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1.
Heredity (Edinb) ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772317

RESUMO

The evergreen broadleaved forests (EBLFs) of Southwest China have a long-term stable environment and support a diverse flora, thus forming a global biodiversity hotspot. However, the key drivers that have shaped the genetic diversity patterns of species in these EBLFs are not well understood. Quercus delavayi, Q. schottkyana, and Q. kerrii are sympatric oak species with different seed biological traits that are typical for these EBLFs. This study combined multilocus phylogeography and ecological niche modeling to screen 33 Q. delavayi populations. Their population genetic structure was inferred in comparison with previous studies on Q. schottkyana and Q. kerrii. The seed germination traits of all three species were also investigated. cpDNAs showed a significant phylogeographic structure in Q. delavayi, which was not detected in Q. schottkyana or Q. kerrii. Quercus delavayi, Q. kerrii, and Q. schottkyana exhibited different pollen-to-seed migration ratios (r = 219, 117, and 22, respectively), which are linked to the germination schedules of acorns. The distributions of Q. delavayi and Q. schottkyana remained long-term stable since the last glacial maximum (LGM) with a similar nSSR genetic gradient change along latitude. Instead, Q. kerrii experienced a prominent range expansion since the LGM with genetic diversification between the East and the West of the Tanaka line due to environmental heterogeneity. These results identify seed traits and environmental heterogeneity as two key drivers that shape the population genetic structure of EBLF trees in Southwest China. These should be considered in regional forestry conservation and management.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31778290

RESUMO

The synthesis of chiral C1 -symmetrical copper(I) complexes supported by chiral carbene ligands is described. These complexes are yellow emitters with modest quantum yields. Circularly polarized luminescence (CPL) spectra show a polarized emission band with dissymmetry factors |glum |=1.2×10-3 . These complexes are the first reported examples of molecular copper(I) complexes exhibiting circularly polarized luminescence. In contrast with most CPL-emitting molecules, which possess either helical or axial chirality, the results presented show that simple chiral architectures are suitable for CPL emission and unlock new synthetic possibilities.

3.
Nat Commun ; 10(1): 5304, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31757956

RESUMO

DNA replication stress-mediated activation of the ATR kinase pathway is important for maintaining genomic stability. In this study, we identified a zinc finger protein, ZFP161 that functions as a replication stress response factor in ATR activation. Mechanistically, ZFP161 acts as a scaffolding protein to facilitate the interaction between RPA and ATR/ATRIP. ZFP161 binds to RPA and ATR/ATRIP through distinct regions and stabilizes the RPA-ATR-ATRIP complex at stalled replication forks. This function of ZFP161 is important to the ATR signaling cascade and genome stability maintenance. In addition, ZFP161 knockout mice showed a defect in ATR activation and genomic instability. Furthermore, low expression of ZFP161 is associated with higher cancer risk and chromosomal instability. Overall, these findings suggest that ZFP161 coordinates ATR/Chk1 pathway activation and helps maintain genomic stability.

4.
BMC Evol Biol ; 19(1): 202, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684859

RESUMO

BACKGROUND: Understanding the origin of genetic variation is the key to predict how species will respond to future climate change. The genus Quercus is a species-rich and ecologically diverse woody genus that dominates a wide range of forests and woodland communities of the Northern Hemisphere. Quercus thus offers a unique opportunity to investigate how adaptation to environmental changes has shaped the spatial genetic structure of closely related lineages. Furthermore, Quercus provides a deep insight into how tree species will respond to future climate change. This study investigated whether closely related Quercus lineages have similar spatial genetic structures and moreover, what roles have their geographic distribution, ecological tolerance, and historical environmental changes played in the similar or distinct genetic structures. RESULTS: Despite their close relationships, the three main oak lineages (Quercus sections Cyclobalanopsis, Ilex, and Quercus) have different spatial genetic patterns and occupy different climatic niches. The lowest level and most homogeneous pattern of genetic diversity was found in section Cyclobalanopsis, which is restricted to warm and humid climates. The highest genetic diversity and strongest geographic genetic structure were found in section Ilex, which is due to their long-term isolation and strong local adaptation. The widespread section Quercus is distributed across the most heterogeneous range of environments; however, it exhibited moderate haplotype diversity. This is likely due to regional extinction during Quaternary climatic fluctuation in Europe and North America. CONCLUSIONS: Genetic variations of sections Ilex and Quercus were significantly predicted by geographic and climate variations, while those of section Cyclobalanopsis were poorly predictable by geographic or climatic diversity. Apart from the different historical environmental changes experienced by different sections, variation of their ecological or climatic tolerances and physiological traits induced varying responses to similar environment changes, resulting in distinct spatial genetic patterns.

5.
Asian J Surg ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31703889

RESUMO

Gastrectomy for cancer is a technically demanding procedure, with postoperative complications (POCs) reported to be in the range of 20%-46%. However, the effect of POCs on long-term survival of gastric cancer patients following surgery is far from conclusive. This systemic review aimed to determine the impact of postoperative complications (POCs) on the long-term survival of patients following surgery for gastric cancer. A systematic electronic search of PubMed and Scopus was performed from inception to June 26, 2018 to identify studies that described the relationship between POCs and long-term survival. Hazard ratios (HRs) for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) from each study were combined using a random-effects model. Sixty-four eligible studies with reported results for 46198 gastric cancer patients were included. A meta-analysis found a statistically significant difference in OS, CSS and RFS between gastric patients with unspecific POCs and no POCs, POCs ≥ Clavien-Dindo grade (CD) 2 and < CD2, major POCs and minor POCs, infectious and non-infectious complications, anastomotic and non-anastomotic complications, and cardiopulmonary and non-cardiopulmonary complications. Subgroup and sensitivity analyses did not significantly change the summary of OS risk estimates between patients with POCs and without POCs. No significant publication bias was observed for the same outcome. The meta-analysis revealed that POCs were associated with worse survival among patients with resected gastric cancer, suggesting that treatment strategies aimed at minimizing POCs may improve oncological outcomes.

6.
Cell Biochem Funct ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710116

RESUMO

Colorectal cancer (CRC) is a common human malignancy that accounts for 600,000 deaths annually worldwide. Chrysophanol, a naturally occurring anthraquinone compound, exhibits anti-neoplastic effects in various cancer cells. The aim of this study was to explore the biological effects of chrysophanol on CRC cells, and determine the underlying mechanism. Chrysophanol inhibited proliferation of and promoted apoptosis in CRC cells by activating the intrinsic mitochondrial apoptotic pathway. In addition, chrysophanol also suppressed tumor growth in vivo and increased the percentage of apoptotic cells in tumor xenografts, without general toxicity. Proteomic iTRAQ analysis revealed decorin (DCN) as the major target of chrysophanol. DCN was upregulated in the tumor tissues following chrysophanol treatment, and ectopic DCN expression markedly augmented the pro-apoptotic effects of chrysophanol in CRC cells. In contrast, DCN knockdown significantly abrogated chrysophanol-induced apoptosis in CRC cells. Taken together, chrysophanol exerts anti-neoplastic effects in vitro and in vivo in CRC cells by modulating DCN, there by highlighting its therapeutic potential in CRC.

7.
J Transl Med ; 17(1): 352, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655604

RESUMO

BACKGROUND: Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer. METHODS: Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial-mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis. RESULTS: In the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-ß treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a-CD36 cells, suggesting that TGF-ß synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-ß in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-ß were up-regulated in C33a-CD36 cells. These results imply that CD36 and TGF-ß interact with each other to promote the EMT in cervical cancer. CONCLUSIONS: Our findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.

8.
New Phytol ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31609470

RESUMO

The tree of life is highly reticulate, with the history of population divergence emerging from populations of gene phylogenies that reflect histories of introgression, lineage sorting and divergence. In this study, we investigate global patterns of oak diversity and test the hypothesis that there are regions of the oak genome that are broadly informative about phylogeny. We utilize fossil data and restriction-site associated DNA sequencing (RAD-seq) for 632 individuals representing nearly 250 Quercus species to infer a time-calibrated phylogeny of the world's oaks. We use a reversible-jump Markov chain Monte Carlo method to reconstruct shifts in lineage diversification rates, accounting for among-clade sampling biases. We then map the > 20 000 RAD-seq loci back to an annotated oak genome and investigate genomic distribution of introgression and phylogenetic support across the phylogeny. Oak lineages have diversified among geographic regions, followed by ecological divergence within regions, in the Americas and Eurasia. Roughly 60% of oak diversity traces back to four clades that experienced increases in net diversification, probably in response to climatic transitions or ecological opportunity. The strong support for the phylogeny contrasts with high genomic heterogeneity in phylogenetic signal and introgression. Oaks are phylogenomic mosaics, and their diversity may in fact depend on the gene flow that shapes the oak genome.

9.
Surgeon ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31601470

RESUMO

Prognosis of patients that have undergone liver resection can be predicted preoperatively. Albumin-Bilirubin (ALBI) is a useful score to evaluate liver function objectively. This score is simple to use, uses objective parameters, and can stratify patients into grades. In combination with other liver cancer scores, the prognosis and survival of patients can be evaluated with more accuracy. Current literatures supporting the use of the ALBI score relating to prognosis of post hepatectomy, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), radiotherapy and systemic therapy are available. Therefore, ALBI score is worthy of clinical application. The following is a review of the current literatures on the ALBI score.

10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(8): 878-884, 2019 Aug 28.
Artigo em Chinês | MEDLINE | ID: mdl-31570674

RESUMO

OBJECTIVE: To assess the value of immunohistochemical analysis for expressions of C3d, C4d, IgG, IgG4, and CD123 in the diagnosis of autoimmune skin diseases.
 Methods: We investigated the expressions of C3d, C4d, IgG, IgG4, and CD123 in paraffin-embedded, formalin-fixed tissues from 27 lupus erythematosus cases, including 8 discoid lupus erythematosus (DLE) cases, 4 subacute cutaneous lupus erythematosus (SCLE) cases, and 15 systemic lupus erythematosus (SLE) cases. Tissues from 15 dermatomyositis (DM) cases, 15 bullous pemphigoid (BP) cases, and 15 pemphigus cases were examined by immunohistochemical analysis. The differences in expression rates of C3d, C4d, IgG, IgG4, and CD123 between immunohistochemical staining and direct immunofluorescence were compared in the diagnosis of these diseases.
 Results: In the lupus erythematosus group, the positive rates of C3d and C4d deposited along the dermoepidermal junction were 85.2% and 51.9%, respectively. In the dermatomyositis group, the positive rates of C3d and C4d deposited along the dermoepidermal junction were 40% and 0, respectively. The expressions of C3d and C4d in lupus erythematosus tissues were significantly higher than those in DM tissues (P<0.05). The expression of CD123 protein in skin lesions of the lupus group was significantly higher than that in the DM group (P<0.05). In the BP group, the positive rates of C3d and C4d deposited along the dermoepidermal junction were 100% and 86.7%, respectively. In the pemphigus group, the positive rates of C3d and C4d deposited in the intercellular space of keratinocytes were 100% and 60%, respectively. The expressions of IgG and IgG4 in pemphigus tissues were higher than those in BP tissues (P<0.05). And the ratios of IgG4 to IgG in the pemphigus group was significantly higher than that in the BP group (P<0.05).
 Conclusion: The assays of C3d and C4d define an important diagnostic adjunct in evaluation of lupus erythematosus, BP and pemphigus. In some cases, it may even replace the direct immunofluorescence as a diagnostic adjunct. The expression of CD123 possesses certain clinical significance for the differential diagnosis of lupus erythematosus, and IgG4 and IgG expressions have adjunctive diagnostic significance for pemphigus.


Assuntos
Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Pênfigo , Complemento C3d , Proteínas do Sistema Complemento , Humanos , Imunoglobulina G , Subunidade alfa de Receptor de Interleucina-3
11.
PLoS One ; 14(10): e0223175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31589643

RESUMO

There is few significant attempt to integrate environmental regulation, government financial support, and corporate technological innovation in a methodological framework. Employing the data of the industrial enterprises with an annual turnover of over 20 million yuan from 30 Chinese provinces or municipalities between 2008 and 2016, this paper applies the fixed effect regression model to reveal the relationships between environmental regulation, government financial support, and corporate technological innovation simultaneously. Results show that: (1) there exists a U-shaped relation between environmental regulation intensity and technological innovation of enterprises which declines first and then climbs up, and China is still at the stage of inhibition before the "inflection point". (2) government financial support does not significantly work on technological innovation directly, but environmental regulation drives this effect to be achieved; when the value of lnER is higher than 3.69, government financial support can significantly facilitate corporate technological innovation. (3) the comparison between regional samples reveals that heterogeneity exists in the influence of environmental regulation intensity and government financial support on corporate technological innovation. The threshold value of enabling effects of environmental regulation in eastern region is higher than that of the central and western region. These results remain consistent after we experiment several robustness checks. Theory and policy implications of our work are discussed.

12.
Int J Phytoremediation ; : 1-8, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31475859

RESUMO

Cadmium (Cd) contamination is the most extensive pollution in China farmland. A greenhouse pot trial was conducted to investigate the effects of cornstalk biochar on Cd accumulation by Phytolacca americana L. (pokeweed) in Cd-contaminated soil. The Cd concentration increased in leaves, shoots, and roots of plants amended with 5% biochar by 79%, 113%, and 32%, respectively, compared with the pokeweed without biochar. The Cd availability, soil Cd speciation, soil fertility, root biomass, and Cd chemical forms in root were investigated to explore the mechanism by which Cd uptake increased in presence of biochar. The extractability of Cd by DTPA decreased in presence of biochar by 30% compared with that of soil without biochar. The increases occurred with dose of biochar increased in available phosphorus, labile organic carbon, and C/N atom ratio. Although, the dry weight of the aboveground part of the pokeweed decreased by 38.5%, however, the weight of roots increased by 20.8%. Root biomass and microbial activity reached maximum in the treatment that recieved 5% biochar. Cd forms extracted by NaCl and acetic acid (HAc) were predominant in root. When 5% biochar applied to soil, HAc-extracted Cd took up maximum of the increase in root.

13.
Mol Med Rep ; 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545412

RESUMO

Lipopolysaccharide (LPS) induces stress inflammation and apoptosis. Pulmonary epithelial cell apoptosis, which accelerates the progression of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), is the leading cause of mortality in patients with ALI/ARDS. The nephroblastoma overexpressed protein (CCN3), an inflammatory modulator, is reported to be a biomarker in ALI. Using the LPS-induced ALI model, this study investigated the expression of CCN3 and its possible molecular mechanism in lung alveolar epithelial cell inflammation and apoptosis. Our data revealed that LPS treatment greatly increased the level of CCN3 in A549 cells. The A549 cells were transfected with specific CCN3 small interfering RNA (siRNA) using transfection reagent. CCN3 siRNA not only largely attenuated the expressions of the inflammatory cytokines interleukin (IL)-1ß and transforming growth factor (TGF)-ß1, but also reduced the apoptotic rate of the AEC II cells and affected the expressions of the apoptosis-associated proteins (Bcl-2 and caspase-3). Furthermore, CCN3 knockdown greatly inhibited the activation of nuclear factor-κB p65 in A549 cells. In addition, TGF-ß/p-Smad inhibitor (TP0427736) and NF-κB inhibitor (PDTC) significantly attenuated the expression level of CCN3 in A549 cells. In conclusion, our data indicated that CCN3 siRNA affected downstream signal through TGF-ß/ p-Smad or NF-κB pathway, leading to the inhibition of cell inflammation and apoptosis in human alveolar epithelial cells.

14.
Biomed Pharmacother ; 118: 109239, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351431

RESUMO

Diazepam could regulate immune system and inflammation, which might be a potential therapeutic agent for pulmonary fibrosis in clinic. This study showed that diazepam reversed LPS-induced inhibition of cell proliferation and promotion of cell apoptosis. Of note, LPS specifically induced Caspase-11 dependent cell pyroptosis, which were significantly attenuated by diazepam or pyroptosis inhibitor necrosulfonamide (NSA) treatment. In addition, α4- and α5-subunits of GABAARs were highly expressed in human bronchial 16HBE cells, human pulmonary epithelial cells (BEAS-2B) and pulmonary epithelial cells isolated from mice (mPECs). Further results showed that only knock-down of α4-GABAARs abrogated the effects of diazepam on LPS induced cell pyroptosis, apoptosis and proliferation. Similiarly, either diazepam or NSA treatment could alleviate development of LPS induced inflammatory reactions and pulmonary fibrosis in mice, which were abrogated by synergistically knocking down α4-GABAARs. Taken together, diazepam alleviated LPS-induced cell pyroptosis and development of pulmonary fibrosis in mice by activating α4-GABAARs.

15.
BMC Infect Dis ; 19(1): 617, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299910

RESUMO

BACKGROUND: The major infectious diseases of hepatitis B has constituted an acute public health challenge in China. An effective and affordable HBV control model is urgently needed. A national project of Community-based Collaborative Innovation HBV (CCI-HBV) demonstration areas has optimized the existing community healthcare resources and obtained initial results in HBV control. METHODS: Based on the existing community healthcare network, CCI-HBV project combined the community health management and health contract signing service for long-staying residents in hepatitis B screening. Moreover, HBV field research strategy was popularized in CCI-HBV areas. After screening, patients with seropositive results were enrolled in corresponding cohorts and received treatment at an early stage. And the uninfected people received medical supports including health education through new media, behavior intervention and HBV vaccinations. In this process, a cloud-based National Information Platform (NIP) was established to collect and store residents' epidemiological data. In addition, a special quality control team was set up for CCI project. RESULTS: After two rounds of screening, HBsAg positive rate dropped from 5.05% (with 5,173,003 people screened) to 4.57% (with 3,819,675 people screened), while the rate of new HBV infections was 0.28 per 100 person-years in the fixed cohorts of 2,584,322 people. The quality control team completed PPS sampling simultaneously and established the serum sample database with 2,800,000 serum samples for unified testing. CONCLUSIONS: CCI-HBV project has established a large-scale field research to conduct whole-population screening and intervention. We analyzed the HBsAg prevalence and new infection rate of HBV in the fixed population for the epidemic trend and intervention effect. The purpose of CCI-HBV project is to establish and evaluate a practical model of grid management and field strategy, to realize the new goal to control hepatitis B in China. To provide policymakers with a feasible model, our results are directly applicable. TRIAL REGISTRATION: The project was funded by the Major Projects of Science Research for the 11th and 12th five-year plans of China, entitled "The prevention and control of AIDS, viral hepatitis and other major infectious diseases", Grant Nos. 2009ZX10004901, 2011ZX10004901, 2013ZX10004904, 2014ZX10004007 and 2014ZX10004008.


Assuntos
Bases de Dados Factuais , Hepatite B/epidemiologia , Adolescente , China/epidemiologia , Computação em Nuvem , Serviços de Saúde Comunitária , Feminino , Política de Saúde , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
16.
Cancer Sci ; 110(9): 2822-2833, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278883

RESUMO

Kinesin family member C1 (KIFC1) is implicated in the clustering of multiple centrosomes to maintain tumor survival and is thought to be an oncogene in several kinds of cancers. In our experiments, we first performed bioinformatics analysis to investigate the expression levels of KIFC1 in bladder cancer (BC) specimens and normal bladder epitheliums and then, using our samples, verified findings by quantitative real-time PCR and western blotting assays. All data showed that KIFC1 was significantly upregulated in BC specimens at both the mRNA and protein levels. Immunohistochemical studies in a cohort of 152 paraffin-embedded BC tissues displayed that upregulated expression of KIFC1 clearly correlated with pT status (P = .014) and recurrent status (P = .002). Kaplan-Meier survival analysis and log-rank test indicated that patients with BC with high KIFC1 expression had both shorter cancer-specific survival (P < .001) and recurrence-free survival time (P < .001) than those with low KIFC1 expression. Furthermore, ectopic downregulation of KIFC1 weakened BC cell proliferation and migration both in vitro and in vivo, whereas upregulation of KIFC1 enhanced this in vitro. Overexpression of KIFC1 phosphorylated GSK3ß and promoted Snail through activating AKT (protein kinase B0) to induce proliferation and epithelial-mesenchymal transition (EMT) and, therefore, substantially promoted BC migration and metastasis. Our study revealed an oncogenic role for KIFC1 to promote BC cell proliferation and EMT via Akt/GSK3ß signaling; KIFC1 might be a promising prognostic biomarker as well as a therapeutic target for BC.


Assuntos
Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal , Glicogênio Sintase Quinase 3 beta/metabolismo , Cinesina/metabolismo , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Regulação para Cima , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Urotélio/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Am J Infect Control ; 47(11): 1358-1364, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31277999

RESUMO

BACKGROUND: Few data are available on hospital-wide incidence of central line-associated bloodstream infection (CLABSI) rates in patients with central venous catheter (CVC) in China, where many systemic obstacles holding back evidence-based guidelines implementation exist. METHODS: This study was conducted prospectively in 2 phases. The baseline and intervention phases were performed in a teaching hospital in China, between January 2017 and October 2018. A systematic quality improvement (SQI) and multidisciplinary teamwork (MDT) CLABSI infection control program was introduced in the intervention phase. In the intensive care units (ICUs) and non-ICUs, CLABSIs were continuously monitored, data collected, then analyzed. RESULTS: After intervention, the CLABSI rate decreased from 2.84-0.56 per 1,000 CVC days in ICUs (P < .001), and from 0.82-0.47 per 1,000 CVC days in non-ICUs (P = .003). The length of time until CLABSI occurrence increased from 8.72-13.60 days in ICUs (P = .046), and from 10.00-12.00 days in non-ICUs (P = .048). The number of multidrug-resistant bacteria isolated from CLABSI episodes decreased both in ICUs and in non-ICUs. CONCLUSIONS: The SQI and MDT CLABSI infection control program is effective in reducing hospital-wide CLABSI in patients with CVC, both in ICUs and in non-ICUs.

18.
Cell Death Differ ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296961

RESUMO

Breast cancer stem cells (BCSCs) are tumor initiating cells that can self-renew and are highly tumorigenic and chemoresistant. Therefore, the identification of factors critical for BCSC function is vital for the development of therapies. Here, we report that DNMT1-mediated FOXO3a promoter hypermethylation leads to downregulation of FOXO3a expression in breast cancer. FOXO3a is functionally related to the inhibition of FOXM1/SOX2 signaling and to the consequent suppression of BCSCs properties and tumorigenicity. Moreover, we found that SOX2 directly transactivates DNMT1 expression and thereby alters the methylation landscape, which in turn feedback inhibits FOXO3a expression. Inhibition of DNMT activity suppressed tumor growth via regulation of FOXO3a/FOXM1/SOX2 signaling in breast cancer. Clinically, we observed a significant inverse correlation between FOXO3a and FOXM1/SOX2/DNMT1 expression levels, and loss of FOXO3a expression or increased expression of FOXM1, SOX2, and DNMT1 predicted poor prognosis in breast cancer. Collectively, our findings suggest an important role of the DNMT1/FOXO3a/FOXM1/SOX2 pathway in regulating BCSCs properties, suggesting potential therapeutic targets for breast cancer.

19.
Plant J ; 100(1): 114-127, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31169939

RESUMO

Phytol is one of the key precursors for tocopherol synthesis in plants, however, the underlying mechanisms concerning the accumulation of tocopherol remain poorly understood. In this study, qVE5, a major QTL affecting tocopherol accumulation in maize kernels was identified via a positional cloning approach. qVE5 encodes a protochlorophyllide oxidoreductase (ZmPORB2), which localizes to the chloroplast. Overexpression of ZmPORB2 increased tocopherol content in both leaves and kernels. Candidate gene association analysis identified a 5/8-bp insertion/deletion (InDel058) in the 5' untranslated region (UTR) as the causal polymorphism in affecting ZmPORB2 expression and being highly associated with tocopherol content. We showed that higher expression of ZmPORB2 correlated with more chlorophyll metabolites in the leaf following pollination. RNA-sequencing and metabolic analysis in near isogenic lines (NILs) support that ZmPORB2 participates in chlorophyll metabolism enabling the production of phytol, an important precursor of tocopherol. We also found that the tocopherol content in the kernel is mainly determined by the maternal genotype, a fact that was further confirmed by in vitro culture experiments. Finally, a PCR-based marker based on Indel058 was developed in order to facilitate the high tocopherol (vitamin E) maize breeding.

20.
Mol Med Rep ; 20(1): 745-754, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180518

RESUMO

The present study aimed to further clarify the genetic mechanisms responsible for the antimicrobial resistance of Serratia marcescens (S. marcescens) using RNA sequencing. Three drug­susceptible S. marcescens strains (named MYQT1, MYQT2, and MYQT3) and three multidrug­resistant S. marcescens strains (named MYQT4, MYQT5, and MYQT6) were isolated from six different patients and subjected to RNA sequencing. Differentially expressed genes (DEGs) between the multidrug­resistant S. marcescens strains and drug­susceptible strains were screened and compared, followed by functional enrichment analysis. In addition, a protein­protein interaction (PPI) network was constructed, and significant modules were extracted from it. Genes enriched in the significant modules were subjected to further enrichment analysis. MYQT3 had very a different expression pattern from MYQT1 and MYQT2, and thus, MYQT3 was excluded from the following analysis. A total of 225 DEGs were identified, of which SMDB11_RS09300 (GTP cyclohydrolase FolE2) was the most significantly upregulated with a log2 FC of 6.4; these DEGs were enriched in different GO terms, including hydrogen sulfide biosynthetic process, sulfur compound transmembrane transporter activity, and ABC transporter complex. Additionally, several genes were identified to be important genes in the PPI network, including SMDB11_RS17755 (upregulated; glutamate synthase large subunit), SMDB11_RS00590 (upregulated; sulfite reductase subunit α), and SMDB11_RS04505 (upregulated; cystathionine ß­synthase). Thus, SMDB11_RS09300, SMDB11_RS17755, SMDB11_RS00590, and SMDB11_RS04505 may play significant roles in the antimicrobial resistance of S. marcescens by participating in folate metabolism or the integrity of cell membranes. However, further experiments are required to clarify these findings.

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