Vera, Spent-coffee, and Corncob derived composites exhibit superior H2S sorption capacity up to 106 mgH2S/gads., 66 mgH2S/gads., and 47 mgH2S/gads. respectively.

High-strength wastewaters from a variety of sources, including the food industry, domestic septage and landfill leachate, are often hauled to municipal wastewater treatment plants (WWTPs) for co-treatment. Due to their high organic loadings, these wastewaters can cause process upsets in both the WWTP’s liquid and solids treatment trains and consume organic treatment capacity, leaving less capacity available to service customers in the catchment area. A novel pre-treatment method, the Waste Activated Sludge-High Rate (WASHR) process, is proposed to optimize the co-treatment of high-strength wastewaters. The WASHR process combines the contact stabilization and sequencing batch reactor processes. It utilizes waste activated sludge from the municipal WWTP as its biomass source, allowing rapid start-up. Bench scale treatment trials of winery wastewater confirm the WASHR process can reduce loadings on the downstream WWTP’s liquid treatment and solids treatment trains. A case study approach is used to confirm the economic viability and environmental sustainability of the WASHR process compared to direct co-treatment using life cycle cost analyses and greenhouse gas emissions estimates.

In the present work, a comparative evaluation of an MBBR unit performance was carried out for the following cases: when adding 3D-printed biocarriers fabricated with 13X and bentonite, when using K1 commercial biocarriers and when not adding biocarriers at all. For the evaluation of the MBBR efficiency, various physicochemical parameters were measured, while static light scattering and optical microscopy observations were additionally used. Finally, biofilm extracted from the biocarriers was evaluated. The findings suggest that there is an optimal biodegradation of the organic load in all MBBR units. The nitrification and denitrification process were improved at the 3D MBBR as compared to the control MBBR and MBBR K1. The dry mass of the biofilm in the 3D-printed biocarriers was two orders of magnitude larger than the one in the K1 biocarriers. What is more, in the K1 biocarriers the mass of the biofilm varied in relation to time, due to the fact that it could not be kept inside the holes, something that was not observed to happen with the 3D-printed biocarriers. Finally, it was observed, mostly in the 3D MBBR and less in the K1 MBBR, that the growth of nitrifying bacteria and heterotrophs inside the units increased the biomass production in the form of SMP, which in turn favored the adhesion of biomass on the surface of biocarriers.

The need for Transit Oriented Development (TOD) around railway stations has been well accepted and continues to be needed in cities looking to regenerate both transit and urban development. Large parts of suburban areas remain without quality transit down Main Roads which are usually filled with traffic resulting in reduced urban value. The need to regenerate both the mobility and land development along such roads will likely be the next big agenda in transport policy. This paper learns from century-old experiences in public-private approaches to railway systems from around the world, along with new insights from entrepreneurship theory and urban planning to create the notion of a ‘Transit Activated Corridor’ (TAC). TAC’s prioritise fast transit and a string of station precincts along urban Main Roads. TOD’s were primarily a government role, whereas TAC’s will be primarily a private sector, entrepreneurship role. The core policy processes for a TAC are outlined with some early case studies. Five design principles for delivering a TAC are presented in this paper, three principles from entrepreneurship theory and two from urban planning. The potential for Trackless Trams to enable TAC’s is used to illustrate how these design processes can be an effective approach for designing, financing and delivering a ‘Transit Activated Corridor’.

Neuroinflammatory responses are implicated in the pathogenesis of neurodegenerative diseases. In neurodegenerative diseases, neuroinflammatory reactions to neuronal injury are modulated by microglial cells, which are vital innate immune cells in the central nervous system. Activated microglial cells release proinflammatory cytokines, mediators, and neurotoxic factors that induce fatal neuronal injury. The present study investigated the anti-neuroinflammatory effects of cudratricusxanthone L (1), which was isolated from Cudrania tricuspidata. This compound reduced the levels of lipopolysaccharide-stimulated inflammatory mediators and cytokines, including nitric oxide, prostaglandin E2, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and IL-12. These effects suggested that cudratricusxanthone L (1) suppressed the nuclear factor-kappa B (NF-κB) signaling pathway. Specifically, cudratricusxanthone L (1) also attenuated the phosphorylation of Jun kinase and inhibited p38 mitogen-activated protein kinase (MAPK) signaling in BV2 and rat primary microglial cells. These results indicated that cudratricusxanthone L (1) effectively repressed neuroinflammatory processes in BV2 and rat primary microglial cells by inhibiting NF-κB and the MAPK signaling pathway.

The annual construction and demolition waste (CDW) generated from EU construction sector was 850 million tons, which represented 31% of the total waste generation and about 28% of CDW was ceramics (bricks and tiles). In this study, the feasibility of using CDW brick powder as the precursor of alkali activated mortar (AAM) and extruded polystyrene (XPS) as the lightweight aggregates to form lightweight brick powder AAM (LW-BP-AAM) for non-structural applications was investigated. The thermal conductivity of LP-BPAAM was 0.112 W/m·K with density of about 1,135 kg/m³ which was lower than the counterparts with similar density in literature. The acid resistance of LW-BP-AAM is comparable to conventional fly ash based AAM and superior than ordinary Portland cement. From the scanning electron microscopy with energy dispersive X-ray spectroscopy, there was no severe damage on the surface of LW-BP-AAM but aluminate was removed from the matrix which was further verified in Fourier transform infrared spectroscopy. The mass and strength loss of LP-BP-AAM was 1.5% and 33%, respectively. Although the compressive strength of the LP-BP-AAM was low (about 1.8 MPa), it can be improved by optimising the particle size of the XPS aggregates.

The most important prognostic factors in curatively treated prostate cancer at the initial diagnosis are T and N stage, histological subtype, Gleason score, initial PSA, PSA density and percentage of core biopsy positivity. Newer, but non-standard prognostic factors are urine PCA3 and genetic markers of prostate cancer. A simple, but seemingly underestimated standard test is serum Calcium (Ca) level, which has been shown by a previous study group to be a good predictor of lethal prostate cancer, but there is scarce evidence regarding the prognostic value of calcium levels at diagnosis. We aimed to determine whether a Ca level in the upper part of normal values has a prognostic value in curatively treated prostate cancer. We have retrospectively included 84 consecutive patients with prostate cancer, who underwent curative radiotherapy (primary or adjuvant; external beam RT with or without brachytherapy). We have performed statistical analysis of available prognostic factors. Ca level at diagnosis was found to be a statistically significant predictor of disease-free survival.

This study explores the potential of titanium disulfide (TiS2) as an active material for aqueous calcium-ion batteries (CIBs). We investigate the electrochemical redox reactions of calcium ions within TiS2 and assess its suitability for use in aqueous CIBs. Additionally, we examine the im-pact of different electrolyte concentrations on TiS2 electrode reactions. Our findings reveal that TiS2 exhibits distinct charge-discharge behaviors in various aqueous calcium-ion electrolytes. Notably, at higher electrolyte concentrations, TiS2 effectively suppresses the hydrogen genera-tion reaction caused by water decomposition, demonstrating its potential as an active material for aqueous CIBs. In-situ X-ray diffraction analysis confirms the intercalation of Ca2+ ions be-tween TiS2 layers during charging. This confirmation is groundbreaking, as it represents the first experimental evidence of calcium ions being electrochemically inserted between TiS2 layers from aqueous solutions, signifying a previously unreported achievement and strongly suggesting TiS2's applicability in aqueous CIBs. X-ray photoelectron spectroscopy analysis further supports the formation of a solid electrolyte interphase (SEI) on the TiS2 electrode surface, contributing to the suppression of electrolyte decomposition reactions. Furthermore, we investigate the influ-ence of anions in the electrolyte on charge-discharge behavior. Our findings suggest that the choice of anion coordinated with Ca2+ ions affects SEI formation and cycling performance. Un-derstanding the role of anions in SEI formation is crucial for optimizing aqueous CIBs. In con-clusion, this research underscores TiS2's potential as an active material for aqueous calcium-ion batteries and emphasizes the importance of electrolyte composition in influencing SEI formation and battery performance. These findings contribute to the development of more sustainable and efficient energy storage technologies.

In Acropora, the complex canals in a coral colony connect all polyps into a holistic network to collaborate in performing biological processes. There are various types of canals, including calice, axial canals, and other internal canals, with structures that are dynamically altered during different coral growth states due to internal calcium transport. However, few studies have considered the regulation of calcium transport in Acropora. In this study, we investigated the morphological changes of the axial canal in six Acropora muricata samples by high resolution micro-computed tomography, observing the patterns of the axial canal during the processes of new branch formation and truncated branch rebuilding. We visualized the formation of a new branch from a calice and deposition of the iconic hexactin skeletons in the axial canal. Furthermore, the diameter and volume changes of the axial canal in truncated branches during rebuilding processes were calculated, revealing that the volume ratio of calcareous deposits in the axial canal exhibit significant increases within the first three weeks, returning to levels in the initial state in the following week. This work indicates that the axial canal can transport calcium to form hexactin skeletons in a new branch and rebuild the tip of a truncated branch. The calcium transport along canal network regulates various growth processes, including budding, branching, skeleton forming, and self-rebuilding of an Acropora colony. Understanding the changes in canal function under normal and extreme conditions will provide theoretical guidance for restoration and protection of coral reefs.

Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. Several major mechanisms cause AF in patients, including a genetic predisposition to develop AF. Genome-wide association studies have identified genetic variants associated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene coding for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research on PITX2-dependent AF is not sufficient for understanding atrial functional proprieties. Linking PITX2 to ion channels, cells, tissues, atria and the whole heart, computational models are necessary for achieving a quantitative understanding of atrial structure and function in PITX2-dependent AF. Computational approaches are used to capture all that we know about PITX2-dependent AF and to develop improved therapies. In the present review, we discuss advances in atrial modelling and focus on the mechanistic links between PITX2 and AF. Challenges in applying models for improving patient health are described, as well as a summary of future perspectives.

For voltage-gated Ca2+ channel (VGCC), its α2δ subunits are traditionally considered to be auxiliary subunits that regulates VGCC trafficking to the plasma membrane. The antiepileptic, antinociceptive and anxiolytic gabapentin (GBP) has previously been shown to bind the VGCC α2δ subunits with high affinity to disrupt VGCC trafficking. Yet, the interaction between GBP and α2δ still remains poorly understood from a structural point of view. For instance, it is not clear yet what the structural implication is of α2δ-1-bound GBP against VGCC trafficking. With a set of experimental data-driven structural analysis of the VGCC α2δ-1 and its ligand GBP, this article postulates for the first time that: 1), α2δ-1 bound GBP stabilizes the α2δ-1-GBP complex structure; 2), α2δ-1 bound GBP restrains the conformational flexibility of α2δ-1; 3), α2δ-1-bound GBP establishes an electrostatic axis consisting of Q535 (Gln535)-R241 (Arg241)-GBP (gabapentin)-D452 (Asp452), which constitutes an energetically favourable contribution towards the structural stability of the α2δ-1-GBP complex and helps restrains the conformational flexibility and local structural rigidification of α2δ-1; and 4), GBP-induced local conformational inflexibility and structural rigidification of α2δ-1 is one key step in the pharmacological disruption of VGCC trafficking by GBP.

Initial water content significantly affects the efficiency of soil stabilization. In this study, the effects of initial water content on the compressibility, strength, microstructure and composition of a lean clay soil stabilized by compound calcium-based stabilizer were investigated by static compaction test, unconfined compression test, optical microscope observations, environment scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction spectroscopy. The results indicate that as the initial water content increases in the range studied, both the compaction energy and the maximum compaction force decrease linearly and there are less soil aggregates or agglomerations, and smaller proportion of large pores in the compacted mixture structure. In addition, for specimens cured with or without external water supply and under different compaction degrees, the variation law of the unconfined compressive strength with initial water content is different and the highest strength value is obtained at various initial water contents. With the increase of initial water content, the percentage of oxygen element tends to increase in the reaction products of the calcium-based stabilizer, whereas the crystalline mineral of the soil did not change obviously.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

The DNA Damage Response (DDR) network and the mitogen-activated protein kinase (MAPK) signaling pathway are crucial mechanisms for the survival of all living beings. An accumulating body of evidence suggests that there is a crosstalk between these two systems, thus favoring the appropriate functioning of multi-cellular organisms. On the other hand, aberrations within these mechanisms are thought to play a vital role in the onset and progression of several diseases, including cancer, as well as in the emergence of drug resistance. Here, we provide an overview of the current knowledge regarding alterations in the DDR machinery and the MAPK signaling pathway, as well as abnormalities in the DDR-MAPK functional crosstalk in multiple myeloma, the second most common hematologic malignancy. We also present the latest advances in the development of anti-myeloma drugs targeting crucial DDR- and MAPK-associated molecular components. These data could potentially be exploited to discover new therapeutic targets and effective biomarkers, as well as for the design of novel clinical trials. Interestingly, they might provide a new approach to increase the efficacy of anti-myeloma therapy by combining drugs targeting the DDR network and the MAPK signaling pathway.

Cold plasma (CP) is an ionised gas containing excited molecules and ions, radicals, free electrons, and emits electric fields and UV radiation. CP is potently antimicrobial and can be applied safely to biological tissue, birthing the field of plasma medicine. Reactive oxygen and nitrogen species (RONS) produced by CP affect biological processes directly or indirectly via the modification of cellular lipids, proteins, DNA, and intracellular signalling pathways. CP can be applied at lower levels for oxidative eustress to activate cell proliferation, motility, migration, and antioxidant production in normal cells, mainly potentiated by the unfolded protein response, Nrf2-activated antioxidant response element and PI3K/Akt pathway, which also activates NFκB. At higher CP exposures, inactivation, apoptosis and autophagy of malignant cells can occur via degradation of PI3K/Akt and MAPK-dependent and -independent activation of the master tumour suppressor p53, leading to caspase-mediated cell death. These opposing responses validate a hormesis approach to plasma medicine. Clinical applications of CP are becoming increasingly realised in wound healing, while clinical effectiveness in tumours is currently coming to light. This review will outline advances in plasma medicine and compare the main redox and intracellular signalling responses to CP in wound healing and cancer.

Perilla frutense var. acuta (Lamiaceae) has been used to treat indigestion, asthma, and allergies in traditional medicine. In this study, luteolin 7-O-diglucuronide (1), apigenin 7-O-diglucuronide (2), and rosmarinic acid (3) were isolated from the leaves of P. frutescens var. acuta. Various approaches were performed to investigate the anti-inflammatory activity of the isolated compounds (1-3) and their working mechanisms. In silico docking simulation demonstrated that 1-3 would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that the Perilla extract and 3 increased PPAR-α luciferase activity [1.71 and 1.61 times of the control (PPAR-α + PPRE, p < 0.001)]. In the NF-κB luciferase assay, 1 suppressed NF-κB activity the most (56.83 % at 5 µM; 74.96 % at 10 µM; 79.86 % at 50 µM). In addition, 1 and 2 inhibited the mRNA expression of NF-κB target genes, including Il6, Mcp1, and Tnfa, at 50 µM, and 3 suppressed the genes at the mRNA level in a dose-dependent manner. We report that 1 and 2 exert anti-inflammatory effects through NF-κB inhibition, and PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of 3.

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to those NRs modulation, OA exhibited prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

Nowadays, bioeconomy and nanotechnology trends push food packaging sector in the re-placement of food additives by biobased antioxidant/antibacterial compounds and their inclusion in nanocarriers to control their release. Herein by following this trend, a rich in thymol-(TO) activated carbon (AC) nanostructure (TO@AC) was prepared and physiochemically characterized with various technics. This TO@AC nanostructure as well as pure AC were extruded with low density polyethylene (LDPE) to develop novel active packaging LDPE/TO@AC and LDPE/AC films. X-ray diffractometry, Fourier Transform Infrared Spectroscopy and Scanning Electron Microscopy measuraments shown high dispersity and capability of both AC and TO@AC in LDPE matrix which was resulted in enhanced tensile and water/oxygen barrier properties of obtained LDPE/AC and LDPE/TO@AC films. LDPE/TO@AC films shown higher elongation at break values and water/oxygen barrier than LDPE/AC films and significant antioxidant activity. TO release kinetics studies shown that by increasing TO@AC content the total TO amount released increased and the constant release rate decreased. Pork fillets wrapped with the optimum active film containing 15 wt.% TO@AC and succeed to prevent lipid oxidation and heme iron loss during storage. Estimation of microbial population of pork fillets shown that this active film could ex-tend the microbiological shelf-life of pork fillets by 2 days

This study identifies new Alkali Activated Composite Mud Mortar to alternate Cement Mortar used for laying masonry works. This study handles both experimental and numerical analysis of strength and durability for mortar, especially bond strength along mortar and brick joints have studied detail and compared with ANSYS. The bond strength has estimated through the triplet brick prism of shear behavior. The strength and deformation characteristics of masonry constituents obtained from these tests depend on the actual composite conduct of masonry. There is always a good reception for environmentally friendly, low energy, new construction materials, and used in preparing mortar/brick unit combinations all around the world. Also, this study fulfills those requirements. Especially, masonry laid with the mud mortar meets all. Fly Ash, Ground Granulated Blast furnace Slag, and Quarry Dust have utilized the new composites' preparation with 8Molority, 10Molority developed excellent strength. The composite specimens are having compression and bond strength, ranging from 4.84-5.14 and 0.12-0.18N/mm2. The mixed ratio of materials has taken (0.5 parts of Fly Ash, 0.5 parts of Steel Slag, 1.75 parts of Soil, and 0.25 parts of Quarry Dust). The samples tested resistance against acidic, sulfate, and alkalinity indicated PH values less than 7 and 9 simultaneously. Compression strength varied from 10-20% and gained more and fit composite used for mortar in masonry works.

Theaflavins, the characteristic and bioactive polyphenols in black tea, possess the potential improvement effects on insulin resistance-associated metabolic abnormalities including obesity and type 2 diebetes. However, the molecular mechanisms of theaflavins improving insulin sensitivity are still not clear. In this study, we investigated the protective effects and mechanisms of theaflavins on palmitic acid-induced insulin resistance in HepG2 cells. Theaflavins could significantly increase glucose uptake of insulin-resistant cells at noncytotoxic doses. This activity was mediated by upregulating the glucose transporter 4 protein expression, increasing the phosphorylation of IRS-1 at Ser307, and reduced the phosphor-Akt (Ser473) level. Moreover, theaflavins were found to enhance mitochondrial DNA copy number through down-regulate the PGC-1β mRNA level and up-regulate PRC mRNA expression in insulin-resistant HepG2 cells. These results indicated that theaflavins could improve free fatty acid-induced hepatic insulin resistance by promoting mitochondrial biogenesis, and were promising functional food and medicines for insulin resistance-related disorders.

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium dynamics, offering important insights into de-velopmental processes, physiological functioning, and disease progression. Neuro-transmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neuro-transmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with calcium dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, GABA, glycine, dopamine, and acetylcholine and their interplay with calcium dynamics. This con-ceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

Several noninvasive vascular biomarkers have been suggested for improving the risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment (L-LT) in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and free of diabetes and L-LT. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score =0 (OR 0.67; 95%CI 0.48-0.92, P=0.01), CAC score >100 (1.59; 1.08-2.39, P=0.01) and with high femoral IMT (1.89; 1.19-3.06, P<0.01), but not with other biomarkers. Our data confirm that in the presence of CAC score =0 in individuals at intermediate risk, L-LT can be avoided, while it should be used in those with CAC score >100. Femoral artery IMT could represent a useful biomarker for decision regarding L-LT, however the reference values according to sex and age should be established in a large healthy population

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands is compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

In this study, Plasma-Activated Water (PAW) was synthesized using a coaxial Dielectric Barrier Discharge (DBD) reactor, benefiting from the elevated capacity of air-flow-assisted DBD discharges to enhance nitrogen-based species concentration. By manipulating operational parameters, including gas flow rate, activation time, and DI water volume, we achieved significant concentrations of Reactive Oxygen and Nitrogen Species (RONS). As a result, the PAW obtained displayed pronounced physicochemical attributes: a pH of 2.06, an ORP of 275mV, conductivity of 3mS/cm, and TDS of 1200 mg/L. A pivotal aspect of this research was the evaluation of the reactor's efficiency, as indicated by metrics like the specific input energy and ozone efficiency yield. The antimicrobial potential of the PAW was also assessed against pathogenic microbes, with remarkable reductions in viability for both Staphylococcus aureus and Escherichia coli (99.99%) and a more moderate decrease for Candida albicans (37%). These findings underscore the capability of the coaxial DBD reactor in crafting high-quality PAW with significant antimicrobial properties, necessitating further studies to validate its broad-spectrum and safe application.

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.

Production and transport of reactive species through plasma-liquid interactions plays a significant role in multiple applications in biomedicine, environment, and agriculture. We experimentally investigated the transport mechanisms of hydrogen peroxide H2O2 and ozone O3, as the typical plasma species, into water. We measured the solvation of gaseous H2O2 and O3 in airflow into water bulk vs. electrosprayed microdroplets while changing the gas and water flow rates, applied voltage that determines the gas-liquid interface area, and treatment time. The solvation rate of H2O2 and O3 increased with the treatment time and the gas-liquid interface area. The total surface area of the electrosprayed microdroplets was larger than that of the bulk, but their lifetime was much shorter. We estimated that only microdroplets with diameters below ~ 40 µm could achieve the saturation by O3 during their lifetime, while the saturation by H2O2 was impossible due to its depletion from air. Besides the short-lived flying microdroplets, the longer-lived bottom microdroplets substantially contributed to H2O2 and O3 solvation in water electrospray. This study contributes to a better understanding of the gaseous H2O2 and O3 transport into water as a function of different parameters and will lead to design optimization of the plasma-liquid interaction systems.

Fabrics comprised of porous fibers could provide effective passive protection against chemical and biological (CB) threats whilst maintaining high air permeability (breathability). Here, we fabricate hierarchically porous fibers consisting of regenerated silk fibroin (RSF) and activated-carbon (AC) prepared through two fiber spinning techniques in combination with ice-templating – namely cryogenic solution blow spinning (Cryo-SBS) and cryogenic wet-spinning (Cryo-WS). The Cryo-WS RSF fibers had exceptionally small macropores (as low as 0.1 µm) and high specific surface areas (SSAs) of up to 79 m2 g-1. The incorporation of AC could further increase the SSA to 210 m2 g-1 (25 wt. % loading) whilst also increasing adsorption capacity for volatile organic compounds (VOCs).

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: &lt; 400 mg, 400–800 mg, and &gt;800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. &gt;10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the &gt;10 postmenopausal years subgroup, daily calcium intake &gt;800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of &gt;800 mg/day decreases the risk of CVD events in women who have been menopausal for &gt;10 years.

Waste biogenic materials from seafood exploitation are valuable resources of new compounds exploitation within the blue bioeconomy concept. Here, we describe the effectiveness of Raman technology implementation as an in-line tool for demineralization process control of crustaceans or gastropods. We produced transparent chitin polymer foils from three waste crustacean shells (C. sapidus, S. mantis and M. squinado) using a slow, green chemical approach employing acetic acid, and showed the progressive process of biogenic carbonate dissolution and increasing the Raman characteristic signal of chitin, in a time dependence manner. It turned that chitin foils obtaining is species-specific, and the demineralization bath of waste shell mixture can be effectively tracked by Raman spectroscopy, for solvent control and the recovery of the calcium acetate as valuable by-product. Comparatively, calcium acetate drug, a compound widely used in kidney failure diseases, or as additive in nutraceuticals and food industry, has been obtained here, following a green demineralization path of the sea snail Rapana venosa intact shell, assisted by Raman tech-nology, using 9% acetic acid (vinegar) solution for 14 days. To validate the final products identity and quality, The process of waste shells demineralization and the final products of the treatment were investigated using various Raman techniques and technologies, cross-validating the results with FT-IR, XRD and SEM-EDX techniques. NIR Raman spectroscopy revealed chitin bands in a time-dependent manner, while Resonance Raman spectroscopy showed the preservation of ca-rotenoids after two weeks of acetic acid treatment. A hand-held flexible TacticID Raman system with a 1064 nm excitation demonstrated its effectiveness as a rapid, in-line decision making tool during process control and revealed excellent reproducibility of the lab-based instrument signal, suitable for in situ evaluation of the demineralization status and solvent saturation control. The calcium acetate recovered from residual treatment solutions was assessed regarding its hydration status, purity, and suitability as recrystallized material for further use as pharmaceutical product or ingredient in complex formulations.

Bacterial Calcium-carbonate Precipitation (BCP) has been studied for multiple applications such as remediation, consolidation and cementation. Isolation and screening of strong calcifying bacteria is the main task of BCP-technique. In this paper we studied CaCO₃ precipitation by different bacteria isolated from a rhizospheric soil in both solid and liquid media. It has been found, through culture-depending studies, that bacteria belonging to Actinobacteria, Gammaproteobacteria and Alphaproteobacteria are the dominant bacteria involved in CaCO₃ precipitation in this environment. Pure and mixed cultures of selected strains were applied for sand biocementation experiments. Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS) analyses of the biotreated samples revealed the biological nature of the cementation and the effectiveness of the biodeposition treatment by mixed cultures. X-ray diffraction (XRD) analysis confirmed that all the calcifying strains selected for sand biocementation precipitated CaCO₃, mostly in the form of calcite. In this study Biolog® Eco-plate is evaluated as a useful method for a more targeted choice of the sampling site with the purpose of obtaining interesting candidates for BCP applications. Furthermore, ImageJ software was investigated, for the first time to our knowledge, as a potential method to screen high CaCO₃ producer strains.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, like empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1β, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate–induced VC in mouse VSMCs to investigate the mechanisms underlying empagliflozin’s therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE−/− mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate–induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE−/− mice on a high-phosphate diet.

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, which represents a critical and abundant population in most solid tumours microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

Concrete is the most commonly used construction material due to its various advantages, such as versatility, familiarity, strength and durability and it will continue to be in demand far into the future. However, with today’s sensitivity to the environmental protection, this material is facing unprecedented challenges due to its high greenhouse gas emission mainly during cement production. This paper investigates one of the promising cement replacement materials, alkali activated cement (AAC) concrete. Being produced mainly from byproduct materials and having a comparable structural performance to conventional concrete, AAC concrete has a potential to transform the construction industry. Mechanical properties such as compressive and flexural strength and the relationship between them are studied. Different source materials such as fly ash (FA), ground granulated blast furnace slag (GGBS), silica fume (SF) and Metakaolin (MK) are used. The effect of the source materials and the activator solutions on the concrete performance is studied. Furthermore, the freeze-thaw resistance of the concrete is studied. The results of the study showed that the behavior of AAC depends highly on the source material combinations as well as type used. The effect of the alkaline solution is also dependent on the source material used. Mixes with higher GGBS content in general showed the highest strength while mixes with MK showed the highest flexural strength. The results from the freeze-thaw test showed that proper design of AAC concrete with a lower water content is critical to achieve a good resistance.