Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton

Versatile 2-(alkylthio)pyrimidine-type and 2-(phenacylamino)thiophene building blocks (4a-d) and 16 were obtained based on an ortho functionalized thiophene derivative 1. A novel series of thieno[2,3-d]pyrimidin-4-one derivatives with annelated bridgehead nitrogen heterocycles was synthesized starting from precursors 4 and 16 through convenient methods. Cyclocondensation of 2-(phenacylthio)pyrimidinone derivative (4b) with sulfuric acid led to the tricyclic thiazole derivative 5. Initial hydrazinolysis of 3-(carbethoxymethyl)pyrimidinone derivative (4d) followed by nitrous acid deamination of the formed N-aminolactam (7) to obtain a N-protodeamino analogue 8a, which on further treatment with formaldehyde and piperidine yielded the respective Mannich-type base 8b. On the other hand, initial hydrazinolysis of 3-unsubstituted pyrimidinone derivative 4a and subsequent acetylation gave the condensed 3-methyltriazole derivative 12, whereas the condensed pyrrole derivative 19 was obtained by heterocyclization of 2-phenacylamine derivative 16 with malononitrile. All newly-obtained thienopyrimidinones with annelated bridgehead nitrogen were screened for their antimicrobial activity against strains of a representative panel of Gram-positive and Gram-negative bacteria as well as fungi together with reference drugs. The compounds under investigation displayed generally good in vitro antibacterial and antifungal activities, with compound 8b that has a N-piperidinylmethyl moiety showing essentially the highest inhibition in both assays. Despite promising antimicrobial activity of N-1-substituted imidazole derivative 8b, the corresponding N-1-unsubstituted analogue 8a displayed poor activity. The heteroannelation of a N-(piperidinylmethyl)imidazole or 3-methyltriazole moiety to the thienopyrimidinone scaffold could be considered as a potential strategy for the development of new therapeutic antimicrobial agents

Path Planning for a 6 DoF Robotic Arm Based on Whale Optimization Algorithm and Genetic Algorithm

The trajectory planning for robotic arms is a significant area of research, given its role in facilitating seamless trajectory execution and enhancing movement efficiency and accuracy. This paper focuses on the development of path planning algorithms for a robotic arm with six degrees of freedom. Specifically, three alternative approaches are explored: polynomial (cubic and quantic), Whale Optimization Algorithm (WOA), and Genetic Algorithm (GA). The comparison of outcomes between different methods revealed that polynomial methods were found to be more straightforward to implement, albeit constrained by the intricacy of the pathway. Upon examining the functioning of the WOA, it has been shown that it is well suited for all types of pathways, regardless of their level of complexity. In addition, when GA is applied, it has been shown less smoothness than WOA but also less complexity. In brief, WOA is deemed superior in the path planning process since it is more thorough in determining the optimal path due to the conical spiral path technique it employs in offering optimized path planning. in comparison to GA, WOA is better in implementation speed and accuracy. However, GA is smoother in start and finish path

Path Planning for a 6 DoF Robotic Arm Based on Whale Optimization Algorithm and Genetic Algorithm

The trajectory planning for robotic arms is a significant area of research, given its role in facilitating seamless trajectory execution and enhancing movement efficiency and accuracy. This paper focuses on the development of path planning algorithms for a robotic arm with six degrees of freedom. Specifically, three alternative approaches are explored: polynomial (cubic and quantic), Whale Optimization Algorithm (WOA), and Genetic Algorithm (GA). The comparison of outcomes between different methods revealed that polynomial methods were found to be more straightforward to implement, albeit constrained by the intricacy of the pathway. Upon examining the functioning of the WOA, it has been shown that it is well suited for all types of pathways, regardless of their level of complexity. In addition, when GA is applied, it has been shown less smoothness than WOA but also less complexity. In brief, WOA is deemed superior in the path planning process since it is more thorough in determining the optimal path due to the conical spiral path technique it employs in offering optimized path planning. in comparison to GA, WOA is better in implementation speed and accuracy. However, GA is smoother in start and finish path

(Z)-Ethyl 2-cyano-2-{2-[5,6-dimethyl-4-(thio­phen-2-yl)-1H-pyrazolo­[3,4-b]pyridin-3-yl]hydrazinylidene}acetate

In the title compound, C17H16N6O2S, an intra­molecular N—H⋯O inter­action generates an S(6) ring. The pyridine ring makes a dihedral angle of 71.38 (11)° with the thio­phene ring. In the crystal, mol­ecules are linked by a pair of N—H⋯N hydrogen bonds, forming an inversion dimer. The dimers are stacked in columns along the b axis through weak inter­molecular C—H⋯N hydrogen bonds

Crosstalk Between Oxidative Stress and Endoplasmic Reticulum (ER) Stress in Endothelial Dysfunction and Aberrant Angiogenesis Associated With Diabetes: A Focus on the Protective Roles of Heme Oxygenase (HO)-1

Type-2 diabetes prevalence is continuing to rise worldwide due to physical inactivity and obesity epidemic. Diabetes and fluctuations of blood sugar are related to multiple micro- and macrovascular complications, that are attributed to oxidative stress, endoplasmic reticulum (ER) activation and inflammatory processes, which lead to endothelial dysfunction characterized, among other features, by reduced availability of nitric oxide (NO) and aberrant angiogenic capacity. Several enzymatic anti-oxidant and anti-inflammatory agents have been found to play protective roles against oxidative stress and its downstream signaling pathways. Of particular interest, heme oxygenase (HO) isoforms, specifically HO-1, have attracted much attention as major cytoprotective players in conditions associated with inflammation and oxidative stress. HO operates as a key rate-limiting enzyme in the process of degradation of the iron-containing molecule, heme, yielding the following byproducts: carbon monoxide (CO), iron, and biliverdin. Because HO-1 induction was linked to pro-oxidant states, it has been regarded as a marker of oxidative stress; however, accumulating evidence has established multiple cytoprotective roles of the enzyme in metabolic and cardiovascular disorders. The cytoprotective effects of HO-1 depend on several cellular mechanisms including the generation of bilirubin, an anti-oxidant molecule, from the degradation of heme; the induction of ferritin, a strong chelator of free iron; and the release of CO, that displays multiple anti-inflammatory and anti-apoptotic actions. The current review article describes the major molecular mechanisms contributing to endothelial dysfunction and altered angiogenesis in diabetes with a special focus on the interplay between oxidative stress and ER stress response. The review summarizes the key cytoprotective roles of HO-1 against hyperglycemia-induced endothelial dysfunction and aberrant angiogenesis and discusses the major underlying cellular mechanisms associated with its protective effects

NIS method for uncertainty estimation of airborne sound insulation measurement in field

In structures, airborne sound insulation is utilized to characterize the acoustic nature of barriers between rooms. However, the assessment of sound insulation index is once in a while troublesome or indeed, even questionable, both in field and laboratory measurements, notwithstanding the way that there are some unified measurement methodology indicated in the ISO 140 series standards. There are issues with the reproducibility and repeatability of the measurement results. A few troubles might be brought on by non-diffuse acoustic fields, non-uniform reverberation time, or blunders of the reverberation time measurements. Some minor issues are additionally postured by flanking transmission. In this paper, investigation of the uncertainties of the above specified measurement parts and their impact on the consolidated uncertainty in 1/3-octave frequency band. The total measurement uncertainty model contributes several different partial uncertainties, which are evaluated by the method of type A or type B. Also, the determination of the sound reduction index decided by ISO 140-4 has been performed

High Serine-arginine Protein Kinase 1 Expression with PTEN Loss Defines Aggressive Phenotype of Prostate Cancer Associated with Lethal Outcome and Decreased Overall Survival

Background: Serine-arginine protein kinase 1 (SRPK1) has been implicated in prostate cancer (PCa) progression. However, its prognostic value and association with ERG and PTEN expression, two of the most common genetic alterations, have not been explored fully. Objective: We assessed the prognostic value of SRPK1 in association with ERG and PTEN in a cohort of patients managed nonsurgically by androgen deprivation therapy (ADT) for advanced disease. Design, setting, and participants: The study cohort consisted of men diagnosed with PCa by transurethral resection of the prostate (TURP; n = 480). The patients were divided into three main groups: incidental (patients with Gleason score [GS] ≤7 with no prior ADT), advanced (patients with GS ≥8 with no prior ADT), and castrate-resistant PCa (patients with prior ADT). Outcome measurements and statistical analysis: A total of 480 TURP samples were assessed by immunohistochemistry for SRPK1, ERG, and PTEN, and results were correlated with Gleason grade group (GG), overall survival (OS), and PCa-specific mortality (PCSM). Results and limitations: High SRPK1 expression was noted in 105/455 (23%) available patient cores. Expression of SRPK1 was associated with Gleason grade grouping (p \u3c 0.0001) with high expression detected in 22/74 (33%) with GG 5. High SRPK1 was not associated with ERG positivity (p = 0.18) but was significantly associated with PTEN intensity (p = 0.001). High SRPK1 was associated with OS (hazard ratio [HR] 1.99; confidence interval [CI]: 1.57–2.54, p \u3c 0.0001) and PCSM (HR 1.64; CI: 1.19–2.26, p \u3c 0.002). Adjusting for Gleason score, patients with high SRPK1 and negative PTEN had the worst clinical outcome for both OS and PCSM compared with other patients (p \u3c 0.0001, HR: 3.02; CI: 1.87–4.88 and HR: 6.40, CI: 3.19–12.85, respectively). Conclusions: High SRPK1 is associated with worse OS and PCSM. Moreover, patients with high SRPK1 expression and loss of PTEN had the worst clinical outcome for OS and cancer-specific mortality. Combined status of SRPK1 and PTEN may provide added value in stratifying patients into various prognostic groups. Patient summary: The expression of serine-arginine protein kinase 1 (SRPK1) combined with PTEN has a significant prognostic role in prostate cancer patients. Patients with high SRPK1 expression and negative PTEN had the worst clinical outcome for overall survival and cancer-specific mortality

Improving productive performance, immunity, and health status of growing rabbits by using honey bee venom (Apis mellifera)

To investigate the effect of bee venom (BV) as a natural growth promotor on growing rabbits as an alternative to antibiotics, sixty 35-day-old Californian male rabbits with an average body weight of 584 ± 9 gm were randomly divided into five equal groups as follows: The 2nd group received drinking water supplied with 10 mg Oxytetracycline (OXT), while the 3rd, 4th, and 5th groups received 2, 4 and 8 mg bee venom (BV)/kg body weight/day in drinking water, and the first group was served as a control group. The growth performance features were positively impacted by adding BV (p ≤ 0.01) compared to the control, whereas LBW and BWG increased and FI reduced. Significantly improved carcass characteristics (p ≤ 0.01) as a result of the BV supplementation. Blood characteristics showed a significant reduction (p ≤ 0.01) in liver enzyme activities and Cholesterol, Triglycerides, and Low-density lipoproteins Cholesterol (LDL) as affected by BV treatment; inversely, total protein and globulin were significantly increased (p ≤ 0.01). Similarly, BV had a positive effect (p ≤ 0.01) on anti-oxidant status (Total anti-oxidant capacity (TAC), Glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT)). In contrast, the lipid peroxidation biomarker (Malondialdehyde (MDA)) was significantly decreased. The immunoglobulin (IgG and IgM) was significantly increased (p ≤ 0.01) by BV treatment. There was a positive effect of low BV levels on decreasing both cecum TBC and pathogenic bacterial count (Salmonella spp., E.coli spp., Proteus spp., and Clostridia spp.) that was significant (p ≤ 0.01). In conclusion, BV can be a natural growth promoter to enhance growth performance traits, immunological and anti-oxidative responses, and reduce pathogenic bacteria in the hindgut of growing rabbits