Background: Endothelial dysfunction (ED) is a marker of vascular damage and the precursor of cardiovascular diseases such as hypertension, which involve inflammation and organ damage. Nitric oxide (NO) produced by eNOS, which is induced by pAKT, plays a crucial role in the function of a healthy endothelium. Methods: A combination of the subfractions SF1 and SF3 (C4) of the aqueous fraction from Cucumis sativus (Cs-Aq) was evaluated to control endothelial dysfunction in vivo, and on HMEC-1 cells to assess the involvement of pAkt in vitro. C57BL/6J mice were daily injected with Ang-II for 10 weeks. Once hypertension was established, Cs-AqC4 or losartan were orally administered along with Ang-II for another 10 weeks. Blood pressure (BP) was measured at weeks 0, 5, 10, 15, and 20. Serum creatinine was quantified; the inflammatory status was evaluated in kidney, and tissue damage and vascular remodeling were studied in liver and aorta. Cs-AqC4 was also evaluated in vitro on HMEC-1 cells stimulated by angiotensin II (Ang-II) to assess the involvement of Akt phosphorylation. Results: Cs-AqC4 decreased systolic and diastolic BP, reversed vascular remodeling, decreased IL-1β and TGF-β and increased IL-10 and decreased kidney and liver damage. In HMEC-1 cells, AKT phosphorylation and NO production were increased. Conclusions: Cs-AqC4 controlled inflammation and vascular remodeling, resulting in BP regulation; it also improved tissue damage associated with ED, probably via Akt activation.

This study employs molecular docking experiments to investigate the binding interactions of Hypericin with key proteins implicated in Alzheimer's disease (AD). Hypericin demonstrated a significant binding energy of -10.1 kcal/mol with ABAD (3-hydroxyacyl-CoA dehydrogenase type II). The analysis revealed multiple binding interactions, including hydrogen bonds with arginine 6, serine 7, and glutamic acid 140, as well as hydrophobic bonds involving leucine 11, aspartic acid 142, and aspartic acid 86. These findings illuminate the intricate molecular interactions between Hypericin and ABAD, suggesting its potential as a lead compound for further therapeutic development in the context of Alzheimer's disease. Additionally, a parallel docking investigation was conducted for Beta-secretase 1 (BACE1), a protein pivotal in the generation of beta-amyloid peptides—a hallmark of Alzheimer's disease. Inhibiting BACE1 activity is considered a promising therapeutic strategy for AD. Computational analyses suggest that Hypericin may serve as a potential inhibitor of BACE1. Molecular Docking results reveal a robust binding affinity between Hypericin and BACE1, supported by a significant binding energy score of -10.3 kcal/mol. Notably, both ABAD and BACE1 exhibit high binding affinity with Hypericin. This theoretical exploration provides an initial understanding of the intricate molecular pathways involved in Alzheimer's disease and proposes Hypericin as a potential therapeutic compound for mitigating its progression.

The new diprotic ligand 3,5-di-tert-butylsalicylaldehyde 4-ethyl-3-thiosemicarbazone, abbreviated H2(3,5-t-Bu2)-sal4eT, exists as the thio-keto tautomer and adopts the E-configuration with respect to the imine double bond as evidenced by single-crystal X-ray analysis and corroborated by spectroscopic characterisation. Upon treatment with Cu(OAc)2·H2O in the presence of either 2,9-dimethyl-1,10-phenanthroline (2,9-Me2-phen) or 1,10-phenanthroline (phen) as a co-ligand in MeOH, this thiosemicarbazone undergoes conformational transformation (relative donor-atom orientations: syn,anti → syn,syn) concomitantly with tautomerization and double deprotonation to afford the ternary copper(II) complexes [Cu{(3,5-t-Bu2)-sal4eT}(2,9-Me2-phen)] (1) and [Cu2{3,5-t-Bu2)-sal4eT}2(phen)] (2). Crystallographic elucidation has revealed that complex 1 is a centrosymmetric dimer of mononuclear copper(II) complex molecules brought about by intermolecular H-bonding. The coordination geometry at the copper(II) centre is best described as distorted square pyramidal in accord with the trigonality index (τ = 0.14). The co-ligand adopts an axial-equatorial coordination mode; hence there is a disparity between its two Cu–N coordinate bonds arising from weakening of the apical one as a consequence of the tetragonal distortion. The axial X-band ESR spectrum of complex 1 is consistent with retention of this structure in solution. Complex 2 is a centrosymmetric dimer of dinuclear copper(II) complex molecules exhibiting intermolecular H-bonding and π-π-stacking interactions. The two copper(II) centres, which are 4.8067(18) Å apart and bridged by the thio-enolate nitrogen of the quadridentate thiosemicarbazonate ligand, display two different coordination geometries, one distorted square planar (τ4 = 0.082) and the other distorted square pyramidal (τ5 = 0.33). Such dinuclear copper(II) thiosemicarbazone complexes, which are crystallographically characterised, are extremely rare. In vitro, complexes 1 and 2 outperform cisplatin as antiproliferative agents in terms of potency and selectivity towards HeLa and MCF-7 cancer cell lines.

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

Under high-frequency operating conditions, the high-speed solenoid valve (HSV) experiences energy loss and heat generation, which significantly impact its operational lifetime. Reducing the energy loss of HSV without compromising its opening response characteristics poses a significant challenge. To address this issue, a finite element simulation model of HSV coupled with a current feedback model is constructed to investigate the synergistic effects of dynamic response and energy loss. Predictive models for the opening response time, HSV driving energy, and Joule energy using Back Propagation neural network (BPNN) are established. Furthermore, a multi-objective optimization study on the current driving strategy using Non-dominated Sorting Genetic Algorithm II (NSGA-II) is conducted. After optimization, although there was a 6.24% increase in the opening response time, both HSV drive energy and Joule energy were significantly reduced by 15.67% and 22.49%, respectively. The proposed multi-objective optimization method for HSV driving strategy holds great significance in improving its working durability.

The present article seeks to analyse the period 1938-1940, when the Romanian interwar democracy was suspended through the promulgation of the anti-liberal Constitution of 27 February 1938. The Constitution abolished the political parties and trade unions, replacing them with new institutions established according to royal decrees: the royal single party, known as the National Renaissance Front (Frontul Renaşterii Naţionale, FRN) and corporations of workers and employers, respectively. Starting from that moment, the regime, through its representatives, made recourse to a nationalist rhetoric directed against the democratic parliamentary system. Moreover, a cult of personality of the monarch can be identified in the speeches of the royal corporatist ‘parliament’, as well as in the doctrine of FRN and the Nation’s Party (its successor), but also in the regime’s youth organisation, ‘The Country’s Sentinel’ (Straja Ţării), whose First Sentinel was the authoritarian monarch himself. Thus, the cult of personality of Carol II represented one of the sources of inspiration for the dictator Nicolae Ceauşescu and for the leaders of this totalitarian regime.

We report a novel dual-band barrier infrared detector (DBIRD) design using type-II superlattices (T2SLs). The DBIRD structure consists of back-to-back barrier diodes: a "blue channel" (BC) diode which has an nBp architecture, an n-type layer of larger bandgap for absorbing blue band infrared/barrier/p-type layer, and a "red channel" (RC) diode which has an pBn architecture, a p-type layer of smaller bandgap for absorbing red band infrared/barrier/n-type layer. Each has a unipolar barrier using a T2SL lattice matched to a GaSb substrate to impede the flow of majority carriers from the absorbing layer. Each channel in the DBIRD can be independently accessed with a low bias voltage, as is preferable for high-speed thermal imaging. Device modeling of DBIRDs and simulation results of the current-voltage characteristics under dark and illuminated conditions are also presented. They predict that dual-band operation of the DBIRD will produce low dark currents and 27-33% quantum efficiencies for the in-band photons in the BC with λc=5.58 μm, and a nearly-constant 33% in the RC with λc=8.05 μm. The spectral quantum efficiency of the BC for 500 K blackbody radiation is approximately 20% over the range of λ=3 − 4.2 μm, while that of the RC has a peak of 42% at 5.7 μm. The DBIRD may provide improved high-speed dual-band imaging in comparison with NBn dual-band detectors.

This study determines the equivalent stress intensity factor (SIF) model that best fits the experimental behavior of low-carbon steel under mixed mode (I and II). The study assessed Tanaka, Richard, and Pook's equivalent SIF models. The theoretical values used for comparison correspond to experimental results in a modified C(T) geometry by machining a hole ahead of the crack tip subjected to fatigue loads with a load ratio of R = 0.1. The comparison involved the SIF for six experimental points and the values computed through the numerical simulation. The Paris, Klesnil, and modified Forman-Newman crack growth models were used with each equivalent SIF to analyze the prediction in the estimated number of cycles. The Klesnil model showed the closest prediction since the error between the calculated and experimentally recorded number of cycles is the lowest. However, the material behavior reflects a reduced crack propagation rate attributed to plasticity in the crack tip. Results suggest that Asaro equivalent SIF conservatively estimates the element lifespan with increasing errors from 2.3% at the start of growth to 27 % at the end of the calculation.

Abstract. The remarks by the Supreme Leader of the Islamic Revolution on the toll of the famines that afflicted occupied Iran in World War I and World War II indicate a desire to incorporate these calamities in Iran’s national narrative and collective memory. His criticism of famine historiography and stated toll numbers, and the unfolding catastrophic famine in Gaza, justify and necessitate a fresh look at each famine’s historiography and toll. This article re-estimates the toll of each famine by including many overlooked and neglected primary sources and in ways not previously done. It builds a trajectory of Iran’s demographic development from 1810 to 1944, and derives the toll of each famine. The World War II famine and typhus epidemics had claimed 5.5 million. World War I famine was also more deadly, though the 1869-73 famine was not far behind. At least 15.5 million Iranians died in the two world wars, a fact nowhere reflected in the history of the conflicts. Iran’s 1944 population of 12 million was unchanged from that of 1850 and a century of population growth obliterated

Due to the retrognathic mandible, an orthodontist frequently observes skeletal class II malocclusion in growing patients. The preferred technique for analyzing and monitoring the temporomandibular joint alterations caused by the functional device is magnetic resonance imaging [MRI]. The study aimed to assess and compare changes in the articular disc's dimension and location before and following the use of various class II correctors to correct the class II molar relation using MRI technology. Methods: 39 adolescent patients aged 15-23 years old [24 girls and 15 boys] who were diagnosed with skeletal Class II division 1 malocclusion based on clearly defined criteria underwent treatment with either the power scope II [PS], Sabbagh Advanced Repositioning Appliance [SARA] and or Dynaflex [DF] with fixed appliances. For fixed functional treatment, the average length of treatment was 5-7 months. The changes in the articular disc dimension and position and condylar position were assessed. The study was done at the Department of Orthodontics at the College of Dentistry, Hawler Medical University in Erbil City. Results: Group DF has a significant effect on the condylar position index and posterior joint space on the closed mouth and disc length on both open and close mouth techniques, and in the group SARA, disc position, and condylar position index on closed mouth technique have shown that significant differences were observed. Conclusion: Class II malocclusions can be effectively corrected by fixed functional appliances. The statistical significance forward movement of the condyle in the glenoid fossa and the posterior movement of the articular disc concerning the condylar head was observed. The mechanism of action of functional appliances appears to include the forward migration of the C-GF complex.

Tunicate orthologs in the human genome comprise just 84 genes of the 19,872 protein-coding genes, yet they stand at the base of the Olfactores clade - which radiated to generate thousands of tunicate and vertebrate species. What were the powerful drivers among the 84 that enabled this process? Many of these orthologs are present in gene families. We discuss the biological role of each family and the orthologs’ quantitative contribution to the family. Most important was the evolution of a second type of cadherin. This, a Type II cadherin, had the property of detaching the cell containing that cadherin from cells that expressed the Type I class. The set of such Type II cadherins could now detach and move away from their Type I neighbours, a process which would eventually evolve into the formation of the neural crest, “ the fourth germ layer”, providing a wide range of possibilities for further evolutionary invention. A second important contribution were key additions to the broad development of the muscle and nerve protein and visual perception tool-kits. These developments in mobility and vision provided the basis for the development of the efficient predatory capabilities of the Vertebrata.

Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. Psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine.

In the history of high-performance polymer composite parts with continuous in-plane fibre reinforcement, the comparatively moderate structural-mechanical properties in their out-of- plane-z-direction and the limited load carrying capability between individual reinforcement layers within the laminated structures have always been one of the greatest challenges. Plenty of research work has been carried out to improve load transfer capability as well as fracture toughness for crack opening events between the reinforcement layers by means of out-of-plane fibre reinforcement implementation, for example by sewing or z-pinning technologies. However, the results have not become established across a wide range of applications so far, because the technologies used have led to considerable losses of in-plane strength properties. In this paper first results are presented for a new method of a low fraction z-fibre reinforcement by means of very thin diameter laser drilled holes filled with short carbon fibres, demonstrating potential to improve Mode II fracture toughness.

The reaction between 5-acetylbarbituric acid and 4-dimethylthiosemicarbazide or 4-hexamethyleneiminyl thiosemicarbazide produces 5-acetylbarbituric-4-dimethylthiosemicarbazone (H2AcbDM) and 5-acetylbarbituric-4N-hexamethyleneiminyl thiosemicarbazone (H2Acbhexim). Eight new complexes with different cooper (II) salts have been prepared and characterized using elemental analysis, molar conductance, UV–vis, ESI-HRMS, FT-IR, magnetic moment, EPR and cyclic voltammetry. In addition, three-dimensional molecular structures of [Cu(HAcbDM)(H2O)2](NO3)·H2O (3a), [Cu(HAcbDM)(H2O)2]ClO4 (4), and [Cu(HAcbHexim)Cl] (6) were determined by single crystal X-ray crystallography, and was carried out an analysis of their supramolecular structure. The H-bonded assemblies were further studied energetically using DFT calculations, MEP surface and QTAIM analyses. In these complexes, the thiosemicarbazone coordinates to the metal ion in an ONS-tridentate manner, in the O-enolate/S-thione form. The electrochemical behavior of the thiosemicarbazones and their copper(II) complexes has been investigated at room temperature using the cyclic voltammetry technique in DMFA. The Cu(II)/Cu(I) redox system was found to be consistent with the quasi-reversible diffusion-controlled process.

In this study, a modular multi-step photometric microflow injection analysis (micro-FIA) system for the automatic determination of Cu(II) in a bioreactor has been developed. The system incorporates diverse 3D-printed modules, including a platform formed by a mixer module to mix Cu(II) with hydroxylamine which reduces Cu(II) to Cu(I) linked to a diluter module via a Tesla valve, a chelation mixer module, a disperser module, and a detector module provided by a LED light source at λ= 455 nm and a light dependence resistor (LDR) as a light intensity detector. The system measures the color intensity resulting from the chelation between Cu(I) and neocuproine. The micro-FIA system has demonstrated good capability for automatic and continuous Cu(II) determination, in a wide range of Cu concentrations from 34 to 2000 mg L-1. The device exhibits a good repeatability (coefficient of variation below 2% across the concentration range), good reproducibility, and has an accuracy of around 100% between 600 to 1900 mg·L-1. Real samples were analyzed using both the micro-FIA system and an atomic absorption spectroscopy method, revealing no statistically significant differences. Additionally, a Tesla valve located before the detector substituted a 3-way solenoid valve, eliminating the need for moving parts.