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1.
PLoS Biol ; 17(10): e3000461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31600191

RESUMO

Dendritic spine development is crucial for the establishment of excitatory synaptic connectivity and functional neural circuits. Alterations in spine morphology and density have been associated with multiple neurological disorders. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. However, the role of DIP2A in the brain remains largely unknown. In this study, we found that deletion of Dip2a in mice induced defects in spine morphogenesis along with thin postsynaptic density (PSD), and reduced synaptic transmission of pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. Furthermore, Dip2a knockout (KO) mice exhibited autism-like behaviors, including excessive repetitive behaviors and defects in social novelty. Importantly, acetylation mimetic cortactin restored the impaired synaptic transmission and ameliorated repetitive behaviors in these mice. Altogether, our findings establish an initial link between DIP2A gene variations in autism spectrum disorder (ASD) and highlight the contribution of synaptic protein acetylation to synaptic processing.

2.
Chem Commun (Camb) ; 55(80): 12004-12007, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31503273

RESUMO

Single-stranded DNA designed G-quadruplexes, modified with lipophilic 12-carbon spacers and cholesterol to span lipid membranes, were developed as smart transmembrane channels for selective and switchable potassium ion (K+) transport across membranes.

3.
Anal Chem ; 91(19): 12538-12545, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31476869

RESUMO

The efficient and precise delivery of antisense oligonucleotides (ASOs) to target cells is of great value in gene silencing. However, the specificity and packaging capacity of delivery system still remains challenging. Here, we designed an i-motif forming-initiated in situ bipedal hybridization chain reaction (pH-Apt-BiHCR) amplification strategy for specific target cells imaging and enhanced gene delivery of ASOs. As a proof of concept, an 8-nt ASO modified with locked nucleic acid (LNA) which is complementary to the seed region of microRNA21 (miR-21) was used for gene silencing studies. Benefiting from the design of hairpin-contained i-motif, the stimuli-responsive assembly of pH-Apt-BiHCR was successfully achieved on MCF-7 cells surface based on the specific recognition of aptamer. Using this strategy, the pH-Apt-BiHCR not only contains repeated fluorescence resonance energy transfer (FRET) units for activatable tumor imaging with high contrast but also arrays with plenty of LNA ASOs as interference molecules for cancer cells inhibition. An in vitro assay showed that this strategy presented an excellent response ability in buffer within a narrow pH range (6.0-7.0) with a transition midpoint (pHT) of 6.44 ± 0.06. Moreover, live cell studies revealed that it realized a specific activatable imaging of target cells, while the ASOs arrayed pH-Apt-BiHCR exhibited improved internalization via an endocytosis pathway and enhanced gene silencing to MCF-7 cells compared to single ASO alone. We believe that this design will inspire the development of novel probes for early diagnosis and therapy of cancer cells.

4.
J Mater Chem B ; 7(39): 5992-5997, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31536078

RESUMO

A near-infrared light triggered photothermal H2S-release platform was developed using a combination of photothermal nanoparticles and thermo-labile precursors, and was exploited for synchronous photothermal stimulation and gas release to suppress cell viability. Polyethyleneimine-dithiocarbamate as a H2S donor was assembled on reduced graphene oxide (rGO) nanosheets by electrostatic adsorption. In the nanocomposites, rGO nanosheets converted near-infrared light into thermal energy and activated the H2S donor to produce H2S. Synchronous photothermal stimulation and H2S gas release resulted in effective killing of cancer cells. This work presents an effective method that suppresses the growth of tumour cells and leads to an improved anti-cell proliferation outcome. Near-infrared light-triggered photothermal stimulation, in combination with H2S gas generation, may offer an effective strategy to further develop a cancer synergistic treatment platform.

5.
J Investig Med ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31431469

RESUMO

Hepatocellular Carcinoma (HCC) is one of the most common malignancies in the world, and is well-known for its bad prognosis. Potassium calcium-activated channel subfamily N member 4 (KCNN4) is a type of intermediate conductance calcium-activated potassium channel, and increasing evidence suggests that KCNN4 contributes to the regulation of invasion and metastasis in a number of cancers. However, its clinical significance and biological function remain unclear in the HCC disease process. In this study, the expression levels of KCNN4 in 86 HCC samples were compared with corresponding paracancerous tissues. sh-RNA was used to reduce the expression of KCNN4 in Hep3B HCC cells in vitro; this was confirmed by Real time-PCR and western blotting. Wound healing, transwell assays and high content analysis were performed to investigate the tumor-promoting characteristics of KCNN4 in Hep3B HCC cells. As results, KCNN4 expression was significantly associated with preoperative serum alpha-fetoprotein level (p=0.038) and TNM stage (p=0.039). Additionally, patients with high KCNN4 amplification in HCC tissue exhibited shorter disease-free survival, whereas there was no statistical significance between KCNN4 amplification and overall survival. Wound healing and transwell assays showed that knockdown of KCNN4 expression could reduce migration and invasion abilities of HCC cells. High content analysis result showed that down-regulated KCNN4 could inhibit the ability of HCC cell proliferation. The mitogen-activated protein kinase (MAPK) pathway is active in cell proliferation, differentiation, migration, senescence, and apoptosis. Matrix metallopeptidase 9 and extracellular signal regulated kinase 1/2 (ERK1/2) were important biomarkers of MAPK/ERK pathway, knockdown of KCNN4 reduced the expression of MMP9 and ERK1/2. These findings showed that KCNN4 promotes HCC invasion and metastasis through the MAPK/ERK pathway.

6.
Analyst ; 144(16): 4917-4924, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31313769

RESUMO

MicroRNAs (miRNAs) are attractive candidates for biomarkers for early cancer diagnosis, and play vital roles in physiological and pathological processes. In this work, we developed a colorimetric and fluorescent dual-mode sensor for miRNA detection based on the optical properties of gold nanoparticles (AuNPs) and the duplex-specific nuclease (DSN)-assisted signal amplification technique. In brief, FAM labelled hairpin probes (HPs) were immobilized on AuNPs, and fluorescence was efficiently quenched by the vicinity of the fluorophores to the AuNPs surface. In the presence of target miRNAs, the HPs could specifically hybridize with miRNAs and the DNA strand in the DNA/RNA heteroduplexes could be subsequently hydrolyzed by DSN. As a result, numbers of fluorophores were released into the solution, resulting in obvious fluorescence signal recovery. Meanwhile, the target miRNAs were able to participate in other hybridization reactions. With the DSN-assisted signal amplification technique, lots of gold nanoparticles were produced with short-chain DNA on their surface, which could aggregate in salt solution and result in a colorimetric detection. The proposed dual-mode strategy offers a sensitive, accurate and selective detection method for miRNAs. One reason is that the stem of the HPs was elaborately designed to avoid hydrolyzation by DSN under optimal conditions, which ensures a relatively low background and high sensitivity. The other is that the dual-mode strategy is more beneficial for enhancing the accuracy and reproducibility of the measurements. Moreover, the unique selective-cutting ability and single-base mismatch differentiation capability of the DSN also give rise to a satisfactory selectivity. This demonstrated that the developed method could quantitatively detect miR-21 down to 50 pM with a linear calibration range from 50 pM to 1 nM, and the analytical assay of target miRNAs in cell lysate samples revealed its great potential for application in biomedical research and clinical diagnostics.


Assuntos
Corantes/química , Endonucleases/química , Ouro/química , Nanopartículas Metálicas/química , MicroRNAs/análise , Técnicas Biossensoriais/métodos , Linhagem Celular , Colorimetria , DNA/química , Humanos , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Conformação de Ácido Nucleico , Ácidos Nucleicos Heteroduplexes/química , Hibridização de Ácido Nucleico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Fluorescência
7.
J Phys Chem A ; 123(30): 6463-6471, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282159

RESUMO

It has been a long-lasting debate whether indigo undergoes excited-state proton transfer and how this contributes to its photostability. A prevailing point of view is that a sub-picosecond excited-state intramolecular single proton transfer occurs; however, it has been studied mostly under dilute solution conditions. In this work, excited-state structural dynamics of indigo oligomers formed at millimolar concentration in dimethyl sulfoxide is investigated using femtosecond visible pump spectroscopy, infrared and visible probe spectroscopies, and steady-state infrared and fluorescence spectroscopies. Experimental evidence indicates the presence of transient intermolecular electronic excited-state proton transfer, which is supported by quantum-chemistry computations. The formed enol species disappears with a time constant of 200-300 fs, followed by a relatively slow nonradiative relaxation to the electronic ground state. Our results reveal new photochemistry of indigo particularly in its oligomeric state.

8.
Theranostics ; 9(15): 4494-4507, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285775

RESUMO

Purpose: Exosomes (EXs) have been increasingly recognized as natural nanoscale vehicles for microRNA (miRNA)-based cell-cell communication and an ideal source of miRNA biomarkers in bodily fluids. Current methods allow bulk analysis of the miRNA contents of EXs, but these approaches are not suitable for the in situ stoichiometry of exosomal miRNAs and fail to reveal phenotypic heterogeneity at the single-vesicle level. This study aimed to develop a single vesicle-based, mild, precise, but versatile method for the in situ quantitative and stoichiometric analysis of exosomal miRNAs. Methods: A total internal reflection fluorescence (TIRF)-based single-vesicle imaging assay was developed for direct visualization and quantification of the single-vesicles of EXs and their miRNA contents in serum microsamples. The assay uses co-delivery of inactive split DNAzymes and fluorescence-quenched substrates into nanosized EXs treated with streptolysin O to produce a target miRNA-activated catalytic cleavage reaction that amplifies the readout of fluorescence signal. We perform the in situ quantitative and stoichiometric analysis of serum exosomal hsa-miRNA-21 (miR-21), a common cancer biomarker, by using the developed TIRF imaging assay. Results: The TIRF imaging assay for serum exosomal miR-21 can distinguish cancer patients from healthy subjects with better performance than conventional real-time polymerase chain reaction (PCR) assay. The exosomal miR-21 level in serum is also informative for monitoring tumor progression and responses to treatment. Moreover, the TIRF assays can readily determine the precise stoichiometry of target exosomal miRNA contents in situ by delivering molecular beacon (MB) probes into EXs. Conclusions: The created TIRF imaging platform shows high applicability to serve as a universal and useful tool for the single-vesicle in situ quantitative and stoichiometric analysis of other disease-associated exosomal miRNAs markers and provide valuable insight into the physiological relevance of EX-mediated miRNA communication.

9.
Anal Chem ; 91(16): 10672-10678, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31355629

RESUMO

In this work, based on mesoporous silica containers (MSNs) with the programmed enzyme-free DNA assembly amplification of catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR), an ultrasensitive electrochemical sensing platform with low background is developed for the detection of microRNA (miRNA). Herein, the electrochemical reporter methylene blue (MB) was sealed in the pores of MSNs by the double-stranded DNA (dsDNA) gate of hairpin DNA H1 and anchor DNA. In the absence of target, neither the CHA nor the HCR process happened, which enabled a low background. After target was added, DNA H1 was displaced from the MSNs surface and participated in the CHA process with the assistance of hairpin DNA H2, which accelerated the release of MB from the MSNs pore. Meanwhile, the CHA products H1-H2 were hybridized with the capture probes (SH-CP) on the electrode surface, which further initiated the HCR process. The released MB from the MSNs will effectively intercalate into long dsDNA polymers of HCR products, resulting in a significant electrochemical response. Taking miRNA-21 as the model target, the proposed sensing platform achieves a satisfactory detection limit down to 0.037 fM, which is lower than that of electrochemical assay with amplification methods. In addition, the strategy shows good selectivity against other miRNAs and is capable in practical analytes. Benefitting from the features of being label-free and enzyme-free and having low background, high sensitivity, and selectivity, this strategy shows great potential in bioanalysis and clinical diagnostics.

10.
Talanta ; 202: 214-220, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171173

RESUMO

A novel nanosensor is developed for selective and highly sensitive detection of phytic acid (PA) based on small-sized conjugated polyelectrolyte dots (Pdots) fabricated from a new conjugated polymer (P1) by a modified reprecipitation method. P1 featuring a π-delocalized backbone bearing meta-substituted pyridyl groups can be endowed with enhanced flexibility and hence is beneficial for the synthesis of ultrasmall Pdots (i.e. Pdot-1, ∼3.8 nm in average diameter) as well as for the binding of Fe3+, thus leading to the obvious fluorescence quenching of Pdot-1 (∼444 nm) in the presence of Fe3+ via an electron transfer (ET) process. In addition, phytic acid with six phosphate groups exhibits strong chelating ability. When phytic acid is added, phytic acid readily binds to Fe3+ and the fluorescence of Pdot-1 around 444 nm can be recovered, rendering the supersensitive and selective sensing of PA. Under the optimum conditions, this ultra-small Pdot-based nanoprobe favors the fluorescent determination of PA with the detection limit as low as 10 nM. Particularly, Pdot-1 with bright blue fluorescence exhibits low cytotoxicity. Furthermore, the small-sized and biocompatible Pdot-1 can be applied to the sensitive fluorescence assay for PA in cell extracts and the efficient imaging of PA in live cells.

11.
J Endocrinol ; 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31176306

RESUMO

Glucocorticoids (GCs) are a class of steroid hormones that regulate numerous physiological events in the human body. Clinically, glucocorticoids are used for anti-inflammatory and immunosuppressive actions via binding with glucocorticoid receptors (GRs). Emerging evidence has also indicated that inappropriate GC and GR levels are detrimental for brain development and eventually lead to severe neurological diseases. However, the roles of GC/GR signaling in brain development are not fully understood. Here, we showed that stable GR expression levels were critical for brain development, because both GR knockdown and overexpression severely impaired neuronal migration. Further studies showed that the multipolar-bipolar transition and leading process development were interrupted in GR-knockdown and GR-overexpressing neurons. To elucidate the underlying mechanism, we screened the protein levels of downstream molecules and identified RhoA as a factor negatively regulated by the GR. Restoration of the RhoA protein level partially rescued the neuronal migration defects in the GR-knockdown and GR-overexpressing neurons, indicating that RhoA played a major role in GR-mediated neuronal migration. These data suggest that an appropriate level of GC/GR signaling is essential for precise control of neuronal migration.

12.
Talanta ; 202: 152-158, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171163

RESUMO

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world, which can lead to considerably high mortality rate. It was reported that the prognosis is extremely poor and survival is often measured in months once CRC metastases become clinically evident. Therefore, the development of effective approach for metastatic CRC cells detection and imaging may potentially be significant and helpful for CRC prognosis and treatment. Therefore, we proposed a sensitive and specific approach for high-metastatic CRC LoVo cells detection and imaging by using terminal deoxynucleotidyl transferase (TdT)-initiated molecule beacons (MBs) arrayed fluorescent aptamer probes (denoted as TMAP). In this approach, the aptamer W3 targeting high-metastatic CRC LoVo cells was elongated to form W3-poly A at the 3'-hydroxyl terminus with repeated A bases in the presence of TdT and dATP. The MBs designed with poly T sequence in the loop were then hybridized with the poly A in the aptamer W3. The TMAP was easily constructed without the need of aptamer modification. It was demonstrated that this approach could specifically detect and image the high-metastatic CRC LoVo cells from the mixture of high-metastatic CRC LoVo cells and non-metastatic HCT-8 cells. Compared with 6-carboxyfluorescein (6-FAM) labeled aptamer W3, the TMAP was demonstrated to have a much stronger fluorescence signal on the target cells, realizing a 4-fold increase in signal-to-background ratio (SBR). Determination by flow cytometry allowed for detection of as low as 23 CRC LoVo cells in 200 µL cell culture medium. The high sensitivity and the capability for using in complicate biological samples imply that this approach holds considerable potential for metastatic CRC detection and therapy.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Neoplasias Colorretais/diagnóstico por imagem , DNA Nucleotidilexotransferase/química , Corantes Fluorescentes/química , Neoplasias Colorretais/metabolismo , DNA Nucleotidilexotransferase/metabolismo , Corantes Fluorescentes/metabolismo , Humanos , Espectrometria de Fluorescência , Células Tumorais Cultivadas
13.
Anal Chem ; 91(14): 9154-9160, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31185714

RESUMO

Activatable aptamer probes (AAPs) are promising in molecular imaging of tumors, but the reported shape-switching-dependent AAPs are still challenged by unsatisfied noise suppression, poor stability, and sophisticated sequence design. To address the problem, we constructed a pH-activatable aptamer probe (pH-AAP) by utilizing an acid-labile acetal linker as the responsive element to be fused with a tumor-targeted aptamer. Specifically, a Cy5-labeled aptamer was connected with the quencher BHQ2 through the acetal group, thus generating pH-AAP with quenched fluorescence. Due to the stable proximity of Cy5 to BHQ2, pH-AAP was found to have ultralow background with a quenching efficiency as high as 98%. In comparison with shape-switching-dependent AAPs, the noise suppression of pH-AAP was well maintained for a much longer time in both serum and mouse body, thus showing a robust fluorescence stability. By a combination of the fluorescence recovery induced by acid hydrolysis of acetal linkers and the tumor-targeted recognition of aptamers, pH-AAP could either specifically anchor the extracellular pH-activated signals on the target cell surface in an acidic tumor microenvironment or be activated by acidic lysosomes after it was internalized into target cells. As proof of concept, in vitro evaluation and in vivo imaging of A549 lung cancer cells were performed by using S6 aptamer as a demonstration. It was indicated that pH-AAP realized washing-free, bispecific, and contrast-enhanced tumor imaging. The strategy is simple and free of sequence modification, which promises to provide a universal platform for sensitive and precise tumor diagnosis.

14.
Anal Chim Acta ; 1070: 88-96, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31103171

RESUMO

Herein, we developed a simple and rapid strategy to synthesize gold/silver bimetallic nanoclusters (Au/Ag NCs) with highly biochemical stability by a one-pot route. The Au/Ag NCs were obtained via a chemical reduction procedure in alkaline aqueous solution at 75 °C within only 20 min by employing bovine serum albumin (BSA) as both ligand and reductant. The as-obtained Au/Ag NCs displayed bright orange fluorescence with an emission peak located at 570 nm and temperature-dependent fluorescence property, which were utilized as fluorescent thermometer directly. More intriguingly, the Au/Ag NCs were very stable against various pH values, ions, biothiols, H2O2, fetal bovine serum (FBS), RPMI 1640 medium and amino acids. Taking advantage of the excellent biochemical stability, a ratiometric fluorescence biosensor, fluorescein-5-isothiocyanate (FITC)-Au/Ag NCs, was constructed for pH sensing based on the incorporation of FITC into the Au/Ag NCs. Furthermore, the ratiometric pH sensor was also successfully applied on the model of HeLa cells.


Assuntos
Ligas/química , Ouro/química , Nanopartículas Metálicas/química , Prata/química , Temperatura Ambiente , Ligas/síntese química , Animais , Técnicas Biossensoriais , Bovinos , Fluoresceína-5-Isotiocianato/química , Fluorescência , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Soroalbumina Bovina/química , Espectrometria de Fluorescência
15.
J Thromb Thrombolysis ; 48(2): 292-298, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31055773

RESUMO

To increase the detection rate of deep vein thrombosis (DVT) and to compare the predictive value of four different risk assessment scales (Caprini, Autar, Pauda, and Khorana scales) for DVT in patients with solid tumors by the receiver operating curve (ROC). A total of 361 patients with all kinds of malignant solid tumors, who accepted anti-tumor therapy in the cancer center between March 3, 2015 to April 13, 2018, were assigned to a group of 230 cases diagnosed with DVT and a control group of 131 cases without DVT. Data were recorded and summarized, and the predictive value of the above four risk assessment scales for DVT in solid tumor patients was compared based on the area under the ROC curve (AUC). The AUC values determined for the Caprini, Autar, Pauda, and Khorana scales were (0.631 ± 0.030), (0.686 ± 0.028), (0.654 ± 0.029), and (0.599 ± 0.032), respectively; maximum sensitivity, specificity, and Youden index were 80.9% for Khorana, 86.3% for Caprini, and 29.6% for Autar scale, respectively. We found no statistically significant differences in the AUC values between Autar and Caprini, Autar and Khorana, as well as Khorana and Pauda (p > 0.05). However, the AUC differences between Autar and Pauda, Caprini and Khorana, as well as Caprini and Pauda were statistically significant (p < 0.05). All four risk assessment models showed some value in the risk prediction of DVT in patients with solid tumors, but every model also exhibited its own restrictions; maximum sensitivity, specificity, and Youden index were 80.9% for Khorana, 86.3% for Caprini, and 29.6% for Autar scale, respectively. We confirmed that the detection rate can be improved by modifying the BMI cut-off value of the scale or by combining appropriate scales.

16.
Biosens Bioelectron ; 137: 96-109, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085403

RESUMO

During the last decades, by virtue of their unique physicochemical properties and potential application in microelectronics, biosensing and biomedicine, metal nanomaterials (MNs) have attracted great research interest and been highly developed. Deoxyribonucleic acid (DNA) is a particularly interesting ligand for templating bottom-up nanopreparation, by virtue of its excellent properties including nanosized geometry structure, programmable and artificial synthesis, DNA-metal ion interaction and powerful molecular recognition. DNA-templated copper nanoparticles (DNA-CuNPs) has been developed in recent years. Because of its advantages including simple and rapid preparation, high efficiency, MegaStokes shifting and low biological toxicity, DNA-CuNPs has been highly exploited for biochemical sensing from 2010, especially as a label-free detection manner, holding advantages in multiple analytical technologies including fluorescence, electrochemistry, surface plasmon resonance, inductively coupled plasma mass spectrometry and surface enhanced Raman spectroscopy. This review comprehensively tracks the preparation of DNA-CuNPs and its application in biosensing, and highlights the potential development and challenges regarding this field, aiming to promote the advance of this fertile research area.

17.
Chronobiol Int ; 36(7): 906-918, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31014126

RESUMO

Circadian rhythm describes the 24-h oscillation in physiology and behavior of living organisms and presents a timing controller for life activity. Studies in recent years have reported that the abnormal expression of clock genes is closely related to the development of common abdominal malignant tumors. The expression of the 14 kinds of clock genes in 6 abdominal malignant tumors from Cancer Genome Atlas (TCGA) data was integrated and analyzed using R and Perl programming languages to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that the overexpression of Per1-3, Cry2, CLOCK, NR1D2 and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis in kidney cancer. In liver cancer, high expressions of Cry2 and RORA were correlated with prolonged overall survival (OS) in patients, while high expressions of NPAS2 and Timeless were correlated with a poor survival. High expression of CLOCK was positively correlated with OS in colon cancer patients. High expression of Cry2 and low expression of DEC1 were associated with a favorable prognosis in pancreatic cancer patients, respectively. Most of these clock-genes expressions were closely related to the clinical stage and degree of tumor differentiation of patients. Aberrant clock gene expression is related to the biological characteristics of abdominal malignant tumors, which likely has a causal role in cancer development and survival.

18.
Chronobiol Int ; 36(6): 739-750, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31014124

RESUMO

Circadian clock genes have become a hot topic in cancer research in recent years, and more and more studies are showing that clock genes are involved in regulating cell proliferation cycle and apoptosis of malignant tumors, neuroendocrine and immune function, and other processes. Lung cancer is a malignant tumor with increasing incidence worldwide. The pathogenesis of lung cancer is extremely complicated and includes genetic factors, living environment, and smoking, and the occurrence of lung cancer is related to the regulation of many oncogenes and tumor suppressor genes. But there are few studies on clock genes in lung cancer. Studies on clock genes may help to better understand the mechanism of lung cancer development for an improved treatment. The expressions of all 14 kinds of clock genes in adenocarcinoma (ADC) and squamous cell carcinoma (SCC), two main kinds of non-small-cell lung cancer (NSCLC), were studied based on integration and analysis of data from The Cancer Genome Atlas (TCGA) to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that overexpression of Cry2, BMAL1, and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis of ADC, and the expression of NPAS2 was associated with the time of patient survival. Additionally, the expression of Cry2 was related to TNM stage. In SCC, high expression of DEC1 was correlated with poor overall survival in patients and the expression of Timeless was associated with the time of patient survival. In NSCLC, circadian clock genes constitute cancer circadian rhythm by interacting with each other, showing that asynchrony with normal tissues, which collectively controlling the occurrence and development of NSCLC.

19.
ACS Appl Mater Interfaces ; 11(14): 13491-13498, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30880387

RESUMO

The fast evolution of metal halide perovskite solar cells has opened a new chapter in the field of renewable energy. High-quality perovskite films as the active layers are essential for both high efficiency and long-term stability. Here, the perovskite films with enlarged crystal grain size and decreased defect density are fabricated by introducing the extremely low-cost and green polymer, ethyl cellulose (EC), into the perovskite layer. The addition of EC triggers hydrogen bonding interactions between EC and the perovskite, passivating the charge defect traps at the grain boundaries. The long chain of EC further acts as a scaffold for the perovskite structure, eliminating the annealing-induced lattice strain during the film fabrication process. The resulting devices with the EC additive exhibit a remarkably enhanced average power conversion efficiency from 17.11 to 19.27% and an improvement of all device parameters. The hysteresis index is found to decrease by three times from 0.081 to 0.027, which is attributed to suppressed ion migration and surface charge trapping. In addition, the defect passivation by EC significantly improves the environmental stability of the perovskite films, yielding devices that retain 80% of their initial efficiency after 30 days in ambient air at 45% relative humidity, whereas the pristine devices without EC fully degrade. This work provides a low-cost and green avenue for passivating defects that improves both the efficiency and operational stability of perovskite solar cells.

20.
Cereb Cortex ; 29(6): 2737-2747, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30843060

RESUMO

Chronic stress has been observed to increase the risk of developing depression and induce neuronal alterations of synaptic plasticity, yet the underlying molecular mechanisms remain unclear. Here, we found that the ubiquitously expressed RNA-binding protein HuR was up-regulated in the medial prefrontal cortex (mPFC) of mice following chronic stress. In adult mice, AAV-Cre-mediated knockout of HuR in the mPFC prevented anxiety-like and depression-like behaviors induced by chronic stress. HuR was also required for the stress-induced dendritic spine loss and synaptic transmission deficits. Moreover, HuRflox/flox;Nex-Cre mice, which induce HuR loss of function from embryonic development, exhibited enhanced synaptic functions. Notably, we ascertained RhoA signaling to be regulated by HuR and involved in the modulation of structural synaptic plasticity in response to chronic stress. Our results demonstrate HuR is a critical modulator for the regulation of stress-induced synaptic plasticity alterations and depression, providing a potential therapeutic target for the treatment of depressive disorders.

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