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1.
EBioMedicine ; 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31594754

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-related tumor. The role of EBV-encoding miR-BART22 is still unclear in NPC. This study aimed to identify the detailed mechanisms by which EBV-miR-BART22 functions as a tumor-promoting factor and evaluate the action of cinobufotalin in treating EBV-miR-BART22-overexpressing NPC cells. METHODS: Using real-time PCR, western blotting, immunohistochemistry, and In situ hybridization, we detected the expression of miR-BART22 and MAP2K4 in tissues and cells, as well as evaluated their clinical relevance in NPC patients. The effects of miR-BART22 on cell metastasis, stemness and DDP chemoresistance were examined by sphere formation assay, side population analysis, transwell, boyden, in vivo xenograft tumor mouse model et al. Western blotting, immunofluorescence staining, luciferase reporter assay, ChIP, EMSA and Co-IP assay et al. were performed to explore the detailed molecular mechanism of EBV-miR-BART22 in NPC. Finally, we estimated the effects and molecular basis of Cinobufotalin on EBV-miR-BART22-overexpressing NPC cells in vitro and in vivo assays. FINDINGS: We observed that EBV-miR-BART22 not only promoted tumor stemness and metastasis, but also enhanced the resistance to Cisplatin (DDP) in vitro and in vivo. Mechanistic analysis indicated that EBV-miR-BART22 directly targeted the MAP2K4 and upregulated non-muscle myosin heavy chain IIA (MYH9) expression by PI3K/AKT/c-Jun-induced transcription. Further, MYH9 interacted with glycogen synthase 3ß(GSK3ß) protein and induced its ubiquitin degradation by activating PI3K/AKT/c-Jun-induced ubiquitin transcription and the latter combined with increased TRAF6 E3 ligase, which further bound to GSK3ß protein. Reductions in the GSK3ß protein thus promoted ß-catenin expression and nuclear translocation, which induced tumor stemness and the epithelial-to-mesenchymal transition (EMT) signals. Furthermore, we observed that cinobufotalin, a new chemically synthesized compound, significantly suppressed EBV-miR-BART22-induced DDP chemoresistance by upregulating MAP2K4 to suppress MYH9/GSK3ß/ß-catenin and its downstream tumor stemness and EMT signals in NPC. Finally, clinical data revealed that increased miR-BART22 and reduced MAP2K4 expression caused the poor prognoses of NPC patients. INTERPRETATION: Our study provides a novel mechanism that cinobufotalin reversed the DDP chemoresistance and EMT induced by EBV-miR-BART22 in NPC.

2.
J Am Chem Soc ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31603672

RESUMO

Physical adsorption of gas molecules in microporous materials is an exothermic process, with desorption entropy driving a decrease in uptake with temperature. Enhanced gas sorption with increasing temperature is rare in porous materials and is indicative of sorbate initiated structural change. Here, sorption of C2H6, C3H6, and C3H8 in a flexible microporous metal-organic framework (MOF) {Cu(FPBDC)]·DMF}n (NKU-FlexMOF-1) (H2FPBDC = 5-(5-fluoropyridin-3-yl)-1,3-benzenedicarboxylic acid) that increases with rising temperature over a practically useful temperature and pressure range is reported along with other small molecule and hydrocarbon sorption isotherms. Single X-ray diffraction studies, temperature-dependent gas sorption isotherms, in situ and variable temperature powder X-ray diffraction experiments, and electronic structure calculations were performed to characterize the conformation-dependent sorption behavior in NKU-FlexMOF-1. In total, the data supports that the atypical sorption behavior is a result of loading-dependent structural changes in the flexible framework of NKU-FlexMOF-1 induced by sorbate-specific guest-framework interactions. The sorbates cause subtle adaptations of the framework distinct to each sorbate providing an induced-fit separation mechanism to resolve chemically similar hydrocarbons through highly specific sorbate-sorbent interactions. The relevant intermolecular contacts are shown to be predominantly repulsion and dispersion interactions. NKU-FlexMOF-1 is also found to be stable in aqueous solutions including toleration of pH changes. These experiments demonstrate the potential of this flexible microporous MOF for cost and energy efficient industrial hydrocarbon separation and purification processes. The efficacy for the separation of C3H6/C3H8 mixtures is explicitly demonstrated using NKU-FlexMOF-1a (i.e., activated NKU-FlexMOF-1) for a particular useful temperature range.

3.
Chem Commun (Camb) ; 55(76): 11354-11357, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31483423

RESUMO

In this work, we show that precise control of the pore size and functionality in an ultramicroporous metal-organic framework platform can finely tune the adsorption selectivity between acetylene and carbon dioxide at will.

4.
Biochem Biophys Res Commun ; 519(4): 697-704, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542234

RESUMO

At present, whether α2-adrenoceptors in the prelimbic cortex (PrL) are involved in Parkinson's disease-related anxiety is unclear. We examined the effects of PrL α2-adrenoceptors on anxiety-like behaviors in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. Compared to the sham operation, the lesion induced anxiety-like responses as measured by the open field test and elevated plus-maze test. Intra-PrL injection of the α2-adrenoceptor agonist clonidine (1.25, 2.5 or 5 µg/rat) produced anxiolytic effects in sham-operated and lesioned rats. Furthermore, intra-PrL injection of the α2-adrenoceptor antagonist idazoxan (1, 2 or 4 µg/rat) induced anxiogenic effects in two groups of rats. The effective doses produced by clonidine and idazoxan in lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of clonidine (5 µg/rat) or idazoxan (4 µg/rat) decreased or increased dopamine (DA) and noradrenaline (NA) and serotonin (5-HT) levels in the medial prefrontal cortex (mPFC) and amygdala in sham-operated and lesioned rats, respectively. These results suggest that α2-adrenoceptors in the PrL are involved in the regulation of anxiety-like behaviors, which is attributable to changes in DA, NA and 5-HT levels in the mPFC and amygdala after activation and blockade of α2-adrenoceptors.

5.
BMC Public Health ; 19(1): 1007, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351463

RESUMO

BACKGROUND: Type 2 diabetes is a major public health problem with considerable personal and societal costs. Adverse childhood experiences (ACE) are associated with a number of serious and chronic health problems in adulthood, but these experiences have not been adequately studied in relation to diabetes in a US national sample. The association between ACE and poor health can be partially explained by greater risky health behaviors (RHB) such as smoking, heavy alcohol use, or obesity. Few studies have examined ACE in relation to adult onset Type 2 diabetes mellitus (T2DM) taking into account the role of RHB. Using longitudinal data from a representative US population sample followed over 30 years, this study examines the impact of ACE on the risk of diabetes onset. METHODS: Data from the 1982 to 2012 waves of the 1979 National Longitudinal Survey of Youth were analyzed, spanning ages 14 to 56. Bivariate and discrete-time survival models were used to assess the relationships between ACE and RHB including smoking, alcohol use, and obesity, and subsequent onset of diabetes. RESULTS: T2DM was reported by almost 10% of participants. Over 30% of women and 21% of men reported 2+ ACE events. Women reporting 2-3 or 4+ ACE events were more likely to develop diabetes with the mean number of ACE events being greater in those with diabetes compared to without (1.28 vs.1.05, p < .0001). For men there was no significant association between ACE and diabetes onset. For women, ACE was associated with heavy drinking, current smoking, and obesity. For men, ACE was associated with being underweight and daily smoking. In multivariate discrete-time survival models, each additional ACE increased risk of T2DM onset (ORadj = 1.14; 95% CI 1.02-1.26) for women but not for men. The relationship in women was attenuated when controlling for body mass index (BMI). CONCLUSION: ACE predicted diabetes onset among women, though this relationship was attenuated when controlling for BMI. Being overweight or obese was significantly more common among women with a history of ACE, which suggests BMI may be on the pathway from ACE to diabetes onset for women.


Assuntos
Experiências Adversas da Infância/estatística & dados numéricos , Diabetes Mellitus Tipo 2/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Feminino , Comportamentos de Risco à Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fatores de Risco , Fumar/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
6.
Int J Cancer ; 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31125123

RESUMO

The biological role of vacuolar protein sorting 33B (VPS33B) has not been examined in colorectal cancer (CRC). We report that VPS33B was downregulated in dextran sulfate sodium/azoxymethane (DSS/AOM) -induced CRC mice models and nicotine-treated CRC cells via the PI3K/AKT/c-Jun pathway. Reduced VPS33B is an unfavorable factor promoting poor prognosis in human CRC patients. VPS33B overexpression suppressed CRC proliferation, intrahepatic metastasis and chemoresistance of cisplatin (DDP) in vivo and in vitro through modulating the epidermal growth factor receptor (EGFR)/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and the downstream cell cycle or EMT-related factors. Furthermore, NESG1 as a newly identified tumor suppressor interacted with VPS33B via colocalization in the cytoplasm, and it was stimulated by VPS33B through the downregulation of RAS/ERK/c-Jun-mediated transcription. NESG1 also activated VPS33B expression via the RAS/ERK/c-Jun pathway. Suppression of NESG1 increased cell growth, migration and invasion via the reversion of the VPS33B-modulating signal in VPS33B-overexpressed cells. Taken together, VPS33B as a tumor suppressor is easily dysregulated by chemical carcinogens and it interacts with NESG1 to modulate the EGFR/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and thus suppress the malignant phenotype of CRC.

7.
Food Chem ; 292: 98-105, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054698

RESUMO

Accurate and early diagnosis of mycotoxin is particularly significant to the food and agricultural product safety. In the present work, a sensitive and effective monitoring method for zearalenone (ZEN) was exploited based on a novel self-enhanced electrochemiluminescence (ECL) aptasensor. The self-enhanced lumonophore was compounded by electrostatically combining amine-functionalized Ru(bpy)32+-doped silica nanoparticles (NH2-Ru@SiO2 NPs) and nitrogen doped graphene quantum dots (NGQDs) together. Since the emitter and co-reactant simultaneously existed in the same nanoparticle, shortened electron-transfer distance and decreased energy loss was obtained. Therefore, self-enhanced ECL aptasensor based on the novel complex expressed the widest linear range of 10 fg mL-1-10 ng mL-1 and the lowest detection limit of 1 fg mL-1 for ZEN detection. More importantly, ZEN produced during the mildew process of corn flour was monitored by the developed aptasensor, which exhibited superior determination and potential application in real samples.


Assuntos
Aptâmeros de Nucleotídeos/química , Medições Luminescentes/métodos , Nanopartículas/química , Zea mays/metabolismo , Zearalenona/análise , 2,2'-Dipiridil/análogos & derivados , 2,2'-Dipiridil/química , Farinha/análise , Grafite/química , Limite de Detecção , Compostos Organometálicos/química , Pontos Quânticos/química , Reprodutibilidade dos Testes , Dióxido de Silício/química , Zea mays/química
8.
Drug Alcohol Depend ; 200: 124-132, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128464

RESUMO

BACKGROUND: This secondary analysis uses data from a recent clinical trial conducted with probationers and parolees with substance use disorders (N = 330) residing in Sober Living Houses (SLHs). The treatment condition received Motivational Interviewing Case Management (MICM), while controls received usual care SLH residency. Both conditions improved on multiple domains, though residents randomized to MICM improved significantly more than usual care controls on criminal justice outcomes. Because MICM is designed to help ex-offenders attain more recovery capital (RC) in multiple domains, we hypothesized MICM participants that already possessed higher RC would show significantly greater improvement at follow-up than usual SLH residents with higher RC. Moreover, MICM and usual SLH residents with low RC would show no differences at 1-year follow-up. METHODS: A latent class analysis (LCA) grouped participants into two patterns of RC: those with low RC and those with high RC. These classes were interacted with study condition to predict change on six Addiction Severity Indices (ASI) at follow-up. RESULTS: MICM was more effective for the higher RC class, with greater improvement in drug, legal, and psychiatric outcomes for those who attended at least three MICM sessions. MICM was no more beneficial than usual care for those in a low RC class. CONCLUSIONS: SLH operators should consider implementation of MICM for residents with more RC resources. Those with fewer recovery resources, such as a history of psychiatric problems or physical/sexual abuse, would benefit from a more intensive intervention to assist them with improving the amount and quality of their RC.

9.
Angew Chem Int Ed Engl ; 58(30): 10209-10214, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31059186

RESUMO

Simultaneous removal of trace amounts of propyne and propadiene from propylene is an important but challenging industrial process. We report herein a class of microporous metal-organic frameworks (NKMOF-1-M) with exceptional water stability and remarkably high uptakes for both propyne and propadiene at low pressures. NKMOF-1-M separated a ternary propyne/propadiene/propylene (0.5 : 0.5 : 99.0) mixture with the highest reported selectivity for the production of polymer-grade propylene (99.996 %) at ambient temperature, as attributed to its strong binding affinity for propyne and propadiene over propylene. Moreover, we were able to visualize propyne and propadiene molecules in the single-crystal structure of NKMOF-1-M through a convenient approach under ambient conditions, which helped to precisely understand the binding sites and affinity for propyne and propadiene. These results provide important guidance on using ultramicroporous MOFs as physisorbent materials.

10.
Med Sci Monit ; 25: 2386-2396, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30938333

RESUMO

BACKGROUND Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. RESULTS In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value <0.001). qRT-PCR confirmed the reliability of the RNA sequencing results. Depletion of the top 5 upregulated mRNAs reversed the resistant index, increased apoptotic SGC7901/DDP cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that the DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton organization, cell binding, signal transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in cancer, regulation of actin cytoskeleton, and pathways in cancer. CONCLUSIONS The present study is the first to interrogate mRNAs profiles in human GC cells with cisplatin resistance using RNA sequencing, which may assist in discovering potential therapeutic targets for cisplatin-resistant GC patients.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Gástricas/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/metabolismo , Cisplatino/farmacologia , Resistência a Múltiplos Medicamentos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , RNA Mensageiro/análise , Reprodutibilidade dos Testes , Transcriptoma/genética
11.
J Colloid Interface Sci ; 546: 92-100, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30904688

RESUMO

We reported a carbon nanohorns/gold nanoparticles composites-based impedimetric aptasensor for carbendazim (CBZ) detection in lettuce and orange juice at picogram levels. The increased electron-transfer resistance, resulting from the formation of CBZ-aptamer complex, was recorded by electrochemical impedance spectroscopy as the aptasensor response for CBZ. Under the optimal conditions, the proposed aptasensor displayed a linear response for CBZ ranging from 1 to 1000 pg mL-1 with a detection limit of 0.5 pg mL-1. Noteworthy, the as-developed aptasensor displayed the lowest detection limit for CBZ among the previously reported methods. Common pesticides (atrazine, thiamethoxam, etc.) with 100-fold concentration did not interfere the CBZ detection. For CBZ detection in lettuce and orange juice, satisfactory recoveries were obtained with standard addition method. Statistics demonstrated that no significant differences were found between the data provided by standard HPLC-MS reference method and developed aptasensing method in term of accuracy and precision. We believe that the proposed aptasensor possesses a potential application for CBZ monitoring in agricultural product and food.


Assuntos
Aptâmeros de Nucleotídeos/química , Benzimidazóis/análise , Carbamatos/análise , Carbono/química , Ouro/química , Nanopartículas/química , Técnicas Biossensoriais , Impedância Elétrica , Técnicas Eletroquímicas , Tamanho da Partícula , Propriedades de Superfície
12.
Med Sci Monit ; 25: 2169-2178, 2019 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-30904920

RESUMO

BACKGROUND Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat colon cancer. Despite impressive initial clinical responses, drug resistance has dramatically compromised the effectiveness of DOX. However, the underlying mechanisms of chemotherapeutic resistance in colon cancer remain poorly understood. MATERIAL AND METHODS In this study, we compared the expression of miR-222-3p in DOX-resistant colon cancer cells (LoVo/ADR) with the corresponding DOX-sensitive parental cells (LoVo/S) using quantitative real-time PCR. In addition, miR-222-3p inhibitors were infected into LoVo/ADR cell lines and the effects of this treatment were assessed. The Cell Counting Kit 8 assay was employed to verify the sensitivity of colon cancer cell lines to DOX. EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry, and in vivo subcutaneous tumorigenesis were used to assess cell proliferation and apoptosis. Transwell and wound healing assays were used to investigate cell migration after adding DOX. Additionally, the expression of forkhead box protein P2 (FOXP2), P-glycoprotein (P-gp) and caspase pathway-associated markers was assessed by western blotting. RESULTS Our results showed that miR-222-3p was upregulated in LoVo/ADR compared with the expression in LoVo/S cells. Additionally, downregulation of miR-222-3p in LoVo/ADR cells increased their sensitivity to DOX, reduced P-gp expression, and activated the caspase pathway. However, the downregulation of FOXP2 could efficiently reverse the effect of miR-222-3p inhibitors on LoVo/ADR cells. CONCLUSIONS Taken together, our results showed that miR-222-3p induced DOX resistance via suppressing FOXP2, upregulating P-gp, and inhibiting the caspase pathway.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Doxorrubicina/farmacologia , Fatores de Transcrição Forkhead/metabolismo , MicroRNAs/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação para Baixo/efeitos dos fármacos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Fatores de Transcrição Forkhead/genética , Humanos , MicroRNAs/genética , Ativação Transcricional , Regulação para Cima/efeitos dos fármacos
13.
J Neuroimmunol ; 330: 155-158, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30904736

RESUMO

Anti-Homer-3 antibody associated cerebellar ataxia is a rare autoimmune cerebellar ataxia, which had been previously reported in 2 cases only. Here we present the third case where a middle-aged female experienced progressive cerebellar ataxia. A novel cerebellar ataxia antibody panel indicated sera of the patient was positive for anti-Homer-3 antibodies and established the diagnosis. Given steroids and long-term mycophenolate mofetil, the patient experienced partial improvement and remained stable in the follow-ups. Our report indicated immune-mediated causes should be considered in the context of 'idiopathic' cerebellar ataxia and immunotherapy could have therapeutic effects.

14.
Int J Biol Macromol ; 129: 601-607, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30738168

RESUMO

After spinal cord injury, microglial cells are activated and converted to an M1 phenotype. Emerging evidence supports the hypothesis that glucose reprogramming accompanies microglial activation. What contributes to the activation of microglia and glucose reprogramming, however, remains unclear. In the current study, we investigated the role and underlying mechanism of a-synuclein in regulating the aerobic glycolysis in microglia. We found that a-synuclein contributed to the reprogramming of glucose metabolism in microglia by promoting glycolysis and inhibiting mitochondrial biogenesis and oxidative phosphorylation. Further studies demonstrated that pyruvate kinase M2 (PKM2), a rate-limiting enzyme in glycolysis, mediated glucose reprogramming regulated by a-synuclein. A co-immunoprecipitation assay and Western blot assay demonstrated that a-synuclein interacted with PKM2. Further studies demonstrated that knockdown of PKM2 in a-synuclein-exposed microglia markedly reduced glycolysis and lactate production. Additionally, a-synuclein exposure promoted migration abilities in glucose-cultured microglia, whereas migration ability was suppressed in PKM2 knockdown microglia. Additionally, the PKM2 activator TEPP-46 promoted migration ability in a-synuclein-treated microglia, compared to treatment with a-synuclein alone. In conclusion, we demonstrate a PKM2-dependent glycolysis of a-synuclein in microglial.


Assuntos
Movimento Celular/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Microglia/citologia , Microglia/efeitos dos fármacos , Piruvato Quinase/metabolismo , alfa-Sinucleína/farmacologia , Animais , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética , Humanos , Microglia/metabolismo , Piruvato Quinase/deficiência , Piruvato Quinase/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
15.
Acta Neuropathol ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30511086

RESUMO

TAR DNA-binding protein 43 (TDP-43) aggregation is the most common pathological hallmark in frontotemporal dementia (FTD) and characterizes nearly all patients with motor neuron disease (MND). The earliest stages of TDP-43 pathobiology are not well-characterized, and whether neurodegeneration results from TDP-43 loss-of-function or aggregation remains unclear. In the behavioral variant of FTD (bvFTD), patients undergo selective dropout of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices. Here, we examined TDP-43 pathobiology within these vulnerable neurons in the FI across a clinical spectrum including 17 patients with sporadic bvFTD, MND, or both. In an exploratory analysis based on our initial observations, we further assessed ten patients with C9orf72-associated bvFTD/MND. VENs and fork cells showed early, disproportionate TDP-43 aggregation that correlated with anatomical and clinical severity, including loss of emotional empathy. The presence of a TDP-43 inclusion was associated with striking nuclear and somatodendritic atrophy. An intriguing minority of neurons lacked detectable nuclear TDP-43 despite the apparent absence of a cytoplasmic TDP-43 inclusion. These cells showed neuronal atrophy comparable to inclusion-bearing neurons, suggesting that the loss of nuclear TDP-43 function promotes neurodegeneration, even when TDP-43 aggregation is inconspicuous or absent.

16.
Nat Mater ; 17(12): 1128-1133, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30397312

RESUMO

There are great challenges in developing efficient adsorbents to replace the currently used and energy-intensive cryogenic distillation processes for olefin/paraffin separation, owing to the similar physical properties of the two molecules. Here we report an ultramicroporous metal-organic framework [Ca(C4O4)(H2O)], synthesized from calcium nitrate and squaric acid, that possesses rigid one-dimensional channels. These apertures are of a similar size to ethylene molecules, but owing to the size, shape and rigidity of the pores, act as molecular sieves to prevent the transport of ethane. The efficiency of this molecular sieve for the separation of ethylene/ethane mixtures is validated by breakthrough experiments with high ethylene productivity under ambient conditions. This material can be easily synthesized at the kilogram scale using an environmentally friendly method and is water-stable, which is important for potential industrial implementation. The strategy of using highly rigid metal-organic frameworks with well defined and rigid pores could also be extended to other porous materials for chemical separation processes.

17.
Onco Targets Ther ; 11: 7385-7394, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425526

RESUMO

Purpose: Accumulating evidence demonstrates that circRNAs regulate diverse cellular processes and cancer progression. However, it remains unclear whether circRNAs play any functional role in esophageal squamous cell carcinoma (ESCC). Materials and methods: The significance of circRNA_100876 in ESCC was analyzed by studying circRNA_100876 expression in ESCC tissues and the association between circRNA_100876 expression and clinicopathologic parameters. The biological effects of circRNA_100876 knockdown by lentivirus-mediated siRNAs on cell proliferation, cell cycle, apoptosis, and migration were investigated in vitro and in vivo. Results: CircRNA_100876 expression was upregulated (P<0.05) and was negatively correlated with survival outcome (P<0.05) in ESCC. Inhibition of proliferation, migration, invasion, and epithelial-mesenchymal transition progression was confirmed after circRNA_100876 depletion. Conclusion: Dysregulation of circRNA_100876 expression leads to poor prognosis in ESCC by accelerating cell proliferation and metastasis.

18.
Sci Adv ; 4(10): eaau1393, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30410983

RESUMO

Metal-organic framework (MOF) membranes show great promise for propene/propane separation, yet a sharp molecular sieving has not been achieved due to their inherent linker mobility. Here, zeolitic imidazolate framework ZIF-8-type membranes with suppressed linker mobility are prepared by a fast current-driven synthesis (FCDS) strategy within 20 min, showing sharpened molecular sieving for propene/propane separation with a separation factor above 300. During membrane synthesis, the direct current promotes the metal ions and ligands to assemble into inborn-distorted and stiffer frameworks with ZIF-8_Cm (a newly discovered polymorph of ZIF-8) accounting for 60 to 70% of the membrane composition. Molecular dynamics simulations further verify that ZIF-8_Cm is superior to ZIF-8_I 4 ¯ 3 m (the common cubic phase) for propene/propane separation. FCDS holds great potential to produce high-quality, ultrathin MOF membranes on a large scale.

19.
Science ; 362(6413): 443-446, 2018 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-30361370

RESUMO

The separation of ethane from its corresponding ethylene is an important, challenging, and energy-intensive process in the chemical industry. Here we report a microporous metal-organic framework, iron(III) peroxide 2,5-dioxido-1,4-benzenedicarboxylate [Fe2(O2)(dobdc) (dobdc4-: 2,5-dioxido-1,4-benzenedicarboxylate)], with iron (Fe)-peroxo sites for the preferential binding of ethane over ethylene and thus highly selective separation of C2H6/C2H4 Neutron powder diffraction studies and theoretical calculations demonstrate the key role of Fe-peroxo sites for the recognition of ethane. The high performance of Fe2(O2)(dobdc) for the ethane/ethylene separation has been validated by gas sorption isotherms, ideal adsorbed solution theory calculations, and simulated and experimental breakthrough curves. Through a fixed-bed column packed with this porous material, polymer-grade ethylene (99.99% pure) can be straightforwardly produced from ethane/ethylene mixtures during the first adsorption cycle, demonstrating the potential of Fe2(O2)(dobdc) for this important industrial separation with a low energy cost under ambient conditions.

20.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(8): 1002-1007, 2018 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-30187878

RESUMO

OBJECTIVE: To study the inhibitory effect of 10-gingerol on the proliferation of hepatocellular carcinoma HepG2 cells and the role of Src/STAT3 signaling pathway in mediating the effect. METHODS: SYBYL-X2.1 software was used to simulate the interaction between 10-gingerol and Src. HepG2 cells treated with 10-gingerol at 1, 3, 10 or µol/L for 24 h were assessed for cell viability using MTT assay, and EdU staining was used to detect the cell proliferation and calculate the number of positive cells. The expressions of p-Src and p-STAT3 were detected using Western blotting, and the mRNA expressions of the target genes of STAT3 (cyclin D1 and CMCC) were detected using qPCR. RESULTS: 10-gingerol was capable of forming hydrogen bond with such Src residues as TRY-340, MET-341, MET-314, ASP-404, and ILE-336. MTT assay showed that 10-gingerol at 3 and 10 µmol/L significantly lowered the viability of HepG2 cells (P < 0.001). Treatment with 1, 3, and 10 µmol/L 10-gingerol significantly reduces the number of EdU-positive HepG 2 cells (P < 0.001). Western blotting showed that 10-gingerol at 3 and 10 µmol/L significantly decreased the phosphorylation levels of Src and STAT3 in HepG2 cells (P < 0.01). 10-gingerol at 1, 3, and 10 µmol/L significantly decreased the mRNA expressions of cyclin D1 and CMCC as shown by qPCR (P < 0.01). CONCLUSIONS: 10-gingerol can dose-dependently inhibit the proliferation of HepG2 cells and suppress the activation of Src and STAT3.

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