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The separation of acetylene from ethylene is a crucial process in the petrochemical industry, because even traces of acetylene impurities can poison the catalysts of ethylene polymerization. Herein, we synthesize a new family of 3D porous aromatic frameworks (PAFs), non-functionalized PAF-28, carbene-functionalized PAF-28 (cPAF-28) and imidazolium-functionalized PAF-28 (iPAF-28), via Sonogashira coupling reactions. These PAFs show high porosity and good thermal stability. Both cPAF-28 and iPAF-28 are proved to be good candidates for C2H2 adsorption, demonstrated by C2H2/C2H4 selectivity of 12.2 and 15.4, and C2H2 capacity of 48 cm3 g-1 and 57 cm3 g-1, which are significantly higher than those of non-functionalized PAF-28 (1.8, 37 cm3 g-1). Furthermore, the cPAF-28 and iPAF-28 display good breakthrough performance and remarkable recyclability for the separation of the C2H2/C2H4 gas mixture. In addition, the C2H2/C2H4 adsorption sites are revealed by DFT calculations. This work sheds a new light on gas molecular recognition by tailoring the pore chemistry of PAFs.
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Objective To explore the anti-tumor activity of oncolytic vaccinia virus expressing CD40L (CD40L-VV) against colorectal cancer. Methods The CD40L-VV was obtained by integrating the sequence of CD40L into the skeleton of oncolytic vaccinia virus(VV). The tumor cells were infected with VV and CD40L-VV to verify their oncolytic activity and the expression of CD40L in vitro. After the tumor model of colorectal cancer was treated with VV and CD40L-VV, the tumor growth was monitored, and the phenotype of tumor infiltrating T cells was analyzed by flow cytometry. The anti-tumor activity of recombinant oncolytic VV was also reflected by detecting the production of cytokine and the proliferation activity of tumor infiltrating T cells. Results Microscopic observation and Western blot assay showed that CD40L-VV could effectively infect tumor cells and express CD40L. Cell viability assay showed that VV and CD40L-VV had dose-dependent lytic ability against tumor cells. The results of tumor transplantation in vivo showed that CD40L-VV had stronger ability to inhibiting tumor growth than VV. Flow cytometry showed that tumor infiltrating T cells in the CD40L-VV group had stronger cytokine secretion ability, stronger proliferative activity and more memory cell phenotypes than those in the VV group. Conclusion CD40L-VV can significantly inhibit the growth of colorectal cancer cells and enhance the anti-tumor activity of T cells in vivo.
Assuntos
Neoplasias Colorretais , Vírus Oncolíticos , Animais , Ligante de CD40/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Camundongos , Vírus Oncolíticos/genética , Linfócitos T , Vaccinia virus/genéticaRESUMO
The imbalance of SUMOylation is related to different cancers, including gastric cancer (GC). Ginkgolic acid (GA) inhibits the growth and invasion of many cancer cells, and it has been reported to restrain SUMOylation. However, the role of GA in GC and whether it functions through SUMOylation remains to be clarified. Our research revealed that GA (15:1) inhibited cell proliferation, migration, epithelial-mesenchymal transition (EMT) and overall protein SUMOylation in BGC823 and HGC27 cells. In addition, knockdown of SUMO1 (small ubiquitin-like modifier) instead of SUMO2/3 played a similar role to GA in cell behaviors. Besides, nuclear IGF-1R (insulin-like growth factor 1 receptor) expression was markedly upregulated in GC cells compared to normal gastric epithelial cells. GA prevented IGF-1R from binding to SUMO1, thereby suppressing its nuclear accumulation. Further research found that IGF-1R directly bound to SNAI2 (snail family zinc finger 2) promoter. The interference of IGF-1R downregulated the mRNA and protein levels of SNAI2, while the overexpression of SUMO1, IGF-1R and UBC9 (SUMO-conjugating enzyme) played the opposite role. Furthermore, the co-transfection of SUMO1, UBC9 and IGF-1R vectors or the overexpression of SNAI2 reversed the inhibitory effects of GA on cell proliferation, migration and EMT. Finally, GA impeded the growth of GC xenografts and decreased the expression of nuclear IGF-1R and SNAI2 in vivo. In conclusion, these findings demonstrated that GA hindered the progression of GC by inhibiting the SUMOylation of IGF-1R. Thus, GA might be a promising therapeutic for GC.
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Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptor IGF Tipo 1/metabolismo , Salicilatos/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/genética , Proteína SUMO-1/antagonistas & inibidores , Proteína SUMO-1/genética , Proteína SUMO-1/metabolismo , Salicilatos/uso terapêutico , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/antagonistas & inibidores , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Sumoilação/efeitos dos fármacos , Transplante HeterólogoRESUMO
BACKGROUND: Cervical cancer (CC) is the second serious health threat in women worldwide. LncRNA (ZNFX1 antisense RNA 1) ZFAS1 has been observed to abnormally express in human cancers. However, the expression pattern, clinical significance and molecular mechanism of ZFAS1 have not been thoroughly studied in CC. METHODS: qRT-PCR was performed to examine the differential expression of ZFAS1 in CC tissues and adjacent normal cervical tissues. Gain- and loss-of-function experiments were constructed to test the functional role of ZFAS1 in CC by CCK-8, colony formation, transwell and xenograft models assays. Luciferase reporter, RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), RNA pull-down assays were used to reveal the underlying mechanisms. RESULTS: We found that ZFAS1 was significantly upregulated in CC tissues. Elevation of ZFAS1 correlated with advanced FIGO stage, lymph node and distant metastasis, and also indicated poor overall survival in patients with CC. Functional experiments demonstrated that ZFAS1 promoted CC cell proliferation, migration and invasion in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistic investigation revealed that ZAFS1 sequestered miR-647, and this RNA-RNA interaction is regulated by METLL3-mediated m6A modification. CONCLUSION: Our findings elucidate the functional roles of ZFAS1 and its m6A modification in CC cells and indicate that ZFAS1 may be a promising target for CC treatment.
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The aim of this study is to characterize demographic and morphologic characteristics of aneurysms located in the anterior communicating artery (ACoA) and to investigate possible associations between these characteristics and aneurysm rupture. We investigated 112 consecutive patients (72 ruptured and 40 unruptured) with ACoA aneurysms from a single-center database. The effects of demographic and morphologic characteristics on the risk of rupture in ACoA aneurysms were tested using univariate and multivariate logistic regression analyses, respectively. We found that larger size, greater size ratio, larger flow angle, irregular shape, and smoking of the patient were associated with the rupture of ACoA aneurysms based on univariate analysis. Size ratio (OR = 3.890, P = 0.003), irregular shape (OR = 1.068, P = 0.001), flow angle (OR = 1.054, P = 0.001), and current smoking (OR = 4.435, P = 0.009) were the strongest factors related to ruptured ACoA aneurysms based on multivariate logistic regression analysis. The areas under the curves for the flow angle and size ratio were 0.742 (95% CI 0.646-0.838; P = 0.001) and 0.736 (95% CI 0.621-0.796; P = 0.001), respectively. The strongest risk factors for rupture include size ratio, irregular shape, flow angle, and current smoking. These features should be taken into consideration to aid in the prediction of the rupture risk of ACoA aneurysms.
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Aneurisma Roto/epidemiologia , Aneurisma Roto/patologia , Artéria Cerebral Anterior , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/patologia , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/patologia , Idoso , Aneurisma Roto/etiologia , Área Sob a Curva , Angiografia Cerebral , Circulação Cerebrovascular , Bases de Dados Factuais , Feminino , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Hemorragia Subaracnóidea/complicaçõesRESUMO
Copolymerization of ethylene (E) and polar vinyl monomers remains a problem because E propagation is hindered. Herein, for the first time, we report the copolymerization of E and polar styrenes (SR ) by using an oxophilic scandium catalyst that exhibits higher turnover frequencies than both E and SR homopolymerizations when R is an electron-withdrawing group. This positive comonomer effect was elucidated through computing reaction profiles of E/SF copolymerization at the DFT (B3PW91) level of theory. It reveals that the secondary interaction between Sc3+ and phenyl of the last and penultimate inserted SF units leads to a decrease of the E insertion barrier, because the electron-withdrawing substituent enhances the electrophilicity of Sc3+ by an inductive effect mediated by the secondary interaction. After three consecutive insertions of the E units, the secondary interaction is lost and the SF insertion is kinetically preferred over the E insertion. This process is in line with the NMR spectrum analyses which show that the resultant copolymers mainly contain SR (E)x SR sequences where x≤3.
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The N-R-quinolinyl-8-amino ligands HL(1-3) (R = 2,6-(i)Pr(2)C(6)H(3) (HL(1)), 2,6-Et(2)C(6)H(3) (HL(2)), 2,6-Me(2)C(6)H(3) (HL(3))) have been prepared, which reacted readily with one equiv. of rare earth metal tris(alkyl)s to afford the corresponding bis(alkyl) complexes L(1)Y(CH(2)SiMe(3))(2)(THF) (1) and L(1-3)Lu(CH(2)SiMe(3))(2)(THF) (2-4) via alkane elimination. Contrastingly, treatment of the in situ generated neodymium tri(alkyl)s with HL(1) afforded a mono(alkyl) neodymium complex (5). Complexes 1, 2 and 5 in combination with aluminium alkyls and organoborates established homogenous ternary systems that exhibited versatile catalytic activities and trans-1,4 selectivities for the polymerization of butadiene, depending on the types of aluminium alkyl, organoborate and rare earth metal used. Furthermore, the trans-1,4 selective copolymerization of butadiene and isoprene was achieved by using the ternary system of 1/AlMe(3)/[Ph(3)C][B(C(6)F(5))(4)]. Both the kinetics of copolymerization and the thermal behavior of the copolymers were investigated.
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In a hospital based case control study, we investigated the association of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, cyclin-dependent kinase inhibitor 2B (CDKN2B) gene, and two genetic variants (rs10757274 and rs2383206) on chromosome region 9p21 with ischemic stroke in Chinese Hans. Two polymorphisms in the CDKN2A gene (rs3088440 and rs3731245) and two polymorphisms in the CDKN2B gene (rs3217992 and rs1063192) were selected by using a strategy of tagging single nucleotide polymorphisms (tSNP). We observed significant association of rs2383206 with ischemic stroke. Subjects with the GG/GA genotype of rs2383206 had a 1.51-fold (95%CI 1.11-2.05, p=0.009) increased risk of stroke, compared with those with the AA genotype. In addition, the GG/GA genotypes of rs2383206 and rs3731245 was associated with an increased risk of large vessel subtype and small vessel subtype of ischemic stroke, respectively, with ORs of 2.09 (95%CI 1.30-3.37, p=0.002) and 1.63 (95%CI 1.06-2.51, p=0.026), respectively. In gene-environmental interaction analysis, elevation of ischemic stroke risk was observed among AG+GG genotype carriers who consume alcohol, smoke cigarette, and have hypertension, with adjusted combined ORs of 2.86(1.51-5.41), 4.30(2.38-7.77), and 13.97(7.78-25.07), respectively, compared with low-risk individuals for rs2383206 (GG carriers who did not consume alcohol, smoke cigarette, and without hypertension). We provide evidence that genetic variants on chromosome region 9p21 may implicated in the prevalence of ischemic stroke in Chinese.
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Isquemia Encefálica/genética , Cromossomos Humanos Par 9 , Inibidor de Quinase Dependente de Ciclina p15/genética , Genes p16 , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Isquemia Encefálica/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologiaRESUMO
Common pathogenic mechanisms may be involved in the prevalence of ischemic stroke and coronary heart disease. Recently, genome-wide association (GWA) studies identified a chromosome region (9p21) that confers the risk of coronary heart disease. In a hospital-based case-control study conducted in Chinese Hans, we tested the hypothesis that the methylthioadenosine phosphorylase (MTAP) gene on chromosome region 9p21 is involved in the aetiology of ischemic stroke using a tagging single nucleotide polymorphism (tSNP) strategy. We observed significant association of rs10118757 in the MTAP gene with ischemic stroke. The G allele of rs10118757 was associated with an increased risk of stroke, with a per-allele OR of 1.31(95% CI, 1.04-1.65, p=0.025). The association remains after controlling for confounding factors including age, gender, body mass index, smoking, alcohol drinking, hypertension, diabetes, and hyperlipidaemia (OR=1.38, 95 CI, 1.02-1.88, p=0.039). In addition, the GA+GG genotype of rs10118757 was associated with the increased risk of an undetermined subtype of ischemic stroke (OR=2.14, 95 CI, 1.35-3.38, p=0.001). Further, we also observed the combined effects of rs10118757 with alcohol drinking and hypertension, which increased the risk of ischemic stroke. Our observations support the hypothesis that the MTAP gene may be involved in the prevalence of ischemic stroke in Chinese Hans.