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Hepatoblastoma (HB), a primary liver tumour, is notorious for its high metastatic potential and poor prognosis. Ganoderma lucidum, an edible mushroom species utilized in traditional Chinese medicine for addressing various tumour types, presents an intriguing avenue for HB treatment. However, the effectiveness of G. lucidum in managing HB and its underlying molecular mechanism necessitates further exploration. Standard in vitro assays were conducted to evaluate the impact of sporoderm-broken spores of G. lucidum (SBSGL) on the malignant characteristics of HB cells. The mechanism of SBSGL in treating HB and its tumour immunomodulatory effects were explored and validated by various experiments, including immunoprecipitation, Western blotting, mRFP-GFP-LC3 adenovirus transfection and co-localization analysis, as well as verified with in vivo experiments in this regard. The results showed that SBSGL effectively inhibited the malignant traits of HB cells and suppressed the O-GlcNAcylation of RACK1, thereby reducing its expression. In addition, SBSGL inhibited immune checkpoints and regulated cytokines. In conclusion, SBSGL had immunomodulatory effects and regulated the malignancy and autophagy of HB by regulating the O-GlcNAcylation of RACK1. These findings suggest that SBSGL holds promise as a potential anticancer drug for HB treatment.
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Hepatoblastoma , Neoplasias Hepáticas , Reishi , Hepatoblastoma/tratamento farmacológico , Hepatoblastoma/genética , Esporos Fúngicos , Autofagia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genéticaRESUMO
OBJECTIVES: To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in macular edema secondary to retinal vein occlusion (RVO-ME) patients. METHODS: An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change [ΔCMT/bl-CMT]) were analyzed. RESULTS: The automatic MPCLEIA system was able to provide results in 45â¯min with only 20⯵L sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26â¯ng/L, 23.57â¯ng/L, 1,110.12â¯ng/L, 105.52â¯ng/L, and 85.39â¯ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤-25â¯% or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category. CONCLUSIONS: Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT.
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Edema Macular , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Sistemas Automatizados de Assistência Junto ao Leito , Interleucina-8 , Edema Macular/diagnóstico , Edema Macular/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Interleucina-6 , Humor Aquoso/metabolismoRESUMO
PURPOSE: To explore if COVID-19 infection and its subsequent immunosuppressant adjustment as well as previous vaccination status are associated with higher risks of uveitis flare in patients with Behcet's disease. METHODS: This retrospective multicenter cohort study was conducted in January 2023 among patients with Behcet's uveitis, during the second wave of the COVID-19 pandemic in China, with an anticipated sample size of 250. The primary objective was to examine the association between COVID-19 infection and the occurrence of uveitis flare. The potential impact of other exposures, including the patient's vaccination status and treatment adjustments to the risk of uveitis flare and the course of COVID-19 infection were also analyzed. RESULTS: 207 patients with COVID-19 infection and 47 patients without COVID-19 infection were included. A total of 127 uveitis flares occurred in the observational period (14.29 events per 100 person-month). COVID-19 infection was found to be significantly associated with a higher rate of uveitis flare (adjusted rate ratio = 4.8, 95% CI 3.7 to 6.3, P < 0.001). However, neither systemic immunosuppressive adjustment nor COVID-19 vaccination status showed a significant association with uveitis flare or the course of COVID-19 infection. CONCLUSIONS: This study provides evidence of an association between COVID-19 infection and an increased risk of uveitis flare in patients with Behcet's disease. However, there was no significant evidence to support that baseline immunosuppressive therapy regimens, treatment adjustment after COVID-19 infection, or vaccination status were associated with higher risks of uveitis flare or prolonged COVID-19 course.
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The study investigated the effect of Compound Shougong Powder(CSGP) on the biological functions of triple-negative breast cancer(TNBC) cells and whether its mechanism of action was related to the epithelial-mesenchymal transition(EMT) signaling pathway. TNBC cells(MDA-MB-231 and BT-549) were treated with different concentrations of CSGP-containing serum. MTS assay was used to detect the effect of CSGP on the proliferation of TNBC cells. The EdU staining was used to detect the effect of CSGP on the proliferation of TNBC cells. Flow cytometry was used to examine the impact of CSGP on apoptosis of TNBC cells. Wound-healing and Transwell assays were used to evaluate the effects of different concentrations of CSGP on the migration and invasion capabilities of TNBC cells. RNA sequencing technology was utilized to elucidate its mechanism. Subsequently, qRT-PCR was performed to measure the mRNA expression levels of E-cadherin, N-cadherin, Slug, Snail, Vimentin, Twist, Zinc finger E-box-Binding homeobox 1(Zeb1), and Zinc finger E-box-Binding homeobox 2(Zeb2). Western blot was used to assess the protein expression levels of Slug, Vimentin, and E-cadherin. After intervention with CSGP, the proliferation of MDA-MB-231 and BT-549 cells significantly decreased, while the apoptosis rate markedly increased. The expression levels of the epithelial marker protein E-cadherin significantly increased, while the expression levels of the EMT-related transcription factors Slug and Vimentin showed a decrease. In conclusion, CSGP inhibits the EMT, thereby suppressing the malignant progression of TNBC.
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Apoptose , Proliferação de Células , Medicamentos de Ervas Chinesas , Transição Epitelial-Mesenquimal , Neoplasias de Mama Triplo Negativas , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Medicamentos de Ervas Chinesas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Pós/química , Caderinas/genética , Caderinas/metabolismoRESUMO
BACKGROUND AND PURPOSE: Hyperphosphorylation of Tau is one of the important pathological features of Alzheimer's disease (AD). Therefore, studying the mechanisms behind Tau hyperphosphorylation is crucial in exploring the pathogenesis of neurological damage in AD. METHODS: In this study, after the establishment of rat models of AD, quantitative phosphoproteomics and proteomics were performed to identify proteins, showing that phosphorylation of microtubule associated protein 1A (MAP 1A) was lower in the model group. Western blot confirmed the changes of MAP 1A in the SD rats, APP/PS1 transgenic mice and cell AD models. To further study the molecular mechanism of recombinant MAP 1A phosphorylation affecting Tau phosphorylation, interfering siRNA-MAP 1A and protein immunoprecipitation reaction analysis were performed in AD cell models. RESULTS: Cyclin-dependent kinase 5 (CDK5) showed reduced binding to MAP 1A and increased binding to Tau, resulting in a decrease in phosphorylated MAP 1A (p-MAP 1A) and an increase in phosphorylated Tau (p-Tau), and MAP 1A silencing promoted binding of CDK5-Tau and increased Tau phosphorylation, thereby reducing the cell survival rate. CONCLUSIONS: In summary, we found that p-MAP 1A downregulation associated with p-Tau upregulation was due to their altered binding forces to CDK5, and MAP 1A could enhance autophosphorylation by competitive binding to CDK5 and antagonise Tau phosphorylation. This leads to neuronal protection and reducing tissue damage levels in AD, which can help better understand the mechanisms of AD pathogenesis.
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Doença de Alzheimer , Animais , Camundongos , Ratos , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Fosforilação , Ratos Sprague-Dawley , Proteínas tau/metabolismo , Regulação para CimaRESUMO
Epitranscriptomics, also known as "RNA epigenetics", is a type of chemical modification that regulates RNA. RNA methylation is a significant discovery after DNA and histone methylation. The dynamic reversible process of m6A involves methyltransferases (writers), m6A binding proteins (readers), as well as demethylases (erasers). We summarized the current research status of m6A RNA methylation in the neural stem cells' growth, synaptic and axonal function, brain development, learning and memory, neurodegenerative diseases, and glioblastoma. This review aims to provide a theoretical basis for studying the mechanism of m6A methylation and finding its potential therapeutic targets in nervous system diseases.
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Metiltransferases , RNA , Metilação , RNA/metabolismo , Metiltransferases/metabolismo , Sistema Nervoso/metabolismoRESUMO
INTRODUCTION: Contact lens discomfort (CLD) acts as a challenging problem, and the associated conjunctival microbiome changes were unclear. MATERIAL AND METHODS: Conjunctival sac swab samples were collected from 12 eyes of nonwearers (NW), 12 eyes of asymptomatic contact lens (ACL) wearers, and 11 eyes of CLD. The V3-V4 region of the 16S rRNA gene sequencing was used to investigate differences among three groups. RESULTS: No differences in alpha diversity were observed among the three groups. The beta diversity showed a distinct microbiome composition between ACL and CLD group (P = 0.018) with principal coordinate analysis. The relative abundance of Firmicutes was significantly higher in CLD (48.18%) than in ACL (13.21%) group (P = 0.018). The abundance of Bacillus in patients with ACL (0.05%) or with CLD (0.02%) were significantly lower than that in the NW (1.27%) group (P = 0.024, 0.028, respectively). Moreover, the abundance of Firmicutes was positively correlated with the OSDI scores in CLD patients (r = 0.817, P < 0. 01, Spearman). DISCUSSIONS: Patients with CLD have various degrees of bacterial microbiota imbalance in the conjunctival sac, compared with NW and ACL groups. CONCLUSION: Firmicutes may serve as a potential biomarker for the CLD patients.
In the current study, we investigated the conjunctival microbiome changes among nonwearers (NW), asymptomatic contact lens (ACL) wearers, and contact lens discomfort (CLD) patients using high-throughput 16S rRNA gene sequencing, and correlated relative abundances of the microbiota with clinical parameters.The relative abundance of Firmicutes was higher in CLD than that in ACL group. The abundance of Bacillus was lower in ACL or CLD group than that in NW group. The abundance of Firmicutes was positively correlated with the OSDI scores in CLD patients.Firmicutes may serve as a potential biomarker for the CLD patients.
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Lentes de Contato Hidrofílicas , Microbiota , Humanos , RNA Ribossômico 16S/genética , Túnica Conjuntiva/microbiologia , Lentes de Contato Hidrofílicas/efeitos adversos , Lentes de Contato Hidrofílicas/microbiologia , Bactérias/genética , Microbiota/genéticaRESUMO
Background: Hepatocellular carcinoma is a rapidly advancing malignancy with a poor prognosis. Therefore, further research is needed on its potential pathogenesis and therapeutic targets. Methods: In this study, the relevant datasets were downloaded from the TCGA database and the key modules were identified using WGCNA in the necroptosis-related gene set, while single-cell datasets were scored using the necroptosis gene set. Differential genes in the high- and low-expression groups were determined using the WGCNA module genes as intersection sets to identify key genes involved in necroptosis in liver cancer. Then, prognostic models were constructed using LASSO COX regression followed by multi-faceted validation. Finally, model genes were found to be correlated with key proteins of the necroptosis pathway and used to identify the most relevant genes, followed by their experimental validation. Subsequently, on the basis of the analysis results, the most relevant SFPQ was selected for cell-level verification. Results: We constructed a prognosis model that included five necroptosis-related genes (EHD1, RAC1, SFPQ, DAB2 and PABPC4) to predict the prognosis and survival of HCC patients. The results showed that the prognosis was more unfavorable in the high-risk group compared to the low-risk group, which was corroborated using ROC curves and risk factor plots. In addition, we further checked the differential genes using GO and KEGG analyses and found that they were predominantly enriched in the neuroactive ligand-receptor interaction pathway. The results of the GSVA analysis demonstrated that the high-risk group was mainly enriched in DNA replication, regulation of the mitotic cycle, and regulation of various cancer pathways, while the low-risk group was predominantly enriched in the metabolism of drugs and xenobiotics using cytochrome P450. SFPQ was found to be the main gene that affects the prognosis and SFPQ expression was positively correlated with the expression of RIPK1, RIPK3 and MLKL. Furthermore, the suppression of SFPQ could inhibit hyper-malignant phenotype HCC cells, while the WB results showed that inhibition of SFPQ expression also resulted in lower expression of necroptosis proteins, compared to the sh-NC group. Conclusions: Our prognostic model could accurately predict the prognosis of patients with HCC to further identify novel molecular candidates and interventions that can be used as alternative methods of treatment for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Prognóstico , Bases de Dados Factuais , Necroptose , Proteínas de Transporte VesicularRESUMO
Glycosylation is a critical post-translational modification (PTM) that affects the function of proteins and regulates cell signaling, thereby regulating various biological processes. Protein oxygen-N-acetylglucosamine (O-GlcNAc) glycosylation modifications are glycochemical modifications that occur within cells in the signal transduction and are frequently found in the cytoplasm and nucleus. Due to the rapid and reversible addition and removal, O-GlcNAc modifications are able to reversibly compete with certain phosphorylation modifications, immediately regulate the activity of proteins, and participate in kinds of cellular metabolic and signal transduction pathways, playing a pivotal role in the regulation of tumors, diabetes, and other diseases. This article provided a brief overview of O-GlcNAc glycosylation modification, introduced its role in altering the progression and immune response regulation of gastrointestinal tumors, and discussed its potential use as a marker of tumor neogenesis.
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Acetilglucosamina , Neoplasias Gastrointestinais , Glicosilação , Humanos , N-Acetilglucosaminiltransferases/metabolismo , Oxigênio/metabolismo , Processamento de Proteína Pós-TraducionalRESUMO
OBJECTIVE: To investigate the relationship between ovulation and pregnancy outcomes in patients undergoing intrauterine insemination (IUI). METHODS: The clinical data from 784 patients, diagnosed with polycystic ovarian syndrome (PCOS) or unexplained infertility, underwent 1624 IUI cycles were analyzed retrospectively. Ovulation was observed by transvaginal ultrasonography on the day of IUI. The clinical pregnancy rate (CPR), abortion rate (AR), and live birth rate (LBR) were analyzed. RESULTS: The study included 1031 pre-ovulation IUI cycles (63.49%) and 593 post-ovulation IUI cycles (36.51%). The CPR was 13.05%, the AR was 15.57%, and the LBR was 11.02%. Ovulation before or after IUI affected the CPR (11.06% VS 16.53%, p = .002) and LBR (9.41% VS 13.83%, p = .006) per cycle, but did not affect the AR (14.91% VS 16.33%, p = .149). The sex ratio of children was not related to ovulation (p = .948). After adjusting for baseline characteristics and logistic regression, the CPR (OR = 1.931, 95% CI 1.062-1.931, p = .019) and LBR (OR = 1.389, 95% CI 1.007-1.916, p = .045) of post-ovulation insemination were higher than those of pre-ovulation insemination significantly. CONCLUSION: Pregnancy outcomes were affected by ovulation on the day of IUI in patients with unexplained infertility or PCOS. Post-ovulation insemination may improve the CPR of IUI.
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Infertilidade , Síndrome do Ovário Policístico , Feminino , Gravidez , Humanos , Resultado da Gravidez , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia , Inseminação Artificial , Estudos Retrospectivos , Taxa de Gravidez , Indução da Ovulação , Inseminação , OvulaçãoRESUMO
Some traditional acidic ionic liquids (AILs) have shown great catalytic potential in esterification; meanwhile, the design and application of more new AILs are expected at present.Tropine-based functionalized acidic ionic liquids (FAILs) were synthesized to realize esterification catalysis for the first time; with aspirin synthesis as the template reaction, key influences on the substrate conversion and product yield of the synthesis, such as IL type, ratio of salicylic acid to acetic anhydride, temperature, reaction time and amount of IL, were investigated. The new tropine-based FAILs exhibited excellent performance in catalytic synthesis of aspirin with 88.7% yield and 90.8% selectivity. Multiple recovery and re-usage of N-(3-propanesulfonic acid) tropine is the cation, and p-toluenesulfonic acid is the anion. ([Trps][OTs]) shows satisfactory results. When [Trps][OTs] was used to catalyze different esterification reactions, it also showed good results. The above studies proved that ionic liquid [Trps][OTs] could serve as an ideal green solvent for esterification reaction, which serves as a suitable substitute for current catalysts.
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Líquidos Iônicos , Ácidos , Aspirina , Catálise , EsterificaçãoRESUMO
Imidazolium-based ionic liquids are wildly used in natural product adsorption and purification. In this work, one typical polymeric ionic liquid (PIL) was synthesized by using L-proline as the anion, which exhibited excellent adsorption capacity toward tea polyphenol epigallocatechin gallate (EGCG). The adsorption conditions were optimized with the response surface method (RSM). Under the optimum conditions, the adsorption capacity of the PIL for EGCG can reach as high as 552 mg/g. Dynamics and isothermal research shows that the adsorption process of EGCG by the PIL particularly meets the quasi-second-order kinetic equation and monolayer adsorption mechanism. According to thermodynamic parameter analysis, the adsorption process is endothermic and spontaneous. The results of theoretical calculation by molecular docking also demonstrated the interaction mechanisms between EGCG and the ionic liquid. Considering the wide application of imidazolium-based ionic liquids in component adsorption and purification, the present study can not only be extended to other similar experimental mechanism validation, but also be representative for guiding the synthesis of PIL and optimization of adsorption conditions.
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Produtos Biológicos , Líquidos Iônicos , Polifenóis , Simulação de Acoplamento Molecular , Polímeros , Chá , ProlinaRESUMO
Objectives: Huangpu Tongqiao Capsule (HPTQC) is a traditional Chinese medicine (TCM) that has been used to treat Alzheimer's disease (AD). This study was to explore the pharmacological action and molecular mechanism of HPTQC in the treatment of AD. Methods: The possible targets of HTPQC were predicted by the molecular docking technique. Intraperitoneal injection of D-galactose and bilateral injection of Aß25-35 in hippocampus induced AD rat model. Morris water maze was used to observe learning and memory function. The primary hippocampal neurons were induced by Aß25-35. Moreover, the apoptosis rate of hippocampal nerve cells was detected through AnnexinV/PI double standard staining. The mRNA and protein levels of GRP78, CHOP, Caspase 12, Caspase 9, and Caspase 3 were detected by PCR and western blot. Results: The prediction results suggest that HPTQC may act on GRP78. HPTQC significantly improved the learning and memory function, and decreased neuronal apoptosis in vivo and in vitro. In addition, HPTQC could decrease the mRNA and protein expression levels of GRP78, CHOP, Caspase12, Caspase9, and Caspase3, and the effect trend was consistent with the specific inhibitor of GRP78. Conclusions: HPTQC has a neuroprotective effect against AD by inhibiting the apoptosis pathway mediated by endoplasmic reticulum stress.
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Responsive molecular devices are one of the core units for molecular electronics, and dynamic covalent bonds (DCBs) provide the opportunity for the fabrication of responsive molecular devices. Herein we employ a single dynamic acyl hydrazone bond to fabricate tailored molecular devices using the scanning tunneling microscopy break-junction technique (STM-BJ) and the eutectic Ga-In technique (EGaIn). We found that the single-DCB-tailored molecular devices exhibited acid-base and/or photo-thermal response with three well-defined molecular conductance states. The reversible switching has the ON/OFF ratio of ≈10 between each state for single-molecule junctions and ≈3 for the SAMs-based molecular junctions. Combined with the density functional theory calculations, we revealed that the multiple conductance states of these molecular junctions originate from the dynamic acyl hydrazone bond exchange and C=N isomerization. Our work opens the avenue towards the design of tailored single-molecule electrical devices by implanting dynamic covalent bonds in molecular architectures.
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Fluorescence imaging is a promising visualization tool and possesses the advantages of in situ response and facile operation; thus, it is widely exploited for bioassays. However, traditional fluorophores suffer from concentration limits because they are always quenched when they aggregate, which impedes applications, especially for trace analysis and real-time monitoring. Recently, novel molecules with aggregation-induced emission (AIE) characteristics were developed to solve the problems encountered when using traditional organic dyes, because these new molecules exhibit weak or even no fluorescence when they are in free movement states but emit intensely upon the restriction of intramolecular motions. Inspired by the excellent performances of AIE molecules, a substantial number of AIE-based probes have been designed, synthesized, and applied to various fields to fulfill diverse detection tasks. According to numerous experiments, AIE probes are more practical than traditional fluorescent probes, especially when used in bioassays. To bridge bioimaging and materials engineering, this review provides a comprehensive understanding of the development of AIE bioprobes. It begins with a summary of mechanisms of the AIE phenomenon. Then, the strategies to realize accurate detection using AIE probes are discussed. In addition, typical examples of AIE-active materials applied in diagnosis, treatment, and nanocarrier tracking are presented. In addition, some challenges are put forward to inspire more ideas in the promising field of AIE-active materials.
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Diagnóstico por Imagem , Animais , Técnicas Biossensoriais , Sistemas de Liberação de Medicamentos , Fluorescência , Humanos , Nanopartículas/químicaRESUMO
Breast cancer is the second leading death cause of cancer death for all women. Previous study suggested that Protein Kinase D3 (PRKD3) was involved in breast cancer progression. In addition, the protein level of PRKD3 in triple-negative breast adenocarcinoma was higher than that in normal breast tissue. However, the oncogenic mechanisms of PRKD3 in breast cancer is not fully investigated. Multi-omic data showed that ERK1/c-MYC axis was identified as a major pivot in PRKD3-mediated downstream pathways. Our study provided the evidence to support that the PRKD3/ERK1/c-MYC pathway play an important role in breast cancer progression. We found that knocking out PRKD3 by performing CRISPR/Cas9 genome engineering technology suppressed phosphorylation of both ERK1 and c-MYC but did not down-regulate ERK1/2 expression or phosphorylation of ERK2. The inhibition of ERK1 and c-MYC phosphorylation further led to the lower protein level of c-MYC and then reduced the expression of the c-MYC target genes in breast cancer cells. We also found that loss of PRKD3 reduced the rate of the cell proliferation in vitro and tumour growth in vivo, whereas ectopic (over)expression of PRKD3, ERK1 or c-MYC in the PRKD3-knockout breast cells reverse the suppression of the cell proliferation and tumour growth. Collectively, our data strongly suggested that PRKD3 likely promote the cell proliferation in the breast cancer cells by activating ERK1-c-MYC axis.
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Neoplasias da Mama/genética , Proliferação de Células/genética , Proteína Quinase Ativada por DNA/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Mama/patologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Oncogenes/genética , Fosforilação/genética , Transdução de Sinais/genéticaRESUMO
A gas sensor made from graphene vertical field effect transistor (VGr-FET) has been fabricated using graphene as the source electrode, C60 thin film as the semiconductor layer and aluminum thin film as the drain electrode. The on/off ratio of transistor gated by bottom electrode with ionic liquid gel as dielectric layer is derived to be 103 from measured source-drain current I ds. The apparent energy barrier height between the graphene and polycrystalline fullerene was calculated from the model of heterojunction diode I-V response curves. The barrier height φ BH was altered by the gating potential vertically applied on graphene sheet, resulting the large on/off ratio of the transistor. The effect of surface adsorption of water vapor, oxygen, ammonia and isoprene gas phase molecules on the I ds was measured. The lower limit of detection (LOD) for ammonia (86 ppb) than that of isoprene (420 ppb) is attributed to the donor nature of ammonia contact with p-type graphene, and the adsorbed donor leads to a corresponding positive gating effect to the VGr-FET. This facile, low cost and quick responsive device shows promise for early diagnose of severe human respiratory diseases.
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The experimental investigation of intermolecular charge transport in π-conjugated materials is challenging. Herein, we describe the investigation of charge transport through intermolecular and intramolecular paths in single-molecule and single-stacking thiophene junctions by the mechanically controllable break junction (MCBJ) technique. We found that the ability for intermolecular charge transport through different single-stacking junctions was approximately independent of the molecular structure, which contrasts with the strong length dependence of conductance in single-molecule junctions with the same building blocks, and the dominant charge-transport path of molecules with two anchors transited from an intramolecular to an intermolecular path when the degree of conjugation increased. An increase in conjugation further led to higher binding probability owing to the variation in binding energies, as supported by DFT calculations.
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Accumulating evidence suggests that noncoding RNAs play a vital role in cancer biology. Circular RNAs (circRNAs), a newly defined class of endogenously widespread noncoding RNAs, have been intensively reported to influence cell function and development, and even cancer prognosis by sponging microRNAs in various types of cancer. Nevertheless, the circRNAs research in hepatocellular carcinoma (HCC) still remains far insufficient. Herein, we investigated the role of a newly defined circRNAs, circ_0005075, in HCC development. We found circ_0005075 was upregulated in HCC tissues. HCC progression was suppressed by downregulation of circ_0005075 in vitro and in vivo, and the suppression was partially reversed by inhibition of microRNA-335 (miR-335) expression. Further, we found the expression of mitogen-activated protein kinase 1 (MAPK1) was substantially regulated by circ_0005075 and miR-335. Mechanically, it was demonstrated that circ_0005075 could directly bind to miR-335 and miR-335 could bind to MAPK1. Our data provide evidence that circ_0005705 promotes the HCC progression by sponging miR-335 and further regulating MAPK1 expression.
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Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/biossíntese , RNA Circular/genética , Animais , Progressão da Doença , Xenoenxertos , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/genéticaRESUMO
Freestanding graphene films are desired to be widely applied in biosensor fabrication due to their distinctive physical properties and improved performance. Chemical vapor deposition has been developed to efficiently fabricate large-area graphene. However, some of the fabricated graphene films might break or be contaminated in the current transferring step using polymers. A stable and high-quality transfer method is needed. Herein, we report on an advanced transfer method of large-area graphene film which uses fullerene as a supporting substrate. Unlike polymers, which are commonly eliminated by being dissolved in an organic solution, fullerene can be easily removed by evaporation in a vacuum because it has a different heat stability to graphene. By using the improved transferring method, the percentage of integrated freestanding films after transferring was increased from 60.7% to 93.4%. The vacuum is beneficial in terms of keeping the brittle freestanding films intact. Graphene films transferred using fullerene showed an advanced flatness and a simplicial elementary composition in comparison to those transferred using polymers. Even through there is trace residue, this stable allotrope of graphene is considered to have almost no impact on biomolecule sensing. These advantages make the fullerene transferring method an attractive candidate for fabricating large-area freestanding graphene films, especially for using in the field of biochemistry analysis and biosensors.