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Acetylcholinesterase (AChE) is a key enzyme used to detect organophosphorus pesticide residues by the enzyme inhibition method. An accidental discovery of a mutant strain with AChE activity was made in our laboratory during the process of AChE expression by Pichia pastoris. The pPIC9K-Drosophila melanogaster acetylcholinesterase (DmAChE)-like expression vector was constructed by codon optimization of this mutant strain, which was transformed into P. pastoris GS115, and positive clones were selected on yeast peptone dextrose (YPD) plate with G418 at 4.0 mg/mL. The GS115-pPIC9K-DmAChE-like strain was subjected to 0.5% methanol induction expression for 120 h, with a protein band at 4.3 kDa found by the tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) pattern of the fermentation supernatant. After preliminary purification by ammonium sulfate precipitation, the enzyme activity was detected to be 76.9 U/(mL⋅min). In addition, the pesticide sensitivity test proved that DmAChE-like is selective and sensitive to organophosphorus pesticides.

The molecular mechanisms underlying the development of osteosarcoma (OS) are not fully understood. In this study, we investigated for the first time the clinical significance and biological activity of centrosomal protein 55 (CEP55) in OS. We found that CEP55 was overexpressed in OS, and the CEP55 expression level in OS was correlated with metastasis and poor prognosis. Through in vitro experiments, we confirmed that CEP55 knockdown significantly induced cell cycle arrest at G1 phase and suppressed OS cell proliferation, migration and invasion. In addition, CEP55 knockdown suppressed OS tumour growth in nude mice. Global gene expression profiling of CEP55-silenced MNNG/HOS cells showed that the AKT pathway might be involved in the regulation of OS cell activity. Two downstream factors of AKT signalling, CCND1 and FN1, were found to have significantly higher expression in tumour tissues, and their mRNA expression levels were strongly correlated with CEP55 expression. To conclude, our data suggest that CEP55 can be used as a prognostic marker for OS, highlighting the significance of CEP55 signalling as a putative therapeutic target.

Background The Musculoskeletal Tumor Society (MSTS) scoring system is a disease-specific instrument to determine the physical and mental health for patients with extremity sarcoma. This study aims to investigate the reliability and validity of the Chinese version of the MSTS, and to evaluate functional outcomes of the surgical treatment of lower extremity sarcoma using the Chinese MSTS. Methods A cohort of 98 patients who had undergone surgery for lower extremity sarcoma were included. All the patients completed the clinical assessment with the Chinese MSTS and the Chinese Toronto Extremity Salvage Score (TESS). Assessment of psychometric properties was carried out through reliability and validity test. The reliability of Chinese MSTS was evaluated through test-retest analysis, inter-observer analysis and internal consistency. The inter-observer and test-retest reliability was analyzed with intra-class correlation coefficient (ICC). The internal consistency was evaluated by Cronbach’s α, with a value >0.70 considered acceptable. The discriminant validity was evaluated through comparison of the MSTS score between patients undergoing amputation surgeries and those undergoing limb-salvage surgeries. The construct validity was evaluated with the factor analysis. Results The mean MSTS score was 21.5 ± 7.1. The ICC was 0.91 (95% confidence interval (CI) = 0.85–0.96) for the test-retest reliability and 0.90 (95% CI = 0.86–0.93) for the inter-observer analysis. The test for internal consistency showed a Cronbach’s α of 0.86 for the MSTS. Patients undergoing amputation surgery had remarkably lower MSTS score than patients undergoing limb-salvage surgeries (18.8 ± 5.4 vs. 23.5 ± 6.3, p = 0.005), which indicated a good discrinimant validity of the Chinese MSTS. The factor analysis indicated a 1-factor model with acceptable goodness of fit. Conclusions The Chinese MSTS scoring system is a reliable and valid instrument with well-accepted psychometric properties. Through application of the Chinese MSTS, we demonstrated that patients receiving limb-salvage surgeries may have better functional outcome and QoL than those undergoing amputation surgeries. Electronic supplementary material The online version of this article (doi:10.1186/s12955-017-0685-x) contains supplementary material, which is available to authorized users.

OBJECTIVE To compare the clinical effects of modified uvulopalatopharyngoplasty (UPPP) with low-temperature plasma with selective nasal cavity vasodilatation with tongue volume reduction for obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS A retrospective analysis based on 156 patients with serious OSAHS was used for the evaluation. These patients were divided into 2 groups according to surgery methods according to 1:1.s. The patients in observation group accepted modified UPPP with low-temperature plasma and selective nasal cavity vasodilatation with tongue root volume reduction on the basis of fully preparation for surgery, while the patients in the control group accepted normal treatment. The clinic effects, operative complications, postoperative relapse, and other indexes were compared. RESULT After 6 months of follow-up visit, the general effective rates of the observation group and control groups were 80.77% and 61.54%, the difference was statistically significant (P

Serum Epstein-Barr virus DNA has been approved for diagnosing nasopharyngeal carcinoma (NPC). The goal of this meta-analysis was to evaluate the clinical value of the serum Epstein-Barr virus DNA in the diagnosis of NPC. The PubMed, Embase, Web of Knowledge, Chinese Wanfang Med Online, and National Knowledge Infrastructure (CNKI) databases were searched to identify suitable studies. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) of the serum Epstein-Barr virus DNA for the diagnosis of NPC were calculated. Summary receiver operating characteristic curves were used to summarize overall test performances. Meta-Disc 1.4 and Stata 12.0 softwares were used to analyze the data. A total of 2,520 patients from ten trials were subjected to meta-analysis. The summary estimates of the serum Epstein-Barr virus DNA for NPC diagnosis were as follows: sensitivity 0.69 (95 % confidence interval (CI) 0.65-0.72), specificity 0.84 (95 % CI = 0.82-0.86), LR + 4.81 (95 % CI = 2.94-7.88), LR - 0.25 (95 % CI = 0.13-0.48), DOR 24.65 (95 % CI = 12.64-48.07), and area under the summary receiver operator characteristic (SROC) curve (AUC) was 0.8979. Our study demonstrates that the serum Epstein-Barr virus DNA could be a useful tumor marker for NPC diagnosis.

BACKGROUND The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To clarify the precise effects of MTHFR polymorphisms on the risk of breast cancer, a systemic review and most comprehensive meta-analysis of all available studies relating MTHFR rs1801133 gene polymorphism to the risk of breast cancer was conducted. METHODS Eligible articles were identified by search of databases including Medline (Mainly PubMed), Embase, Web of Science, Chinese Biomedical Literature database (CBM), CNKI and Wanfang Medical databases. Crude ORs with 95% CIs were used to assess the strength of association. RESULTS Finally, a total of 83 studies with 35,029 cases and 38,990 controls were included. Overall, MTHFR rs1801133 gene polymorphism was proved to contribute to the risk of breast cancer under all genetic models (TT vs. CC: Pheterogeneity

Side-ring-modified thiostrepton (TSR) derivatives that vary in their quinaldic acid (QA) substitution possess more potent biological activities and better pharmaceutical properties than the parent compound. In this work, we sought to introduce fluorine onto C-7′ or C-8′ of the TSR QA moiety via precursor-directed mutational biosynthesis to obtain new TSR variants. Unexpectedly, instead of the target product, the exogenous chemical feeding of 7-F-QA into the ΔtsrT mutant strain resulted in a unique TSR analog with an incomplete side-ring structure and an unoxidized QA moiety (1). Accordingly, two cytochrome P450 genes, tsrP and tsrR, were in-frame deleted to elucidate the candidate responsible for the monooxidation of the QA moiety in TSR. The unfluorinated analog of compound 1 that was thus isolated from ΔtsrP (2) and the abolishment of TSR production in ΔtsrR revealed not only the biosynthetic logic of the TSR side-ring but also the essential checkpoint in TSR maturation before macro-ring closure.

SummaryThiostrepton (TSR), often referred as to a parent compound in the thiopeptide family, is a bimacrocyclic member that features a quinaldic acid (QA) moiety-containing side ring appended to the characteristic core system. QA biosynthesis requires an unusual ring-expanding conversion, showing a methyl transfer onto and a rearrangement of the indole part of L-tryptophan to give a quinoline ketone. Herein, we report that the process involves the activities of the radical methyltransferase TsrT, aminotransferase TsrA, dehydrogenase TsrE, and cyclase TsrD. TsrU, a stereospecific oxidoreductase, catalyzes the further conversion of the ketone into an enantiomerically pure S-alcohol. Elucidation of this chemistry, which is common in the biosynthesis of a number of thiopeptides sharing a QA side ring system, facilitates analog generation, as shown by the achievement of region-specific fluorination of thiostrepton with the improved antibacterial activity.

Background The aim of this study was to investigate the association of insulin-like growth factor-1 receptor (IGF-1R) with metastasis and prognosis of osteosarcoma patients. Methods RT-PCR and Western blot assays were performed to detect IGF-1R mRNA and protein expression in 26 osteosarcoma and noncancerous bone tissues. Immunohistochemistry was performed to analyze the correlation of IGF-1R expression in 84 osteosarcoma tissues with clinicopathological factors or survival of patients. Lentivirus-mediated RNA interference system was employed to downregulate IGF-1R expression and analyze the effects of IGF-1R downregulation on invasion and metastasis of osteosarcoma cells. Results The relative levels of IGF-1R mRNA and protein expression were significantly higher in osteosarcoma tissues than in corresponding noncancerous bone tissues. The expression of IGF-1R protein was closely associated with surgical stage and distant metastasis of osteosarcoma patients. Osteosarcoma patients with high IGF-1R expression had poorer survival, and multivariate Cox analyses showed that high IGF-1R expression was an independent prognostic maker. Lentivirus-mediated targeting IGF-1R could significantly inhibit adhesion, migration, invasion, and metastasis of osteosarcoma cells, which might be correlated with of inactivation of Akt signaling pathway. Conclusions IGF-1R is an independent prognostic marker for osteosarcoma patients and increased expression of this molecular is correlated with metastasis of osteosarcoma. J. Surg. Oncol. 2012; 105:235–243. © 2011 Wiley Periodicals, Inc.

To evaluate the clinical efficacy of uni- and polyaxial locking osteosynthesis systems in the management of proximal humeral fractures in elderly patients, totally 76 cases were reviewed including 18 cases of two-part (Neer classification), 36 cases of three-part, and 22 cases of four-part fractures. All the patients received open reduction and internal fixation with proximal humerus internal locking osteosynthesis system (PHILOS) or Numelock systems designed for proximal humerus. Results showed no significant difference between groups considering the Constant–Murley scores assessed at 6 and 12 months, postoperatively. Satisfactory outcomes were achieved in 73.7 and 75.0% of the patients from the PHILOS and Numelock groups, respectively. Complications included four cases of varus malunion, one case of screw cut-out, and another case of avascular necrosis. Both of the PHILOS and Numelock systems showed equally good results considering fixation stability and functional outcomes of proximal humeral fractures in elderly patients.

The overexpression of the type 1 insulin-like growth factor receptor (IGF-1R) has been reported to be associated with malignant transformation, tumor development and chemo- or radioresistance of tumor cells. Previously, we have reported that inhibition of IGF-1R could reverse the radioresistance of human osteosarcoma cells. However, whether inhibition of IGF-1R could enhance chemosensitivity of ostesosarcoma cells is unclear. In this study, lentivirus-mediated shRNA was employed to downregulate endogenous IGF-1R expression to study the function of IGF-1R in chemoresistance of osteosarcoma cells. Results showed that lentivirus-mediated shRNA targeting IGF-1R combined with chemotherapy (CDDP or DTX) could lead to growth suppression of osteosarcoma cells not only in vitro but also in vivo. Moreover, inhibition of IGF-1R gene combined with chemotherapy also synergistically enhanced Caspase-3-mediated apoptosis of osteosarcoma cells. The synergistical enhancement of apoptosis might be associated with downregulation of Bcl-2 and upregulation of Bax in osteosarcoma cells induced by IGF-1R inhibition. Therefore, the overexpression of IGF-1R gene might play important roles in chemoresistance of osteosarcoma cells, and lentivirus-mediated RNAi targeting IGF-1R would be an attractive anti-cancer strategy to chemosensitization of osteosarcoma cell.

The cobalt–salen complex (C1:[(salen)Co3+(OAc)]; salen= N,N′-bis(salicylidene)ethylenediamine, OAc=acetate) was found to efficiently promote the hydration of terminal alkynes to give methyl ketones in the presence of the H2SO4 cocatalyst. In addition, the one-pot transformation of alkynes into chiral alcohols through tandem catalysis by catalyst C1 coupled with a ruthenium–TsDPEN complex (C3: [(R,R-TsDPEN)Ru2+(cymene)]; TsDPEN=(1R,2R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine, cymene=1-methyl-4-(1-methylethyl)benzene) catalyst was realized with excellent yields and enantioselectivities.

A benzimidazole-based nonheme manganese complex efficiently catalyzes benzylic, aliphatic C–H as well as tertiary C–H oxidation with hydrogen peroxide as the oxidant in the presence of acetic acid as additive. 18O labeling experiments suggest the reaction may proceed via a high-valent manganese-oxo intermediate.

The 5-endo chlorocycloetherification proceeds rapidly under catalyst-free-conditions to give β-chlorotetrahydrofurans in high yields.

The relationship of bladder cancer with the presence of X-ray cross-complementing group 3(XRCC3) genetic polymorphism Thr241Met has been reported with inconsistent results. The objective of this study was to quantitatively evaluate the association between this polymorphism and bladder cancer susceptibility. A comprehensive research was conducted through PubMed, Medline, Embase, and Web of Science databases up to Aug. 20, 2013. Pooled odds ratio and 95 % confidence interval were calculated using a fixed or random effects model. Statistical analysis was performed with Stata 12.0 software. Of the 18 case-control studies selected for this meta-analysis, a total of 5,667 bladder cancer cases and 7,609 controls were included. The combined results based on all studies suggested that XRCC3 Thr241Met was associated with bladder cancer risk under homozygote and recessive models. When stratifying for ethnicity, significant association was found in Caucasians under homozygote and recessive models. This meta-analysis suggests that XRCC3 Thr241Met polymorphism is a risk factor for bladder cancer risk. However, further well-designed studies are required to confirm our findings.

using an easily available quaternary ammonium salt derived from cinchonine as organocatalyst

A novel series of tetradentate N4 ligands is prepared and successfully applied in the Fe-catalyzed asymmetric epoxidation of a diversity of di- and trisubstituted enones.

A variety of magnetic nanoparticles of ferrite complex oxides is prepared and tested in the N-arylation of imidazole.

the “Hundred Talents Program” of the Chinese Academy of Sciences and the National Natural Science Foundation of China (20873166;21073210;21133011)

The methodology works efficiently for numerous secondary alcohols including benzylic alcohols with ortho substituted aromatic rings.

A series of biaryl-bridged salalen ligands together with their titanium complexes have been designed and synthesized. The Ti complexes could serve as highly efficient catalysts for the asymmetric epoxidation of a wide range of olefins, giving the corresponding epoxides with high ee values.

Both enantiomers of nitriles (III) can be prepared by modifying the salen-titanium catalyst.

The catalyst can be conveniently recovered by an external magnet and reused several times without loss of its catalytic activity.

Best results are achieved with iodides whereby, substrates with electron-withdrawing groups like the nitro derivative (Ib) give the desired products even in the absence of the catalyst system.

Two new tetradentate ligands derived from salen have been prepared and their titanium complexes are used as chiral catalysts in the enantioselective silylcyanation of aldehydes, which give the silyl ethers of cyanohydrins in moderate to good enantiomeric excesses.

A new type of chiral tridentate ligands were prepared and their Zn complexes were examined for the asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes, which gave rise to good yields and moderate enantioselectivities.

A variety of olefins is efficiently transformed to the corresponding epoxides by Ti-catalyzed asymmetric reaction using novel salan/salalen ligands, e.g. (I) or (II).

A novel series of chiral tetradentate N4 ligands together with their manganese complexes have been designed and synthesized. With 1 mol % manganese catalyst loading, the enantioselective epoxidation of olefins proceeds with nearly full conversion and enantiomeric excess values of up to 89 % for the first time.

The use of (NHC)CuI complex in combination with a N-heterocyclic carbene precursor as catalyst for the double carbonylation of aryl Iodides and secondary amines solves the problem of using the precious metal Pd and phosphine ligands. The new protocol requires a nonprecious metal catalyst and has greater generality than those previously reported.

SummaryThiostrepton (TSR) is an archetypal thiopeptide antibiotic possessing a quinaldic acid (QA) moiety in the side ring system. According to the mechanism of TSR previously known to target bacterial ribosome, we recently designed and biosynthesized several TSR derivatives that varied in QA substitution. Utilizing these thiopeptide antibiotics to treat the intracellular pathogen Mycobacterium marinum, we herein report a novel mode of action of TSRs, which induce ER stress-mediated autophagy to enhance host cell defense. This intracellular response, which is sensitive to the modification of the QA group, serves as an indirect but unignorable mechanism for eliminating intracellular pathogens. TSRs are thus the only type of antibiotics, to our knowledge, with the dual action on both the parasitic bacteria and the infected host cells. The newly observed mechanism of TSRs may inspire the future change in the treatment of intracellular pathogens, by taking host response into account.