With the development and application of energy Internet technology,the collaborative interaction of“source network,load and storage”has becomethe development trend of power grid dispatching.The large-scale access of...With the development and application of energy Internet technology,the collaborative interaction of“source network,load and storage”has becomethe development trend of power grid dispatching.The large-scale access of renewableenergy on the load side,the unified management of adjustable loads,and theparticipation of multiple parties in energy operations have put forward requirementsfor the safety,credibility,openness,and transparency of the load dispatchingenvironment.Under the environment of carbon emission reduction,the paperproposed an architecture of the scheduling data blockchain,based on the in-depthstudy of blockchain.Moreover,smart contracts are used to realize the applicationscenario of load dispatching instruction evidence on the blockchain.The contentand storage mode of scheduling instruction evidence on blockchain are studied.And different storage modes are adopted according to the actual needs.Andthe smart contract system realizes the evidence generation of power dispatchinginstruction.This is the basis for the normal circulation of power dispatchinginstruction evidence.The research significance of this paper is highlighted as follows.The data and information generated in the power dispatching process arestored as evidence.On the one hand,it can provide a basis for settlement betweenpower production and dispatching companies and power users.On the other hand,it can prepare for distributed transactions in the power grid under the environmentof carbon emission reduction.展开更多
Cancer cell receives extracellular signal inputs to obtain a stem-like status,yet how tumor microenvironmental(TME)neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive...Cancer cell receives extracellular signal inputs to obtain a stem-like status,yet how tumor microenvironmental(TME)neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive.Here,a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element(CRE)transcription factors are convergent activators for cancer stemness.Deconvolution of transcriptomic profiles,specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity.Specifically,neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis,where ATF1 serves as a conserved hub.Upon activation by norepinephrine,ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM,thereby orchestrating nuclear reprograming and mitochondrial rejuvenating.Accordingly,single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells.These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program,suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals.展开更多
Background:Overexpression of Aurora-A(AURKA)is a feature of breast cancer and associates with adverse prognosis.The selective Aurora-A inhibitor alisertib(MLN8237)has recently demonstrated promising antitumor response...Background:Overexpression of Aurora-A(AURKA)is a feature of breast cancer and associates with adverse prognosis.The selective Aurora-A inhibitor alisertib(MLN8237)has recently demonstrated promising antitumor responses as a single agent in various cancer types but its phase III clinical trial was reported as a failure since MLN8237 did not show an apparent effect in prolonging the survival of patients.Thus,identification of potential targets that could enhance the activity of MLN8237 would provide a rationale for drug combination to achieve better therapeutic outcome.Methods:Here,we conducted a systematic synthetic lethality CRISPR/Cas9 screening of 507 kinases using MLN8237 in breast cancer cells and identified a number of targetable kinases that displayed synthetic lethality interactions with MLN8237.Then,we performed competitive growth assays,colony formation assays,cell viability assays,apoptosis assays,and xenograft murine model to evaluate the synergistic therapeutic effects of Haspin(GSG2)depletion or inhibition with MLN8237.For mechanistic studies,immunofluorescence was used to detect the state of microtubules and the localization of Aurora-B and mitotic centromere-associated kinesin(MCAK).Results:Among the hits,we observed that Haspin depletion or inhibition marginally inhibited breast cancer cell growth but could substantially enhance the killing effects of MLN8237.Mechanistic studies showed that co-treatment with Aurora-A and Haspin inhibitors abolished the recruitment of Aurora-B and mitotic centromere-associated kinesin(MCAK)to centromeres which were associated with excessive microtubule depolymerization,kinetochore-microtubule(KT-MT)attachment failure,and severe mitotic catastrophe.We further showed that the combination of MLN8237 and the Haspin inhibitor CHR-6494 synergistically reduced breast cancer cell viability and significantly inhibited both in vitro and in vivo tumor growth.Conclusions:These findings establish Haspin as a synthetic lethal target and demonstrate CHR-6494 as a potential combinational drug for promoting the therapeutic effects of MLN8237 on breast cancer.展开更多
Yunnanozoans(including Yunnanozoon and Haikouella)are important representatives of the primitive vertebrates in the Early Cambrian Chengjiang fauna.For Yunnanozoans,we know less about Yunnanozoon than about Haikouella...Yunnanozoans(including Yunnanozoon and Haikouella)are important representatives of the primitive vertebrates in the Early Cambrian Chengjiang fauna.For Yunnanozoans,we know less about Yunnanozoon than about Haikouella due to the poor preservation of Yunnanozoon.Up to now,there have been some reports that Haikouella had developed gill rays,while there have been no reports on Yunnanozoon.In this paper,we described our new findings of the distinct gill rays of Yunnanozoon lividum based on new well-preserved material collected from the Lower Cambrian Maotianshan Shale in Xiaolantian of Yunnan Province,China.This study provides new data on the evolutionary relationship of the primitive vertebrates and their early evolution.展开更多
Background:Aneurysm of basilar perforator was rarely reported in the literature.It is difficult to treat due to its small size and deep-seated location.Excessive treatment may cause complications that resulted from is...Background:Aneurysm of basilar perforator was rarely reported in the literature.It is difficult to treat due to its small size and deep-seated location.Excessive treatment may cause complications that resulted from ischemic events of parent perforators.Therefore,it is important to make clinical strategy for such patients to improve the prognosis.Case presentation:One case,who presented as spontaneous subarachnoid hemorrhage,despite the negative result in computed tomography angiography firstly,was diagnosed angiographically as a ruptured aneurysm of the basilar perforator.A good clinical outcome of the case was achieved during the follow-up after conservative observation for 2 months,as well as the disappearance of previous lesion from angiography.Conclusions:Aneurysm located at perforator of basilar trunk was rare and difficult to treat.Conservative observation for certain cases with periodic angiography follow-up was considered in order to prevent the patients from potential iatrogenic effects.展开更多
基金supported by Science and Technology Program of State Grid Corporation of China under Grant(No.5100-202155319A-0-0-00).
文摘With the development and application of energy Internet technology,the collaborative interaction of“source network,load and storage”has becomethe development trend of power grid dispatching.The large-scale access of renewableenergy on the load side,the unified management of adjustable loads,and theparticipation of multiple parties in energy operations have put forward requirementsfor the safety,credibility,openness,and transparency of the load dispatchingenvironment.Under the environment of carbon emission reduction,the paperproposed an architecture of the scheduling data blockchain,based on the in-depthstudy of blockchain.Moreover,smart contracts are used to realize the applicationscenario of load dispatching instruction evidence on the blockchain.The contentand storage mode of scheduling instruction evidence on blockchain are studied.And different storage modes are adopted according to the actual needs.Andthe smart contract system realizes the evidence generation of power dispatchinginstruction.This is the basis for the normal circulation of power dispatchinginstruction evidence.The research significance of this paper is highlighted as follows.The data and information generated in the power dispatching process arestored as evidence.On the one hand,it can provide a basis for settlement betweenpower production and dispatching companies and power users.On the other hand,it can prepare for distributed transactions in the power grid under the environmentof carbon emission reduction.
基金This research work was supported by the National Key R&D Program of China(2019YFA0110300 to Q.L.)the National Natural Science Foundation of China(No.82003096 to R.G.,No.82002943 to B.H.,No.81820108024 to Q.L.and No.81972594 to M.Y.)+1 种基金the Natural Science Foundation of Guangdong(2017A030313608 to Q.L.)the Science and Technology Planning Project of Guangzhou(201804020044 to Q.L.).
文摘Cancer cell receives extracellular signal inputs to obtain a stem-like status,yet how tumor microenvironmental(TME)neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive.Here,a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element(CRE)transcription factors are convergent activators for cancer stemness.Deconvolution of transcriptomic profiles,specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity.Specifically,neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis,where ATF1 serves as a conserved hub.Upon activation by norepinephrine,ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM,thereby orchestrating nuclear reprograming and mitochondrial rejuvenating.Accordingly,single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells.These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program,suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals.
基金This research work was supported by the National Key R&D Program of China(2019YFA0110300 and 2017YFA0505600-04 to QL)the National Natural Science Foundation of China(81820108024 and 81630005 to QL,81773166 to ZFW)+2 种基金the Innovative Research Team at the University of Ministry of Education of China(IRT-17R15 to QL)the Natural Science Foundation of Guangdong(2016A030311038 and 2017A030313608 to QL,2017A020215098 to ZFW)the Science and Technology Planning Project of Guangzhou(201804020044 to QL).
文摘Background:Overexpression of Aurora-A(AURKA)is a feature of breast cancer and associates with adverse prognosis.The selective Aurora-A inhibitor alisertib(MLN8237)has recently demonstrated promising antitumor responses as a single agent in various cancer types but its phase III clinical trial was reported as a failure since MLN8237 did not show an apparent effect in prolonging the survival of patients.Thus,identification of potential targets that could enhance the activity of MLN8237 would provide a rationale for drug combination to achieve better therapeutic outcome.Methods:Here,we conducted a systematic synthetic lethality CRISPR/Cas9 screening of 507 kinases using MLN8237 in breast cancer cells and identified a number of targetable kinases that displayed synthetic lethality interactions with MLN8237.Then,we performed competitive growth assays,colony formation assays,cell viability assays,apoptosis assays,and xenograft murine model to evaluate the synergistic therapeutic effects of Haspin(GSG2)depletion or inhibition with MLN8237.For mechanistic studies,immunofluorescence was used to detect the state of microtubules and the localization of Aurora-B and mitotic centromere-associated kinesin(MCAK).Results:Among the hits,we observed that Haspin depletion or inhibition marginally inhibited breast cancer cell growth but could substantially enhance the killing effects of MLN8237.Mechanistic studies showed that co-treatment with Aurora-A and Haspin inhibitors abolished the recruitment of Aurora-B and mitotic centromere-associated kinesin(MCAK)to centromeres which were associated with excessive microtubule depolymerization,kinetochore-microtubule(KT-MT)attachment failure,and severe mitotic catastrophe.We further showed that the combination of MLN8237 and the Haspin inhibitor CHR-6494 synergistically reduced breast cancer cell viability and significantly inhibited both in vitro and in vivo tumor growth.Conclusions:These findings establish Haspin as a synthetic lethal target and demonstrate CHR-6494 as a potential combinational drug for promoting the therapeutic effects of MLN8237 on breast cancer.
基金supported by the Chinese Academy of Sciences (No.KZCX3-SW-141)the National Natural Science Foundation of China (Grants No.40302004 and 40432006)+1 种基金the National Science Foundation of Yunnan Province (No.2005D0002Z)the Open Foundation of Yunnan Key Laboratory for Palaeontology。
文摘Yunnanozoans(including Yunnanozoon and Haikouella)are important representatives of the primitive vertebrates in the Early Cambrian Chengjiang fauna.For Yunnanozoans,we know less about Yunnanozoon than about Haikouella due to the poor preservation of Yunnanozoon.Up to now,there have been some reports that Haikouella had developed gill rays,while there have been no reports on Yunnanozoon.In this paper,we described our new findings of the distinct gill rays of Yunnanozoon lividum based on new well-preserved material collected from the Lower Cambrian Maotianshan Shale in Xiaolantian of Yunnan Province,China.This study provides new data on the evolutionary relationship of the primitive vertebrates and their early evolution.
基金Suzhou high tech zone medical&health science&technology program(2018Z014)Suzhou science&technology development program(SYS2019067)
文摘Background:Aneurysm of basilar perforator was rarely reported in the literature.It is difficult to treat due to its small size and deep-seated location.Excessive treatment may cause complications that resulted from ischemic events of parent perforators.Therefore,it is important to make clinical strategy for such patients to improve the prognosis.Case presentation:One case,who presented as spontaneous subarachnoid hemorrhage,despite the negative result in computed tomography angiography firstly,was diagnosed angiographically as a ruptured aneurysm of the basilar perforator.A good clinical outcome of the case was achieved during the follow-up after conservative observation for 2 months,as well as the disappearance of previous lesion from angiography.Conclusions:Aneurysm located at perforator of basilar trunk was rare and difficult to treat.Conservative observation for certain cases with periodic angiography follow-up was considered in order to prevent the patients from potential iatrogenic effects.