The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is the...The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.展开更多
Quantitative glacial chronologies of past glaciations are sparse in the Himalaya, and mostly absent in the Kashmir Himalaya. We used cosmogenicBe exposure dating, and geomorphological mapping to reconstruct glacial ad...Quantitative glacial chronologies of past glaciations are sparse in the Himalaya, and mostly absent in the Kashmir Himalaya. We used cosmogenicBe exposure dating, and geomorphological mapping to reconstruct glacial advances of the Thajwas Glacier(TG) in the Great Himalayan Range of the Kashmir Himalaya. FromBe exposure dating of ten moraine boulders, four glacial stages with ages ~20.77 ±2.28 ka, ~11.46 ± 1.69 ka, ~9.12 ± 1.39 ka and ~4.19 ± 0.78 ka, were identified. The reconstructed cosmogenic radionuclide ages confirmed the global Last Glacial Maximum(g LGM), Younger Dryas, Early Holocene, and Neoglaciation episodes. As per area and volume change analyses, the TG has lost 51.1 km~2 of its area and a volume of 2.64 km~3 during the last 20.77 ± 2.28 ka. Overall, the results suggested that the TG has lost 64% of area and 73% of volume from the Last glacial maximum to Neoglaciation and about 85.74% and 87.67% of area and volume, respectively, from Neoglaciation to the present day. The equilibrium line altitude of the TG fluctuated from 4238 m a.s.l present to3365 m a.s.l during the g LGM(20.77 ± 2.28 ka). The significant cooling induced by a drop in mean ambient temperature resulted in a positive mass balance of the TG during the g LGM. Subsequently the melting accelerated due to the continuing rise of the global ambient temperature. Paleo-glacial history reconstruction of the Kashmir Himalaya, with its specific geomorphic and climatic setting, would help close the information gap about the chronology of past regional glacial episodes.展开更多
文摘The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.
基金conducted with the help of grants from the Department of Science and Technology (DST), Government of India under the sponsored research project titled “Centre of Excellence for Glacial Studies in Western Himalaya”granting fellowship to Omar Jaan Paul under the project No. UFR-59313。
文摘Quantitative glacial chronologies of past glaciations are sparse in the Himalaya, and mostly absent in the Kashmir Himalaya. We used cosmogenicBe exposure dating, and geomorphological mapping to reconstruct glacial advances of the Thajwas Glacier(TG) in the Great Himalayan Range of the Kashmir Himalaya. FromBe exposure dating of ten moraine boulders, four glacial stages with ages ~20.77 ±2.28 ka, ~11.46 ± 1.69 ka, ~9.12 ± 1.39 ka and ~4.19 ± 0.78 ka, were identified. The reconstructed cosmogenic radionuclide ages confirmed the global Last Glacial Maximum(g LGM), Younger Dryas, Early Holocene, and Neoglaciation episodes. As per area and volume change analyses, the TG has lost 51.1 km~2 of its area and a volume of 2.64 km~3 during the last 20.77 ± 2.28 ka. Overall, the results suggested that the TG has lost 64% of area and 73% of volume from the Last glacial maximum to Neoglaciation and about 85.74% and 87.67% of area and volume, respectively, from Neoglaciation to the present day. The equilibrium line altitude of the TG fluctuated from 4238 m a.s.l present to3365 m a.s.l during the g LGM(20.77 ± 2.28 ka). The significant cooling induced by a drop in mean ambient temperature resulted in a positive mass balance of the TG during the g LGM. Subsequently the melting accelerated due to the continuing rise of the global ambient temperature. Paleo-glacial history reconstruction of the Kashmir Himalaya, with its specific geomorphic and climatic setting, would help close the information gap about the chronology of past regional glacial episodes.
