Search

The decline of cell function caused by ageing directly impacts the therapeutic effects of autologous stem cell transplantation for heart repair. The aim of this study was to investigate whether overexpression of neuron‐derived neurotrophic factor (NDNF) can rejuvenate the adipose‐derived stem cells in the elderly and such rejuvenated stem cells can be used for cardiac repair. Human adipose‐derived stem cells (hADSCs) were obtained from donors age ranged from 17 to 92 years old. The effects of age on the biological characteristics of hADSCs and the expression of ageing‐related genes were investigated. The effects of transplantation of NDNF over‐expression stem cells on heart repair after myocardial infarction (MI) in adult mice were investigated. The proliferation, migration, adipogenic and osteogenic differentiation of hADSCs inversely correlated with age. The mRNA and protein levels of NDNF were significantly decreased in old (>60 years old) compared to young hADSCs (

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.

e16256 Background: Although pyroptosis is critical for macrophages against pathogen infection, its role in cancer cells remains elusive. GSDMC is a pyroptosis executioner newly identified in cancer cells and have been shown to facilitate inflammatory tumor death. However, the expression of GSDMC in Pancreatic Ductal Adenocarcinoma (PDAC), its prognostic significance and possible impact on reshaping tumor immune microenviroment in PDAC is still unknown. Methods: We investigated the expression level of GSDMC using TNM plotter with TCGA and GTEx databases, the prognostic value of GSDMC in PDAC using Kaplan-Meier plotter with TCGA, GTEx and TCGA databases. The correlations between GSDMC and immune infiltration in PDAC were calculated using TIMER2.0 and TIDE with TCGA database. We further validated the prognostic value of GSDMC with immunohistochemistry(IHC) staining on a tissue microarray of 172 cases of PDAC patients receiving treatment in our institution. Correlations between expression of GSDMC and tumor infiltration lymphacytes(TILs) cells were also analyzed on tissue samples of those 172 PDAC patients. Results: TNM plotter analysis shows that the expression of GSDMC in PDAC tumor tissue is 10.49 folds higher than it is in pancreatic normal tissues (p = 8.86*e-56). Results from Kaplan-Meier plotter analysis shows high expression of GSDMC is significantly correlated with poorer overall survival(OS), HR = 1.8(1.19−2.71) logrank P = 0.004 and shorter relapse free survival (RFS), HR = 4.6(1.94−10.88), Logrank P = 0.00014 in PDAC. Analysis with TIMER2.0 and TIDE platform shows that expression of GSDMC is positively correlated with immunosuppressive cells, Cancer Associated Fiberblast (CAF) and Meyloid Derived Tumor Suprresso Cells(MDTSC). IHC staining analysis results is also consistent with aformentioned bioinformatic analysis, showing that high GSDMC expression correlated with shorter OS and reduced Tils infiltration. Conclusions: Our findings suggest that high expression of GSDMC is related to poor prognosis and compromised immune cell infiltration in PDAC. GSDMC holds promise for serving as a valuable prognostic marker and therapeutic target in PDAC.

The presence of high level of antibiotics in the antibiotic fermentation residue is one of the main reasons that prevent their direct disposal or further use as a resource. In this study, the feasibility of using the hydrothermal pretreatment for removing oxytetracycline (OTC) from its fermentation residue and enhancing anaerobic digestion was evaluated under different temperatures i.e. 110, 130, 150 and 170°C. The results showed that the removal rate of OTC increased as a function of temperature, and hydrothermal treatment at 130°C for 5 min was found sufficient to reduce the concentration of OTC from 3.9 mg/g to less than the detection limit (i.e., 0.25 ng/g). Biochemical methane potential tests showed that the cumulative methane production over 23 d was 73.7, 215.9, 656.8, and 439.0NmL CH4/gVS for the raw residue and the residue treated at 130, 150, and 170°C for 5 min, respectively. At the same time, the abundances of tetracycline resistance genes were reduced by hydrothermal treatments followed by anaerobic digestion. Conclusively, it is suggested that hydrothermal treatment at 150°C for 5 min was found beneficial for OTC fermentation residues ensuring the removal of OTC and further use of the residue for anaerobic digestion.

In order to further improve the accuracy of propellant gauging during the geosynchronous satellite transfer orbit, combined with the existing propellant gauging method, a time series analysis method for satellite propellant consumption fusion algorithm is proposed. The error characteristics of the prediction data are analyzed according to the principle of different gauging methods. On the basis of this, the variance of each gauging method is estimated by time series analysis and the optimal weighted fusion estimation based on least squares method is given. The practical application shows that the fusion algorithm can make full use of the advantages of different gauging methods and provide a more reasonable estimation of the real-time propellant consumption.

We determined the effects of the

The rapid increase in carbapenem resistance among gram-negative bacteria has renewed focus on the importance of polymyxin antibiotics (colistin or polymyxin E). However, the recent emergence of plasmid-mediated colistin resistance determinants (mcr-1, -2, -3, -4, -5, -6, and -7), especially mcr-1, in carbapenem-resistant Enterobacteriaceae is a serious threat to global health. Here, we characterized a novel mobile colistin resistance gene, mcr-8, located on a transferrable 95,983-bp IncFII-type plasmid in Klebsiella pneumoniae. The deduced amino-acid sequence of MCR-8 showed 31.08%, 30.26%, 39.96%, 37.85%, 33.51%, 30.43%, and 37.46% identity to MCR-1, MCR-2, MCR-3, MCR-4, MCR-5, MCR-6, and MCR-7, respectively. Functional cloning indicated that the acquisition of the single mcr-8 gene significantly increased resistance to colistin in both Escherichia coli and K. pneumoniae. Notably, the coexistence of mcr-8 and the carbapenemase-encoding gene blaNDM was confirmed in K. pneumoniae isolates of livestock origin. Moreover, BLASTn analysis of mcr-8 revealed that this gene was present in a colistin- and carbapenem-resistant K. pneumoniae strain isolated from the sputum of a patient with pneumonia syndrome in the respiratory intensive care unit of a Chinese hospital in 2016. These findings indicated that mcr-8 has existed for some time and has disseminated among K. pneumoniae of both animal and human origin, further increasing the public health burden of antimicrobial resistance.

The aim of this study was to assess the presence of mobile colistin resistance in bacteria isolated from the swine production environment and to analyze the genomic environment of the new colistin resistance gene mcr-3. Anal swabs and environmental samples were collected from a commercial pig farm. Direct sample testing (DST) for mcr genes and isolation of colistin-resistant isolates was performed. The mcr-3-positive isolates were subjected to whole genome sequencing (WGS). Transferability and genomic location analyses of mcr-3 gene were performed using conjugation and S1 nuclease-PFGE with Southern blotting assays, respectively. The antimicrobial susceptibility profiles of the mcr-carrying isolates were determined using the agar dilution method. A total of 65 samples were collected. The DST rates of mcr-1 (64.6%, 42/65) and mcr-3 (40.0%, 26/65) were considerably higher than the rates of mcr-1-positive E. coli (49.2%, 32/65) and mcr-3-positive E. coli (7.7%, 5/65) isolated from these samples, respectively. The five mcr-3-positive isolates were derived from different sources (pig, fly and soil) and four of the five isolates were also positive for mcr-1. The mcr-3 genes were located on IncP-1 plasmids in three isolates or IncHI2 plasmids in two isolates. Several mobile elements, including IS4321, ΔTnAs2 or ISKpn40, were identified in the flanking regions of mcr-3 in the E. coli isolates. In conclusion, the mobile colistin resistance genes mcr-1 and mcr-3 are prevalent in the monitored pig farm and its surrounding environment. Due to their location on broad-host range IncP-1 plasmids and their proximity to different IS sequences, mcr-3 gene might have excellent opportunities for transmission.

Reduced quantity and quality of stem cells in aged individuals hinders cardiac repair and regeneration after injury. We used young bone marrow (BM) stem cell antigen 1 (Sca-1) cells to reconstitute aged BM and rejuvenate the aged heart, and examined the underlying molecular mechanisms. BM Sca-1+ or Sca-1- cells from young (2-3 months) or aged (18-19 months) GFP transgenic mice were transplanted into lethally irradiated aged mice to generate 4 groups of chimeras: young Sca-1+ , young Sca-1- , old Sca-1+ , and old Sca-1- . Four months later, expression of rejuvenation-related genes (Bmi1, Cbx8, PNUTS, Sirt1, Sirt2, Sirt6) and proteins (CDK2, CDK4) was increased along with telomerase activity and telomerase-related protein (DNA-PKcs, TRF-2) expression, whereas expression of senescence-related genes (p16INK4a , P19ARF , p27Kip1 ) and proteins (p16INK4a , p27Kip1 ) was decreased in Sca-1+ chimeric hearts, especially in the young group. Host cardiac endothelial cells (GFP- CD31+ ) but not cardiomyocytes were the primary cell type rejuvenated by young Sca-1+ cells as shown by improved proliferation, migration, and tubular formation abilities. C-X-C chemokine CXCL12 was the factor most highly expressed in homed donor BM (GFP+ ) cells isolated from young Sca-1+ chimeric hearts. Protein expression of Cxcr4, phospho-Akt, and phospho-FoxO3a in endothelial cells derived from the aged chimeric heart was increased, especially in the young Sca-1+ group. Reconstitution of aged BM with young Sca-1+ cells resulted in effective homing of functional stem cells in the aged heart. These young, regenerative stem cells promoted aged heart rejuvenation through activation of the Cxcl12/Cxcr4 pathway of cardiac endothelial cells.

Cardiac repair depends on angiogenesis and cell proliferation. Previously we identified Canopy 2 (CNPY2) as a secreted angiogenic growth factor which promotes neovascularization. We investigated the role of CNPY2 in cardiac repair following myocardial infarction (MI) and the possible mediators involved using Cnpy2 knockout (KO) mice and human cardiac tissue.Cardiac tissue from patients with end-stage heart failure had significantly lower endogenous CNPY2 expression compared to samples from control patients. CNPY2 expression in mouse hearts significantly decreased following MI. Significantly less leukocyte and endothelial cell proliferation was found in Cnpy2 KO than wild-type (WT) mice post MI which contributed to impaired angiogenesis, tissue repair, and decreased cardiac function (fractional shortening: WT: 21.1 ± 2.1% vs. KO: 16.4 ± 1.6%, p .01 at day 28 post MI). RT-qPCR revealed significantly increased p16Cardiac injury and progressive heart failure were associated with decreased CNPY2 levels in both humans and mice. Knockout of Cnpy2 resulted in up-regulation of p16

The global emergence of plasmid-mediated colistin resistance genes mcr-1 and mcr-3 has threatened the role of the “last resort” drug colistin in the defense against infections caused by multidrug-resistant Gram-negative bacteria. However, functional differences between these two genes in mediating colistin resistance remains poorly understood. Protein sequence alignment of MCR-3 and MCR-1 was therefore conducted in Clustal Omega to identify sequence divergence. The molecular recognition of lipid A head group phosphatidylethanolamine and MCR-3 enzyme was studied by homology modeling and molecular docking, with the catalytic mechanism of MCR-3 also being explored. Thr277 in MCR-3 was validated as the key amino acid residue responsible for the catalytic reaction using site-directed mutagenesis and was shown to act as a nucleophile. Lipid A modification induced by the MCR-3 and MCR-1 enzymes was confirmed by electrospray ionization time-of-flight mass spectrometry. Far-UV circular dichroism spectra of the MCR-3 and MCR-1 enzymes suggested that MCR-3 was more thermostable than MCR-1, with a melting temperature of 66.19°C compared with 61.14°C for MCR-1. These data provided molecular insight into the functional differences between mcr-3 and mcr-1 in conferring colistin resistance.

The aim of this study was to determine the clinicopathological features, surgical management, and prognosis of solid pseudopapillary neoplasms (SPNs) of the pancreas.This study conducted a retrospective analysis of 97 patients who underwent surgery for a pathologically confirmed SPN in five hospitals between January 1996 and December 2014.The 97 cases included 93 female and 4 male patients, and the average age was 31.2 years. The tumor was located in the body or tail (70.1%), the head (20.6%), and the neck (9.3%). All patients underwent surgical exploration, including distal pancreatectomy (63.9%), pancreaticoduodenectomy (20.6%) (partial portal vein or superior mesenteric vein resection and artificial vascular graft reconstruction performed in 4.1% of the patients), central pancreatectomy (10.3%), enucleation (5.2%), and liver resection (1.0%). 16.5% of the patients had malignant tumors. The positive rate of Ki-67 was 66.7% in patients diagnosed with a malignant neoplasm and was comparable to 8.4% of the patients diagnosed to have a benign neoplasm (p 0.001). After a median follow-up of 70.1 months, three patients had recurrence and one patient died of liver metastasis.SPN is a rare neoplasm with low malignant potential. Surgical resection is warranted even in the presence of local invasion or metastases as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential and poor outcome of SPNs.

The global emergence of plasmid-mediated colistin resistance genes mcr-1 and mcr-3 has threatened the role of the “last-resort” drug colistin in the defense against infections caused by multidrug-resistant Gram-negative bacteria. However, functional differences between these two genes in mediating colistin resistance remain poorly understood. Protein sequence alignment of MCR-3 and MCR-1 was therefore conducted in Clustal Omega to identify sequence divergence. The molecular recognition of lipid A head group phosphatidylethanolamine and MCR-3 enzyme was studied by homology modeling and molecular docking, with the catalytic mechanism of MCR-3 also being explored. Thr277 in MCR-3 was validated as the key amino acid residue responsible for the catalytic reaction using site-directed mutagenesis and was shown to act as a nucleophile. Lipid A modification induced by the MCR-3 and MCR-1 enzymes was confirmed by electrospray ionization–time of flight mass spectrometry. Far-UV circular dichroism spectra of the MCR-3 and MCR-1 enzymes suggested that MCR-3 was more thermostable than MCR-1, with a melting temperature of 66.19°C compared with 61.14°C for MCR-1. These data provided molecular insight into the functional differences between mcr-3 and mcr-1 in conferring colistin resistance.

Volume 61, no. 5, e02233-16, 2017, [https://doi.org/10.1128/AAC.02233-16][1]. Page 8, Acknowledgments, line 2: The first grant number from the National Natural Science Foundation of China should be 31530076 instead of 31370046. [1]: /lookup/doi/10.1128/AAC.02233-16

Two adjacent colistin resistance gene variants, termed mcr-3.3 and mcr-3 -like, were identified in the chromosome of an Aeromonas veronii isolate obtained from retail chicken meat. The variants showed 95.20% and 84.19% nucleotide sequence identity, respectively, to mcr-3 from porcine Escherichia coli . Functional cloning indicated that only mcr-3.3 conferred polymyxin resistance in both E. coli and Aeromonas salmonicida . The mcr-3.3-mcr-3 -like segment was also observed in other Aeromonas species, including A. media , A. caviae , and A. hydrophila .

Metallo-β-lactamase gene bla VIM was identified on the chromosome of four Pseudomonas sp. isolates from a chicken farm, including one Pseudomonas aeruginosa isolate from a swallow ( Yanornis martini ), one Pseudomonas putida isolate from a fly, and two P. putida isolates from chickens. The four isolates shared two variants of bla VIM -carrying genomic contexts that resemble the corresponding regions of clinical metallo-β-lactamase-producing Pseudomonas spp. Our study suggests that the surveillance of carbapenemase-producing bacteria in livestock and their surrounding environment is urgently needed.

Carbapenem-resistant Enterobacteriaceae (CRE) have spread worldwide, leaving very few treatment options available. New Delhi metallo-beta-lactamase (NDM) is the main carbapenemase mediating CRE resistance and is of increasing concern. NDM-positive Enterobacteriaceae of human origin are frequently identified; however, the emergence of NDM, and particularly novel variants, in bacteria of food animal origin has never been reported. Here, we characterize a novel NDM variant (assigned NDM-17) identified in a β-lactam-resistant sequence type 48 (ST48) Escherichia coli strain that was isolated from a chicken in China. Compared to NDM-1, NDM-17 had three amino acid substitutions (V88L, M154L, and E170K) that confer significantly enhanced carbapenemase activity. Compared to NDM-5, NDM-17 had only one amino acid substitution (E170K) and slightly increased isolate resistance to carbapenem, as indicated by increased MIC values. The gene encoding NDM-17 ( bla NDM-17 ) was located on an IncX3 plasmid, which was readily transferrable to recipient E. coli strain J53 by conjugation, suggesting the possibility of the rapid dissemination of bla NDM-17 . Enzyme kinetics showed that NDM-17 could hydrolyze all β-lactams tested, except for aztreonam, and had a significantly higher affinity for all β-lactams tested than did NDM-5. The emergence of this novel NDM variant could pose a threat to public health because of its transferability and enhanced carbapenemase activity.

Water deficiency seriously restricts the agricultural production in Northern China. Soil tillage practices can conserve water and increase yield effectively, but the regional applicability of soil tillage practices has not been systematically studied so far. It is significant to study the regional characteristics of tillage practices on water-conserving and yield-increasing so that the optimal practices for improving the crop water production and maintaining the agricultural sustainable development can be determined. This study applied the meta-analysis method to analyze results extracted from 156 peer-reviewed published papers conducted at 62 agricultural experimental sites for evaluating the effects of commonly used tillage practices, i.e., No-tillage (NT), Subsoiling (SS), Mulching (M), Ridge and Furrow Planting without Mulching (F), and Ridge and Furrow Planting with Mulching (F–M) on crop yield, water consumption and water use efficiency (WUE) of wheat and maize in Northern China. The results showed that NT only increased yield of winter wheat in North-central China and spring maize in Northeast China. SS increased wheat and maize yield by 16.3 ± 3.2 % and 9.2 ± 3.0 %, and increased water consumption by 8.4 ± 3.4 % and 1.8 ± 1.8 %, respectively. M increased the yield of wheat and maize by 14.9 ± 2.9 % and 17.7 ± 6.2 %, respectively, while it did not increase the water consumption. F increased the yield of wheat by 5.0 ± 1.1 %. F–M increased wheat and maize yield by 18.9 ± 6.3 % and 36.6 ± 11.8 %, respectively. This study recommends that, SS is suitable for winter wheat and summer maize in North-central China. M and F–M are suitable for spring maize in North-central China as well as wheat and maize in Northwest and Northeast China

The prediction of the propellant remaining is related to the use efficiency of the propellant, it is of great significance for the estimation of the remaining life of the spacecraft. The gauging uncertainty of the commonly used propellant remaining prediction method is high, and the single gauging method can not meet the higher requirements of long life satellites on-orbit management. In order to further improve the accuracy of the spacecraft propellant remaining prediction, combined with the characteristics of the existing propellant remaining estimation method, a real-time estimation method of propellant remaining is proposed. The algorithm combines two gauging methods to further improve the reliability of propellant consumption estimation. The practical application shows that the algorithm can effectively reduce the disadvantages of the BK method and the PVT method, and provide a more reasonable estimation of the real-time propellant remaining.

By 2030, the global population will be 8.5 billion, placing pressure on international poultry production, of which China is a key producer1. From April 2017, China will implement the withdrawal of colistin as a growth promoter, removing over 8,000 tonnes per year from the Chinese farming sector2. To understand the impact of banning colistin and the epidemiology of multi-drug-resistant (MDR) Escherichia coli (using blaNDM and mcr-1 as marker genes), we sampled poultry, dogs, sewage, wild birds and flies. Here, we show that mcr-1, but not blaNDM, is prevalent in hatcheries, but blaNDM quickly contaminates flocks through dogs, flies and wild birds. We also screened samples directly for resistance genes to understand the true breadth and depth of the environmental and animal resistome. Direct sample testing for blaNDM and mcr-1 in hatcheries, commercial farms, a slaughterhouse and supermarkets revealed considerably higher levels of positive samples than the blaNDM- and mcr-1-positive E. coli, indicating a substantial segment of unseen resistome-a phenomenon we have termed the 'phantom resistome'. Whole-genome sequencing identified common blaNDM-positive E. coli shared among farms, flies, dogs and farmers, providing direct evidence of carbapenem-resistant E. coli transmission and environmental contamination.

Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16+ cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1+) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.

Natural killer T-cell lymphoma (NKTCL) was classified as a distinct entity in the World Health Organization classification of tumors of hematopoietic and lymphoid tissues in both 2001 and 2008 [1]....

Autologous bone marrow mesenchymal stem cell (BM-MSC) transplantation is a novel strategy for treating ischemic heart disease. However, limited benefits have been reported in aging patients. Rejuvenation of aged human BM-MSCs (hBM-MSCs) could be a means to improve the efficacy of stem cell transplantation in older patients. While it has been shown that sirtuin 6 (SIRT6) is an important antiaging factor in various cells, the role of SIRT6 in hBM-MSCs remains unknown. The hBM-MSCs from different ages were cultured for quantifying SIRT6 expression by mRNA and Western blotting. The cell proliferative and migration abilities were evaluated by BrdU staining, cell growth curves, and scratch assay. Senescence-associated β-galactosidase (SA-β-Gal) activity and aging-associated p16 (cyclin-dependent kinase inhibitor 2A) expression were also quantified. The knockdown of SIRT6 in hBM-MSCs was used to investigate its impact on aging. SIRT6 expression increased with age, while the proliferative and migration abilities of aged hBM-MSCs were decreased compared with young cells. Knockdown of SIRT6 impaired the proliferative, migration, and oxidative stress resistance potentials of BM-MSCs. SA-β-Gal activity and p16 expression were increased in aged cells compared with young ones and in siRNA SIRT6 knockdown cells compared with their controls. Aging results in compensatory overexpression of SIRT6 in hBM-MSCs. Downregulation of SIRT6 in these cells resulted in less cell proliferation and migration but increased SA-β-Gal activity and p16 expression. These results suggest that SIRT6 regulates the aging process in hBM-MSCs and could serve as a target for their rejuvenation.

In this work, a density function theory (DFT) study is presented for the HNS/HSN isomerization assisted by 1–4 water molecules on the singlet state potential energy surface (PES). Two modes are considered to model the catalytic effect of these water molecules: (i) water molecule(s) participate directly in forming a proton transfer loop with HNS/HSN species, and (ii) water molecules are out of loop (referred to as out-of-loop waters) to assist the proton transfer. In the first mode, for the monohydration mechanism, the heat of reaction is 21.55 kcal · mol−1 at the B3LYP/6-311++G** level. The corresponding forward/backward barrier lowerings are obtained as 24.41/24.32 kcal · mol−1 compared with the no-water-assisting isomerization barrier T (65.52/43.87 kcal · mol−1). But when adding one water molecule on the HNS, there is another special proton-transfer isomerization pathway with a transition state 10T′ in which the water is out of the proton transfer loop. The corresponding forward/backward barriers are 65.89/65.89 kcal · mol−1. Clearly, this process is more difficult to follow than the R–T–P process. For the two-water-assisting mechanism, the heat of reaction is 19.61 kcal · mol−1, and the forward/backward barriers are 32.27/12.66 kcal · mol−1, decreased by 33.25/31.21 kcal · mol−1 compared with T. For trihydration and tetrahydration, the forward/backward barriers decrease as 32.00/12.60 (30T) and 37.38/17.26 (40T) kcal · mol−1, and the heat of reaction decreases by 19.39 and 19.23 kcal · mol−1, compared with T, respectively. But, when four water molecules are involved in the reactant loop, the corresponding energy aspects increase compared with those of the trihydration. The forward/backward barriers are increased by 5.38 and 4.66 kcal · mol−1 than the trihydration situation. In the second mode, the outer-sphere water effect from the other water molecules directly H-bonded to the loop is considered. When one to three water molecules attach to the looped water in one-water in-loop-assisting proton transfer isomerization, their effects on the three energies are small, and the deviations are not more than 3 kcal · mol−1 compared with the original monohydration-assisting case. When adding one or two water molecules on the dihydration-assisting mechanism, and increasing one water molecule on the trihydration, the corresponding energies also are not obviously changed. The results indicate that the forward/backward barriers for the three in-loop water-assisting case are the lowest, and the surrounding water molecules (out-of-loop) yield only a small effect. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

Paired box 6 (PAX6) plays a significant role in the development of human neuroectodermal epithelial tissues. Previous studies have suggested that the PAX6 promoter is hypermethylated in breast cancer and that it is involved in breast cancer cell proliferation. The present study aimed to investigate the expression of PAX6 in invasive breast cancer tissues, and to evaluate its prognostic significance. Immunohistochemistry (IHC) was used to detect PAX6 expression on a breast cancer tissue microarray containing tissues from 111 patients. Associations of PAX6 expression with staging and prognosis were analyzed. PAX6 was mainly expressed in the nucleus. The PAX6 staining intensity was not associated with age, histological grade, lymph node status, tumor size, or progesterone receptor and human epidermal growth factor receptor 2 expression (all P>0.05). A high level of PAX6 staining was more frequent in estrogen receptor (ER)-negative cases compared with ER-positive cases (43.9 vs. 25.7%; P=0.049). After a median follow-up time of 110 months, the patients with low PAX6 expression exhibited an improved survival rate compared with the patients with high PAX6 expression (P

Tasks scheduling problem in cloud computing is NP-hard, and it is difficult to attain an optimal solution, so we can use intelligent optimization algorithms to approximate the optimal solution, such as ant colony optimization algorithm. In order to solve the task scheduling problem in cloud computing, a period ACO_based scheduling algorithm (PACO) has been proposed in this paper. PACO uses ant colony optimization algorithm in cloud computing, with the first proposed scheduling period strategy and the improvement of pheromone intensity update strategy. The experiments results show that, PACO has a good performance both in makespan and load balance of the whole cloud cluster.

In recent years, the mobile metallo-β-lactamase (MBL) genes have been found to correspond to one of the most important resistance characters identified in Gram-negative bacteria, severely affecting clinical chemotherapy and threatening public health. The prevalence of mobile MBL genes and their flanking regions in Gram-negative bacteria from diseased pigs in China was investigated. A total of 334 lung samples from diseased pigs were screened for Gram-negative bacteria classified as non-susceptible to meropenem (MIC≥4 mg·L-1). Six isolates, including three Escherichia coli, two Acinetobacter baumanii and one A. calcoaeticus, exhibited MBL production and carried the blaNDM-1 gene. S1-PFGE and Southern blot analysis showed that the blaNDM-1 gene was located on the chromosome of one A. baumanii isolate and on plasmids of various sizes in the other five isolates. MIC testing using broth microdilution revealed that all blaNDM-1-carrying isolates and some of their transconjugants exhibited resistance to almost all β-lactams tested. Whole genome sequencing revealed that the flanking region of the blaNDM-1 gene from all porcine isolates had high levels of similarity with the corresponding regions in human isolates. One porcine E. coli isolate carrying blaNDM-1 was typed as ST48, a common sequence type in human E. coli isolates. These results suggest the possibility of human-to-food animal transfer of blaNDM-1-producing E. coli, highlighting the need for surveillance of carbapenemase producers among bacteria from food animals. In addition, the prudent use of antimicrobial agents to decrease the opportunities for co-selection of carbapenemase genes in food animals is also urgently needed.