Limited by low tumor immunogenicity and the immunosuppressive tumor microenvironment(TME),triple-negative breast cancer(TNBC)has been poorly responsive to immunotherapy so far.Herein,a Ca&Mn dual-ion hybrid nanost...Limited by low tumor immunogenicity and the immunosuppressive tumor microenvironment(TME),triple-negative breast cancer(TNBC)has been poorly responsive to immunotherapy so far.Herein,a Ca&Mn dual-ion hybrid nanostimulator(CMS)is constructed to enhance anti-tumor immunity through ferroptosis inducing and innate immunity awakening,which can serve as a ferroptosis inducer and immunoadjuvant for TNBC concurrently.On one hand,glutathione(GSH)depletion and reactive oxygen species(ROS)generation can be achieved due to the mixed valence state of Mn in CMS.On the other hand,as an exotic Ca2+supplier,CMS causes mitochondrial Ca2+overload,which further amplifies the oxidative stress.Significantly,tumor cells undergo ferroptosis because of the inactivation of glutathione peroxidase 4(GPX4)and accumulation of lipid peroxidation(LPO).More impressively,CMS can act as an immunoadjuvant to awaken innate immunity by alleviating intra-tumor hypoxia and Mn2+-induced activation of the STING signaling pathway,which promotes polarization of tumor-associated macrophages(TAMs)and activation of dendritic cells(DCs)for antigen presentation and subsequent infiltration of tumor-specific cytotoxic T lymphocytes(CTLs)into tumor tissues.Taken together,this work demonstrates a novel strategy of simultaneously inducing ferroptosis and awakening innate immunity,offering a new perspective for effective tumor immunotherapy of TNBC.展开更多
To reduce harmful sulfur content in lubricant additives, making use of isosterism has been shown to be an effective strategy. When thiobenzothiazole compounds were used as templates, the exchange of sulfur atoms in th...To reduce harmful sulfur content in lubricant additives, making use of isosterism has been shown to be an effective strategy. When thiobenzothiazole compounds were used as templates, the exchange of sulfur atoms in the thiazole ring with oxygen atoms and NH groups produced twelve isosteres. Similarly, 2-benzothiazole- S-carboxylic acid esters were used as template molecules to produce six isosteres. About 30% of the isosteres exhibited a satisfactory deviation of ±5% relative to the template, ignoring the specific changes in the base oils, the differences in molecular structure, and the friction or wear properties. The template molecules and isosteres in triisodecyl trimellitate exhibited better tribological properties than in trimethylolpropane trioleate or bis(2- ethylhexyl) adipate. Comparative molecular field analysis(CoM FA)- and comparative molecular similarity index analysis(CoMSIA)-quantitative structure tribo-ability relationship(QSTR) models were employed to study the correlation of molecular structures between the base oils and additives. The models indicate that the higher the structural similarities of the base oils and additives are, the more synergetic the molecular force fields of the lubricating system are; the molecular force fields creating synergistic effects will improve tribological performance.展开更多
This paper exploits a novel and unique opportunity to reveal the evolution of income volatility and consumption insurance from 1992 to 2014 in urban China.We found that(i)the average household experienced a downward t...This paper exploits a novel and unique opportunity to reveal the evolution of income volatility and consumption insurance from 1992 to 2014 in urban China.We found that(i)the average household experienced a downward trend in income and consumption volatility.Although the global financial crisis in 2008 caused a slight spike,it did not reverse the downward trend.(i)Households'ability to smooth income shocks improved significantly,and the consumption insurance against permanent(transitory)income shocks increased from 0.6172(0.8307)to 0.7453(0.8742)-that is,the transmission of permanent(transitory)income shocks to consumption decreased by 33.46(25.69)percent from 2004 to 2014.(ii)Welfare analysis indicates that the positive insurance effect counteracted the negative effects of lower economic growth in the 2010-2014period.Income and consumption volatility,and consumption insurance were heterogeneous across income sources,consumption categories,and various demographic characteristics,which have important implications forunderstandingChina's economictransition.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2021YFB3801000)the National Natural Science Foundation of China(Grant No.32030061)+3 种基金the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000)the Shanghai Sailing Program(Grant No.21YF1454200)Shanghai International Cooperation Project(Grant No.23490712900)All the animal experiments were performed with the approval of the Tongji University Experimental Animal Center,and the animal biomedical research authorization number is TJLAC-020-228.
文摘Limited by low tumor immunogenicity and the immunosuppressive tumor microenvironment(TME),triple-negative breast cancer(TNBC)has been poorly responsive to immunotherapy so far.Herein,a Ca&Mn dual-ion hybrid nanostimulator(CMS)is constructed to enhance anti-tumor immunity through ferroptosis inducing and innate immunity awakening,which can serve as a ferroptosis inducer and immunoadjuvant for TNBC concurrently.On one hand,glutathione(GSH)depletion and reactive oxygen species(ROS)generation can be achieved due to the mixed valence state of Mn in CMS.On the other hand,as an exotic Ca2+supplier,CMS causes mitochondrial Ca2+overload,which further amplifies the oxidative stress.Significantly,tumor cells undergo ferroptosis because of the inactivation of glutathione peroxidase 4(GPX4)and accumulation of lipid peroxidation(LPO).More impressively,CMS can act as an immunoadjuvant to awaken innate immunity by alleviating intra-tumor hypoxia and Mn2+-induced activation of the STING signaling pathway,which promotes polarization of tumor-associated macrophages(TAMs)and activation of dendritic cells(DCs)for antigen presentation and subsequent infiltration of tumor-specific cytotoxic T lymphocytes(CTLs)into tumor tissues.Taken together,this work demonstrates a novel strategy of simultaneously inducing ferroptosis and awakening innate immunity,offering a new perspective for effective tumor immunotherapy of TNBC.
基金supported by National Natural Science Foundation of China(Grant No.51675395)
文摘To reduce harmful sulfur content in lubricant additives, making use of isosterism has been shown to be an effective strategy. When thiobenzothiazole compounds were used as templates, the exchange of sulfur atoms in the thiazole ring with oxygen atoms and NH groups produced twelve isosteres. Similarly, 2-benzothiazole- S-carboxylic acid esters were used as template molecules to produce six isosteres. About 30% of the isosteres exhibited a satisfactory deviation of ±5% relative to the template, ignoring the specific changes in the base oils, the differences in molecular structure, and the friction or wear properties. The template molecules and isosteres in triisodecyl trimellitate exhibited better tribological properties than in trimethylolpropane trioleate or bis(2- ethylhexyl) adipate. Comparative molecular field analysis(CoM FA)- and comparative molecular similarity index analysis(CoMSIA)-quantitative structure tribo-ability relationship(QSTR) models were employed to study the correlation of molecular structures between the base oils and additives. The models indicate that the higher the structural similarities of the base oils and additives are, the more synergetic the molecular force fields of the lubricating system are; the molecular force fields creating synergistic effects will improve tribological performance.
基金supported financially by the Major Project of National Social Science Fund(Grant No.22ZDA108)the National Science Foundation of China(No.72104163)+1 种基金the Humanities and Social Science Fund Project of the Ministry of Education of China(No.21XJC790016)the Liberal Arts Development Fund of Nankai University(No.ZB22BZ0315)。
文摘This paper exploits a novel and unique opportunity to reveal the evolution of income volatility and consumption insurance from 1992 to 2014 in urban China.We found that(i)the average household experienced a downward trend in income and consumption volatility.Although the global financial crisis in 2008 caused a slight spike,it did not reverse the downward trend.(i)Households'ability to smooth income shocks improved significantly,and the consumption insurance against permanent(transitory)income shocks increased from 0.6172(0.8307)to 0.7453(0.8742)-that is,the transmission of permanent(transitory)income shocks to consumption decreased by 33.46(25.69)percent from 2004 to 2014.(ii)Welfare analysis indicates that the positive insurance effect counteracted the negative effects of lower economic growth in the 2010-2014period.Income and consumption volatility,and consumption insurance were heterogeneous across income sources,consumption categories,and various demographic characteristics,which have important implications forunderstandingChina's economictransition.
