Abstract Astragaloside IV (AS-IV) has been shown to possess cardioprotective effect. However, the specific mechanism of AS-IV in myocardial infarction (MI) remains unclear. Our results showed that AS-IV intervention observably enhanced cell viability and reduced cell apoptosis, oxidative stress levels and inflammatory factor secretion. Expression of MIRT1 was significantly up-regulated in hypoxia-treated cells. In addition, ALCAM overexpression reversed the effects of AS-IV intervention on hypoxia-treated cell functions. MIRT1 facilitated Runx3 promoter methylation and its downregulated expression by recruiting DNA methyltransferase 3B (DNMT3B) to the Runx3 promoter region through binding with suppressor of Zeste 12 protein homolog (Suz12). Runx3 silencing reversed the effects of MIRT1 inhibition on hypoxia-treated cell functions. Betulinic acid suppressed the effects of AS-IV intervention on the behaviors of hypoxia-treated cells. AS-IV treatment improved the cardiac functions of mice with MI. Taken together, these findings demonstrated that AS-IV treatment inhibits DNMT3B-mediated Runx3 promoter methylation by restraining Suz12 expression and further blocks the NF-κB signaling pathway, and in turn improves the cardiac functions of mice with MI.

A series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2-23.2 µg/mL) and PTP1B (IC50 = 2.9-21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.

Posterior long-segment spinal fusion may lead to proximal junctional kyphosis (PJK). The present study sought to identify the appropriate fusion levels required in order to prevent PJK using finite element analysis. A finite element model was constructed based on the whole-spine computed tomography findings of a healthy adult. Nine commonly used posterior spinal fusion methods were selected. Stress on the annulus fibrosis fibers, the posterior ligamentous complex, and the vertebrae after various spinal fusions in the upright position were compared. This study was divided into two groups: non-fusion and fusion. In the former, the stress between the T10 and the upper thoracic vertebrae was higher. Comparing thoracic and lumbar segments in the fusion group, the peak stress values of the upper instrumented vertebrae (UIV) were mainly observed in T2 and L2 whilst those of the UIV+1 were observed in T10 and L2. After normalization, the peak stress values of the UIV and UIV+1 were located in T2 and L2. Similarly, the peak stress values of the annulus fibrosus at the upper adjacent level were on T10 and L2 after normalization. However, the peak stress values of the interspinal/supraspinal complex forces were concentrated on T11, T12, and L1 after normalization whilst the peak stress value of the pedicle screw was on T2. Controversy remains over the fusion of T10, and this study simulated testing conditions with gravitational loading only. However, further assessment is needed prior to reaching definitive conclusions.

Through decreasing the sample size, the regular faceted rectangular Al2Cu phase crystal was prepared under directional solidification. Effects of sample size on the microstructure morphologies and orientations of intermetallic Al2Cu phase crystal growth at 10 µm/s have been characterized and investigated. The transverse-section microstructure of primary Al2Cu phase crystal transited from L-shaped pattern to regular faceted rectangular pattern with a single preferred orientation at [001] direction with sample size decreasing. By using the serial sectioning technique, the three-dimensional (3D) microstructure of Al2Cu phase in 0.45 mm sample was observed as rectangular parallelepiped. Moreover, the faceted interfaces of Al2Cu phase crystal were determined as {110} planes. Based on growth characteristics of the Al2Cu phase crystal, a growth mode in different sizes samples under directional solidification was proposed. The experimental results show that a regular microstructure with preferred single orientation can be achieved in small-size sample during directional solidification.

A previously reported o-nitrobenzaldehyde (ONBA) degrading bacterium Pseudomonas sp. ONBA-17 was further identified and characterized. Based on results of DNA base composition and DNA-DNA hybridization, the strain was identified as P. putida. Its degradation effect enhanced with increase of inoculum amount and no lag phase was observed. Higher removal rate was achieved under shaking conditions. All tested ONBA with different initial concentrations could be completely degraded within 5 d. In addition, degradative enzyme(s) involved was confirmed as intra-cellular distributed and constitutively expressed. Effects of different compounds on relative activity of degradative enzyme(s) within cell-free extract were also evaluated. Finally, 2-nitrobenzoic acid and 2, 3-dihydroxybenzoic acid were detected as metabolites of ONBA degradation by P. putida ONBA-17, and relevant metabolic pathway was preliminary proposed. This study might help with future research in better understanding of nitroaromatics biodegradation.

Neste estudo, uma nova série de derivados de 4H-[1,2,4]triazina[3,4-a]ftalazin-4-ona substituídos em C-7 foi sintetizada como potenciais agentes anticonvulsivantes. Suas atividades anticonvulsivantes foram avaliadas pelo teste do eletrochoque máximo (MES), e suas neurotoxicidades, pelo teste 'rotarod' de neurotoxicidade. Os resultados farmacológicos mostraram que a 7-hexiloxi-4H-[1,2,4]triazina[3,4-a]ftalazin-4-ona, 4e, foi a mais potente, com dose efetiva (ED50) de 6,6 mg kg-1 e dose tóxica mediana (TD50) de 39,4 mg kg-1, proporcionando um índice de proteção (PI=TD50 /ED50) de 6,0.

In this study, a novel series of 7-substituted-4H-[1,2,4]triazino[3,4-a]phthalazin-4-one derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that 7-hexyloxy-4H-[1,2,4]triazino[3,4-a]phthalazin-4-one 4e was the most potent with median effective dose (ED50) value of 6.6 mg kg-1, median toxicity dose (TD50) of 39.4 mg kg-1, providing a protective index (PI=TD50 /ED50) value of 6.0.