Precise Confinement and Position Distribution of Atomic Cu and Zn in ZSM-5 for CO2 Hydrogenation to Methanol.

CuZn-based catalysts are widely used in CO2 hydrogenation, which may effectively convert CO2 to methanol and alleviate CO2 emission issues. The precise design of a model catalyst with a clear atomic structure is crucial in studying the relationship between structure and catalytic activity. In this work, a one-pot strategy was used to synthesize CuZn@ZSM-5 catalysts with approximately two Cu atoms and one Zn atom per unit cell. Atomic Cu and Zn species are confirmed to be located in the [54.6.102] and [62.104] tilings, respectively, by using magic-angle spinning nuclear magnetic resonance spectroscopy (MAS NMR), synchrotron X-ray powder diffraction (SXRD) and high-signal-to-noise-ratio annular dark field scanning transmission electron microscopy (High SNR ADF-STEM). Catalytic hydrogenation of CO2 to methanol was used as a model reaction to investigate the activity of the catalyst with confined active species. Compared to the Cu@ZSM-5, Zn@ZSM-5 and their mixture, the CuZn@ZSM-5 catalyst with a close Cu-Zn distance of 4.5 Å achieves a comparable methanol space-time yield (STY) of 92.0 mgmethanol·gcatal-1·h-1 at 533 K and 4 MPa with high stability. This method is able to confine one to three metal atoms in the zeolite channel and avoid migration and agglomeration of the atoms during the reaction, which maintains the stability of the catalyst and provides an efficient way for adjustment of the type and number of metal atoms along with the distances between them in zeolites.

Production of Atosiban's Key Intermediate Pentapeptide: Synthetic Approaches to the Development of a Peptide Synthesis with Less Racemization and Simplifier Purification Process.

The key intermediate NH2-Ile-Thr(Bzl)-Asn-Cys(Bzl)-Pro-COOH of Atosiban was prepared from N-Boc-S-Bzl-cysteine by the stepwise lengthening of the chain according to the repetitive N,O-bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) strategy. This synthetic route required no chromatography purification and can be readily performed, yielding a highly pure pentapeptide compound.

Release of the additive metals from 3 commonly used plastics during the degradation under the treatment of UV irradiation.

Additive metals are continuously released into the environment during the photo-degradation of plastics into microplastics, but this phenomenon has not been reported by many studies. Herein, we investigated the surface morphology changes along with the release of additive metals (Cr, Mn, Fe, Co, Cu, Zn, and Pb) during the degradation of three types of plastics, i.e., polypropylene (PP), polyethylene terephthalate (PET) and polyvinyl chloride (PVC), under UV light irradiation. FTIR results showed that 168 days of UV-irradiation led to the primary degradation of each plastic sample. The metal release could be found after 70 days UV-irradiation. The rate of metal release for the three plastics showed the following order: PP > PET ≈ PVC. In addition, the distribution and concentrations of the metals in the plastic could influence the release characteristics of each metal. Low release rate of Fe symbolized by the total metal release in the range of 4.28 ~10.27% as evident from the results of the primary degradation experiment, indicated the release of Fe occurring in the late stage of the plastic degradation or even in the microplastics-formation stage. As for the release of Co from PP, it was far lower than that of the other elements (0.35%), showing the same release characteristics as that of Fe. On the contrary, the release ratio of Pb from PP was 78.89% and was mainly concentrated in the early stage of the plastic degradation. The results help understanding the release behavior of the additive metals during the degradation of typical plastics under ultraviolet light irradiation.

CXCL1 stimulates decidual angiogenesis via the VEGF-A pathway during the first trimester of pregnancy.

Angiogenesis is critical to establishing a successful pregnancy. The chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that is an important chemokine involved in the processes of angiogenesis and arteriogenesis; however, little is known about its role in decidual angiogenesis. Effects of CXCL1 on cell proliferation and migration (propidium iodide staining and wound healing assays) of HUVEC cells were determined. The angiogenesis roles of CXCL1 in HUVEC-HTR8/SVneo co-culture system were detected by the tube formation assay. Signal transduction pathways in HUVEC cells in response to CXCL1 were determined by in-cell western analyses. In vivo, mice were injected with (1) PBS (Group A) or (2) CXCL1-neutralizing antibody (Group B) or (3) CXCL1-neutralizing antibody plus recombinant VEGF-A protein (Group C) from E1 to E5 and sacrificed at E6.5 of pregnancy. The decidual angiogenesis in mice was examined by immunohistochemistry of cluster designation 34 (CD34), and the expression levels of vascular endothelial growth factor-A (VEGF-A) in the decidual cells and vascular endothelial growth factor receptor 2 (VEGFR2) in decidual vascular endothelial cells were also tested. Exogenous recombinant human CXCL1 supported endothelial cell proliferation and migration, and this effect was blocked by CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. The tube formation of HUVEC-HTR8/SVneo co-culture system was significantly stimulated by CXCL1, but this effect was markedly abrogated once they were pretreated with CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. In addition, the level of vascular endothelial growth factor A (VEGF-A) expression in HUVEC cells was increased by CXCL1, and this level was suppressed by CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. In vivo, compared with Group A (n = 3), decidual angiogenesis was significantly reduced in Group B by CD34 immunostaining. But compared with Group B, decidual angiogenesis was significantly increased in Group C. In addition, the expression of VEGF-A and VEGFR2 was significantly increased after neutralizing of CXCL1 in Group B. In conclusions, CXCL1 may play essential roles in decidual angiogenesis during the first trimester, and this function may be mediated in part via altering VEGF-A expression.

Elevated expression of EP4 in human decidua is associated with delayed embryo expulsion during medical abortion by promoting decidual cell proliferation.

Purpose: Mifepristone in conjunction with misoprostol, is widely used in China as an effective medical abortifacient. However, a small proportion of women experience the unpleasant side effects of prolonged vaginal bleeding caused by delayed embryo expulsion. The aims of this study were to determine whether the expression levels of prostanoid receptors in human decidua are associated with delayed embryo expulsion in mifepristone-misoprostol induced an early medical abortion.Methods: Discharged decidua tissues were collected from females undergoing an artificial abortion (AA) (n = 28), females with early embryo expulsion during a medical abortion (EEMA) (n = 20) and delayed embryo expulsion in medical abortion (DEMA) (n = 30). The expression levels of prostanoid receptors in human decidua were assessed with immunohistochemistry and real-time PCR methods. Further, the RNAi method was used to silence prostanoid receptors 4 (EP4) in the primary decidual cells and human endometrial adenocarcinoma cell line Ishikawa cells in vitro and cell cycle analysis of these cells was performed.Results: All five prostanoid receptors (EP1-4, FP) were observed in human early pregnancy decidua. The protein and mRNA expression level of EP4 in the DEMA group were all significantly higher than that in the EEMA group. EP4 silence induced G1/S arrest of primary decidual cells and Ishikawa cells in vitro.Conclusions: Elevated expression level of EP4 in human decidua was significantly associated with delayed embryo expulsion in early medical abortion by promoting decidual cell proliferation. Detailed studies on the nature of roles EP4 plays in human decidua will help us to develop more effective prevention and noninvasive intervention approaches for delayed embryo expulsion during a medical abortion.

A novel method for preparing Eligulstat through chiral resolution.

Eliglustat is a ceramide glucosyltransferase inhibitor work as first line oral therapy for adults with Gaucher disease type 1 (a rare disease) at present. Although the eliglustat in enantiomerically pure forms is obtained by asymmetric syntheses, the reported methods suffer from many limits when it comes to industrial applications. Therefore, the preparation of a racemic mixture followed by resolution can still be a viable and straightforward alternative, especially when it could be adapted to large scale. Herein, we developed an effective and practical synthetic route to prepare stereoisomers mixture of eliglustat, and a novel chiral resolution method to prepare eliglustat. Using 1,1'-Binaphthyl-2,2'-diyl -hydrogenphosphate (BNDHP) as resolution reagent, optical pure eliglustat (e.e. >99%, 13.97% total yield) could be obtained after recrystallization.

A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation.

Pasireotide is a multi-receptor ligand somatostatin analogue approved for medical treatment of Cushing's disease and acromegaly. The liquid-phase total synthesis of pasireotide-a 18-membered cyclic hexapeptide-was achieved by the 3 + 2 + 1 strategy, and the Pro1-Phe6 peptide bond was selected as the final cyclization position. Two key fragments were simply synthesized using N,O-bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) as coupling agents, and processes of the two key fragments were simple without any chromatographic purification. The current synthesis method is easily scalable and produces the target peptide with an overall yield of 15%.

Ag/Pyridine Co-Mediated Oxidative Arylthiocyanation of Activated Alkenes.

An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via radical addition/cyclization cascade process was developed. This reaction could be carried out under mild conditions to provide biologically interesting 3-alkylthiocyanato-2-oxindoles in good to excellent yields. Mechanistic studies suggested a unique NCS• radical addition path and clarified the dual roles of catalytic pyridine as base and crucial ligand to accelerate the oxidation of Ag(I) to Ag(II), which is likely oxidant responsible for the formation of NCS• radical. These mechanistic results may impact the design and refinement of other radical based reactions proceeding through catalytic oxidations mediated by Ag(I)-pyridine/persulfate. The chemical versatility of thiocyanate moiety was also highlighted via SCN-tailoring chemistry in post-synthetic transformation for new S-C(sp³/sp²/sp), S-P, and S-S bonds constructions. The protocol provides an easy access to many important bioisosteres in medicinal chemistry and an array of sulfur-containing 2-oxindoles that are difficult to prepare by other approaches.

Pseudolaric acid B induces endometrial cancer Ishikawa cell apoptosis and inhibits metastasis through AKT-GSK-3ß and ERK1/2 signaling pathways.

Pseudolaric acid B (PAB) is the most active constituent extracted from the bark of Pseudolarix kaempferi, which has been used as an antifungal remedy in traditional Chinese medicine. It is reported to have cytotoxicity to many tumor cell lines. In this study, we investigated the effects of PAB against human endometrial cancer Ishikawa cells. We found that PAB inhibited Ishikawa cell proliferation, and induced cell apoptosis and G2/M phase arrest through a mechanism involving AKT-GSK-3ß and ERK1/2 signaling pathways. PAB also suppressed the Ishikawa cell adhesion, invasion, migration, and colony formation ability by increasing the expression of E-cadherin, Ezrin, and Kiss-1, and decreasing the expression of matrix metalloproteinase-9 and vascular endothelial growth factor. Taken together, these data indicated that PAB can be expected to be a novel treatment agent for endometrial cancer therapy.

Elevated mRNA expression of PGF2α receptor splice variant 2(FP-V2) in human decidua is associated with incomplete mifepristone-misoprostol-induced early medical abortion by regulation of interleukin-8.

OBJECTIVE: The combination of mifepristone and misoprostol is an established method for the induction of early abortion, but 15% of women still experience the unpleasant side effect of incomplete medical abortion. The purpose of this study was to determine whether prostaglandin (PG) F2α receptor (FP) and its two isoforms (FP-V1 and FP-V2) in human decidua are associated incomplete abortion. METHODS: Forty women who underwent medical abortion were recruited. Among them, there were 20 cases of incomplete abortion. The other 20 cases of complete abortion were used as controls. The expression levels of FP, FPV1 and FP-V2 in the decidua between of the two groups was detected by quantitative real-time polymerase chain reaction (PCR). Additionally, FP-V2 was knocked down using specific small interfering RNAs (siRNAs) in the primary cultures of decidual cells. The expression levels of cytokines in FP-V2 knockdown primary decidual cells and control decidual cells were detected by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS: The FP and FP-V2 mRNA expression in the incomplete group was significantly higher than that in the complete group (p < 0.05). IL-8 was up-regulated by FP-V2 knockdown in primary-cultured decidual cells (p < 0.05). CONCLUSIONS: These results suggested that the elevated expression of FP-V2 in human decidua is significantly associated with incomplete mifepristone-misoprostol-induced early medical abortion and that IL-8 could be lined to this process.

Cyclophilin A Enhances Cell Proliferation and Xenografted Tumor Growth of Early Gastric Cancer.

BACKGROUND: Recently Cyclophilin A (CypA) was identified as a candidate target protein in gastric carcinoma. However, the role of CypA in gastric cancer (GC) has not been investigated extensively so far. AIM: The purpose of this study was to determine the expression pattern of CypA in human GC, and to explore the effects of suppressed CypA expression on cell proliferation and xenografted tumor growth of gastric cancer. METHODS: In the present study, we detected the expression pattern of CypA in human GC by immunohistochemistry analysis. Further, the RNAi method was used to silence CypA, and colony formation assay, growth curves, cell cycle and mouse xenograft were analysed. RESULTS: An elevated expression of CypA in GC tissues compared with normal gastric mucosa was observed, especially in TNM stage-I and intestinal type of tumor. CypA was overexpressed in most GC cell lines and endogenous expression of CypA correlated with cell growth phenotypes. Transient suppression of CypA reduced the proliferation of BGC-823 and SGC-7901 GC cell lines. Exogenous CypA promoted the proliferation of NCI-N87 GC cells in a concentration dependent manner. Further study revealed that stable CypA silencing inhibited the proliferation, prevented cell cycle and reduced autophagy of BGC-823 GC cells in vitro through suppressing the ERK1/2 signal pathway. Stable CypA silencing also inhibited the growth of xenografted tumor of BGC-823 GC cell in nude mice. CONCLUSIONS: These results indicate a special function mode for CypA of playing more important roles in the early stage of gastric tumorigenesis and suggest CypA as a new molecular target of diagnosis and treatment for GC patients.

A novel FBN2 mutation in a Chinese family with congenital contractural arachnodactyly.

Congenital contractural arachnodactyly (CCA, OMIM: 121050) is an autosomal dominant condition that shares skeletal features with Marfan syndrome (MFS, OMIM: 154700), including contractures, arachnodactyly, dolichostenomelia, scoliosis, crumpled ears and pectus deformities but excluding the ocular and cardiovascular complications that characterize MFS. These two similar syndromes result from mutations in two genes belonging to the fibrillin family, FBN1 and FBN2, respectively. We successfully identified a novel FBN2 mutation (C1406R) in a Chinese family with CCA for over five generations. This mutation was detected in the patients of this family but not in the seven unaffected family members or 100 normal individuals. SIFT and PolyPhen analyses suggested that the mutation was pathogenic. We identified a missense mutation in the calcium binding-epidermal growth factor (cbEGF)-like domain. Our study extends the mutation spectrum of CCA and confirms a relationship between mutations in the FBN2 gene and the clinical findings of CCA.

TGFA and IRF6 contribute to the risk of nonsyndromic cleft lip with or without cleft palate in northeast China.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) are common birth defects with a complex etiology. Multiple interacting loci and possible environmental factors influence the risk of NSCL/P. 12 single nucleotide polymorphisms (SNPs) in 7 candidate genes were tested using an allele-specific primer extension for case-control and case-parent analyses in northeast China in 236 unrelated patients, 185 mothers and 154 fathers, including 128 complete trios, and 400 control individuals. TGFA and IRF6 genes showed a significant association with NSCL/P. In IRF6, statistical evidence of an association between rs2235371 (p = 0.003), rs2013162 (p<0.0001) and NSCL/P was observed in case-control analyses. Family based association tests (FBATs) showed over-transmission of the C allele at the rs2235371 polymorphism (p = 0.007). In TGFA, associations between rs3771494, rs3771523 (G3822A), rs11466285 (T3851C) and NSCL/P were observed in case-control and FBAT analyses. Associations between other genes (BCL3, TGFB3, MTHFR, PVRL1 and SUMO1) and NSCL/P were not detected.

Identification of the keratin 9 (KRT9) N161S mutation in a Chinese kindred with epidermolytic palmoplantar keratoderma.

We present a family from Northeast China affected by epidermolytic palmoplantar keratoderma (EPPK) in which we confirmed the presence of the N161S mutation as the result of a 548A>G transition in exon1 of the keratin 9 gene. Genomic DNA from peripheral blood of all available members in this family was used for amplification of exon 1 of KRT9 by polymerase chain reaction. The mutation was detected by direct sequence analysis and identified by restriction endonuclease DdeI digestion. The finding of the same mutation in all available patients, together with the previous reports of the disease, strongly suggested that position 161 of the KRT9 gene also represents a mutation "hotspot" for EPPK. Our result is an important contribution to the investigation of the genotype/phenotype correlation and affords molecular genetic knowledge for future clinical diagnosis and gene therapy of EPPK.

[Biotransformation of dehydroepiandrosterone by hairy root cultures of Anisodus tanguticus].

AIM: To modify the structure of dehydroepiandrosterone (DHEA). METHODS: Using hairy root cultures of Anisodus tanguticus to perform biotransformation of DHEA, using chromatographic and spectral techniques to isolate and identify the products. RESULTS: (1) The MS medium without plant hormone was suitable for the growth of the hairy root. (2) DHEA was converted into five products: androst-4-ene-3, 17-dione (I); 6alpha-hydroxyandrost-4-ene-3, 17-dione (II); 6alpha, 17beta-dihydroxyandrost-4-ene-3-one (III); androst-4-ene-3, 6, 17-trione (IV) and 17beta-hydroxyandrost-4-ene-3-one (V). CONCLUSION: It is the first time to use hairy root cultures of Anisodus tanguticus for the biotransformation of DHEA and five DHEA-related compounds were obtained.