Objective:The purpose of this study was to explore the function and gene expression regulation of the newly identified lnc RNA DPP10-AS1 in lung cancer,and its potential value as a prognostic biomarker.Methods:q RT-PC...Objective:The purpose of this study was to explore the function and gene expression regulation of the newly identified lnc RNA DPP10-AS1 in lung cancer,and its potential value as a prognostic biomarker.Methods:q RT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues.The effects of DDP10-AS1 on DPP10 expression,cell growth,invasion,apoptosis,and in vivo tumor growth were investigated in lung cancer cells by Western blot,rescue experiments,colony formation,flow cytometry,and xenograft animal experiments.Results:The novel antisense lnc RNA DPP10-AS1 was found to be highly expressed in cancer tissues(P<0.0001),and its upregulation predicted poor prognosis in patients with lung cancer(P=0.0025).Notably,DPP10-AS1 promoted lung cancer cell growth,colony formation,and cell cycle progression,and repressed apoptosis in lung cancer cells by upregulating DPP10 expression.Additionally,DPP10-AS1 facilitated lung tumor growth via upregulation of DPP10 protein in a xenograft mouse model.Importantly,DPP10-AS1 positively regulated DPP10 gene expression,and both were coordinately upregulated in lung cancer tissues.Mechanically,DPP10-AS1 was found to associate with DPP10 m RNA but did not enhance DPP10 m RNA stability.Hypomethylation of DPP10-AS1 and DPP10 contributed to their coordinate upregulation in lung cancer.Conclusions:These findings indicated that the upregulation of the antisense lnc RNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10.DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.展开更多
Objective: To describe the clinical characteristics and coronary features of patients with coronary ectasia and aneurysm (CEA) in China. Methods: This was a single center, retrospective clinical study. Patients with C...Objective: To describe the clinical characteristics and coronary features of patients with coronary ectasia and aneurysm (CEA) in China. Methods: This was a single center, retrospective clinical study. Patients with CEA who diagnosed by coronary artery angiography (CAG) from April 2003 to October 2009, were enrolled. All patients were followed up by the call or clinic visit. The primary outcome was all-cause mortality or cardiovascular readmission. Results: A total of 39 patients (27 male, mean age 59.5 ± 12.6 years) diagnosed with CEA, with a prevalence of 0.6% (a total of 6,130 patients underwent CAG during the same period). Thirty-six patients constituted the study population, due to 3 patients lost of follow-up. The median follow-up was 27 months (1 - 76). The single vessel was involved in 11 patients (31%), two vessels were involved in 14 patients (38%) and three or more vessels were involved in 11 patients (31%). The most common involved vessel was left anterior descending branch (n = 27), followed by right coronary artery (n = 23), left circumflex branch (n = 20) and left main branch (n = 9). There was no death during the follow-up. The primary outcome was observed in 8 (22%) patients. The use of clopidogrel and statins were associated with lower rate of cardiovascular readmission. Conclusion The incidence of CEA was low among patients who referred for CAG in China. The majority of patients had the involvement of multiple vessels, and left anterior descending branch was the most common involved vessel. The CEA patients may benefit from clopidogrel and statins.展开更多
Artificial intelligence(AI)algorithms in combination with continuous monitoring technologies have the potential to revolutionize chronic disease management.The recent innovations in both continuous glucose monitoring(...Artificial intelligence(AI)algorithms in combination with continuous monitoring technologies have the potential to revolutionize chronic disease management.The recent innovations in both continuous glucose monitoring(CGM)and the closed-loop highlight the far-reaching potential of AI biosensors for individual healthcare.This review summarizes some of the most advanced progress made in CGM biosensing.We will focus on three main applications of AI algorithms in diabetes management:closed-loop control algorithms,glucose predictions,and calibrations.The challenges and opportunities of AI technologies for CGM in individualized and proactive medicine will also be discussed.展开更多
The anomalous Hall effect in epitaxial Fe(110)films grown on Ga As(110) is investigated as a function of both film thickness and temperature. The Berry curvatureinduced intrinsic contribution of 996 X 1cm 1is determin...The anomalous Hall effect in epitaxial Fe(110)films grown on Ga As(110) is investigated as a function of both film thickness and temperature. The Berry curvatureinduced intrinsic contribution of 996 X 1cm 1is determined experimentally for the first time. Together with 821 X 1cm 1in Fe(111) and 1100 X 1cm 1in Fe(001)obtained earlier, we show unambiguously the anisotropy of the Berry curvature contribution to the anomalous Hall effect in single-crystal Fe.展开更多
A resurging interest in targeted covalent inhibitors(TCIs)focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target.p97 is an emerging protein target for cancer therapy,vi...A resurging interest in targeted covalent inhibitors(TCIs)focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target.p97 is an emerging protein target for cancer therapy,viral infections and neurodegenerative diseases.Extensive efforts were devoted to the development of p97 inhibitors.The most promising inhibitor of p97 was in phase 1 clinical trials,but failed due to the off-target-induced toxicity,suggesting the selective inhibitors of p97 are highly needed.We report herein a new type of TCIs(i.e.,FL-18)that showed proteome-wide selectivity towards p97.Equipped with a Michael acceptor and a basic imidazole,FL-18 showed potent inhibition towards U87 MG tumor cells,and in proteome-wide profiling,selectively modified endogenous p97 as confirmed by in situ fluorescence scanning,label-free quantitative proteomics and functional validations.FL-18 selectively modified cysteine residues located within the D2 ATP site of p97.This covalent labeling of cysteine residue in p97 was verified by LC-MS/MS-based site-mapping and site-directed mutagenesis.Further structure-activity relationship(SAR)studies with FL-18 analogs were established.Collectively,FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity,thus providing a promising scaffold for cancer therapy.展开更多
A series of novel phenyl-urea derivatives which can simultaneously activate gluco kinase(GK)and peroxisome proliferator-activated receptorγ(PPARγ)was designed and prepared,and their activation of GK and PPARγ was e...A series of novel phenyl-urea derivatives which can simultaneously activate gluco kinase(GK)and peroxisome proliferator-activated receptorγ(PPARγ)was designed and prepared,and their activation of GK and PPARγ was evaluated.The structure--activity relationships of these compounds are also described.Three compounds showed potent ability to activate both GK and PPARγ.The possible binding mode of one of these compounds with GK and PPARγ were predicted by molecular docking simulation.展开更多
Electromagnetic vortices, which describe the orbital angular momentum(OAM) carrying waves with a helical phase front, have recently attracted much interest in a radio frequency domain due to their potential applicatio...Electromagnetic vortices, which describe the orbital angular momentum(OAM) carrying waves with a helical phase front, have recently attracted much interest in a radio frequency domain due to their potential applications in many diverse areas. In an OAM-based scenario, the antenna for OAM mode multiplexing/demultiplexing plays an essential role in controlling the overall system performance. In this paper, we demonstrated theoretically and experimentally an easily realized OAM antenna based on the traveling-wave circular loop structure for efficiently multiplexing/demultiplexing multiple OAM modes; in addition, its general propagation characteristics including the polarization, divergence, and radiation pattern are mathematically analyzed. Schemes for antenna size reduction and various radiation pattern manipulations have also been discussed to realize a more flexible and compact system.展开更多
In all the connexin-associated human diseases, deafness is one of the most important diseases with high frequency. The mu- tations of GJB2 (gap junction protein β2, also called connexin 26, Cx26) gene link with non...In all the connexin-associated human diseases, deafness is one of the most important diseases with high frequency. The mu- tations of GJB2 (gap junction protein β2, also called connexin 26, Cx26) gene link with nonsyndromic or syndromic senso- rineural hearing loss and were shown to account for a large proportion of congenital deaf cases in many studied populations (del Castillo and del Castillo, 2011). For example, the 235de1C mutation in GJB2 shows the frequency of approximately 1% and is the most frequent mutation in East Asian population (Yan et al., 2003). Many efforts have been put to study the function of Gjb2 gene in both mouse model and human. In mouse, extensive deletion of Gjb2 causes embryo lethal due to the decreased transplacental glucose uptake, which was not found in human (Takata and Hirano, 1997; Gabriel et al., 1998). In human, GJB2 deficiency is not able to cause embryo lethal (D'Andrea et al., 2002). However, the study of GJB2-associated hearing loss is hampered by many difficulties, such as unobtainable human cochlea and acoustic nerve tissues, and therefore the GJB2-associated hearing loss are underlying mechanisms of still remaining unclear.展开更多
Spurious-free dynamic range(SFDR)limited by intermodulation distortions is a usually accepted measure for dynamic performance of a photonic time-stretched analog-to-digital converter(ADC).In this paper,SFDR improvemen...Spurious-free dynamic range(SFDR)limited by intermodulation distortions is a usually accepted measure for dynamic performance of a photonic time-stretched analog-to-digital converter(ADC).In this paper,SFDR improvement in a photonic time-stretched ADC based on third-order predistortion is proposed.The third-order predistortion is achieved optically within an integrated dual-parallel Mach–Zehnder modulator(DPMZM).The mechanism of SFDR improvement with third-order predistortion in the DPMZM is theoretically analyzed.Compared with a conventional scheme without predistortion,the experimental results show that the SFDR improvement of∼26 dB in the proposed scheme is proved.展开更多
With no dark zone in the propagation path and the same divergence angles,different plane spiral orbital angular momentum(PSOAM)beams can be superposed easily in the transverse plane.In this paper,a stacked resonator a...With no dark zone in the propagation path and the same divergence angles,different plane spiral orbital angular momentum(PSOAM)beams can be superposed easily in the transverse plane.In this paper,a stacked resonator antenna based on substrate integrated waveguide is proposed,which is a compact planar waveguide structure.To obtain the structured EM wave which is superposed by the PSOAM waves(3;4;5;6)at 10 GHz,eight ring resonators are placed symmetrically on the two sides of the center plane and excited simultaneously.Simulation results,including distributions of the electric field,far-field results and purity analysis,are given,indicating that PSOAM beams can be generated with good performances.By controlling the initial phases of different PSOAM waves,beam steering can be realized with the same radiation patterns,which has great potentials in communication and radar detection.展开更多
基金supported in part by research grants from the Non-profit Technology Research Program of Zhejiang(Grant No.LGF18H160006)the Natural Science Foundation of Zhejiang(Grant No.LQ18H200001)+3 种基金the Non-profit Technology Research Program of Ningbo(Grant No.2019C50040)the Natural Science Foundation of Ningbo(Grant No.2018A610204)the Major Project for Science and Technology Innovation 2025 of Ningbo(Grant No.2019B10037)the K.C.Wong Magna Fund at Ningbo University。
文摘Objective:The purpose of this study was to explore the function and gene expression regulation of the newly identified lnc RNA DPP10-AS1 in lung cancer,and its potential value as a prognostic biomarker.Methods:q RT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues.The effects of DDP10-AS1 on DPP10 expression,cell growth,invasion,apoptosis,and in vivo tumor growth were investigated in lung cancer cells by Western blot,rescue experiments,colony formation,flow cytometry,and xenograft animal experiments.Results:The novel antisense lnc RNA DPP10-AS1 was found to be highly expressed in cancer tissues(P<0.0001),and its upregulation predicted poor prognosis in patients with lung cancer(P=0.0025).Notably,DPP10-AS1 promoted lung cancer cell growth,colony formation,and cell cycle progression,and repressed apoptosis in lung cancer cells by upregulating DPP10 expression.Additionally,DPP10-AS1 facilitated lung tumor growth via upregulation of DPP10 protein in a xenograft mouse model.Importantly,DPP10-AS1 positively regulated DPP10 gene expression,and both were coordinately upregulated in lung cancer tissues.Mechanically,DPP10-AS1 was found to associate with DPP10 m RNA but did not enhance DPP10 m RNA stability.Hypomethylation of DPP10-AS1 and DPP10 contributed to their coordinate upregulation in lung cancer.Conclusions:These findings indicated that the upregulation of the antisense lnc RNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10.DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.
文摘Objective: To describe the clinical characteristics and coronary features of patients with coronary ectasia and aneurysm (CEA) in China. Methods: This was a single center, retrospective clinical study. Patients with CEA who diagnosed by coronary artery angiography (CAG) from April 2003 to October 2009, were enrolled. All patients were followed up by the call or clinic visit. The primary outcome was all-cause mortality or cardiovascular readmission. Results: A total of 39 patients (27 male, mean age 59.5 ± 12.6 years) diagnosed with CEA, with a prevalence of 0.6% (a total of 6,130 patients underwent CAG during the same period). Thirty-six patients constituted the study population, due to 3 patients lost of follow-up. The median follow-up was 27 months (1 - 76). The single vessel was involved in 11 patients (31%), two vessels were involved in 14 patients (38%) and three or more vessels were involved in 11 patients (31%). The most common involved vessel was left anterior descending branch (n = 27), followed by right coronary artery (n = 23), left circumflex branch (n = 20) and left main branch (n = 9). There was no death during the follow-up. The primary outcome was observed in 8 (22%) patients. The use of clopidogrel and statins were associated with lower rate of cardiovascular readmission. Conclusion The incidence of CEA was low among patients who referred for CAG in China. The majority of patients had the involvement of multiple vessels, and left anterior descending branch was the most common involved vessel. The CEA patients may benefit from clopidogrel and statins.
基金Shenzhen Stability Support Plan,Grant/Award Number:20200806163622001National Natural Science Foundation of China,Grant/Award Numbers:21804007,21890742SZU Top Ranking Project,Grant/Award Number:86000000210。
文摘Artificial intelligence(AI)algorithms in combination with continuous monitoring technologies have the potential to revolutionize chronic disease management.The recent innovations in both continuous glucose monitoring(CGM)and the closed-loop highlight the far-reaching potential of AI biosensors for individual healthcare.This review summarizes some of the most advanced progress made in CGM biosensing.We will focus on three main applications of AI algorithms in diabetes management:closed-loop control algorithms,glucose predictions,and calibrations.The challenges and opportunities of AI technologies for CGM in individualized and proactive medicine will also be discussed.
基金supported by the National Basic Research Program of China(2015CB921400 and 2011CB921802)the National Natural Science Foundation of China(11374057,11434003 and 11421404)
文摘The anomalous Hall effect in epitaxial Fe(110)films grown on Ga As(110) is investigated as a function of both film thickness and temperature. The Berry curvatureinduced intrinsic contribution of 996 X 1cm 1is determined experimentally for the first time. Together with 821 X 1cm 1in Fe(111) and 1100 X 1cm 1in Fe(001)obtained earlier, we show unambiguously the anisotropy of the Berry curvature contribution to the anomalous Hall effect in single-crystal Fe.
基金the funding support from Institute of Materia Medica,Peking Union Medical College,CAMS Innovation Fund for Medical Sciences(CIFMS)(2017-I2M-4-005,China)The Natural Science Foundation of China(No.22177136)+1 种基金the Synthetic Biology Research&Development Programme(SBP)of National Research Foundation(SBP-P4 and SBP-P8)of Singapore。
文摘A resurging interest in targeted covalent inhibitors(TCIs)focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target.p97 is an emerging protein target for cancer therapy,viral infections and neurodegenerative diseases.Extensive efforts were devoted to the development of p97 inhibitors.The most promising inhibitor of p97 was in phase 1 clinical trials,but failed due to the off-target-induced toxicity,suggesting the selective inhibitors of p97 are highly needed.We report herein a new type of TCIs(i.e.,FL-18)that showed proteome-wide selectivity towards p97.Equipped with a Michael acceptor and a basic imidazole,FL-18 showed potent inhibition towards U87 MG tumor cells,and in proteome-wide profiling,selectively modified endogenous p97 as confirmed by in situ fluorescence scanning,label-free quantitative proteomics and functional validations.FL-18 selectively modified cysteine residues located within the D2 ATP site of p97.This covalent labeling of cysteine residue in p97 was verified by LC-MS/MS-based site-mapping and site-directed mutagenesis.Further structure-activity relationship(SAR)studies with FL-18 analogs were established.Collectively,FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity,thus providing a promising scaffold for cancer therapy.
基金This project was financially supported as National S&T Major Special Project on Major New Drug Innovation(No.2009zx09103-036)by the National Nature Science Foun-dation of China(No.30572256).
文摘A series of novel phenyl-urea derivatives which can simultaneously activate gluco kinase(GK)and peroxisome proliferator-activated receptorγ(PPARγ)was designed and prepared,and their activation of GK and PPARγ was evaluated.The structure--activity relationships of these compounds are also described.Three compounds showed potent ability to activate both GK and PPARγ.The possible binding mode of one of these compounds with GK and PPARγ were predicted by molecular docking simulation.
基金National Natural Science Foundation of China(NSFC)(61371030,61571391)National Basic Research Program of China(973 program)(2014CB340005)
文摘Electromagnetic vortices, which describe the orbital angular momentum(OAM) carrying waves with a helical phase front, have recently attracted much interest in a radio frequency domain due to their potential applications in many diverse areas. In an OAM-based scenario, the antenna for OAM mode multiplexing/demultiplexing plays an essential role in controlling the overall system performance. In this paper, we demonstrated theoretically and experimentally an easily realized OAM antenna based on the traveling-wave circular loop structure for efficiently multiplexing/demultiplexing multiple OAM modes; in addition, its general propagation characteristics including the polarization, divergence, and radiation pattern are mathematically analyzed. Schemes for antenna size reduction and various radiation pattern manipulations have also been discussed to realize a more flexible and compact system.
基金supported by grants from the National Key Basic Research Programs of China (Nos. 2012CB966600 and 2012CB967900)the National Natural Science Foundation Project (No. 31371506)the 12th Five-Year National Key Technologies R&D Program (No. 2012BAI12B00)
文摘In all the connexin-associated human diseases, deafness is one of the most important diseases with high frequency. The mu- tations of GJB2 (gap junction protein β2, also called connexin 26, Cx26) gene link with nonsyndromic or syndromic senso- rineural hearing loss and were shown to account for a large proportion of congenital deaf cases in many studied populations (del Castillo and del Castillo, 2011). For example, the 235de1C mutation in GJB2 shows the frequency of approximately 1% and is the most frequent mutation in East Asian population (Yan et al., 2003). Many efforts have been put to study the function of Gjb2 gene in both mouse model and human. In mouse, extensive deletion of Gjb2 causes embryo lethal due to the decreased transplacental glucose uptake, which was not found in human (Takata and Hirano, 1997; Gabriel et al., 1998). In human, GJB2 deficiency is not able to cause embryo lethal (D'Andrea et al., 2002). However, the study of GJB2-associated hearing loss is hampered by many difficulties, such as unobtainable human cochlea and acoustic nerve tissues, and therefore the GJB2-associated hearing loss are underlying mechanisms of still remaining unclear.
基金the National Basic Research Program of China(973 Program)(Grant No.2012CB315703)the Natural Science Foundation of China(Grant Nos.61371029 and 60971060).
文摘Spurious-free dynamic range(SFDR)limited by intermodulation distortions is a usually accepted measure for dynamic performance of a photonic time-stretched analog-to-digital converter(ADC).In this paper,SFDR improvement in a photonic time-stretched ADC based on third-order predistortion is proposed.The third-order predistortion is achieved optically within an integrated dual-parallel Mach–Zehnder modulator(DPMZM).The mechanism of SFDR improvement with third-order predistortion in the DPMZM is theoretically analyzed.Compared with a conventional scheme without predistortion,the experimental results show that the SFDR improvement of∼26 dB in the proposed scheme is proved.
基金This work was supported by the National Natural Science Foundation of China(No.61571391).
文摘With no dark zone in the propagation path and the same divergence angles,different plane spiral orbital angular momentum(PSOAM)beams can be superposed easily in the transverse plane.In this paper,a stacked resonator antenna based on substrate integrated waveguide is proposed,which is a compact planar waveguide structure.To obtain the structured EM wave which is superposed by the PSOAM waves(3;4;5;6)at 10 GHz,eight ring resonators are placed symmetrically on the two sides of the center plane and excited simultaneously.Simulation results,including distributions of the electric field,far-field results and purity analysis,are given,indicating that PSOAM beams can be generated with good performances.By controlling the initial phases of different PSOAM waves,beam steering can be realized with the same radiation patterns,which has great potentials in communication and radar detection.