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1.
J Nanosci Nanotechnol ; 20(2): 828-839, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383078

RESUMO

At present, high-performance cement-based composites are widely used, and they are prone to early cracking due to their high autogenous shrinkage stress. In this research, the uniformly dispersed GNPs were added into high-performance cementitious materials. The autogenous shrinkage of high-performance cementitious matrix materials with different incorporation of GNPs was also researched with water to cement ratio of 0.25, 0.30 and 0.35. According to hydration heat, hydration products, microstructure and porosity of GNPs cementitious matrix materials, the microcosmic mechanism for autogenous shrinkage was also investigated. It was testified that moderate addition of GNPs decreased the autogenous shrinkage of cement-based composites. Moreover, the autogenous shrinkage value was minimal after treatment with 0.10 wt% GNPs cement paste sample for 7 days, at the water to cement ratio of 0.35, and the depressed percentage of autogenous shrinkage reached 81.60% compared with the blank sample.

2.
Aging (Albany NY) ; 112019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479419

RESUMO

p75 neurotrophin receptor (p75NTR) has been implicated in Alzheimer's disease (AD). However, whether p75NTR is involved in Tau hyperphosphorylation, one of the pathologies observed in AD, remains unclear. In our previous study, the extracellular domain of p75NTR blocked amyloid beta (Aß) toxicity and attenuated Aß-induced Tau hyperphosphorylation. Here we show that, in the absence of Aß, p75NTR regulates Tau phosphorylation in the transgenic mice with the P301L human Tau mutation (pR5). The knockout of p75NTR in pR5 mice attenuated the phosphorylation of human Tau. In addition, the elevated activity of kinases responsible for Tau phosphorylation including glycogen synthase kinase 3 beta; cyclin-dependent-kinase 5; and Rho-associated protein kinase was also inhibited when p75NTR is knocked out in pR5 mice at 9 months of age. The increased caspase-3 activity observed in pR5 mice was also abolished in the absence of p75NTR. Our study also showed that p75NTR is required for Aß- and pro-brain derived neurotrophin factor (proBDNF)-induced Tau phosphorylation, in vitro. Overall, our data indicate that p75NTR is required for Tau phosphorylation, a key event in the formation of neurofibrillary tangles, another hallmark of AD. Thus, targeting p75NTR could reduce or prevent the pathologic hyperphosphorylation of Tau.

3.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.

4.
J Phys Chem A ; 123(34): 7337-7350, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31373814

RESUMO

The mixed quantum-classical dynamical approaches have been widely used to study nonadiabatic phenomena in photochemistry and photobiology, in which the time evolutions of the electronic and nuclear subsystems are treated based on quantum and classical mechanics, respectively. The key issue is how to deal with coherence and decoherence during the propagation of the two subsystems, which has been the subject of numerous investigations for a few decades. A brief description on Ehrenfest mean-field and surface-hopping (SH) methods is first provided, and then different algorithms for treatment of quantum decoherence are reviewed in the present paper. More attentions were paid to quantum trajectory mean-field (QTMF) method under the picture of quantum measurements, which is able to overcome the overcoherence problem. Furthermore, the combined QTMF and SH algorithm is proposed in the present work, which takes advantages of the QTMF and SH methods. The potential to extend the applicability of the QTMF method was briefly discussed, such as the generalization to other type of nonadiabatic transitions, the combination with multiscale computational models, and possible improvements on its accuracy and efficiency by using machine-learning techniques.

5.
Cancer Med ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31464090

RESUMO

RIG-I is associated with the occurrence and development of many tumors. However, the role of RIG-I in radiotherapy and chemotherapy in NPC has not been reported to date. In our study, RIG-I expression was significantly reduced in chemoradiotherapy-resistant NPC tissues and cells compared with that in therapy-sensitive tissues and cells. RIG-I expression increased in nonresistant NPC cells, including CNE1 and CNE2, in a dose-dependent manner with increasing chemotherapy drug concentration or radiotherapy dose. RIG-I overexpression promoted radiotherapy and chemotherapy sensitivity in NPC cells, leading to cellular apoptosis and increased expression of the proapoptotic factors BAX and caspase-3. Similarly, RIG-I knockdown in NPC cells promoted chemoradiotherapy resistance and reduced apoptosis. Analysis of microarray data indicated that the expression of IFN/JAK2 and endoplasmic reticulum (ER) stress response markers, such as JAK2, STAT1, IRF9, IFNB1, IRF3, p-IRF3, XBP1, ATF6, IFIT2, and ISG15, was inhibited in chemoradiotherapy-resistant cells compared with that in sensitive cells. Conversely, activation of IFN/JAK2 and ER stress response pathways in NPC cells reduced paclitaxel resistance and increased apoptosis. RIG-I promotes IFN/JAK2 and ER stress response-mediated apoptosis to inhibit chemoradiation resistance in nasopharyngeal carcinoma.

6.
BMC Plant Biol ; 19(1): 354, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412779

RESUMO

BACKGROUND: High temperature is a major environmental stress that limits plant growth and agriculture productivity. Mitogen-activated protein kinases (MAPKs) are highly conserved serine and threonine protein kinases that participate in response to diverse environmental stresses in plants. A total of 16 putative SlMAPK genes are identified in tomato, and SlMAPK3 is one of the most extensively studied SlMAPKs. However, the role of SlMAPK3 in response to heat stress is not clearly understood in tomato plants. In this study, we performed functional analysis of SlMAPK3 for its possible role in response to heat stress. RESULTS: qRT-PCR analyses revealed that SlMAPK3 relative expression was depressed by heat stress. Here, wild-type (WT) tomato plants and CRISPR/Cas9-mediated slmapk3 mutant lines (L8 and L13) were used to investigate the function of SlMAPK3 in response to heat stress. Compared with WT plants, slmapk3 mutants exhibited less severe wilting and less membrane damage, showed lower reactive oxygen species (ROS) contents, and presented higher both activities and transcript levels of antioxidant enzymes, as well as elevated expressions of genes encoding heat stress transcription factors (HSFs) and heat shock proteins (HSPs). CONCLUSIONS: CRISPR/Cas9-mediated slmapk3 mutants exhibited more tolerance to heat stress than WT plants, suggesting that SlMAPK3 was a negative regulator of thermotolerance. Moreover, antioxidant enzymes and HSPs/HSFs genes expression were involved in SlMAPK3-mediated heat stress response in tomato plants.

7.
Neurobiol Dis ; 132: 104567, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394202

RESUMO

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.

8.
Neuropsychologia ; 133: 107177, 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31454630

RESUMO

Pain is typically expressed through various sensory (e.g., visual and auditory) modalities: the human voice conveys information about social and affective communication. While the empathic responses to others' pain in the visual modality are modulated by top-down attention constraints, it remains unclear whether empathy for such expressions in the auditory modality also involves such top-down modulation mechanisms. Therefore, the present study investigates how neural correlates of empathic processes to others' vocal pain are modulated by the task-instructed attention manipulations. Each participant completed the following three tasks: (1) Pain Judgment Task, in which participants were instructed to pay attention to pain cues in vocal stimuli, (2) Gender Judgment Task, in which participants were instructed to pay attention to non-pain cues in vocal stimuli; (3) Passive Listening Task, a control task in which participants were instructed to passively listen to the vocal stimuli without any required response. The earlier frontal-central N1 response to either others' painful or neutral voice was greater in the Pain Judgment Task than in the other two tasks, suggesting a general attention modulation on the bottom-up sensory processing of vocal stimuli. The frontal-central P2 responses to others' painful voices was greater in the Pain Judgment Task than in the other two tasks, but not to others' neutral voices, thus suggesting selective attention modulation on the P2 response to others' pain. Late positive complex (LPC) to others' painful and neutral voices differed significantly regardless of task manipulations, thus suggesting empathic pain modulation on LPC response. All these results demonstrated top-down attention modulation on affective sharing responses others' vocal pain, but not on cognitive appraisal process of others' vocal pain.

9.
Epigenomics ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31355678

RESUMO

Aim: To investigate the effect of UBE2T gene on radiotherapy for osteosarcoma. Materials & methods: Gene Expression Omnibus database, RT-qPCR and immunohistochemical analysis were performed. Cell proliferation and cell cycle experiments were conducted after knockdown of UBE2T. Cell scratch, reactive oxygen species production and apoptosis experiments were conducted after the combination of radiotherapy and UBE2T silencing. Then the xenograft mode was further conducted. Results: UBE2T was highly expressed in human osteosarcoma. Suppression of UBE2T inhibited osteosarcoma cell proliferation and induced cell cycle arrest at the G2/M phase. Downregulation of UBE2T combined with radiation can substantially inhibit clonal formation and migration, and promote apoptosis of osteosarcoma cells in vitro and in vivo. Conclusion: UBE2T downregulation can enhance the radiosensitivity of osteosarcoma in vitro and in vivo.

10.
JAMA Netw Open ; 2(7): e197621, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31339548

RESUMO

Importance: There are a limited number of predictive biomarkers for hyperprogressive disease (HPD), which is induced by immune checkpoint blockade (ICB) therapy. Objective: To evaluate the association of biomarkers in serum with the response to ICB therapy in patients with metastatic gastrointestinal tract cancer. Design, Setting, and Participants: Cohort study in which patients with metastatic gastrointestinal tract cancer treated with ICB were enrolled at the Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China, from August 1, 2015, to July 31, 2017, with the last follow-up date on January 1, 2018. Serum samples were collected at baseline and during the first visit to the clinic after starting treatment. Data analysis was conducted from January 16, 2018, to September 1, 2018. Exposures: A total of 59 factors, including cytokines/chemokines, growth factors, and soluble checkpoint-related proteins in serum, were examined by multiplexed bead immunoassays. Main Outcomes and Measures: Tree-based estimators were used to evaluate the importance of serum protein levels to ICB treatment response. Progression-free survival and overall survival analyses were conducted with the Kaplan-Meier method and log-rank test. Results: In total, 56 patients were examined. All patients with HPD (5 [8.9%]) had significantly lower mean (SD) levels of serum monocyte chemoattractant protein 1 than patients without HPD at baseline (53.4 [17.3] pg/mL vs 106.4 [48.4] pg/mL; P = .02). All patients with HPD were also identified by lower leukemia inhibitory factor levels (<13.28 pg/mL) and higher cluster of differentiation 152 levels (≥31.81 pg/mL). Among the remaining 51 patients, responders with esophageal squamous cell carcinoma (ESCC) or colorectal cancer (CRC) showed larger decreases in interleukin 1 receptor antagonist levels than nonresponders (ESCC: -55.02% [95% CI, -86.52% to -23.51%] vs 43.44% [95% CI, 11.93% to 74.96%]; P < .001; CRC: -35.82% [95% CI, -67.38% to -4.26%] vs 59.14% [95% CI, -72.34% to 190.6%]; P = .04). Responders with gastric cancer (GC) had larger increases in brain-derived neurotrophic factor levels than nonresponders (44.77% [95% CI, 10.76% to 78.79%] vs -26.2% [95% CI, -58.53% to 6.12%]; P = .003). Furthermore, early decreases in serum interleukin 1 receptor antagonist in patients with metastatic ESCC and CRC were associated with longer progression-free survival (ESCC: not reached vs 2.1 months; hazard ratio, 0.19; 95% CI, 0.04 to 0.95; P = .04; CRC: not reached vs 2.1 months; hazard ratio, 0.06; 95% CI, 0.01 to 0.38; P < .001). Early increases in brain-derived neurotrophic factor levels in patients with metastatic GC were associated with longer progression-free survival (not reached vs 4.2 months; hazard ratio, 0.15; 95% CI, 0.03 to 0.84; P = .03). Conclusions and Relevance: In this study, baseline serum levels of monocyte chemoattractant protein 1, leukemia inhibitory factor, and cluster of differentiation 152 were associated with hyperprogressive metastatic gastrointestinal cancer among patients receiving ICB. An early decrease in serum interleukin 1 receptor antagonist levels in patients with metastatic ESCC or CRC and an early increase in serum brain-derived neurotrophic factor levels in patients with metastatic GC were better able to identify who would respond to ICB compared with microsatellite stability status or programmed cell death ligand 1 expression.

11.
Phys Chem Chem Phys ; 21(31): 17109-17117, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31339132

RESUMO

The semiclassical approaches such as the Meyer-Miller mapping Hamiltonian in conjunction with the symmetrical quasi-classical windowing (MM/SQC) method have been widely used to study nonadiabatic processes in photochemistry but still limited to model Hamiltonians. In this work we implemented the MM/SQC method combined with electronic structure calculations at the level of OM2/MRCI and the on-the-fly nonadiabatic dynamics simulations. The two-state-involved photoisomerization process of cis-azobenzene is employed as a realistic molecular system for validation. The MM/SQC method is able to reproduce the experimental results and provides an alternative to the conventional surface hopping simulations. The optimal windowing procedures such as the window functions and parameters in MM/SQC are suggested for future applications.

12.
BMC Cancer ; 19(1): 705, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315610

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) were approved to have a significant antitumor activity in various tumor types. In practice, some patients do not seem to benefit from ICIs but rather to have accelerating disease. The aim of this study was to evaluate hyperprogression in patients with malignant tumors of digestive system treated with ICIs. METHODS: Medical records from consecutive patients with malignant tumors of digestive system treated with ICIs in Peking University Cancer Hospital were retrospectively collected. Tumor growth kinetics (TGK) on immunotherapy and TGK pre-immunotherapy were collected and TGK ratio (TGKR) was calculated. Hyperprogression was defined as TGKR≥2. RESULTS: From August 2016 to May 2017, 25 evaluable patients were identified from 45 patients with malignant tumors of digestive system. Five patients were considered as having hyperprogression. Three of 5 were neuroendocrine carcinomas (NECs) and the other 2 were adenocarcinomas. Four of 5 were treated with programmed cell death ligand 1 (PD-L1) inhibitor, the other one was treated with PD-L1 inhibitor combined with cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitor. Pseudoprogression was observed in 2 patients. CONCLUSIONS: Hyperprogression was observed in a fraction of patients with malignant tumors of digestive system treated with ICIs. Further investigation is urgently needed.

13.
Cancer Med ; 8(11): 5000-5011, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31293053

RESUMO

PURPOSE: This study aimed to investigate the characteristics of colonic neuroendocrine neoplasms (NENs) and to validate the prognostic value of the European Neuroendocrine Tumor Society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems. METHODS: A total of 167 and 1248 patients with colonic NENs from 12 medical centers across China and from the Surveillance, Epidemiology, and End Results (SEER) cancer registry in the United States, respectively, were reviewed. Patients were staged according to the ENETS and AJCC 8th staging systems. RESULTS: Clinicopathological features of colonic NENs in the Chinese cohort and SEER cohort were significantly distinct. In both the Chinese cohort and the SEER cohort, colonic neuroendocrine carcinoma (NEC) and mixed adeno-neuroendocrine carcinoma (MANEC) were more frequent in the midgut than in the hindgut. Tumors originating from the midgut tended to be larger and at a more advanced stage than those from the hindgut. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC. CONCLUSIONS: Our study revealed that tumors originating from the midgut and the hindgut shared different clinicopathological features. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC.

14.
Theranostics ; 9(12): 3485-3500, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281492

RESUMO

Background: Liver is the most common metastatic site in advanced colorectal cancer. Most patients with colorectal cancer liver metastasis (CRLM) do not benefit from current treatment. Patient-derived xenografts (PDXs) with defined molecular signatures are attractive models for preclinical studies. Methods: Successfully established PDXs were evaluated to elucidate their fidelity of patients' biologic characteristics (pathologic, genetic and protein properties, together with chemosensitivity). The genomic variations of PDXs were analyzed by next-generation sequencing to explore the underlying molecular mechanism of metastasis and potential therapeutic targets. Results: CRLM (N=73) showed a significantly higher successful PDX establishment rate than primary specimens (N=26; 76.7% vs. 57.7%). CRLM PDXs recapitulated the pathologic, genetic and protein properties of parental tumors, as well as chemosensitivity. Frequent altered genes in PDXs showed high consistency compared to patients' genomic alterations and were enriched in MAPK, ErbB, cell cycle, focal adhesion pathways for CRLM PDXs, whereas primary tumor-derived PDXs only exhibited genomic variations involving ErbB and cell cycle. The genetic alterations showed high concordance between paired PDXs from primary and metastatic tissues, except for recurrent gene mutations (ARID1A, CDK8, ETV1, STAT5B and WNK3) and common copy number gains in chromosomes 20q (e.g., SRC/AURKA). Several potential drug targets such as KRAS, HER2, and FGFR2 were validated using corresponding inhibitors. Additionally, PDX models could also be used in screening efficient regimens for patients with no druggable alterations. Conclusion: This study has successfully established and validated a large panel of molecularly annotated platforms from patients with CRLM for preclinical studies.

15.
Exp Cell Res ; 383(1): 111500, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306656

RESUMO

Oxaliplatin has been widely applied in clinical tumor chemotherapy, the treatment failure of which mainly blames on low susceptibility resulted from intrinsic or acquired drug resistance in tumor cells. Microenvironmental hypoxia is one of the important pathological features of solid tumors, which is closely related to the radiochemotherapy tolerance and poor prognosis. Cinnamaldehyde is extracted from Cinnamomum cassia with inhibiting effect against kinds of tumors. In this study, we demonstrated that hypoxia reduced the sensitivity to oxaliplatin in colorectal cancer (CRC) cells via inducing EMT and stemness. Nonetheless, cinnamaldehyde increased the curative effect of oxaliplatin by promoting apoptosis both in vitro and in vivo. Mechanistically, cinnamaldehyde and oxaliplatin synergistically reversed hypoxia-induced EMT and stemness of CRC cells and suppressed hypoxia-activated Wnt/ß-catenin pathway synergistically. These consequences uncovered the potential therapeutic value of cinnamaldehyde and provided novel ideas on improving the sensitivity of oxaliplatin in CRC therapy.

16.
Genomics ; 111(4): 986-996, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31307632

RESUMO

The underlying mechanisms of macrophage polarization have been detected by genome-wide transcriptome analysis in a variety of mammals. However, the transcriptome profile of rat genes in bone marrow-derived macrophages (BMM) at different activation statuses has not been reported. Therefore, we performed RNA-Sequencing to identify gene expression signatures of rat BMM polarized in vitro with different stimuli. The differentially expressed genes (DEGs) among unactivated (M0), classically activated pro-inflammatory (M1), and alternatively activated anti-inflammatory macrophages (M2) were analyzed by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In this study, not only we have identified the changes of global gene expression in rat M0, M1 and M2, but we have also made clear systematically the key genes and signaling pathways in the differentiation process of M0 to M1 and M2. These will provide a foundation for future researches of macrophage polarization.

17.
BMC Pregnancy Childbirth ; 19(1): 254, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331286

RESUMO

BACKGROUND: Poor sleep, including symptoms of insomnia are common during pregnancy and postpartum periods. Poor sleep during the perinatal period is linked to impaired daytime functioning, mood disturbance, and risk for chronic insomnia. Cognitive behavioural therapy (CBT) is consistently shown to be efficacious in treating insomnia, but it is largely inaccessible to new mothers, and surprisingly, not part of current perinatal care. This study aims to evaluate the feasibility and efficacy of a scalable CBT-based intervention for better sleep quality. METHODS: In this single-blind randomised controlled trial, eligible nulliparous women are randomised in a 1:1 ratio to either the intervention (CBT) or active control (healthy diet) condition. The interventions are provided from the third trimester till 6 months postpartum. The primary outcome is maternal sleep quality and secondary outcomes are maternal sleep-related impairment, mood, health-related quality of life, relationship satisfaction, and mother-infant-relationship, all assessed using validated instruments at 30- (baseline) and 35 weeks gestation (pregnancy endpoint), and 1.5, 3, and 6 months (postpartum endpoint) after childbirth, with follow-up assessments conducted at 1-year and 2-year postpartum. DISCUSSION: This study has the potential to address the need for an evidence-based, non-pharmacological sleep intervention tailored for the pregnancy and postpartum periods. The intervention is designed to maximise reach and minimise cost, with the potential to scale up and incorporate in routine perinatal care. With outcomes measured at 8 time points, from the third trimester of pregnancy to 2-year postpartum, this study has the potential to examine both short- and long-term impact on maternal sleep and wellbeing. TRIAL REGISTRATION: ACTRN12616001462471 ; retrospectively registered on 19/10/2016.

18.
Water Environ Res ; 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31233653

RESUMO

Presented in this paper is an annual review of literatures published in 2018 on topics relating to analytical methods for pesticides and herbicides. According to the different techniques, this review is divided into six sections, including extraction methods; chromatographic or mass spectrometric techniques; electrochemical techniques; spectrophotometric techniques; chemiluminescence and fluorescence methods; and biochemical assays. PRACTITIONER POINTS: Totally 134 relevant research articles are summarized. The review is divided into six parts according to the techniques. Chromatographic and mass spectrometric methods are the most widely used.

19.
J Phys Chem Lett ; 10(12): 3376-3380, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31181937

RESUMO

The charge-transport properties of charge-transfer complexes (CTCs) play a key role in the potential applications toward novel optoelectronic devices. We have systematically studied the charge-transport properties of perylene-F4TCNQ CTCs with different stoichiometric ratios by first-principles calculations. Our calculated results showed that 1P1F4 (perylene-F4TCNQ 1:1) exhibits a higher charge-carrier mobility than 3P2F4 (perylene-F4TCNQ 3:2) due to the strong interlayer interactions in 3P2F4. Compared with the perylene-TCNQ CTC, the higher charge-carrier mobility in perylene-F4TCNQ CTC indicates that introducing fluorine atoms can enhance the charge-carrier mobility due to stronger intermolecular interactions. More importantly, the experimental measurements carried out with 1P1F4- and 3P2F4-based field-effect transistors are consistent with the theoretical predictions. Our study reveals that tuning the charge-transport properties in CTCs by controlling the stoichiometry between the donor and acceptor is a promising strategy in accelerating the development of high-performance organic electronic materials.

20.
Cancer Med ; 8(10): 4766-4781, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31243897

RESUMO

BACKGROUND: As the most abundant epigenetic modification on mRNAs and long non-coding RNAs, N6-methyladenosine (m6A) modification extensively exists in mammalian cells. Controlled by writers (methyltransferases), readers (signal transducers), and erasers (demethylases), m6A influences mRNA structure, maturation, and stability, thus negatively regulating protein expression in a post-translational manner. Nevertheless, current understanding of m6A's roles in tumorigenesis, especially in gastric cancer (GC) remains to be unveiled. In this study, we assessed m6A's clinicopathological relevance to GC and explored the underlying mechanisms. METHODS: By referring to a proteomics-based GC cohort we previously generated and the TCGA-GC cohort, we merged expressions of canonical m6A writers (METTL3/METTL14), readers (YTHDF1/YTHDF2/YTHDF3), and erasers (ALKBH5/FTO), respectively, as W, R, and E signatures to represent m6A modification. We stratified patients according to these signatures to decipher m6A's associations with crucial mutations, prognosis, and clinical indexes. m6A's biological functions in GC were predicted by gene set enrichment analysis (GSEA) and validated by in vitro experiments. RESULTS: We discovered that W and R were potential tumor suppressive signatures, while E was a potential oncogenic signature in GC. According to W/R/E stratifications, patients with low m6A-indications were accompanied with higher mutations of specific genes (CDH1, AR, GLI3, SETBP1, RHOA, MUC6, and TP53) and also demonstrated adverse clinical outcomes. GSEA suggested that reduced m6A was correlated with oncogenic signaling and phenotypes. Through in vitro experiments, we proved that m6A suppression (represented by METTL14 knockdown) promoted GC cell proliferation and invasiveness through activating Wnt and PI3K-Akt signaling, while m6A elevation (represented by FTO knockdown) reversed these phenotypical and molecular changes. m6A may also be involved in interferon signaling and immune responses of GC. CONCLUSIONS: Our work demonstrated that low-m6A signatures predicted adverse clinicopathological features of GC, while the reduction of RNA m6A methylation activated oncogenic Wnt/PI3K-Akt signaling and promoted malignant phenotypes of GC cells.

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