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Nitrogen doping has been recognized as an important strategy to enhance the oxygen reduction reaction (ORR) activity of carbon-encapsulated transition metal catalysts (TM@C). However, previous reports on nitrogen doping have tended to result in a random distribution of nitrogen atoms, which leads to disordered electrostatic potential differences on the surface of carbon layers, limiting further control over the materials' electronic structure. Herein, a gradient nitrogen doping strategy to prepare nitrogen-deficient graphene and nitrogen-rich carbon nanotubes encapsulated cobalt nanoparticles catalysts (Co@CNTs@NG) is proposed. The unique gradient nitrogen doping leads to a gradual increase in the electrostatic potential of the carbon layer from the nitrogen-rich region to the nitrogen-deficient region, facilitating the directed electron transfer within these layers and ultimately optimizing the charge distribution of the material. Therefore, this strategy effectively regulates the density of state and work function of the material, further optimizing the adsorption of oxygen-containing intermediates and enhancing ORR activity. Theoretical and experimental results show that under controlled gradient nitrogen doping, Co@CNTs@NG exhibits significantly ORR performance (Eonset = 0.96 V, E1/2 = 0.86 V). At the same time, Co@CNTs@NG also displays excellent performance as a cathode material for Zn-air batteries, with peak power density of 132.65 mA cm-2 and open-circuit voltage (OCV) of 1.51 V. This work provides an effective gradient nitrogen doping strategy to optimize the ORR performance.
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The electrochemical nitrogen reduction reaction is a crucial process for the sustainable production of ammonia for energy and agriculture applications. However, the reaction's efficiency is highly dependent on the activation of the inert N≡N bond, which is hindered by the electron back-donation to the π* orbitals of the N≡N bond, resulting in low eNRR capacity. Herein, we report a main-group metal-non-metal (O-In-S) eNRR catalyst featuring a dynamic proton bridge, with In-S serving as the polarization pair and O functioning as the dynamic electron pool. In-situ spectroscopic analysis and theoretical calculations reveal that the In-S polarization pair acts as asymmetric dual-sites, polarizing the N≡N bond by concurrently back-donating electrons to both the πx* and πy* orbitals of N2, thereby overcoming the significant band gap limitations, while inhibiting the competitive hydrogen evolution reaction. Meanwhile, the O dynamic electron pool acts as a "repository" for electron storage and donation to the In-S polarization pair. As a result, the O-In-S dynamic proton bridge exhibits exceptional NH3 yield rates and Faradaic efficiencies (FEs) across a wide potential window of 0.3 V, with an optimal NH3 yield of 80.07 ± 4.25 µg h-1 mg-1 and an FE of 38.01 ± 2.02%, outperforming most previously reported catalysts.
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Osmotic power, a clean energy source, can be harvested from the salinity difference between seawater and river water. However, the output power densities are hampered by the trade-off between ion selectivity and ion permeability. Here we propose an effective strategy of double angstrom-scale confinement (DAC) to design ion-permselective channels with enhanced ion selectivity and permeability simultaneously. The fabricated DAC-Ti0.87 O2 membranes possess both Ti atomic vacancies and an interlayer free spacing of ≈2.2â Å, which not only generates a profitable confinement effect for Na+ ions to enable high ion selectivity but also induces a strong interaction with Na+ ions to benefit high ion permeability. Consequently, when applied to osmotic power generation, the DAC-Ti0.87 O2 membranes achieved an ultrahigh power density of 17.8â W m-2 by mixing 0.5/0.01â M NaCl solution and up to 114.2â W m-2 with a 500-fold salinity gradient, far exceeding all the reported macroscopic-scale membranes. This work highlights the potential of the construction of DAC ion-permselective channels for two-dimensional materials in high-performance nanofluidic energy systems.
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BACKGROUND: Endometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence suggests that epigenetic regulation is crucial in reproduction. However, the role of N6-methyladenosine (m6A) modification of RNA in endometriosis-related infertility requires further investigation. METHODS: We examined the expression of m6A and methyltransferase-like 3 (METTL3) in endometrial samples taken from normal fertile women in the proliferative phase (the NP group) or the mid-secretory phase (the NS group) or from women with endometriosis-related infertility at the mid-secretory phase (the ES group). We treated primary endometrial stromal cells (ESCs) with medroxyprogesterone acetate and 8-Bromo-cyclic adenosine monophosphate for in vitro decidualization and detected the expression of m6A, METTL3, and decidual markers. We analyzed the expression of m6A, METTL3, and forkhead box O1 (FOXO1) in ESCs from normal fertile women (the ND group) or women with endometriosis-related infertility (the ED group). We also assessed the expression of m6A, METTL3, and decidual markers, as well as the embryo adhesion rate, upon METTL3 overexpression or knockdown. Additionally, we investigated the role of METTL3 in embryo implantation in vivo by applying mice with endometriosis. Furthermore, we performed RNA stability assays, RNA immunoprecipitation (RIP), and methylated RIP assays to explore the mechanisms underlying the regulation of FOXO1 by METTL3-mediated m6A. RESULTS: The expression of m6A and METTL3 was reduced only in the NS group; the NP and ES groups demonstrated increased m6A and METTL3 levels. m6A and METTL3 levels decreased in ESCs with prolonged decidual treatment. Compared to the ND group, m6A and METTL3 levels in the ED group increased after decidual treatment, whereas the expression of FOXO1 decreased. METTL3 overexpression suppressed the expression of decidual markers and embryo implantation in vitro; METTL3 knockdown exhibited the opposite effect. Inhibition of METTL3 promoted embryo implantation in vivo. Furthermore, we observed that METTL3-mediated m6A regulated the degradation of FOXO1 mRNA through YTHDF2, a m6A binding protein. CONCLUSIONS: METTL3-regulated m6A promotes YTHDF2-mediated decay of FOXO1 mRNA, thereby affecting cellular decidualization and embryo implantation. These findings provide novel insights into the development of therapies for women with endometriosis-related infertility.
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Endometriose , Infertilidade Feminina , Animais , Feminino , Humanos , Camundongos , Endometriose/complicações , Endometriose/genética , Epigênese Genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Células Estromais/metabolismo , Fatores de Transcrição/genética , Infertilidade Feminina/metabolismoRESUMO
How to overcome the problem of fast capacity fading and low sulfur utilization is the key to promote the practical applications of lithium-sulfur (Li-S) batteries. Based on the fact that sulfur-functionalized graphene oxide (GO-S) can avoid the loss of sulfur/polysulfides through the strong C-S interaction, and the zeolitic imidazolate framework (ZIF-67) can capture sulfur and catalyze lithium polysulfide (Li2Sx, 4 ≤ x ≤ 8), the combination of ZIF-S (ZIF-67 after combining with sulfur) with GO-S can be expected to be an excellent electrode material for Li-S batteries due to the synergistic effect. Herein, ZIF-S@GO-S (n) nanocomposites (n = 1, 2, and 3 for the mass ratio of ZIF-67/GO of 4:1, 6:1, and 8:1, respectively) as the cathode materials in Li-S batteries were successfully fabricated, and ZIF-S@GO-S (2) showed better electrochemical performances and cycle stability with a high specific capacity of 1529.5 mA h g-1 at the initial cycle and 792 mA h g-1 after 500 cycles at 0.1 C (1 C = 1675 mA h g-1). The fact that ZIF-S@GO-S (n) can simultaneously improve the conductivity and utilization of S (C-S···S8 and C-S···SxLi2) and the conversion kinetics of Li2Sx (4 ≤ x ≤ 8) provides a new avenue for designing and fabricating promising cathodes for high-performance Li-S batteries.
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BACKGROUND: Advanced paternal age (APA) is associated with decreased fertility, but the mechanism underlying APA remains unknown. CircRNAs have been reported to be ideal candidate biomarkers for diagnostic and therapeutic applications in many diseases and are also involved in spermatogenesis. Hence, we aimed to assess the circRNA expression profile of spermatozoa from aging men. METHODS AND RESULTS: We recruited 6 subjects, including 3 in the younger group (men age < 40) and 3 in the APA group (men age ≥ 40). RNA sequencing was exploited to identify the expression profiles of circRNAs between the two groups. The expression levels of circRNAs were validated using real-time quantitative polymerase chain reaction (RT-qPCR). Kyoto Encyclopedia of Genes and Genomes biological pathway analysis and Gene Ontology analysis were performed to evaluate the functions of differentially expressed circRNAs (DE-circRNAs) between the two groups. In total, 18,787 circRNAs were sequenced in the spermatozoa of two groups. Our analysis revealed that there were 1056 downregulated circRNAs and 1228 upregulated circRNAs between the two groups, and KEGG analysis showed they were mainly involved in pathways including the DNA repair signaling pathway, meiotic recombination signaling pathway, and PI3K/AKT signaling pathway. CONCLUSIONS: In conclusion, our study suggested that circRNAs play a vital role in spermatozoa from aging men and provided a fresh perspective on the specific regulatory mechanism of spermatozoa from aging men.
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MicroRNAs , RNA Circular , Masculino , Humanos , RNA Circular/genética , Fosfatidilinositol 3-Quinases/genética , Espermatozoides , Envelhecimento/genética , MicroRNAs/genéticaRESUMO
This data article presents data from the China Migrants Dynamic Survey (CMDS), a multi-wave, large-scale national cross-sectional survey of China's internal migrants from 2009 to 2018. The CMDS is an annual questionnaire survey conducted by the former National Health and Family Planning Commission (NHFPC) of the People's Republic of China. The respondents included in this survey are internal migrants over 15 years old. The sample was drawn from the China Migrant Population Information System, using multi-stage stratified sampling method and the probability proportional-to-size (PPS) cluster sampling strategy. Between 2009 and 2018, there were 1,527,650 internal migrants from 23 provinces, 5 autonomous regions and 4 municipalities participated in the surveys. The survey tools were a series of self-designed questionnaires with high inheritance and consistency designed and implemented by the NHFPC. The questionnaires mainly contain basic information of the respondents and their family members, migration status, healthcare or health behaviors, public health service utilization, social insurance, social integration, and family planning. The dataset is currently the most widely used survey data on China's internal migrants, offering information on migration patterns, healthcare and health behaviors, use of public health services, access to social security, social integration, and family planning, which are valuable for health planning, health decision-making, and health equity research.
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Serviços de Planejamento Familiar , Migrantes , Estados Unidos , Humanos , Adolescente , Estudos Transversais , China/epidemiologia , Inquéritos e QuestionáriosRESUMO
To address the poor cycling stability and low rate capability of MoS2 as electrode materials for lithium-ion batteries (LIBs), herein, the CoS2 /MoS2 /PDDA-rGO/PMo12 nanocomposites are constructed via a simple hydrothermal process, combining the advantages of all three, namely, CoS2 /MoS2 heterojunction and polyoxometalates (POMs) provide abundant catalytically active sites and increase the multi-electron transfer ability, and the positively charged poly(diallyldimethylammonium chloride) modified reduced graphene oxide (PDDA-rGO) improve electronic conductivity and effectively prevent the aggregation of MoS2 , meanwhile stabilize the negatively charged [PMo12 O40 ]3- . After the electrochemical testing, the resulting CoS2 /MoS2 /PDDA-rGO/PMo12 nanocomposite achieved 1055â mA h g-1 initial specific capacities and stabilized at 740â mA h g-1 after 150 cycles at 100â mA g-1 current density. And the specific capacities of MoS2 , MoS2 /PDDA-rGO, CoS2 /MoS2 , and CoS2 /MoS2 /PDDA-rGO were 201, 421, 518, and 589 at 100â mA g-1 after 150 cycles, respectively. The fact of the greatly improving capacity of MoS2 -based nanocomposites suggests its potential for high performance electrode materials of LIBs. Moreover, the lithium storage mechanism of CoS2 /MoS2 /PDDA-rGO/PMo12 has been discussed on the basis of cyclic voltammetry with different scan rates.
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PURPOSE: Ang II regulates RhoGDI1 stability and cell proliferation via SUMOylation. However, how Ang II regulates RhoGDI1 SUMOylation remains unknown. In this study, we focused on revealing the effects of E1 subunits (Aos1 and Uba2) on RhoGDI1 SUMOylation in HA-VSMC proliferation. METHODS: The expressions of Aos1, Uba2, and SUMO1 were suppressed by siRNA transfection. HA-VSMCs were treated with Ang II (100 nM) for 24 h. RhoGDI1 SUMOylation and ubiquitination were checked by co-immunoprecipitation. Cell proliferation was detected by EdU assay. RESULTS: Uba2 or Aos1 suppression significantly inhibited Ang II-induced SUMO2/3 modification of RhoGDI1 and cell proliferation, while not affecting SUMO1 modification of RhoGDI1. In addition, Uba2 or Aos1 suppression promoted RhoGDI1 ubiquitination and degradation. These indicate that both Uba2 and Aos1 are necessary for SUMO2/3 modification of RhoGDI1 that participates in cell proliferation by regulating RhoGDI1 ubiquitination and stability. Moreover, SUMO1 suppression did not affect RhoGDI1 ubiquitination and degradation and cell proliferation in Ang II-induced VSMCs, suggesting that SUMO1 modification does not participate in RhoGDI1 stability and cell proliferation. CONCLUSION: This study reveals the differences between SUMO2/3 and SUMO1 modification in regulating RhoGDI1 stability and Ang II-mediated cell proliferation. Schematic summary of roles of SUMO1 and SUMO2/3 modification of RhoGDI1 in regulating RhoGDI1 stability and cell proliferation in Ang II-treated HA-VSMCs.
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Músculo Liso Vascular/fisiologia , Proteína SUMO-1/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Enzimas Ativadoras de Ubiquitina/metabolismo , Ubiquitinas/metabolismo , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/metabolismo , Angiotensina II/metabolismo , Proliferação de Células/fisiologia , Humanos , Contração Muscular/fisiologia , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Sumoilação , UbiquitinaçãoRESUMO
BACKGROUND: Mental disorders impose heavy burdens on patients' families and children. It is imperative to provide family-focused services to avoid adverse effects from mental disorders on patients' families and children. However, implementing such services requires a great deal of involvement of mental health workers. This study investigated the attitudes, knowledge, skills, and practices in respect to family-focused practices (FFP) in a sample of Chinese mental health workers. METHODS: A cross-sectional study design was employed to examine the attitudes, knowledge, skills, and practices of a convenience sample of Chinese mental health workers in respect to FFP, using the Chinese version of the Family-Focused Mental Health Practice Questionnaire (FFMHPQ). RESULTS: In total, 515 mental health workers participated in our study, including 213 psychiatrists, 269 psychiatric nurses, and 34 allied mental health professionals (20 clinical psychologists, 9 mental health social workers, and 4 occupational therapists). Compared with psychiatric nurses, psychiatrists and allied mental health professionals provided more support for families and children of patients with mental illness and were more willing to receive further training in FFP. However, there were no significant differences on knowledge, skills, and confidence across different profession types. After adjusting for demographic and occupational variables, previous training in FFP was positively associated with mental health workers' knowledge, skills, and confidence about FFP, but not actual support to families and children. CONCLUSIONS: Professional differences on FFP exist in Chinese mental health workers. Training is needed to engage psychiatrists and other allied workforce in dissemination and implementation of FFP in China.
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Transtornos Mentais , Enfermagem Psiquiátrica , Criança , China , Estudos Transversais , Pessoal de Saúde , Humanos , Transtornos Mentais/terapia , Saúde MentalRESUMO
Due to the redox properties closely related to numerous physiological and pathological processes, biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), have received considerable attention in biological science. On account of the important physiological roles of these biothiols, it is of profound significance to develop sensitive and selective detection of biothiols to understand their biological profiles. In this work, we reported an efficient fluorescent probe, PHPQ-SH, for detecting biothiols in vitro and vivo, based on the phenothiazine-HPQ skeleton, with DNBS (2,4-dinitrobenzenesulfonate) as the response unit. Probe PHPQ-SH exhibited brilliant sensing performances toward thiols, including a large Stokes shift (138 nm), excellent sensitivity (for GSH, LOD = 18.3 nM), remarkable fluorescence enhancement (163-fold), low cytotoxicity, rapid response (8 min), and extraordinary selectivity. Finally, the probe PHPQ-SH illustrated herein was capable of responding and visualizing biothiols in MCF-7 cells and zebrafish.
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Técnicas Biossensoriais , Corantes Fluorescentes/isolamento & purificação , Quinazolinonas/química , Compostos de Sulfidrila/isolamento & purificação , Animais , Corantes Fluorescentes/química , Glutationa/química , Células HeLa , Humanos , Células MCF-7 , Imagem Óptica , Fenotiazinas , Compostos de Sulfidrila/química , Peixe-ZebraRESUMO
As an abundant marine xanthophyll, fucoxanthin (FX) exhibits a broad range of biological activities. The preparation of high-purity FX is in great demand, however, most of the available methods require organic solvents which cannot meet the green chemistry standard. In the present study, a simple and efficient purification approach for the purification of FX from the brown seaweed Sargassum horneri was carried out. The FX-rich ethanol extract was isolated by octadecylsilyl (ODS) column chromatography using ethanol-water solvent as a gradient eluent. The overwhelming majority of FX was successfully eluted by the ethanol-water mixture (9:1, v/v), with a recovery rate of 95.36%. A parametric study was performed to optimize the aqueous ethanol precipitation process by investigating the effects on the purity and recovery of FX. Under the optimal conditions, the purity of FX was 91.07%, and the recovery rate was 74.98%. Collectively, the eco-friendly method was cost-efficient for the purification of FX. The developed method provides a potential approach for the large-scale production of fucoxanthin from the brown seaweed Sargassum horneri.
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Etanol/química , Sargassum/química , Xantofilas/química , Xantofilas/isolamento & purificação , CromatografiaRESUMO
The formulation of expert consensus on clinical application of Chinese patent medicines, in means of exploring the effective combination of experience and evidence to form a research method in line with the characteristics of Chinese patent medicines, is an important transitional stage for clinical researches on Chinese patent medicines. Pre-searching is a new step in the formulation of expert consensus on clinical application of Chinese patent medicines. Before steps of interview and investigation on clinical application, pre-searching is conducted to collect publications and literature on certain variety and similar Chinese patent medicines; the publications on related medical classics and formulas of this variety; the recommendation condition of this variety in clinical practice guidelines and expert consensus; and the medication regimens recommended in disease-specific guidelines. Pre-searching is designed to know about the advantages of certain variety of Chinese patent medicine as well as its potential problems recorded in the literature, which is helpful to find out the clinical positioning of Chinese patent medicines, develop reasonable clinical questions and provide ideas for formal literature searching. However, it is not the direct basis for developing clinical questions. Moreover, interviews and investigations are still needed to further clarify the clinical positioning of Chinese patent medicines and develop reasonable questions. This paper took expert consensus on clinical application of Yanshen Jianwei Capsules as an example to introduce the pre-searching process and methods used during formulation of expert consensus on clinical application of Chinese patent medicines, and to further discuss the role of pre-searching to facilitate the formulation of clinical questions on selection of participants, interventions, controls and outcomes.
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Medicamentos de Ervas Chinesas , Medicamentos sem Prescrição , Cápsulas , China , Consenso , Humanos , Medicina Tradicional ChinesaRESUMO
A temporal dissipative Kerr soliton (DKS) frequency comb can be generated in an optical micro-cavity relying on the rigid balance between cavity decay (dispersion) and parametric gain (nonlinear phase modulation) induced by an intense pump laser. In practice, to maintain such delicate double balances experienced by the intracavity soliton pulses, it requires precise control of the pump laser frequency and power, as well as the micro-cavity parameters. However, to date there still lacks experimental demonstration that simultaneously stabilizes all these key parameters to enhance the long-term DKS stability. Here, we demonstrate continuous working of a on-chip DKS microcomb for a record-breaking 14 days without showing any sign of breakdown. Such improved microcomb stability is enabled mainly by robust pump power coupling to the micro-cavity utilizing packaged planar-lightwave-circuit mode converters, and faithful locking of the pump frequency detuning via an auxiliary laser heating method. In addition to superior stability, the demonstrated DKS microcomb system also achieves favorable compactness, with all the accessory modules being assembled into a standard 4U case. We hope that our demonstration could prompt the practical utilization of Kerr microcombs in real-world applications.
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A new 12-tungstovanadate-templated 3D nanocage framework, Ag10(µ4-ttz)4(H2O)4(VW12O40) (VW12@MOCF), was designed based on a "molecular library", hydrothermally synthesized, structurally characterized, and explored as anode material for lithium-ion batteries (LIBs). Combination of the structural superiority of VW12@MOCF with the good electrical conductivity of the single-walled carbon nanotubes (SWNTs) renders the VW12@MOCF/SWNT-2 nanocomposite reasonable electrochemical performance and stability as anode materials of LIBs. The successful cooperative fabrication of nanocages and polyoxometalate (POMs) must initiate extensive research interests.
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BACKGROUND: In this study, we investigated the mechanism of Rho GTPases signaling on Ang II-mediated cell migration and dedifferentiation in human aortic vascular smooth muscle cells (HA-VSMCs) and an Ang II-infusion mouse model. METHODS: Cells were pretreated with different inhibitors or Ang II. Cell migration was detected by Wound healing and Transwell assay. Mice were treated with Ad-RhoA-shRNA virus or Irbesartan or fasudil and then infused with Ang II. RESULTS: Ang II treatment induced HA-VSMCs migration in a dose- and time-dependent manner and reduced the expression of VSMC contractile proteins. These effects were significantly suppressed by the inhibition of Ang II type 1 receptor (AT1 receptor), RhoA, and Rho-associated kinase (ROCK). Furthermore, Ang II treatment promoted the activation of RhoA and ROCK, which was reduced by AT1 receptor inhibition. Meanwhile, Ang II treatment induced F-actin polymerization, which was inhibited after ROCK inhibition. In mice, Ang II infusion increased VSMC migration into the neointima and reduced VSMC differentiation proteins levels, and these effects were shown to be dependent on AT1 receptor and RhoA/ROCK pathway. CONCLUSION: This study reveals a novel mechanism by which Ang II regulates RhoA/ROCK signaling and actin polymerization via AT1 receptor and then affects VSMC dedifferentiation.
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Citoesqueleto de Actina/efeitos dos fármacos , Angiotensina II/farmacologia , Desdiferenciação Celular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/genética , Quinases Associadas a rho/genética , Proteína rhoA de Ligação ao GTP/genética , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Citoesqueleto de Actina/genética , Citoesqueleto de Actina/metabolismo , Actinas/genética , Actinas/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Irbesartana/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Polimerização/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Transdução de Sinais , Vasodilatadores/farmacologia , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Breast cancer (BC) is a fatal malignancy, which has a high incidence and mortality across the world. Circular RNAs (circRNAs) have crucial roles in tumor initiation and progression. In this project, a newly found circRNA, circ_0103552 was explored. Quantitative real-time polymerase chain reaction was applied to measure its expression in the patients' tissue specimens and cells. In addition, Fisher's exact test, Kaplan-Meier curves and Cox regression model were conducted to discover the clinical significance of circ_0103552. Cell viability, clone-forming ability, apoptosis, and metastatic properties of BC cells were evaluated by gain/loss-of-function assays. Dual luciferase reporter assay was applied to illuminate its mechanisms. As data indicated, circ_0103552 was significantly elevated in BC tissue samples and cells. In addition, its expression correlates with clinical severity and dismal prognosis. Furthermore, circ_0103552 could facilitate cell growth, clone-forming ability, migration and invasion, and decrease apoptotic cells. For the mechanism exploration, circ_0103552 could directly sponge miR-1236 to execute oncogenic activities in BC cells. In summary, this study provides a novel circRNA in tumorigeneis and progression of BC and may help to develop effective therapeutic target for this devastating disease.
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Neoplasias da Mama/genética , Carcinogênese/genética , MicroRNAs/genética , RNA Circular/genética , Apoptose/genética , Neoplasias da Mama/patologia , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
Synthetic CRISPR-Cas transcription factors enable the construction of complex gene-expression programs, and chemically inducible systems allow precise control over the expression dynamics. To provide additional modes of regulatory control, we have constructed a chemically inducible CRISPR activation (CRISPRa) system in yeast that is mediated by recruitment to MS2-functionalized guide RNAs. We use reporter gene assays to systematically map the dose dependence, time dependence, and reversibility of the system. Because the recruitment function is encoded at the level of the guide RNA, it is straightforward to target multiple genes and independently regulate expression dynamics at individual targets. This approach provides a new method to engineer sophisticated, multigene programs with precise control over the dynamics of gene expression.
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Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , RNA Guia de Cinetoplastídeos/genética , Saccharomyces cerevisiae/genética , Expressão GênicaRESUMO
Temporarily storing light occupies a pivotal position in all-optical packet switching network and microwave photonics. An integrated optical buffer with large capacity and low loss is demonstrated on a silica wafer. The optical buffer consists of four silica waveguide delay lines connected by five thermo-optic switches. With different switch combinations applied, related delay lines are selected to realize a different storage time in the buffer, and a storage time up to 100 ns with a 10-ns step size is implemented. By optimizing the fabrication process and introducing the offsets between straight and bending waveguides, the propagation loss as low as ~1.08 dB/m is achieved. This large-capacity and low-loss buffer enables broad applications in optical communications and microwave photonics.
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Background: Epigenetic silencing of tumor suppressor genes plays important role in acute myeloid leukemia (AML). Recently, SPRED1, a negative regulator of the RAS MAPK pathway, is identified as a tumour suppressor downregulated in AML. However, little is known regarding its underlying dysregulation in AML. In this study, we investigated methylation status of SPRED1 promoters and their association with mRNA levels in AML. Methods: Methylation level were measured in four regions of SPRED1 (#1: 310 bp ~ 723 bp, #2: 810 bp ~ 1299 bp, #3: 1280 bp ~ 1742 bp and #4: 1715 bp ~ 2059 bp) in a total of 16 patients with de novonon-acute promyelocytic leukemia (non-APL) and three patients who got complete remission after induction treatment using the Sequenom MassARRAY platform. Quantitative real-time polymerase chain reaction (q-RT PCR) was used to analyze SPRED1 mRNA levels. Results: AML patients had a significantly higher average methylation level than controls at regions of #1_CpG_1 (p= 0.04) and #1_CpG_11 (p =0.002). The methylation values for #1_CpG_11 were negatively correlated with mRNA levels (r= -0.558, p=0.013) but there was no significant association between #1_CpG_1 methylation status and mRNA levels (r=-0.103, p=0.675) in AML patients. There was no significant difference in the methylation level when comparing with clinical biochemical parameters and treatment response (p>0.05). Mutations of epigenetic regulation genes such as DNMT3A, TET2 and IDH1/2 were most frequently observed in patients with higher methylation levels. Decreased methylation levels were revealed in three patients who got complete remission. Conclusions: Aberrant methylation statuses of the SPRED1 promoter regions are associated with the downregulation of gene transcription in AML. The methylation level is probably associated with the treatment response of AML. Mutations of epigenetic regulation genes might be involved in the epigenetic aberration of SPRED1.