Divergent [2 + n] Heteroannulation of ß-CF3-1,3-enynes with Alkyl Azides via Hydrogen Atom Transfer and Radical Substitution.

A copper-promoted divergent intermolecular [2 + n] heteroannulation of ß-CF3-1,3-enynes with alkyl azides via alkyl radical-driven HAT and radical substitution (C-C bond formation) to form four- to ten-membered saturated N-heterocycles is developed. This method enables the aryl-induced or kinetically controlled site selective functionalization of the remote C(sp3)-H bonds at positions 2, 3, 4, 5, 6, 7, or 8 toward the nitrogen atom through triplet nitrene formation, radical addition across the C═C bond, HAT and radical substitution cascades, and features a broad substrate scope, excellent site selectivity, and facile late-stage derivatization of bioactive molecules. Initial deuterium-labeling and control experiments shed light on the reaction mechanism via nitrene formation and HAT.

HOXA5 inhibits the proliferation and metastasis of cervical squamous cell carcinoma by suppressing the ß-catenin/Snail signaling.

HOXA5, as a transcription factor, plays an important role in a variety of malignant tumors. Nevertheless, its biological role in cervical squamous cell carcinoma (CSCC) is largely unknown. In our study, we aimed to explore the function of HOXA5 in CSCC and its molecular mechanism. Immunohistochemistry showed that HOXA5 expression was downregulated in human CSCC tissues and HOXA5 staining was negatively correlated with tumor size and histological grade of CSCC. Ectopic expression of HOXA5 inhibited proliferative and metastatic abilities of CSCC cells in vitro and in vivo. Furthermore, overexpression of HOXA5 inhibited the cell cycle by arresting the S/G2 phase by flow cytometry and that was related to the downregulation of Cyclin A. Further study showed that HOXA5 suppressed EMT by inhibiting the ß-catenin/Snail signaling resulting in reduced metastasis of CSCC cells. Altogether, our results suggested that HOXA5 inhibited the proliferation and metastasis via repression of the ß-catenin/Snail pathway, proposing the potential role of HOXA5 in the prevention and treatment of CSCC.

Nickel-Catalyzed C-S Reductive Cross-Coupling of Alkyl Halides with Arylthiosilanes toward Alkyl Aryl Thioethers.

A nickel-catalyzed C-S reductive cross-coupling of alkyl halides with arylthiosilanes for producing alkyl aryl thioethers is developed. This reaction is initiated by umpolung transformations of arylthiosilanes followed by C-S reductive cross-coupling with alkyl halides to manage an electrophilic alkyl group onto the electrophilic sulfur atom and then construct a C(sp3)-S bond, and features exquisite chemoselectivity, excellent tolerance of diverse functional groups, and wide applications for late-stage modification of biologically relevant molecules.

Rhodium-Catalyzed Reductive trans-Alkylacylation of Internal Alkynes via a Formal Carborhodation/C-H Carbonylation Cascade.

A rhodium-catalyzed reductive annulation cascade reaction that consists of a formal anti-carborhodation of a C≡C bond and an aromatic C-H carbonylation cascade for producing cyclopenta[de]quinoline-2,5(1H,3H)-diones is described. This method uses the Mn reductant to reductively regenerate the active rhodium species, hence obviating the need for prefunctionalization, and represents a new route to the carbonylation of aromatic C-H bonds with alkynes leading to aryl vinyl ketone frameworks.

miR­760 mediates hypoxia-induced proliferation and apoptosis of human pulmonary artery smooth muscle cells via targeting TLR4.

MicroRNAs (miRNAs) have a key role in the pathogenesis of pulmonary arterial hypertension (PAH), a disease characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells. In the present study, miR­760 was demonstrated to be downregulated in PAH lung tissues compared with normal lung tissues, an effect that may be associated with the development of PAH. Hypoxia is an important stimulus for human pulmonary artery smooth muscle cell (hPASMC) proliferation and the occurrence of PAH. Therefore, the effect of miR­760 in hypoxia­treated and normal hPASMCs was investigated. Expression of exogenous miR­760 decreased cell proliferation in hypoxia­induced hPASMCs, and promoted cell apoptosis with an increase in the BCL2 associated X/BCL2 ratio and the expression levels of Caspase­3 and Caspase­9. In addition, overexpression of miR­760 suppressed the migration of hPASMCs under hypoxic conditions. Furthermore, miR­760 was demonstrated to mediate its anti­proliferation effect via the regulation of toll­like receptor 4 (TLR4), a direct target of miR­760. The results revealed that knockdown of TLR4 restrained the hypoxia­induced hPASMC proliferation and induced cell apoptosis. The present study uncovered a novel regulatory pathway involving miR­760 and suggested that miR­760 may be explored as a potential therapy for PAH in the future.

[Preparation of Iron-Aluminum Modified Diatomite and Its Immobilization in Cadmium-Polluted Soil].

To improve the in-situ immobilization effect of diatomite on cadmium (Cd)-contaminated soil, diatomite was modified by hydroxyl iron-aluminum (Fe-Al). The soil incubation experiments were carried out to investigate the effect of Fe/Al molar ratio, OH/cation of molar ratio, pillaring agent aging time, (Fe+Al)/diatomite ratio, pillaring temperature, and pillaring product aging time on the immobilization of Cd in soils. The changes in properties of diatomite before and after modification were analyzed by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The results showed that:the optimal preparation conditions for modification were:Fe/Al molar ratio=1:8, OH/cation molar ratio 2.0-2.2, pillaring agent aging time=2 d, (Fe+Al)/diatomite ratio=10 mmol·g-1, pillaring temperature=60℃, pillaring product aging time=2 d. The hydroxyl-Fe-Al-modified diatomite significantly reduced the content of exchangeable Cd in soil, and the modification reduced soil exchangeable Cd from 11.83% to 39.52%. The SEM and FTIR analyses of hydroxyl-Fe-Al-modified diatomite revealed increase in the specific surface area of diatomite and the amount of the Si-O-H groups. After modification, the hydroxyl-Fe-Al successfully exchanged into the diatom shell forming available pillars, thus increasing channel spacing and enhancing the microporous surface activity. The modification with hydroxyl-Fe-Al increased the immobilization effect of diatomite on Cd in soil. The modification methods and data from this study will help increase the application of diatomite materials for the immobilization of soil containing heavy metals.

Effect of Cd on growth, physiological response, Cd subcellular distribution and chemical forms of Koelreuteria paniculata.

Koelreuteria paniculata were cultivated in nutrient solution with different concentrations of Cd (0, 50, 150, 250 and 500 µM) and sampled after 90 days. The resistance, translocation, accumulation and stress responses in Koelreuteria paniculata were investigated by hydroponic experiments. The results showed that Koelreuteria paniculata is an efficient Cd excluder that can tolerate high concentrations of Cd (up to 150-250 µM of Cd). The concentration of Cd never exceeds 5 ppm in leaves and 10 ppm in roots. The high concentration of Cd (≥ 250 µM) had a toxic effect on K. paniculata and significantly restricted the plant growth. The accumulation ability of Cd by different plant tissues followed the sequence of roots > leaves > stems. The bioconcentration factors and translocation factors both were less than 1. Cd has the highest content in the cell wall and is migrated to soluble fractions and organelles at high concentrations. Undissolved Cd phosphate, pectates and protein-bound Cd were the predominant forms. The low concentration of Cd (≤150 µM) promoted the synthesis of soluble proteins, AsA and GSH, while high concentration of Cd clearly inhibited the physiological and biochemical process, caused membrane lipid peroxidation and severe membrane damages, and increased MDA and H2O2 contents. POD, CAT and SOD exhibited positive and effective responses to low concentration Cd stress, but could not remove the toxicity caused by high concentration Cd stress. The content of IAA, GA and ZT decreased and ABA content was significantly increased under high-concentration Cd stress.

Expression and clinical significance of HOXA5, E-cadherin, and ß-catenin in cervical squamous cell carcinoma.

OBJECTIVES: HOXA5 has been identified as a biomarker in pathogenesis of several cancers, such as non-small cell lung cancer (NSCLC) and breast cancer cells. The role has not been explored in cervical squamous cell carcinoma (CSCC). METHODS: Tissues of 120 cases with CSCC and 30 controls with chronic cervicitis were constructed from our archived surgical pathology files and staining with HOXA5. Additional antibodies to E-cadherin and ß-catenin were stained for comparison. For each marker, low expression was defined as staining score 0 to 3 points, whereas high expression referred to 4 points and above. Fifty-four patients in this research with cervical cancer were followed up for prognostic assessment. RESULT: HOXA5 had high expression in chronic cervicitis and low in CSCC (P=0.004). The positivity rates of HOXA5 in patients without muscular layer invasion (MLI) and lymphatic invasion (LI) was higher than that in metastasis (113 vs. 17; 117 vs. 3). Consistently, low expression of HOXA5 was more common in poorly differentiated carcinoma, CSCC subjects without MLI and LI. Expression of E-cadherin and ß-catenin was parallel with the expression of HOXA5. Additionally, patients with higher expression of HOXA5 had much more favorable prognosis than those with lower expression among follow up of the 54 patients. CONCLUSION: In parallel with E-cadherin and ß-catenin, low expression of HOXA5 was more common in CSCC patients with poor differentiation, without MLI and LI, among those which showed poor prognosis.

Isolation, characterization and cardiac differentiation of human thymus tissue derived mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) are promising candidate donor cells for replacement of cardiomyocyte loss during ischemia and in vitro generation of myocardial tissue. We have successfully isolated MSCs from the discarded neonatal thymus gland during cardiac surgery. The thymus MSCs were characterized by cell-surface antigen expression. These cells have high ability for proliferation and are able to differentiate into osteoblasts and adipocytes in vitro. For cardiac differentiation, the cells were divided into 3 groups: untreated control; 5-azacytidine group and sequential exposure to 5-azacytidine, bone morphogenetic protein 4, and basic fibroblast growth factor. Thymus MSCs showed a fibrolast-like morphology and some differentiated cells increased in size, formed a ball-like appearance over time and spontaneously contracting cells were observed in sequential exposure group. Immunostaining studies, cardiac specific genes/protein expression confirmed the cardiomyocyte phenotype of the differentiated cells. These results demonstrate that thymus MSCs can be a promising cellular source for cardiac cell therapy and tissue engineering.