A series of novel antitumor agents-the solanesylpiperazinotriamine derivatives were designed and synthesized, their structures were confirmed by IR,^ 1H-NMR, MS, and element analysis. The preliminary tests showed that...A series of novel antitumor agents-the solanesylpiperazinotriamine derivatives were designed and synthesized, their structures were confirmed by IR,^ 1H-NMR, MS, and element analysis. The preliminary tests showed that at low micromolar concentrations these compounds exhibited obvious toxicity on tumor cells in vitro, and the synergistic effect on clinical antitumor agent indicated that at noncytotoxic concentrations they also evidently enhanced the curative effect of vincristine.展开更多
Objective: To investigate the relationship between the transcription of ANRIL, P15, P14 and P16 at the same locus and the regulation mechanism of ANRIL.Methods: Publicly available database of Cancer Cell Line Encycl...Objective: To investigate the relationship between the transcription of ANRIL, P15, P14 and P16 at the same locus and the regulation mechanism of ANRIL.Methods: Publicly available database of Cancer Cell Line Encyclopedia(CCLE) was used in bioinformatic analyses. Methylation of Cp G islands was detected by denaturing high performance liquid chromatography(DHPLC). Gene transcript levels were determined using quantitative real-time polymerase chain reaction(q RTPCR) assays. An engineered P16-specific transcription factor and DNA methyltransferase were used to induce P16-specific DNA demethylation and methylation.Results: The expression level of ANRIL was positively and significantly correlated with that of P16 but not with that of P15 in the CCLE database. This was confirmed in human cell lines and patient colon tissue samples. In addition, ANRIL was significantly upregulated in colon cancer tissues. Transcription of ANRIL and P16 was observed only in cell lines in which the P16 alleles were unmethylated and not in cell lines with fully methylated P16 alleles.Notably, P16-specific methylation significantly decreased transcription of P16 and ANRIL in BGC823 and GES1 cells. In contrast, P16-specific demethylation re-activated transcription of ANRIL and P16 in H1299 cells(P〈0.001).Alteration of ANRIL expression was not induced by P16 expression changes.Conclusions: ANRIL and P16 are coordinately transcribed in human cells and regulated by the methylation status of the P16 Cp G islands around the transcription start site.展开更多
The AlGaN/GaN-based sensor is a promising POCT(point-of-care-testing)device featuring miniaturization,low cost,and high sensitivity.BNP is an effective protein biomarker for the early diagnosis of HF(heart failure).In...The AlGaN/GaN-based sensor is a promising POCT(point-of-care-testing)device featuring miniaturization,low cost,and high sensitivity.BNP is an effective protein biomarker for the early diagnosis of HF(heart failure).In this work,a novel AlGaN/GaN device with the Kelvin connection structure and the corresponding detection technique was proposed.This technique can effectively suppress the background noise and improve the SNR(signal-to-noise ratio).A BNP detection experiment was carried out to verify the effectiveness of this technique.It is shown that compared with that of the traditional detection method,the LOD(limit of detection)was improved from 0.47 ng/mL to 1.29 pg/mL.The BNP detection experiment was also carried out with a traditional electrochemical Au-electrode sensor with the same surface functionalization steps.The AlGaN/GaN sensor showed a better LOD than the Au-electrode sensor.Moreover,the influence of AlGaN/GaN sensor package on background noise was investigated with the mechanism of the noise source revealed.Finally,based on the optimized package,the optimal SNR quiescent operating point of the AlGaN/GaN sensor was determined.By biasing the sensor at the optimal quiescent operating point and immobilizing the magnetic beads with anti-BNP on the gate of the AlGaN/GaN sensor,the LOD for BNP detection was further improved to 0.097 pg/mL.展开更多
2D MXene-Ti3C2Tx has demonstrated promising application prospects in various fields;however,it fails to function properly in biosensor setups due to restacking and anodic oxidation problems.To expand beyond these exis...2D MXene-Ti3C2Tx has demonstrated promising application prospects in various fields;however,it fails to function properly in biosensor setups due to restacking and anodic oxidation problems.To expand beyond these existing limitations,an effective strategy to for modifying the MXene by covalently grafting first-generation poly(amidoamine)dendrimers onto an MXene in situ(MXene@PAMAM)was reported herein.When used as a conjugated template,the MXene not only preserved the high conductivity but also conferred a specific 2D architecture and large specific surface areas for anchoring PAMAM.The PAMAM,an efficient spacer and stabilizer,simultaneously suppressed the substantial restacking and oxidation of the MXene,which endowed this hybrid with improved electrochemical performance compared to that of the bare MXene in terms of favorable conductivity and stability under anodic potential.Moreover,the massive amino terminals of PAMAM offer abundant active sites for adsorbing Au nanoparticles(AuNPs).The resulting 3D hierarchical nanoarchitecture,AuNPs/MXene@PAMAM,had advanced structural merits that led to its superior electrochemical performance in biosensing.As a proof of concept,this MXene@PAMAM-based nanobiosensing platform was applied to develop an immunosensor for detecting human cardiac troponin T(cTnT).A fast,sensitive,and highly selective response toward the target in the presence of a[Fe(CN)6]^(3-/4-)redox marker was realized,ensuring a wide detection of 0.1-1000 ng/mL with an LOD of 0.069 ng/mL.The sensor's signal only decreased by 4.38%after 3 weeks,demonstrating that it exhibited satisfactory stability and better results than previously reported MXene-based biosensors.This work has potential applicability in the bioanalysis of cTnT and other biomarkers and paves a new path for fabricating high-performance MXenes for biomedical applications and electrochemical engineering.展开更多
基金This work was supported by the National Natural Science Foundation of China (No. 20472016)as well as by Henan Natural Science Foundation (No. 0423031800 No. 512001300).
文摘A series of novel antitumor agents-the solanesylpiperazinotriamine derivatives were designed and synthesized, their structures were confirmed by IR,^ 1H-NMR, MS, and element analysis. The preliminary tests showed that at low micromolar concentrations these compounds exhibited obvious toxicity on tumor cells in vitro, and the synergistic effect on clinical antitumor agent indicated that at noncytotoxic concentrations they also evidently enhanced the curative effect of vincristine.
基金supported by the National Natural Science Foundation of China (No. 91640108)the 973 Program of China (No. 2015CB553902)
文摘Objective: To investigate the relationship between the transcription of ANRIL, P15, P14 and P16 at the same locus and the regulation mechanism of ANRIL.Methods: Publicly available database of Cancer Cell Line Encyclopedia(CCLE) was used in bioinformatic analyses. Methylation of Cp G islands was detected by denaturing high performance liquid chromatography(DHPLC). Gene transcript levels were determined using quantitative real-time polymerase chain reaction(q RTPCR) assays. An engineered P16-specific transcription factor and DNA methyltransferase were used to induce P16-specific DNA demethylation and methylation.Results: The expression level of ANRIL was positively and significantly correlated with that of P16 but not with that of P15 in the CCLE database. This was confirmed in human cell lines and patient colon tissue samples. In addition, ANRIL was significantly upregulated in colon cancer tissues. Transcription of ANRIL and P16 was observed only in cell lines in which the P16 alleles were unmethylated and not in cell lines with fully methylated P16 alleles.Notably, P16-specific methylation significantly decreased transcription of P16 and ANRIL in BGC823 and GES1 cells. In contrast, P16-specific demethylation re-activated transcription of ANRIL and P16 in H1299 cells(P〈0.001).Alteration of ANRIL expression was not induced by P16 expression changes.Conclusions: ANRIL and P16 are coordinately transcribed in human cells and regulated by the methylation status of the P16 Cp G islands around the transcription start site.
基金supported in part by the National Natural Science Foundation of China under Grants 52077200 and 5l807175in part by the Zhejiang Natural Science Outstanding Young Scholar Foundation under Grant LR21E070001.
文摘The AlGaN/GaN-based sensor is a promising POCT(point-of-care-testing)device featuring miniaturization,low cost,and high sensitivity.BNP is an effective protein biomarker for the early diagnosis of HF(heart failure).In this work,a novel AlGaN/GaN device with the Kelvin connection structure and the corresponding detection technique was proposed.This technique can effectively suppress the background noise and improve the SNR(signal-to-noise ratio).A BNP detection experiment was carried out to verify the effectiveness of this technique.It is shown that compared with that of the traditional detection method,the LOD(limit of detection)was improved from 0.47 ng/mL to 1.29 pg/mL.The BNP detection experiment was also carried out with a traditional electrochemical Au-electrode sensor with the same surface functionalization steps.The AlGaN/GaN sensor showed a better LOD than the Au-electrode sensor.Moreover,the influence of AlGaN/GaN sensor package on background noise was investigated with the mechanism of the noise source revealed.Finally,based on the optimized package,the optimal SNR quiescent operating point of the AlGaN/GaN sensor was determined.By biasing the sensor at the optimal quiescent operating point and immobilizing the magnetic beads with anti-BNP on the gate of the AlGaN/GaN sensor,the LOD for BNP detection was further improved to 0.097 pg/mL.
基金supported by the National Natural Science Foundation of China(Grant Nos.31627801,61901412)the Science and Technology Project of Zhejiang Province(Grant Nos.2019C03066,LGF19H180022).
文摘2D MXene-Ti3C2Tx has demonstrated promising application prospects in various fields;however,it fails to function properly in biosensor setups due to restacking and anodic oxidation problems.To expand beyond these existing limitations,an effective strategy to for modifying the MXene by covalently grafting first-generation poly(amidoamine)dendrimers onto an MXene in situ(MXene@PAMAM)was reported herein.When used as a conjugated template,the MXene not only preserved the high conductivity but also conferred a specific 2D architecture and large specific surface areas for anchoring PAMAM.The PAMAM,an efficient spacer and stabilizer,simultaneously suppressed the substantial restacking and oxidation of the MXene,which endowed this hybrid with improved electrochemical performance compared to that of the bare MXene in terms of favorable conductivity and stability under anodic potential.Moreover,the massive amino terminals of PAMAM offer abundant active sites for adsorbing Au nanoparticles(AuNPs).The resulting 3D hierarchical nanoarchitecture,AuNPs/MXene@PAMAM,had advanced structural merits that led to its superior electrochemical performance in biosensing.As a proof of concept,this MXene@PAMAM-based nanobiosensing platform was applied to develop an immunosensor for detecting human cardiac troponin T(cTnT).A fast,sensitive,and highly selective response toward the target in the presence of a[Fe(CN)6]^(3-/4-)redox marker was realized,ensuring a wide detection of 0.1-1000 ng/mL with an LOD of 0.069 ng/mL.The sensor's signal only decreased by 4.38%after 3 weeks,demonstrating that it exhibited satisfactory stability and better results than previously reported MXene-based biosensors.This work has potential applicability in the bioanalysis of cTnT and other biomarkers and paves a new path for fabricating high-performance MXenes for biomedical applications and electrochemical engineering.