3,4‐Bis(bromomethyl)thieno[2,3‐b]thiophene: Versatile Precursors for Novel Bis(triazolothiadiazines), Bis(quinoxalines), Bis(dihydrooxadiazoles), and Bis(dihydrothiadiazoles)

A synthesis of novel bis(triazolothiadiazines) 11 , 12 , 13 , 14 , bis(quinoxalines) 16 and 17 , bis(thiadiazoles) 24 and 25 , and bis(oxadiazole) 31 , which are linked to the thieno[2,3‐b]thiophene core via phenoxymethyl group, was reported. Thus, reaction of the bis(α‐bromoketones) 6 and 7 with the corresponding 4‐amino‐3‐mercapto‐1,2,4‐triazole derivatives 8 , 9 , 10 in ethanol–DMF mixture in the presence of a few drops of triethylamine as a catalyst under reflux afforded the novel bis(5,6‐dihydro‐s‐triazolo[3,4‐b]thiadiazines) 11 , 12 , 13 , 14 in 60–72% yields. The bis(quinoxalines) 16 and 17 were also synthesized as a sole product in high yields by the reaction of 6 and 7 with o‐phenylenediamine 15 in refluxing acetonitrile in the presence of piperidine as a catalyst. Cyclization of the bis(aldehyde thiosemicarbazones) 20 and 21 with acetic anhydride afforded the corresponding bis(4,5‐dihydro‐1,3,4‐thiadiazolyl) derivatives 24 and 25 in good yield. Bis(5‐phenyl‐2,3‐dihydro‐1,3,4‐oxadiazole) derivative 31 could be obtained in 67% yield by cyclization of the appropriate bis(N‐phenylhydrazone) 29 in refluxing acetic anhydride for 3 h.     

Phytochemical Analysis,Pharmacological and Safety Evaluations of Halophytic Plant,Salsola cyclophylla

Salsola cyclophylla, an edible halophyte, is traditionally used for inflammation and pain. To confirm the claimed anti-inflammatory and analgesic properties, a detailed study on respective pharmacological actions was undertaken. The activities are contemplated to arise from its phytoconstituents. The LC-MS analysis of S. cyclophylla 95% aqueous-ethanolic extract revealed the presence of 52 compounds belonging to phenols, flavonoids, coumarins, and aliphatics class. A high concentration of Mn, Fe, and Zn was detected by atomic absorption spectroscopic analysis. The ethyl acetate extract showed the highest flavonoid contents (5.94 ± 0.04 mg/g, Quercetin Equivalents) and Fe2⁺-chelation (52%) potential with DPPH radicals-quenching IC₅₀ at 1.35 ± 0.16 mg/mL, while the aqueous ethanolic extract exhibited maximum phenolics contents (136.08 ± 0.12 mg/g, gallic acid equivalents) with DPPH scavenging potential at IC₅₀ 0.615 ± 0.06 mg/mL. Aqueous ethanolic extract and standard quercetin DPPH radicals scavenging’s were equal potent at 10 mg/mL concentrations. The aqueous ethanolic extract showed highest analgesic effect with pain reduction rates 89.86% (p = 0.03), 87.50% (p < 0.01), and 99.66% (p = 0.0004) after 60, 90, and 120 min, respectively. Additionally, aqueous ethanolic extract exhibited the highest anti-inflammation capacity at 41.07% (p < 0.0001), 34.51% (p < 0.0001), and 24.82% (p < 0.0001) after 2, 3, and 6 h of extract’s administration, respectively. The phytochemical constituents, significant anti-oxidant potential, remarkable analgesic, and anti-inflammatory bioactivities of extracts supported the traditionally claimed anti-inflammatory and analgesic plant activities.     

Oriental Hornet (Vespa orientalis) Larval Extracts Induce Antiproliferative,Antioxidant, Anti-Inflammatory,and Anti-Migratory Effects on MCF7 Cells

The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of Vespa orientalis larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (Bax, caspase3, and p53) and decreased expression of the anti-apoptotic gene Bcl2; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator Nrf2 and its downstream target HO-1; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene MMP9 and upregulation of the anti-migratory gene TIMP1; and (5) downregulation of inflammation-related genes (NFκB and IL8). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of Vespa orientalis larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.     

Ck-regularity for the $$\bar \partial $$ -equation with a support condition

Let D be a C ^d q-convex intersection, d ≥ 2, 0 ≤ q ≤ n ? 1, in a complex manifold X of complex dimension n, n ≥ 2, and let E be a holomorphic vector bundle of rank N over X. In this paper, C ^k -estimates, k = 2, 3,...,∞, for solutions to the \(\bar \partial \)-equation with small loss of smoothness are obtained for E-valued (0, s)-forms on D when n ? q ≤ s ≤ n. In addition, we solve the \(\bar \partial \)-equation with a support condition in C ^k -spaces. More precisely, we prove that for a \(\bar \partial \)-closed form f in C _0,q ^k (X D,E), 1 ≤ q ≤ n ? 2, n ≥ 3, with compact support and for ε with 0 < ε < 1 there exists a form u in C _0,q?1 ^k?ε (X D,E) with compact support such that \(\bar \partial u = f\) in \(X\backslash \bar D\). Applications are given for a separation theorem of Andreotti-Vesentini type in C ^k -setting and for the solvability of the \(\bar \partial \)-equation for currents.     

Heat transfer characteristics of staggered wing-shaped tubes bundle at different angles of attack

An experimental and numerical study has been conducted to clarify heat transfer characteristics and effectiveness of a cross-flow heat exchanger employing staggered wing-shaped tubes at different angels of attack. The water-side Re_w and the air-side Re_a were at 5 × 10² and at from 1.8 × 10³ to 9.7 × 10³, respectively. The tubes arrangements were employed with various angles of attack θ_1,2,3 from 0° to 330° at the considered Re_a range. Correlation of Nu, St, as well as the heat transfer per unit pumping power (ε) in terms of Re_a and design parameters for the studied bundle were presented. The temperature fields around the staggered wing-shaped tubes bundle were predicted by using commercial CFD FLUENT 6.3.26 software package. Results indicated that the heat transfer increased with the angle of attack in the range from 0° to 45°, while the opposite was true for angles of attack from 135° to 180°. The best thermal performance and hence the efficiency η of studied bundle occurred at the lowest Re_a and/or zero angle of attack. Comparisons between the experimental and numerical results of the present study and those, previously, obtained for similar available studies showed good agreements.     

Latent ruthenium initiators containing fluoro aryloxide ligands

A new ligand, methyl 2,3,5,6-tetrafluoro-4-oxybenzoate (C₈H₃F₄O₃), combining an electron withdrawing group (C₆F₄) to tune the reactivity with an anchor group (CO₂Me) for immobilization on supports, was used to prepare four new ruthenium initiators, viz. Ru(C₈H₃F₄O₃)₂(CHPh)(3-Br-C₅H₅N)(H₂IMes) and Ru(C₈H₃F₄O₃)₂XL, where X = C,N-(CHCH₂CH₂-2-C₅H₄N) and L = PⁱPr₃, PCy₃ or H₂IMes. The new ligand greatly reduced the reactivity of the ruthenium centre at room temperature. The ¹H NMR and DSC investigation for the ROMP of norbornene dicarboximide monomers clearly demonstrated that the Ru(C₈H₃F₄O₃)₂XL initiators were inactive at room temperature and required elevated temperatures for their activation.     

A digital microfluidic method for dried blood spot analysis

Blood samples stored as dried blood spots (DBSs) are emerging as a useful sampling and storage vehicle for a wide range of applications. Unfortunately, the surging popularity of DBS samples has not yet been accompanied by an improvement in automated techniques for extraction and analysis. As a first step towards overcoming this challenge, we have developed a prototype microfluidic system for quantification of amino acids in dried blood spots, in which analytes are extracted, mixed with internal standards, derivatized, and reconstituted for analysis by (off-line and in-line) tandem mass spectrometry. The new method is fast, robust, precise, and most importantly, compatible with automation. We propose that the new method can potentially contribute to a new generation of analytical techniques for quantifying analytes in DBS samples for a wide range of applications.     

Revealing the ionization ability of binding site I of human serum albumin using 2-(2'-hydroxyphenyl)benzoxazole as a pH sensitive probe

The ability of site I of human serum albumin (HSA) to bind medium sized molecules is important for the distribution, metabolism, and efficacy of many drugs. Herein, we show that this binding site has the ionization ability that may alter the drug structure during the process of its delivery. We reveal this ability by employing 2-(2'-hydroxyphenyl)benzoxazole (HBO) as a pH sensitive probe. Binding of HBO in site I is studied here at physiological pH 7.2 using steady-state and lifetime spectroscopic measurements, molecular docking and molecular dynamics (MD) simulation methods. The complex photophysics of HBO and the unique fluorescence signature of its anionic form indicate that, upon binding with HSA, the molecule exists in equilibrium between the anionic and the syn-keto forms. The position of HBO inside the binding site was determined experimentally by measuring the fluorescence quenching of W214, the sole tryptophan residue in HSA. The ionization degree of HBO inside the binding site was estimated to be close to the ionization degree of HBO in an aqueous solution of pH 10. This was concluded by comparing the fluorescence behavior of bound HBO to that of HBO in different solvents and in aqueous solutions of different pH values. Molecular docking and MD simulations show that HBO binds in site I close to W214, confirming the experimental results, and pinpoint the dominant role of hydrophobic interactions in the binding site. The formation of the anionic form is proposed to be due to through-space interaction between the OH group of HBO and both R222 and I290 with a binding mode similar to that of warfarin in site I. Comparison of the results with those of HBO mixed with key amino acids in solution indicates the importance of through-space interaction in the formation of the anion, similar to enzymatic reactions.