Photoredox-Enabled Deconstructive [5 + 1] Annulation Approach to Isoquinolones from Indanones in Water.

We disclose a deconstructive [5 + 1] annulation protocol for the synthesis of isoquinolones through a nitrogen insertion into abundant indanones. This method exploits photoredox-catalyzed ring-opening of oxime esters. The reaction proceeds smoothly with water as the reaction medium and tolerates a range of functional groups on diverse thiophenols, amines, or indanones. Moreover, the representative isoquinolones exhibit promising antifungal activities.

Fluorosulfonyl Arylation of Alkynes via Electron Donor-Acceptor Photoactivation.

A radical fluorosulfonyl arylation of alkynes with sulfuryl chlorofluoride as the FSO2 radical precursor via electron donor-acceptor photoactivation driven by daylight or a blue light-emitting diode is disclosed. A series of valuable benzo-fused carbocycles and heterocycles have been produced with simple operation under mild conditions in the absence of any external catalysts or additives. The synthetic potential of this protocol has further demonstrated excellent scalability, as well as diverse postderivatizations, including SuFEx reactions and other useful cascade reactions.

Radical Hydro-Fluorosulfonylation of Propargylic Alcohols via Electron Donor-Acceptor Photoactivation.

A radical hydro-fluorosulfonylation of propargyl alcohols with FSO2Cl is presented based on the photoactivation of the electron donor-acceptor (EDA) complex. The reaction avoids the requirement for photocatalysts, bases, hydrogen donor reagents, any other additives, and harsh conditions, enabling the facile synthesis of various functionalized γ-hydroxy (E)-alkenylsulfonyl fluorides. These multifunctional sulfonyl fluorides can be further diversified, providing access to various privileged molecules of biological relevance.

A hemostatic sponge derived from chitosan and hydroxypropylmethylcellulose.

Hemostatic materials are of great significance for rapid control of bleeding, especially in military trauma and traffic accidents. Chitosan (CS) hemostatic sponges have been widely concerned and studied due to their excellent biocompatibility. However, the hemostatic performance of pure chitosan sponges is poor due to the shortcoming of strong rigidity. In this study, CS and hydroxypropylmethylcellulose (HPMC) were combined to develop a safe and effective hemostatic composite sponges (CS/HPMC) for hemorrhage control by a simple mixed-lyophilization strategy. The CS/HPMC exhibited excellent flexibility (the flexibility was 74% higher than that of pure CS sponges). Due to the high porosity and procoagulant chemical structure of the CS/HPMC, it exhibited rapid hemostatic ability in vitro (BCI was shortened by 50% than that of pure CS sponges). The good biocompatibility of the obtained CS/HPMC was confirmed via cytotoxicity, hemocompatibility and skin irritation tests. The CS/HPMC can induced the erythrocyte and platelets adhesion, resulting in significant coagulation acceleration. The CS/HPMC had excellent performance in vivo assessments with shortest clotting time (40 s) and minimal blood loss (166 mg). All above results proved that the CS/HPMC had great potential to be a safe and rapid hemostatic material.

Fractionation of poplar wood with different acid hydrotropes: Lignin dissolution behavior and mechanism evaluation.

Acid hydrotropes was considered a green medium for efficient wood fractionation at mild conditions. This study reported a comparative study on the dissolution of lignin in different acid hydrotropes, including p-toluenesulfonic acid (p-TsOH), 4-hydroxybenzenesulfonic acid (4-HSA), 5-sulfosalicylic acid (5-SSA), and maleic acid (MA). Under identical treatment conditions (80 °C, 60 min, and 70 % acid concentration), the removal of wood lignin varied significantly among four acid hydrotropes, 4-HSA exhibited the highest removal rate at 88.0 %, followed by p-TsOH at 81.2 %, 5-SSA at 51.1 %, and MA at 26.2 %. The molecular mechanism of the lignin dissolution was analyzed by quantum chemistry (QC) calculation and molecular dynamics (MD) simulation. The higher absorb free energy (E(absorb)) of the 4-HSA and veratrylglycerol-ß-guaiacyl ether (VG) complex (E(absorb) = 17.97 kcal/mol), and the p-TsOH and VG complex (E(absorb) = 17.16 kcal/mol) contributed to a higher efficiency of lignin dissolution. Under the same level of lignin removal (~ 60 %), the four acid hydrotropes showed variations in the ß-O-4 content of the extracted lignin: 4-HSA (3.1 %) < 5-SSA (10.4 %) < p-TsOH (15.9 %) < MA (63.7 %). The acidity and critical aggregation concentrations of acid hydrotropes were found to influence the content of ß-O-4 bonds in the extracted lignin.

Succession of endophytic bacterial community and its contribution to cinnamon oil production during cinnamon shade-drying process.

Cinnamon oil is a blend of secondary metabolites and is widely used as spice. Endophytic bacteria are always related to the secondary metabolites production. However, the potential of endophytic bacteria communities for cinnamon oil production during cinnamon shade-drying process is still not clear. In this study, we investigated the composition and metabolic function of endophytic bacterial community during 80-day shade-drying process. The temporal dynamics of essential oil content and its dominant constituents were analyzed. The succession of endophytic bacterial community from d0 to d80 was identified. The influence of endophytic bacterial community evolution on cinnamon oil is significant positive. Predictive functional analysis indicated that shade-drying process was rich in Saccharopolyspora that produce enzymes for the conversion of phenylalanine to cinnamaldehyde. These findings enhance our understanding of the functional bacterial genera and functional genes involved in the production of cinnamon oil during cinnamon shade-drying process.

Discovery of novel 1,3,5-triazine derivatives as potent inhibitor of cervical cancer via dual inhibition of PI3K/mTOR.

This study describes the synthesis of novel 1,3,5-triazine derivatives as potent inhibitors of cervical cancer. The compounds were initially tested for inhibition of PI3K/mTOR, where they showed significant inhibitory activity. The top-ranking molecule (compound 6 h) was further tested against class I PI3K isoforms, such as PI3Kα, PI3Kß, PI3Kγ and PI3Kδ, where it showed the most significant activity against PI3Kα. Compound 6 h was then tested for anti-cancer activity against triple-negative breast cancer cells (MDA-MB321), human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human liver cancer cells (HepG2), and it showed the greatest potency against HeLa cells. The effects of compound 6 h were further evaluated against the HeLa cells, where it showed significant attenuation of cell viability by inducing cell cycle arrest in the G1 phase. Compound 6 h induced apoptosis and reduced migration and invasion of HeLa cells. Western blotting analysis showed that 6 h inhibited PI3K and mTOR with positive modulation of Bcl-2 and Bax levels in HeLa cells. The effects of compound 6 h were also investigated in a tumour xenograft mouse model, where it showed reduction of tumour volume and weight. It also inhibited the PI3K/Akt/mTOR signalling cascade in xenograft tumour tissues, as evidenced by western blotting analysis. The results of the present study suggest the possible utility of the designed 1,3,5-triazine derivative as a potent inhibitor of cervical cancer.

Synthesis and biological activity of pyridine acylhydrazone derivatives of isopimaric acid.

Pyridine acylhydrazone derivatives of isopimaric acid were synthesized and characterized. The minimum inhibitory concentrations of the compounds against five bacteria were determined and most of the compounds displayed some degree of antibacterial activity. The results showed that antimicrobial activity against Streptococcus pneumoniae improved when halogen atoms were introduced into the isopimaric acid, especially when one bromine atom was introduced in the para-position of isopimaric acid. Compound isopimaric acid (5-bromo pyridine-2-formaldehyde) acylhydrazone exhibited a significant antitumorial activity against hepatocarcioma cells (HepG-2) and breast cancer cells (MDA-MB-231), with inhibition degrees of 74.21% and 70.39%, respectively, at 100 µM.[Formula: see text].

Taraxastane inhibits the proliferation, migration and invasion of human cervical cancer by inducing ROS- mediated necrosis like cell death, cell cycle arrest and modulation of JNK/MAPK signaling pathway.

PURPOSE: A good number of anticancer studies have focused on the evaluation of plant derived natural products against different types of human cancers. Triterpenes, belonging to terpenoid class of plant secondary metabolites, have been reported to function as potent anticancer agents. The current study was designed to investigate the anticancer potential of Taraxastane against human cervical cancer cells. METHODS: MTT assay and DAPI staining were used for determining the cell viability. DCFH-DA and DiOC6 based estimations were employed for determination of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), respectively. Flow cytometry technique was used for analysis of cell cycle and necrosis. Analysis of cell migration and invasion was performed by wound heal and transwell assays, repectively. Protein expression was analyzed by Western blotting. RESULTS: MTT assay showed that Taraxastane inhibited the proliferation of DoTc2 cervical cancer cells in a concentration-dependent manner with an IC50 of 20µM, whereas it had lesser effect on the proliferation of normal human cervical cells. The molecule was seen to increase the ROS concentration along with decreasing MMP. Flow cytometry showed that Taraxastane didn't induce cell apoptosis in DoTc2 cells and anticancer effects were mainly in the form of DoTc2 cell necrosis. This was also evident from the western blot analysis of Bax and BCl-2 proteins whose concentration remained unchanged under Taraxastane treatment. Taraxastane treatment led to cell cycle arrest at G2/M checkpoint without any effect on Cyclin D protein expression. Western blotting of JNK and p-38 proteins showed that Taraxastane blocks the JNK/MAPK signaling pathway by preventing the phosphorylation of the former in a dose-dependent manner. Finally, the wound healing and transwell assays showed that Taraxastane inhibited the migration and invasion of cervical cancer cells, which indicates the role of Taraxastane in the prevention of cancer metastasis. CONCLUSION: To conclude, Taraxastane has remarkable anti- proliferative effect on human cervical cancer cells and thus may prove as a vital lead molecule for discovery of anticancer drugs.

Expression of alpha-methylacyl-CoA racemase in vaginal gastric-type adenocarcinoma and uterine clear cell carcinoma.

BACKGROUND: Alpha-methylacyl-coenzyme A racemase (AMACR, P504S) is a commonly used marker in immunohistochemical diagnosis of prostate cancer. Recent studies identified P504S markers of the clear cell histotype in the ovary and/or endometrium. Gastric-type adenocarcinoma (GAS) is difficult to diagnose histologically, particularly when there is crossover with clear cell carcinoma (CCC). However, the significance of P504S for differentially diagnosing GAS and CCC is unclear. AIM: To evaluate P504S as a potential diagnostic marker of GAS and CCC. SETTINGS AND DESIGN: We analyzed P504S expression in 48 cervical carcinomas (32 GAS and 16 CCC), as well as the expression of other markers including hepatocyte nuclear factor-1 beta (HNF-1ß) and NapsinA. MATERIAL AND METHODS: The expression differences of HNF-1ß, NapsinA, and P504S in GAS and CCC were detected by immunohistochemistry. Immunohistochemical histoscores based on the intensity and extent of staining were calculated. RESULTS: The positive rates of HNF-1ß in GAS and CCC were 90.32% and 75%, respectively. (χ2 = 2.251, P = 0.663). The positive rates of NapsinA in GAS and CCC were 19.36% and 81.25%, respectively. (χ2 = 47.332, P < 0.01). The positive rates of P504S in GAS and CCC were 16.13% and 81.25%, respectively. (χ2 = 41.420, P < 0.01). HNF-1ß was frequently expressed in GAS and CCC, while NapsinA and P504S were frequently expressed in CCC, and reduced or lost in GAS. CONCLUSION: NapsinA and P504S can be used to differentiate between GAS and CCC.

Synthesis of a multifunctional hard monomer from rosin: the relationship of allyl structure in maleopimarate and UV-curing property.

Rosin is an important forestry resource with a specific three-membered phenanthrene ring structure, which can improve the mechanical resistance of polymer coatings. In this paper, a high purity rosin monomer, tri-allyl maleopimarate containing three allyl groups has been synthesized. The yield of the monomer product was 93.2% with the purity of 96.1%. The structure of the synthesized monomer was characterized through gas chromatography (GC), mass spectrometry (MS), hydrogen nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR) and elemental analysis. Additionally, we present new experimental results regarding the polymerization reaction under ultraviolet (UV) irradiation. The cured film of tri-allyl maleopimarate exhibited good mechanical properties. The films were also characterized through thermogravimetric (TG) and differential scanning calorimetry (DSC) analyses and a mechanism for polymerization was proposed. Overall, a facile catalytic process for the valorization of rosin in the field of UV polymerization is reported.

ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs.

Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway.

Involvement of the IRE1α-XBP1 pathway and XBP1s-dependent transcriptional reprogramming in metabolic diseases.

The X-box binding protein 1 (XBP1) is not only an important component of the unfolded protein response (UPR), but also an important nuclear transcription factor. Upon endoplasmic reticulum stress, XBP1 is spliced by inositol-requiring enzyme 1 (IRE1), thereby generating functional spliced XBP1 (XBP1s). XBP1s functions by translocating into the nucleus to initiate transcriptional programs that regulate a subset of UPR- and non-UPR-associated genes involved in the pathophysiological processes of various diseases. Recent reports have implicated XBP1 in metabolic diseases. This review summarizes the effects of XBP1-mediated regulation on lipid metabolism, glucose metabolism, obesity, and atherosclerosis. Additionally, for the first time, we present XBP1s-dependent transcriptional reprogramming in metabolic diseases under different conditions, including pathology and physiology. Understanding the function of XBP1 in metabolic diseases may provide a basic knowledge for the development of novel therapeutic targets for ameliorating these diseases.