Controlled Synthesis of α-CF2H or α-CF2Cl Styrenes from the Same Precursors: Dehydrazinative Hydrogenation or Chlorination of 3,3-Difluoroallyl Hydrazines.

By carefully choosing the reaction conditions, we have developed the controllable FeCl3- or CuCl2-mediated dehydrazinative hydrogenation or chlorination of 3,3-difluoroallyl hydrazines to access α-CF2H or α-CF2Cl styrenes. The current reaction provides for the first time a facile method for the direct and selective synthesis of α-CF2H and α-CF2Cl styrenes starting from the same precursors, which is easy to scale up and displays a broad substrate scope and good functional group tolerance. Moreover, product derivatization experiments demonstrated that the resulting α-CF2Cl styrenes are practical and versatile building blocks for the diversified synthesis of fluorinated molecules.

Effects of Multi-Walled Carbon Nanotubes and Nano-Silica on Root Development, Leaf Photosynthesis, Active Oxygen and Nitrogen Metabolism in Maize.

Carbon nanotubes (MWCNTs) and nano-silica (nano-SiO2) are widely used in the field of life science because of their special physical and chemical properties. In this study, the effects of different concentrations of MWCNTs (0 mg·L-1, 200 mg·L-1, 400 mg·L-1, 800 mg·L-1 and 1200 mg·L-1) and nano-SiO2 (0 mg·L-1, 150 mg·L-1, 800 mg·L-1, 1500 mg·L-1 and 2500 mg·L-1) on maize seedling growth and relative mechanisms were explored. The main results are as follows: MWCNTs and nano-SiO2 can promote the growth of maize seedlings, and promote plant height, root length, the dry and fresh weight of seedlings, root-shoot ratio and so on. The ability to accumulate dry matter increased, the relative water content of leaves increased, the electrical conductivity of leaves decreased, the stability of cell membranes improved and the water metabolism ability of maize seedlings increased. The treatment of MWCNTs with 800 mg·L-1 and nano-SiO2 with 1500 mg·L-1 had the best effect on seedling growth. MWCNTs and nano-SiO2 can promote the development of root morphology, increase root length, root surface area, average diameter, root volume and total root tip number and improve root activity, so as to improve the absorption capacity of roots to water and nutrition. After MWCNT and nano-SiO2 treatment, compared with the control, the contents of O2·- and H2O2 decreased, and the damage of reactive oxygen free radicals to cells decreased. MWCNTs and nano-SiO2 can promote the clearance of reactive oxygen species and maintain the complete structure of cells, so as to slow down plant aging. The promoting effect of MWCNTs treated with 800 mg·L-1 and nano-SiO2 treated with 1500 mg·L-1 had the best effect. After treatment with MWCNTs and nano-SiO2, the activities of key photosynthesis enzymes PEPC, Rubisco, NADP-ME, NADP-MDH and PPDK of maize seedlings increased, which promoted the opening of stomata, improved the fixation efficiency of CO2, improved the photosynthetic process of maize plants and promoted plant growth. The promoting effect was the best when the concentration of MWCNTs was 800 mg·L-1 and the concentration of nano-SiO2 was 1500 mg·L-1. MWCNTs and nano-SiO2 can increase the activities of the enzymes GS, GOGAT, GAD and GDH related to nitrogen metabolism in maize leaves and roots, and can increase the content of pyruvate, so as to promote the synthesis of carbohydrates and the utilization of nitrogen and promote plant growth.

Translation and Linguistic Validation of the Assessment of Physical Activity in Frail Older People into Simplified Chinese Using Cognitive Interviewing Methodology.

The Assessment of Physical Activity in Frail Older People (APAFOP) is a patient-reported outcome measure assessing physical activity among community-dwelling older adults. However, this instrument has not been verified in the Chinese context. Thus, we translated the APAFOP into Chinese and then linguistically validated the Chinese version of APAFOP (APAFOP-C) by following the guidelines developed by Beaton and Willis. The translation process took 6 months. We identified nine translation issues in the translation process, of which experiential equivalence issues were the most frequent. It took three rounds of cognitive interviews to achieve linguistic validity, and the most significant issues were related to the layout of the questionnaire identified during the cognitive interview. In conclusion, the items of the APAFOP-C were considered comprehensive and relevant to assessing the physical activities of frail older adults in China. This study has laid the foundation for future evaluation of its measurement properties.

Characterizing corn-straw-degrading actinomycetes and evaluating application efficiency in straw-returning experiments.

Corn straw is an abundant lignocellulose resource and by-product of agricultural production. With the continuous increase in agricultural development, the output of corn straw is also increasing significantly. However, the inappropriate disposal of straw results in wasting of resources, and also causes a serious ecological crisis. Screening microorganisms with the capacity to degrade straw and understanding their mechanism of action is an efficient approach to solve such problems. For this purpose, our research group isolated three actinomycete strains with efficient lignocellulose degradation ability from soil in the cold region of China: Streptomyces sp. G1T, Streptomyces sp. G2T and Streptomyces sp. G3T. Their microbial properties and taxonomic status were assessed to improve our understanding of these strains. The three strains showed typical characteristics of the genus Streptomyces, and likely represent three different species. Genome functional annotation indicated that most of their genes were related to functions like carbohydrate transport and metabolism. In addition, a similar phenomenon also appeared in the COG and CAZyme analyses, with a large number of genes encoding carbohydrate-related hydrolases, such as cellulase, glycosidase and endoglucanase, which could effectively destroy the structure of lignocellulose in corn straw. This unambiguously demonstrated the potential of the three microorganisms to hydrolyze macromolecular polysaccharides at the molecular level. In addition, in the straw-returning test, the decomposing consortium composed of the three Streptomyces isolates (G123) effectively destroyed the recalcitrant bonds between the various components of straw, and significantly reduced the content of active components in corn straw. Furthermore, microbial diversity analysis indicated that the relative abundance of Proteobacteria, reportedly associated with soil antibiotic resistance and antibiotic degradation, was significantly improved with straw returning at both tested time points. The microbial diversity of each treatment was also dramatically changed by supplementing with G123. Taken together, G123 has important biological potential and should be further studied, which will provide new insights and strategies for appropriate treatment of corn straw.

Silver-Catalyzed Cascade Cyclization of Amino-NH-1,2,3-Triazoles with 2-Alkynylbenzaldehydes: An Access to Pentacyclic Fused Triazoles.

An operationally simple Ag(I)-catalyzed approach for the synthesis of isoquinoline and quinazoline fused 1,2,3-triazoles was developed by a condensation and amination cyclization cascade of amino-NH-1,2,3-triazoles with 2-alkynylbenzaldehydes involving three new C-N bond formations in one manipulation, in which the group of -NH of the triazole ring serves as a nucleophile to form the quinazoline skeleton. The efficient protocol can be applied to a variety of substrates containing a range of functional groups, delivering novel pentacyclic fused 1,2,3-triazoles in good-to-excellent yields.

Doyle-Kirmse reaction using 3,3-difluoroallyl sulfide and N-sulfonyl-1,2,3-triazole: an efficient access to gem-difluoroallylated multifunctional quaternary carbon.

A Doyle-Kirmse reaction of N-sulfonyl-1,2,3-triazole with 3,3-difluoroallyl sulfide through a Rh(ii)-catalyzed [2,3]-sigmatropic rearrangement has been developed, which provides an efficient access to multifunctional quaternary centers containing aryl, imino, thio, and brominated gem-difluoroallyl groups. The reaction features broad substrate scope with moderate to excellent yields. The applicability of the method is confirmed by gram-scale synthesis and further transformations.

Synthesis of Polysubstituted Fused Pyrroles by Gold-Catalyzed Cycloisomerization/1,2-Sulfonyl Migration of Yndiamides.

Yndiamides (bis-N-substituted alkynes) are valuable precursors to azacycles. Here we report a cycloisomerization/1,2-sulfonyl migration of alkynyl-yndiamides to form tetrahydropyrrolopyrroles, unprecedented heterocyclic scaffolds that are relevant to medicinal chemistry. This functional group tolerant transformation can be achieved using Au(I) catalysis that proceeds at ambient temperature, and a thermally promoted process. The utility of the products is demonstrated by a range of reactions to functionalize the fused pyrrole core.

Au(I)-Catalyzed Oxidative Functionalization of Yndiamides.

Yndiamides, underexplored cousins of ynamides, offer rich synthetic potential as doubly nitrogenated two carbon building blocks. Here we report a gold-catalyzed oxidative functionalization of yndiamides to access unnatural amino acid derivatives, using a wide range of nucleophiles as a source of the amino acid side chain. The transformation proceeds under mild conditions, is highly functional group tolerant, and displays excellent regioselectivity through subtle steric differentiation of the yndiamide nitrogen atom substituents.

Concentration distribution and assessment of heavy metals in surface sediments in the Zhoushan Islands coastal sea, East China Sea.

In an effort to assess the potential contamination and determine the environmental risks associated with heavy metals, 51 surface sediment samples (0-4 cm) were collected in the Zhoushan Islands coastal sea of the East China Sea (ECS). The heavy metal concentrations, grain size and total organic carbon (TOC) contents of these surface sediments were comprehensively analyzed. The results showed that the order of the average concentrations of heavy metals is Zn > Cr > Cu > Pb > As > Cd > Hg. Zn, Cr, Cd and Hg exhibit similar distribution and which derived from a common source, however, Cu, Pb and As present different distribution. The metal enrichment factor (EF) and geoaccumulation index (Igeo) values both suggest that Cu and Cd likely pose environmental risks. The results of this study could provide scientific data to authorities in charge of sustainable marine management.

Advances in polycyclization cascades in natural product synthesis.

Cascade reactions (also known as domino reactions) are arguably the most powerful means to achieve the construction of multiple ring systems in a single step. In this Tutorial Review, highlights in cascade polycyclizations applied to natural product syntheses over the last five years are discussed, including pericyclic, ionic, metal-catalyzed, organocatalytic, and radical processes. Significant developments in each of these fields that have advanced the state-of-the-art are a particular focus, including photochemical and electrochemical methods, novel biomimetic routes, and enantioselective cascades.

Copper-catalyzed cross-coupling and sequential allene-mediated cyclization for the synthesis of 1,2,3-triazolo[1,5-a]quinolines.

In this paper, a tandem reaction involving copper-catalyzed cross-coupling and allene-mediated cyclization of 1-(2-ethynylaryl)-1,4-disubstituted-1,2,3-triazole with N-tosylhydrazone has been developed. This method features operational simplicity, excellent functional group compatibility, broad substrate scope, and easily available feedstock, providing an efficient and practical strategy for the synthesis of highly functionalized 1,2,3-triazolo[1,5-a]quinolines.

Copper-Catalyzed Intramolecular C-H Alkoxylation of Diaryltriazoles: Synthesis of Tricyclic Triazole Benzoxazines.

An efficient copper-catalyzed intramolecular C-H alkoxylation of 1,4-disubstituted 1,2,3-triazoles has been developed. The chemistry was applied to a wide range of substrates, generating tricyclic benzoxazine-fused 1,2,3-triazoles in good yields. Mechanistic studies suggest that a radical pathway may be involved in this transformation. The triazole products were found to exhibit strong antifungal activity against ginseng root-rot disease, demonstrating their potential as a scaffold in medicinal chemistry research.

Glucocorticoids inhibits the repair of airway epithelial cells via the activation of wnt pathway.

BACKGROUND: The purpose of this study was to explore the effect of Wnt pathway on the inhibition of airway epithelial cells repair by glucocorticoid. MATERIALS AND METHODS: The expression of E-cadherin in asthma mice model was detected by immunocytochemistry. XAV939 was used to treat 16HBE, and the expressions of related genes were determined by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, migration and cell cycle were analyzed by methylthiazolyldiphenyl-tetrazolium bromide, wound healing and flow cytometry, respectively. RESULTS: In asthma mice model, the lung tissue was impaired. After dexamethasone treatment, the airway inflammation was relieved and the expression of E-cadherin was reduced. Dexamethasone increased the expressions of Wnt7b, LRP5, ß-catenin and CyclinD1, inhibited cell viability and migration and arrested cell cycle, whereas XAV939 produced the opposite effects. In addition, XAV939 suppressed Wnt pathway that activated by dexamethasone. CONCLUSION: Glucocorticoid could inhibit cell proliferation and migration via regulating Wnt pathway to affect cell cycle, thus inhibiting the repair of airway epithelial after injury.

gem-Difluoroallylation of Aryl Diazoesters via Catalyst-Free, Blue-Light-Mediated Formal Doyle-Kirmse Reaction.

A first example of low-energy blue-light-mediated formal Doyle-Kirmse reaction for gem-difluoroallylation of aryl diazoesters has been developed. A variety of highly functionalized gem-difluoroallyl containing esters bearing transformable sulfur and bromine groups were efficiently assembled with broad substrate scope under mild, catalyst-free, and additive-free conditions. The reaction represents a practical and environmentally friendly approach for C-CF2 bond formation based on rearrangement strategy, which will find potential applications among drug discovery and development.

Dynamic change of PD-L1 expression on circulating tumor cells in advanced solid tumor patients undergoing PD-1 blockade therapy.

Background: Tumor PD-L1 levels have predictive value in PD-1/PD-L1 checkpoint blockade therapies, yet biopsies can only provide baseline information. Whether PD-L1 expression on circulating tumor cells (CTCs) could serve as an alternative biomarker is of great interest. Design: We established an immunofluorescence assay for semi-quantitative assessment of the PD-L1 expression levels on CTCs with four categories (PD-L1negative, PD-L1low, PD-L1medium and PD-L1high). 35 patients with different advanced gastrointestinal tumors were enrolled in a phase 1 trial of a PD-1 inhibitor, IBI308. The CTC numeration and the PD-L1 expression levels were analyzed. Results: Prior the treatment of IBI308, 97% (34/35) patients had CTCs, ranging from1 to 70 (median 7). 74% (26/35) had PD-L1positive CTCs, and 60% (21/35) had at least one PD-L1high CTCs. The disease control (DC) rate in PD-L1high patients (48%) is much higher than the others (14%). The group with at least 20% abundance of PD-L1high CTCs had even higher DC rate of 64% (9/14), with only 14% DC rate for the rest (3/21). We also observed that the count changes of total CTC, PD-L1postive CTC and PD-L1high CTC correlate quite well with disease outcome (P<0.001, P = 0.002 and 0.007, respectively). In addition, the abundance of PD-L1high CTCs at baseline had predicative significance for progression free survival (PFS). Conclusions: We revealed that the abundance of PD-L1high CTCs at baseline might serve as a predictor to screen patients for PD-1/PD-L1 blockade therapies and measuring the dynamic changes of CTC could indicate the therapeutic response at early time.

The correlation of KAI1, Slug and vasculogenic mimicry in the prediction of metastasis and prognosis in colorectal carcinoma.

KAI1 and the epithelial-mesenchymal transition regulator Slug, as well as vasculogenic mimicry (VM), play a significant role in the process of metastasis and prognosis in many human cancers. This study investigated the relationship of KAI1, Slug and VM and their connection with clinicopathological features, metastasis and their prognostic value in colorectal carcinoma (CRC). Immunohistochemistry was performed to analyze the expression of KAI, Slug, VM, E-cadherin (E-cad) and vimentin in 134 human CRC and corresponding normal mucosal tissues. The results showed that the protein expressions of KAI1, Slug and VM in tumor tissues were significantly different from adjacent normal mucosal tissues. The expression of KAI1 was negatively related, while the expressions of Slug and VM are positively related with differentiation, lymph node metastasis, distant metastasis and TNM stage. KAI1 was negatively related, while VM was positively related with invasion. The expression of KAI1 showed a negative correlation with Slug and VM. Moreover, the expression of Slug was positively associated with VM. A Kaplan-Meier analysis showed that the expression of Slug and VM was negatively and KAI1 expression was positively correlated with overall survival. Low KAI1 expression and high Slug and VM expression showed a poorer prognosis in CRC. Multivariate Cox regression analysis showed that the expression of KAI1, Slug, VM and TNM stage were independent predictors of OS in CRC. The expression of KAI1, Slug and VM was correlated with metastasis and prognosis. These findings suggest that KAI1, Slug and VM can be novel therapeutic targets to predict metastasis and prognosis in CRC patients.

Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma.

Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in regulating the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating immune cells (TILs) in the tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Archival formalin-fixed, paraffin-embedded ESCC samples from treatment-naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy were collected between 2004 and 2014. Expression of PD-L1 in ESCC tumor specimens was assessed by immunohistochemistry (IHC), and the degree of TIL infiltration was evaluated by examining hematoxylin and eosin-stained (H&E) specimens. PD-L1+ as defined as ≥1% of tumor cell membranes showing ≥1+ intensity. In 428 patients, specimens from 341 (79.7%) were PD-L1+. In the definitive treatment group (patients who received curative esophagectomy or definitive [chemo-]radiation therapy), PD-L1 positivity was associated with a significantly shorter DFS and OS. In the palliative chemotherapy group exhibited, neither PFS nor OS correlated significantly with PD-L1 expression. PD-L1 expression was positively associated with TIL density. In 17 paired tumor tissues collected before and after treatment, an increase in PD-L1 expression was associated with disease progression, whereas a decrease in PD-L1 expression was associated with response to chemotherapy or disease control. So, PD-L1 expression was associated with a significantly worse prognosis in patients with ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients.

The proteome and phosphoproteome of maize pollen uncovers fertility candidate proteins.

Maize is unique since it is both monoecious and diclinous (separate male and female flowers on the same plant). We investigated the proteome and phosphoproteome of maize pollen containing modified proteins and here we provide a comprehensive pollen proteome and phosphoproteome which contain 100,990 peptides from 6750 proteins and 5292 phosphorylated sites corresponding to 2257 maize phosphoproteins, respectively. Interestingly, among the total 27 overrepresented phosphosite motifs we identified here, 11 were novel motifs, which suggested different modification mechanisms in plants compared to those of animals. Enrichment analysis of pollen phosphoproteins showed that pathways including DNA synthesis/chromatin structure, regulation of RNA transcription, protein modification, cell organization, signal transduction, cell cycle, vesicle transport, transport of ions and metabolisms, which were involved in pollen development, the following germination and pollen tube growth, were regulated by phosphorylation. In this study, we also found 430 kinases and 105 phosphatases in the maize pollen phosphoproteome, among which calcium dependent protein kinases (CDPKs), leucine rich repeat kinase, SNF1 related protein kinases and MAPK family proteins were heavily enriched and further analyzed. From our research, we also uncovered hundreds of male sterility-associated proteins and phosphoproteins that might influence maize productivity and serve as targets for hybrid maize seed production. At last, a putative complex signaling pathway involving CDPKs, MAPKs, ubiquitin ligases and multiple fertility proteins was constructed. Overall, our data provides new insight for further investigation of protein phosphorylation status in mature maize pollen and construction of maize male sterile mutants in the future.

[A preliminary study of the inhibitive efficacy of iodized linoleic acid and its fluorodeoxyuridine ester in hepatocellular cancer].

OBJECTIVE: To explore the potential of iodized linoleic acid (ILA) and its 5-fluoro-deoxyuridine ester (IFU) to inhibit hepatocellular carcinoma (HCC) cells in vitro and tumors in vivo. METHODS: ILA and its constituent component IFU were chemically synthesized, purified, and confirmed by 1H-NMR. The HCC cell lines, QGY-7703 (5-fluorouracil (5-FU) treatment sensitive) and SMMC-7721 (5-FU resistant), were treated with ILA, IFU, 5-FU, or traditional lipiodol for 72 hours. Survival rates of the treated cells were assessed by the methyl thiazolyl tetrazolium method, and used to calculate the IC50 and IC90. In addition, thirty nude mice were subcutaneously inoculated with SMMC-7721 cells and randomly divided two weeks later into four treatment groups (n = 6 each) for intra-tumoral injection of ILA, IFU, 5-FU, lipiodol or DMSO (controls). The rate of tumor inhibition (RTI) was calculated for each group at week 4 after treatment. RESULTS: For the cultured SMMC-7721 cells, the inhibitory concentrations for ILA, IFU, and 5-FU were: IC50: 134.38 mumol/L, 17.55 mumol/L, and 7.38 mumol/L; IC90: 192.88 mumol/L, 97.63 mumol/L, and more than 200 mumol/L. For the cultured QGY-7703 cells, the inhibitory concentrations for ILA, IFU, and 5-FU were: IC50: 109.55 mumol/L, 44.79 mumol/L, and 98.06 mumol/L; IC90: all, more than 200 mumol/L. In both cell types, the IC50 of lipiodol was more than 400 mumol/L. Compared with the RTI of the control mice (100%), the RTI of ILA-treated mice was 31.9% (t = 2.37, P less than 0.05), of IFU-treated mice was 56.9% (t = 4.91, P less than 0.01), and of 5-FU-treated mice was 31.0% (t = 2.59, P less than 0.05). The RTI of IFU was significantly stronger than that of either ILA or 5-FU (P less than 0.05). The lipiodol treatment showed no inhibition effect on tumors (P more than 0.05). CONCLUSION: ILA and IFU can effectively inhibit the growth of HCC cells in vitro and tumors in vivo. Furthermore, IFU outperforms ILA in inhibiting HCC growth.