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1.
Cell Death Dis ; 11(2): 85, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015323

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disease with a strong heritability, but recent evidence suggests that epigenetic dysregulation may also contribute to the pathogenesis of ASD. Especially, increased methylation at the MECP2 promoter and decreased MECP2 expression were observed in the brains of ASD patients. However, the causative relationship of MECP2 promoter methylation and ASD has not been established. In this study, we achieved locus-specific methylation at the transcription start site (TSS) of Mecp2 in Neuro-2a cells and in mice, using nuclease-deactivated Cas9 (dCas9) fused with DNA methyltransferase catalytic domains, together with five locus-targeting sgRNAs. This locus-specific epigenetic modification led to a reduced Mecp2 expression and a series of behavioral alterations in mice, including reduced social interaction, increased grooming, enhanced anxiety/depression, and poor performance in memory tasks. We further found that specifically increasing the Mecp2 promoter methylation in the hippocampus was sufficient to induce most of the behavioral changes. Our finding therefore demonstrated for the first time the casual relationship between locus-specific DNA methylation and diseases symptoms in vivo, warranting potential therapeutic application of epigenetic editing.

2.
Int J Mol Sci ; 21(3)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32033479

RESUMO

The aim of this study was to isolate and identify angiotensin I-converting enzyme (ACE) inhibitory peptides from sesame protein through simulated gastrointestinal digestion in vitro, and to explore the underlying mechanisms by molecular docking. The sesame protein was enzymatically hydrolyzed by pepsin, trypsin, and α-chymotrypsin. The degree of hydrolysis (DH) and peptide yield increased with the increase of digest time. Moreover, ACE inhibitory activity was enhanced after digestion. The sesame protein digestive solution (SPDS) was purified by ultrafiltration through different molecular weight cut-off (MWCO) membranes and SPDS-VII (< 3 kDa) had the strongest ACE inhibition. SPDS-VII was further purified by NGC Quest™ 10 Plus Chromatography System and finally 11 peptides were identified by Nano UHPLC-ESI-MS/MS (nano ultra-high performance liquid chromatography-electrospray ionization mass spectrometry/mass spectrometry) from peak 4. The peptide GHIITVAR from 11S globulin displayed the strongest ACE inhibitory activity (IC50 = 3.60 ± 0.10 µM). Furthermore, the docking analysis revealed that the ACE inhibition of GHIITVAR was mainly attributed to forming very strong hydrogen bonds with the active sites of ACE. These results identify sesame protein as a rich source of ACE inhibitory peptides and further indicate that GHIITVAR has the potential for development of new functional foods.

3.
J Phys Chem Lett ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073860

RESUMO

Negative thermal expansion (NTE) is an intriguing property for not only fundamental studies but also technological applications. However, few NTE materials are available compared with the huge amount of positive thermal expansion (PTE) ones. Discovery of new NTE materials remains challenging. Here, we report a chemical modification strategy to transform thermal expansion from positive to negative in the cubic magnetic compounds of (Zr,Nb)Fe2 by tuning magnetic exchange interaction. Furthermore, an isotropic zero thermal expansion (ZTE) can be established in Zr0.8Nb0.2Fe2 (αl = 1.4 × 10-6 K-1, 3 ~ 470 K) over a broad temperature range which is even wider than the prototype Invar alloy of Fe0.64Ni0.36. The NTE of (Zr,Nb)Fe2 is originated from the weakened magnetic exchange interaction and the increased d electrons of Fe by the Nb chemical substitution, so that the magnetovolume effect overwhelms the contribution of anharmonic lattice vibration.

4.
Epigenomics ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052657

RESUMO

Aim: Circular RNAs (circRNAs) are essential for stem cell differentiation. This study aimed to investigate their exact mechanism of action in human adipose-derived stem cell (hADSC) osteogenesis. Materials & methods: Isolated hADSCs were cultured in growth medium or osteogenic medium, then total RNA was extracted for circRNA microarray, hierarchical cluster, gene ontology, regulating pathway and circRNA-miRNA-mRNA network analyses. Results: A total of 171 circRNAs were upregulated and 119 were downregulated in induced groups compared with those in noninduced groups. Eight circRNAs, 40 miRNAs and 342 mRNAs were selected to construct a competing circRNA-miRNA-mRNA network. Conclusion: These findings may provide novel insight into altered and specific circRNAs that might function as competing endogenous RNAs in hADSCs during osteogenic differentiation.

5.
Apoptosis ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32056038

RESUMO

Treatment of advanced BRAFV600-mutant melanoma using BRAF inhibitors (BRAFi) eventually leads to drug resistance and selects for highly metastatic tumor cells. We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets. We discovered miR-152-5p was a potential regulator mediating melanoma drug resistance and metastasis. Functionally, knockdown of miR-152-5p significantly compromised the metastatic ability of BRAFi-resistant melanoma cells and overexpression of miR-152-5p promoted the formation of slow-cycling phenotype. Furthermore, we explored the cause of how and why miR-152-5p affected metastasis in depth. Mechanistically, miR-152-5p targeted TXNIP which affected metastasis and BRAFi altered the methylation status of MIR152 promoter. Our study highlights the crucial role of miR-152-5p on melanoma metastasis after BRAFi treatment and holds significant implying that discontinuous dosing strategy may improve the benefit of advanced BRAFV600-mutant melanoma patients.

6.
Adv Mater ; : e1906054, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048409

RESUMO

Graphene nanoribbons (GNRs) have attracted much interest due to their largely modifiable electronic properties. Manifestation of these properties requires atomically precise GNRs which can be achieved through a bottom-up synthesis approach. This has recently been applied to the synthesis of width-modulated GNRs hosting topological electronic quantum phases, with valence electronic properties that are well captured by the Su-Schrieffer-Heeger (SSH) model describing a 1D chain of interacting dimers. Here, ultralow bandgap GNRs with charge carriers behaving as massive Dirac fermions can be realized when their valence electrons represent an SSH chain close to the topological phase boundary, i.e., when the intra- and interdimer coupling become approximately equal. Such a system has been achieved via on-surface synthesis based on readily available pyrene-based precursors and the resulting GNRs are characterized by scanning probe methods. The pyrene-based GNRs (pGNRs) can be processed under ambient conditions and incorporated as the active material in a field effect transistor. A quasi-metallic transport behavior is observed at room temperature, whereas at low temperature, the pGNRs behave as quantum dots showing single-electron tunneling and Coulomb blockade. This study may enable the realization of devices based on carbon nanomaterials with exotic quantum properties.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31957191

RESUMO

OBJECTIVE: The global burden of rectal gastrointestinal stromal tumor (GIST) is increasing. However, a limited number of reports hinder our ability to reach a definitive conclusion regarding the current treatment and prognosis. In this study, we outline our experience with open transanal resection of rectal GIST following neoadjuvant therapy with imatinib mesylate (IM). PATIENTS AND METHODS: We retrospectively analyzed 11 patients with rectal GISTs treated with neoadjuvant IM therapy and open transanal resection between April 2011 and April 2017 in Shanghai Changzheng Hospital. RESULTS: The patients had 400-600 mg/day IM once daily for a median of 7 months (range: 3-9 months). Tumor size, distance from the lower margin of the tumor to the anal verge (AV), mitotic rates and mutation analysis were assessed on pretreatment biopsy. After reassessment, all 11 patients underwent transanal R0 resection. With median follow-up of 28 months (range: 8-80 months), there was no tumor recurrence or metastasis. CONCLUSION: Open transanal resection of rectal GIST after neoadjuvant treatment with IM has good surgical and survival outcomes.

9.
Chem Commun (Camb) ; 56(11): 1685-1688, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31939943

RESUMO

From an interplay of high-resolution UHV-STM imaging and DFT calculations, we have achieved on-surface synthesis of graphyne nanowires through stepwise reactions involving two different types of dehalogenative homocoupling reactions (i.e., C(sp3)-Br and C(sp2)-Br). This study would further supplement our database of on-surface synthesis and provide us with an alternative and efficient strategy for the fabrication of desired nanostructures/nanomaterials.

11.
Dev Comp Immunol ; 106: 103601, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31899306

RESUMO

Bombyx mori bidensovirus (BmBDV) infects silkworm midgut and causes chronic flacherie disease; however, the interaction between BmBDV and silkworm is unclear. Twenty-four hours after BmBDV infection, the midgut was extracted for RNA-seq to analyze the factors associated with BmBDV-invasion and the early antiviral immune response in silkworms. The total reads from each sample were more than 16100000 and the number of expressed genes exceeded 8200. There were 334 upregulated and 272 downregulated differentially expressed genes (DEGs). Gene ontology analysis of DEGs showed that structural constituents of cuticle, antioxidant, and immune system processes were upregulated. Further analysis revealed BmBDV-mediated induction of BmorCPR23 and BmorCPR44, suggesting possible involvement in viral invasion. Antioxidant genes that protect host cells from virus-induced oxidative stress, were significantly upregulated after BmBDV infection. Several genes related to peroxisomes, apoptosis, and autophagy-which may be involved in antiviral immunity-were induced by BmBDV. These results provide insights into the mechanism of BmBDV infection and host defense.

12.
Mol Oncol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951095

RESUMO

Patients with metastatic gastric cancer (GC) have a poor prognosis; however, the molecular mechanism of GC metastasis remains unclear. Here, we employed bioinformatics to systematically screen the metastasis-associated genes and found that the levels of basal cell adhesion molecule (BCAM) were significantly increased in GC tissues from patients with metastasis, as compared to those without metastasis. The upregulation of BCAM was also significantly associated with a shorter survival time. Depletion of BCAM inhibited GC cell migration and invasion. Knockout (KO) of BCAM by the CRISPR/Cas9 system reduced the invasion and metastasis of GC cells. To explore the mechanism of BCAM upregulation, we identified a previously uncharacterized BCAM sense lncRNA that spanned from exon 6 to intron 6 of BCAM, and named it as BCAM-associated long noncoding RNA (BAN). Knockdown of BAN inhibited BCAM expression at both mRNA and protein levels. Knockdown of BAN suppressed GC cell migration and invasion, which was effectively rescued by ectopic expression of BCAM. Further clinical data showed that BAN upregulation was associated with GC metastasis and poor prognosis. Importantly, BAN expression was also significantly associated with that of BCAM in GC tissues. Taken together, these results indicate that increased expression of BCAM and its sense lncRNA BAN promote GC cell invasion and metastasis, and are associated with poor prognosis of GC patients.

13.
J Am Chem Soc ; 142(6): 3088-3093, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31952444

RESUMO

Negative thermal expansion (NTE) behaviors have been observed in various types of compounds. The achievement in the merits of promising low-cost and facile NTE oxides remains challenging. In the present work, a simple and low-cost Cu2P2O7 has been found to exhibit the strongest NTE among the oxides (αV ∼ -27.69 × 10-6 K-1, 5-375 K). The complex NTE mechanism has been investigated by the combined methods of high-resolution synchrotron X-ray diffraction, neutron powder diffraction, X-ray pair distribution function, extended X-ray absorption fine structure spectroscopy, and density functional theory calculations. Interesting, the direct experimental evidence reveals that the coupling twist and rotation of PO4 and CuO5 polyhedra are the inherent factors for the NTE nature of Cu2P2O7, which is triggered by the transverse vibrations of oxygen atoms. The present new NTE material of Cu2P2O7 also has been verified for the practical application.

14.
Oncol Res Treat ; : 1-7, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31945768

RESUMO

INTRODUCTION: The adverse effect of fractures by different aromatase inhibitor (AI) drugs has not been thoroughly assessed in real-world studies. OBJECTIVE: To assess the adverse events of fractures of real-world breast cancer patients caused by AI therapy through the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: The FAERS data from January 2004 to December 2018 were sorted out and analyzed for correlations between fractures and AI use. Disproportionate analysis and Bayesian analysis were adopted to quantify the signal, the association between the AIs and fractures. The onset time and outcome of fractures after different AI regimens were also compared. RESULTS: Out of 23,064 adverse reports, 657 fracture reports (2.85%) were analyzed. Anastrozole showed a positive association with 4 detection methods, while letrozole and exemestane did so with 2. More exemestane-related reports (44.62%) resulted in initial or prolonged hospitalization than anastrozole (30.12%, p = 0.013) and letrozole (29.43%, p = 0.006). The fracture onset time showed no significant difference among anastrozole, letrozole, and exemestane (median onset time: 46.95, 34.25, and 40.58 months, respectively; p = 0.236). CONCLUSIONS: Anastrozole should be prescribed with more medical care. Analysis of FAERS data identified fracture risk tendencies with AI regimens, which supported continuous monitoring, risk evaluations, and further comparative studies.

16.
Angew Chem Int Ed Engl ; 59(3): 1334-1339, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31729821

RESUMO

On-surface synthesis offers a versatile approach to prepare novel carbon-based nanostructures that cannot be obtained by conventional solution chemistry. Graphene nanoribbons (GNRs) have potential for a variety of applications. A key issue for their application in molecular electronics is in the fine-tuning of their electronic properties through structural modifications, such as heteroatom doping or the incorporation of non-benzenoid rings. In this context, the covalent fusion of GNRs and porphyrins (Pors) is a highly appealing strategy. Herein we present the selective on-surface synthesis of a Por-GNR hybrid, which consists of two Pors connected by a short GNR segment. The atomically precise structure of the Por-GNR hybrid has been characterized by bond-resolved scanning tunneling microscopy (STM) and noncontact atomic force microscopy (nc-AFM). The electronic properties have been investigated by scanning tunneling spectroscopy (STS), in combination with DFT calculations, which reveals a low electronic gap of 0.4 eV.

17.
Int J Biol Macromol ; 142: 311-319, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593736

RESUMO

Safety assessment must be conducted before the commercial release of transgenic silkworms. This study was conducted to assess the potential of transferring transgenic DNA from silkworms to other organisms. One hundred hatched male chickens were evenly assigned into 4 groups (T1-4). Groups T1-3 were fed transgenic silkworms P3+5UI with enhanced green fluorescent protein DNA (EGFP) inserted, A4SOR with superoxide reductase DNA (SOR) inserted, and normal silkworm, respectively. Each chicken was fed one silkworm larva every day for 3 weeks. T4 was the normal feeding control. Twenty chickens were randomly selected from each treatment for sacrifice at 22 days of age. The serum was collected individually for biochemical examination, revealing no difference in the analyzed serum parameters between T4 and T1-3. DNA from the duodenum, jejunum, ileum, liver, kidney, and jejunal digesta was extracted for PCR analysis of EGFP, SOR, silkworm housekeeping gene TIF-4A, and chicken ovalbumin gene. No transgenic DNA or TIF-4A was detected in the digesta and tissues of chickens. The same results were observed in chicken upon increasing the amount and frequency of feeding transgenic silkworms, suggesting that the transgenic DNA from silkworms was degraded in the digestive tract and not transferred into the tissues of chicken. This study revealed that transferr recombinant DNA from transgenic silkworm to another organism is unlikely.

18.
J Hazard Mater ; 384: 121262, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31586922

RESUMO

In the case of a sharp increase in the price of dyes, the dyes concentration of in wastewater is important for environmental protection and industrial costs reduction. In this study, we grafted single-layer amino groups onto the surface of the hollow glass microspheres by a two-step simple synthesis, and the anionic dyes adsorption process reaches equilibrium within 10 min. The as-synthesized adsorbent has self-floating ability to achieve high-efficiency surface solid-liquid separation with water. SEM, EDS, SBET, FT-IR, XPS, TGA characterizations results demonstrated the successful grafting of amino groups and the important role of the pretreatment process in the two-step synthesis. The results of adsorption isotherms and kinetics show the adsorption process belongs to single-layer adsorption with equal adsorption sites, and the adsorption capacities for acid orange 7 and amaranth reach 428.99 mg g-1 and 145.62 mg g-1, respectively. Regeneration of the adsorbent and concentration of the dye solutions can be achieved by dispersing the separated adsorbent in alkaline solution, the maximum concentrated concentration of acid orange 7 and amaranth was 6321.57 mg L-1 and 2431.84 mg L-1, respectively. This study provides new insights for the solid-liquid separation of water treatment agents and the resource regenerating of dyeing wastewater.

19.
Nanoscale ; 12(1): 271-276, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31819937

RESUMO

In this study, we have grown epitaxial wurtzite structured InAs nanosheets using Au catalysts on a GaAs{111}B substrate by molecular beam epitaxy. Through detailed electron microscopy characterization studies on grown nanosheets, it was found that these wurtzite structured InAs nanosheets grew epitaxially on the GaAs{111}B substrate, with {0001[combining macron]} catalyst/nanosheet interfaces and extensive {112[combining macron]0} surfaces. It was anticipated that the epitaxially grown InAs nanosheet can be triggered by a high supersaturation in catalysts, leading to an inclined growth leaving the substrate surface, and driven by the small lattice mismatch between the nanosheets and the substrate, with the orientation relationship of (0001[combining macron])InAs//(112[combining macron])GaAs. This study provides insights into achieving epitaxial free-standing III-V nanosheet growth.

20.
J Cell Physiol ; 235(3): 2037-2048, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31612481

RESUMO

The aim of this study was to identify key genes related to the progression of colon adenocarcinoma (COAD), and to investigate the regulatory network of hub genes and transcription factors (TFs). Dataset GSE20916 including 44 normal colon, 55 adenoma, and 36 adenocarcinoma tissue samples was used to construct co-expression networks via weighted gene co-expression network. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the objective module were performed using the online Database for Annotation, Visualization and Integrated Discovery. Hub genes were identified by taking the intersection of differentially expressed genes between dataset GSE20916 and GSE39582 and validated using The Cancer Genome Atlas (TCGA) database. The correlations between microRNA (miRNA) and hub genes were analyzed using the online website StarBase. Cytoscape was used to establish a regulatory network of TF-miRNA-target gene. We found that the orange module was a key module related to the tumor progression in COAD. In datasets GSE20916 and GSE39582, a total of eight genes (BGN, SULF1, COL1A1, FAP, THBS2, CTHRC1, COL5A2, and COL1A2) were selected, which were closely related with patients' survivals in TCGA database and dataset GSE20916. COAD patients with higher expressions of each hub gene had a worse prognosis than those with lower expressions. A regulatory network of TF-miRNA-target gene with 144 TFs, 26 miRNAs, and 7 hub genes was established, including model KLF11-miR149-BGN, TCEAL6-miR29B2-COL1A1, and TCEAL6-miR29B2-COL1A2. In conclusion, during the progression of COAD, eight core genes (BGN, SULF1, COL1A1, FAP, THBS2, CTHRC1, COL5A2, and COL1A2) play vital roles. Regulatory networks of TF-miRNA-target gene can help to understand the disease progression and optimize treatment strategy.

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