Small Methods
·
2021
·Vol. 5
·期 7
·2100423
·
IF 14.188
Mingzhe Shao,Dapeng Liu,Baolin Yan,Xilan Feng,Xiaojuan Zhang,Yu Zhang
Inorganic nanomaterials have attracted much attention as enzyme mimics because of simple and stable spatial conformation of those artificially synthesized nanocatalysts. Cu 2 O, as an important kind of narrow band gap semiconductor, is identified as effective as visible-light-driven photocatalysts, which can catalyze decomposition of H 2 O 2 into reactive oxygen species. Moreover, after forming Cu x O/CeO 2 hybrids, the strongly coupled interface between the two components will further improve their catalytic performance. In this paper, the authors try to construct FTO/TiO 2 /Cu x O/CeO 2 (1 < x < 2) nanohybrids with such a kind of active interface via a layer-by-layer electrodeposition strategy by aid of the following surface etching process. It is found that FTO/TiO 2 /Cu x O/CeO 2 exhibits good peroxidase mimic activity in the dark but much better performance under visible light irradiation (λ ≥ 420 nm) during catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine substrates in the presence of H 2 O 2 . Detailed characterizations disclose that the construction of TiO 2 /Cu 2 O pn-heterojunctions do effectively accelerate separation of photogenerated carriers, and the formation of a highly active Cu x O/CeO 2 interface is synergistically favorable for selectively generating singlet oxygen to boost the catalytic performance of FTO/TiO 2 /Cu x O/CeO 2 .
研究领域:
材料科学
·
催化化学
·
纳米技术
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2020
·
IF 6.155
Liquan Yao,Limei Lin,Hui Liu,Fengying Wu,Jianmin Li,Shuiyuan Chen,Zhigao Huang,Guilin Chen
Antimony chalcogenide Sb 2 (S, Se) 3 is attracting a lot of attention as photovoltaic absorber owing to its rewarding photoelectric properties, low toxicity, and earth abundance. However, its device efficiency is still limited by the absorber material quality and device interface recombination. In this work, a fluorine-doped tin oxide (FTO) substrate with ultra-thin SnO 2 layer and a low-cost stabilized carbon paste are introduced as a front and back contact layer respectively in Sb 2 (S, Se) 3 based planar solar cells. Over 5.2 % efficiency is demonstrated in the structure of FTO/SnO 2 /CdS/Sb 2 (S, Se) 3 /Carbon/Ag, where the Sb 2 (S, Se) 3 is prepared by hydrothermal technique. The complementary device physics characterizations reveal that the interfacial recombination between TCO and CdS is significantly suppressed by the introduction of ultra-thin SnO 2 layer, which is profited from the leakage protection and bandgap offset engineering by its high resistivity and suitable conduction band minimum. Meanwhile, the successful adoption of the low-cost stabilized carbon as a back contact here shows an enormous potential to replace the conventional organic hole transport materials and noble metal. We hope this work can provide positive guidance to optimize Sb 2 (S, Se) 3 based planar solar cells in the future.
研究领域:
材料科学
·
光伏技术
·
可再生能源
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DOI
高影响因子
FASEB JOURNAL
·
2023
·Vol. 37
·期 6
·e22964
·
IF 4.8
Fei Sun,Cheng An,Can Liu,Ying Hu,Yue Su,Zhixiang Guo,Hong Che,Shenglin Ge
Cardiac ischemia/reperfusion (I/R) injury is a complicated pathological event, which has close association with pyroptosis. This study uncovered the regulatory mechanisms of fat mass and obesity-associated protein (FTO) in NLRP3-mediated pyroptosis during cardiac I/R injury. H9c2 cells were stimulated with oxygen–glucose deprivation/reoxygenation (OGD/R). Cell viability and pyroptosis were detected by CCK-8 and flow cytometry. Western blotting or RT-qPCR was performed to analyze target molecule expression. NLRP3 and Caspase-1 expression was observed by immunofluorescence staining. IL-18 and IL-1β production was detected by ELISA. The total m6A and m6A level of CBL was determined by dot blot assay and methylated RNA immunoprecipitation-qPCR, respectively. The interaction between IGF2BP3 and CBL mRNA was confirmed by RNA pull-down and RIP assays. The protein interaction between CBL and β-catenin and β-catenin ubiquitination were evaluated by Co-IP. Myocardial I/R model was established in rats. We determined infarct size by TTC staining and pathological changes by H&E staining. LDH, CK-MB, LVFS, and LVEF were also assessed. FTO and β-catenin were down-regulated, while CBL was up-regulated by OGD/R stimulation. FTO/β-catenin overexpression or CBL silencing restrained OGD/R-induced NLRP3 inflammasome-mediated pyroptosis. CBL repressed β-catenin expression via ubiquitination and degradation. FTO reduced the mRNA stability of CBL by inhibiting m6A modification. CBL-mediated ubiquitination and degradation of β-catenin were involved in FTO-induced pyroptosis inhibition during myocardial I/R injury. FTO inhibits NLRP3-mediated pyroptosis to attenuate myocardial I/R injury via repressing CBL-induced ubiquitination degradation of β-catenin.
研究领域:
心脏病学
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分子生物学
·
细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Taorong Shen,Xing Huang,Yanfei Zhang,Yanli Tong,Yakun Shi,Jianhe Guo,Xiaoyong Zou,Yuzhi Xu,Zong Dai
Fat mass and obesity-associated protein (FTO) plays a crucial role in regulating the dynamic modification of N6-methyladenosine (m6A) in eukaryotic mRNA. Sensitive detection of the FTO level and efficient evaluation of the FTO demethylase activity are of great importance to early cancer diagnosis and anticancer drug discovery, which are currently challenged by limited sensitivity/precision and low throughput. Herein, a robust strategy based on the dephosphorylation switch DNAzyme-rolling circle amplification (RCA) circuit, termed DSD-RCA, is developed for highly sensitive detection of FTO and inhibitor screening. Initially, the catalytic activity of DNAzyme is silenced by engineering with an m6A modification in its catalytic core. Only in the presence of target FTO can the methyl group on DNAzyme be eliminated, resulting in the activation of the catalytic activity of DNAzyme and thus cleaving the hairpin substrate to release numerous primers. Different from the conventional methods that use the downstream cleavage primer with the original 3′-hydroxyl end directly as the RCA primer with the problem of high background signal, which should be compensated by additional separation and wash steps in heterogeneous format, our DSD-RCA assay uses the upstream cleavage primer with a 2′,3′-cyclic phosphate terminus at the 3′-end serving as an intrinsically blocked 3′ end. Only after a dephosphorylation reaction mediated by T4 polynucleotide kinase can the upstream cleavage primers with a resultant 3′-hydroxyl end be extended by RCA. With the high signal-to-noise ratio and homogeneous property, the proposed platform can sensitively detect FTO with a limit of detection of 31.4 pM, and the relative standard deviations (RSDs %) ranging from 0.8 to 2.0% were much lower than the heterogeneous methods. The DSD-RCA method was applied for analyzing FTO in cytoplasmic lysates from different cell lines and tissues of breast cancer patients and further used for screening FTO inhibitors without the need for separation or cleaning, providing an opportunity for achieving high throughput and demonstrating the potential applications of this strategy in disease diagnostics, drug discovery, and biological applications.
研究领域:
生物化学
·
分子生物学
·
癌症研究
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药物发现
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 37
·30769-30775
·
IF 3.289
Tao Ye,Yong Xiang,Hong Ji,Congjin Hu,Gang Wu
Reversible electrodeposition-based electrochromic devices are highly promising for extensive applications owing to their facile and low-cost fabrication. Herein, a novel electrodeposition-based electrochromic device with reversible three-state optical transformation, i.e. transparent, mirror, and black, was fabricated by introducing a fluorine-doped tin oxide (FTO) electrode modified with commonly available and inexpensive titanium dioxide (TiO2) nanoparticles. Typically, the fabricating strategy mainly involved three procedures, namely obtaining a stable dispersion of TiO2 nanoparticles by milling, achieving a surface modification of the FTO electrode with TiO2 nanoparticles by spin-coating and sintering, and assembling the device by sandwiching gel electrolyte between the modified FTO electrode and a flat FTO electrode. By applying different voltages for a short while, this transparent smart device can be immediately switched to black (+2.5 V/20 s) or mirror (−2.5 V/20 s) state by depositing Ag on the surface of the modified or unmodified FTO electrode respectively. There is below 1% transmittance in the black state and over 80% reflectance in the mirror state for the device. By changing the surface structure of the TiO2 modified FTO electrode, the optical properties of the device in different states can be controlled effectively. Moreover, the optical transformation exhibited good stability over 1500 cycles of testing.
研究领域:
材料科学
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电化学
·
光电
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产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2017
·Vol. 29
·期 16
·1602639
·
IF 19.791
Hua-Shang Rao,Wen-Guang Li,Bai-Xue Chen,Dai-Bin Kuang,Cheng-Yong Su
Organometal trihalide perovskites have been attracting intense attention due to their enthralling optoelectric characteristics. Thus far, most applications focus on polycrystalline perovskite, which however, is overshadowed by single crystal perovskite with superior properties such as low trap density, high mobility, and long carrier diffusion length. In spite of the inherent advantages and significant optoelectronic applications in solar cells and photodetectors, the fabrication of large-area laminar perovskite single crystals is challenging. In this report, an ingenious space-limited inverse temperature crystallization method is first demonstrated to the in situ synthesis of 120 cm 2 large-area CH 3 NH 3 PbBr 3 crystal film on fluorine-doped tin oxide (FTO) glass. Such CH 3 NH 3 PbBr 3 perovskite crystal film is successfully applied to narrowband photodetectors, which enables a broad linear response range of 10 −4 –10 2 mW cm −2 , 3 dB cutoff frequency ( f 3 dB ) of ≈110 kHz, and high narrow response under low bias −1 V.
研究领域:
材料科学
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光电子学
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半导体器件
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晶体生长
·
光电探测技术
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Yan Zhang,Qing-nan Li,Kaiyue Zhou,Qinfeng Xu,Chun-yang Zhang
The fat mass and obesity-associated enzyme (FTO) can catalyze the demethylation of N6-methyladenosine (m6A) residues in mRNA, regulates the cellular level of m6A modification, and plays a critical role in human obesity and cancers. Herein, we develop a single-quantum-dot (QD)-based fluorescence resonance energy transfer (FRET) sensor for the identification of specific FTO demethylase inhibitors. The FTO-mediated demethylation of m6A can induce the cleavage of demethylated DNA to generate the biotinylated DNA fragments, which may function as capture probes to assemble the Cy5-labeled reporter probes onto the QD surface, enabling the occurrence of FRET between the QD and Cy5. The presence of inhibitors can inhibit the FTO demethylation and consequently abolish FRET between the QD and Cy5. The inhibition effect of inhibitors upon FTO demethylation can be simply evaluated by monitoring the decrease of Cy5 counts. We use this nanosensor to screen several small-molecule inhibitors and identify diacerein as a highly selective inhibitor of FTO. Diacerein can inhibit the demethylation activity of endogenous FTO in HeLa cells. Interestingly, diacerein is neither a structural mimic of 2-oxoglutarate (2-OG) nor a chelator of metal ions, and it can selectively inhibit FTO demethylation by competitively binding the m6A-containing substrate.
研究领域:
生物化学
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分子生物学
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癌症研究
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药物发现
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Hao Tian,Hongpei Deng,Xinlong Liu,Chang Liu,Chuan Zhang,Kam W. Leong,Jing Ruan,Xianqun Fan
Uveal melanoma (UM) is the most prevalent primary ocular malignancy in adults, with high lethality and limited effective treatment options. Despite identified driver mutations in GNAQ , GNA11 , and BAP1 , therapeutic advancements have been minimal. This study highlights the pivotal role of N6-methyladenosine (m 6 A) modifications in UM pathogenesis and progression, focusing on the demethylase FTO as a therapeutic target. Elevated FTO expression in UM tissues correlates with decreased m 6 A levels, increased aggressiveness, and poor prognosis. The FTO inhibitor meclofenamic acid (MA) restored m 6 A levels, upregulated SLC7A11, and induced disulfidptosis, a unique form of cell death triggered by GSH depletion and NADPH consumption. To address MA's limitations in bioavailability and tumor targeting, we developed an MA-loaded nucleic acid nanodrug (SNAMA). SNAMA demonstrated effective tumor growth inhibition in orthotopic and metastatic UM models through GSH-responsive release and m 6 A-mediated disulfidptosis activation. Incorporating a PD-L1 aptamer into SNAMA further improved tumor targeting and immune modulation, enhancing therapeutic efficacy. This study identifies FTO as a critical target for UM therapy and introduces SNAMA-apt as a promising nanodrug. The findings offer a foundation for m 6 A-targeted approaches in UM and other malignancies, addressing bioavailability, targeting, and immune evasion challenges.
研究领域:
肿瘤学
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分子生物学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 12
·1-16
·
IF 8.1
Hou Rui,Sun Xinrui,Cao Shiyao,Wang Yadong,Jiang Luo
The metabolic reprogramming in high-grade serous ovarian carcinoma (HGSOC) affects the tumor stemness, which mediates tumor recurrence and progression. Knowledge of the stemness and metabolic characteristics of HGSOC is insufficient. Squalene epoxidase (SQLE), a key enzyme in cholesterol metabolism, was significantly upregulated in HGSOC samples with a fold change of about 4 in the RNA sequencing analysis. SQLE was positively related to peritoneal metastasis and poor prognosis of HGSOC patients. Functionally, SQLE drove cancer cell proliferation and inhibited apoptosis to accelerate HGSOC growth. SQLE was highly expressed in ALDH + CD133 + FACS-sorted cells derived from HGSOC cells and ovarian cancer stem cells (OCSCs)-enriched tumorspheres. SQLE overexpression resulted in enhanced CSC-like properties, including increased tumorsphere formation and stemness markers expression. In vivo, SQLE not only promoted cell line-derived xenografts growth but extended the OCSCs subpopulation of single-cell suspension. Moreover, non-targeted metabolomics profiling from UPLC-MS/MS system identified 90 differential metabolites responding to SQLE overexpression in HGSOC cells. Among them, the dysfunctional metabolisms of cholesterol and glutathione were involved in the maintenance of HGSOC stemness. Previous studies showed the alteration of N6-Methyladenosine (m6A) modification in HGSOC development. Herein, the m6A modification in the 3’UTR and CDS regions of SQLE mRNA was increased due to upregulated methyltransferases WTAP and downregulated demethylases FTO, which was recognized by m6A-binding proteins IGF2BP3, rather than IGF2BP1 or IGF2BP2, thereby stabilizing the SQLE mRNA. These results suggested that SQLE was a novel potential clinical marker for predicting the HGSOC development and prognosis, as well as a potential therapeutic target of HGSOC.
研究领域:
肿瘤学
·
分子生物学
·
代谢组学
·
癌症生物学
·
表观遗传学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Yan Wang,Zhiqiang Cheng,Jing Xu,Meina Lai,Liming Liu,Min Zuo,Lin Dang
Excessive activation of signal transducer and activator of transcription 3 (STAT3) is implicated in breast cancer (BC) chemoresistance, but its underlying mechanism is not fully understood. There are STAT3 binding sites in fat mass and obesity-associated protein (FTO) promoter region, thus STAT3 may regulate the transcription of FTO. This study aimed to investigate the correlation between FTO and STAT3 in BC chemoresistance. Herein, FTO and STAT3 were highly expressed in doxorubicin-resistant BC (BC-DoxR) cells. CHIP assay verified the binding between STAT3 and FTO promoter in BC-DoxR cells. Dual luciferase reporter assay showed that FTO promoter activity was inhibited by S3I-201 (STAT3 inhibitor) but enhanced by epidermal growth factor (EGF, STAT3 activator) in BC-DoxR and BC cells. FTO mRNA and protein expression were suppressed by S3I-201 in BC-DoxR cells and EGF-stimulated BC cells. Notably, FTO regulated total N6-methyladenosine (m6A) levels in BC-DoxR and BC cells but could not affect STAT3 mRNA expression, indicating that FTO was not involved in the m6A modification of STAT3. However, FTO could activate STAT3 signaling in BC-DoxR and BC cells. Besides, FTO knockdown inhibited the doxorubicin resistance of BC-DoxR cells, while FTO overexpression enhanced the doxorubicin resistance and weakened the doxorubicin sensitivity of BC cells. Moreover, decreased doxorubicin resistance by STAT3 knockdown was abolished by FTO overexpression and decreased doxorubicin sensitivity by STAT3 overexpression was reversed by FTO knockdown, indicating that FTO was implicated in STAT3-mediated doxorubicin resistance and impairment of doxorubicin sensitivity of BC cells. Altogether, our findings provide a mechanism underlying BC doxorubicin resistance.
研究领域:
肿瘤学
·
分子生物学
·
癌症生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Nano
·
2022
·
IF 13.364
X. Cui,Y. Zhou,Y. Zheng,L. Cao,L. Gao,J. Duan,H. Yin,S. Ai
N 6 -methyladenosine (m 6 A) is the most abundant and dynamic reversible modification of mRNA in eukaryotes discovered in the mid-1970s, which is widely involved in various physiological processes. Fat mass and obesity-associated protein (FTO protein) is not only a demethylase for m 6 A, but also a carcinogenic factor for many human cancers. Therefore, it is very important to build a simple and sensitive platform for simultaneous detection of m 6 A and FTO protein. To achieve this aim, a novel photoelectrochemical biosensor was constructed with the antibody-free detection strategy of DTT mediated –SH functionalization of m 6 A triggered by FTO protein catalyzed m 6 A oxidation . To achieve high detection sensitivity, CdS/Bi 2 MoO 6 /MoSe 2 system with matched energy gap was employed as photoactive material. To achieve high detection selectivity , the –CH 3 of m 6 A in the captured RNA sequence (m 6 A RNA) on the electrode surface was oxidized by FTO protein to form hydroxymethyl, followed with the covalent reaction of DTT with hydroxymethyl, making the labeling of m 6 A with –SH. Finally, a CdS nanoparticle was modified on the electrode through the specific covalent reaction between –SH and Cd, achieving the improvement of the photocurrent with the matched energy band . Under the optimal experimental conditions, the biosensor showed linear range from 0.001 to 50 nM and 0.0005–500 μg/L with the detection limit of 0.37 pM and 0.034 ng/L (S/N = 3) for m 6 A RNA and FTO protein, respectively. The applicability of the developed method was assessed by investigating the effect of entacapone on FTO protein activity.
研究领域:
生物化学
·
分析化学
·
生物技术
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2023
·
IF 5.4
Xiuyuan Wang,Shusheng Yu,Yuqiu He,Fuan Wang,Xiaoqing Liu
Comprehensive Summary A label-free deoxyribozyme (DNAzyme) biosensor for m 6 A demethylase activity detection is developed. When demethylase FTO (Fat mass and obesity-associated protein), an important m 6 A demethylase of ALKBH demethylase family is present, the m 6 A group is specifically demethylated, and the cleavage activity of DNAzyme is restored. This allows the cleavage product that contains G-quadruplex sequence to bind to thioflavin T (ThT) and generate fluorescence signals. The biosensor shows high specificity and sensitivity, and fast reaction speed. Our study demonstrates a new design of allosteric DNAzyme for sensing. This method represents the first label-free nucleic acid biosensor for FTO assay, providing a feasible route towards inhibitors screening.
研究领域:
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子