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Free Piston linear Generator (FPLG) engine fueled by compressed natural gas (CNG) has recently gained increased research attention. However, due to the low-velocity burning and poor lean limit of CNG fuel, the FPLG engine combustion stability, performance, and efficiency are still low. Hydrogen has a greater burning velocity with wider flame limits that could extend the lean burn limits and combustion characteristics of CNG. This paper compares pure CNG and 10% hydrogen-enriched CNG at various ignition speeds (0.6 ms, 0.8 m/s, and 1 m/s), injection positions (0 mm, 5 mm, 10 mm and 15 mm), and lambda ratios (0.9, 1.4 and 1.7) on the combustion characteristics, performance, and conversion efficiency are duly discussed. The findings show that the FPLG combustion stability limits increase with the hydrogen addition into the CNG. The CNG in-cylinder pressure increases significantly when the injection position is advanced, whereas the hydrogen addition reduces the influence of the injection position. The heat release rate increases by 15.62% and 23.72% with hydrogen addition, corresponding to the advanced and retarded injection positions. Consequently, the hydrogen addition increases the power RMS to 209.21 W and 232.64 W with an increment of 3.46% and 3.13%, respectively. Conclusively, the hydrogen addition into the CNG evidently shortens the combustion duration while improving the heat release rate, combustion stability, power RMS, Cycle-to-Cycle variation, and conversion efficiency.

This study investigated the behavior of semi-lightweight self-consolidating concrete (SLWSCC) and lightweight vibrated concrete (LWVC) beams developed with improved shear capacity and cracking behavior. Fourteen concrete beams were cast with different types of lightweight aggregates (either fine or coarse expanded slate aggregates), total binder contents (550 kg/m3 and 600 kg/m3), fiber lengths (8 mm and 12 mm), and different fiber volume fractions (0.3%, 0.5%, and 1%). The experimental results were also compared with several code-based equations and selected proposed models from the literature that predict the shear strength of reinforced concrete beams with and without fibers. The inclusion of shorter polyvinyl alcohol (PVA) fibers appeared to have more influence on improving the shear performance and cracking behavior of SLWSCC beams compared to longer fibers. It was also found that using expanded slate fine aggregate exhibited better results in terms of the beams’ load-carrying capacity, post-diagonal cracking resistance, and energy absorption capacity compared to using expanded slate coarse aggregate. The highest increases in the shear capacity, deformation capacity, post-diagonal cracking resistance, and energy absorption capacity were observed in LWVC beams, as it was possible to use a higher percentage of PVA fibers (1%) because of the absence of self-compactability restrictions.

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.

Objective: Oxidative stress (OS) plays a key role in the etiology of unexplained male infertility. Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve semen quality and OS in infertile men with idiopathic oligoasthenoteratospermia (OAT), but the underlying mechanism is unknown. Therefore, the present study was undertaken to investigate the effect of CoQ10 on OS markers and sperm DNA damage in infertile patients with idiopathic OAT. Methods: This prospective controlled study included 50 patients with idiopathic OAT and 50 fertile men who served as controls. All patients underwent a comprehensive medical assessment. Patients and controls received 200 mg of oral CoQ10 once daily for 3 months. Semen and blood were collected and analyzed for sperm parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity, catalase, sperm DNA fragmentation (SDF), and serum hormonal profile. Results: The administration of CoQ10 to patients with idiopathic OAT significantly improved sperm quality and seminal antioxidant status and significantly reduced total ROS and SDF levels compared to pre-treatment values. Conclusion: CoQ10, at a dose of 200 mg/day for 3 months, may be a potential therapy for infertile patients with idiopathic OAT, as it improved sperm parameters and reduced OS and SDF in these patients.

This study aimed to utilize cholesterol conjugation of 5-fluorouracil (5-FUC) and liposomal formulas to enhance the partitioning of 5-FU into low density lipoprotein (LDL) to target hepatocellular carcinoma (HCC). Thus, 5-FU and 5-FUCwere loaded into liposomes. Later, the direct loading and transfer of 5-FU, and 5-FUC from liposomes into LDL were attained. The preparations were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and cytotoxicity using the HepG2 cell line. Moreover, the drug deposition into the LDL and liver tissues was investigated. The present results revealed that liposomal preparations have a nanosize range (155 − 194 nm), negative zeta potential (- 0.82 to – 16 mV), entrapment efficiency of 69% for 5-FU, and 66% for 5-FUC. Moreover, LDL particles have a nanosize range (28–49 nm), negative zeta potential (- 17 to −27 mV), and the entrapment efficiency is 11% for 5-FU and 85% for 5-FUC. Furthermore, 5-FUC loaded liposomes displayed a sustained release profile (57%) at 24 h compared to fast release (92%) of 5-FU loaded liposomes. 5-FUC and liposomal formulas enhanced the transfer of 5-FUC into LDL compared to 5-FU. 5-FUC loaded liposomes and LDL have greater cytotoxicity against HepG2 cell lines compared to 5-FU and 5-FUC solutions. Moreover, the deposition of 5-FUC in LDL (26.87ng/mg) and liver tissues (534 ng/gm tissue) was significantly increased 5-FUC liposomes compared to 5-FU (11.7 ng/g tissue) liposomal formulation. In conclusion, 5-FUC is a promising strategy for hepatic targeting of 5-FU through LDL-mediated gateway., Graphical abstract

The chitosan chains were integrated with MCM-48 mesoporous silica in an eco-friendly composite (CH/MCM-48) of enhanced adsorption capacity. The prepared CH/MCM-48 composite was applied in systematic retention of U (VI) as well as Sr (II) ions from water as the commonly detected radioactive pollutants. It displayed promising retention capacities of 261.3 mg/g and 328.6 mg/g for U (VI) and Sr (II) considering the equilibrium time interval that was identified after 420 min. The composite showed the kinetic behavior of the Pseudo-First order model and the isotherm properties of the Langmuir assumption. The thermodynamic assessment of the reactions validated the retention of both U (VI) and Sr (II) ions by spontaneous, favorable, and exothermic reactions. Based on the theoretical values of entropy (−5.94 kJ mol−1 (U (VI)) and −2.93 kJ mol−1 (Sr (II))), Gibbs free energy (less than 20 kJ mol−1), and Gaussian energy (5.77 kJ mol−1 (U (VI)) and 4.56 kJ mol−1 (Sr (II))) the uptake processes are related to physical adsorption reactions. The CH/MCM-48 composite is of significant recyclability and showed considerable affinities for the studied radioactive ions even in the presence of other metal ions (Cd (II), Pb (II), Zn (II), and Co (II)).

Sildenafil has been identified as the first agent for treating male erectile dysfunction and is a selective inhibitor of phosphodiesterase 5 (PDE5). Its chemical structure consists of three moieties named; 1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one, 5-(2-ethoxy-1-ylsulfonyl)phenyl and 4-methylpiperazine. Many articles are reported the cytotoxic activity of each moiety individually. The combination into a single molecule (sildenafil) of these three structural features could have promising anti-cancer and cytotoxic effects. The study evaluated sildenafil cytototoxic activity in vitro against mammalian cell lines: MCF-7, HCT-116, HeLa cells and A-549 cells with their IC50 values. Sildenafil showed considerable cytotoxic activity (IC50 = 28.2 ± 0.92, 45.2 ± 1.5, 30.5 ± 0.87 and 60.5 ± 3.2 μg/mL) against HCT-116, MCF-7, A-549 and HeLa cells, respectively. HCT-116 was the most sensitive cell line towards sildenafil followed by A-549, A375, MCF-7 and HeLa cells. These findings shed light on the antitumor activity of sildenafil and its possible impact on potentiating of cytokines, antitumor and anti-inflammatory markers in tumour cells. These effects might be related to the structure feature of sildenafil.

Graphical abstract, Modulation of the structure and function of biomaterials is essential for advancing bio-nanotechnology and biomedicine. Microtubules (MTs) are self-assembled protein polymers that are essential for fundamental cellular processes and key model compounds for the design of active bio-nanomaterials. In this in silico study, a 0.5 μs-long all-atom molecular dynamics simulation of a complete MT with approximately 1.2 million atoms in the system indicated that a nanosecond-scale intense electric field can induce the longitudinal opening of the cylindrical shell of the MT lattice, modifying the structure of the MT. This effect is field-strength- and temperature-dependent and occurs on the cathode side. A model was formulated to explain the opening on the cathode side, which resulted from an electric-field-induced imbalance between electric torque on tubulin dipoles and cohesive forces between tubulin heterodimers. Our results open new avenues for electromagnetic modulation of biological and artificial materials through action on noncovalent molecular interactions.

The aim of this work is to study the thermal performance of four configurations of absorber plates of solar air collectors under three levels of air mass flow rates (0.0199, 0.047 and 0.120kg/s) and fabricate an efficient and cheap solar air collector from recyclable aluminum cans. Solar air collectors were manufactured and tested under prevailing weather conditions of Shebin El-Kom city (30˚.54'N and 31 E), Egypt. Comparisons between the temperature difference of air across the collector and thermal efficiencies of the flat, aluminum cans, and v-corrugated plate solar air collectors were presented. The results revealed that the maximum thermal efficiency was obtained at mass flow rate of 0.047kg/s for an solar air collector with an absorber plate made of single layer of recyclable aluminum cans) type-I), whereas the lowest thermal efficiency was obtained for the solar air collector without cans (flat plate). The thermal efficiency of the solar air collectors depends principally on the solar radiation, surface geometry of the collectors and air mass flow rate.

Ocimum forskolei (Habak), Lamiaceae, is an endemic species from Yemen and KSA; where our present study was aimed at investigating the Metabolic profiling coupled with LC HR-MS analysis of the dichloromethane fraction from the aerial parts of that plant with a special emphasis on ursolic acid as the major predominating compound from this fraction. Histopathological evaluation of ursolic acid in different doses against indomethacin-induced ulcers in rats revealed a highly significant and dose dependent protection. With the dose level of 50 mg/kg b.w., Ursolic acid gave an ulcer index of 1.33 ± 0.33 and 97.8% inhibition, compared to cimetidine as a standard with 3.0 ± 0.58 and 95.2%. To rationalize this activity, docking on various macromolecular targets was performed, followed by molecular dynamics on the most promising target; the M3 receptor. A high binding energy of -344 kJ/mol is predicted between Ursolic acid and the protein indicating the stability of the predicted pose.

A new series of N-acyl hydrazones (4a-g) derived from indole-3-propionic acid (IPA) were synthesized. These N-acyl hydrazones were prepared by the reaction of 3-(1H-indol-3-yl) propane hydrazide and aldehyde in the existence of glacial acetic acid as a catalyst. 1HNMR and FT-IR analyses were used to identify the synthesized compounds and they were in vitro evaluated as antibacterial agents against six different types of microorganisms by using well diffusion method. All the tested N-acyl hydrazones (4a-g) displayed moderate activity against the Gram-negative E.coli, comparable to that of Amoxicillin. Some of the tested N-acyl hydrazones also exhibited intermediate activity against some of the examined Gram-positive and Gram-negative bacteria. While no activity was exhibited by any of the examined compounds against the Gram-positive S. aureus.

Oxidative stress (OS) is a key contributing factor in 30–80% of male infertility cases. To date, several antioxidant treatments have been put forth to manage OS-induced male infertility. This study intended to elucidate the impact of coenzyme Q10 (CoQ10) and selenium on seminal fluid parameters and antioxidant status in infertile men with idiopathic oligoasthenoteratospermia (OAT). In this prospective study, 70 patients with idiopathic OAT were randomly allocated to receive CoQ10 (200 mg/day) or selenium (200 μg/day) for 3 months. Semen quality parameters (following WHO guidelines, 5th edition), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activities were compared before and after the treatment. The results of the study showed an increase in sperm concentration with CoQ10 treatment (p

Obesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

A straightforward green synthesis of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 6 is reported from ninhydrin 1 via condensation with ethyl acetoacetate, followed by cyclization with hydrazine hydrate in water as a benign solvent. Tetraazafluoranthen-3-thione 7 was obtained using Lawesson’s reagent. N-alkylated tetraazafluoranthen-3-one 8–12 and S-alkylated analogues 13–15 were synthesized via alkylation. The investigation of the unique reactivity of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one/thione toward the alkylation and aza-Michael additions was explored.

A nickel(II)dibenzotetramethyltetraaza[14]annulene complex (Nitmtaa) is prepared and immobilized on amino-functionalized TUD-1 (N-TUD-1) via a Ni–N (NH2) bond to obtain a stable and reusable new nanocatalyst named as Nitmtaa@N-TUD-1. The catalytic activity performance of this new nanocatalyst was evaluated in the epoxidation of cyclohexene under ambient conditions (25 °C, 1 atm) using meta-chloroperoxybenzoic acid (m-CPBA) as the oxidant, and CH2Cl2/CH3CN (1 : 1 v/v) as the solvent. (3-Aminopropyl)triethoxysilane (APTES) was first grafted on the TUD-1 surface, then Nitmtaa was added and coordinated with amine groups on the TUD-1 surface to produce the nanocatalyst Nitmtaa@N-TUD-1. The structure and morphology of the obtained nanocatalyst were studied using SEM, HR-TEM, BET analysis, FTIR spectroscopy, and powder XRD analysis. The thermal stability was investigated using TGA and DTA. HR-TEM and XRD results revealed a high dispersion of Nitmtaa on the TUD-1 surface. The obtained nanocatalyst exhibited an immediate and quantitative epoxidation reaction of cyclohexene to cyclohexene oxide under ambient conditions with a high turnover frequency (TOF) of ∼42.11 s−1. Moreover, the catalyst Nitmtaa@N-TUD-1 maintained the high catalytic activity performance and exhibited high stability in four successive cycles. The atomic absorption spectroscopy (AAS) experiments performed on the filtrate after each cycle showed a negligible leaching of Nitmtaa from the support N-TUD-1. A plausible reaction mechanism pathway is also proposed.

Herein, the mono and dialkylation of pyridazino[4,5-b]indole were achieved with a set of alkylating agents, including amyl bromide, allyl bromide, benzyl bromide and ethyl chloroacetate in the presence of K2CO3/acetone or KOH/DMSO. The hydrazinolysis of mono and di-esters 10 and 11 gave the target hydrazides 12 and 13, which displayed promising, potent, and significant cytotoxic activity against the MCF-7 cell line with IC50 values of 4.25 and 5.35 μm compared to that of the standard drug 5-FU (IC50 6.98 μm), respectively. RT-PCR analysis of the most active compound 12 was performed to determine its mode of action through the up-regulation of pro-apoptotic genes and inhibition of anti-apoptotic and PI3K/AKT/mTOR genes. The findings were consistent with the proposed mechanism illustrated in the in silico study. Further, the in vivo analysis exhibited its potent anti-cancer activity through the prolongation of survival parameters, and inhibition of ascetic fluid parameters in EAC-bearing mice.

Obesity is a medical condition associated with serious medical and psycho-social consequences and an augmented body fat mass. Several compounds were suggested to counteract obesity and fat accumulation with variable degrees of success. Searching for a safe and effective anti-adipogenic substance, we found that cuminaldehyde-rich essential oil extracted from Calligonum comosum potentially mediate activities. The results showed that C. comosum essential oil and its major component cuminaldehyde, selectively caused significant reduction in the viability of 3T3-L1 cells when compared to fibroblasts. Furthermore, cuminaldehyde caused significant reduction in the lipid content, glucose uptake and levels of both triglycerides and cholesterol in adipocytes. Moreover, the formation of 3D-adipocyte pellets in the presence of cuminaldeyde was affected. Adipocytes matured in the presence of cuminaldehyde have significant reduction in the expression of adipocyte-specific transcripts, CAAT-enhancer binding protein alpha (CEBPa) and Peroxisome proliferator-activated receptor gamma (PPARg). Taken together, these results demonstrate a potential inhibitory role of cuminaldehyde extracted from C. comosum oil on lipid accumulation. Consequently, cuminaldeyde can be considered as a new potential anti-adipogenic agent for prevention and treatment of obesity.

Four different new Schiff basses tethered indolyl-triazole-3-thione hybrid were designed and synthesized. X-ray single crystal structure, tautomerism, DFT, NBO and Hirshfeld analysis were explored. X-ray crystallographic investigations with the aid of Hirshfeld calculations were used to analyze the molecular packing of the studied systems. The H···H, H···C, S···H, Br···C, O···H, C···C and N···H interactions are the most important in the molecular packing of 3. In case of 4, the S···H, N···H, S···C and C···C contacts are the most significant. The results obtained from the DFT calculations indicated that the thione tautomer is energetically lower than the thiol one by 13.9545 and 13.7464 kcal/mol for 3 and 4, respectively. Hence, the thione tautomer is the most stable one which agree with the reported X-ray structure. In addition, DFT calculations were used to compute the electronic properties while natural bond orbital calculations were used to predict the stabilization energies due to conjugation effects. Both compounds are polar where 4 (3.348 Debye) has a higher dipole moment than 3 (2.430 Debye).

A new compounds named 3-4′-bipyrazoles 2 and 3 were synthesized in high chemical yield from a reaction of pyran-2,4-diketone 1 with aryl hydrazines under thermal conditions in MeOH. Compound 2 was unambiguously confirmed by single-crystal X-ray analysis. It crystalizes in a triclinic crystal system and space group P-1. Its crystal structure was found to be in good agreement with the spectral characterizations. With the aid of Hirshfeld calculations, the H…H (54.8–55.3%) and H…C (28.3–29.2%) intermolecular contacts are the most dominant, while the O…H (5.8–6.5%), N…H (3.8–4.6%) and C…C (3.0–4.9%) are less dominant. The compound has a polar nature with a net dipole moment of 6.388 Debye. The BD(2)C31-C32→BD*(2)N4-C34 (27.10 kcal/mol), LP(1)N5→BD*(2)C31-C32 (36.90 kcal/mol), BD(1)C32-C34→BD*(1)C18-C31 (6.78 kcal/mol) and LP(1)N4→BD*(1)N5-C31 (7.25 kcal/mol) are the strongest π→π*, n→π*, σ-σ* and n→σ* intramolecular charge transfer processes, respectively.

Our previous study revealed that the treatment of 5-aza-2-deoxycytidine (5-aza) inhibited while treatment of suberoylanilide hydroxamic acid (SAHA) enhanced the adipogenic differentiation of MG-63 cells. In this study, we examined the transcriptomic profiles of the derived adipocyte-like cells from MG-63 cells in the presence of 5-aza (Treatment 1) and SAHA (Treatment 2). Genome wide expression analysis showed high within sample variability for the adipocytes derived with 5-aza versus vehicle. Additionally, the expression profile of 5-aza derived cells was separated from the other sample groups. Differential analysis on the pairwise comparison of 5-aza versus control and SAHA versus 5-aza identified 1290 and 1086 differentially expressed (DE) genes, respectively. Furthermore, some overlap was observed between the up and down-regulated DE genes of 5-aza versus control and SAHA versus control (jaccard score 0.3) as well as between the differentially regulated genes of 5-aza versus control and 5-aza versus SAHA (jaccard score 0.29). A total of 73 transcription factors (TFs) were differentially expressed across all the pair wise comparisons with some overlap between the under and over expressed TFs of 5-aza versus control and 5-aza versus SAHA (jaccard score 0.29). Unsupervised clustering of TFs showed that the samples within the group are consistent in expression and the samples cluster in accordance with the group. Several GO terms related to enhanced adipogenesis such as neutral lipid biosynthetic process, lipid metabolic processes, cellular amide metabolic processes and cellular carbohydrate metabolic processes were enriched in the down regulated genes of 5-aza derived adipocytes versus control, indicating 5-aza inhibit the adipogenic differentiation of MG-63 cells. GSEA analysis on selected gene sets of MAPK and PI3K signaling pathway in MSigDB identified the pathways were up-regulated in 5-aza versus control. This study revealed that inhibition of MG-63 adipogenesis due to 5-aza treatment is associated with large transcriptomics changes and further research is needed to unravel the roles of these genes in the adipogenesis.

Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment. The 17-item Hamilton Depression Rating Scale (HRSD17) scores gauged depressive symptom severity. More significant metabolic changes were found after 8 weeks than 4 weeks post baseline. Within the tryptophan pathway, we noted significant reductions in serotonin (5HT) and increases in indoles that are known to be influenced by human gut microbial cometabolism. 5HT, 5-hydroxyindoleacetate (5HIAA), and the ratio of 5HIAA/5HT showed significant correlations to temporal changes in HRSD17 scores. In the tyrosine pathway, changes were observed in the end products of the catecholamines, 3-methoxy-4-hydroxyphenylethyleneglycol and vinylmandelic acid. Furthermore, two phenolic acids, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid, produced through noncanconical pathways, were increased with drug exposure. In the purine pathway, significant reductions in hypoxanthine and xanthine levels were observed. Examination of metabolite interactions through differential partial correlation networks revealed changes in guanosine–homogentisic acid and methionine–tyrosine interactions associated with HRSD17. Genetic association studies using the ratios of these interacting pairs of metabolites highlighted two genetic loci harboring genes previously linked to depression, neurotransmission, or neurodegeneration. Overall, exposure to escitalopram/citalopram results in shifts in metabolism through noncanonical pathways, which suggest possible roles for the gut microbiome, oxidative stress, and inflammation-related mechanisms.

Purpose: The purpose of this research was to compare the effectiveness of platelet rich fibrin (PRF), alvogyl and zinc oxide/ eugenol (ZOE) intra-alveolar dressings for pain relief and socket healing (Epithelialization) in dry socket management and to study relevant epidemiological features.Patients and methods: A total of 45 patients with alveolar osteitis were randomly divided into three groups; Group (A) patients received PRF, Group (B) patients received Alvogyl and Group (C) patients received ZOE dressing. All the patients were evaluated for Pain (VAS), degree of inflammation, healthy granulation tissue formation and number of exposed socket walls (socket epithelialization) at 1st, 3rd, 7th, and 14th post-operative day. Results: Group A (PRF) showed better and faster socket healing than Group B and C. However, symptomatic pain relief was faster in Group B (Alvogyl) than in Group A and C.Conclusion: PRF in this study illustrates the promising results to be used effectively as the suitable dressing material in the management of alveolar osteitis. PRF treated cases showed a shorter time required for complete and fast clinical healing.

Objective: Diabetic complications involve multiple pathological pathways, including hyperglycemia-induced oxidative stress and inflammation. Combination therapy is usually employed to improve treatment outcomes and to lower potential adverse effects. In this study, we evaluated the effects of antidiabetic and antihypertensive agents, glibenclamide (GLI) and losartan (LT), on diabetes mellitus (DM)-associated metabolic changes in rats. Materials and Methods: Streptozotocin-induced diabetic animals were orally treated with GLI 5 mg/kg and/or LT 25 mg/kg for 4 weeks. Blood glucose, insulin, aspartate aminotransferase, alanine aminotransferase, urinary creatinine, and urea levels were measured. Serum, liver, and kidney values of inflammatory markers, such as interleukin-1β, tumor necrosis factor alpha, and interleukin-6 were assessed, along with lipid peroxidation products (e.g., thiobarbituric acid reactive substances), endogenous antioxidants (e.g., glutathione), as well as antioxidant enzyme activities (e.g., catalase, superoxide dismutase, and glutathione peroxidase). Finally, histological changes in liver and kidney tissues were evaluated. Results: DM markedly induced systemic, hepatic, and renal inflammation and lowered antioxidant defense mechanisms. Treatment of diabetic rats with either GLI or LT significantly improved liver and kidney functions and histological structure. Moreover, both medications reduced signs of oxidative stress and inflammation in blood, liver, and kidney samples. Combining GLI and LT showed similar protective potential against systemic, hepatic, and renal oxidative stress and inflammation. Conclusion: Adding LT to GLI therapy revealed prospective antioxidant and anti-inflammatory action, while no synergistic or additive effects were observed.

The aim of this study was to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating oxidative stress, dyslipidemia, and hyperglycemia commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into eight experimental groups, fed on a normal diet or high-fat diet (HFD), then given mangosteen extract (400 mg /kg /day) and/or curcumin (80 mg/kg /day) for 6 weeks. Oxidative stress markers, glucose, and lipid fractions were measured in the sera. Mangosteen pericarp extract (MPE) induced a remarkable decrease in BMI (from 0.86 to 0.81 gm/cm2), while curcuma either alone or in combination was more effective, as treated rats recorded BMIs of 0.78 and 0.79 gm/cm2, respectively. Regarding the antioxidant effects, MPE induced a significant increase of GSH in obese rats (123.86 ± 15.53 μg/ml vs 288.72 ± 121.37 μg/ml). As anti-atherogenic agents MPE demonstrate significant effect recorded higher level of HDL-C in treated animals, but ineefective as anti-dyslipidemic agent. Curcumin was more effective in reducing LDL-C levels in obese rats. Both extracts effectively reduced blood glucose. The present study demonstrated that MPE and curcumin were independently and synergistically effective in treating obesity-induced atherogenesis.

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium-chain and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines—including arginine, proline, and methionine sulfoxide—were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism, and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17 ≤ 7) and those who gained no meaningful benefits (17). Remitters exhibited (a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine, and serotonin; and (b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2, and PC aa C36:4. These findings suggest that mitochondrial energetics—including acylcarnitine metabolism, transport, and its link to β-oxidation—and lipid membrane remodeling may play roles in SSRI treatment response.

Liver cancer is the most common type of cancer in many countries. New studies and statistics show rising liver cancer worldwide, so it is essential to seek new agents for this type of cancer. PIM1 has an attractive target in the discovery of cancer medications as it is very much expressed in a variety of malignancies and influences such as tumorigenesis, cell cycle progression, cellular proliferation, apoptosis, and cell migration. Accordingly, a series of pyridones and pyridine-amides were synthesized and tested for anti-liver cancer activity. In the synthetic strategy 4,6-diaryl-3-cyano-2-pyridones 3a-n were synthesized using one-pot four component synthetic method. Structural modifications were done on 4,6-diphenyl-3-cayno-2-pyridone 3a to enhance the activity. Alkylation in the presence of K2CO3 afforded the O-alkylated products 4–6. The acetoxy hydrazide 7 was synthesized and cyclized into 1,3,4-oxadiazolethione 8 which alkylated on sulfur to give 10. Azide-coupling method was used to couple the 2-(pyridin-2-yloxy)acetohydrazide 7 to different amines and amino acid esters to furnish the products 12a-e and 13a-b. The synthesized derivatives were subjected to cytotoxic screening against HepG2 and THLE-2 cells, Compounds 10, 12e and 13a have a remarkable cytotoxic activity with IC50 values (10.7–13.9 µM). Compound 7 was found to be more cytotoxic by showing the lowest IC50 value of 7.26 compared to 5-FU (IC50 = 6.98 µM). It inhibited cell growth by 76.76%. Additionally, it significantly stimulated apoptotic liver cancer cell death with 49.78-fold (22.90% compared to 0.46% for the control) arresting cell cycle Pre-G1 with 35.16% of a cell population, compared to 1.57% for the control. Moreover, it validated the intrinsic apoptosis through upregulation of P53, and other related genes, with inhibition of anti-apoptotic genes through PIM-1 inhibition.

The 3-(1H-indol-2-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-ol 2 was obtained exclusively in the enol configuration starting from triazolyl-indole derivative 1 and alkyl halo-esters in the presence of K2CO3. Chemical structure elucidations with the aid of physicochemical characterizations were used to predict its molecular structure while single crystal X-ray diffraction technique was used to shed the light on the supramolecular structure of 2. DFT calculations agreed very well with the reported X-ray structure where the most stable form thermodynamically is the enol form. Its optimized geometry agreed very well with the experimental structure where the correlation coefficients between the calculated and experimental geometric parameters are very close to 1. Using Hirshfeld analysis, the most significant intermolecular contacts are the N…H, H…C(π), O…H, S…H and C…C contacts. peerReviewed

Chitosan/zeolite-A nanocomposite (CH/ZA) was synthesized as a potential carrier for levofloxacin (LVOX) of enhanced technical properties. The CH/ZA composite displayed enhanced loading capacity (425 mg/g) as compared to chitosan (188.8 mg/g) and zeolite-A (234.6 mg/g). The loading behavior follows Pseudo-Second-order and Langmuir as kinetic and isotherm models. The equilibrium studies, Gaussian energy (8.15 KJ/mol), and thermodynamic parameters demonstrate homogenous and monolayer loading by complex chemical and physical reactions that are of spontaneous and exothermic nature. The CH/ZA composite is of slow and continuous release profile (200h) with 94.3% as the maximum release percentage. The release reactions are of non-Fickian behavior involving both diffusion and erosion mechanisms. The loading of LVOX into CH/ZA induced its anti-inflammatory effect against the cytokine production (IL-6 and IL-8) within the human bronchial epithelia cells (NL20). The cytotoxicity studies on the normal cells demonstrated a high safety value for the composite.

Two new hits of triazolyl-indole containing two different alkylsulfanyl analogues named tert-butyl 2-((4-amino-5-(1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)thio)acetate 2, and ethyl 2-((4-amino-5-(1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)thio)acetate 3 were synthesized via reaction of 4-amino-5-(1H-indol-2-yl)-1,2,4-triazol-3(2H)-thione 1 with tert-butyl bromoacetate and ethyl chloroacetate in the presence of base (Et3N). The molecular structure of 2, and 3 was confirmed by single-crystal X-ray diffraction and 1H/13C- NMR spectroscopic techniques. In compound 2, the molecular packing depends on significant O...H (9.3%), N...H (12.4%) and S...H (3.1%) as well as relatively weak C...H (14.1%), S...C (2.1%), H...H (50.5%) and S...S (0.9%) contacts. Similarly, the strong O...H (11.0-12.3%) and N...H (13.1-13.6%) hydrogen bonds as well as weak C...H (15.3-16.4%), S...N (0.8-1.7%) and H...H (43.6-43.9%) are the most important interactions compound in 3. Both compounds are polar molecules where hit 2 (0.980 Debye) is less polar than 3 analogue (5.029 Debye). The atomic charge distribution and molecular electrostatic potential map as well as the reactivity descriptors were also discussed. The calculated NMR and UV-Vis spectra of the studied compounds were computed and compared with the experimental data. The different σ→σ*, π→π*, n→σ* and n→π* donor-acceptor interactions were investigated using NBO analysis. peerReviewed

Background Oxidative stress has been implicated in male infertility through decrease in sperm quality. However, men with normal semen parameters (normozoospermia) may be unable to fertilize their partners even when they have normal sperm function. Thus, they would be considered infertile. The purpose of this study was to investigate the role of oxidative stress in the pathogenesis of unexplained male infertility. Methods In this case–control study, infertile men with normozoospermia (n = 46) and fertile control group (n = 21) underwent seminal fluid analyses according to WHO 2010 criteria. Serum and seminal plasma levels of total antioxidant capacity (TAC), glutathione, malondialdehyde, uric acid and albumin were also measured using colorimetric methods. Results The level of total antioxidant capacity in both serum and seminal plasma was significantly lower in normozoospermic infertile men in comparison with fertile group (p Conclusion Low TAC level induces oxidative stress and consequently causes sperm dysfunction and male infertility. Estimation of TAC can be a useful tool in the diagnosis of male infertility. Antioxidant supplementation should be considered in the treatment of oxidative stress-induced male infertility.

The rules governing Medicinal Products in the European Union necessitates the production of cell-based therapy in good manufacturing practice facilities. The produced cells may need several hours in transportation to reach the application sites. In this study, we investigated four candidate solutions for transporting human keratinocytes. The solutions are (1) normal saline, (2) saline with 2.5% human serum albumin (Saline + HSA), (3) chemically defined, xeno-free keratinocyte media and (4) keratinocyte media with pituitary bovine extract (PBE-media). One million keratinocytes from three donors were suspended in each solution and kept at 4 °C for up to 24 h. Cells kept in Saline + HSA showed higher viability after 1, 3 and 24 h. Then, equal number of viable cells were seeded on collagenous matrix and cultured for 48 h. The adhesion and colonization were higher in the cells kept in PBE-media, while the keratinocyte surface marker, cytokeratin 14, was present in all studied groups. These results confirmed the suitability of Saline + HSA as a cell transportation solution for clinical use, which will be the choice for the planned clinical trial. Keratinocyte PBE-media can be an alternative for cells transported for research purpose, if the same media type is going to be used in the following experiments. Funding: Open Access funding provided by Linköping University Library

Nickel(II)dibenzotetramethyltetraaza[14]annulene complex (Nitmtaa) was synthetized and immobilized on post amino-functionalized SBA-15 (N-SBA-15) to obtain a stable and reusable nanocatalyst named as Nitmtaa@N-SBA-15. Here (3-aminopropyl)triethoxysilane (APTES) was first grafted on the surface SBA-15, then Nitmtaa was added and coordinated on the silica surface via APTES amine groups. The structure and morphology, and thermal stability of the prepared nanocatalyst was investigated using SEM, HR-TEM, BET, FT-IR, powder XRD, and TGA. HR-TEM and XRD results revealed a high dispersion of Nitmtaa on the SBA-15 surface. The catalytic activity of this nanocatalyst was evaluated in the epoxidation of styrene, under ambient conditions, using meta-chloroperoxybenzoic acid (m-CPBA) as the oxygen donor. This nanocatalyst showed an immediate and quantitative epoxidation of styrene with high turn-over-frequency ∼31.58 s−1. Moreover, the superior catalytic activity and high stability of Nitmtaa@N-SBA-15 could be maintained after four successive cycles. A possible reaction mechanism is also proposed.

Benzylsulfanyl-triazolyl-indole scaffold was synthesized through coupling of 4-amino-5-(1H-indol-2-yl)-1,2,4-triazol-3(2H)-thione and benzyl bromide in EtOH under basic conditions (K2CO3). The benzylation direction was deduced from the 13C NMR signal found at 35.09 ppm, assigned for the methylene carbon of the benzyl group, this value indicates that the benzyl group attacks sulfur, not nitrogen. 1H NMR, 13C NMR, COSY, HMQC, HRMS and X-ray single crystal diffraction analysis were used for structure assignment. The desired compound accomplished in good yield. Hirshfeld analysis revealed the importance of the short N...H (1.994&ndash, 2.595 Ǻ), S&hellip, H (2.282 Ǻ) and C&hellip, H (2.670 Ǻ) contacts as well as the weak &pi, &pi, stacking interactions in the molecular packing of benzylthio-triazolyl-indole scaffold. Its electronic and structural aspects were predicted using density functional theory (DFT) calculations and the reactivity descriptors as well. The Uv-Vis spectral bands were assigned based on the time-dependant density functional theory TD-DFT calculations, while the gauge-including atomic orbitals (GIAO) method was used to predict the 1H and 13C NMR chemical shifts.

The designed target compound of N-acetyl indole linked to a fused triazolo/thiadiazole scaffold was synthesized via the reaction of 4-amino-5-(1H-indol-2-yl)-1,2,4-triazol-3(2H)-thione as the starting material with acetic anhydride under reflux conditions for 6 h, resulting in an excellent and pure chemical yield. The structural features of the designed compound were confirmed using spectroscopic tools including single crystal X-ray diffraction analysis along with 1H-NMR, 13C-NMR, 2D-NMR, and high resolution mass spectrometry. Using Hirshfeld analysis, we determined the molecular packing depends on strong interactions (O&middot, &middot, H and N&middot, H) along with weak interactions (S&middot, H, C&middot, H and H&middot, H). The shortest contacts corresponding to the N3&middot, H12 (2.490 &Aring, ), N2&middot, H5 (2.503 &Aring, ), and O1&middot, H2 (2.490 &Aring, ) interactions were confirmed based on the Hirshfeld analysis. The calculated dipole moment was 6.6557 Debye. The atomic charge distribution, molecular electrostatic potential map, and reactivity descriptors are also discussed. The computed NMR spectra of the requisite compound correlated well with the results obtained experimentally. The UV-Vis electronic spectra of the requisite compound were simulated using the TD-DFT method and compared with the experimental data. The different &sigma, &rarr, &sigma, *, &pi, &pi, *, n&rarr, *, and n&rarr, * donor&ndash, acceptor interactions and their interaction energies stabilized the studied system to 9.84, 20.65, 29.33, and 45.82 kcal/mol, respectively.

The work aimed to improve both absorption and hepatic availability of sofosbuvir. Bilosomes and galactose-anchored bilosomes were investigated as potential nanocarriers for this purpose. Sofosbuvir is a class III drug with high solubility and low permeability. Thus, the drug entrapment into lipid-based galactose-anchored carriers would enhance drug permeability and improve its liver availability. The galactosylated taurocholate was designed and synthesized based on molecular docking studies, where both galactose and taurocholate molecules were connected in a way to avoid affecting crucial interactions and avoid steric clashes with their cellular uptake receptors. The suggested nano-carriers were prepared using a thin-film hydration technique with sodium taurocholate and span 60 as stabilizers. The prepared formulae were statistically optimized using a central composite design. The optimized plain and galactosylated formulae, composed of SAA to drug ratio of 1:1 w/w and sodium taurocholate to span ratio of 10:1 w/w, have a vesicular size, zeta potential and entrapment efficiency in the range of 140–150 nm, −50 mV and 85%, respectively. The optimized formulae were lyophilized to increase their physical stability and facilitate accurate drug dosing. In vivo results showed that Sofosbuvir availability in the liver was significantly increased after oral administration of the plain and the galactosylated bilosomal formulae when compared to the oral drug solution with relative targeting efficiencies (RTIs) of 1.51 and 3.66, respectively. These findings confirmed the hypothesis of considering the galactosylated bilosomes a promising nanocarrier to efficiently target sofosbuvir to the liver.

A multicomponent synthesis was empolyed for the synthesis of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 1. An interesting cyclization was obtained when the amino-ester 1 reacted with ethyl isothiocyanate to give the benzo[4,5]thieno[2,3-d][1,3]thiazin-4-one 3. Acylation of the amino-ester 1 with chloroacetyl chloride in DCM and Et3N afforded the acylated ester 4. The amino-ester 1 was cyclized to benzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one 8, which was reacted with some alkylating agents leading to alkylation at nitrogen 9&ndash, 13. Hydrazide 14 was utilized as a synthon for the synthesis of the derivatives 15&ndash, 19. Chloro-thieno[2,3-d]pyrimidine 20 was synthesized and reacted with the hydrazine hydrate to afford the hydrazino derivative 21, which was used as a scaffold for getting the derivatives 22&ndash, 28. Nucleophilic substitution reactions were used for getting the compounds 29&ndash, 35 from chloro-thieno[2,3-d]pyrimidine 20. In the way of anticancer therapeutics development, the requisite compounds were assessed for their cytotoxicity in vitro against MCF-7 and HepG-2 cancer cell lines. Twelve compounds showed an interesting antiproliferative potential with IC50 from 23.2 to 95.9 &micro, M. The flow cytometric analysis results showed that hit 4 induces the apoptosis in MCF-7 cells with a significant 26.86% reduction in cell viability. The in vivo study revealed a significant decrease in the solid tumor mass (26.6%) upon treatment with compound 4. Moreover, in silico study as an agonist for inhibitors of JAK2 and prediction study determined their binding energies and predicted their physicochemical properties and drug-likeness scores.

Coenzyme Q10 has shown promise in treating male infertility; however, there are inconsistencies across the published data. We undertook a quantitative meta-analysis by pooling data from three placebo-controlled randomised clinical trials (RCTs) in order to evaluate the efficacy of CoQ10 in improving semen parameters. Sperm count, sperm motility, sperm forward motility, sperm morphology and CoQ10 level in the seminal plasma were measured and quantitatively correlated with CoQ10 oral administration. Pooled analysis showed a significant impact of CoQ10 in improving sperm motility and forward motility, without a significant impact on sperm count, sperm morphology, ejaculate volume or seminal plasma level of CoQ10. Efficacy assessment suggested that CoQ10 shows better results at higher doses and when administered for a period of more than 3 months but not longer than 6 months. We conclude that CoQ10 has a profound effect on sperm motility and a meagre effect on all other parameters. Therefore, CoQ10 can be used for treating asthenozoospermic infertility with the dosage and duration depending upon the severity of the disorder and the patient's response to the treatment.

The physical and thermal properties and free radical co-polymerization of new poly(N-isopropylacrylamide) (PNIPAAm) derivatives: ethylene diamine (EDA), 1,3-diaminopropane (DAP), Urea (Ur) and thiourea (TUr) were studied. In each copolymer the low critical solution temperature (LCST) which was observed at (32°C ± 1). The thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) investigations of hydrogels shows that the loss of swelled water starts from (20°C). The swelling behaviors of all copolymers was studied into two ways and at different temperatures, were the best swelled hydrogels are PNIPAAm-co-TUr at (25°C), PNIPAAm at (35°C), and PNIPAAm-co-EDA at (45°C) based on medical cotton as a surface. The ability of water swelling has been varied according to the functions group of the co-monomer and the way of it connection in polymer chain that’s due to hydrogen bonding with water. The medical cotton shows a good water swelling surface more than Iraqi fluff and tail cottons. The surface area of these polymers has been determined by Brunauer–Emmett–Teller (BET) were PNIPAAm-co-EDA have the highest surface area (9.357 m2/g), and the PNIPAAm-co-Ur have the lowest one (0.055 m2/g). It revealed different values according to linking terminal of these monomers in PNIPAAm backbone.

Graphical abstract, Reactive oxygen species (ROS) are produced as by-products of several intracellular metabolic pathways and are reduced to more stable molecules by several protective pathways. The presence of high levels of ROS can be associated with disturbance of cell function and could lead to apoptosis. The presence of ROS within the physiological range has many effects on several signalling pathways. In stem cells, this role can range between keeping the potency of the naive stem cells to differentiation towards a certain lineage. In addition, the level of certain ROS would change according to the differentiation stage. For example, the presence of ROS can be associated with increasing the proliferation of mesenchymal stem cells, decreasing the potency of embryonic stem cells and adding to the genomic stability of induced pluripotent stem cells. ROS can enhance the differentiation of stem cells into cardiomyocytes, adipocytes, endothelial cells, keratinocytes and neurons. In the meantime, ROS inhibits osteogenesis and enhances the differentiation of cartilage to the hypertrophic stage, which is associated with chondrocyte death. Thus, ROS may form a link between naïve stem cells in the body and the environment. In addition, monitoring of ROS levels in vitro may help in tissue regeneration studies.

This paper investigates experimentally and analytically the shear performance of RC beams made of recycled coarse aggregate (RCA). Previous studies showed that the partial replacement of the virgin coarse aggregate by recycled one results in decrease the shear strength of RC beams. Consequently, the main target of the this research was to compensate such decrease in the shear strength by providing internal short fibers and using cured recycled coarse aggregate instead of crude recycled coarse aggregate. A total of eleven simply supported RC beams made of recycled coarse aggregate along with one conventional concrete beam were tested under incremental four-point loading scheme. The considered parameters were the recycled coarse aggregate replacement ratio (15, 30 and 45%), the shear span-to-depth ratio (1, 2 and 3) and the fiber volumetric ratio (1, 1.5 and 2%). In addition, to improve the physical and mechanical properties of the recycled coarse aggregate (RCA), two curing methods for the RCA were implemented using cement slurry and Styrene Butadiene Rubber (SBR) compound. The experimental results showed that increasing the replacement ratio of the RCA resulted in decrease the shear capacity proportionally. The percentages of decreases in the shear capacities were about 8%, 14% and 19%, respectively, for RC beams provided by RCA replaced by 15%, 30% and 45%. In addition, it was shown that providing internal short fibers by volumetric ratios of 1%, 1.5% and 2% enabled the RC beams made of 30% partial replacement of the recycled coarse aggregate to compensate the decreases in the shear capacities (14%) and to increase their shear capacities by about 13%, 15% and 22% compared to those of the control beam, respectively. Furthermore, for RC beams made of 30% partial replacement of the RCA, the shear capacities decreased by about 2%, 14% and 37%, respectively, for beams having shear span-to-depth ratio of 1, 2 and 3. Besides, it was shown that, the cured recycled coarse aggregate enabled the RC beams made of 30% partial replacement to exhibit improved shear performance. However, the curing method based on cement slurry showed higher improvement since the restored shear capacities were about 15% and 3% for beams provided by cured coarse aggregate based on cement slurry and compound SBR, respectively compared to that of the beam made of crude RCA. Finally, an equation for estimating the shear capacity of RC beams made of recycled coarse aggregate was proposed and it showed satisfactory results when verified against the experimental findings of the current research as well as of other researches where the maximum variations were about 8.5% and 22%, respectively.

A new series of nitrogen and sulfur heterocyclic systems were efficiently synthesized by linking the following four rings: indole; 1,2,4-triazole; pyridazine; and quinoxaline hybrids. The strength of the acid that catalyzes the condensation of 4-amino-5-(1H-indol-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 1 with aromatic aldehydes controlled the final product. Reflux in glacial acetic acid yielded Schiff bases 2−6, whereas concentrated HCl in ethanol resulted in a cyclization product at C-3 of the indole ring to create indolo-triazolo-pyridazinethiones 7−16. This fascinating cyclization approach was applicable with a wide range of aromatic aldehydes to create the target cyclized compounds in excellent yield. Additionally, the coupling of the new indolo-triazolo-pyridazinethiones 7−13 with 2,3-bis(bromomethyl)quinoxaline, as a linker in acetone and K2CO3, yielded 2,3-bis((5,6-dihydro-14H-indolo[2,3-d]-6-aryl-[1,2,4-triazolo][4,3-b]pyridazin-3 ylsulfanyl)methyl)quinoxalines 19−25 in a high yield. The formation of this new class of heterocyclic compounds in high yields warrants their use for further research. The new compounds were characterized using nuclear magnetic resonance (NMR) and mass spectral analysis. Compound 6 was further confirmed by the single crystal X-ray diffraction technique.

A series of triazolo-thiadiazepines 4a&ndash, k were synthesized with excellent yields using dehydrated PTSA as a catalyst in toluene. Two triazolo-thiadiazines were obtained, 8a was formed directly by reflux in ethanol, whereas, PTSA promoted the formation of 8b. The molecular structure of the formed triazolo-thiadiazepines is identical to the imine-form 4a&ndash, k and not the enamine-tautomer 6a&ndash, k. The structures of the newly synthesized triazolo-thiadiazepines 4a&ndash, k and triazolo-thiadiazines 8a&ndash, b were elucidated using NMR (1H, and 13C), 2D NMR, HRMS, and X-ray single crystal. Furthermore, 4a was deduced using X-ray single crystal diffraction analysis. These new thiadiazepine hits represent an optimized series of previously synthesized indole-triazole derivatives for the inhibition of EGFR. The cytotoxicity activity against two cancer cell lines including human liver cancer (HEPG-2) and breast cancer (MCF-7) was promising, with IC50 between 12.9 to 44.6 &micro, g/mL and 14.7 to 48.7 &micro, g/mL for the tested cancer cell lines respectively, compared to doxorubicin (IC50 4.0 &micro, g/mL). Docking studies revealed that the thiadiazepine scaffold presented a suitable anchor, allowing good interaction of the various binding groups with the enzyme binding regions and sub-pockets.