As a 37-amino acid vasoactive neuropeptide, calcitonin gene-related peptide （CGRP） is widely distributed in nervous systems. The studies and clinical applications of CGRP are limited by its peptide nature and short ...As a 37-amino acid vasoactive neuropeptide, calcitonin gene-related peptide （CGRP） is widely distributed in nervous systems. The studies and clinical applications of CGRP are limited by its peptide nature and short half-life. A series of peptide analogues of the α-form of CGRP were synthesized. Afterwards, by using in vitro metabolic and activity studies, we prepared two high affinity analogues with significantly improved plasma stability.展开更多
The acetyl ester plays an important role for protection of the hydroxyl groups in carbohydrates synthesis.In the present study,we described an efficient deprotection of acetyl group of pentacyclic triterpenoid by usin...The acetyl ester plays an important role for protection of the hydroxyl groups in carbohydrates synthesis.In the present study,we described an efficient deprotection of acetyl group of pentacyclic triterpenoid by using methanolic ammonia in THF solution.Good selectivity for cleaving gal-C2-OAc group of 3β-hydroxy-olean-12-en-28-oic acid 28-N-2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside(3) was achieved in the presence of methanolic ammonia within 4 h at low temperature(-60℃) in a yield of 56%.The reaction disclosed here provides a new method for the synthesis of C2 selective modified carbohydrates,which is more useful than conventional synthesis procedure that usually requires many steps including temporary regioselective protection and deprotection.When the reaction temperature was increased from -60℃ to room temperature,the cleavage of the other three acetyl groups of galactose in an order of C4-OAc>C3-OAc>C6-OAc was observed.Based on this study,a plausible route for the deacetylation reaction has been proposed.展开更多
Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic ...Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin(CD) via "click chemistry" can improve their solubility and anti-HCV entry potency. In the present work,four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by ~1H NMR, ^(13)C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity(AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.展开更多
Correction to:Radiation Detection Technology and Methods(2024)8:1-1105.https://doi.org/10.1007/s41605-024-00463-y.In this article all authors name was missing in the springer link.It has been corrected.The original ar...Correction to:Radiation Detection Technology and Methods(2024)8:1-1105.https://doi.org/10.1007/s41605-024-00463-y.In this article all authors name was missing in the springer link.It has been corrected.The original article has been corrected.展开更多
Two wetland maps for the entire China have been produced based on Landsat data acquired around 1990 and 2000. Wetlands in China have been divided into 3 broad categories with 15 sub-categories except rice fields. In 1...Two wetland maps for the entire China have been produced based on Landsat data acquired around 1990 and 2000. Wetlands in China have been divided into 3 broad categories with 15 sub-categories except rice fields. In 1990, the total wetland area in China was 355208 km2 whereas in 2000 it dropped to 304849 km2 with a net loss of 50360 km2. During an approximate 10-year period, inland wetland reduced from 318326 to 257922 km2, coastal wetland dropped from 14335 to 12015 km2, while artificial wetland increased from 22546 to 34911 km2. The greatest natural wetland loss occurred in Heilongjiang, Inner Mon- golia, and Jilin with a total loss of over 57000 km2 of wetland. In western China, over 13000 km2 of wetlands were newly formed in Xinjiang, Tibet, and Qinghai. About 12000 km2 of artificial wetlands were also added for fish farm and reservoir constructions. The newly formed wetlands in western China were caused primarily by climate warming over that region whereas the newly created artificial wetlands were caused by economic developments. China’s wetland loss is caused mainly by human activities.展开更多
A series of triterpene dimers bearing different scaffold were designed and synthesized via CuAAC reaction. Their anti-HCV entry activities were evaluated by HCVpp and VSVpp entry assays. It was found that echinocystic...A series of triterpene dimers bearing different scaffold were designed and synthesized via CuAAC reaction. Their anti-HCV entry activities were evaluated by HCVpp and VSVpp entry assays. It was found that echinocystic acid （EA） and its dimer were still necessary for maintaining anti-HCV entry activity, and replacement of EA by other triterpenes might significantly decrease its anti-viral activities. Using a linker bearing a piperazine group, compound 14 dramatically increased its potency with IC50 at 2.87 nmol/L. In addition, the undesired hemolytic effect of all these compounds was removed.展开更多
Interleukin-2(IL-2)is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells(Tregs)and effector cells,leading to paradoxical consequences.Here,we report a strategy that exploite...Interleukin-2(IL-2)is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells(Tregs)and effector cells,leading to paradoxical consequences.Here,we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine(FSY)into IL-2 for proximity-enabled covalent binding to IL-2Rαto selectively promote Treg activation.We found that FSY-bearing IL-2 variants,such as L72-FSY,covalently bound to IL-2Rαvia sulfur-fluoride exchange when in proximity,resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells.Further assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation,as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3(LAG-3)and enhanced expression of programmed cell death protein-1(PD-1).Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease(GvHD)resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 treatment.The efficacy of L72-FSY was further improved by N-terminal PEGylation,which increased its circulatory retention for preferential and sustained effects.This proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies.展开更多
The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 3...The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.展开更多
Against the background of global climate change, the increasing heat health risk from the combined effect of changes in high temperature, exposure, vulnerability, and other factors has become a growing concern.Yet the...Against the background of global climate change, the increasing heat health risk from the combined effect of changes in high temperature, exposure, vulnerability, and other factors has become a growing concern.Yet the low number of temperature observation stations is insufficient to represent the complex changes in urban heatwaves, and subdistrict-scale(town, township, neighborhood committee, and equivalent) heat health risk and adaptability assessments are still limited. In this study, we built daytime and nighttime high-temperature interpolation models supported by data from 225 meteorological stations in Beijing.The models performed well at interpolating the cumulative hours of high temperature and the interpolation quality at night was better than that during the day. We further established a methodological framework for heat health risk and adaptability assessments based on heat hazard, population exposure, social vulnerability, and adaptability at the subdistrict scale in Beijing. Our results show that the heat health risk hotspots were mainly located in the central urban area,with 81 hotspots during the day and 76 at night. The average value of the heat health risk index of urban areas was 5.60 times higher than that of suburban areas in the daytime,and 6.70 times higher than that of suburban areas in the night. Greater population density and higher intensity of heat hazards were the main reasons for the high risk in most heat health risk hotspots. Combined with a heat-adaptive-capacity evaluation for hotspot areas, this study suggests that 11high-risk and low-adaptation subdistricts are priority areas for government action to reduce heat health risk in policy formulation and urban development.展开更多
Deep cross-modal clustering has been developing at a rapid pace and attracted great attention.It aims to pursue a consistent subspace from different modalities by conventional neural network and achieve remarkable clu...Deep cross-modal clustering has been developing at a rapid pace and attracted great attention.It aims to pursue a consistent subspace from different modalities by conventional neural network and achieve remarkable clustering performance. However, most existing deep cross-modal clustering methods do not simultaneously take care of the inherently different information for each modality and local geometric structure for all cross-modal data, which inevitably results in the degradation of clustering performance. In this paper, we propose a novel method named Deep Consistent-Inherent Cross-Modal Subspace Clustering(i.e. DCCSC) to tackle these problems of cross-modal clustering. Our method can preserve the inherent independence of each modality while exploring the consistent information amongst different modalities. Meanwhile, a neighbor graph is embedded into the proposed deep cross-modal subspace clustering framework to maintain the local geometry structure of the original data and learn a shared subspace representation. Therefore, we integrate the consistent-inherent learning and the local structure learning into a unified deep framework to significantly improve the cross-modal subspace clustering performance. Experimental results demonstrate that our proposed method can achieve the superior clustering performance compared with the state-of-the-art methods on four benchmark datasets.展开更多
文摘As a 37-amino acid vasoactive neuropeptide, calcitonin gene-related peptide （CGRP） is widely distributed in nervous systems. The studies and clinical applications of CGRP are limited by its peptide nature and short half-life. A series of peptide analogues of the α-form of CGRP were synthesized. Afterwards, by using in vitro metabolic and activity studies, we prepared two high affinity analogues with significantly improved plasma stability.
基金supported by the National Natural Science Foundation of China(Nos.21572015,21877007,81703540 and 21702007)China Postdoctoral Science Foundation(No.2018M631796)+2 种基金Technology Plan Foundation of Liaoning Province(No.20170520063)Chinese Medicine Related Scientific Research Project of Dalian(No.17Z2013)the open funding of the State Key Laboratory of Phytochemistry and Plant Resources in West China。
文摘The acetyl ester plays an important role for protection of the hydroxyl groups in carbohydrates synthesis.In the present study,we described an efficient deprotection of acetyl group of pentacyclic triterpenoid by using methanolic ammonia in THF solution.Good selectivity for cleaving gal-C2-OAc group of 3β-hydroxy-olean-12-en-28-oic acid 28-N-2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside(3) was achieved in the presence of methanolic ammonia within 4 h at low temperature(-60℃) in a yield of 56%.The reaction disclosed here provides a new method for the synthesis of C2 selective modified carbohydrates,which is more useful than conventional synthesis procedure that usually requires many steps including temporary regioselective protection and deprotection.When the reaction temperature was increased from -60℃ to room temperature,the cleavage of the other three acetyl groups of galactose in an order of C4-OAc>C3-OAc>C6-OAc was observed.Based on this study,a plausible route for the deacetylation reaction has been proposed.
基金supported by the National Natural Science Foundation of China (Nos. 81573269, 21572015, 21877007, 91753202 and 21702007)and the open funding of the State Key Laboratory of Phytochemistry and Plant Resources in West China
文摘Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin(CD) via "click chemistry" can improve their solubility and anti-HCV entry potency. In the present work,four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by ~1H NMR, ^(13)C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity(AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.
文摘Correction to:Radiation Detection Technology and Methods(2024)8:1-1105.https://doi.org/10.1007/s41605-024-00463-y.In this article all authors name was missing in the springer link.It has been corrected.The original article has been corrected.
基金supported by a major research grant from National Natural Science Foundation of China (Grant No. 30590370)National Science and Technology Support Program (Grant No. 2006BAJ10B02)
文摘Two wetland maps for the entire China have been produced based on Landsat data acquired around 1990 and 2000. Wetlands in China have been divided into 3 broad categories with 15 sub-categories except rice fields. In 1990, the total wetland area in China was 355208 km2 whereas in 2000 it dropped to 304849 km2 with a net loss of 50360 km2. During an approximate 10-year period, inland wetland reduced from 318326 to 257922 km2, coastal wetland dropped from 14335 to 12015 km2, while artificial wetland increased from 22546 to 34911 km2. The greatest natural wetland loss occurred in Heilongjiang, Inner Mon- golia, and Jilin with a total loss of over 57000 km2 of wetland. In western China, over 13000 km2 of wetlands were newly formed in Xinjiang, Tibet, and Qinghai. About 12000 km2 of artificial wetlands were also added for fish farm and reservoir constructions. The newly formed wetlands in western China were caused primarily by climate warming over that region whereas the newly created artificial wetlands were caused by economic developments. China’s wetland loss is caused mainly by human activities.
基金Acknowledgement This work was supported by the National Natural Science Foundation of China （No. 81560560）, Open-Fund Program of the State Key Laboratory of Natural and Biomimetic Drugs （No. K20160209） and Yunnan Basic Research Project （No. 14051789）.
文摘A series of triterpene dimers bearing different scaffold were designed and synthesized via CuAAC reaction. Their anti-HCV entry activities were evaluated by HCVpp and VSVpp entry assays. It was found that echinocystic acid （EA） and its dimer were still necessary for maintaining anti-HCV entry activity, and replacement of EA by other triterpenes might significantly decrease its anti-viral activities. Using a linker bearing a piperazine group, compound 14 dramatically increased its potency with IC50 at 2.87 nmol/L. In addition, the undesired hemolytic effect of all these compounds was removed.
基金This study was supported by grants from the National Key Research and Development Program of China(2019ZX09739)National Natural Science Foundation of China(82230060,82271831,81788101,82204258)+3 种基金Chinese Academy of Medical Science Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1-016,2021-I2M-1-017,2021-I2M-1-047,2021-I2M-1-040,2021-I2M-1-016,2021-I2M-1-026)Natural Science Foundation of Beijing(7222263)Beijing Capital Health Development Fund(2020-2-4019)Fundamental Research Funds for the Central Universities(3332022108).
文摘Interleukin-2(IL-2)is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells(Tregs)and effector cells,leading to paradoxical consequences.Here,we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine(FSY)into IL-2 for proximity-enabled covalent binding to IL-2Rαto selectively promote Treg activation.We found that FSY-bearing IL-2 variants,such as L72-FSY,covalently bound to IL-2Rαvia sulfur-fluoride exchange when in proximity,resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells.Further assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation,as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3(LAG-3)and enhanced expression of programmed cell death protein-1(PD-1).Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease(GvHD)resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 treatment.The efficacy of L72-FSY was further improved by N-terminal PEGylation,which increased its circulatory retention for preferential and sustained effects.This proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies.
基金support from diverse funding sources,including the National Key Program for S&T Research and Development of the Ministry of Science and Technology(MOST),Yifang Wang's Science Studio of the Ten Thousand Talents Project,the CAS Key Foreign Cooperation Grant,the National Natural Science Foundation of China(NSFC)Beijing Municipal Science&Technology Commission,the CAS Focused Science Grant,the IHEP Innovation Grant,the CAS Lead Special Training Programthe CAS Center for Excellence in Particle Physics,the CAS International Partnership Program,and the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.
基金This work was jointly supported by the National Key Research and Development Program of China(2019YFC0507805)the Strategic Leading Science and Technology Program of the Chinese Academy of Sciences(XDA20020202).We express our sincere appreciation to the anonymous reviewers for their constructive comments.
文摘Against the background of global climate change, the increasing heat health risk from the combined effect of changes in high temperature, exposure, vulnerability, and other factors has become a growing concern.Yet the low number of temperature observation stations is insufficient to represent the complex changes in urban heatwaves, and subdistrict-scale(town, township, neighborhood committee, and equivalent) heat health risk and adaptability assessments are still limited. In this study, we built daytime and nighttime high-temperature interpolation models supported by data from 225 meteorological stations in Beijing.The models performed well at interpolating the cumulative hours of high temperature and the interpolation quality at night was better than that during the day. We further established a methodological framework for heat health risk and adaptability assessments based on heat hazard, population exposure, social vulnerability, and adaptability at the subdistrict scale in Beijing. Our results show that the heat health risk hotspots were mainly located in the central urban area,with 81 hotspots during the day and 76 at night. The average value of the heat health risk index of urban areas was 5.60 times higher than that of suburban areas in the daytime,and 6.70 times higher than that of suburban areas in the night. Greater population density and higher intensity of heat hazards were the main reasons for the high risk in most heat health risk hotspots. Combined with a heat-adaptive-capacity evaluation for hotspot areas, this study suggests that 11high-risk and low-adaptation subdistricts are priority areas for government action to reduce heat health risk in policy formulation and urban development.
文摘Deep cross-modal clustering has been developing at a rapid pace and attracted great attention.It aims to pursue a consistent subspace from different modalities by conventional neural network and achieve remarkable clustering performance. However, most existing deep cross-modal clustering methods do not simultaneously take care of the inherently different information for each modality and local geometric structure for all cross-modal data, which inevitably results in the degradation of clustering performance. In this paper, we propose a novel method named Deep Consistent-Inherent Cross-Modal Subspace Clustering(i.e. DCCSC) to tackle these problems of cross-modal clustering. Our method can preserve the inherent independence of each modality while exploring the consistent information amongst different modalities. Meanwhile, a neighbor graph is embedded into the proposed deep cross-modal subspace clustering framework to maintain the local geometry structure of the original data and learn a shared subspace representation. Therefore, we integrate the consistent-inherent learning and the local structure learning into a unified deep framework to significantly improve the cross-modal subspace clustering performance. Experimental results demonstrate that our proposed method can achieve the superior clustering performance compared with the state-of-the-art methods on four benchmark datasets.
