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BACKGROUND: Collagen triple helix repeat containing-1 (CTHRC1), an extracellular matrix protein, is highly expressed in hepatocellular carcinoma (HCC) and linked to poor prognosis. Nevertheless, the precise mechanism of CTHRC1 in HCC is unclear. METHODS: Agena MassARRAY® Methylation Analysis assessed the methylation level of CTHRC1 in the promoter region. Functional assays were conducted to investigate the effects of CTHRC1 knockdown in Hep3B2.1 cells. RNA sequencing identified differentially expressed genes and lncRNAs associated with angiogenesis after CTHRC1 knockdown. Furthermore, differential alternative splicing (AS) and gene fusion events were analyzed using rMATS and Arriba. RESULTS: In HCC cell lines, CTHRC1 was highly expressed and associated with hypomethylation. Downregulation of CTHRC1 inhibited Hep3B2.1 cell proliferation, migration, and invasion, blocked cells in the G1/S phase, and promoted apoptosis. We obtained 34 mRNAs and 7 lncRNAs differentially expressed between the NC and CTHRC1 inhibitor groups. Additionally, we found 4 angiogenesis-related mRNAs and lncRNAs significantly correlated with CTHRC1. RT-qPCR results showed that knockdown of CTHRC1 in Hep3B2.1 cells resulted in significantly aberrant expression of CXCL6, LINC02127, and AC020978.8. Moreover, the role of CTHRC1 in HCC development may be associated with events, like 12 AS events and 5 pairs of fusion genes. CONCLUSIONS: High expressed CTHRC1 is associated with hypomethylation and may promote HCC development, involving events like angiogenesis, alternative splicing, and gene fusion.
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Currently, clinically available drug-loaded embolic microspheres have some shortcomings, such as being invisible with standard medical imaging modalities and only being able to carry positively charged drugs. The visualization of drug-loaded microspheres is very important for real-time monitoring of embolic position to improve the therapeutic effect. Meanwhile, the visualization of microspheres can enable postoperative reexamination, which is helpful for evaluating the embolization area and guiding the subsequent treatment. In addition, microspheres capable of loading different charged drugs can increase the choice of chemotherapeutic drugs and provide more possibilities for treatment. Therefore, it is of great importance to explore drug-loaded microspheres capable of multimodal imaging and loading drugs with different charges for transarterial chemoembolization (TACE) treatment of liver tumors. In our study, we designed a kind of nano-assembled microspheres (NAMs) that can realize computer X-ray tomography (CT)/magnetic resonance imaging (MRI)/Raman multimodal imaging, be loaded with positively and negatively charged drugs and test their imaging ability, drug loading and biological safety. The microspheres have strong attenuation performance for CT, high T2 relaxation for MRI and good sensitivity for surface enhanced Raman spectroscopy (SERS). At the same time, our microspheres can also load the positively charged drug, doxorubicin (DOX), and negatively charged drug Cisplatin. One gram of NAMs can hold 168 mg DOX or 126 mg Cisplatin, which has good drug loading and sustained-release capacity. Cell experiments also showed that the nano-assembled microspheres had good biocompatibility. Therefore, as multimodal developed drug loaded microspheres, nano assembled microspheres have great potential in TACE treatment of liver cancer.
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Few studies have been performed to investigate the effect of vitamin D supplementation and T2DM in type 2 diabetic animal models. The present study aimed to explore the relationship between early 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the incidence of T2DM and determine whether early 1,25(OH)2D3 supplementation was associated with inflammation in KK-Ay mice. The KK-Ay mice were divided into 4 vitamin D treatment groups, the low-dose vitamin D supplementation group (VDS-L, 1.5 µg/kg 1,25(OH)2D3), moderate-dose vitamin D supplementation group (VDS-M, 3.0 µg/kg 1,25(OH)2D3), high-dose vitamin D supplementation group (VDS-H, 6.0 µg/kg 1,25(OH)2D3) and the model control group (MC). C57BL/6J mice were used as the controls. The treatment period lasted for 9 wk. During this treatment period, fasting blood glucose (FBG) level of the mice was measured on a weekly basis. The levels of lipid profile, insulin and inflammation biomarkers were determined after 9 wk of 1,25(OH)2D3 intragastric gavage. After 9 wk of 1,25(OH)2D3 intragastric gavage, FBG level was significantly decreased in the vitamin D treatment groups compared with the MC group. The number of T2DM incidence in the VDS-L group (n=7), VDS-M group (n=5) and VDS-H group (n=3) was lower than those in the MC group (n=10) on week 9. Moreover, serum C-reactive protein (CRP) and interleukin-6 (IL-6) in the vitamin D treatment groups were significantly suppressed by 1,25(OH)2D3 administration compared with the MC group. Early 1,25(OH)2D3 supplementation could effectively lower the incidence of T2DM via ameliorating inflammation in KK-Ay mice.
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Diabetes Mellitus Tipo 2 , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos , Incidencia , Inflamación/tratamiento farmacológico , Inflamación/prevención & control , Ratones , Ratones Endogámicos C57BL , Vitamina D/análogos & derivadosRESUMEN
BACKGROUND: Oculomotor nerve palsy (ONP) is a common symptom of posterior communicating artery aneurysm (PcomAA) that can lead to impaired eye movement and pupil dilation. Currently, surgical clipping and endovascular embolization are the two most popular treatment methods for PcomAA-induced ONP; however, the recovery outcome between the two methods remains to be elucidated. METHODS: In the present study, we thoroughly compared the pretreatment factors and recovery outcome of the two treatments on 70 patients with PcomAA-induced ONP. The patients were separated into two groups based on the treatment that was received. Pretreatment factors, including age, sex, time period between ONP onset and treatment, ONP type, aneurysm diameter, status of subarachnoid hemorrhage and aneurysm rupture were recorded for each individual patient. Recovery outcome of the patients was assessed over a 12-month period. RESULTS: No significant differences were observed in any of the analyzed factors. Importantly, we revealed a significantly higher full recovery rate for the patients receiving the surgical clipping treatment than the ones that received the endovascular embolization treatment. In addition, we showed that patients' age was negatively correlated with the recovery extent in both treatment groups. CONCLUSIONS: The outcome of our study suggests that surgical clipping might be a better option to treat PcomAA-induced ONP.
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Embolización Terapéutica/métodos , Procedimientos Endovasculares/métodos , Aneurisma Intracraneal/terapia , Enfermedades del Nervio Oculomotor/etiología , Recuperación de la Función , Adulto , Anciano , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Instrumentos QuirúrgicosRESUMEN
Long non-coding RNAs (lncRNAs) are closely associated with tumorigenesis of various malignancies, including glioma. However, the roles of most lncRNAs in glioma remain undiscovered. The present study for the first time explored the roles of NFIA-AS2 in glioma. Based on informatic analyses by online database, lncRNA NFIA-AS2 in glioma tissues was overexpressed and further confirmed in glioma tissues and cells by quantitative real-time PCR (qRT-PCR). High expression of NFIA-AS2 was closely correlated with poor prognosis and might be an independent prognostic factor for PFS and OS. Functionally, silenced NFIA-AS2 could remarkably hinder glioma cell proliferation, migration and invasion, and cause the apoptosis. Mechanistic investigation disclosed that NFIA-AS2 interacted with miR-655-3p and inversely connected with miR-655-3p in glioma. Additionally, miR-655-3p was proved to regulate the expression of ZFX. Final rescue assay demonstrated that ZFX overexpression or miR-655-3p downregulation could neutralize the suppressive effects of NFIA-AS2 knockdown on glioma progression. In conclusion, this study firstly reported that NFIA-AS2 could promote the progression of glioma by targeting the miR-665-3p/ZFX axis, which highlighted that NFIA-AS2 could be a novel biomarker and therapeutic target for glioma patients.
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Regulación Neoplásica de la Expresión Génica/genética , Expresión Génica/genética , Glioma/genética , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , MicroARNs/metabolismo , Factores de Transcripción NFI/genética , ARN Largo no Codificante/genética , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Glioma/terapia , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Terapia Molecular Dirigida , Factores de Transcripción NFI/metabolismo , Invasividad Neoplásica/genética , ARN Largo no Codificante/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: Several studies have indicated that inflammatory markers were associated with the risk of mild cognitive impairment (MCI) in type 2 diabetes (T2D). Serum folate was related to MCI as well as inflammation. However, no studies have investigated the association between inflammatory markers and MCI taking account of serum folate level in T2D patients. This study aimed to conduct a case-control study to evaluate the association between inflammatory markers and MCI taking account of serum folate level in Chinese patients with T2D. METHODS: This study consisted of 126 T2D patients (63 cases with MCI and 63 controls without MCI). Clinical parameters, serum folate, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were measured. Spearman correlation analysis and logistic regression analysis were used to analyze the association between the inflammatory markers and the risk of MCI in T2D patients. RESULTS: There were higher serum hs-CRP, IL-6 and TNF-α in T2D cases with MCI compared with the controls. Serum folate was negatively correlated with hs-CRP, TNF-α, and IL-6 (P < 0.05). In multivariate analysis, there were significant associations between serum IL-6 or hs-CRP and MCI after adjusting for the confounding variables, however, the association between hs-CRP and MCI disappeared after further adjusting for serum folate. Further subgroup analysis revealed that the significant association between hs-CRP and MCI only existed in the low folate subgroup (< 7.0 µg/L; OR = 3.34, 95% CI: 1.05-10.64), not in the high folate subgroup (≥7.0 µg/L; OR = 2.16, 95% CI: 0.68-6.88) after adjusting for the confounding variables. CONCLUSIONS: Serum IL-6 and hs-CRP were associated with the risk of MCI in Chinese patients with T2D. Serum folate might modify the association between serum hs-CRP and MCI in T2D patients.
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Disfunción Cognitiva/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Anciano , Proteína C-Reactiva/metabolismo , China/epidemiología , Disfunción Cognitiva/sangre , Disfunción Cognitiva/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Ácido Fólico/sangre , Humanos , Interleucina-6/sangre , Modelos Logísticos , Análisis Multivariante , Oportunidad Relativa , Factor de Necrosis Tumoral alfa/sangreRESUMEN
The association of serum vitamin D deficiency and metabolic risk factors in Chinese adults with prediabetes (PreDM) has not been investigated. The present study aimed to investigate the association of serum vitamin D deficiency and metabolic risk factors in Chinese adults with PreDM. In this cross-sectional study, we stratified 412 PreDM patients into vitamin D sufficient, vitamin D insufficient and vitamin D deficient subgroups. The physical examination data was collected. Serum 25-hydroxyvitamin D3 [25(OH)D3] were measured by high performance liquid chromatography. The prevalence of vitamin D deficiency and insufficiency in PreDM patients were 30.58% and 26.70%, respectively. Compared with the vitamin D deficient group, the prevalence of metabolic syndrome, central obesity, hyperglycemia and hypertension were higher than those in the vitamin D insufficient or sufficient group (p<0.05). Moreover, the prevalence of dyslipidemia in the vitamin D deficient group was higher than those in the vitamin D sufficient group (p<0.05). We observed an inverse relationship between 25(OH)D3 levels and waist circumference, triglyceride, and serum uric acid (ß=-0.315; ß=-0.134; ß=-0.239), a positive relationship between 25(OH)D3 levels and high-density lipoprotein cholesterol (ß=0.197) after adjusting for age, sex and body mass index. Vitamin D deficiency is very common among PreDM patients in China and this deficiency is related to metabolic risk factors.
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Estado Prediabético , Deficiencia de Vitamina D , Adulto , Anciano , China/epidemiología , HDL-Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Prediabético/complicaciones , Estado Prediabético/epidemiología , Factores de Riesgo , Triglicéridos/sangre , Ácido Úrico/sangre , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Circunferencia de la Cintura , Adulto JovenRESUMEN
Gliomas are the most common type of malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotypes. Despite advances in treatments during past decades, prognosis of the disease remains poor, with a median survival time of 12-14 months. Future studies on the molecular mechanism of the disease may provide the theoretical basis to identify new targets for effective therapies. The present study revealed that in glioblastoma cells, the overexpression of cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1) promoted proliferation, while silencing of CYP27A1 inhibited proliferation, without affecting migration and invasion. CYP27A1 protein was upregulated in glioblastoma tissues, indicating that CYP27A1 is an oncogene. The downregulation of specific microRNAs (miRNA) may contribute to the upregulation of oncogenes in glioblastoma. A common strategy was used to predict target miRNAs of CPY27A1 using the miRanda algorithm. miR-211 and miR-204 could target the 3'untranslated region of CPY27A1 mRNA. Additional studies confirmed that the overexpression of miR-204 inhibited CPY27A1 expression in glioblastoma cells. Finally, it was identified that miR-204 was downregulated in glioblastoma and that its overexpression inhibited proliferation, migration and invasion in glioblastoma cells. Thus, it was concluded that miR-204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma.
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BACKGROUND/AIMS: The mechanism, by which vitamin D influences inflammatory biomarkers in type 2 diabetes mellitus (T2DM), is not very well known. Thus, a meta-analysis of randomized controlled trials was conducted to assess the effect of vitamin D supplementation on some inflammatory biomarkers in T2DM subjects. METHODS: We searched randomized controlled trials from PubMed and the Cochrane Library in October 2017 and conducted a meta-analysis to evaluate the effectiveness of vitamin D supplementation on high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Either a fixed-effects or a random-effects model was used to calculate pooled effects. RESULTS: We identified 13 studies that met our inclusion criteria. The results indicated that the vitamin D supplementation significant decreased the hs-CRP level by 0.45 µg/mL, whereas the vitamin D supplementation did not influence the TNF-α and IL-6. Subgroup analysis showed that vitamin D significantly lowered hs-CRP by 0.34 µg/mL among trials with a daily vitamin D dose ≤4,000 IU and by 0.31 µg/mL among trials with time of vitamin D supplementation > 12 weeks. CONCLUSIONS: Vitamin D supplementation is beneficial for the reduction of hs-CRP inT2DM subjects but does not have a significant influence on TNF-α and IL-6 in T2DM subjects.
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Diabetes Mellitus Tipo 2/sangre , Suplementos Dietéticos , Vitamina D/administración & dosificación , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Humanos , Interleucina-6/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Factor de Necrosis Tumoral alfa/sangre , Vitaminas/administración & dosificaciónRESUMEN
BACKGROUND: The association of vitamin D status and inflammation prediabetes mellitus (PreDM) individuals has not been investigated. We investigated the association of serum 25-hydroxyvitamin D3 (25(OH) D3) with adipokines and inflammatory markers in persons with PreDM. METHODS: In this cross-sectional study, we stratified 418 nondiabetic subjects as having PreDM or normal fasting glucose (NFG), and divided PreDM or NFG subjects into vitamin D sufficient, vitamin D insufficient and vitamin D deficient subgroups. 25(OH) D3 concentrations were determined by HPLC. Serum tumor necrosis factor-α (TNF-α), interleiukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP), adiponectin, leptin and resistin were measured by ELISA. RESULTS: In the PreDM group, compared with those in the vitamin D sufficient subgroup, vitamin D insufficient subgroup and vitamin D deficient subgroup had higher concentrations of hs-CRP and leptin (P<0.05). In the PreDM-deficient or PreDM-insufficient subgroup, mean hs-CRP and leptin concentration was higher than in the PreDM-sufficient, NFG-deficient, NFG-insufficient and NFG-sufficient subgroups (P<0.05). Serum 25(OH) D3 concentrations were inversely associated with hs-CRP and leptin concentrations after adjusted the BMI only in the PreDM group (P<0.05). At the multivariate analysis, hs-CRP and leptin were the major determinant of 25(OH) D3 concentration (ß=-0.174 and ß=-0.171, respectively). CONCLUSIONS: 25(OH) D3 status in PreDM individuals was inversely correlated with concentrations of hs-CRP and leptin, suggesting their involvement in the inflammation response between vitamin D status and PreDM.
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Adipoquinas/sangre , Calcifediol/sangre , Estado Prediabético/sangre , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Inflamación/sangre , Modelos Lineales , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Glioblastoma is the most common type of primary brain tumor in adults, and is usually fatal in a short duration. Acquiring a better understanding of the pathogenic mechanisms of glioblastoma is essential to the design of effective therapeutic strategies. Grb2-associated binding protein 2 (GAB2) is a member of the daughter of sevenless/Gab family of scaffolding adapters, and has been reported to be important in the development and progression of human cancer. Previously, it has been reported that GAB2 is expressed at high levels in glioma, and may serve as a useful prognostic marker for glioma and a novel therapeutic target for glioma invasion intervention. Elucidating why GAB2 is overexpressed in glioma, and investigating how to downregulate it will assist in further understanding the pathogenesis and progression of the disease, and to offer novel targets for therapy. The present study used in situ hybridization to detect microRNA (miR)197 expression levels and Targetscan to predict that the 3'-UTR of GAB2 was targeted by miR-197. Northern blotting and reverse transcriptionquantitative polymerase chain reaction were also conducted in the current study. miR-197 is downregulated in glioblastoma tissues, compared with adjacent normal tissues, however it involvement continues to be detected in the disease. The results of the present study demonstrated that miR197, as a tumor suppressor gene, inhibited proliferation by regulating GAB2 in glioblastoma cells. Furthermore, GAB2 was not only upregulated in glioma, but its expression levels were also associated with the grades of glioma severity. In addition, overexpression of GAB2 suppressed the expression of miR197 in glioblastoma cells. Therefore, restoration of miR197 and targeting GAB2 may be used, in conjunction with other therapies, to prevent the progression of glioblastoma.
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Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Neoplasias Encefálicas/metabolismo , Proliferación Celular , Glioblastoma/metabolismo , MicroARNs/biosíntesis , Proteínas de Neoplasias/biosíntesis , ARN Neoplásico/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Anciano , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Femenino , Glioblastoma/genética , Glioblastoma/patología , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Proteínas de Neoplasias/genética , ARN Neoplásico/genéticaRESUMEN
Glioblastoma is the most common primary malignancy of the adult central nervous system (CNS) and is associated with an exceptionally poor prognosis. Elucidation of the pathogenesis and molecular changes will help us to further understand the pathogenesis and progression of the disease and offer new therapeutic targets. FUS1 (TUSC2, tumor suppressor candidate 2) is a tumor-suppressor gene located on human chromosome 3p21. Restoration of FUS1 function in human non-small cell lung cancer (NSCLC) cells was found to significantly inhibit tumor cell growth and modulate the chemosensitivity of lung cancer cells. Yet, its role in human glioblastoma has rarely been addressed. In the present study, we demonstrated that low expression of FUS1 was detected in high-grade human glioma, implying that FUS1 expression is negatively associated with progression of the disease. Subsequent studies confirmed that FUS1 overexpression inhibited the proliferation, migration and invasion of human glioblastoma cells. In addition, we found that FUS1 overexpression significantly upregulated miR-197 expression in the glioblastoma cells. We also revealed that miR-197 suppressed the proliferation, migration and invasion of the cells as well as the silencing of miR-197 attenuated the biological functions of FUS1. Using human glioblastoma tissue samples, we demonstrated that miR-197 is negatively associated with metastasis. All the results demonstrated that FUS1 acts as a tumor-suppressor gene by upregulating miR-197 in human glioblastoma and implied that restoration of FUS1 and miR-197 could be new therapeutic strategies for glioblastoma.
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Proliferación Celular/genética , Glioblastoma/genética , MicroARNs/biosíntesis , Proteínas Supresoras de Tumor/biosíntesis , Adulto , Anciano , Línea Celular Tumoral , Movimiento Celular/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Glioblastoma/patología , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica/genética , Estadificación de Neoplasias , Proteínas Supresoras de Tumor/genéticaRESUMEN
This study evaluates the bleaching efficiency of the hydrogen peroxide bleaching process combined with laccase-mediated system pretreatment (LMS-HPBP) in the treatment of scoured cotton fabric. By changing the factors of laccase-mediated system pretreatment and the hydrogen peroxide bleaching process and examining the subsequent whiteness value and retained tensile strength of the samples, we find three LMS-HPBP processes that are more environment friendly than the conventional hydrogen peroxide bleaching process (CHPBP): (i) bleaching with lower dosage of hydrogen peroxide; (ii) bleaching at reduced temperature; (iii) bleaching for shortened duration. Whiteness, retained tensile strength and K/S values of cotton fabric samples treated by i-iii processes were similar to or higher than those by CHPBP. X-ray diffraction (XRD) analysis also demonstrated that the three processes rendered fabric of both lower crystallinity and bigger crystallite size than those by CHPBP. In addition, the "green" short-flow process was developed to treat cotton fabric and the results obtained shows this method is feasible as a new energy-saving process.
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Blanqueadores/química , Fibra de Algodón , Tecnología Química Verde/métodos , Peróxido de Hidrógeno/química , Lacasa/metabolismo , Estudios de Factibilidad , Tecnología Química Verde/economía , Concentración de Iones de Hidrógeno , Temperatura , Trametes/enzimología , Triazoles/químicaRESUMEN
Superhydrophobic surfaces were fabricated by the complex coating of silica nanoparticles with functional groups onto cotton textiles to generate a dual-size surface roughness, followed by hydrophobization with stearic acid, 1H, 1H, 2H, 2H-perfluorodecyltrichlorosilane or their combination. The wettability and morphology of the as-fabricated surfaces were investigated by contact angle measurement and scanning electron microscopy. Characterizations by transmission electron microscopy, Fourier transformation infrared spectroscopy, and thermal gravimetric analysis were also conducted.