The identification of driver mutations and drugs that inhibit their activity has been a major therapeutic advance for patients with advanced lung adenocarcinoma. Unfortunately, the success of these drugs is limited by...The identification of driver mutations and drugs that inhibit their activity has been a major therapeutic advance for patients with advanced lung adenocarcinoma. Unfortunately, the success of these drugs is limited by the universal development of resistance. Treatment failure can result from inadequate drug exposure or selection of resistant malignant clones. Clinically distinct mechanisms of disease progression have been identified and can inform treatment decisions. Investigations into the biochemical mechanisms of tyrosine kinase inhibitor resistance may provide additional therapeutic targets by which the efficacy of targeted therapy can be improved.展开更多
Fungal stromata were recently discovered in association with charcoal and burnt soil aggregates during an archaeological survey in the Chaˆtillon-sur-Seine forest massif.The wood and soil in the samples were dated to ...Fungal stromata were recently discovered in association with charcoal and burnt soil aggregates during an archaeological survey in the Chaˆtillon-sur-Seine forest massif.The wood and soil in the samples were dated to the medieval period(between 738 and 1411 AD).Light microscopy and scanning electron microscopy revealed that a few of the stromatal fragments still contained ascospores.Their macromorphological characters were described and secondary metabolite profiles were generated using high performance liquid chromatography with diode array and mass spectrometric detection(HPLC–DAD/MS).The combination of these two data lines then allowed species identification.Most of the fragments were assigned to Hypoxylon fragiforme,the type species of the Hypoxylaceae(Xylariales).Two further species whose stromata grew on the fossil charcoal could be tentatively identified as Jackrogersella cohaerens and(more tentatively)as Hypoxylon vogesiacum.These three species are still commonly encountered in the forests of Central Europe today.Furthermore,the HPLC-HRMS data of H.fragiforme suggested the presence of unknown azaphilone dimers and of further new pigments.These archaeological compounds were compared to fresh stromata of H.fragiforme collected in Germany and subjected to the same analytical protocol.While the major components in both samples were identified as the known mitorubrin type azaphilones and orsellinic acid,the chemical structures of seven novel complex azaphilone pigments,for which we propose the trivial names rutilins C-D and fragirubrins A-E,were elucidated using spectral methods(NMR and CD spectroscopy,high resolution mass spectrometry).It appears that these pigments had indeed persisted for millennia in the fossil stromata.展开更多
文摘The identification of driver mutations and drugs that inhibit their activity has been a major therapeutic advance for patients with advanced lung adenocarcinoma. Unfortunately, the success of these drugs is limited by the universal development of resistance. Treatment failure can result from inadequate drug exposure or selection of resistant malignant clones. Clinically distinct mechanisms of disease progression have been identified and can inform treatment decisions. Investigations into the biochemical mechanisms of tyrosine kinase inhibitor resistance may provide additional therapeutic targets by which the efficacy of targeted therapy can be improved.
文摘Fungal stromata were recently discovered in association with charcoal and burnt soil aggregates during an archaeological survey in the Chaˆtillon-sur-Seine forest massif.The wood and soil in the samples were dated to the medieval period(between 738 and 1411 AD).Light microscopy and scanning electron microscopy revealed that a few of the stromatal fragments still contained ascospores.Their macromorphological characters were described and secondary metabolite profiles were generated using high performance liquid chromatography with diode array and mass spectrometric detection(HPLC–DAD/MS).The combination of these two data lines then allowed species identification.Most of the fragments were assigned to Hypoxylon fragiforme,the type species of the Hypoxylaceae(Xylariales).Two further species whose stromata grew on the fossil charcoal could be tentatively identified as Jackrogersella cohaerens and(more tentatively)as Hypoxylon vogesiacum.These three species are still commonly encountered in the forests of Central Europe today.Furthermore,the HPLC-HRMS data of H.fragiforme suggested the presence of unknown azaphilone dimers and of further new pigments.These archaeological compounds were compared to fresh stromata of H.fragiforme collected in Germany and subjected to the same analytical protocol.While the major components in both samples were identified as the known mitorubrin type azaphilones and orsellinic acid,the chemical structures of seven novel complex azaphilone pigments,for which we propose the trivial names rutilins C-D and fragirubrins A-E,were elucidated using spectral methods(NMR and CD spectroscopy,high resolution mass spectrometry).It appears that these pigments had indeed persisted for millennia in the fossil stromata.
