Treatment of large bone defects derived from bone tumor surgery is typically performed in multiple separate operations,such as hyperthermia to extinguish residual malignant cells or implanting bioactive materials to i...Treatment of large bone defects derived from bone tumor surgery is typically performed in multiple separate operations,such as hyperthermia to extinguish residual malignant cells or implanting bioactive materials to initiate apatite remineralization for tissue repair;it is very challenging to combine these functions into a material.Herein,we report the first photothermal(PT)effect in bismuth(Bi)-doped glasses.On the basis of this discovery,we have developed a new type of Bi-doped bioactive glass that integrates both functions,thus reducing the number of treatment cycles.We demonstrate that Bi-doped bioglasses(BGs)provide high PT efficiency,potentially facilitating photoinduced hyperthermia and bioactivity to allow bone tissue remineralization.The PT effect of Bi-doped BGs can be effectively controlled by managing radiative and non-radiative processes of the active Bi species by quenching photoluminescence(PL)or depolymerizing glass networks.In vitro studies demonstrate that such glasses are biocompatible to tumor and normal cells and that they can promote osteogenic cell proliferation,differentiation,and mineralization.Upon illumination with near-infrared(NIR)light,the bioglass(BG)can efficiently kill bone tumor cells,as demonstrated via in vitro and in vivo experiments.This indicates excellent potential for the integration of multiple functions within the new materials,which will aid in the development and application of novel biomaterials.展开更多
High-temperature superconducting(HTS)technology provides an alternative approach to achieve compact transformers.Addressing AC loss in the HTS winding is crucial for HTS transformer applications.Most numerical AC loss...High-temperature superconducting(HTS)technology provides an alternative approach to achieve compact transformers.Addressing AC loss in the HTS winding is crucial for HTS transformer applications.Most numerical AC loss studies on HTS transformers have neglected the influence of iron cores.This work carries out an AC loss study to explore the impact of an iron core on the HTS windings in a 3-phase HTS 1 MVA transformer coupled with it.AC loss simulations for the transformer winding both with and without the iron core are conducted by adopting the three-dimensional(3D)T-A homogenization method.When the iron core is incorporated,the saturation magnetic fields of iron materials,flux diverters(FDs)with different geometries,and variations in turn spacings in the LV winding composed of Roebel cables are considered to investigate their influence on the AC loss of the transformer winding.The inclusion of the iron core leads to a 1.2%increase in AC loss for the transformer winding while simulating at the rated current.We attribute this slight difference to the non-inductive winding structure of the transformer winding,where a strong magnetic field generated in the space between the LV and HV windings effectively shields the influence of the iron core.展开更多
AC loss is one of the greatest obstacles for high‐temperature superconducting(HTS)applications.In some HTS applications,coated conductors carry non‐sinusoidal currents.Thus,it is important to investigate the effect ...AC loss is one of the greatest obstacles for high‐temperature superconducting(HTS)applications.In some HTS applications,coated conductors carry non‐sinusoidal currents.Thus,it is important to investigate the effect of various waveforms on AC loss in coated conductors.In this work,transport AC loss in a 4 mm‐wide REBCO coated conductor carrying sinusoidal and non‐sinusoidal currents,is numerically investigated.The current amplitudes,the frequency of the transport current,and n‐value are varied.Non‐sinusoidal transport current waveforms studied include square,five types of trapezoidal,and triangular waveforms.Simulated results show that,for a given current amplitude,AC loss for the square current waveform is the greatest,that for the triangular waveform is the smallest.The sequence of AC loss in the conductor for different current waveforms coincides with the penetration depth,which implies the penetration depth determines the AC loss of the coated conductor.Furthermore,the transport AC loss in the conductor was found to decrease with frequency as f2=n for non‐sinusoidal transport current.展开更多
Lanthanide chelates and copper-free‘click’chemistry have important uses for targeted molecular imaging and therapeutic strategies.Herein,we report the complexation of lanthanides to a tetrazine-functionalised DO3A m...Lanthanide chelates and copper-free‘click’chemistry have important uses for targeted molecular imaging and therapeutic strategies.Herein,we report the complexation of lanthanides to a tetrazine-functionalised DO3A macrocyclic chelator and the tetrazine-TCO ligation between the lanthanide(DO3A-tetrazine)complexes and a TCO-PEG_(4)-functionalised rhodamine as a model agent.The luminescent and magnetic properties of the resultant dual-modal conjugates are described.The tetrazine moiety was found to sensitise terbium luminescence,resulting in a‘turn-off’effect upon its transformation to the dihydropyridazine linker,with the rhodamine moiety then dominating the fluorescence emissions.The T_(1) relaxivities of Gd(DO3A-tetrazine)and Gd(DO3A-PEG_(4)-rhodamine)were found to be similar to[Gd(DOTA)]−(Dotarem®).As a proof-of-concept in vivo test,the click conjugates were delivered to mice brains using the combination of focused ultrasound and microbubbles,with neuron uptake of the probes observed.展开更多
Mass cytometry with antibodies labelled with stable metal isotopes enables both sensitive imaging and the quantification of protein expression in biological samples.Typically,these specimens are exposed to a panel of ...Mass cytometry with antibodies labelled with stable metal isotopes enables both sensitive imaging and the quantification of protein expression in biological samples.Typically,these specimens are exposed to a panel of labelled antibodies ex vivo,after sample collection.Here,we have developed a rhodium-labelled immunoconjugate of the HER2-targeted therapeutic IgG1 antibody,trastuzumab,and evaluated its in vivo biodistribution using mass cytometry techniques.A Rh^(3+)complex of a macrobicyclic sarcophagine(sar,3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane)chelator was appended with a dibromopyridazinedione(DBPD),to produce a novel disulfide bond labelling molecule,“Rh-sar-DBPD”.Rh-sar-DBPD was site-specifically conjugated to trastuzumab via its four native solvent-accessible disulfide bonds,to yield a near homogeneous,well-defined and stable pyridazinedione(PD)immunoconjugate,Rh-sar-PD-trastuzumab,in which four Rh-sar-PD groups were attached per molecule of trastuzumab.Inductively coupled plasma mass spectrometry(ICP-MS)and laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS)were then applied to measure ^(103)Rh content,as a proxy for Rh-sar-PD-trastuzumab accumulation,in in vitro and in vivo studies.ICP-MS in vitro studies indicated HER2-mediated uptake of Rh-sar-PD-trastuzumab in HER2-expressing breast cancer cells,with LA-ICP-MS images showing intercellular heterogeneity in Rh-sar-PD-trastuzumab uptake.To study the in vivo biodistribution of Rh-sar-PD-trastuzumab,female NSG mice bearing orthotopic HCC1954 breast cancer tumours were administered the immunoconjugate.Quantitative ICP-MS of ^(103)Rh signal in dissected tissues indicated receptor-specific HER2-mediated uptake in tumours,as well as accumulation in the spleen and liver.Finally,LA-ICP-MS imaging analysis of tumour and ovary tissue sections showed heterogeneous uptake in HER2-expressing HCC1954 tumour cells and follicular granulosa cells of the ovaries,which are known to express growth factor receptors.To the best of our knowledge,this is the first report in which both ICP-MS and LA-ICP-MS have been used on tissue exposed to a metal-tagged antibody in vivo,enabling quantification of the biodistribution of the novel immunoconjugate,Rh-sar-PD-trastuzumab,in a murine model of breast cancer.展开更多
In this work,we designed and synthesised a new cyclometallated iridium(Ⅲ)nitrone complex[Ir(bpz)2(bpy-nitrone)](PF_(6))(1)(Hbpz=benzo[a]phenazine;bpy-nitrone=4-((methyl(oxido)imino)methyl)-4’-methyl-2,2’-bipyridine...In this work,we designed and synthesised a new cyclometallated iridium(Ⅲ)nitrone complex[Ir(bpz)2(bpy-nitrone)](PF_(6))(1)(Hbpz=benzo[a]phenazine;bpy-nitrone=4-((methyl(oxido)imino)methyl)-4’-methyl-2,2’-bipyridine)as a bioorthogonally activatable phototheranostic agent.Complex 1 displayed very weak emission and singlet oxygen(^(1)O_(2))photosensitisation in solutions due to the quenching nitrone moiety.However,upon the strain-promoted alkyne–nitrone cycloaddition(SPANC)reaction with bicyclo[6.1.0]non-4-yne(BCN),which converted the nitrone unit to a non-quenching isoxazoline derivative,the complex exhibited a substantial increase in emission intensity in the near-infrared region and^(1)O_(2)generation efficiency.Given that mitochondria are a crucial target in cancer therapy,we prepared a series of BCN-functionalised phosphonium cations(BCN-Phos-n),each bearing different substituents,to serve as mitochondrial-targeting vectors for delivering complex 1 to the mitochondria via the bioorthogonal SPANC reaction.Notably,complex 1 exhibited more significant emission turn-on upon reaction with BCN-Phos-5 and BCN-Phos-6(I/I_(o)=24.7 and 14.1,respectively),attributed to their increased hydrophobicity resulting from the methylation or methoxylation of the phenyl rings on the phosphonium cation.Live-cell confocal imaging and flow cytometric analyses revealed that complex 1 showed larger emission enhancement in HeLa cells pretreated with BCN-Phos-5 or BCN-Phos-6 compared to other BCN-Phosn analogues.Co-staining experiments confirmed that the resultant luminescent isoxazoline cycloadducts predominantly accumulated in the mitochondria.Additionally,both dark and light-induced cytotoxicity of complex 1 increased upon pretreatment of the cells with BCN-Phos-5 or BCN-Phos-6.Our results demonstrate that the theranostic potential of transition metal nitrone complexes can be significantly enhanced via strategic structural manipulation of their bioorthogonal reaction partners.展开更多
Applied-field magnetoplasmadynamic(AF-MPD)thrusters have been proposed as highly propellant-efficient thrusters for satellites and spacecraft.The electromagnets for these devices have only been reducible to practical ...Applied-field magnetoplasmadynamic(AF-MPD)thrusters have been proposed as highly propellant-efficient thrusters for satellites and spacecraft.The electromagnets for these devices have only been reducible to practical dimensions with the maturation of high-temperature superconductors.We report the development and ground testing of such a magnet which has been designed and constructed with the intention of deploying to the International Space Station and testing in orbit.The magnet is of dimensions suitable for accommodating a small thruster,will be cooled by a miniature space-compatible cryocooler and energized by a flux pump.It can generate a magnetic field of up to 760 mT operating at around 77 K in that configuration.A passive magnetic shield has been incorporated in order to comply with stray-field requirements of the ISS when operating at the target operational field of 300 mT.展开更多
基金financial support from the Program for Innovative Research Team in University of Ministry of Education of China(Grant No.IRT_17R38)the National Natural Science Foundation of China(Grant No.51672085)+2 种基金the Key Program of Guangzhou Scientific Research Special Projects(Grant No.201607020009)the Joint Fund of Ministry of Education of Chinathe Fundamental Research Funds for the Central Universities.
文摘Treatment of large bone defects derived from bone tumor surgery is typically performed in multiple separate operations,such as hyperthermia to extinguish residual malignant cells or implanting bioactive materials to initiate apatite remineralization for tissue repair;it is very challenging to combine these functions into a material.Herein,we report the first photothermal(PT)effect in bismuth(Bi)-doped glasses.On the basis of this discovery,we have developed a new type of Bi-doped bioactive glass that integrates both functions,thus reducing the number of treatment cycles.We demonstrate that Bi-doped bioglasses(BGs)provide high PT efficiency,potentially facilitating photoinduced hyperthermia and bioactivity to allow bone tissue remineralization.The PT effect of Bi-doped BGs can be effectively controlled by managing radiative and non-radiative processes of the active Bi species by quenching photoluminescence(PL)or depolymerizing glass networks.In vitro studies demonstrate that such glasses are biocompatible to tumor and normal cells and that they can promote osteogenic cell proliferation,differentiation,and mineralization.Upon illumination with near-infrared(NIR)light,the bioglass(BG)can efficiently kill bone tumor cells,as demonstrated via in vitro and in vivo experiments.This indicates excellent potential for the integration of multiple functions within the new materials,which will aid in the development and application of novel biomaterials.
基金New Zealand Ministry of Business,Innovation and Employment(MBIE)Strategic Science Investment Fund“Advanced Energy Technology Platforms”under contract No.RTVU2004.
文摘High-temperature superconducting(HTS)technology provides an alternative approach to achieve compact transformers.Addressing AC loss in the HTS winding is crucial for HTS transformer applications.Most numerical AC loss studies on HTS transformers have neglected the influence of iron cores.This work carries out an AC loss study to explore the impact of an iron core on the HTS windings in a 3-phase HTS 1 MVA transformer coupled with it.AC loss simulations for the transformer winding both with and without the iron core are conducted by adopting the three-dimensional(3D)T-A homogenization method.When the iron core is incorporated,the saturation magnetic fields of iron materials,flux diverters(FDs)with different geometries,and variations in turn spacings in the LV winding composed of Roebel cables are considered to investigate their influence on the AC loss of the transformer winding.The inclusion of the iron core leads to a 1.2%increase in AC loss for the transformer winding while simulating at the rated current.We attribute this slight difference to the non-inductive winding structure of the transformer winding,where a strong magnetic field generated in the space between the LV and HV windings effectively shields the influence of the iron core.
基金supported by the New Zealand Ministry of Business,Innovation and Employment under Catalyst Space and Fusion project“International Science Co‐operation on Superconductor Technologies”contract number RTVU1916supported by the New Zealand Ministry of Business,Innovation and Employment under the Advanced Energy Technology Platform program“High power electric motors for large scale transport”contract number RTVU2004.
文摘AC loss is one of the greatest obstacles for high‐temperature superconducting(HTS)applications.In some HTS applications,coated conductors carry non‐sinusoidal currents.Thus,it is important to investigate the effect of various waveforms on AC loss in coated conductors.In this work,transport AC loss in a 4 mm‐wide REBCO coated conductor carrying sinusoidal and non‐sinusoidal currents,is numerically investigated.The current amplitudes,the frequency of the transport current,and n‐value are varied.Non‐sinusoidal transport current waveforms studied include square,five types of trapezoidal,and triangular waveforms.Simulated results show that,for a given current amplitude,AC loss for the square current waveform is the greatest,that for the triangular waveform is the smallest.The sequence of AC loss in the conductor for different current waveforms coincides with the penetration depth,which implies the penetration depth determines the AC loss of the coated conductor.Furthermore,the transport AC loss in the conductor was found to decrease with frequency as f2=n for non‐sinusoidal transport current.
基金funding from the EPSRC Centre for Doctoral Training in Smart Medical Imaging(EP/S022104/1)the Department of Bioengineering,Imperial College London+4 种基金supported by funding from the EPSRC grant(EP/X01374X/1)funding from the Rosetrees Trust and the John Black Charitable Foundation(Grant No.A2200)supported by an Imperial College London President’s Scholarship.S.V.M.acknowledges funding from her Imperial College Research Fellowship.M.F.L.received funding from Cancer Research UK(No.190133,DRCMDP-Nov24/100005)the Rosetrees Trust and the John Black Charitable Foundation(Grant No.A2200)the Brain Tumour Charity(Grant No.QfC_2018_10387).
文摘Lanthanide chelates and copper-free‘click’chemistry have important uses for targeted molecular imaging and therapeutic strategies.Herein,we report the complexation of lanthanides to a tetrazine-functionalised DO3A macrocyclic chelator and the tetrazine-TCO ligation between the lanthanide(DO3A-tetrazine)complexes and a TCO-PEG_(4)-functionalised rhodamine as a model agent.The luminescent and magnetic properties of the resultant dual-modal conjugates are described.The tetrazine moiety was found to sensitise terbium luminescence,resulting in a‘turn-off’effect upon its transformation to the dihydropyridazine linker,with the rhodamine moiety then dominating the fluorescence emissions.The T_(1) relaxivities of Gd(DO3A-tetrazine)and Gd(DO3A-PEG_(4)-rhodamine)were found to be similar to[Gd(DOTA)]−(Dotarem®).As a proof-of-concept in vivo test,the click conjugates were delivered to mice brains using the combination of focused ultrasound and microbubbles,with neuron uptake of the probes observed.
基金CRUK for a Cancer Research UK Career Establishment Award(C63178/A24959)the EPSRC(EP/S032789/1,EP/T517793/1 and EP/S022104/1)the Wellcome Trust(212885/Z/18/Z)。
文摘Mass cytometry with antibodies labelled with stable metal isotopes enables both sensitive imaging and the quantification of protein expression in biological samples.Typically,these specimens are exposed to a panel of labelled antibodies ex vivo,after sample collection.Here,we have developed a rhodium-labelled immunoconjugate of the HER2-targeted therapeutic IgG1 antibody,trastuzumab,and evaluated its in vivo biodistribution using mass cytometry techniques.A Rh^(3+)complex of a macrobicyclic sarcophagine(sar,3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane)chelator was appended with a dibromopyridazinedione(DBPD),to produce a novel disulfide bond labelling molecule,“Rh-sar-DBPD”.Rh-sar-DBPD was site-specifically conjugated to trastuzumab via its four native solvent-accessible disulfide bonds,to yield a near homogeneous,well-defined and stable pyridazinedione(PD)immunoconjugate,Rh-sar-PD-trastuzumab,in which four Rh-sar-PD groups were attached per molecule of trastuzumab.Inductively coupled plasma mass spectrometry(ICP-MS)and laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS)were then applied to measure ^(103)Rh content,as a proxy for Rh-sar-PD-trastuzumab accumulation,in in vitro and in vivo studies.ICP-MS in vitro studies indicated HER2-mediated uptake of Rh-sar-PD-trastuzumab in HER2-expressing breast cancer cells,with LA-ICP-MS images showing intercellular heterogeneity in Rh-sar-PD-trastuzumab uptake.To study the in vivo biodistribution of Rh-sar-PD-trastuzumab,female NSG mice bearing orthotopic HCC1954 breast cancer tumours were administered the immunoconjugate.Quantitative ICP-MS of ^(103)Rh signal in dissected tissues indicated receptor-specific HER2-mediated uptake in tumours,as well as accumulation in the spleen and liver.Finally,LA-ICP-MS imaging analysis of tumour and ovary tissue sections showed heterogeneous uptake in HER2-expressing HCC1954 tumour cells and follicular granulosa cells of the ovaries,which are known to express growth factor receptors.To the best of our knowledge,this is the first report in which both ICP-MS and LA-ICP-MS have been used on tissue exposed to a metal-tagged antibody in vivo,enabling quantification of the biodistribution of the novel immunoconjugate,Rh-sar-PD-trastuzumab,in a murine model of breast cancer.
文摘In this work,we designed and synthesised a new cyclometallated iridium(Ⅲ)nitrone complex[Ir(bpz)2(bpy-nitrone)](PF_(6))(1)(Hbpz=benzo[a]phenazine;bpy-nitrone=4-((methyl(oxido)imino)methyl)-4’-methyl-2,2’-bipyridine)as a bioorthogonally activatable phototheranostic agent.Complex 1 displayed very weak emission and singlet oxygen(^(1)O_(2))photosensitisation in solutions due to the quenching nitrone moiety.However,upon the strain-promoted alkyne–nitrone cycloaddition(SPANC)reaction with bicyclo[6.1.0]non-4-yne(BCN),which converted the nitrone unit to a non-quenching isoxazoline derivative,the complex exhibited a substantial increase in emission intensity in the near-infrared region and^(1)O_(2)generation efficiency.Given that mitochondria are a crucial target in cancer therapy,we prepared a series of BCN-functionalised phosphonium cations(BCN-Phos-n),each bearing different substituents,to serve as mitochondrial-targeting vectors for delivering complex 1 to the mitochondria via the bioorthogonal SPANC reaction.Notably,complex 1 exhibited more significant emission turn-on upon reaction with BCN-Phos-5 and BCN-Phos-6(I/I_(o)=24.7 and 14.1,respectively),attributed to their increased hydrophobicity resulting from the methylation or methoxylation of the phenyl rings on the phosphonium cation.Live-cell confocal imaging and flow cytometric analyses revealed that complex 1 showed larger emission enhancement in HeLa cells pretreated with BCN-Phos-5 or BCN-Phos-6 compared to other BCN-Phosn analogues.Co-staining experiments confirmed that the resultant luminescent isoxazoline cycloadducts predominantly accumulated in the mitochondria.Additionally,both dark and light-induced cytotoxicity of complex 1 increased upon pretreatment of the cells with BCN-Phos-5 or BCN-Phos-6.Our results demonstrate that the theranostic potential of transition metal nitrone complexes can be significantly enhanced via strategic structural manipulation of their bioorthogonal reaction partners.
基金supported by the New Zealand Ministry of Business,Innovation and Employment under contract RTVU2003.
文摘Applied-field magnetoplasmadynamic(AF-MPD)thrusters have been proposed as highly propellant-efficient thrusters for satellites and spacecraft.The electromagnets for these devices have only been reducible to practical dimensions with the maturation of high-temperature superconductors.We report the development and ground testing of such a magnet which has been designed and constructed with the intention of deploying to the International Space Station and testing in orbit.The magnet is of dimensions suitable for accommodating a small thruster,will be cooled by a miniature space-compatible cryocooler and energized by a flux pump.It can generate a magnetic field of up to 760 mT operating at around 77 K in that configuration.A passive magnetic shield has been incorporated in order to comply with stray-field requirements of the ISS when operating at the target operational field of 300 mT.
