Anaplastic thyroid cancer(ATC)is a rare but highly lethal disease.ATCs are resistant to standard therapies and are extremely difficult to manage.The stepwise cell dedifferentiation results in the impairment of the iod...Anaplastic thyroid cancer(ATC)is a rare but highly lethal disease.ATCs are resistant to standard therapies and are extremely difficult to manage.The stepwise cell dedifferentiation results in the impairment of the iodine-metabolizing machinery and the infeasibility of radioiodine treatment in ATC.Hence,reinducing iodine-metabolizing gene expression to restore radioiodine avidity is considered as a promising strategy to fight against ATC.In the present study,capsaicin(CAP),a natural potent transient receptor potential vanilloid type 1(TRPV1)agonist,was discovered to reinduce ATC cell differentiation and to increase the expression of thyroid transcription factors(TTFs including TTF-1,TTF-2,and PAX8)and iodine-metabolizing proteins,including thyroidstimulating hormone receptor(TSHR),thyroid peroxidase,and sodium iodine symporter(NIS),in two ATC cell lines,8505C and FRO.Strikingly,CAP treatment promoted NIS glycosylation and its membrane trafficking,resulting in a significant enhancement of radioiodine uptake of ATC cells in vitro.Mechanistically,CAP-activated TRPV1 channel and subsequently triggered Ca2þinflux,cyclic adenosine monophosphate(cAMP)generation,and cAMP-responsive element-binding protein(CREB)signal activation.Next,CREB recognized and bound to the promoter of SLC5A5 to facilitate its transcription.Moreover,the TRPV1 antagonist CPZ,the calcium chelator BAPTA,and the PKA inhibitor H-89 effectively alleviated the redifferentiation exerted by CAP,demonstrating that CAP might improve radioiodine avidity through the activation of the TRPV1–Ca2þ/cAMP/PKA/CREB signaling pathway.In addition,our study indicated that CAP might trigger a novel cascade to redifferentiate ATC cells and provide unprecedented opportunities for radioiodine therapy in ATC,bypassing canonical TSH–TSHR pathway.展开更多
A new and convenient procedure is developed for the preparation of N-sulfonylbenzotriazoles from sodium sulfinates and benzotriazoles using molecular iodine as catalyst via the S-N bond formation reaction. This cataly...A new and convenient procedure is developed for the preparation of N-sulfonylbenzotriazoles from sodium sulfinates and benzotriazoles using molecular iodine as catalyst via the S-N bond formation reaction. This catalytic radical sulfonylation proceeds efficiently in air at room temperature under neutral conditions, and in short reaction time, to afford the corresponding N-sulfonylbenzotriazoles in good yields, thus extending the catalytic application of molecular iodine in organic synthesis.展开更多
Background Radiation detection has been a main interest for researchers as all kind of produced particles in atomic and subatomic physics based on the measurement systems so-called detector.Detection efficiency is one...Background Radiation detection has been a main interest for researchers as all kind of produced particles in atomic and subatomic physics based on the measurement systems so-called detector.Detection efficiency is one of the main parameters in detection system besides many other different parameters of the detector.The detector in experimental physics is an instrument that converts radiation energy into an electrical signal,and this is achieved basically by either ionization or excitation.The choice for any type of a detector(gas-filled,scintillation or semiconductor)for any application depends upon the X-ray of gamma energy range of interest.A working model is therefore developed which is capable of describing the overall NaI(Tl)detection efficiency as a function of several known parameters.Purpose The attenuation coefficients for the bismuth borate glasses with different concentrations were measured using gamma spectroscopy technique.The numerical absolute efficiency calibration of a detector can be determined by In-Situ Object Calibration Software(ISOCS)and Monte Carlo Neutral Particle version 5(MCNP5)techniques which does not require any calibration standards or reference materials.Methods By using the ISOCS and MCNP5 methodologies,the full energy peak efficiency of a scintillator detector(3“X3”NaI(Tl))exposed to Co-60 and Cs-137 gamma ray sources with average accuracy range 0.126–1.224%for the used samples can be detected.The used materials are ternary and are located between the detector and the source to determine the attenuation coefficients for these samples by using the calculated full energy peak efficiencies of a detector.Results The average accuracy ranged from−1.808 to 1.960%for linear attenuation coefficient(μ),while it ranged from−1.999 to 1.888%and from−1.924 to 1.960%for half value layer(HVL)and mass linear attenuation coefficient(μm),respectively.Conclusion The calculated values of the absolute full energy peak efficiency have been used to determine the attenuation coefficients of materials with different concentrations and different densities.The results proved the validation of ISOCS and MCNP to determine the absolute full energy peak efficiency of the detector which can be used to determine the attenuation coefficients for the simulated samples and it is a good tool to be used when experimental methods are not available.展开更多
基金supported by grants from the National Natural Science Foundation of China(81972503 and 82103656).
文摘Anaplastic thyroid cancer(ATC)is a rare but highly lethal disease.ATCs are resistant to standard therapies and are extremely difficult to manage.The stepwise cell dedifferentiation results in the impairment of the iodine-metabolizing machinery and the infeasibility of radioiodine treatment in ATC.Hence,reinducing iodine-metabolizing gene expression to restore radioiodine avidity is considered as a promising strategy to fight against ATC.In the present study,capsaicin(CAP),a natural potent transient receptor potential vanilloid type 1(TRPV1)agonist,was discovered to reinduce ATC cell differentiation and to increase the expression of thyroid transcription factors(TTFs including TTF-1,TTF-2,and PAX8)and iodine-metabolizing proteins,including thyroidstimulating hormone receptor(TSHR),thyroid peroxidase,and sodium iodine symporter(NIS),in two ATC cell lines,8505C and FRO.Strikingly,CAP treatment promoted NIS glycosylation and its membrane trafficking,resulting in a significant enhancement of radioiodine uptake of ATC cells in vitro.Mechanistically,CAP-activated TRPV1 channel and subsequently triggered Ca2þinflux,cyclic adenosine monophosphate(cAMP)generation,and cAMP-responsive element-binding protein(CREB)signal activation.Next,CREB recognized and bound to the promoter of SLC5A5 to facilitate its transcription.Moreover,the TRPV1 antagonist CPZ,the calcium chelator BAPTA,and the PKA inhibitor H-89 effectively alleviated the redifferentiation exerted by CAP,demonstrating that CAP might improve radioiodine avidity through the activation of the TRPV1–Ca2þ/cAMP/PKA/CREB signaling pathway.In addition,our study indicated that CAP might trigger a novel cascade to redifferentiate ATC cells and provide unprecedented opportunities for radioiodine therapy in ATC,bypassing canonical TSH–TSHR pathway.
文摘A new and convenient procedure is developed for the preparation of N-sulfonylbenzotriazoles from sodium sulfinates and benzotriazoles using molecular iodine as catalyst via the S-N bond formation reaction. This catalytic radical sulfonylation proceeds efficiently in air at room temperature under neutral conditions, and in short reaction time, to afford the corresponding N-sulfonylbenzotriazoles in good yields, thus extending the catalytic application of molecular iodine in organic synthesis.
文摘Background Radiation detection has been a main interest for researchers as all kind of produced particles in atomic and subatomic physics based on the measurement systems so-called detector.Detection efficiency is one of the main parameters in detection system besides many other different parameters of the detector.The detector in experimental physics is an instrument that converts radiation energy into an electrical signal,and this is achieved basically by either ionization or excitation.The choice for any type of a detector(gas-filled,scintillation or semiconductor)for any application depends upon the X-ray of gamma energy range of interest.A working model is therefore developed which is capable of describing the overall NaI(Tl)detection efficiency as a function of several known parameters.Purpose The attenuation coefficients for the bismuth borate glasses with different concentrations were measured using gamma spectroscopy technique.The numerical absolute efficiency calibration of a detector can be determined by In-Situ Object Calibration Software(ISOCS)and Monte Carlo Neutral Particle version 5(MCNP5)techniques which does not require any calibration standards or reference materials.Methods By using the ISOCS and MCNP5 methodologies,the full energy peak efficiency of a scintillator detector(3“X3”NaI(Tl))exposed to Co-60 and Cs-137 gamma ray sources with average accuracy range 0.126–1.224%for the used samples can be detected.The used materials are ternary and are located between the detector and the source to determine the attenuation coefficients for these samples by using the calculated full energy peak efficiencies of a detector.Results The average accuracy ranged from−1.808 to 1.960%for linear attenuation coefficient(μ),while it ranged from−1.999 to 1.888%and from−1.924 to 1.960%for half value layer(HVL)and mass linear attenuation coefficient(μm),respectively.Conclusion The calculated values of the absolute full energy peak efficiency have been used to determine the attenuation coefficients of materials with different concentrations and different densities.The results proved the validation of ISOCS and MCNP to determine the absolute full energy peak efficiency of the detector which can be used to determine the attenuation coefficients for the simulated samples and it is a good tool to be used when experimental methods are not available.
