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Abstract: Development of fluorescent probes for Hg2+ has become a hot topic in modern chemical research due to its high toxicity. In this paper, we for the first time report the synthesis and application of a thioether spirocyclic rhodamine B derivative (TR) as an efficient fluorescent probe for Hg2+. TR was synthesized using a simple procedure under mild condition. By employing a thioether spirocycle instead of classic spirolactam as recognition unit, our proposed probe TR is acidity-insensitive, and exhibits a pH-independent and ultrasensitive response to Hg2+. The probe works well within a wide pH range from 3.5 to 11.5, and exhibits a 350-fold fluorescence enhancement upon 0.5equiv of Hg2+ triggered, with a detection limit of 2.5nM estimated for Hg2+. In virtue of the strong thiophilic characteristic of Hg2+, the response of the probe to Hg2+ is instantaneous and highly selective, which make it favorable for cellular Hg2+ imaging applications. It has been preliminarily used for highly sensitive monitoring of Hg2+ level in living cells with satisfying resolution, demonstrating its value of the practical applications in biological systems. [Copyright &y& Elsevier]

The ability to efficiently generate integration-free induced pluripotent stem cells (iPSCs) from the most readily available source—peripheral blood—has the potential to expedite the advances of iPSC-based therapies. We have successfully generated integration-free iPSCs from cord blood (CB) CD34+ cells with improved oriP/EBNA1-based episomal vectors (EV) using a strong spleen focus forming virus (SFFV) long terminal repeat (LTR) promoter. Here we show that Yamanaka factors (OCT4, SOX2, MYC, and KLF4)-expressing EV can also reprogram adult peripheral blood mononuclear cells (PBMNCs) into pluripotency, yet at a very low efficiency. We found that inclusion of BCL-XL increases the reprogramming efficiency by approximately 10-fold. Furthermore, culture of CD3−/CD19− cells or T/B cell-depleted MNCs for 4–6 days led to the generation of 20–30 iPSC colonies from 1 ml PB, an efficiency that is substantially higher than previously reported. PB iPSCs express pluripotency markers, form teratomas, and can be induced to differentiate in vitro into mesenchymal stem cells, cardiomyocytes, and hepatocytes. Used together, our optimized factor combination and reprogramming strategy lead to efficient generation of integration-free iPSCs from adult PB. This discovery has potential applications in iPSC banking, disease modeling and regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract: The double-strand DNA (dsDNA) can act as an efficient template for the formation of copper nanoparticles (Cu NPs) with high fluorescence, whereas the single-strand DNA (ssDNA) cannot support the formation of Cu NPs. This difference in fluorescent signal generation can be used for the detection of nuclease cleavage activity. Thus, a label-free strategy for sensitive detection of nuclease has been developed. The sensor contains a complete complementary dsDNA which acts as a template for the formation of Cu NPs and generation of fluorescence signal. The enzyme S1 nuclease was taken as the model analyte. Upon addition of S1 nuclease into the sensing system, the DNA was cleaved into fragments, preventing the formation of the Cu NPs and resulting in low fluorescence. In order to achieve the system''s best sensing performance, a series of experimental conditions were optimized. Under the optimized experimental conditions, the sensor exhibits excellent performance (e.g., a detection limit of 0.3UmL−1 with high selectivity). This possibly makes it an attractive platform for the detection of S1 nuclease and other biomolecules. [Copyright &y& Elsevier]

Abstract: This study sought to determine the cellular and molecular mechanisms of cyclooxygenase-2 (COX2) gene therapy to accelerate fracture repair in a mouse multiple tibial fractures model. The lenti-COX2 (or lenti-gfp control vector) was injected into fractures on day 1 post-fracture. At days 3–7, the COX2 treatment increased Sdf1-, Cxcr4-, Nes-, and Podxl-expressing mesenchymal stem cells (MSCs) within fracture calluses, suggesting an enhanced MSC recruitment or expansion. The COX2-treated mice formed smaller cartilaginous calluses that had less cartilage tissues than control mice. The expression of Sox9 mRNA was 7-fold less in COX2-treated than in control calluses at day 14, implying that COX2 reduces chondrocytic differentiation of MSCs. The therapy also enhanced angiogenesis as reflected by increased immunostaining of CD31, vWF, and α-SMA over controls in the cartilaginous callus at day 14–21. At which time, the COX2 gene therapy promoted bony remodeling of the cartilaginous callus to bridge the fracture gap that was accompanied by 2-fold increase in osteoclasts along the surface of the woven bone and an onset of osteogenesis. Blocking angiogenesis with daily injection of endostatin from day 4 to day 10 into fracture sites blocked the COX2-mediated reduction of callus size that was associated with an increase in hypertrophic chondrocytes and concomitant reduction in osteoclasts. In conclusion, COX2 accelerates fracture healing in part through three biological actions: 1) increased recruitment/expansion of MSCs; 2) decreased cartilaginous callus formation; and 3) increased angiogenesis-dependent cartilage remodeling. These effects were associated with an earlier onset of bony bridging of the fracture gap. [Copyright &y& Elsevier]

The effect of the cellular reprogramming process per se on mutation load remains unclear. To address this issue, we performed whole exome sequencing analysis of induced pluripotent stem cells (iPSCs) reprogrammed from human cord blood (CB) CD34+ cells. Cells from a single donor and improved lentiviral vectors for high-efficiency (2–14%) reprogramming were used to examine the effects of three different combinations of reprogramming factors: OCT4 and SOX2 (OS), OS and ZSCAN4 (OSZ), OS and MYC and KLF4 (OSMK). Five clones from each group were subject to whole exome sequencing analysis. We identified 14, 11, and 9 single nucleotide variations (SNVs), in exomes, including untranslated regions (UTR), in the five clones of OSMK, OS, and OSZ iPSC lines. Only 8, 7, and 4 of these, respectively, were protein-coding mutations. An average of 1.3 coding mutations per CB iPSC line is remarkably lower than previous studies using fibroblasts and low-efficiency reprogramming approaches. These data demonstrate that point nucleotide mutations during cord blood reprogramming are negligible and that the inclusion of genome stabilizers like ZSCAN4 during reprogramming may further decrease reprogramming-associated mutations. Our findings provide evidence that CB is a superior source of cells for iPSC banking. [ABSTRACT FROM AUTHOR]

Abstract: A new and facile strategy using double-stranded DNA-copper nanoparticles (dsDNA-Cu NPs) as fluorescence reporters for the highly sensitive and selective detection of l-histidine was demonstrated. In the dsDNA-Cu NPs-based sensing system, the fluorescence was quenched considerably upon the addition of l-histidine. Under the optimized experimental conditions, the probe exhibits excellent performance (e.g., a satisfactory detection limit of 5μM and high specificity). Our in situ method requires no covalent attachment of DNA to a fluorophore, which could significantly reduce the cost and simplify the procedure for l-histidine detection. Moreover, the proposed sensing system could be applicable for the detection of target biomolecule in complex biological samples. These striking properties make it an attractive platform for the direct detection of l-histidine. [Copyright &y& Elsevier]

Abstract: A aggregation-induced emission-based fluorescent probe 1 for Zn2+ was designed and simply synthesized by condensation of salicylaldehyde with aqueous hydrazine. The experimental conditions were first optimized. It was found that N, N-Dimethylformamide (DMF) was the best solvent for the Zn2+-triggered aggregation of compound 1 compared with other solvents. The emission intensity was gradually increased, accompanied by the simultaneous red shift of the maximum emission peak with increasing Zn2+ concentrations. A red shift about 45 nm was achieved when Zn2+ concentration is 100 μM. Compared with other Zn2+ fluorescent sensors based on aggregation-induced emission (AIE), compound 1 can detect a lower concentration of Zn2+ with a detection limit of 0.1 μM. Compound 1 also exhibited good selectivity toward Zn2+. The aggregation was verified by the dynamic light scattering (DLS) results, with a Zn2+ concentration-dependent size observed. It was also directly confirmed by TEM analyses. [Copyright &y& Elsevier]

Abstract: The effects of Nb on strain-induced precipitation and softening were quantified by means of the Gleeble-3500 thermo-mechanical simulator and inductively coupled plasma-atomic emission spectrometry (ICP-AES). The results show that Nb cannot completely dissolve during the reheating processes in the high Nb steels. The undissolved precipitates act as heterogenous nucleation sites for the precipitates induced by the strain, and prolong the strain-induced precipitation start time shown in the stress relaxation curves. The strain-induced precipitation start time is linearly related to the content of supersaturated Nb (the difference between dissolved Nb content after soaking and dissolved Nb content in equilibrium at corresponding deformation temperature). Increasing the content of supersaturated Nb can shift the nose of the precipitation C-curve to shorter time and higher temperatures. The effect of content of supersaturated Nb on precipitation increases along with the decrease of temperature. The softening ratio is linear with dissolved Nb content before the strain-induced precipitation and with precipitable Nb content after the strain-induced precipitation. The precipitates induced by strain have more strong retarding effect on the static recrystallization than the solid solution of Nb atoms. However, with the increase of the average precipitate radius, the retarding effect of precipitate rapidly decreases. [Copyright &y& Elsevier]

The reprogramming of cord blood (CB) cells into induced pluripotent stem cells (iPSCs) has potential applications in regenerative medicine by converting CB banks into iPSC banks for allogeneic cell replacement therapy. Therefore, further investigation into novel approaches for efficient reprogramming is necessary. Here, we show that the lentiviral expression of OCT4 together with SOX2 (OS) driven by a strong spleen focus-forming virus (SFFV) promoter in a single vector can convert 2% of CB CD34+ cells into iPSCs without additional reprogramming factors. Reprogramming efficiency was found to be critically dependent upon expression levels of OS. To generate transgene-free iPSCs, we developed an improved episomal vector with a woodchuck post-transcriptional regulatory element (Wpre) that increases transgene expression by 50%. With this vector, we successfully generated transgene-free iPSCs using OS alone. In conclusion, high-level expression of OS alone is sufficient for efficient reprogramming of CB CD34+ cells into iPSCs. This report is the first to describe the generation of transgene-free iPSCs with the use of OCT4 and SOX2 alone. These findings have important implications for the clinical applications of iPSCs. [ABSTRACT FROM AUTHOR]

Abstract: The hot deformation behaviors of six high-Nb steels were investigated by hot compression methods on a Gleeble-3500 thermo-mechanical simulator. The amount of Nb in solution and/or in precipitates of the specimens deformed at different conditions was determined by inductively coupled plasma–atomic emission spectrometry (ICP–AES). The effects of dissolved Nb and precipitates on hot deformation behavior were discussed. The results show that Nb cannot be completely dissolved in the high-Nb steels during the reheating process, and the undissolved precipitates do not influence the dynamic recrystallization due to their larger size. Moreover, the undissolved precipitates more effectively influence the peak stress instead of peak strain. Strain induced precipitation occurs during the hot deformation process. However, the precipitates cannot delay the dynamic recrystallization because of the longer induction period. The deformation activation energy presents a perfect linear correlation as a function of the amount of Nb in solutions, and each addition of Nb by 1wt% would lead to an increase of the deformation activation energy by 1599.9±137.7kJ/mol. [Copyright &y& Elsevier]

Abstract: A nonenzymatic electrochemical biosensor was developed for the detection of glucose based on an electrode modified with palladium nanoparticles (PdNPs)-functioned graphene (nafion–graphene). The palladium nanoparticle–graphene nanohybrids were synthesized using an in situ reduction process. Nafion–graphene was first assembled onto an electrode to chemically adsorb Pd2+. And Pd2+ was subsequently reduced by hydrazine hydrate to form PdNPs in situ. Such a PdNPs–graphene nanohybrids-based electrode shows a very high electrochemical activity for electrocatalytic oxidation of glucose in alkaline medium. The proposed biosensor can be applied to the quantification of glucose with a wide linear range covering from 10μM to 5mM (R =0.998) with a low detection limit of 1μM. The experiment results also showed that the sensor exhibits good reproducibility and long-term stability, as well as high selectivity with no interference from other potential competing species. [Copyright &y& Elsevier]

Abstract: Glycinyl fipronil, a new fipronil derivative with 5-amine acylated by glycine, was synthesized. The phloem mobility of the synthesized derivative was higher that of the parent compound in intact soybean seedling and its insecticidal activity against the 3rd instar larvae of Plutella xylostella was comparable with that of fipronil. [Copyright &y& Elsevier]

Abstract: Highly ordered Ni nanowire arrays (NiNWAs) were synthesized for the first time using a template-directed electropolymerization strategy with a nanopore polycarbonate (PC) membrane template, and their morphological characterization were examined by scanning electron microscopy (SEM) and transmission electron microscope (TEM). A NiNWAs based electrode shows very high electrochemical activity for electrocatalytic oxidation of glucose in alkaline medium, which has been utilized as the basis of the fabrication of a nonenzymatic biosensor for electrochemical detection of glucose. The biosensor can be applied to the quantification of glucose with a linear range covering from 5.0×10−7 to 7.0×10−3 M, a high sensitivity of 1043μAmM−1 cm−2, and a low detection limit of 1×10−7 M. The experiment results also showed that the sensor exhibits good reproducibility and long-term stability, as well as high selectivity with no interference from other oxidable species. [Copyright &y& Elsevier]

Abstract: In order to obtain a full-length expression plasmid for the p53 inhibitor protein, iASPP, fractional amplification was used to clone its full-length coding sequence (CDS) region. The amplified PCR product was then digested and inserted into the pMD19-T simple vector and subcloned into the pCDNA3.1(+) vector. A recombinant eukaryotic expression vector containing the complete CDS region of iASPP was successfully constructed. pcDNA3.1(+)/iASPP was able to express iASPP protein in an in vitro translation system and in cells. Its biological activity was verified using Western blotting, immunoprecipitation and cell apoptosis analysis. This successful preparation of a full-length iASPP expression plasmid lays the foundations for further studies on the function of iASPP. [Copyright &y& Elsevier]

The methylation status of the androgen receptor gene (AR) in leukemia cell lines was investigated. Results showed the presence of both methylated and unmethylated CpG islands of the AR promotor in leukemia cell lines. In the normal blood samples, only unmethylated bands were observed. In 15 bone marrow samples from patients with leukemia, 12 cases (80%) showed both methylated and unmethylated alleles and 3 cases (20%) showed only methylated alleles. To understand whether AR mRNA and protein expression are reduced by methylation, we treated leukemia cells with 5-Aza-Dc and detected the expression of mRNA and protein by RT-PCR and immunohistochemistry. The treatment of 5-Aza-Dc increased AR expression in all cell lines researched. This study indicates that reduced AR mRNA expression in leukemia cell lines was in part related to DNA methylation. The aberrant methylation of AR gene could be one molecular and genetic alteration in leukemia. [ABSTRACT FROM AUTHOR]

The CRISPR/Cas9 system has been used for genome editing of human and mouse cells. In this study, we established a protocol for gene knockout (KO) in mouse hematopoietic stem cells (HSCs). HSCs were highly purified from the bone marrow of tamoxifen-treated Cas9-EGFP/Cre-ER transgenic mice, maintained in serum-free polyvinyl alcohol culture with cytokines, lentivirally transduced with sgRNA-Crimson, and transplanted into lethally irradiated mice with competitor cells. Previous studies of Pax5 KO mice have shown B cell differentiation block. To verify our KO HSC strategy, we deleted Pax5 gene in 600 CD201+CD150+CD48−c-Kit+Sca-1+Lin− cells (HSC1 cells), highly enriched in myeloid-biased HSCs, and CD201+CD150−CD48− c-Kit+Sca-1+Lin− cells (HSC2 cells), highly enriched in lymphoid-biased HSCs. As predicted, both Pax5 KO HSC1 and HSC2 cells showed few B cells in the peripheral blood and the accumulation of pro-B cells in the bone marrow of recipient mice. Our data suggesetd that myeloid-biased and lymphoid-biased HSCs share a common B cell differentiation pathway. This population-specific KO strategy will find its applications for gene editing in a varity of somatic cells, particuarly rare stem and progenitor cells from different tissues. • Highly efficient CRISPR/Cas9 gene knockout in mouse hematopoietic stem cells. • EGFP expression indicated the induced Cas9 expression. • Crimson expression indicated successful lentiviral sgRNA transduction. • Pax5 knockout hematopoietic stem cells displayed expected phenotype. [ABSTRACT FROM AUTHOR]

Retroviral vector-mediated HSC gene therapy has been used to treat individuals with a number of life-threatening diseases. However, some patients with SCID-X1 developed retroviral vector-mediated leukemia after treatment. The selective growth advantage of gene-modified cells in patients with SCID-X1 suggests that the transgene may have played a role in leukemogenesis. Here we report that 2 of 2 dogs and 1 of 2 macaques developed myeloid leukemia approximately 2 years after being transplanted with cells that overexpressed homeobox B4 (HOXB4) and cells transduced with a control gammaretroviral vector that did not express HOXB4. The leukemic cells had dysregulated expression of oncogenes, a block in myeloid differentiation, and overexpression of HOXB4. HOXB4 knockdown restored differentiation in leukemic cells, suggesting involvement of HOXB4. In contrast, leukemia did not arise from the cells carrying the control gammaretroviral vector. In addition, leukemia did not arise in 5 animals with high-level marking and polyclonal long-term repopulation following transplantation with cells transduced with an identical gammaretrovirus vector backbone expressing methylguanine methyltransferase. These findings, combined with the absence of leukemia in many other large animals transplanted with cells transduced with gammaretroviral vectors expressing genes other than HOXB4, show that HOXB4 overexpression poses a significant risk of leukemogenesis. Our data thus suggest the continued need for caution in genetic manipulation of repopulating cells, particularly when the transgene might impart an intrinsic growth advantage. [ABSTRACT FROM AUTHOR]

Abstract: An electrochemical amplification immunoassay is reported using biocatalytic metal deposition coupled with anodic stripping voltammetric detection. In this method, the captured antibody was first immobilized onto a gold electrode via a self-assembled layer. After a sandwich immunoreaction, alkaline phosphatase-labeled antibody was bound to the gold electrode. The alkaline phosphatase on the electrode catalyzes the hydrolysis of ascorbic acid 2-phosphate to produce ascorbic acid. The latter, in turn, reduced silver ions on the electrode surface, leading to the deposition of silver onto the protein-modified electrode surface. The deposited metal was electrochemically stripped into solution and then measured by anodic stripping voltammmetry. Compared with the direct voltammetric detection of ascorbic acid, anodic stripping voltammetric detection of metal ions is more sensitive. For the amount of deposited silver relates to the amount of enzyme-generated ascorbic acid, which was controlled by the amount of enzyme bound on the electrode surface, the stripping current signal reflects the amount of target protein, achieving a linearly relationship in the range from 5 to 1000ngmL−1 in a logarithmic plot with a detection limit of 2.2ngmL−1. The utilization of the high biocatalytic activity of enzyme and the sensitive anodic stripping voltammetry to detect metal ions dramatically enhanced the sensitivity in immunoassay. [Copyright &y& Elsevier]

Abstract: A successively signal-amplified electrochemical immunoassay has been reported on the basis of the biocatalytic deposition of silver nanoparticles with their subsequent enlargement by nanoparticle-promoted catalytic precipitation of silver from the silver-enhancer solution. The immunoassay was carried out based on a heterogeneous sandwich procedure using polystyrene microwells to immobilize antibody. After all the processes comprising the formation of immunocomplex, biocatalytic deposition of silver nanoparticles and following silver enhancement were completed, the silver on polystyrene microwells was dissolved and quantified by anodic stripping voltammetry (ASV). The effect of relevant experimental conditions, including the concentration of ascorbic acid 2-phosphate (AA-p) substrate and Ag(I) ions, the biocatalytic deposition time, and of crucial importance, the silver enhancement time, were investigated and optimized. The anodic stripping peak current was proportional to the concentration of human IgG in a dynamic range of 0.1–10ngml−1 with a detection limit of 0.03ngml−1. Scanning electron microscope (SEM) was applied to characterize the silver nanoparticles before and after silver enhancement on the surface of polystyrene microplates. By coupling the highly catalytic effect of enzyme and nanoparticles to successively amplify the analytical signal, the sensitivity of immunoassay was enhanced so dramatically that this approach would be a promising strategy to achieve a lower detection limit for bioassays. [Copyright &y& Elsevier]

Abstract: A sensitive immunosensor using colloidal gold as electrochemical label is described. In this method, the capture protein was first immobilized on a carbon paste electrode surface through passive adsorption to bind quantitatively with corresponding antigen and colloidal gold labeled antibody to perform a sandwich assay. To detect the amount of the colloidal gold captured on the electrode surface, the colloid was first oxidized electrochemically to produce AuCl4 − ions which were adsorbed strongly on the electrode surface. Adsorptive voltammetry was then employed for the determination of the adsorbed AuCl4 − ions. A linear relationship between reduction wave peak current and the antigen concentration (human IgG) from 10 to 500ng/ml is obtained with a detection limit of 4.0ng/ml. [Copyright &y& Elsevier]

Abstract: By grafting with poly(amidoamine) (PAMAM) dendrimer, novel carbon nanotube (CNT) nano-composites have been successfully prepared. The novel functionalized matrix with plenty amino groups circumvents the troublesome solubility problem of CNTs in solvents, especially in water, greatly expanding the scope of the application of carbon nanotubes. The GO x and HRP immobilized CNT-PAMAM based on the functional CNTs was synthesized. The bi-enzymatic CNT-PAMAM nano-composites are highly dispersible in water and show very promising applications in the fabrication of mediator-free bi-enzymatic biosensors for sensitive detection of glucose. The cooperation of nano-composite between CNT and high dense GO x and HRP results in very high sensitivity to glucose with a current response of 2200nAmM−1 and fast response (∼1s). The modified electrode exhibits a wide linear response range for glucose from 4.0μM to 1.2mM (R =0.9971, N =15), with a detection limit of 2.5μM. The negative electrode potential of −0.34V is favorable for glucose detection in real samples without interference caused by other biomolecules. [Copyright &y& Elsevier]

Background: Weight gain and type 2 diabetes mellitus (DM) are often linked to antipsychotics treatment. The aim of the study is to investigate serum free fatty acids (FFA) levels in schizophrenic patients who received long-term antipsychotics treatment, and to explore the associations between serum FFA and fasting blood glucose, and insulin resistance. Methods: 308 inpatients with schizophrenia who met with the criteria of DSM-IV were recruited into this study, and were divided into four groups: control subjects, single obesity, impaired glucose tolerance (IGT) and type 2 DM according to different body mass index, fasting blood glucose level and 2-hour postprandial blood glucose. Serum FFA was measured with colorimetry. Serum insulin and leptin were measured with radioimmunoassay respectively. Results: There was a significant elevation in serum FFA levels in schizophrenic patients who received long-term antipsychotics treatment, especially in single obesity, IGT, and DM groups. The elevated serum FFA was remarkably positive correlated with fasting blood glucose and insulin resistance. Conclusions: The study suggested the elevated serum FFA in schizophrenic patients with long-term antipsychotics treatment affected the blood glucose metabolism, may have played an important role in insulin resistance and type 2 DM, and was also an important trait of metabolic syndromes. [Copyright &y& Elsevier]

Abstract: The p53 protein is one of the best-known tumour suppressors. Recently discovered ASPP1 and ASPP2 are specific activators of p53. To understand, if apoptosis-stimulating protein of p53 (ASPP) inactivation offers a selective advantage to tumors that have wild-type p53, we measured the mRNA expression of ASPP1 and ASPP2 in tumor cell lines retaining wide-type p53. In addition, the CpG island methylation status of ASPP1 gene and ASPP2 gene in the 5′-untranslated region was also investigated in order to understand the possible cause of abnormal expression of ASPP1 and ASPP2 in the tumor cell lines retaining wide-type p53. The data showed that mRNA expression of ASPP1 and ASPP2 is downregulated and CpG island tested is hypermethylated. These results indicated that ASPP CpG island aberrant methylation could be one molecular and genetic alteration in wild-type p53 tumours. [Copyright &y& Elsevier]

To explore if it is correlated in human tumor cells that the expression of LDH homologous gene and LDH isoenzymes, we used RT-PCR-SSCP technique to measure the relative expression of genes with homologous sequences. The combination of PCR using common primers designed in the highly conserved regions and single-strand conformation polymorphism analysis of the products is used for quantitative determination of the proportions of LDH-A mRNA in human cancer cell lines. The proportion is compared with that of the activities of isoenzymes. The results indicated that the enzyme activity of LDH-A was consistent with mRNA levels in the human tumor cell. The present procedure using a single pair of primers for two fragments can overcome disadvantages in quantitative analysis using multiplex PCR. Template concentrations and PCR cycles did not affect the proportions of LDH-A and LDH-B in the product. [Copyright &y& Elsevier]

We report the use of simple μ-oxo-bis[tetraphenylporphinatoiron(III)] ([TPPFeIII]2O) as a catalyst for the selective oxidation of cyclohexane into cyclohexanone and cylcohexanol with air. This is the first time that [TPPFeIII]2O has been used as a catalyst for the aerobic liquid phase oxidation of cyclohexane in absence of any cocatalyst or coreductants. The oxidation of cyclohexane catalyzed by a very small amount of [TPPFeIII]2O gave 90% selectivity to cyclohexanol and cyclohexanone at 12.55% yield and catalyst turnover numbers of 90,000 (based on the metal) under the conditions of 398 K and 0.6 MPa. We showed that the reaction yields and the turnover numbers of the catalyst changed with reaction temperature, pressure and the amount of catalyst. In contrast with the corresponding monoironporphyrin, chloro[tetraphenylporphinatoiron(III)] (TPPFeIIICl), the oxidation of cyclohexane catalyzed by (TPPFeIII)2O with air had higher yields and greater turnovers. [Copyright &y& Elsevier]

Primary cell culture in vitro suffers from cellular senescence. We hypothesized that expansion on decellularized extracellular matrix (dECM) deposited by simian virus 40 large T antigen (SV40LT) transduced autologous infrapatellar fat pad stem cells (IPFSCs) could rejuvenate high-passage IPFSCs in both proliferation and chondrogenic differentiation. In the study, we found that SV40LT transduced IPFSCs exhibited increased proliferation and adipogenic potential but decreased chondrogenic potential. Expansion on dECMs deposited by passage 5 IPFSCs yielded IPFSCs with dramatically increased proliferation and chondrogenic differentiation capacity; however, this enhanced capacity diminished if IPFSCs were grown on dECM deposited by passage 15 IPFSCs. Interestingly, expansion on dECM deposited by SV40LT transduced IPFSCs yielded IPFSCs with enhanced proliferation and chondrogenic capacity but decreased adipogenic potential, particularly for the dECM group derived from SV40LT transduced passage 15 cells. Our immunofluorescence staining and proteomics data identify matrix components such as basement membrane proteins as top candidates for matrix mediated IPFSC rejuvenation. Both cell proliferation and differentiation were endorsed by transcripts measured by RNASeq during the process. This study provides a promising model for in-depth investigation of the matrix protein influence on surrounding stem cell differentiation. [ABSTRACT FROM AUTHOR]

Here we report the peroxidase-like Au@Pt nanozyme as an integrated nanosensor for selective detection of silver ions (Ag+), where the nanozyme plays the roles as both the signal trigger and reporter simultaneously. This method relies on two critical chemical reactions, including (1) the unique inhibitory effect of Ag+ on the nanozyme triggered H 2 O 2 decomposition at weak acid environment and (2) H 2 O 2 induced Ag+ reduction onto the nanozyme surface at basic environment, leading to a blueshift in the localized surface plasmonic resonance wavelength (LSPR λ max) of the nanosensor. With this simple strategy, we demonstrated the sensitive and selective detection of Ag+ over a dynamic range from 0.5 to 1000 μM with a limit of detection (LOD) of 500 nM by UV–visible spectroscopy, which is below the permitted level of Ag+ in drinking water by U.S. Environmental Protection Agency (EPA). This method also exhibits satisfying recovery efficiency for Ag+ detection both in tap water and spring water from the Yuelu Mountain. With this satisfying sensing performance and excellent stability of nanoprobes, this strategy is promising for the detection of Ag+ in environment monitoring and food safety analysis. The peroxidase-like Au@Pt nanozyme was proposed as a novel integrated nanosensor for selective and sensitive detection of Ag+ by LSPR spectroscopy, which relies on the unique inhibitory effect of Ag+ on the nanozyme triggered H 2 O 2 decomposition at weak acid environment and residual H 2 O 2 induced Ag+ reduction onto the nanozyme surface at basic environment. Image 1 • The unique inhibitory effect of Ag+ on the Au@Pt nanozyme triggered H 2 O 2 decomposition was disclosed. • A new nanosensor was constructed with Au@Pt nanozyme which acts as the signal trigger and reporter. • Facile Ag+ sensing by LSPR spectroscopy with satisfying sensing performances was achieved. [ABSTRACT FROM AUTHOR]

Taking advantage of the super-quenching effect of the cationic perylene derivative on adjacent fluorophores, we for the first time reported a DNAzyme–perylene complex-based strategy for constructing fluorescence catalytic biosensors with improved sensitivity. [ABSTRACT FROM AUTHOR]

The use of a nanoscale DNA–Au dendrimer as a signal amplifier was proposed for the universal design of functional DNA-based ultra-sensitive SERS biosensors. This novel design combines the high specificity of functional DNA with the high sensitivity of surface-enhanced Raman scattering (SERS) spectroscopy, resulting in sensitivity superior to that of previously reported sensors. [ABSTRACT FROM AUTHOR]

• This R-CDs have deep tissue penetration ability, little damage to biological matrix. • They were successfully used to monitor the change of intracellular polarity. • They can discriminate polarity differences between normal and cancer cell lines. • This nanoprobe possesses dual mitochondria and lysosome targetability Intracellular polarity has a large impact on the activity of a series of biomolecules or maintain the function of particular domains. Therefore, monitoring the changing of intracellular polarity can great improve the understanding its functions in living cell level. Herein, by employing p-phenylenediamine as precursor, we prepared a red emissive carbon dots based nanoprobe for real-time sensing polarity in living cells. With the increasing of the polarity, a large red shift of fluorescence emission wavelength was obtained and the fluorescence intensity of red emissive carbon dots decreased about 11-fold when the solvent changed from 10 % to 99 % water. The red emissive carbon dots possess high quantum yield, high photo-stability, good biocompatibility as well as robust dual targetability for mitochondria and lysosome. Finally, the red emissive carbon dots were successfully used to discriminate polarity differences between normal and cancer cell lines. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS)‐based cancer therapy, such as photodynamic therapy (PDT), is subject to the hypoxia and overexpressed glutathione (GSH) found in the tumor microenvironment (TME). Herein, a novel strategy is reported to continuously and simultaneously regulate tumor hypoxia and reducibility in order to achieve the desired therapeutic effect. To accomplish this, a biocompatible nanoplatform (MnFe2O4@metal–organic framework (MOF)) is developed by integrating a coating of porphyrin‐based MOF as the photosensitizer and manganese ferrite nanoparticle (MnFe2O4) as the nanoenzyme. The synthetic MnFe2O4@MOF nanoplatform exhibits both catalase‐like and glutathione peroxidase‐like activities. Once internalized in the tumor, the nanoplatform can continuously catalyze H2O2 to produce O2 to overcome the tumor hypoxia by cyclic Fenton reaction. Meanwhile, combined with the Fenton reaction, MnFe2O4@MOF is able to persistently consume GSH in the presence of H2O2, which decreases the depletion of ROS upon laser irradiation during PDT and achieves better therapeutic efficacy in vitro and in vivo. Moreover, the nanoplatform integrates a treatment modality with magnetic resonance imaging, along with persistent regulation of TME, to promote more precise and effective treatment for future clinical application. [ABSTRACT FROM AUTHOR]

Background: Generation of induced pluripotent stem cells (iPSCs) from human peripheral blood provides a convenient and low-invasive way to obtain patient-specific iPSCs. The episomal vector is one of the best approaches for reprogramming somatic cells to pluripotent status because of its simplicity and affordability. However, the efficiency of episomal vector reprogramming of adult peripheral blood cells is relatively low compared with cord blood and bone marrow cells. Methods: In the present study, integration-free human iPSCs derived from peripheral blood were established via episomal technology. We optimized mononuclear cell isolation and cultivation, episomal vector promoters, and a combination of transcriptional factors to improve reprogramming efficiency. Results: Here, we improved the generation efficiency of integration-free iPSCs from human peripheral blood mononuclear cells by optimizing the method of isolating mononuclear cells from peripheral blood, by modifying the integration of culture medium, and by adjusting the duration of culture time and the combination of different episomal vectors. Conclusions: With this optimized protocol, a valuable asset for banking patient-specific iPSCs has been established. [ABSTRACT FROM AUTHOR]

Review: 150 refs. [ABSTRACT FROM AUTHOR]

Das Hexaazatrinaphthylen‐Radikalanion …… wurde als stabiles Kaliumsalz synthetisiert und in intakter Form an CoII koordiniert, wie R. A. Layfield et al. in der Zuschrift auf S. 5567 ff. beschreiben. Das Bild zeigt einen Kaliumkronenether als Fliegende Untertasse, die ein Elektron hinunter zum HAN‐Liganden in einem trimetallischen Cobalt(II)‐Komplex beamt. Die Reduktion des HAN‐Liganden verstärkt drastisch die Austauschkopplung innerhalb des radikalverbrückten molekularen Magneten. [ABSTRACT FROM AUTHOR]

Review: 132 refs. [ABSTRACT FROM AUTHOR]

Insertional mutagenesis resulting from the integration of retroviral vectors has led to the discovery of many oncogenes associated with leukemia. We investigated the role of HOXC6, identified by proximal provirus integration in a large animal hematopoietic stem cell gene therapy study, for a potential involvement in hematopoietic stem cell activity and hematopoietic cell fate decision. HOXC6 was overexpressed in the murine bone marrow transplantation model and tested in a competitive repopulation assay in comparison to the known hematopoietic stem cell expansion factor, HOXB4. We have identified HOXC6 as a factor that enhances competitive repopulation capacity in vivo and colony formation in vitro. Ectopic HOXC6 expression also induced strong myeloid differentiation and expansion of granulocyte-macrophage progenitors/common myeloid progenitors (GMPs/CMPs) in vivo, resulting in myeloid malignancies with low penetrance (3 of 17 mice), likely in collaboration with Meis1 because of a provirus integration mapped to the 3' region in the malignant clone. We characterized the molecular basis of HOXC6-induced myeloid differentiation and malignant cell transformation with complementary DNA microarray analysis. Overexpression of HOXC6 induced a gene expression signature similar to several acute myeloid leukemia subtypes when compared with normal GMPs/CMPs. These results demonstrate that HOXC6 acts as a regulator in hematopoiesis and is involved in malignant transformation. [ABSTRACT FROM AUTHOR]

We have recently reported that a group of human adenoviruses (HAdVs) uses desmoglein 2 (DSG2) as a receptor for infection. Among these are the widely distributed serotypes HAdV-B3 and HAdV-B7, as well as a newly emerged strain derived from HAdV-B14. These serotypes do not infect rodent cells and could not up until now be studied in small-animal models. We therefore generated transgenic mice containing the human DSG2 locus. These mice expressed human DSG2 (hDSG2) at a level and in a pattern similar to those found for humans and nonhuman primates. As an initial application of hDSG2-transgenic mice, we used a green fluorescent protein (GFP)-expressing HAdV-B3 vector (Ad3-GFP) and studied GFP transgene expression by quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry subsequent to intranasal and intravenous virus application. After intranasal application, we found efficient transduction of bronchial and alveolar epithelial cells in hDSG2-transgenic mice. Intravenous Ad3-GFP injection into hDSG2-transgenic mice resulted in hDSG2-dependent transduction of epithelial cells in the intestinal and colon mucosa. Our findings give an explanation for clinical symptoms associated with infection by DSG2-interacting HAdVs and provide a rationale for using Ad3-derived vectors in gene therapy [ABSTRACT FROM AUTHOR]