Palladium-Catalyzed Iodine Assisted Carbonylation of Indoles with ClCF2CO2Na and Alcohols.

A palladium-catalyzed iodine-assisted carbonylation reaction of indoles with readily available ClCF2CO2Na and alcohols has been developed. This protocol provides a practical and efficient approach to highly regioselective indole-3-carboxylates via a preiodination strategy of indoles. Different from classic carbonylation using toxic and difficult-to-handle carbon monoxide, this operationally simple and scalable reaction employed difluorocarbene as the carbonyl surrogate.

Near-infrared light-heatable platinum nanozyme for synergistic bacterial inhibition.

The development of non-antibiotic strategies for bacterial disinfection is of great clinical importance. Among recently developed different antimicrobial strategies, nanomaterial-mediated approaches, especially the photothermal way and reactive oxygen species (ROS)-generating method, show many significant advantages. Although promising, the clinical application of nanomaterials is still limited, owing to the potential biosafety issues. Further improvement of the antimicrobial activity to reduce the usage, and thus reduce the potential risk, is an important way to increase the clinical applicability of antibacterial nanomaterials. In this paper, an antimicrobial nanostructure with both an excellent photothermal effect and peroxidase-like activity was constructed to achieve efficient synergistic antimicrobial activity. The obtained nano-antimicrobial agent (ZIF-8@PDA@Pt) can not only efficiently catalyze the production of ROS from H2O2 to cause damage to bacteria but also convert the photon energy of near-infrared light into thermal energy to kill bacteria, and the two synergistic effects induced in a highly efficient antimicrobial activity. This study not only offers a new nanomaterial with efficient antibacterial activity but also proposes a new idea for constructing synergistic antibacterial properties.

Photochemical "Cut and Sew" Transformations of Ethynylbenziodoxolone Reagents and Diazo Compounds.

Herein, we disclose a visible-light-induced oxy-alkynylation of diazo compounds with ethynylbenziodoxolones. The efficient protocol provides a mild and metal-free methodology to synthesize propargylic esters in moderate to good yields. Notably, this metal-free carbene transfer reaction appears to involve an oxonium ylide intermediate, followed by intramolecular ligand exchange and reductive elimination.

Explosive Characteristics and Kinetic Mechanism of Methane-Air Mixtures under High-Temperature Conditions.

In the gas extraction and utilization process of coal mines, gas (mainly containing methane) explosion accidents happen occasionally under high-temperature conditions, causing serious casualties and economic losses. To reveal the mechanism and risk evolution of methane explosion under high-temperature conditions and control such accidents, the explosive characteristics of methane at 25∼200 °C were experimentally investigated by establishing a test platform for gas explosion under high-temperature conditions. In the experiments, three conditions were considered: the concentration near the upper explosion limit (CNUEL) (15.47 vol %), stoichiometric concentration (SC), and concentration near the lower explosion limit (4.68 vol %). Furthermore, the explosion pressure of methane-air mixtures and sensitivity characteristics of key free radicals at different high temperatures were determined based on the GRI-Mech 3.0 reaction mechanism of methane and using software CHEMKIN-PRO. The results show that at SC, P max decreases, while (DP/DT)max remains unchanged as the temperature increases, indicating a gradual decrease in the explosion risk. Near the explosion limits, P max and (DP/DT)max both grow as an exponential function, which implies that the explosion risk gradually increases. The temperature rise exerts a greater effect in improving the risk of explosion overpressure of methane at CNUEL (15.47 vol %), and compared with P max, the temperature rise has a greater improvement effect on (DP/DT)max. In the early stage of consuming methane, methane at SC mainly has two chemical reaction paths: CH4 → CH3 → CH3O → CH2O → HCO → CO and CH4 → CH3 → HCO → CO. The former and the latter to some extent separately promote and inhibit the explosive reactions. As the temperature increases, the proportion of methane consumed by the former reduces, while that by the latter slightly increases. The temperature rise inhibits the increase in the explosion risk of methane at SC, which is consistent with the experimental results.

Insights into the plateau adaptation of Salvia castanea by comparative genomic and WGCNA analyses.

INTRODUCTION: Salvia castanea, a wild plant species is adapted to extreme Qinghai-Tibetan plateau (QTP) environments. It is also used for medicinal purposes due to high ingredient of tanshinone IIA (T-IIA). Despite its importance to Chinese medicinal industry, the mechanisms associated with secondary metabolites accumulation (i.e. T-IIA and rosmarinic acid (RA)) in this species have not been characterized. Also, the role of special underground tissues in QTP adaptation of S. castanea is still unknown. OBJECTIVES: We explored the phenomenon of periderm-like structure in underground stem center of S. castanea with an aim to unravel the molecular evolutionary mechanisms of QTP adaptation in this species. METHODS: Morphologic observation and full-length transcriptome of S. castanea plants were conducted. Comparative genomic analyses of S. castanea with other 14 representative species were used to reveal its phylogenetic position and molecular evolutionary mechanisms. RNA-seq and WGCNA analyses were applied to understand the mechanisms of high accumulations of T-IIA and RA in S. castanea tissues. RESULTS: Based on anatomical observations, we proposed a "trunk-branches" developmental model to explain periderm-like structure in the center of underground stem of S. castanea. Our study suggested that S. castanea branched off from cultivated Danshen around 16 million years ago. During the evolutionary process, significantly expanded orthologous gene groups, 24 species-specific and 64 positively selected genes contributed to morphogenesis and QTP adaptation in S. castanea. RNA-seq and WGCNA analyses unraveled underlying mechanisms of high accumulations of T-IIA and RA in S. castanea and identified NAC29 and TGA22 as key transcription factors. CONCLUSION: We proposed a "trunk-branches" developmental model for the underground stem in S. castanea. Adaptations to extreme QTP environment in S. castanea are associated with accumulations of high secondary metabolites in this species.

Visible Light-Promoted Diazoacetates and Nitriles Generating Nitrilium Ions Trapped by Benzotriazoles and Carboxylic Acids.

A visible light-promoted generation of nitrilium ions from diazoacetates and nitriles has been developed. The reaction utilized visible light transformation of diazoacetates to the free carbene that could be trapped by nitriles to generate nitrilium ions, followed by nucleophilic attack on the benzotriazoles and carboxylic acids. This protocol provides an efficient and practical approach to N-imidoylbenzotriazoles and diacylglycine esters in good to excellent yields.

Visible-Light-Induced 1,6-Enynes Triggered C-Br Bond Homolysis of Bromomalonates: Solvent-Controlled Divergent Synthesis of Carbonylated and Hydroxylated Benzofurans.

Visible-light-induced 1,6-enyne-triggered C-Br bond homolysis of bromomalonates has been developed. This transition-metal-free, photocatalyst-free, and oxidant- and additive-free protocol affords an efficient approach for divergent synthesis of carbonylated and hydroxylated benzofurans from 1,6-enynes and bromomalonates under mild conditions. Significantly, mechanistic studies reveal that the homolysis of C-Br bonds appears to experience an energy-transfer pathway, and the atom-transfer radical addition products are the key intermediates to generate carbonylated and hydroxylated benzofurans.

Facile Fabrication of Fluorine-Free, Anti-Icing, and Multifunctional Superhydrophobic Surface on Wood Substrates.

Building superhydrophobic protective layers on the wood substrates is promising in terms of endowing them with multiple functions, including water-repellent, self-cleaning, anti-icing functions. In this study, multifunctional superhydrophobic wood was successfully fabricated by introducing SiO2 sol and superhydrophobic powder (PMHOS). The SiO2 sol was prepared using tetraethoxysilane as a precursor and ethanol was used as the dispersant. The PMHOS was synthesized using poly(methylhydrogen)siloxane (PMHS) and ethanol. As a result, the obtained superhydrophobic wood had a water contact angle (WCA) of 156° and a sliding angle (SA) of 6° at room temperature. The obtained superhydrophobic wood exhibited excellent repellency toward common liquid (milk, soy sauce, juice, and coffee). The superhydrophobic layer on the wood surface also exhibited good durability after a series of mechanical damages, including finger wiping, tape peeling, knife scratching, and sandpaper abrasion. In addition, the obtained superhydrophobic wood showed excellent anti-icing properties.

Isolation and Identification of Bone Marrow Mesenchymal Stem Cells from Forest Musk Deer.

The forest musk deer (Moschus berezovskii) is an endangered animal that produces musk that is utilized for medical applications worldwide, and this species primarily lives in China. Animal-derived musk can be employed as an important ingredient in Chinese medicine. To investigate the properties of bone marrow mesenchymal stem cells (MSCs) obtained from the bone marrow of forest deer for future application, MSCs were isolated and cultivated in vitro. The properties and differentiation of these cells were assessed at the cellular and gene levels. The results show that 81,533 expressed genes were detected by RNA sequencing, and marker genes of MSCs were expressed in the cells. Karyotype analysis of the cells determined the karyotype to be normal, and marker proteins of MSCs were observed to be expressed in the cell membranes. Cells were differentiated into osteoblasts, adipocytes, and chondroblasts. The expression of genes related to osteoblasts, adipocytes, and chondroblasts was observed to be increased. The results of this study demonstrate that the properties of the cells isolated from bone marrow were in keeping with the characteristics of MSCs, providing a possible basis for future research.

Histone deacetylase inhibitors promote epithelial-mesenchymal transition in Hepatocellular Carcinoma via AMPK-FOXO1-ULK1 signaling axis-mediated autophagy.

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related deaths globally because of high metastasis and recurrence rates. Elucidating the molecular mechanisms of HCC recurrence and metastasis and developing effective targeted therapies are expected to improve patient survival. The promising anti-cancer agents for the treatment of hematological malignancies, histone deacetylase inhibitors (HDIs), have limited effects against epithelial cell-derived cancers, including HCC, the mechanisms involved have not been elucidated. Herein, we studied the molecular mechanisms underlying HDI-induced epithelial-mesenchymal transition (EMT) involving FOXO1-mediated autophagy. Methods: The biological functions of HDIs in combination with autophagy inhibitors were examined both in vitro and in vivo. Cell autophagy was assessed using the generation of mRFP-GFP-LC3-expressing cells and fluorescent LC3 puncta analysis, Western blotting, and electron microscopy. An orthotopic hepatoma model was established in mice for the in vivo experiments. Results: Our study provided novel mechanistic insights into HDI-induced EMT mediated by the autophagy AMPK-FOXO1-ULK1-Snail signaling axis. We demonstrated that autophagy served as a pro-metastasis mechanism in HDI-treated hepatoma cells. HDIs induced autophagy via a FOXO1-dependent pathway, and FOXO1 inhibition promoted HDI-mediated apoptosis in hepatoma cells. Thus, our findings provided novel insights into the molecular mechanisms underlying HDI-induced EMT involving FOXO1-mediated autophagy and demonstrated that a FOXO1 inhibitor exerted a synergistic effect with an HDI to inhibit cell growth and metastasis in vitro and in vivo. Conclusion: We demonstrated that HDIs triggers FOXO1-dependent autophagy, which ultimately promotes EMT, limiting the clinical outcome of HDI-based therapies. Our study suggests that the combination of an HDI and a FOXO1 inhibitor is an effective therapeutic strategy for the treatment of HCC.

The complete chloroplast genome of Russian sage Salvia yangii B. T. Drew (Lamiaceae).

The complete chloroplast genome of Russian sage Salvia yangii B. T. Drew was assembled in this study. The genome is 151,473 bp in length and contained 129 encoded genes in total, including 84 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The result of phylogenetic analysis based on 15 chloroplast genomes revealed that S. yangii is closely related to common sage (Salvia officinalis) in Lamiaceae.

Associations between Dietary Glycemic Index and Glycemic Load Values and Cardiometabolic Risk Factors in Adults: Findings from the China Health and Nutrition Survey.

Studies investigating the associations between dietary glycemic index (GI) and glycemic load (GL) values and cardiometabolic risk factors (CMRF) among Chinese populations are strikingly limited. To assess the associations between dietary GI and GL values and CMRF, including dyslipidemia, hyperglycemia, and hyperuricemia in Chinese adults, we extracted data of 7886 apparently healthy adults from the 2009 wave of the China Health and Nutrition Survey. Dietary GI and GL values were calculated using data collected from three consecutive 24 h dietary recalls. Fasting lipid, glucose, and uric acid concentrations were measured and CMRF were defined on the basis of established criteria. There were no significant associations between dietary GI values and CMRF, and analyzing the data by age, sex, body mass index (BMI), and region did not alter these results. Dietary GL values were positively associated with prevalence of hyperuricemia in all participants (Q4 compared with Q1: odds ratio (OR) = 1.46; 95% CI: 1.14, 1.87; p-trend = 0.0030) and prevalence of hypercholesterolemia in participants ≥ 60 years old (Q5 compared with Q1: OR = 1.72; 95% CI: 1.11, 2.68; p-trend < 0.0010). Higher dietary GL but not GI values were associated with increased prevalence of hyperuricemia in apparently healthy Chinese adults and hypercholesterolemia in older Chinese adults. Further studies are required to confirm the public health implication of these findings.

Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy.

Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote or suppress tumor development, so it is a "double-edged sword" in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.

Histone deacetylase inhibitors upregulate Snail via Smad2/3 phosphorylation and stabilization of Snail to promote metastasis of hepatoma cells.

Hepatocellular carcinoma (HCC) remains the third most common cause of cancer-related mortality. Resection and transplantation are the only curative treatments available, but are greatly hampered by high recurrence rates. Histone deacetylase inhibitors (HDACIs) are considered to be promising anticancer agents in drug development. Currently, four HDACIs have been granted Food and Drug Administration (FDA) approval for cancer. HDACIs have shown significant efficacy in hematological malignancies. However, they have limited effects in epithelial cell-derived cancers, including HCC, and the mechanisms of these are not elucidated. In this study, our results demonstrated that HDACIs were able to induce epithelial-mesenchymal transitions (EMT) in hepatoma cells which are believed to trigger tumor cell invasion and metastasis. We found that HDACIs promoted the expression of Snail and Snail-induced EMT was critical for HDACI-initiated invasion and metastasis. We indicated that HDACIs upregulated Snail in two ways. Firstly, HDACIs upregulated Snail at the transcriptional level by promoting Smad2/3 phosphorylation and nuclear translocation, then combined with the promoter to activate the transcription of Snail. Secondly, we showed that HDACIs regulated the stabilization of Snail via upregulating the expression of COP9 signalosome 2 (CSN2), which combined with Snail and exposed its acetylation site, then promoted acetylation of Snail, thereby inhibiting its phosphorylation and ubiquitination to repress the degradation of Snail. All these results highlighted that HDACIs have limited effects in HCC, and the use of HDACIs combined with other targeted strategies to inhibit EMT, which explored in this study is a promising treatment method for treating HCC.

Curcumin downregulates the expression of Snail via suppressing Smad2 pathway to inhibit TGF-ß1-induced epithelial-mesenchymal transitions in hepatoma cells.

Hepatocellular carcinoma (HCC) remains the third cause of cancer-related mortality. Resection and transplantation are the only curative treatments available but are greatly hampered by high recurrence rates and development of metastasis, the initiation of cancer metastasis requires migration and invasion of cells, which is enabled by epithelial-mesenchymal transitions (EMT). TGF-ß1 is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation and apoptosis. TGF-ß1 is known as a major inducer of EMT, and it was reported that TGF-ß1 induced EMT via Smad-dependent and Smad-independent pathways. However, the extrinsic signals of TGF-ß1 regulated the EMT in hepatoma cells remains to be elucidated, and searching drugs to inhibit TGF-ß1 induced EMT may be considered to be a potentially effective therapeutic strategy in HCC. Fortunately, in this study, we found that curcumin inhibited TGF-ß1-induced EMT in hepatoma cells. Furthermore, we demonstrated that curcumin inhibited TGF-ß1-induced EMT via inhibiting Smad2 phosphorylation and nuclear translocation, then suppressing Smad2 combined with the promoter of Snail which inhibited the transcriptional expression of Snail. These findings suggesting curcumin could be a useful agent for antitumor therapy and also a promising drug combined with other strategies to preventing and treating HCC.