This study describes a previously unidentified Neoproterozoic mafic dyke emplaced in the northern flank of the Langshan Tectonic Belt. This dyke intruded into the micaquartz schist of the Zhaertaishan Group, and yield...This study describes a previously unidentified Neoproterozoic mafic dyke emplaced in the northern flank of the Langshan Tectonic Belt. This dyke intruded into the micaquartz schist of the Zhaertaishan Group, and yielded an age of 908 ± 8 Ma. The youngest U-Pb ages of micaquartz schist from the Zhaertaishan Group in the Langshan area were 1118 ± 33 Ma,1187 ± 3 Ma and 1189 ± 39 Ma,suggesting that the depositional age of the protolith of the schist was between 908 ± 8 Ma and 1118 ± 33 Ma. In addition, 436 U-Pb age data and 155 Lu-Hf isotopic data from six samples in the Langshan Tectonic Belt and one Permian greywacke from the Wuhai area show distinct differences between the northern and southern flanks of the Main Langshan area. The U-Pb ages of the northern flank are primarily Meso-Neoproterozoic; similar ages have not been identified in the southern flank to date.Moreover, two-stage Hf model ages of the northern flank feature three age peaks at ～900 Ma,～1700 Ma and ～2600 Ma; this differs from Hf model ages of the southern flank, which feature one strong age peak at ～2700 Ma. These results suggest that the northern and southern flanks of the Main Langshan area have different geochronologic characteristics and should be divided further. Based on the U-Pb ages and Hf model ages, the northern and southern flanks of the Main Langshan area are named the North and South Langshan Tectonic Belts. Comparison of the U-Pb age and two-stage Hf model age distributions from the North Langshan Tectonic Belt, South Langshan Tectonic Belt, Alxa Block and the North China Craton(NCC) reveal that the North Langshan Tectonic Belt is similar to the Alxa Block and that the South Langshan Tectonic Belt is similar to the NCC. In addition, the zircon U-Pb age of 860 ±7 Ma commonly observed in the Alxa Block was detected in the Permian greywacke from the Wuhai area of the NCC, which suggests that the amalgamation of the North and South Langshan Tectonic belts(i.e.,the amalgamation of the Alxa Block and the NCC), occurred between Devonian and late Permian.展开更多
Background:Lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options.Emerging evidence shows that heat shock factor 1(HSF1)drives diversified transcriptom...Background:Lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options.Emerging evidence shows that heat shock factor 1(HSF1)drives diversified transcriptome to promote tumor growth and serves as a promising therapeutic target.However,the roles of HSF1 in lymphatic metastasis remain largely unknown.Herein,we aimed to illustrate the clinical roles and mechanisms of HSF1 in the lymphatic metastasis of bladder cancer and explore its therapeutic potential.Methods:We screened the most relevant gene to lymphatic metastasis among overexpressed heat shock factors(HSFs)and heat shock proteins(HSPs),and analyzed its clinical relevance in three cohorts.Functional in vitro and in vivo assays were performed in HSF1-silenced and-regained models.We also used Coimmunoprecipitation to identify the binding proteins of HSF1 and chromatin immunoprecipitation and dual-luciferase reporter assays to investigate the transcriptional program directed by HSF1.The pharmacological inhibitor of HSF1,KRIBB11,was evaluated in popliteal lymph node metastasis models and patientderived xenograft models of bladder cancer.Results:HSF1 expression was positively associated with lymphatic metastasis status,tumor stage,advanced grade,and poor prognosis of bladder cancer.Importantly,HSF1 enhanced the epithelial-mesenchymal transition(EMT)of cancer cells in primary tumor to initiate metastasis,proliferation of cancer cells in lymph nodes,and macrophages infiltration to facilitate multistep lymphatic metastasis.Mechanistically,HSF1 interacted with protein arginine methyltransferase 5(PRMT5)and jointly induced the monomethylation of histone H3 at arginine 2(H3R2me1)and symmetric dimethylation of histone H3 at arginine 2(H3R2me2s).This recruited the WD repeat domain 5(WDR5)/mixed-lineage leukemia(MLL)complex to increase the trimethylation of histone H3 at lysine 4(H3K4me3);resulting in upregulation of lymphoid enhancer-binding factor 1(LEF1),matrix metallopeptidase 9(MMP9),C-C motif chemokine ligand 20(CCL20),and E2F transcription factor 2(E2F2).Application of KRIBB11 significantly inhibited the lymphatic metastasis of bladder cancer with no significant toxicity.Conclusion:Our findings reveal a novel transcriptional program directed by the HSF1-PRMT5-WDR5 axis during the multistep process of lymphatic metastasis in bladder cancer.Targeting HSF1 could be a multipotent and promising therapeutic strategy for bladder cancer patients with lymphatic metastasis.展开更多
The Late Paleozoic volcanic rocks are widespread in the Western Tianshan,and mainly consist of basalt,trachyte,trachy-andesite,andesite and rhyolite.However,the formation timing and tectonic implications of the volcan...The Late Paleozoic volcanic rocks are widespread in the Western Tianshan,and mainly consist of basalt,trachyte,trachy-andesite,andesite and rhyolite.However,the formation timing and tectonic implications of the volcanic rocks remain controversial.To obtain a comprehensive dataset with adequate spatial coverage,we collected the published zircon U-Pb age data of the Late Paleozoic volcanic rocks in the Western Tianshan,and mapped the temporal and spatial distribution of these volcanic rocks.Our compiled dataset indicates that the volcanic rocks in the Western Tianshan were formed in two major stages:Late Silurian-Early Carboniferous and Late Carboniferous-Middle Permian.The southward subduction of the Northern Tianshan Ocean formed a large number of Late Silurian-Early Carboniferous volcanic rocks.The flare-up of Late Carboniferous to Middle Permian magmatism in the NTOB was considered to be the response of the slab-roll back of the northern Tianshan Ocean.Therefore,arc magma assemblage and spatial-temporal distribution are of great significance to identify the dynamic mechanism transformation of subduction zone.展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 41473015)a research grant from the Institute of Crustal Dynamics, CEA (ZDJ2014-02+2 种基金 ZDJ2017-05)the Tutor Foundation of the China University of Geosciences (Beijing) (Grant No. 53200859400)the China Geological Survey Projects (Grant Nos. 12120114041401 and 12120113015700)
文摘This study describes a previously unidentified Neoproterozoic mafic dyke emplaced in the northern flank of the Langshan Tectonic Belt. This dyke intruded into the micaquartz schist of the Zhaertaishan Group, and yielded an age of 908 ± 8 Ma. The youngest U-Pb ages of micaquartz schist from the Zhaertaishan Group in the Langshan area were 1118 ± 33 Ma,1187 ± 3 Ma and 1189 ± 39 Ma,suggesting that the depositional age of the protolith of the schist was between 908 ± 8 Ma and 1118 ± 33 Ma. In addition, 436 U-Pb age data and 155 Lu-Hf isotopic data from six samples in the Langshan Tectonic Belt and one Permian greywacke from the Wuhai area show distinct differences between the northern and southern flanks of the Main Langshan area. The U-Pb ages of the northern flank are primarily Meso-Neoproterozoic; similar ages have not been identified in the southern flank to date.Moreover, two-stage Hf model ages of the northern flank feature three age peaks at ～900 Ma,～1700 Ma and ～2600 Ma; this differs from Hf model ages of the southern flank, which feature one strong age peak at ～2700 Ma. These results suggest that the northern and southern flanks of the Main Langshan area have different geochronologic characteristics and should be divided further. Based on the U-Pb ages and Hf model ages, the northern and southern flanks of the Main Langshan area are named the North and South Langshan Tectonic Belts. Comparison of the U-Pb age and two-stage Hf model age distributions from the North Langshan Tectonic Belt, South Langshan Tectonic Belt, Alxa Block and the North China Craton(NCC) reveal that the North Langshan Tectonic Belt is similar to the Alxa Block and that the South Langshan Tectonic Belt is similar to the NCC. In addition, the zircon U-Pb age of 860 ±7 Ma commonly observed in the Alxa Block was detected in the Permian greywacke from the Wuhai area of the NCC, which suggests that the amalgamation of the North and South Langshan Tectonic belts(i.e.,the amalgamation of the Alxa Block and the NCC), occurred between Devonian and late Permian.
基金National Key Research and Development Program of China,Grant/Award Number:2018YFA0902803National Natural Science Foundation of China,Grant/Award Numbers:81825016,82072827,81961128027,81702523,81972383,82102957+5 种基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Numbers:2021B1515020009,2020A1515010888,2019A1515010188Science and Technology Program of Guangzhou,Grant/Award Number:202102010002Guangdong Special Support Program,Grant/Award Number:2017TX04R246Guangdong Province Higher Vocational Colleges&Schools Pearl River Scholar Funded Scheme(for Tianxin Lin)Guangdong Provincial Clinical Research Center for Urological Diseases,Grant/Award Number:2020B1111170006Guangdong Science and Technology Department,Grant/Award Numbers:2020B1212060018,2018B030317001。
文摘Background:Lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options.Emerging evidence shows that heat shock factor 1(HSF1)drives diversified transcriptome to promote tumor growth and serves as a promising therapeutic target.However,the roles of HSF1 in lymphatic metastasis remain largely unknown.Herein,we aimed to illustrate the clinical roles and mechanisms of HSF1 in the lymphatic metastasis of bladder cancer and explore its therapeutic potential.Methods:We screened the most relevant gene to lymphatic metastasis among overexpressed heat shock factors(HSFs)and heat shock proteins(HSPs),and analyzed its clinical relevance in three cohorts.Functional in vitro and in vivo assays were performed in HSF1-silenced and-regained models.We also used Coimmunoprecipitation to identify the binding proteins of HSF1 and chromatin immunoprecipitation and dual-luciferase reporter assays to investigate the transcriptional program directed by HSF1.The pharmacological inhibitor of HSF1,KRIBB11,was evaluated in popliteal lymph node metastasis models and patientderived xenograft models of bladder cancer.Results:HSF1 expression was positively associated with lymphatic metastasis status,tumor stage,advanced grade,and poor prognosis of bladder cancer.Importantly,HSF1 enhanced the epithelial-mesenchymal transition(EMT)of cancer cells in primary tumor to initiate metastasis,proliferation of cancer cells in lymph nodes,and macrophages infiltration to facilitate multistep lymphatic metastasis.Mechanistically,HSF1 interacted with protein arginine methyltransferase 5(PRMT5)and jointly induced the monomethylation of histone H3 at arginine 2(H3R2me1)and symmetric dimethylation of histone H3 at arginine 2(H3R2me2s).This recruited the WD repeat domain 5(WDR5)/mixed-lineage leukemia(MLL)complex to increase the trimethylation of histone H3 at lysine 4(H3K4me3);resulting in upregulation of lymphoid enhancer-binding factor 1(LEF1),matrix metallopeptidase 9(MMP9),C-C motif chemokine ligand 20(CCL20),and E2F transcription factor 2(E2F2).Application of KRIBB11 significantly inhibited the lymphatic metastasis of bladder cancer with no significant toxicity.Conclusion:Our findings reveal a novel transcriptional program directed by the HSF1-PRMT5-WDR5 axis during the multistep process of lymphatic metastasis in bladder cancer.Targeting HSF1 could be a multipotent and promising therapeutic strategy for bladder cancer patients with lymphatic metastasis.
基金supported by the National Key Research and Development Project (No.2019YFA0708601)the National Natural Science Foundation of China (Nos.41573045,41873060,and 41830216)+1 种基金the China Geological Survey (No.DD20221649)the Fund from the Key Laboratory of Deep-Earth Dynamics of Ministry of Natural Resources (No.J1901-5)
文摘The Late Paleozoic volcanic rocks are widespread in the Western Tianshan,and mainly consist of basalt,trachyte,trachy-andesite,andesite and rhyolite.However,the formation timing and tectonic implications of the volcanic rocks remain controversial.To obtain a comprehensive dataset with adequate spatial coverage,we collected the published zircon U-Pb age data of the Late Paleozoic volcanic rocks in the Western Tianshan,and mapped the temporal and spatial distribution of these volcanic rocks.Our compiled dataset indicates that the volcanic rocks in the Western Tianshan were formed in two major stages:Late Silurian-Early Carboniferous and Late Carboniferous-Middle Permian.The southward subduction of the Northern Tianshan Ocean formed a large number of Late Silurian-Early Carboniferous volcanic rocks.The flare-up of Late Carboniferous to Middle Permian magmatism in the NTOB was considered to be the response of the slab-roll back of the northern Tianshan Ocean.Therefore,arc magma assemblage and spatial-temporal distribution are of great significance to identify the dynamic mechanism transformation of subduction zone.
