Visible-Light-Driven Unsymmetric gem-Difunctionalization of Vinyl Azides with Thiosulfonates or Selenosulfonates.

Thiosulfonylation and selenosulfonylation of vinyl azides with thiosulfonates and selenosulfonates were achieved using Cu(dap)2Cl as a photosensitizer under visible-light irradiation. This reaction is the application of a vinyl azide substrate in a group transfer radical addition (GTRA) reaction, through ß-difunctionalization, to obtain a variety of unsymmetric difunctionalized N-unprotected enamines.

Indole-Fused Benzoxepine Synthesis via Visible-Light-Driven Aerobic Dehydrogenative [5 + 2] Annulation.

A photocatalyzed oxidative dehydrogenative annulation between 2-(1H-indol-2-yl)phenols and alkenylphenols is presented. Various indole-fused benzoxepines can be obtained at room temperature using atom-efficient strategies. This method not only avoids the use of stoichiometric amounts of oxidants but also exhibits excellent atom economy by generating H2O as the only theoretical byproduct.

Photocatalytic redox-neutral selective single C(sp3)-F bond activation of perfluoroalkyl iminosulfides with alkenes and water.

Visible-light-promoted site-selective and direct C-F bond functionalization of polyfluorinated iminosulfides was accomplished with alkenes and water under redox-neutral conditions, affording a diverse array of γ-lactams with a fluoro- and perfluoroalkyl-substituted carbon centre. A variety of perfluoroalkyl units, including C2F5, C3F7, C4F9, and C5F11 underwent site-selective defluorofunctionalization. This protocol allows high chemoselectivity control and shows excellent functional group tolerance. Mechanistic studies reveal that the remarkable changes of the electron geometries during the defluorination widen the redox window between the substrates and the products and ensure the chemoselectivity of single C(sp3)-F bond cleavage.

Meyer-Schuster-Type Rearrangement of Propargylic Alcohols into α-Selenoenals and -enones with Diselenides.

We describe a mild and broadly applicable protocol for the preparation of a diverse array of multisubstituted α-selenoenals and -enones from readily accessible propargylic alcohols and diselenides. The transformation proceeds via the Selectfluor-promoted selenirenium pathway, which enables selenenylation/rearrangement of a variety of propargylic alcohols. Gram-scale experiments showed the potential of this synergistic protocol for practical application.

Controllable synthesis of 2- and 3-aryl-benzomorpholines from 2-aminophenols and 4-vinylphenols.

We present herein a method for the controllable synthesis of 3-aryl-benzomorpholine and 2-aryl-benzomorpholine cycloadducts via cross-coupling/annulation between electron-rich 2-aminophenols and 4-vinylphenols. Molecular oxygen was successfully used in the reaction as the terminal oxidant and the complete inversion of chemoselectivity was achieved by the adjustment of the solvents and bases at room temperature.

Application of a Blockchain Platform to Manage and Secure Personal Genomic Data: A Case Study of LifeCODE.ai in China.

BACKGROUND: The rapid development of genetic and genomic technologies, such as next-generation sequencing and genome editing, has made disease treatment much more precise and effective. The technologies' value can only be realized by the aggregation and analysis of people's genomic and health data. However, the collection and sharing of genomic data has many obstacles, including low data quality, information islands, tampering distortions, missing records, leaking of private data, and gray data transactions. OBJECTIVE: This study aimed to prove that emerging blockchain technology provides a solution for the protection and management of sensitive personal genomic data because of its decentralization, traceability, encryption algorithms, and antitampering features. METHODS: This paper describes the case of a blockchain-based genomic big data platform, LifeCODE.ai, to illustrate the means by which blockchain enables the storage and management of genomic data from the perspectives of data ownership, data sharing, and data security. RESULTS: Blockchain opens up new avenues for dealing with data ownership, data sharing, and data security issues in genomic big data platforms and realizes the psychological empowerment of individuals in the platform. CONCLUSIONS: The blockchain platform provides new possibilities for the management and security of genetic data and can help realize the psychological empowerment of individuals in the process, and consequently, the effects of data self-governance, incentive-sharing, and security improvement can be achieved. However, there are still some problems in the blockchain that have not been solved, and which require continuous in-depth research and innovation in the future.

Thiocyanate radical mediated dehydration of aldoximes with visible light and air.

We developed a new means of activating aldoximes by an in situ generated thiocyanate radical from ammonium thiocyanate and molecular oxygen at room temperature. With a catalytic amount of organic dye aizenuranine as the photocatalyst, the dehydration of aldoximes proceeds smoothly under visible light irradiation, providing a simple to handle, excellent functional group tolerance, and metal-free protocol for a wide range of nitriles.

Comparative transcriptome analysis of Rosa chinensis 'Slater's crimson China' provides insights into the crucial factors and signaling pathways in heat stress response.

Heat stress limits the growth of roses and adversely affects the yield and the quality of the rose cut-flowers. To investigate the heat stress response (HSR) mechanisms of rose, we compared the transcriptome profiling generated from Rosa chinensis 'Slater's crimson China' exposed to heat stress for five different time duration (0, 0.5, 2, 6, 12 h). Overall, 6175 differentially expressed genes (DGEs) were identified and exhibited different temporal expression patterns. Up-regulated genes related to chaperone-mediated protein folding, signal transduction and ROS scavenging were rapidly induced after 0.5-2 h of heat treatment, which provides evidence for the early adjustments of heat stress response in R. chinensis. While the down-regulated genes related to light reaction, sucrose biosynthesis, starch biosynthesis and cell wall biosynthesis were identified after as short as 6 h of heat stress, which indicated the ongoing negative effects on the physiology of R. chinensis. Using weighted gene co-expression network analysis, we found that different heat stress stages could be delineated by several modules. Based on integrating the transcription factors with upstream enriched DNA motifs of co-expressed genes in these modules, the gene regulation networks were predicted and several regulators of HSR were identified. Of particular importance was the discovery of the module associated with rapid sensing and signal transduction, in which numerous co-expressed genes related to chaperones, Ca2+ signaling pathways and transcription factors were identified. The results of this study provided an important resource for further dissecting the role of candidate genes governing the transcriptional regulatory network of HSR in Rose.

Developing glutathione-activated catechol-type diphenylpolyenes as small molecule-based and mitochondria-targeted prooxidative anticancer theranostic prodrugs.

Developing concise theranostic prodrugs is highly desirable for personalized and precision cancer therapy. Herein we used the glutathione (GSH)-mediated conversion of 2,4-dinitrobenzenesulfonates to phenols to protect a catechol moiety and developed stable pro-catechol-type diphenylpolyenes as small molecule-based prooxidative anticancer theranostic prodrugs. These molecules were synthesized via a modular route allowing creation of various pro-catechol-type diphenylpolyenes. As a typical representative, PDHH demonstrated three unique advantages: (1) capable of exploiting increased levels of GSH in cancer cells to in situ release a catechol moiety followed by its in situ oxidation to o-quinone, leading to preferential redox imbalance (including generation of H2O2 and depletion of GSH) and final selective killing of cancer cells over normal cells, and is also superior to 5-fluorouracil and doxorubicin, the widely used chemotherapy drugs, in terms of its ability to kill preferentially human colon cancer SW620 cells (IC50 = 4.3 µM) over human normal liver L02 cells (IC50 = 42.3 µM) with a favourable in vitro selectivity index of 9.8; (2) permitting a turn-on fluorescent monitoring for its release, targeting mitochondria and therapeutic efficacy without the need of introducing additional fluorophores after its activation by GSH in cancer cells; (3) efficiently targeting mitochondria without the need of introducing additional mitochondria-directed groups.

Designing dichlorobinaphthoquinone as a prooxidative anticancer agent based on hydrogen peroxide-responsive in situ production of hydroxyl radicals.

Compared with normal cells, cancer cells harbor increased levels of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), and therefore are more vulnerable to further ROS production. This biochemical difference favors the idea of developing new powerful selective prooxidative anticancer agents. However, it still remains a challenge to design them by targeting this difference. Herein, we report the designed dichlorobinaphthoquinone as a prooxidative anticancer agent which is capable of exploiting increased levels of H2O2 of cancer cells to produce in situ lethal hydroxyl radicals (HO•) and thereby kill them selectively, a design strategy inspired from Zhu et al.'s work on the molecular mechanism for metal-independent production of HO•.

A 1,8-naphthalimide-based turn-on fluorescent probe for imaging mitochondrial hydrogen peroxide in living cells.

Hydrogen peroxide (H2O2) produced from mitochondria has attracted much attention on account of its physiological and pathological functions. Therefore, monitoring mitochondrial H2O2 levels in living cells is of great significance for understanding its functions. We report here a mitochondria-targeted H2O2 probe, Mito-HP, which was designed based on the 1,8-naphthalimide fluorogen by incorporation of a triphenylphosphonium targeting group and a boronate-based molecule switch. The probe demonstrates desired properties such as high selectivity, "turn-on" fluorescence response, excellent water solubility and physiological pH-response along with low cytotoxicity. Fluorescence colocalization studies indicate that the probe is capable of targeting the mitochondria of HeLa cells and is sensitive to the exogenous and endogenous production of H2O2 with a turn-on fluorescence increase.

Keto-enol-based modification on piperlongumine to generate a potent Cu(II) ionophore that triggers redox imbalance and death of HepG2 cells.

Altered redox status including higher levels of copper in cancer cells than in normal cells inspired many researchers to develop copper ionophores targeting this status. We have recently found that flavon-3-ol (3-HF) works as a potent Cu(II) ionophore by virtue of its keto-enol moiety. To further emphasize the significance of this moiety for developing Cu(II) ionophores, we herein designed a ß-diketo analog of piperlongumine, PL-I, characterized by the presence of high proportion of the keto-enol form in dimethylsulfoxide and chloroform, and identified its keto-enol structure by NMR and theoretical calculations. Benefiting from deprotonation of its enolic hydroxyl group, this molecule is capable of facilitating the transport of Cu(II) through cellular membranes to disrupt redox homeostasis of human hepatoma HepG2 cells and trigger their death.

Diagnosis of chronic heart failure by the soluble suppression of tumorigenicity 2 and N-terminal pro-brain natriuretic peptide.

OBJECTIVE: Our study was to explore the roles between serum soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) while evaluating ventricular function to properly diagnose chronic heart failure (CHF). METHODS: In total, 197 CHF patients were recruited and classified into ventricular function's II, III, and IV groups, and 106 healthy people into normal control group. To detect concentrations of Sst2 and NT-proBNP, ELISA and electro-chemiluminescence immuno assay were implemented. An automatic biochemical analyzer was used to determine the levels of the following: blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and uric acid (UA). A receiver operating characteristic (ROC) curve was adopted to detect the diagnostic value sST2 and NT-ProBNP in CHF and the logistic regression analysis involving the risk factors of CHF. RESULTS: Serum sST2 and NT-proBNP concentrations were increased significantly in the ventricular function's II, III, and IV groups in a manner dependent on concentration as opposed to the manner the normal control group occupied. The area under the curve (AUC) of sST2, found NT-proBNP and sST2+NT-proBNP to be 0.942 (95% CI: 0.917-0.966), 0.920 (95% CI: 0.891-0.948), and 0.968 (95% CI: 0.953-0.984), respectively. sST2, NT-proBNP, UA, and Cr were verified as important risk factors of CHF. CONCLUSION: Serum sST2 and NT-ProBNP could act as diagnostic indicators for CHF.

Developing piperlongumine-directed glutathione S-transferase inhibitors by an electrophilicity-based strategy.

We report a case of successful design of glutathione S-transferase (GST) inhibitors via a natural product-inspired and electrophilicity-based strategy. Based on this strategy, a novel piperlongumine analog (PL-13) bearing a para-trifluoromethyl group and an α-chlorine on its aromatic and lactam rings, respectively, surfaced as a promising GST inhibitor, thereby overcoming cisplatin resistance in lung cancer A549 cells.

[Analysis and comprehensive evaluation on cold resistance of six varieties of Michelia]. / 6种含笑属植物抗寒性分析与综合评价.

Taking six varieties of Michelia as test materials, their responses under cold situation in the field were investigated and the semilethal low temperatures were calculated by fitting Logistic equation. The nine structure indexes of leaf tissue were observed by paraffin section, and a comprehensive evaluation on cold resistance of different varieties was given according to subordinate function value analysis. The results showed that the relative electrical conductivity of six varieties of Michelia was significantly positively correlated with the semilethal low temperature (LT50) of 3 h 0-25 ℃ treatment. From high to low, the order of LT50, which ranged between -20.48 ℃and -8.67 ℃, was M. maudiae ＞ M. maudiae var. rubicunda ＞ M. wilsonii ＞ M. 'liubanhanxiao' â™€× M. shiluensis ♂ ＞ M. platypetala ＞ M. 'liubanhanxiao'. The epidermal anticlinal walls of six varieties of Michelia leaves had 1-2 layers and showed slightly sinuated shape. The leaf had 1-3 layers of palisade tissue cells and the differences among the indexes of nine anatomical structures were extremely significant. The thickness of palisade tissue, ratio between palisade tissue and spongy tissue, and thickness of the vein were the key factors affecting cold resistance. The order of cold resistance of six varieties of Michelia, from the strong to the weak, was M. 'liubanhanxiao' ＞ M. platypetala ＞ M. 'liubanhanxiao' â™€× M. shiluensis ♂＞M. wilsonii ＞ M. maudiae var. rubicunda ＞ M. maudiae, which was basically consistent with the result of field investigation.

Designing piperlongumine-directed anticancer agents by an electrophilicity-based prooxidant strategy: A mechanistic investigation.

Piperlongumine (PL), a natural electrophilic alkaloid bearing two α, ß-unsaturated imides, is a promising anticancer molecule by targeting the stress response to reactive oxygen species (ROS). Considering that ROS generation depends on electrophilicity of PL, PL-CL was designed as its analog by introducing the α-substituent chlorine on the lactam ring to increase moderately its electrophilicity. In comparison with the parent molecule, this molecule was identified as a stronger ROS (O2(∙-) and H2O2) inducer and cytotoxic agent, and manifested more than 15-fold selectivity toward A549 cells over normal WI-38 cells. Mechanistic study uncovers for the first time that the selenoprotein thioredoxin reductase (TrxR) is one of the targets by which PL-CL promotes the ROS generation. Stronger intracellular TrxR inhibition and higher accumulation of ROS (O2(∙-) and H2O2) are responsible for more effective S-phase arrest and mitochondria-mediated apoptotic induction of A549 cells by PL-CL than PLvia p53-p21-cyclinA/CDK2 and ASK1-JNK/p38 signaling cascade pathways, respectively. This work provides an example of successfully designing PL-directed anticancer agent by an electrophilicity-based prooxidant (ROS-generating agent) strategy and gives added confidence for extending this strategy to other natural products.

Visible-Light-Driven Intermolecular [2+2] Cycloadditions between Coumarin-3-Carboxylates and Acrylamide Analogs.

This paper reports a room temperature visible-light-driven protocol for the intermolecular [2+2] cycloadditions between coumarin-3-carboxylates and acrylamides analogs by an energy-transfer process. Using an iridium complex FIrPic as a photosensitizer and a 3 W blue LED as a light source, an array of cyclobutabenzocypyranones were prepared in moderate to excellent yields.

Influence of side chain structure changes on antioxidant potency of the [6]-gingerol related compounds.

[6]-Gingerol and [6]-shogaol are the major pungent components in ginger with a variety of biological activities including antioxidant activity. To explore their structure determinants for antioxidant activity, we synthesized eight compounds differentiated by their side chains which are characteristic of the C1-C2 double bond, the C4-C5 double bond or the 5-OH, and the six- or twelve-carbon unbranched alkyl chain. Our results show that their antioxidant activity depends significantly on the side chain structure, the reaction mediums and substrates. Noticeably, existence of the 5-OH decreases their formal hydrogen-transfer and electron-donating abilities, but increases their DNA damage- and lipid peroxidation-protecting abilities. Additionally, despite significantly reducing their DNA strand breakage-inhibiting activity, extension of the chain length from six to twelve carbons enhances their anti-haemolysis activity.

Tailoring 3,3'-dihydroxyisorenieratene to hydroxystilbene: finding a resveratrol analogue with increased antiproliferation activity and cell selectivity.

Four novel compounds were designed by "tailoring" 3,3'-dihydroxyisorenieratene (a natural carotenoid) based on an isoprene unit retention truncation strategy. Among them, the smallest molecule 1 (2,3,6,2',3',6'-hexamethyl-4,4'-dihydroxy-trans-stilbene) was concisely synthesized in a one-pot Stille-Heck tandem sequence, and surfaced as a promising lead molecule in terms of its selective antiproliferative activity mediated by blocking the NCI-H460 cell cycle in G1 phase. Additionally, theoretical calculations and cell uptake experiments indicate that the unique polymethylation pattern of compound 1 significantly induces a conformational change shift out of planarity and increases its cell uptake and metabolic stability. The observation should be helpful to rationally design resveratrol-inspired antiproliferative agents.

An effective strategy to develop active cinnamic acid-directed antioxidants based on elongating the conjugated chains.

To optimize antioxidant activity and lipophilicity of cinnamic acid derivatives (CAs) including ferulic acid, sinapic acid, 3,4-dimethoxycinnamic acid, and p-hydroxycinnamic acid, four analogs bearing an additional double bond between their aromatic ring and propenoic acid moiety were designed and synthesized based on the conjugated chain elongation strategy. The antioxidant performance of the CAs were investigated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH)-scavenging, ferric reducing/antioxidant power, cyclic voltammetry, DNA strand breakage-inhibiting and anti-haemolysis activity assays. It was found that CAs with elongation of conjugated chains display increased DPPH-scavenging, DNA strand breakage-inhibiting and anti-haemolysis activities as compared to their parent molecules, due to their improved hydrogen atom-donating ability and lipophilicity. Overall, this work highlights an effective strategy to develop potential CA-directed antioxidants by elongating their conjugated chain.