Search Results (16)

Heart failure is associated with dysregulation in cellular Ca²⁺ that could involve sarcolemmal L-type Ca²⁺ currents (LTCCs). Building on previous observations showing that recombinant Ca_V1.2 channels are upregulated by phosphorylated calmodulin (CaM) variants, the cellular mechanism(s) underlying this posttranslational modification was investigated in cultured cardiomyocytes. Whole-cell LTCCs decreased by ≈75% after silencing the gene coding for casein kinase 2 (CK2), a constitutively active kinase in cardiomyocytes, or after its pharmacological inhibition. The overexpression of the dominant negative phosphoresistant single, double T79A/S81A, or triple T79A/S81A/S101A CaM variants resulted in a similar inhibition. In contrast, the overexpression of CaM WT or its double T79D/S81D and triple T79D/S81D/S101D phosphomimetic variants curtailed the downregulation of LTCCs caused by CK2 partial knockdown, suggesting that CK2 is responsible for the posttranslational modification of these CaM target residues. Catecholamines, triggering the protein kinase A (PKA) cascade, partially rescued LTCCs treated with siRNA without or after the overexpression of either CaM WT or stimulating CaM phosphomimetic variants. More importantly, they thwarted the negative impact of the phosphoresistant CaM variants, altogether arguing that CK2 and PKA are acting in synergy to regulate the activity of LTCCs. We conclude that CK2-mediated phosphorylation processes exacerbate the Ca²⁺ load associated with heart failure. Full article

The amount of sphingosine 1-phosphate (S1P) found in the synovial tissue of individuals with rheumatoid arthritis is five times greater than that in those with osteoarthritis. Our study aims to determine whether inhibiting S1P₂ can mitigate collagen-induced rheumatoid arthritis (CIA) by using an S1P₂ antagonist, JTE-013, alongside DBA-1J S1pr2 wild-type (WT) and knock-out (KO) mice. CIA causes increases in arthritis scores, foot swelling, synovial hyperplasia, pannus formation, proteoglycan depletion, cartilage damage, and bone erosion, but these effects are markedly reduced when JTE-013 is administered to S1pr2 WT mice. CIA also elevates mRNA expression levels of pro-inflammatory Th1/Th17 cytokines in the foot and spleen, which are significantly decreased by JTE-013 in S1pr2 WT mice. Additionally, CIA raises Th1/Th17 and Treg cell counts, while JTE-013 reduces these elevations in the spleens of S1pr2 WT mice. Treatment with JTE-013 or the absence of S1pr2 curtails the differentiation of naïve T cells into Th1 and Th17 cells in a dose-dependent manner. In SW982 human synovial cells, JTE-013 lowers LPS-induced increases in pro-inflammatory cytokine levels. Overall, these findings propose that blocking S1P₂ in immune and synovial cells may alleviate rheumatoid arthritis symptoms and offer a potential therapeutic approach. Full article

The intricate composition of wastewater impedes the recycling of agricultural and industrial effluents. This study aims to investigate the potential of sisal leaf wastewater (SLW), both water-treated (WTSLW) and alkali-treated (ATSLW), as a substitute for the alkali activator (NaOH solution) in the production of slag-powder- and fly-ash-based composites, with a focus on the effects of WTSLW substitution ratios and sisal leaf soaking durations. Initially, the fresh properties were assessed including electrical conductivity and fluidity. A further analysis was conducted on the influence of both WTSLW and ATSLW on drying shrinkage, density, and mechanical strength, including flexural and compressive measures. Microstructural features were characterized using SEM and CT imaging, while XRD patterns and FTIR spectra were employed to dissect the influence of WTSLW substitution on the composite’s products. The results show that incorporating 14 wt% WTSLW into the composite enhances 90-day flexural and compressive strengths by 34.8% and 13.2%, respectively, while WTSLW curtails drying shrinkage. Conversely, ATSLW increases porosity and decreases density. Organic constituents in both WTSLW and ATSLW encapsulated in the alkaline matrix fail to modify the composites’ chemical composition. These outcomes underscore the potential for sustainable construction materials through the integrated recycling of plant wastewater and solid by-products. Full article

Policosanol is a mixture of long-chain aliphatic alcohols (LCAAs) derived from various plant and insect origins that are marketed by various companies with distinct formulations and brand names. Policosanols offer several beneficial effects to treat dyslipidemia and hypertension; however, a comprehensive functionality comparison of various policosanol brands has yet to be thoroughly explored. In the present study five distinct policosanol brands from different origins and countries, Raydel-policosanol, Australia (PCO1), Solgar-policosanol, USA (PCO2), NutrioneLife-monacosanol, South Korea (PCO3), Mothernest-policosanol, Australia (PCO4), and Peter & John-policosanol, New Zealand (PCO5) were compared via dietary supplementation (1% in diet, final wt/wt) to zebrafish for six weeks to investigate their impact on survivability, blood lipid profile, and functionality of vital organs under the influence of a high-cholesterol diet (HCD, final 4%, wt/wt). The results revealed that policosanol brands (PCO1–PCO5) had a substantial preventive effect against HCD-induced zebrafish body weight elevation and hyperlipidemia by alleviating total cholesterol (TC) and triglycerides (TG) in blood. Other than PCO3, all the brands significantly reduced the HCD’s elevated low-density lipoprotein cholesterol (LDL-C). On the contrary, only PCO1 displayed a significant elevation in high-density lipoprotein cholesterol (HDL-C) level against the consumption of HCD. The divergent effect of PCO1–PCO5 against HCD-induced hepatic damage biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), was observed. PCO1, PCO2, and PCO4 efficiently curtailed the AST and ALT levels; however, PCO3 and PCO5 potentially aggravated the HCD’s elevated plasma AST and ALT levels. Consistently, the hepatic histology outcome revealed the least effectiveness of PCO3 and PCO5 against HCD-induced liver damage. On the contrary, PCO1 exhibited a substantial hepatoprotective role by curtailing HCD-induced fatty liver changes, cellular senescent, reactive oxygen species (ROS), and interleukin-6 (IL-6) production. Likewise, the histological outcome from the kidney, testis, and ovary revealed the significant curative effect of PCO1 against the HCD-induced adverse effects. PCO2–PCO5 showed diverse and unequal results, with the least effective being PCO3, followed by PCO5 towards HCD-induced kidney, testis, and ovary damage. The multivariate interpretation based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) validated the superiority of PCO1 over other policosanol brands against the clinical manifestation associated with HCD. Conclusively, different brands displayed distinct impacts against HCD-induced adverse effects, signifying the importance of policosanol formulation and the presence of aliphatic alcohols on the functionality of policosanol products. Full article

The investigation of interconnection technologies is crucial for advancing semiconductor packaging technology. This study delved into the various methods of achieving electrical interconnections, focusing on the sintering process and composition of the epoxy. Although silver (Ag) has traditionally been utilized in the sintering process, its high cost often precludes widespread commercial applications. Copper (Cu) is a promising alternative that offers advantages, such as cost-effectiveness and high thermal and electrical conductivities. However, the mechanical robustness of the oxide layers formed on Cu surfaces results in several challenges. This research addresses these challenges by integrating epoxy, which has advantages such as adhesive capabilities, chemical resistance, and robust mechanical properties. The chemical reactivity of the epoxy was harnessed to both fortify adhesion and inhibit oxide layer formation. However, the optimal sintering performance required considering both the composite composition (20 wt% epoxy) and the specific sintering conditions (pre-heating at 200 °C and sintering at 250 °C). The experimental findings reveal a balance in the incorporation of epoxy (20 wt%) for the desired electrical and mechanical properties. In particular, the bisphenol A epoxy (Da)-containing sintered Cu chip exhibited the highest lab shear strength (35.9 MPa), whereas the sintered Cu chip without epoxy represented the lowest lab shear strength of 2.7 MPa. Additionally, the introduction of epoxy effectively curtailed the onset of oxidation in the sintered Cu chips, further enhancing their durability. For instance, 30 days after sintering, the percentage of oxygen atoms in the Da-containing sintered Cu chip (4.5%) was significantly lower than that in the sintered Cu chip without epoxy (37.6%), emphasizing the role of epoxy in improving Cu oxidation resistance. Similarly, the samples sintered with bisphenol-based epoxy binders exhibited the highest electrical and thermal conductivities after 1 month. This study provides insights into interactions between epoxy, carboxylic acid, solvents, and Cu during sintering and offers a foundation for refining the sintering conditions. Full article

When navigating the environmental exigencies precipitated by global pandemics, the escalation of mask waste presents a multifaceted dilemma. In this avant-garde research, we unveil a novel approach: harnessing the sterilized shredded mask residues (SMRs), predominantly composed of 100 wt. % polypropylene, as pioneering modifiers for asphalt. Distinct proportions of SMR (e.g., 3, 6, and 9 wt. %) were judiciously integrated with fresh–virgin base AP-5 asphalt and subjected to an extensive suite of state-of-the-art examinations, encompassing thin-layer chromatography-flame ionization detection (TLC-FID), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and specific rheological metrics. The TLC-FID diagnostic trajectories highlighted the nuanced rejuvenating influence of SMR on the binder, a facet reinforced by a pronounced elevation in the thermodynamic stability index (I_C). The FT-IR spectra elucidated SMR’s preeminent role as a filler, negating notions of chemical reactivity. The TGA analyses unveiled an elevated thermal onset of degradation, signposting enhanced thermal resilience, whereas the DSC readings illuminated a superior thermal comportment at lower extremities. The SEM evaluations rendered a clearer panorama: there was heightened textural perturbation at escalated SMR incorporations, yet the 3 wt. % concoction showcased an optimal, coherent microtexture symbiosis with asphalt. The rheological scrutinies revealed a systematic trajectory: a diminishing penetration and ductility countered by ascending softening points and viscosity metrics. The coup de maître stemmed from the DSR analyses, unequivocally validating SMR’s unparalleled prowess in curtailing rutting distress. This seminal inquiry not only posits a blueprint for refined pavement longevity but also champions a sustainable countermeasure to pandemic-propelled waste, epitomizing the confluence of environmental prudence an d infrastructural fortitude. Full article

Aqueous solutions of water and ethylene glycol (EG) are prevalently employed in braking, heat transfer, and lubrication systems. However, the precise mechanism through which water content affects the lubricative attributes of EG solutions remains elusive. This research systematically examines the tribological characteristics of EG solutions at varying concentrations using a ceramic–TiAlN friction-pair system. As the concentration of EG increases, the sequential transformation of the associated molecular complex structure in the lubricating medium can be described as follows: [H₂O]_m·EG → [H₂O]_m·[EG]_n → H₂O·[EG]_n. Among them, the stoichiometric coefficients “m” and “n” are the simplest mole ratio of H₂O and EG in the molecular complex structure, respectively. The most favorable EG concentration was determined to be 50 wt.%. At this concentration, a flexible molecular complex adsorption structure ([H₂O]_m·[EG]_n) with a significant bearing capacity (due to intense hydrogen bonding) forms on the surface of the friction pair, which results in a reduction in the running-in duration and facilitates the achievement of superlubricity, and the coefficient of friction (COF) is about 0.0047. Solutions containing 50 wt.% EG enhance the load-bearing ability and hydrophilicity of the lubricating medium. Moreover, they minimize the roughness of the worn region and curtail the adhesive forces and shear stress at the frictional interface, enabling the realization of superlubricity. Consequently, this research offers valuable insights into the optimal water-to-EG ratio, revealing the mechanism of a superlubricity system that possesses exceptional tribological attributes and holds significant potential for practical applications. Full article

Current COVID-19 vaccines are effective countermeasures to control the SARS-CoV-2 virus pandemic by inducing systemic immune responses through intramuscular injection. However, respiratory mucosal immunization will be needed to elicit local sterilizing immunity to prevent virus replication in the nasopharynx, shedding, and transmission. In this study, we first compared the immunoprotective ability of a chimpanzee replication–deficient adenovirus–vectored COVID-19 vaccine expressing a stabilized pre–fusion spike glycoprotein from the ancestral SARS-CoV-2 strain Wuhan–Hu–1 (BV-AdCoV-1) administered through either aerosol inhalation, intranasal spray, or intramuscular injection in cynomolgus monkeys and rhesus macaques. Compared with intranasal administration, aerosol inhalation of BV-AdCoV-1 elicited stronger humoral and mucosal immunity that conferred excellent protection against SARS-CoV-2 infection in rhesus macaques. Importantly, aerosol inhalation induced immunity comparable to that obtained by intramuscular injection, although at a significantly lower dose. Furthermore, to address the problem of immune escape variants, we evaluated the merits of heterologous boosting with an adenovirus–based Omicron BA.1 vaccine (C68–COA04). Boosting rhesus macaques vaccinated with two doses of BV-AdCoV-1 with either the homologous or the heterologous C68–COA04 vector resulted in cross–neutralizing immunity against WT, Delta, and Omicron subvariants, including BA.4/5 stronger than that obtained by administering a bivalent BV-AdCoV-1/C68–COA04 vaccine. These results demonstrate that the administration of BV-AdCoV-1 or C68–COA04 via aerosol inhalation is a promising approach to prevent SARS-CoV-2 infection and transmission and curtail the pandemic spread. Full article

The development of a stable and highly active photocatalyst has garnered significant attention in the field of wastewater treatment. In this study, a novel technique involving a facile stirring method was devised to fabricate an array of g-C₃N₄/ZnO nanowire (ZnO NW) composites. Through the introduction of g-C₃N₄ to augment the generation of electron-hole pairs upon exposure to light, the catalytic efficacy of these composites was found to surpass that of the pristine ZnO NWs when subjected to simulated sunlight. The photocatalytic performance of a 20 mg·L⁻¹ methylene blue solution was found to be highest when the doping rate was 25 wt%, resulting in a degradation rate of 99.1% after 60 min. The remarkable enhancement in catalytic efficiency can be ascribed to the emergence of a captivating hetero-junction at the interface of g-C₃N₄ and ZnO NWs, characterized by a harmoniously aligned band structure. This alluring arrangement effectively curtailed charge carrier recombination, amplified light absorption, and augmented the distinct surface area, culminating in a notable boost to the photocatalytic prowess. These findings suggest that the strategic engineering of g-C₃N₄/ZnO NW heterostructures holds tremendous promise as a pioneering avenue for enhancing the efficacy of wastewater treatment methodologies. Full article

A novel control strategy to manage the integration of a wind turbine (WT) and an energy storage unit to an existing stand-alone microgrid servicing an oil and gas (O&G) rig is the topic of this paper. The control strategy includes a primary and a secondary controller that, using the battery in tandem with the WT, does not require any dump load (A). The secondary controller includes an energy management system (EMS) which uses the estimated wind production and other specific local information to size the battery to avoid the curtailment of the WT (B) and simultaneously provide the framework for the economic analysis (C). Points A, B and C are the main novelties introduced with this work. Additionally, a primary controller operates the original microgrid source, a gas turbine (GT), at its maximum efficiency through an active power control strategy to lower fuel consumption, by prioritizing the exploitation of the renewable energy source through the combination EMS and battery sizing. The microgrid is simulated and the combined controller of the battery and GT bench-tested. Full article

In South Korea, Renewable Energy Sources (RES) have been increasing with the application of energy policies, such as Feed in Tariff (FIT) and the Renewable Portfolio Standard (RPS). However, a rapid increase in RES supply leads to an uncertain power supply due to the intermittent output of RES. A representative example is the curtailment of Wind Turbines (WT), which frequently occurs in Jeju Island, South Korea. The proportion of RES power on Jeju Island is 67%, and there are cases where WT is curtailed among the operable sections to maintain the balance of power supply and demand. This paper applies Power-to-Gas (P2G) technology to hydrogenate, store, and utilize unused power to solve this problem. In this paper, Aewol-eup in Jeju Island is selected as a target site for case study. An Integrated Energy System (IES) for various energy operations is designed to control RES output. This paper proposes the optimal facility configuration and finally drives the optimal design and operation solution of IES by analyzing the objective functions and focusing on the Independent Power Producer (IPP) perspective. Full article

Distributed energy resources (DERs) and demand side management (DSM) strategy implementation in smart grids (SGs) lead to environmental and economic benefits. In this paper, a new DSM strategy is proposed for the day-ahead scheduling problem in SGs with a high penetration of wind energy to optimize the tri-objective problem in SGs: operating cost and pollution emission minimization, the minimization of the cost associated with load curtailment, and the minimization of the deviation between wind turbine (WT) output power and demand. Due to climatic conditions, the nature of the wind energy source is uncertain, and its prediction for day-ahead scheduling is challenging. Monte Carlo simulation (MCS) was used to predict wind energy before integrating with the SG. The DSM strategy used in this study consists of real-time pricing and incentives, which is a hybrid demand response program (H-DRP). To solve the proposed tri-objective SG scheduling problem, an optimization technique, the multi-objective genetic algorithm (MOGA), is proposed, which results in non-dominated solutions in the feasible search area. Besides, the decision-making mechanism (DMM) was applied to find the optimal solution amongst the non-dominated solutions in the feasible search area. The proposed scheduling model successfully optimizes the objective functions. For the simulation, MATLAB 2021a was used. For the validation of this model, it was tested on the SG using multiple balancing constraints for power balance at the consumer end. Full article

Non-small cell lung cancer (NSCLC) is a lethal non-immunogenic malignancy and proto-oncogene ROS-1 tyrosine kinase is one of its clinically relevant oncogenic markers. The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation. To curtail this resistance, researchers developed lorlatinib against the mutated kinase. In the present study, a receptor-ligand pharmacophore model exploiting the key features of lorlatinib binding with ROS-1 was exploited to identify inhibitors against the wild-type (WT) and the mutant (MT) kinase domain. The developed model was utilized to virtually screen the TimTec flavonoids database and the retrieved drug-like hits were subjected for docking with the WT and MT ROS-1 kinase. A total of 10 flavonoids displayed higher docking scores than lorlatinib. Subsequent molecular dynamics simulations of the acquired flavonoids with WT and MT ROS-1 revealed no steric clashes with the Arg2032 (MT ROS-1). The binding free energy calculations computed via molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) demonstrated one flavonoid (Hit) with better energy than lorlatinib in binding with WT and MT ROS-1. The Hit compound was observed to bind in the ROS-1 selectivity pocket comprised of residues from the β-3 sheet and DFG-motif. The identified Hit from this investigation could act as a potent WT and MT ROS-1 inhibitor. Full article

It is essential to develop effective mine waste management approaches and mine site reclamation techniques to curtail the adverse effects of mining processes on the natural environment. This study focuses on the use of partially desulphurized tailings as a moisture-retaining layer in an insulation cover with capillary barrier effects (ICCBE). Tailings were obtained from a nickel ultramafic ore processing plant at a mining company located in a continuous permafrost region of northern Québec, Canada. The geochemical response of tailings at two different sulphur contents (0.4 and 0.8 wt%), with and without ICCBEs, was tested by applying eight freeze-thaw and wetting cycles. Desulphurization of the tailings allowed to reduce the content of sulphide minerals by about 90%, from ~22 wt% to around 1.2–2.2 wt%. Column kinetic geochemical tests showed that Ni leaching was significantly reduced to concentrations ranging between 0.01–0.22 mg L⁻¹ compared to 0.63–1.92 mg L⁻¹ from the raw tailings (thanks to the desulphurization process). Zinc release was maintained around 0.04–1.72 mg L⁻¹ compared to 0.4–3.69 mg L⁻¹ from the raw tailing. Although all the columns produced leachates displaying circumneutral to slightly alkaline pH, the columns with ICCBE are expected to prevent acid mine drainage generation longer than the other columns due to reduced sulphide content and a constantly high degree of saturation maintained by capillary barrier effects. Full article

In the paper, a new method of long-term planning of operation and development of the distribution system, taking into account operational aspects such as power flows, power losses, voltage levels, and energy balances, is presented. The developed method allows for the allocation and selection of the power of Renewable Energy Sources (RES), control of energy storage (ES), curtailing of RES production (EC), and the development of the distribution grid (GD). Different types of RES and loads are considered, represented by generation/demand profiles reflecting their typical operating conditions. RES allocation indicates the node in the distribution system and the power level for each type of RES that may be built. Energy storage (ES) allows generation to be transferred from the demand valley to the peak load. Curtailment of RES generation indicates the moment and level of power by which generation will be reduced, while the grid development (GD) determines between which network nodes a new power line should be built. All these activities allow to minimize the costs of planning work and development of the distribution system at a specific level of energy consumption from RES in the analyzed distribution system using a Mixed Integer-Linear Programming (MILP). Full article