The Zintl compound Mg3Sb2 has been recently identified as promising thermoelectric material owing to its high thermoelectric performance and cost-effective,nontoxicity and environment friendly characteristics.However,...The Zintl compound Mg3Sb2 has been recently identified as promising thermoelectric material owing to its high thermoelectric performance and cost-effective,nontoxicity and environment friendly characteristics.However,the intrinsically p-type Mg3Sb2 shows low figure of merit（z T = 0.23 at 723 K） for its poor electrical conductivity.In this study,a series of Mg（3-x）LixSb2 bulk materials have been prepared by high-energy ball milling and spark plasma sintering（SPS） process.Electrical transport measurements on these materials revealed significant improvement on the power factor with respect to the undoped sample,which can be essentially attributed to the increased carrier concentration,leading to a maximum z T of0.59 at 723 K with the optimum doping level x = 0.01.Additionally,the engineering z T and energy conversion efficiency are calculated to be 0.235 and 4.89%,respectively.To our best knowledge,those are the highest values of all reported p-type Mg3Sb2-based compounds with single element doping.展开更多
Ammonia plays an important role in cellular metabolism.However,ammonia is considered a toxic product.In bone marrow-derived mesenchymal stem cells,multipotent stem cells with high expression of glutamine synthetase(GS...Ammonia plays an important role in cellular metabolism.However,ammonia is considered a toxic product.In bone marrow-derived mesenchymal stem cells,multipotent stem cells with high expression of glutamine synthetase(GS)in bone marrow,ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs.As a major nutritional amino acid for biosynthesis,glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation.The activation of mTOR can promote cell entry into S phase,thereby enhancing DNA synthesis and cell proliferation.Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity.Then,the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation.These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia.展开更多
From the perspective of management,this paper sorted out the management thoughts of the Chinese Television Historical Comedy Drama Li Wei the Magistrate.Then,on the basis of the sorting,it analyzed and summarized the ...From the perspective of management,this paper sorted out the management thoughts of the Chinese Television Historical Comedy Drama Li Wei the Magistrate.Then,on the basis of the sorting,it analyzed and summarized the management ideas and actions of characters in the drama.Finally,it summarized the application of management measures in the management of organizations,including making clear management responsibilities,using limited resources to maximize benefits,being strict with relatives,and practicing forbearance all the time,to improve the overall efficiency and benefits of enterprises and organizations.展开更多
Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages...Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the microenvironment.Colony-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid tumors.There are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor microenvironment.Here,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian cancer.We found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor prognosis.Treatment by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in vivo.Blockade of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.展开更多
Mesenchymal stem cell(MSC)-mediated immunomodulation has been harnessed for the treatment of human diseases,but its underlying mechanism has not been fully understood.Dead cells,including apoptotic cells have immunomo...Mesenchymal stem cell(MSC)-mediated immunomodulation has been harnessed for the treatment of human diseases,but its underlying mechanism has not been fully understood.Dead cells,including apoptotic cells have immunomodulatory properties.It has been repeatedly reported that the proportion of nonviable MSCs in a MSC therapeutic preparation varied from 5-50%in the ongoing clinical trials.It is conceivable that the nonviable cells in a MSC therapeutic preparation may play a role in the therapeutic effects of MSCs.We found that the MSC therapeutic preparation in the present study had about 5%dead MSCs(DMSCs),characterized by apoptotic cells.Namely,1×10^(6) MSCs in the preparation contained about 5×10^(4) DMSCs.We found that the treatment with even 5×10^(4) DMSCs alone had the equal therapeutic effects as with 1×10^(6) MSCs.This protective effect of the dead MSCs alone was confirmed in four mouse models,including concanavalin A(ConA)-and carbon tetrachloride(CCI4)-induced acute liver injury,LPS-induced lung injury and spinal cord injury.We also found that the infused MSCs died by apoptosis in vivo.Furthermore,the therapeutic effect was attributed to the elevated level of phosphatidylserine(PS)upon the injection of MSCs or DMSCs.The direct administration of PS liposomes(PSLs)mimic apoptotic cell fragments also exerted the protective effects as MSCs and DMSCs.The Mer tyrosine kinase(MerTK)deficiency or the knockout of chemokine receptor C-C motif chemokine receptor 2(CCR2)reversed these protective effects of MSCs or DMSCs.These results revealed that DMSCs alone in the therapeutic stem cell preparation or the apoptotic cells induced in vivo may exert the same immunomodulatory property as the'living MSCs preparation"through releasing PS,which was further recognized by MerTK and participated in modulating immune cells.展开更多
Scientific knowledge of lunar lithologies was first acquired in the 1960s-1970s.The space race between the United States(U.S.)and Soviet Union has promoted numerous manned and robotic lunar exploration missions.Utiliz...Scientific knowledge of lunar lithologies was first acquired in the 1960s-1970s.The space race between the United States(U.S.)and Soviet Union has promoted numerous manned and robotic lunar exploration missions.Utilizing datasets from these missions,the first series of lunar geologic maps was prepared and published by the U.S.Geological Survey(USGS)The definition of lunar geological features in these maps was mostly based on morphological characteristics but lacked lithological constraints owing to the incompleteness of the compositional datasets avail-able.After two decades of silence,a new era of lunar exploration began in the 1990s when the Galileo spacecraft flew by the Moon during its gravity-assisted maneuvers.The very successful orbital missions,the Clementine and Lunar Prospector(LP),provided the first global geochemical and mineralogical(multispectral,gamma ray,neutron,etc.)datasets of the lunar surface.展开更多
The tectonic evolution of the Moon is driven by both endogenic(e.g.,magmatism)and exogenic(e.g.,meteorite impact)forces.A tectonic map of the Moon provides key information about the spatiotemporal distribution of stru...The tectonic evolution of the Moon is driven by both endogenic(e.g.,magmatism)and exogenic(e.g.,meteorite impact)forces.A tectonic map of the Moon provides key information about the spatiotemporal distribution of structures and tectonic units.Although the Moon has no plate tectonics,its surface can be divided into different terranes due to the uneven evolution[1].We define these terranes as tectonic units.Structures,such as craters and faults,are the basic elements of the tectonic units.As a synthesis of current knowledge on lunar tectonics and evolutionary history,lunar tectonic maps are a fundamental resource for scientific research,exploration planning,and landing site selection[2].展开更多
After online publication of the article1,the authors noticed one inadvertent mistake in Fig.5a that needs to be corrected.In detail,the pathological picture of PBS group in Fig.5a is inadvertently duplicated as the im...After online publication of the article1,the authors noticed one inadvertent mistake in Fig.5a that needs to be corrected.In detail,the pathological picture of PBS group in Fig.5a is inadvertently duplicated as the image of PBS group in Fig.7b in the main text.This duplication is a result of errors in figure assembly,and the correct Fig.5 is provided as follows.The key findings of the article are not affected by these corrections.展开更多
The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening.Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the...The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening.Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2,which greatly limits its application in routine research.Here,we gen erate a mouse model of COVID-19 un der a gen eral laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome(ARDS)observed in huma ns.Briefly,human ACE2-tra nsge nic(MCE2)mice were in tratracheally in stilled with the formaldehyde-inactivated SARS-CoV-2,resulting in a rapid weight loss and detrimental changes in lung structure and function.The pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation,hemorrhage,necrotic debris,and hyaline membrane formation.The production of fatal cytokines(IL-β,TNF-α,and IL-6)and the infiltration of activated neutrophils,inflammatory monocyte-macrophages,and T cells in the lung were also determined,suggesting the activation of an adaptive immune response.Therapeutic strategies,such as dexamethasone or passive antibody therapy,could effectively ameliorate the disease progression in this model.Therefore,the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.U1601213 and 51572287)the Key Research Program of Frontier Sciences of the Chinese Academy of Sciences(Grant No.QYZDB-SSW-SLH013)
文摘The Zintl compound Mg3Sb2 has been recently identified as promising thermoelectric material owing to its high thermoelectric performance and cost-effective,nontoxicity and environment friendly characteristics.However,the intrinsically p-type Mg3Sb2 shows low figure of merit（z T = 0.23 at 723 K） for its poor electrical conductivity.In this study,a series of Mg（3-x）LixSb2 bulk materials have been prepared by high-energy ball milling and spark plasma sintering（SPS） process.Electrical transport measurements on these materials revealed significant improvement on the power factor with respect to the undoped sample,which can be essentially attributed to the increased carrier concentration,leading to a maximum z T of0.59 at 723 K with the optimum doping level x = 0.01.Additionally,the engineering z T and energy conversion efficiency are calculated to be 0.235 and 4.89%,respectively.To our best knowledge,those are the highest values of all reported p-type Mg3Sb2-based compounds with single element doping.
基金supported by the National Natural Science Foundation of China(No.81602492)the National Science Fund for Excellent Young Scholars National Science Fund for Excellent Young Scholars(No.32122052)National Natural Science Foundation Regional Innovation and Development(No.U19A2003).
文摘Ammonia plays an important role in cellular metabolism.However,ammonia is considered a toxic product.In bone marrow-derived mesenchymal stem cells,multipotent stem cells with high expression of glutamine synthetase(GS)in bone marrow,ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs.As a major nutritional amino acid for biosynthesis,glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation.The activation of mTOR can promote cell entry into S phase,thereby enhancing DNA synthesis and cell proliferation.Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity.Then,the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation.These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia.
基金Humanities and Social Science Project of Shandong Province in 2019"Study on the Innovation and Operating Mechanism of the Cooperation Model of Sports and Tourism Enterprises in Shandong Province"(19-ZC-GL-02)General Project of 2019 Education Reform Project of Taishan University"National First-class Professional Tourism Management to Promote Educational Talents Training Model Optimization and Practice Plan by Competition"(201925)+2 种基金Youth Innovation Talent Induction Plan Project of Colleges and Universities in 2019"Tourism Industry Investment Risk and Management Innovation Team"General Project of Shandong Province Undergraduate Education Reform Project"Research on Innovation and Practice of Internationalized Talent Training Model for Tourism Management"(M2018X291)Digital Shandong Special Program of Shandong Provincial Social Science Planning Project"Research on Innovation of Element Structure,Institutional Environment and High-quality Development Path of Tourism Economy"(20CCXJ28).
文摘From the perspective of management,this paper sorted out the management thoughts of the Chinese Television Historical Comedy Drama Li Wei the Magistrate.Then,on the basis of the sorting,it analyzed and summarized the management ideas and actions of characters in the drama.Finally,it summarized the application of management measures in the management of organizations,including making clear management responsibilities,using limited resources to maximize benefits,being strict with relatives,and practicing forbearance all the time,to improve the overall efficiency and benefits of enterprises and organizations.
基金supported by the National Science Foundation for Excellent Young Scholars(China)(No.32122052)the National Natural Science Foundation Regional Innovation and Development(China)(No.U19A2003).
文摘Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the microenvironment.Colony-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid tumors.There are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor microenvironment.Here,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian cancer.We found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor prognosis.Treatment by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in vivo.Blockade of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.
基金This work was supported by the National Natural Science Foundation Regional Innovation and Development(number U19A2003)National Major Scientific and Technological Special Project for"Significant New Drugs Development”(number 2018ZX09733001)+3 种基金Excellent Youth Foundation of the Sichuan Scientific Committee Grant in China(number 2019JDJQ008)Development Program of China(number 2016YFA0201402)the National Natural Science Foundation of China(number 81800421)the National Natural Science Foundation of China(number 81821002).
文摘Mesenchymal stem cell(MSC)-mediated immunomodulation has been harnessed for the treatment of human diseases,but its underlying mechanism has not been fully understood.Dead cells,including apoptotic cells have immunomodulatory properties.It has been repeatedly reported that the proportion of nonviable MSCs in a MSC therapeutic preparation varied from 5-50%in the ongoing clinical trials.It is conceivable that the nonviable cells in a MSC therapeutic preparation may play a role in the therapeutic effects of MSCs.We found that the MSC therapeutic preparation in the present study had about 5%dead MSCs(DMSCs),characterized by apoptotic cells.Namely,1×10^(6) MSCs in the preparation contained about 5×10^(4) DMSCs.We found that the treatment with even 5×10^(4) DMSCs alone had the equal therapeutic effects as with 1×10^(6) MSCs.This protective effect of the dead MSCs alone was confirmed in four mouse models,including concanavalin A(ConA)-and carbon tetrachloride(CCI4)-induced acute liver injury,LPS-induced lung injury and spinal cord injury.We also found that the infused MSCs died by apoptosis in vivo.Furthermore,the therapeutic effect was attributed to the elevated level of phosphatidylserine(PS)upon the injection of MSCs or DMSCs.The direct administration of PS liposomes(PSLs)mimic apoptotic cell fragments also exerted the protective effects as MSCs and DMSCs.The Mer tyrosine kinase(MerTK)deficiency or the knockout of chemokine receptor C-C motif chemokine receptor 2(CCR2)reversed these protective effects of MSCs or DMSCs.These results revealed that DMSCs alone in the therapeutic stem cell preparation or the apoptotic cells induced in vivo may exert the same immunomodulatory property as the'living MSCs preparation"through releasing PS,which was further recognized by MerTK and participated in modulating immune cells.
基金supported by the National Science and Technology Infrastructure Work Projects(2015FY210500)Key Research Program of Frontier Sciences,Chinese Academy of Sciences(QYZDY-SSW-DQC028)+5 种基金Strategic Priority Program of Chinese Academy of Sciences(XDB41000000)the National Natural Science Foundation of China(42102280,41972322,and 11941001)the Natural Science Foundation of Shandong Province(ZR2021QD016)the China Postdoctoral Science Foundation(2020M682164)the State Scholarship Fund(201706220310)。
文摘Scientific knowledge of lunar lithologies was first acquired in the 1960s-1970s.The space race between the United States(U.S.)and Soviet Union has promoted numerous manned and robotic lunar exploration missions.Utilizing datasets from these missions,the first series of lunar geologic maps was prepared and published by the U.S.Geological Survey(USGS)The definition of lunar geological features in these maps was mostly based on morphological characteristics but lacked lithological constraints owing to the incompleteness of the compositional datasets avail-able.After two decades of silence,a new era of lunar exploration began in the 1990s when the Galileo spacecraft flew by the Moon during its gravity-assisted maneuvers.The very successful orbital missions,the Clementine and Lunar Prospector(LP),provided the first global geochemical and mineralogical(multispectral,gamma ray,neutron,etc.)datasets of the lunar surface.
基金supported by the National Science and Technology Infrastructure Work Projects(2015FY210500)the Key Research Program of Frontier Sciences,Chinese Academy of Sciences(QYZDY-SSW-DQC028)+1 种基金the Strategic Priority Program of Chinese Academy of Sciences(XDB41000000)the National Natural Science Foundation of China(41772346,41372337,and 40971187)。
文摘The tectonic evolution of the Moon is driven by both endogenic(e.g.,magmatism)and exogenic(e.g.,meteorite impact)forces.A tectonic map of the Moon provides key information about the spatiotemporal distribution of structures and tectonic units.Although the Moon has no plate tectonics,its surface can be divided into different terranes due to the uneven evolution[1].We define these terranes as tectonic units.Structures,such as craters and faults,are the basic elements of the tectonic units.As a synthesis of current knowledge on lunar tectonics and evolutionary history,lunar tectonic maps are a fundamental resource for scientific research,exploration planning,and landing site selection[2].
文摘After online publication of the article1,the authors noticed one inadvertent mistake in Fig.5a that needs to be corrected.In detail,the pathological picture of PBS group in Fig.5a is inadvertently duplicated as the image of PBS group in Fig.7b in the main text.This duplication is a result of errors in figure assembly,and the correct Fig.5 is provided as follows.The key findings of the article are not affected by these corrections.
基金This work is supported by the National Natural Science Foundation Regional Innovation and Development(No.U19A2003)National Major Scientific and Technological Special Project for"Significant New Drugs Development"(No.2018ZX09733001)+1 种基金the Excellent Youth Foundation of Sichuan Scientific Committee Grant in China(No.2019JDJQ008)the Development Program of China(No.2016YFA0201402).
文摘The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening.Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2,which greatly limits its application in routine research.Here,we gen erate a mouse model of COVID-19 un der a gen eral laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome(ARDS)observed in huma ns.Briefly,human ACE2-tra nsge nic(MCE2)mice were in tratracheally in stilled with the formaldehyde-inactivated SARS-CoV-2,resulting in a rapid weight loss and detrimental changes in lung structure and function.The pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation,hemorrhage,necrotic debris,and hyaline membrane formation.The production of fatal cytokines(IL-β,TNF-α,and IL-6)and the infiltration of activated neutrophils,inflammatory monocyte-macrophages,and T cells in the lung were also determined,suggesting the activation of an adaptive immune response.Therapeutic strategies,such as dexamethasone or passive antibody therapy,could effectively ameliorate the disease progression in this model.Therefore,the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS.
