Identifying a device and detecting a change in its position is critical for secure devices management in the Internet of Things(IoT).In this paper,a device management system is proposed to track the devices by using a...Identifying a device and detecting a change in its position is critical for secure devices management in the Internet of Things(IoT).In this paper,a device management system is proposed to track the devices by using audio-based location distinction techniques.In the proposed scheme,traditional cryptographic techniques,such as symmetric encryption algorithm,RSA-based signcryption scheme,and audio-based secure transmission,are utilized to provide authentication,non-repudiation,and confidentiality in the information interaction of the management system.Moreover,an audio-based location distinction method is designed to detect the position change of the devices.Specifically,the audio frequency response(AFR)of several frequency points is utilized as a device signature.The device signature has the features as follows.(1)Hardware Signature:different pairs of speaker and microphone have different signatures;(2)Distance Signature:in the same direction,the signatures are different at different distances;and(3)Direction Signature:at the same distance,the signatures are different in different directions.Based on the features above,amovement detection algorithmfor device identification and location distinction is designed.Moreover,a secure communication protocol is also proposed by using traditional cryptographic techniques to provide integrity,authentication,and non-repudiation in the process of information interaction between devices,Access Points(APs),and Severs.Extensive experiments are conducted to evaluate the performance of the proposed method.The experimental results show that the proposedmethod has a good performance in accuracy and energy consumption.展开更多
Alzheimer’s disease(AD)is a typical neurodegenerative disease that leads to irreversible neuronal degeneration,and effective treatment remains elusive due to the unclear mechanism.We utilized biocompatible mesenchyma...Alzheimer’s disease(AD)is a typical neurodegenerative disease that leads to irreversible neuronal degeneration,and effective treatment remains elusive due to the unclear mechanism.We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241(EVs-AM1241)to protect against neurodegenerative progression and neuronal function in AD model mice.According to the results,EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241.The Morris water maze(MWM)and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved.In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning.Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloidβ(Aβ)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241.Moreover,EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton,indicating that they enhanced neuronal regeneration.RNA sequencing revealed that EVs-AM1241 facilitated Aβphagocytosis,promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway.Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in modelmice,indicating that they are very promising particles for treating AD.展开更多
The possible effects of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin Ⅱ receptor blockers(ARBs)on COVID-19 disease severity have generated considerable debate.We performed a single-center,retrospectiv...The possible effects of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin Ⅱ receptor blockers(ARBs)on COVID-19 disease severity have generated considerable debate.We performed a single-center,retrospective analysis of hospitalized adult COVID-19 patients in Wuhan,China,who had definite clinical outcome(dead or discharged)by February 15,2020.Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes.The medical records from 702 patients were screened.Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication,40 patients were receiving ACEI/ARB as part of their regimen,and 61 patients were on antihypertensive medication other than ACEI/ARB.We observed no statistically significant differences in percentages of in-hospital mortality(28%vs.34%,P=0.46),ICU admission(20%vs.28%,P=0.37)or invasive mechanical ventilation(18%vs.26%,P=0.31)between patients with or without ACEI/ARB treatment.Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes.Our findings confirm the lack of an association between chronic receipt of reninangiotensin system antagonists and severe outcomes of COVID-19.Patients should continue previous antihypertensive therapy until further evidence is available.展开更多
Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia(SCAP).We prospectively enrolled consecutive SCAP patients admitted to ICU.Bronch...Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia(SCAP).We prospectively enrolled consecutive SCAP patients admitted to ICU.Bronchoscopy was performed at bedside within 48 h of ICU admission,and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid.The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy.Sixty-seven patients were included.Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota(R2=0.033;P=0.018),followed by acute kidney injury(AKI;R2=0.032;P=0.011)and plasma MIP-1βlevel(R2=0.027;P=0.044).Random forest identified that the families Prevotellaceae,Moraxellaceae,and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results.Multivariable Cox regression showed that the increase inα-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements.The positive bacteria lab test results,AKI,and plasma MIP-1βlevel were associated with patients’lung microbiota composition on ICU admission.The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.展开更多
Pristine graphene (PG) has been demonstrated to be an excellent substrate for Raman enhancement, which is called graphene-enhanced Raman scattering. However, the chemically inert and hydrophobic surface of PG hinders ...Pristine graphene (PG) has been demonstrated to be an excellent substrate for Raman enhancement, which is called graphene-enhanced Raman scattering. However, the chemically inert and hydrophobic surface of PG hinders the adsorption of molecules especially in aqueous solutions, and consequently limits the Raman enhanced efficiency. Here, we synthesized defective graphene (DG) films by chemical vapor deposition on Au, which has a defect density of ~2.0 ×10^11 cm^-2. The DG shows a much better wettability than PG towards dye solution. Combining with the strong adsorption ability of defects to molecules, DG shows greatly enhanced efficiency than PG with perfect lattice. For example, the detection limit for rhodamine B can reach 2×10^9 M for DG while it is on the order of 10^-7 M for PG. In addition, DG has high enhancement uniformity and the Au substrate can be reused after electrochemical bubbling transfer. These advantages suggest the great potential of the DG grown on Au for practical applications in environmental monitoring.展开更多
Destruction of the lung parenchyma may result in the formation of cysts,cavities and bullae.Definition of the type of destructive lesion is best achieved by high-resolution computed tomography(HRCT)scans of the chest(...Destruction of the lung parenchyma may result in the formation of cysts,cavities and bullae.Definition of the type of destructive lesion is best achieved by high-resolution computed tomography(HRCT)scans of the chest(TrotmanDickenson,2014).The loss of lung parenchyma may展开更多
Targeted alpha-therapy(TAT) is increasingly attractive due to its extraordinary antitumor efficacy.However,the supply of α-emitters for TAT is insufficient and under control by a limited number of countries.^(212)Pb ...Targeted alpha-therapy(TAT) is increasingly attractive due to its extraordinary antitumor efficacy.However,the supply of α-emitters for TAT is insufficient and under control by a limited number of countries.^(212)Pb is a promising α-emitter with an optimal half-life(10.6 h) and favored decay chain.Of interest,^(212)Pb can be extracted directly from natural thorium,which may be abundant in the mining waste of rare-earth,uranium,etc.Indeed,radioactive thorium waste has been a longstanding environmental challenge that needs immediate action.Developing an on-demand and facile process to isolate ^(212)Pb from natural thorium would be ideal to meet the above challenges,yet is difficult.In theory,the ratio of ^(212)Pb tonatTh is below 10^(-13)in commercially available thorium salts.As a pilot study,2.2 MBq of ^(212)Pb was successfully extracted from a 5 L solution of thorium nitrate by using a Pb-selective resin.The radiochemical purity of ^(212)Pb is over 99.9% according to gamma-ray analysis.The purified^(212)Pb was applied to radiolabel a couple of peptides used in clinics(i.e.PSMA,TATE and FAPI-04),and the radiochemical yields are>85%.Of note,^(212)Pb can be repeatedly separated from the thorium solution every 2 days.In summary,a practical and scalable method was developed to isolate^(212)Pb for potentially clinical use,which may be of great importance as it does not require either cyclotron or nuclear reactor.展开更多
To prevent polysulfides from dissolution into electrolyte,we propose a novel and simple approach to nitrogen-doped carbon foams which contain hierarchically porous structure and are decorated with zinc nanodots throug...To prevent polysulfides from dissolution into electrolyte,we propose a novel and simple approach to nitrogen-doped carbon foams which contain hierarchically porous structure and are decorated with zinc nanodots through one-pot carbonization and activation process.These carbon foams,which serve as hosts for sulfur in lithium battery,can provide a conducting network and shorter diffusion length for Liions.Specially,the zinc nanodots derived from the carbothermal reaction of ZnCl_(2) at high temperature can interact with sulfur/polysulfides by strong chemisorption.In addition,the zinc nanodots can also facilitate the conversion reaction between Li_(2)S_(x)(2<x<8)and Li_(2)S/Li_(2)S_(2).Therefore,Zn@NCFs/S cathode presents high sulfur utility and large capacity.展开更多
A nuclear reaction-induced dynamic therapy,denoted as nucleodynamic therapy(NDT),has been invented that triggers immunogenic cell death and successfully treats metastatic tumors due to its unexpected abscopal effect.G...A nuclear reaction-induced dynamic therapy,denoted as nucleodynamic therapy(NDT),has been invented that triggers immunogenic cell death and successfully treats metastatic tumors due to its unexpected abscopal effect.Gadolinium neutron capture therapy(GdNCT)is binary radiotherapy based on a localized nuclear reaction that produces high-energy radiations(e.g.,Auger electrons,γ-rays,etc.)in cancer cells when^(157Gd)is irradiated with thermal neutrons.Yet,its clinical application has been postponed due to the poor ability of Auger electrons andγ-rays to kill cells.Here,we engineered a^(157Gd)-porphyrin framework that synergizes GdNCT and dynamic therapy to efficiently produce both•OH and immunogenic 1O2 in cancer cells,thereby provoking a strong antitumor immune response.This study unveils the fact and mechanism that NDT heats tumor immunity.Another unexpected finding is that the Auger electron can be the most effective energy-transfer medium for radiation-induced activation of nanomedicines because its nanoscale trajectory perfectlymatches the size of nanomaterials.Inmouse tumormodels,NDT causes nearly complete regression of both primary and distant tumor grafts.Thus,this^(157Gd)-porphyrin framework radioenhancer endows GdNCT with the exotic function of triggering dynamic therapy;its applicationmay expand in clinics as a new radiotherapy modality that utilizes GdNCT to provoke whole-body antitumor immune response for treating metastases,which are responsible for 90%of all cancer deaths.展开更多
Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the ...Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.Methods:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after recruitment.Additionally,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit.The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.Results:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids group.The AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid group.However,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by corticosteroids.During 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical significance.No significant difference was observed for NAbs.However,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or NAbs.Additionally,corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group,but the results were not statistically significant(adjusted hazard ratio 0.71,95%CI 0.50-1.00;P=0.0508).Conclusion:Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies.Throughout the decay phase,from the acute phase to the half-year follow-up visit,short-term and low-dose corticosteroids did not significantly affect humoral responses,except for accelerating the waning of short-lived antibodies.展开更多
基金This work is supported by Demonstration of Scientific and Technology Achievements Transform in Sichuan Province under Grant 2022ZHCG0036National Natural Science Foundation of China(62002047).
文摘Identifying a device and detecting a change in its position is critical for secure devices management in the Internet of Things(IoT).In this paper,a device management system is proposed to track the devices by using audio-based location distinction techniques.In the proposed scheme,traditional cryptographic techniques,such as symmetric encryption algorithm,RSA-based signcryption scheme,and audio-based secure transmission,are utilized to provide authentication,non-repudiation,and confidentiality in the information interaction of the management system.Moreover,an audio-based location distinction method is designed to detect the position change of the devices.Specifically,the audio frequency response(AFR)of several frequency points is utilized as a device signature.The device signature has the features as follows.(1)Hardware Signature:different pairs of speaker and microphone have different signatures;(2)Distance Signature:in the same direction,the signatures are different at different distances;and(3)Direction Signature:at the same distance,the signatures are different in different directions.Based on the features above,amovement detection algorithmfor device identification and location distinction is designed.Moreover,a secure communication protocol is also proposed by using traditional cryptographic techniques to provide integrity,authentication,and non-repudiation in the process of information interaction between devices,Access Points(APs),and Severs.Extensive experiments are conducted to evaluate the performance of the proposed method.The experimental results show that the proposedmethod has a good performance in accuracy and energy consumption.
基金supported by the National Key Research and Development Program (grant no. 2021YFA1101301)the National Natural Science Foundation of China (grant no. 82225027, 82271419, 81820108013, 62127810, 81901902)+1 种基金Shanghai Rising-Star Program (grant no. 22QA1408200)the Fundamental Research Funds for the Central Universities(no. 22120220555, no. 22120230292, no. 22120230138)
文摘Alzheimer’s disease(AD)is a typical neurodegenerative disease that leads to irreversible neuronal degeneration,and effective treatment remains elusive due to the unclear mechanism.We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241(EVs-AM1241)to protect against neurodegenerative progression and neuronal function in AD model mice.According to the results,EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241.The Morris water maze(MWM)and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved.In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning.Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloidβ(Aβ)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241.Moreover,EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton,indicating that they enhanced neuronal regeneration.RNA sequencing revealed that EVs-AM1241 facilitated Aβphagocytosis,promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway.Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in modelmice,indicating that they are very promising particles for treating AD.
基金supported by the National Natural Science Foundation of China(51325205,51290273,51521091,and 51861135201)the Chinese Academy of Sciences(XDB30000000,and ZDBS-LY-JSC027)+2 种基金Liaoning Revitalization Talents Program(XLYC1808013)the Program for Guangdong Introducing Innovative and Enterpreneurial Teams(2017ZT07C341)the Development and Reform Commission of Shenzhen Municipality for the development of the“Low-Dimensional Materials and Devices”discipline,and the Economic,Trade and Information Commission of Shenzhen Municipality for the“2017 Graphene Manufacturing Innovation Center Project”(201901171523).
基金This work was supported by Major Projects of National Science and Technology on New Drug Creation and Development(Nos.2020ZX09201001 and 2020ZX09201012)Chinese Academy of Medical Sciences(CAMS)Emergency Project of COVID-19(No.2020HY320001).
文摘The possible effects of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin Ⅱ receptor blockers(ARBs)on COVID-19 disease severity have generated considerable debate.We performed a single-center,retrospective analysis of hospitalized adult COVID-19 patients in Wuhan,China,who had definite clinical outcome(dead or discharged)by February 15,2020.Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes.The medical records from 702 patients were screened.Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication,40 patients were receiving ACEI/ARB as part of their regimen,and 61 patients were on antihypertensive medication other than ACEI/ARB.We observed no statistically significant differences in percentages of in-hospital mortality(28%vs.34%,P=0.46),ICU admission(20%vs.28%,P=0.37)or invasive mechanical ventilation(18%vs.26%,P=0.31)between patients with or without ACEI/ARB treatment.Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes.Our findings confirm the lack of an association between chronic receipt of reninangiotensin system antagonists and severe outcomes of COVID-19.Patients should continue previous antihypertensive therapy until further evidence is available.
基金funded by the National Key Research and Devclopment Program of China(No,2017YFC1309301)the CAMS Innovation Fund for Medical Sciences(CIFMS:No.2018-12M-1-003)+1 种基金the National Science Grant for Distinguished Young Scholars(No.81425001/H0104)the Ministry of Science and Technology of China No.2017ZX10103004).
文摘Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia(SCAP).We prospectively enrolled consecutive SCAP patients admitted to ICU.Bronchoscopy was performed at bedside within 48 h of ICU admission,and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid.The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy.Sixty-seven patients were included.Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota(R2=0.033;P=0.018),followed by acute kidney injury(AKI;R2=0.032;P=0.011)and plasma MIP-1βlevel(R2=0.027;P=0.044).Random forest identified that the families Prevotellaceae,Moraxellaceae,and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results.Multivariable Cox regression showed that the increase inα-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements.The positive bacteria lab test results,AKI,and plasma MIP-1βlevel were associated with patients’lung microbiota composition on ICU admission.The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
基金supported by the National Key R&D Program of China (No. 2016YFA0200101)the National Natural Science Foundation of China (Nos. 51325205, 51290273, 51521091, and 51861135201)+1 种基金Chinese Academy of Sciences (No. 174321KYSB20160011)the Strategic Priority Research Program of Chinese Academy of Sciences (No. XDB30000000)
文摘Pristine graphene (PG) has been demonstrated to be an excellent substrate for Raman enhancement, which is called graphene-enhanced Raman scattering. However, the chemically inert and hydrophobic surface of PG hinders the adsorption of molecules especially in aqueous solutions, and consequently limits the Raman enhanced efficiency. Here, we synthesized defective graphene (DG) films by chemical vapor deposition on Au, which has a defect density of ~2.0 ×10^11 cm^-2. The DG shows a much better wettability than PG towards dye solution. Combining with the strong adsorption ability of defects to molecules, DG shows greatly enhanced efficiency than PG with perfect lattice. For example, the detection limit for rhodamine B can reach 2×10^9 M for DG while it is on the order of 10^-7 M for PG. In addition, DG has high enhancement uniformity and the Au substrate can be reused after electrochemical bubbling transfer. These advantages suggest the great potential of the DG grown on Au for practical applications in environmental monitoring.
基金supported by the National High Technology Research and Development Program of China (863 Program) (No. 2012AA02A201)supported by the Intramural Research Program,National Institutes of Health, National Heart, Lung and Blood Institute,USA
文摘Destruction of the lung parenchyma may result in the formation of cysts,cavities and bullae.Definition of the type of destructive lesion is best achieved by high-resolution computed tomography(HRCT)scans of the chest(TrotmanDickenson,2014).The loss of lung parenchyma may
基金funded by Beijing Municipal Natural Science Foundation (No. Z200018)the Special Foundation of Beijing Municipal Education Commission (No. 3500–12020123)+2 种基金the National Natural Science Foundation of China (Nos. U1867209 and 21778003)the Ministry of Science and Technology of the People’s Republic of China (No. 2017YFA0506300)Li Ge-Zhao Ning Life Science Youth Research Foundation (No. LGZNQN202004)。
文摘Targeted alpha-therapy(TAT) is increasingly attractive due to its extraordinary antitumor efficacy.However,the supply of α-emitters for TAT is insufficient and under control by a limited number of countries.^(212)Pb is a promising α-emitter with an optimal half-life(10.6 h) and favored decay chain.Of interest,^(212)Pb can be extracted directly from natural thorium,which may be abundant in the mining waste of rare-earth,uranium,etc.Indeed,radioactive thorium waste has been a longstanding environmental challenge that needs immediate action.Developing an on-demand and facile process to isolate ^(212)Pb from natural thorium would be ideal to meet the above challenges,yet is difficult.In theory,the ratio of ^(212)Pb tonatTh is below 10^(-13)in commercially available thorium salts.As a pilot study,2.2 MBq of ^(212)Pb was successfully extracted from a 5 L solution of thorium nitrate by using a Pb-selective resin.The radiochemical purity of ^(212)Pb is over 99.9% according to gamma-ray analysis.The purified^(212)Pb was applied to radiolabel a couple of peptides used in clinics(i.e.PSMA,TATE and FAPI-04),and the radiochemical yields are>85%.Of note,^(212)Pb can be repeatedly separated from the thorium solution every 2 days.In summary,a practical and scalable method was developed to isolate^(212)Pb for potentially clinical use,which may be of great importance as it does not require either cyclotron or nuclear reactor.
文摘To prevent polysulfides from dissolution into electrolyte,we propose a novel and simple approach to nitrogen-doped carbon foams which contain hierarchically porous structure and are decorated with zinc nanodots through one-pot carbonization and activation process.These carbon foams,which serve as hosts for sulfur in lithium battery,can provide a conducting network and shorter diffusion length for Liions.Specially,the zinc nanodots derived from the carbothermal reaction of ZnCl_(2) at high temperature can interact with sulfur/polysulfides by strong chemisorption.In addition,the zinc nanodots can also facilitate the conversion reaction between Li_(2)S_(x)(2<x<8)and Li_(2)S/Li_(2)S_(2).Therefore,Zn@NCFs/S cathode presents high sulfur utility and large capacity.
基金funded by the Ministry of Science and Technology of the People’s Republic of China(Grant No.2021YFA1601400)the Central Guidance for Local Science and Technology Development Projects(No.202138-03)+4 种基金the National Nature Science Foundation of China(Grant No.U1867209)the Beijing Municipal Natural Science Foundation(Grant No.Z200018)Changping Laboratory under the project number(2021C-07-01)the Special Foundation of Beijing Municipal Education Commission(Grant No.3500-12020123)Li Ge-Zhao Ning Life Science Youth Research Foundation(LGZNQN202004)to Z.L.We thank the facility support from the Analytical Instrumentation Center of Peking University.
文摘A nuclear reaction-induced dynamic therapy,denoted as nucleodynamic therapy(NDT),has been invented that triggers immunogenic cell death and successfully treats metastatic tumors due to its unexpected abscopal effect.Gadolinium neutron capture therapy(GdNCT)is binary radiotherapy based on a localized nuclear reaction that produces high-energy radiations(e.g.,Auger electrons,γ-rays,etc.)in cancer cells when^(157Gd)is irradiated with thermal neutrons.Yet,its clinical application has been postponed due to the poor ability of Auger electrons andγ-rays to kill cells.Here,we engineered a^(157Gd)-porphyrin framework that synergizes GdNCT and dynamic therapy to efficiently produce both•OH and immunogenic 1O2 in cancer cells,thereby provoking a strong antitumor immune response.This study unveils the fact and mechanism that NDT heats tumor immunity.Another unexpected finding is that the Auger electron can be the most effective energy-transfer medium for radiation-induced activation of nanomedicines because its nanoscale trajectory perfectlymatches the size of nanomaterials.Inmouse tumormodels,NDT causes nearly complete regression of both primary and distant tumor grafts.Thus,this^(157Gd)-porphyrin framework radioenhancer endows GdNCT with the exotic function of triggering dynamic therapy;its applicationmay expand in clinics as a new radiotherapy modality that utilizes GdNCT to provoke whole-body antitumor immune response for treating metastases,which are responsible for 90%of all cancer deaths.
基金supported by the National Natural Science Foundation of China(No.82200009)the National Key Research and Development Program of China(No.2021YFC0864700)+1 种基金the National Natural Science Foundation of China(No.81930063)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS No.2021-I2M-1-048).
文摘Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.Methods:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after recruitment.Additionally,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit.The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.Results:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids group.The AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid group.However,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by corticosteroids.During 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical significance.No significant difference was observed for NAbs.However,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or NAbs.Additionally,corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group,but the results were not statistically significant(adjusted hazard ratio 0.71,95%CI 0.50-1.00;P=0.0508).Conclusion:Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies.Throughout the decay phase,from the acute phase to the half-year follow-up visit,short-term and low-dose corticosteroids did not significantly affect humoral responses,except for accelerating the waning of short-lived antibodies.
