Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Althoug...Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules,such as short half-life,lipophilicity,non-selectivity,and poor stability,it remains challenging to prepare NO nanomedicines with simple composition,multiple functions and enhanced therapeutic efficacy.Herein,we build a liquid metal nanodroplet(LMND)-based NO nanogenerator(LMND@HSG)that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine)(HSG)ligand.Mechanically,the tumor microenvironment specifically triggers a cascade process of glutathione elimination,reactive oxygen species(ROS)generation,and NO release.According to actual demand,the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts.Along with the intrinsic anticancer property of LMND(ROS-mediated apoptosis and anti-angiogenesis),LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone.Fromthis study,leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.展开更多
Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptide...Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptides through positron emission tomography(PET)imaging needed investigation.Herein,the chicken CAM tumor models were established,and their feasibility was evaluated for evaluating the imag-ing properties of radiolabeled peptides using a 68Ga-labeled HER2 affibody.Methods:Two human breast cancer cell lines were inoculated into chicken CAM and mice,respectively.The tumor-targeting potential and pharmacokinetic profile of a 68Ga-labeled affibody,68Ga-MZHER,in both tumor models were also determined.Results:The tumor-formation time in chicken CAM model was shorter than that of mouse model.The uptake values of human epithelial growth factor receptor-2(HER2)-positive Bcap37 tumors in chicken CAM and mouse models were 5.36±0.26%ID/g and 5.26±0.43%ID/g at 30 min postinjection of 68Ga-MZHER,respectively.At the same time points,the uptake values of HER2-negative MDA-MB-231 tumors in the chicken CAM models and mouse models were 1.57±0.15%ID/g and 1.67±0.25%ID/g,respectively.Ex vivo biodistribution confirmed that more radioactivity accu-mulated in Bcap37 tumors than in MDA-MD-231 tumors in both CAM and mouse models.Conclusion:In this study,the CAM tumor model was successfully prepared.The chicken CAM model is a novel tool for quickly determining the in vivo properties of radiolabeled peptides targeting biomarkers.It may be beneficial for early monitoring of the therapeutic effect of a new drug through PET imaging with specific peptides.展开更多
In the present work,the irradiation hardening behavior of a Chinese low-activation ferritic/martensitic steel CLF-1,a candidate for fusion reactor blankets,is studied.Specimens were irradiated with high-energy14N and5...In the present work,the irradiation hardening behavior of a Chinese low-activation ferritic/martensitic steel CLF-1,a candidate for fusion reactor blankets,is studied.Specimens were irradiated with high-energy14N and56Fe ions at the terminal of a cyclotron to three successively increasing damage levels of 0.05,0.1 and 0.2 displacements per atom(dpa)at about-50°C.The energy of the incident ions was dispersed to 11 successively decreasing grades using an energy degrader,thereby generating an atomic displacement damage plateau in the specimens from the surface to a depth of 25μm,which is sufficiently broad for the Vickers hardness test.Eight different loads(i.e.98 mN,196 m N,490 m N,980 m N,1.96 N,4.9 N,9.8 N and 19.6 N)were applied to the specimens to obtain the depth profiles of the Vickers hardness by using a microhardness tester.Hardening was observable at the lowest damage level,and increased with increasing irradiation dose.A power-law correlation of the Vickers hardness with the damage level(HV0=1.49+0.76 dpa0.31)is proposed.Testing with a nano-indentation technique was also performed,and a linear relationship between the Vickers micro-hardness and the nanohardness(HV0=0.83 H0)was observed.A comparison with other RAFM steels(CLAM,JLF-1,F82 H,EUROFER97 etc.)under neutron or charged particle irradiation conditions shows that most of the RAFM steels exhibit similar power-law exponents in the dose dependence of irradiation hardening.The difference in the irradiation hardening may be attributed to differences in microstructure prior to irradiation.展开更多
Bismuth-based materials have attracted broad research interest as catalysts for electrocatalytic CO_(2)reduction(ECR)to formate in recent years.Most studies have been focused on exploring materials with high activity,...Bismuth-based materials have attracted broad research interest as catalysts for electrocatalytic CO_(2)reduction(ECR)to formate in recent years.Most studies have been focused on exploring materials with high activity,selectivity,durability,while little attention has been paid to the catalysts structure stability especially under working conditions of CO_(2)electrolysis.Here,starting from the precursor of bismuth oxide formate nanowires(BiOCOOH NWs),it was found that BiOCOOH NWs were easy to electrochemically evolve into two-dimensional sheet structure in CO_(2)-saturated KHCO3 solution and would further reconstitute into larger ultrathin bismuth nanosheets covered with amorphous oxide thin layer(Bi/BiO_(x)NSs).However,in Ar-saturated HCOONa solution,the one-dimensional structure could be maintained and reconstructed into rough porous bismuth nanowires(Bi NWs).Bi NWs showed less stability during ECR,which also generated surface amorphous oxide layer and further fragmentated into nanoparticles or nanosheets.Bi/BiO_(x)NSs showed better activity,selectivity,stability than Bi NWs,thanks to the high exposing active sites,enhancing CO_(2)adsorption and charge transfer.The demonstrated electrolyte dependence of structure evolution for bismuth-based catalysts and their performance for CO_(2)electroreduction could provide guidance for the design and synthesis of efficient catalysts.展开更多
The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenyl...The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and species-specificity.Here,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates.Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort.Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility.Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the axoneme.Examination of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme.Using an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the flagellum.These findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP transfer.In conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.展开更多
基金the National Natural Science Foundation of China(22075114,32371434,82301630)the Natural Science Foundation of Jiangsu Province(BK20211034)the financial support from Jiangsu Provincial Medical Key Laboratory(Key Laboratory of Nuclear Medicine).
文摘Nitric oxide(NO)modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies.Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules,such as short half-life,lipophilicity,non-selectivity,and poor stability,it remains challenging to prepare NO nanomedicines with simple composition,multiple functions and enhanced therapeutic efficacy.Herein,we build a liquid metal nanodroplet(LMND)-based NO nanogenerator(LMND@HSG)that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine)(HSG)ligand.Mechanically,the tumor microenvironment specifically triggers a cascade process of glutathione elimination,reactive oxygen species(ROS)generation,and NO release.According to actual demand,the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts.Along with the intrinsic anticancer property of LMND(ROS-mediated apoptosis and anti-angiogenesis),LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone.Fromthis study,leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.
基金This study was supported by the National Natural Science Foundation of China(grant numbers:31972644,32272959)the University Synergy Innovation Program of Anhui Province(grant number:GXXT-2019-035)+1 种基金the Jiangsu Provincial Medical Innovation Team(grant number:CXTDA2017024)the leading technology foundation research project of Jiangsu Province(grant number:BK20192005).
文摘Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptides through positron emission tomography(PET)imaging needed investigation.Herein,the chicken CAM tumor models were established,and their feasibility was evaluated for evaluating the imag-ing properties of radiolabeled peptides using a 68Ga-labeled HER2 affibody.Methods:Two human breast cancer cell lines were inoculated into chicken CAM and mice,respectively.The tumor-targeting potential and pharmacokinetic profile of a 68Ga-labeled affibody,68Ga-MZHER,in both tumor models were also determined.Results:The tumor-formation time in chicken CAM model was shorter than that of mouse model.The uptake values of human epithelial growth factor receptor-2(HER2)-positive Bcap37 tumors in chicken CAM and mouse models were 5.36±0.26%ID/g and 5.26±0.43%ID/g at 30 min postinjection of 68Ga-MZHER,respectively.At the same time points,the uptake values of HER2-negative MDA-MB-231 tumors in the chicken CAM models and mouse models were 1.57±0.15%ID/g and 1.67±0.25%ID/g,respectively.Ex vivo biodistribution confirmed that more radioactivity accu-mulated in Bcap37 tumors than in MDA-MD-231 tumors in both CAM and mouse models.Conclusion:In this study,the CAM tumor model was successfully prepared.The chicken CAM model is a novel tool for quickly determining the in vivo properties of radiolabeled peptides targeting biomarkers.It may be beneficial for early monitoring of the therapeutic effect of a new drug through PET imaging with specific peptides.
基金sponsored by the National Magnetic Confinement Fusion Program(No.2011GB108003)National Natural Science Foundation of China(No.U1532262)。
文摘In the present work,the irradiation hardening behavior of a Chinese low-activation ferritic/martensitic steel CLF-1,a candidate for fusion reactor blankets,is studied.Specimens were irradiated with high-energy14N and56Fe ions at the terminal of a cyclotron to three successively increasing damage levels of 0.05,0.1 and 0.2 displacements per atom(dpa)at about-50°C.The energy of the incident ions was dispersed to 11 successively decreasing grades using an energy degrader,thereby generating an atomic displacement damage plateau in the specimens from the surface to a depth of 25μm,which is sufficiently broad for the Vickers hardness test.Eight different loads(i.e.98 mN,196 m N,490 m N,980 m N,1.96 N,4.9 N,9.8 N and 19.6 N)were applied to the specimens to obtain the depth profiles of the Vickers hardness by using a microhardness tester.Hardening was observable at the lowest damage level,and increased with increasing irradiation dose.A power-law correlation of the Vickers hardness with the damage level(HV0=1.49+0.76 dpa0.31)is proposed.Testing with a nano-indentation technique was also performed,and a linear relationship between the Vickers micro-hardness and the nanohardness(HV0=0.83 H0)was observed.A comparison with other RAFM steels(CLAM,JLF-1,F82 H,EUROFER97 etc.)under neutron or charged particle irradiation conditions shows that most of the RAFM steels exhibit similar power-law exponents in the dose dependence of irradiation hardening.The difference in the irradiation hardening may be attributed to differences in microstructure prior to irradiation.
基金the National Natural Science Foundation of China(Nos.21203200 and 91545201)the National Key Research and Development Program of China(Nos.2017YFA0206802 and 2017YFA0700103).
文摘Bismuth-based materials have attracted broad research interest as catalysts for electrocatalytic CO_(2)reduction(ECR)to formate in recent years.Most studies have been focused on exploring materials with high activity,selectivity,durability,while little attention has been paid to the catalysts structure stability especially under working conditions of CO_(2)electrolysis.Here,starting from the precursor of bismuth oxide formate nanowires(BiOCOOH NWs),it was found that BiOCOOH NWs were easy to electrochemically evolve into two-dimensional sheet structure in CO_(2)-saturated KHCO3 solution and would further reconstitute into larger ultrathin bismuth nanosheets covered with amorphous oxide thin layer(Bi/BiO_(x)NSs).However,in Ar-saturated HCOONa solution,the one-dimensional structure could be maintained and reconstructed into rough porous bismuth nanowires(Bi NWs).Bi NWs showed less stability during ECR,which also generated surface amorphous oxide layer and further fragmentated into nanoparticles or nanosheets.Bi/BiO_(x)NSs showed better activity,selectivity,stability than Bi NWs,thanks to the high exposing active sites,enhancing CO_(2)adsorption and charge transfer.The demonstrated electrolyte dependence of structure evolution for bismuth-based catalysts and their performance for CO_(2)electroreduction could provide guidance for the design and synthesis of efficient catalysts.
基金supported by National Key Research and Development Program of China(2022YFC2702702,2021YFC2700901)the National Natural Science Foundation of China(81971441,82171607,32000584)+3 种基金the University Outstanding Young Talents Support Program(gxyq2021174)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310002)Anhui Provincial Natural Science Foundation(2208085Y31)the Natural Science Foundation of Jiangsu Province(BK20230004).
文摘The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and species-specificity.Here,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates.Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort.Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility.Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the axoneme.Examination of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme.Using an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the flagellum.These findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP transfer.In conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.
