A Facile and Efficient Synthesis of Some (6E)-Hydroximino-4-En-3-One Steroids, Steroidal Oximes From Cinachyrella spp. Sponges

Using β-sitosterol as a starting material, (6E)-hydroximino-24-ethylcholest-4-en-3-one (1), a natural steroidal oxime from Cinachyrella alloclada and C. apion, was synthesized in four steps with a high overall yield. First, β-sitosterol (5a) is transformed into the corresponding 24-ethylcholest-4-en-3,6-dione (6a) via oxidation with pyridinium chlorochromate (PCC). Selective reduction of 6a by NaBH4 in the presence of CoCl2 gives 24-ethylcholest- 4-en-3β-ol-6-one (7a). The reaction of 7a with hydroxylamine hydrochloride offers the oxime 8a and the oxidation of 8a by Jones reagent gives the target steroid 1. (6E)-Hydroximinocholest-4-en-3-one (2) and (6E)-hydroximino-24-ethylcholest-4,22-dien-3-one (4) were synthesized by a similar method. The cytotoxicity of the synthesized compounds against sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells were investigated. The presence of a cholesterol-type side chain appears to be necessary for the biological activity

Petrology, Physical Properties, and Diagenetic Characteristics of Glutenite Reservoir: An Example from the Upper Urho Formation in Zhongguai Salient, Junggar Basin, China

AbstractThe Upper Urho Formation on the northwest margin of the Junggar Basin is a key formation for oil and gas exploration. Based on the core observation, combined with the analysis of cast thin section, scanning electron microscope, energy dispersive spectrum, X-ray diffraction, fluid inclusion, and porosity-permeability test, the petrological characteristics, physical properties, diagenesis types, and their effects on the physical properties of the glutenite reservoir of Upper Urho Formation were studied systematically. The results show that the lithology of reservoir of the Upper Urho Formation in Zhongguai Salient is mainly conglomerate with a small amount of sandstone. The permeability of conglomerate is generally higher than that of sandstone, and the physical properties of granule conglomerate and fine pebble conglomerate are relatively better. The reservoir experienced complicated diagenesis, mainly including compaction, cementation, and dissolution, also including filler shrink seam and metasomatism. At present, the reservoir of Upper Urho Formation in Zhongguai Salient is mainly at the middle diagenetic stage A period and partly at the middle diagenetic stage B period. The original porosity lost by compaction is the largest, which is the fundamental reason for low porosity and low permeability of reservoir. The influence of cementation on reservoir physical properties has two sides. On the one hand, the development of cementation is the main reason for low porosity and low permeability of reservoir. On the other hand, the early cementation resists compaction to a certain extent and provides a material basis for the later dissolution. The reservoir of Upper Urho Formation in Zhongguai Salient is deeply buried and has experienced strong compaction and cementation, and the reservoir properties are poor, but the secondary pore space formed by dissolution improves the reservoir properties to some extent. The study concluded that the dense glutenite reservoirs of the Upper Urho Formation can develop relatively high-quality reservoirs on a local scale, which is of guiding significance for the exploration of the Upper Urho Formation

MicroRNA-323a-3p Promotes Pressure Overload-Induced Cardiac Fibrosis by Targeting TIMP3

Background/Aims: Cardiac fibrosis is a major cause of diverse cardiovascular diseases. MicroRNAs have recently been proven a novel class of regulators of cardiac fibrosis. In this study, we sought to investigate the role of miR-323a-3p and its mechanisms in regulating cardiac fibrosis. Methods: The transverse aortic constriction (TAC) mice model was induced and neonatal cardiac fibroblasts (CFs) were cultured. MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay was used to detect the cell viability. Echocardiography was used to evaluate cardiac function. Masson’s Trichrome stain was used to evaluate the development of fibrosis. Luciferase activity assay was performed to confirm the miRNA’s binding site. Real-time PCR and Western blot were used to evaluate the level of mRNA and protein. Results: MiR-323a-3p was found up-regulated in myocardial tissues subjected to TAC and in CFs cultured with Angiotensin Ⅱ (Ang Ⅱ). Overexpression of miR-323a-3p significantly increased the mRNA levels of collagen Ⅰ, collagen Ⅲ, MMP2 and MMP9, while inhibition of miR-323a-3p prevented the proliferation, collagen production and the protein level of transforming growth factor (TGF-β) in rat neonatal CFs. Strikingly, injection of antagomiR-323a-3p elevated cardiac function and inhibited the expression of TGF-β in the TAC mice. TIMP3 was a direct target of miR-323a-3p, as the overexpression of miR-323a-3p decreased the protein and mRNA levels of TIMP3. In the CFs with pre-treatment of Ang Ⅱ, siRNA-TIMP abolished the effects of AMO-323a-3p on the inhibition of the proliferation of CFs, the down-regulation of collagen Ⅰ and collagen Ⅲ, and the expression of TGF-β. Conclusion: Our findings provide evidence that miR-323a-3p promotes cardiac fibrosis via miR-323a-3p-TIMP3-TGF-β pathway. miR-323a-3p may be a new marker for cardiac fibrosis progression and that inhibition of miR-323a-3p may be a promising therapeutic target for the treatment of cardiac fibrosis

3D bioactive composite scaffolds for bone tissue engineering

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed

Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats

Background/Aims: Troxerutin, also known as vitamin P4, has been commonly used in the treatment of chronic venous insufficiency (CVI) disease. However, its effect on in vivo myocardial ischemia/reperfusion (I/R) injury, a model that closely mimics acute myocardial infarction in humans, is still unknown. Methods: The myocardial I/R injury rat model was created with troxerutin preconditioning. Myocardial infarct size was evaluated by the Evans blue-TTC method. Hemodynamic parameters, including the heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximal rate of rise in blood pressure in the ventricular chamber (+dp/dt max), and maximal rate of decline in blood pressure in the ventricular chamber (-dp/dt max) were monitored. Serum TNF-α and IL-10 were determined by ELISA kit. Cell apoptosis was detected by MTT method. Results: Troxerutin preconditioning significantly reduced myocardial infarct size, improved cardiac function, and decreased the levels of creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the I/R injury rat model. The serum and mRNA levels of TNF-α and IL-10 as well as some apoptosis markers (Bax, Caspase 3) also decreased. Moreover, troxerutin pretreatment markedly increased the phosphorylation of Akt, and blocking PI3K activity by LY294002 abolished the protective effect of troxerutin on I/R injury. Conclusion: Troxerutin preconditioning protected against myocardial I/R injury via the PI3K/Akt pathway

Effect of Recrystallization on Hot Deformation Mechanism of TA15 Titanium Alloy under Uniaxial Tension and Biaxial Gas Bulging Conditions

To investigate the effect of recrystallization on hot deformation mechanism of TA15 titanium alloy, rolled sheet and laser-welded tubes before and after recrystallization annealing were tested by uniaxial tensile tests and biaxial gas bulging respectively. The results show that both of the initial rolled sheet and the as-welded tube consisted of equiaxed α microstructure with high initial dislocation density. During uniaxial tensile tests, a quasi-steady flow state was achieved at 800o C, 0.001 s-1 , which demonstrated the best formability with a maximum elongation of 536%. Significant recrystallization occurred at the early stage of tensile deformation and the grain size was found to decrease first and then increase. Significant recrystallization also occurred at the early stage of the biaxial gas bulging of the as-welded tube. During the bulging of the annealed tube consisting of equiaxed α with low initial dislocation density, dynamic recrystallization (DRX) was the main microstructure evolution characteristic, but most of the DRX occurred at the middle-late stage. The relatively coarse equiaxed α and increasing fraction of low angle grain boundaries during deformation may restrict the occurrence of grain boundary sliding (GBS), which resulted in the relatively worse formability of the annealed tube. However, recrystallization which happened widely at the early stage, increased the fraction of high angle grain boundaries, refined the microstructure, promoted the occurrence of GBS and enhanced the formability of the initial rolled sheet and as-welded tube. It was also found that the stress state had no effect on the DRX mechanism for TA15 at 800o C, which was confirmed to be discontinuous dynamic recrystallization under both uniaxial tension and biaxial gas bulging conditions

Phylogeny and species delimitation of the genus Longgenacris and Fruhstorferiola viridifemorata species group (Orthoptera: Acrididae: Melanoplinae) based on molecular evidence.

Phylogenetic positions of the genus Longgenacris and one of its members, i.e. L. rufiantennus are controversial. The species boundaries within both of L. rufiantennus+Fruhstorferiola tonkinensis and F. viridifemorata species groups are unclear. In this study, we explored the phylogenetic positions of the genus Longgenacris and the species L. rufiantennus and the relationships among F. viridifemorata group based on the 658-base fragment of the mitochondrial gene cytochrome c oxidase subunit I (COI) barcode and the complete sequences of the internal transcribed spacer regions (ITS1 and ITS2) of the nuclear ribosomal DNA. The phylogenies were reconstructed in maximum likelihood framework using IQ-TREE. K2P distances were used to assess the overlap range between intraspecific variation and interspecific divergence. Phylogenetic species concept and NJ tree, K2P distance, the statistical parsimony network as well as the generalized mixed Yule coalescent model (GMYC) were employed to delimitate the species boundaries in L. rufiantennus+F. tonkinensis and F. viridifemorata species groups. The results demonstrated that the genus Longgenacris should be placed in the subfamily Melanoplinae but not Catantopinae, and L. rufiantennus should be a member of the genus Fruhstorferiola but not Longgenacris. Species boundary delimitation confirmed the presence of oversplitting in L. rufiantennus+F. tonkinensis and F. viridifemorata species groups and suggested that each group should be treated as a single species

Effect of recrystallization on hot deformation mechanism of TA15 titanium alloy under uniaxial tension and biaxial gas bulging conditions

To investigate the effect of recrystallization on hot deformation mechanism of TA15 titanium alloy, rolled sheet and laser-welded tubes before and after recrystallization annealing were tested by uniaxial tensile tests and biaxial gas bulging respectively. The results show that both of the initial rolled sheet and the as-welded tube consisted of equiaxed alpha microstructure with high initial dislocation density. During uniaxial tensile tests, a quasi steady flow state was achieved at 800 degrees C, 0.001 s-1, which demonstrated the best formability with a maximum elongation of 536%. Significant recrystallization occurred at the early stage of tensile deformation and the grain size was found to decrease first and then increase. Significant recrystallization also occurred at the early stage of the biaxial gas bulging of the as-welded tube. During the bulging of the annealed tube consisting of equiaxed a with low initial dislocation density, dynamic recrystallization (DRX) was the main microstructure evolution characteristic, but most of the DRX occurred at the middle-late stage. The relatively coarse equiaxed a and increasing fraction of low angle grain boundaries during deformation may restrict the occurrence of grain boundary sliding (GBS), which resulted in the relatively worse formability of the annealed tube. However, recrystallization which happened widely at the early stage, increased the fraction of high angle grain boundaries, refined the microstructure, promoted the occurrence of GBS and enhanced the formability of the initial rolled sheet and as-welded tube. It was also found that the stress state had no effect on the DRX mechanism for TA15 at 800 degrees C, which was confirmed to be discontinuous dynamic recrystallization under both uniaxial tension and biaxial gas bulging conditions

Modeling intercalation chemistry with multi-redox reactions by sparse lattice models in disordered rocksalt cathodes

Modern battery materials can contain many elements with substantial site disorder, and their configurational state has been shown to be critical for their performance. The intercalation voltage profile is a critical parameter to evaluate the performance of energy storage. The application of commonly used cluster expansion techniques to model the intercalation thermodynamics of such systems from \textit{ab-initio} is challenged by the combinatorial increase in configurational degrees of freedom as the number of species grows. Such challenges necessitate efficient generation of lattice models without over-fitting and proper sampling of the configurational space under charge balance in ionic systems. In this work, we introduce a combined approach that addresses these challenges by (1) constructing a robust cluster-expansion Hamiltonian using the sparse regression technique, including $\ell_0\ell_2$-norm regularization and structural hierarchy; and (2) implementing semigrand-canonical Monte Carlo to sample charge-balanced ionic configurations using the table-exchange method and an ensemble-average approach. These techniques are applied to a disordered rocksalt oxyfluoride Li$_{1.3-x}$Mn$_{0.4}$Nb$_{0.3}$O$_{1.6}$F$_{0.4}$ (LMNOF) which is part of a family of promising earth-abundant cathode materials. The simulated voltage profile is found to be in good agreement with experimental data and particularly provides a clear demonstration of the Mn and oxygen contribution to the redox potential as a function of Li content