The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-inf...The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.展开更多
Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exh...Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exhibit substantial regional heterogeneity and display variable responses to different neurological diseases.Such diversity in astrocyte morphology and function is essential for understanding both normal brain function and the underlying mechanisms of neurological disorders.To investigate this heterogeneity,we developed a novel method for the selective and sparse labeling of astrocytes in various brain regions.This technique utilizes a dual adeno-associated virus system that allows for the expression of Cre recombinase and enhanced green fluorescent protein under the control of the glial fibrillary acidic protein(GfaABC1D)promoter.The system was tested in C57BL/6J mice and successfully labeled astrocytes across multiple brain regions.The method enabled the detailed visualization of individual astrocytes-including their intricate peripheral processes-through three-dimensional reconstructions from confocal microscopy images.Furthermore,the labeling efficiency of this dual adeno-associated virus technology was validated by examining astrocyte function in a spared nerve injury model and through chemogenetic modulation.This innovative approach holds great promise for future research because it enables a more comprehensive understanding of astrocyte variation not only in spared nerve injury but also in a broad spectrum of neurological diseases.The ability to selectively label and study astrocytes in different brain regions provides a powerful tool for exploring the complexities of these essential cells and their roles in physiological and pathological conditions.展开更多
Golgi apparatus(GA)-associated secretome runs through the endomembrane system and is critical for inter-and intracellular communication networks.However,achieving in situ dissection of the GA-associated secretome rema...Golgi apparatus(GA)-associated secretome runs through the endomembrane system and is critical for inter-and intracellular communication networks.However,achieving in situ dissection of the GA-associated secretome remains challenging owing to the scarcity of specific labeling methods.This work develops an aggregation-induced emission(AIE)luminogen-mediated photocatalytic proximity labeling strategy that allows profiling of the GA-associated secretome with high spatiotemporal precision.Leveraging an AIE luminogen-derived GA-targeting photocatalyst,this strategy achieves efficient labeling of proteins in minutes within the Golgi lumen upon light activation,which enables spatiotemporally resolved modification of histidine and tyrosine residues.We succeed in profiling secretome in both living HeLa cells and hard-to-transfect macrophage HMC3 cells,and a significant subset of GA-associated secretome with 80%specificity is determined,linking the distinct GA-associated secretory profiles to cellular characteristics.The method is further applied to proteome mapping of brain and bone metastatic lung cancer cells,which reveals the underlying roles the GA-associated secretome plays in extracellular matrix organization during metastasis.This work delivers a robust tool to break the dilemma of chemical labeling of GA-associated secretome in living cells,and provides mechanistic insights into secretion regulation at the subcellular level.展开更多
Objective: Xueteng-related herbs include Spatholobi Caulis(Jixueteng in Chinese), Sargentodoxae Caulis(Daxueteng in Chinese), Kadsurae Caulis(Dianjixueteng in Chinese), and other medicinal plant stems that release red...Objective: Xueteng-related herbs include Spatholobi Caulis(Jixueteng in Chinese), Sargentodoxae Caulis(Daxueteng in Chinese), Kadsurae Caulis(Dianjixueteng in Chinese), and other medicinal plant stems that release reddish-brown juices after being cut. However, similarity in phonetic spelling and sound leads to their misuse in clinic or commercial circulation. Accurate labeling is imperative as well as effective for species identification.Methods: In this study, the ITS2 sequences of 76 samples of Xueteng-related herbs were obtained and analyzed to identify them. And then they were converted into QR codes using the open source PHP QR code. Also, a DNA barcode reference library was established according to these sequences and was used to authenticate the 25 samples of Xueteng-related herbs collected from the market.Results: The lengths of the ITS2 sequences of different Xueteng-related herbs ranged from 207 to 235 bp and the GC contents were 57.5%-71.0%. Jixueteng, Daxueteng, and Dianjixueteng were clustered into three clades respectively in the neighbor-joining(NJ) phylogenetic tree, and the efficiency of the BLAST method was 100%. The ITS2 sequences of different Xueteng-related herbs were presented vividly and specifically in QR code. Twenty-two of all 25 commercial samples were consistent with the original labels, whereas three samples marked "Dianjixueteng" were authenticated as "Jixueteng".Conclusion: QR code labeling system based on DNA barcode is an effective labeling system of Xuetengrelated herbs for their circulation regulation.展开更多
As one important type of post-translational modifications(PTMs),protein lysine succinylation regulates many important biological processes.It is also closely involved with some major diseases in the aspects of Cardiom...As one important type of post-translational modifications(PTMs),protein lysine succinylation regulates many important biological processes.It is also closely involved with some major diseases in the aspects of Cardiometabolic,liver metabolic,nervous system and so on.Therefore,it is imperative to predict the succinylation sites in proteins for both basic research and drug development.In this paper,a novel predictor called i Succ Lys-BLS was proposed by not only introducing a new machine learning algorithm—Broad Learning System,but also optimizing the imbalanced data by randomly labeling samples.Rigorous cross-validation and independent test indicate that the success rate of i Succ Lys-BLS for positive samples is overwhelmingly higher than its counterparts.展开更多
Bioorthogonal cleavage and ligation reactions together form one more integrated system about the repertoire of bioorthogonal chemistry,capacitating an array of thrilling new biological applications.The bond-cleavage t...Bioorthogonal cleavage and ligation reactions together form one more integrated system about the repertoire of bioorthogonal chemistry,capacitating an array of thrilling new biological applications.The bond-cleavage type and position of biomolecular remain a great challenge,which determines the metabolic pathway of the targets in living systems.Herein we designed two linkages of methylene and carbonyl group attached the N-3 position of the 5-ethynyl-2’-deoxyuridine(EdU)base or the oxygen atom at deoxyribose 3’position to a photocaging group,which would be cleaved by irradiation with 365 nm ultraviolet light.EdU derivatives linked by methylene at the N-3 position had better photodecage efficiency and stability in the absence of light.This paper provides a strategy for studying the nucleoside metabolic pathways in cells,which can easily and conveniently evaluate the effect of the position and type of the linkages.The developed strategy affords a reference for controlling spatial and temporal metabolism of small-molecule drugs,allowing direct manipulation of intact cells under physiological conditions.展开更多
A kind of packet labeling algorithm for autonomous system is introduced. The fairness of the algorithm for each traffic stream in the integrated-services is analyzed. It is shown that the rate of each stream in the in...A kind of packet labeling algorithm for autonomous system is introduced. The fairness of the algorithm for each traffic stream in the integrated-services is analyzed. It is shown that the rate of each stream in the integrated-services would converge to a stable value if the transmittfing or forwarding rates converge to that of the receiving exponentially.展开更多
On the basis of inner-system labeling signaling used in the integrated access system,a kind of inner-system labeling algorithm is introduced in this paper, and the fairness of the algorithm for each traffic stream in ...On the basis of inner-system labeling signaling used in the integrated access system,a kind of inner-system labeling algorithm is introduced in this paper, and the fairness of the algorithm for each traffic stream in the integrated-services is analyzed. The base of this algorithm is Class of Services (CoS), and each packet entering the relative independent area (an autonomous system) would be labeled according to the service type or Quality of Service (QoS) in demand,and be scheduled and managed within the system (the system can be enlarged if conforming to the same protocol). The experimental results show that each of the stream rate in the integratedservices would converge to a stable value if the rates of transmitting converge to that of the receiving exponentially, that is, the effective traffic of each stream would be fair.展开更多
Buildings represent a significant share of the world’s energy consumption,and the sector has drawn the attention of governments,which have adopted policies to reduce energy expenditure.The Certifications of Energy Ef...Buildings represent a significant share of the world’s energy consumption,and the sector has drawn the attention of governments,which have adopted policies to reduce energy expenditure.The Certifications of Energy Efficiency in Buildings stand out as one possible solution to achieve this goal,employed in several countries worldwide.The European Union presents advanced energy assessment programs for buildings,being a reference and model for several other regulations in the world.The Energy Certification System for Buildings(SCE)of Portugal is considered a success case,reflected in the significant number of energy certificates issued.The Brazilian Labeling Program for Building(PBE Edifica),first launched in 2009,does not find a broad application today in the Brazilian scenario.This work shows a synthesis of the European Energy Performance of Buildings Directive(EPBD)and the Brazilian and Portuguese regulations’history.A qualitative comparison is made between the SCE and the PBE Edifica to verify a European and a developing country’s regulations with a certain degree of cultural and climatic similarities.Through this comparison,proposals are made for improvements to Brazilian certification,seeking to improve its energy planning and energy policy concerning its building stock.The suggestions for improvement presented may also be appropriate for other developing countries that have started and have not yet successfully implemented their energy certification programs in buildings.展开更多
Intelligent fault diagnosis technology plays an indispensable role in ensuring the safety,stability,and efficiency of railway operations.However,existing studies have the following limitations.1)They are typical black-...Intelligent fault diagnosis technology plays an indispensable role in ensuring the safety,stability,and efficiency of railway operations.However,existing studies have the following limitations.1)They are typical black-box models that lacks interpretability as well as they fuse features by simply stacking them,overlooking the discrepancies in the importance of different features,which reduces the credibility and diagnosis accuracy of the models.2)They ignore the effects of potentially mistaken labels in the training datasets disrupting the ability of the models to learn the true data distribution,which degrades the generalization performance of intelligent diagnosis models,especially when the training samples are limited.To address the above items,an interpretable few-shot framework for fault diagnosis with noisy labels is proposed for train transmission systems.In the proposed framework,a feature extractor is constructed by stacked frequency band focus modules,which can capture signal features in different frequency bands and further adaptively concentrate on the features corresponding to the potential fault characteristic frequency.Then,according to prototypical network,a novel metric-based classifier is developed that is tolerant to mislabeled support samples in the case of limited samples.Besides,a new loss function is designed to decrease the impact of label mistakes in query datasets.Finally,fault simulation experiments of subway train transmission systems are designed and conducted,and the effectiveness as well as superiority of the proposed method are proved by ablation experiments and comparison with the existing methods.展开更多
This paper addresses the verification of strong currentstate opacity with respect to real-time observations generated from a discrete-event system that is modeled with time labeled Petri nets. The standard current-sta...This paper addresses the verification of strong currentstate opacity with respect to real-time observations generated from a discrete-event system that is modeled with time labeled Petri nets. The standard current-state opacity cannot completely characterize higher-level security. To ensure the higher-level security requirements of a time-dependent system, we propose a strong version of opacity known as strong current-state opacity. For any path(state-event sequence with time information)π derived from a real-time observation that ends at a secret state, the strong current-state opacity of the real-time observation signifies that there is a non-secret path with the same real-time observation as π. We propose general and non-secret state class graphs, which characterize the general and non-secret states of time-dependent systems, respectively. To capture the observable behavior of non-secret states, a non-secret observer is proposed.Finally, we develop a structure called a real-time concurrent verifier to verify the strong current-state opacity of time labeled Petri nets. This approach is efficient since the real-time concurrent verifier can be constructed by solving a certain number of linear programming problems.展开更多
Implementing Outlines for the Chinese Environmental Labeling Program Byawarding certificates and labels to related manufacturers in accordance with certain environmentallabeling standards, environmental labeling, also...Implementing Outlines for the Chinese Environmental Labeling Program Byawarding certificates and labels to related manufacturers in accordance with certain environmentallabeling standards, environmental labeling, also called ''Green Label''or ''Eco-label'', certifies viagovernmental departments or public and private organizations that the whole process of producing,using, recalling and disposing of manufacturers'' products is in compliance with certainenvironmental requirements. Many countries are establishing and promoting environmental labelingplans. Environmental labeling, as an important promotion means for prevention and control ofpollution in a market-oriented manner, is being extended and developed constantly across the world.展开更多
Site-specific protein labeling plays important roles in drug discovery and illuminating biological processes at the molecular level.However,it is challenging to label proteins with high specificity while not affecting...Site-specific protein labeling plays important roles in drug discovery and illuminating biological processes at the molecular level.However,it is challenging to label proteins with high specificity while not affecting their structures and biochemical activities.Over the last few years,a variety of promising strategies have been devised that address these challenges including those that involve introduction of small-size peptide tags or unnatural amino acids(UAAs),chemical labeling of specific protein residues,and affinity-driven labeling.This review summarizes recent developments made in the area of site-specific protein labeling utilizing genetically encoding-and chemical-based methods,and discusses future issues that need to be addressed by researchers in this field.展开更多
Semantic segmentation is a core task in computer vision that allows AI models to interact and understand their surrounding environment. Similarly to how humans subconsciously segment scenes, this ability is crucial fo...Semantic segmentation is a core task in computer vision that allows AI models to interact and understand their surrounding environment. Similarly to how humans subconsciously segment scenes, this ability is crucial for scene understanding. However, a challenge many semantic learning models face is the lack of data. Existing video datasets are limited to short, low-resolution videos that are not representative of real-world examples. Thus, one of our key contributions is a customized semantic segmentation version of the Walking Tours Dataset that features hour-long, high-resolution, real-world data from tours of different cities. Additionally, we evaluate the performance of open-vocabulary, semantic model OpenSeeD on our own custom dataset and discuss future implications.展开更多
In 2012, Ponraj et al. defined a concept of k-product cordial labeling as follows: Let f be a map from V(G)to { 0,1,⋯,k−1 }where k is an integer, 1≤k≤| V(G) |. For each edge uvassign the label f(u)f(v)(modk). f is c...In 2012, Ponraj et al. defined a concept of k-product cordial labeling as follows: Let f be a map from V(G)to { 0,1,⋯,k−1 }where k is an integer, 1≤k≤| V(G) |. For each edge uvassign the label f(u)f(v)(modk). f is called a k-product cordial labeling if | vf(i)−vf(j) |≤1, and | ef(i)−ef(j) |≤1, i,j∈{ 0,1,⋯,k−1 }, where vf(x)and ef(x)denote the number of vertices and edges respectively labeled with x (x=0,1,⋯,k−1). Motivated by this concept, we further studied and established that several families of graphs admit k-product cordial labeling. In this paper, we show that the path graphs Pnadmit k-product cordial labeling.展开更多
The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their bin...The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of 125I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically 125I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).展开更多
Nanoclays have large specific surface area,good adsorption properties,and biocompatibility that have great potential for drug delivery applications[1].Evaluating the in vivo metabolic pathways of nanoclays can help to...Nanoclays have large specific surface area,good adsorption properties,and biocompatibility that have great potential for drug delivery applications[1].Evaluating the in vivo metabolic pathways of nanoclays can help to understand their pharmacodynamic sites and the toxicological effects caused by their in vivo retention time[2].展开更多
Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(R...Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(Reiter and Leroux,2017;Wallmeier et al.,2020).To date,over 180 ciliopathy-associated genes have been identified(Reiter and Leroux,2017),yet the underlying mechanisms remain poorly understood.展开更多
Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxi...Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxidative damage and microvascular permeability in ALI.Accurate detection of ONOO^(−)would facilitate early diagnosis and intervention in ALI.Near-infrared fluorescence(NIRF)probes offer new solutions due to their sensitivity,depth of tissue penetration,and imaging capabilities.However,the developed ONOO^(−)fluorescent probes face problems such as interference from other reactive oxygen species and easy intracellular diffusion.To address these issues,we introduced an innovative self-immobilizing NIRF probe,DCI2F-OTf,which was capable of monitoring ONOO^(−)in vitro and in vivo.Importantly,leveraging the high reactivity of the methylene quinone(QM)intermediate,DCI2F-OTf was able to covalently label proteins in the presence of ONOO^(−),enabling in situ imaging.In mice models of ALI,DCI2F-OTf enabled real-time imaging of ONOO^(−)levels and found that ONOO^(−)was tightly correlated with the progression of ALI.Our findings demonstrated that DCI2F-OTf was a promising chemical tool for the detection of ONOO^(−),which could help to gain insight into the pathogenesis of ALI and monitor treatment efficacy.展开更多
Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy.However,the lack of diagnostic accuracy of traditional clinical serum biomarkers carcinoembryonic antigen(CEA)and cancer antigen 19-9(CA19-9)results in ...Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy.However,the lack of diagnostic accuracy of traditional clinical serum biomarkers carcinoembryonic antigen(CEA)and cancer antigen 19-9(CA19-9)results in patients being diagnosed at an advanced stage.Herein,we developed a novel method of ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)for relative quantification based on the non-specific enzyme pronase E and an isotope mass spectrometry(MS)probe 3-benzoyl/(benzoyl-2,3,4,5,6-d5)-2-oxothiazolidine-4-carboxylic acid(d0/d5-BOTC)to screen novel glycan biomarkers.We applied the method in a cohort of 102 serum samples(including 51 healthy volunteers(HV),26 stage II CRC,and 25 stage III CRC)and 90 tissue samples(including 45 paracancerous tissue and 45 cancerous tissue).Results revealed that the serum levels of H5N4F,H5N4F3SA,H4N5F1SA,and H5N4SA2 in CRC patients were significantly different from those in HV(P<0.01).The area under the curve values of H5N4F,H5N4F3SA,and H4N5F1SA in serum samples were 0.77,0.71,and 0.91,respectively.The clinical diagnostic accuracies of these glycans ranged from 65%to 91%,which were significantly higher than those of CEA.Additionally,differential glycan profiles in tissues were further examined using the same method and compared with serum levels.H5N4F was found to be significantly down-regulated in all CRC groups(P<0.0001),indicating strong specificity for CRC diagnosis.The glycans identified in this study are expected to serve as potential biomarkers for the early diagnosis of CRC,offering valuable reference points for clinical diagnosis and treatment.展开更多
基金supported by the National Natural Science Foundation of China (No.22007008)the LiaoNing Revitalization Talents Program (No.XLYC1907021)the Fundamental Research Funds for the Central Universities (Nos.DUT23YG120,DUT19RC(3)009)。
文摘The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.
基金National Natural Science Foundation of China,No.32271148(to JW)the National Key Research and the Development Program of China,No.2023M740625(to ML)+1 种基金the Natural Science Foundation of Guangdong Province,Nos.2021B1515120050(to HW)and 2023A1515110782(to ML)and Key R&D Program of Ningxia Hui Autonomous Region,No.2024BEG02027(to JW).
文摘Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exhibit substantial regional heterogeneity and display variable responses to different neurological diseases.Such diversity in astrocyte morphology and function is essential for understanding both normal brain function and the underlying mechanisms of neurological disorders.To investigate this heterogeneity,we developed a novel method for the selective and sparse labeling of astrocytes in various brain regions.This technique utilizes a dual adeno-associated virus system that allows for the expression of Cre recombinase and enhanced green fluorescent protein under the control of the glial fibrillary acidic protein(GfaABC1D)promoter.The system was tested in C57BL/6J mice and successfully labeled astrocytes across multiple brain regions.The method enabled the detailed visualization of individual astrocytes-including their intricate peripheral processes-through three-dimensional reconstructions from confocal microscopy images.Furthermore,the labeling efficiency of this dual adeno-associated virus technology was validated by examining astrocyte function in a spared nerve injury model and through chemogenetic modulation.This innovative approach holds great promise for future research because it enables a more comprehensive understanding of astrocyte variation not only in spared nerve injury but also in a broad spectrum of neurological diseases.The ability to selectively label and study astrocytes in different brain regions provides a powerful tool for exploring the complexities of these essential cells and their roles in physiological and pathological conditions.
基金support from the National Key R&D Program of China(2023YFA0913902)the National Natural Science Foundation of China(32088101,22074140,and 22474136)the Dalian Institute of Chemical Physics,Chinese Academy of Sciences(DICP-I202316).
文摘Golgi apparatus(GA)-associated secretome runs through the endomembrane system and is critical for inter-and intracellular communication networks.However,achieving in situ dissection of the GA-associated secretome remains challenging owing to the scarcity of specific labeling methods.This work develops an aggregation-induced emission(AIE)luminogen-mediated photocatalytic proximity labeling strategy that allows profiling of the GA-associated secretome with high spatiotemporal precision.Leveraging an AIE luminogen-derived GA-targeting photocatalyst,this strategy achieves efficient labeling of proteins in minutes within the Golgi lumen upon light activation,which enables spatiotemporally resolved modification of histidine and tyrosine residues.We succeed in profiling secretome in both living HeLa cells and hard-to-transfect macrophage HMC3 cells,and a significant subset of GA-associated secretome with 80%specificity is determined,linking the distinct GA-associated secretory profiles to cellular characteristics.The method is further applied to proteome mapping of brain and bone metastatic lung cancer cells,which reveals the underlying roles the GA-associated secretome plays in extracellular matrix organization during metastasis.This work delivers a robust tool to break the dilemma of chemical labeling of GA-associated secretome in living cells,and provides mechanistic insights into secretion regulation at the subcellular level.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-3-016)the Key Projects of the National Science and Technology Pillar Program(No.2011BAI07B08)
文摘Objective: Xueteng-related herbs include Spatholobi Caulis(Jixueteng in Chinese), Sargentodoxae Caulis(Daxueteng in Chinese), Kadsurae Caulis(Dianjixueteng in Chinese), and other medicinal plant stems that release reddish-brown juices after being cut. However, similarity in phonetic spelling and sound leads to their misuse in clinic or commercial circulation. Accurate labeling is imperative as well as effective for species identification.Methods: In this study, the ITS2 sequences of 76 samples of Xueteng-related herbs were obtained and analyzed to identify them. And then they were converted into QR codes using the open source PHP QR code. Also, a DNA barcode reference library was established according to these sequences and was used to authenticate the 25 samples of Xueteng-related herbs collected from the market.Results: The lengths of the ITS2 sequences of different Xueteng-related herbs ranged from 207 to 235 bp and the GC contents were 57.5%-71.0%. Jixueteng, Daxueteng, and Dianjixueteng were clustered into three clades respectively in the neighbor-joining(NJ) phylogenetic tree, and the efficiency of the BLAST method was 100%. The ITS2 sequences of different Xueteng-related herbs were presented vividly and specifically in QR code. Twenty-two of all 25 commercial samples were consistent with the original labels, whereas three samples marked "Dianjixueteng" were authenticated as "Jixueteng".Conclusion: QR code labeling system based on DNA barcode is an effective labeling system of Xuetengrelated herbs for their circulation regulation.
基金the National Natural Science Foundation of China(61761023,31760315)the Natural Science Foundation of Jiangxi Province,China(20202BABL202004,20202BAB202007)the Scientific Research Plan of the Department of Education of Jiangxi Province(GJJ190695)。
文摘As one important type of post-translational modifications(PTMs),protein lysine succinylation regulates many important biological processes.It is also closely involved with some major diseases in the aspects of Cardiometabolic,liver metabolic,nervous system and so on.Therefore,it is imperative to predict the succinylation sites in proteins for both basic research and drug development.In this paper,a novel predictor called i Succ Lys-BLS was proposed by not only introducing a new machine learning algorithm—Broad Learning System,but also optimizing the imbalanced data by randomly labeling samples.Rigorous cross-validation and independent test indicate that the success rate of i Succ Lys-BLS for positive samples is overwhelmingly higher than its counterparts.
基金supported by the National Natural Science Foundation of China(Nos.21432008,91753201 and 21721005)the large-scale instrument and equipment sharing foundation of Wuhan University。
文摘Bioorthogonal cleavage and ligation reactions together form one more integrated system about the repertoire of bioorthogonal chemistry,capacitating an array of thrilling new biological applications.The bond-cleavage type and position of biomolecular remain a great challenge,which determines the metabolic pathway of the targets in living systems.Herein we designed two linkages of methylene and carbonyl group attached the N-3 position of the 5-ethynyl-2’-deoxyuridine(EdU)base or the oxygen atom at deoxyribose 3’position to a photocaging group,which would be cleaved by irradiation with 365 nm ultraviolet light.EdU derivatives linked by methylene at the N-3 position had better photodecage efficiency and stability in the absence of light.This paper provides a strategy for studying the nucleoside metabolic pathways in cells,which can easily and conveniently evaluate the effect of the position and type of the linkages.The developed strategy affords a reference for controlling spatial and temporal metabolism of small-molecule drugs,allowing direct manipulation of intact cells under physiological conditions.
文摘A kind of packet labeling algorithm for autonomous system is introduced. The fairness of the algorithm for each traffic stream in the integrated-services is analyzed. It is shown that the rate of each stream in the integrated-services would converge to a stable value if the transmittfing or forwarding rates converge to that of the receiving exponentially.
文摘On the basis of inner-system labeling signaling used in the integrated access system,a kind of inner-system labeling algorithm is introduced in this paper, and the fairness of the algorithm for each traffic stream in the integrated-services is analyzed. The base of this algorithm is Class of Services (CoS), and each packet entering the relative independent area (an autonomous system) would be labeled according to the service type or Quality of Service (QoS) in demand,and be scheduled and managed within the system (the system can be enlarged if conforming to the same protocol). The experimental results show that each of the stream rate in the integratedservices would converge to a stable value if the rates of transmitting converge to that of the receiving exponentially, that is, the effective traffic of each stream would be fair.
文摘Buildings represent a significant share of the world’s energy consumption,and the sector has drawn the attention of governments,which have adopted policies to reduce energy expenditure.The Certifications of Energy Efficiency in Buildings stand out as one possible solution to achieve this goal,employed in several countries worldwide.The European Union presents advanced energy assessment programs for buildings,being a reference and model for several other regulations in the world.The Energy Certification System for Buildings(SCE)of Portugal is considered a success case,reflected in the significant number of energy certificates issued.The Brazilian Labeling Program for Building(PBE Edifica),first launched in 2009,does not find a broad application today in the Brazilian scenario.This work shows a synthesis of the European Energy Performance of Buildings Directive(EPBD)and the Brazilian and Portuguese regulations’history.A qualitative comparison is made between the SCE and the PBE Edifica to verify a European and a developing country’s regulations with a certain degree of cultural and climatic similarities.Through this comparison,proposals are made for improvements to Brazilian certification,seeking to improve its energy planning and energy policy concerning its building stock.The suggestions for improvement presented may also be appropriate for other developing countries that have started and have not yet successfully implemented their energy certification programs in buildings.
基金supported in part by the National Key R&D Program of China under Grant 2022YFB4300601in part by the State Key Laboratory of Advanced Rail Autonomous Operation under Grant RAO2023ZZ003.
文摘Intelligent fault diagnosis technology plays an indispensable role in ensuring the safety,stability,and efficiency of railway operations.However,existing studies have the following limitations.1)They are typical black-box models that lacks interpretability as well as they fuse features by simply stacking them,overlooking the discrepancies in the importance of different features,which reduces the credibility and diagnosis accuracy of the models.2)They ignore the effects of potentially mistaken labels in the training datasets disrupting the ability of the models to learn the true data distribution,which degrades the generalization performance of intelligent diagnosis models,especially when the training samples are limited.To address the above items,an interpretable few-shot framework for fault diagnosis with noisy labels is proposed for train transmission systems.In the proposed framework,a feature extractor is constructed by stacked frequency band focus modules,which can capture signal features in different frequency bands and further adaptively concentrate on the features corresponding to the potential fault characteristic frequency.Then,according to prototypical network,a novel metric-based classifier is developed that is tolerant to mislabeled support samples in the case of limited samples.Besides,a new loss function is designed to decrease the impact of label mistakes in query datasets.Finally,fault simulation experiments of subway train transmission systems are designed and conducted,and the effectiveness as well as superiority of the proposed method are proved by ablation experiments and comparison with the existing methods.
基金supported by the Special Fund for Scientific and Technological Innovation Strategy of Guangdong Province(2022A0505030025)the Science and Technology Fund,FDCT,Macao SAR(0064/2021/A2)
文摘This paper addresses the verification of strong currentstate opacity with respect to real-time observations generated from a discrete-event system that is modeled with time labeled Petri nets. The standard current-state opacity cannot completely characterize higher-level security. To ensure the higher-level security requirements of a time-dependent system, we propose a strong version of opacity known as strong current-state opacity. For any path(state-event sequence with time information)π derived from a real-time observation that ends at a secret state, the strong current-state opacity of the real-time observation signifies that there is a non-secret path with the same real-time observation as π. We propose general and non-secret state class graphs, which characterize the general and non-secret states of time-dependent systems, respectively. To capture the observable behavior of non-secret states, a non-secret observer is proposed.Finally, we develop a structure called a real-time concurrent verifier to verify the strong current-state opacity of time labeled Petri nets. This approach is efficient since the real-time concurrent verifier can be constructed by solving a certain number of linear programming problems.
文摘Implementing Outlines for the Chinese Environmental Labeling Program Byawarding certificates and labels to related manufacturers in accordance with certain environmentallabeling standards, environmental labeling, also called ''Green Label''or ''Eco-label'', certifies viagovernmental departments or public and private organizations that the whole process of producing,using, recalling and disposing of manufacturers'' products is in compliance with certainenvironmental requirements. Many countries are establishing and promoting environmental labelingplans. Environmental labeling, as an important promotion means for prevention and control ofpollution in a market-oriented manner, is being extended and developed constantly across the world.
基金supported by the National Key R&D Program of China(No.2021YFC2103600)the National Natural Science Foundation of China(Nos.22278224,22478191)+1 种基金the Project of Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the State Key Laboratory of Materials Oriented Chemical Engineering(No.KL21-08)。
文摘Site-specific protein labeling plays important roles in drug discovery and illuminating biological processes at the molecular level.However,it is challenging to label proteins with high specificity while not affecting their structures and biochemical activities.Over the last few years,a variety of promising strategies have been devised that address these challenges including those that involve introduction of small-size peptide tags or unnatural amino acids(UAAs),chemical labeling of specific protein residues,and affinity-driven labeling.This review summarizes recent developments made in the area of site-specific protein labeling utilizing genetically encoding-and chemical-based methods,and discusses future issues that need to be addressed by researchers in this field.
文摘Semantic segmentation is a core task in computer vision that allows AI models to interact and understand their surrounding environment. Similarly to how humans subconsciously segment scenes, this ability is crucial for scene understanding. However, a challenge many semantic learning models face is the lack of data. Existing video datasets are limited to short, low-resolution videos that are not representative of real-world examples. Thus, one of our key contributions is a customized semantic segmentation version of the Walking Tours Dataset that features hour-long, high-resolution, real-world data from tours of different cities. Additionally, we evaluate the performance of open-vocabulary, semantic model OpenSeeD on our own custom dataset and discuss future implications.
文摘In 2012, Ponraj et al. defined a concept of k-product cordial labeling as follows: Let f be a map from V(G)to { 0,1,⋯,k−1 }where k is an integer, 1≤k≤| V(G) |. For each edge uvassign the label f(u)f(v)(modk). f is called a k-product cordial labeling if | vf(i)−vf(j) |≤1, and | ef(i)−ef(j) |≤1, i,j∈{ 0,1,⋯,k−1 }, where vf(x)and ef(x)denote the number of vertices and edges respectively labeled with x (x=0,1,⋯,k−1). Motivated by this concept, we further studied and established that several families of graphs admit k-product cordial labeling. In this paper, we show that the path graphs Pnadmit k-product cordial labeling.
基金Institutional support was provided by the project of the Czech Academy of Sciences,Czech Republic(to the Institute of Organic Chemistry and Biochemistry)(Project No.:RVO 61388963)This work was supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases(Programme EXCELES)funded by the European Union's Next Generation EU(Project No.:LX22NPO5104)the Czech Science Foundation,Czech Republic(Grant No.:23-05805S).
文摘The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of 125I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically 125I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).
基金supported by National Key Research and Development Program of China(Grant No.:2023YFF0716000)National Natural Science Foundation of China(Grant No.:82071965)+1 种基金Major plan of Jointly Constructed Project by the Science and Technology Department of the State Administration of Traditional Chinese Medicine and the Zhejiang Provincial Administration of Traditional Chinese Medicine,China(Grant No.:GZY-ZJ-KJ-24025)Zhejiang Provincial Natural Science Foundation of China(Grant No.:LQ23H180005).
文摘Nanoclays have large specific surface area,good adsorption properties,and biocompatibility that have great potential for drug delivery applications[1].Evaluating the in vivo metabolic pathways of nanoclays can help to understand their pharmacodynamic sites and the toxicological effects caused by their in vivo retention time[2].
基金supported by grants from the National Key Research and Development Program of China(2019YFA0802704)the National Natural Science Foundation of China(31771620)+2 种基金the Natural Science Foundation of Chongqing,China(CSTB2022NSCQMSX1424)Research Startup Fund of Southwest University(SWU117064)Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention&Henan Key Laboratory of Population Defects Prevention(ZD202302)。
文摘Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(Reiter and Leroux,2017;Wallmeier et al.,2020).To date,over 180 ciliopathy-associated genes have been identified(Reiter and Leroux,2017),yet the underlying mechanisms remain poorly understood.
基金supported by the National Natural Science Foundation of China(Nos.22264013,21961010)Hainan Province Science and Technology Special Fund(Nos.ZDYF2021SHFZ219,ZDYF2022SHFZ037)+4 种基金Special Funds of S&T Cooperation and Exchange Projects of Shanxi Province(No.202204041101040)Natural Science Research Talent Project of Hainan Medical University(No.JBGS202101)Postgraduate Innovative Research Project of Hainan(No.Qhys2021-384)Hainan Province Clinical Medical Center(2021)Project for Functional Materials and Molecular Imaging Science Innovation Group of Hainan Medical University.
文摘Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxidative damage and microvascular permeability in ALI.Accurate detection of ONOO^(−)would facilitate early diagnosis and intervention in ALI.Near-infrared fluorescence(NIRF)probes offer new solutions due to their sensitivity,depth of tissue penetration,and imaging capabilities.However,the developed ONOO^(−)fluorescent probes face problems such as interference from other reactive oxygen species and easy intracellular diffusion.To address these issues,we introduced an innovative self-immobilizing NIRF probe,DCI2F-OTf,which was capable of monitoring ONOO^(−)in vitro and in vivo.Importantly,leveraging the high reactivity of the methylene quinone(QM)intermediate,DCI2F-OTf was able to covalently label proteins in the presence of ONOO^(−),enabling in situ imaging.In mice models of ALI,DCI2F-OTf enabled real-time imaging of ONOO^(−)levels and found that ONOO^(−)was tightly correlated with the progression of ALI.Our findings demonstrated that DCI2F-OTf was a promising chemical tool for the detection of ONOO^(−),which could help to gain insight into the pathogenesis of ALI and monitor treatment efficacy.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82173782 and 32160234)the Science and Technology Development Project of Jilin Province of China(Project Nos.:20240602103RC,YDZJ202301ZYTS340,and YDZJ202201ZYTS596).
文摘Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy.However,the lack of diagnostic accuracy of traditional clinical serum biomarkers carcinoembryonic antigen(CEA)and cancer antigen 19-9(CA19-9)results in patients being diagnosed at an advanced stage.Herein,we developed a novel method of ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)for relative quantification based on the non-specific enzyme pronase E and an isotope mass spectrometry(MS)probe 3-benzoyl/(benzoyl-2,3,4,5,6-d5)-2-oxothiazolidine-4-carboxylic acid(d0/d5-BOTC)to screen novel glycan biomarkers.We applied the method in a cohort of 102 serum samples(including 51 healthy volunteers(HV),26 stage II CRC,and 25 stage III CRC)and 90 tissue samples(including 45 paracancerous tissue and 45 cancerous tissue).Results revealed that the serum levels of H5N4F,H5N4F3SA,H4N5F1SA,and H5N4SA2 in CRC patients were significantly different from those in HV(P<0.01).The area under the curve values of H5N4F,H5N4F3SA,and H4N5F1SA in serum samples were 0.77,0.71,and 0.91,respectively.The clinical diagnostic accuracies of these glycans ranged from 65%to 91%,which were significantly higher than those of CEA.Additionally,differential glycan profiles in tissues were further examined using the same method and compared with serum levels.H5N4F was found to be significantly down-regulated in all CRC groups(P<0.0001),indicating strong specificity for CRC diagnosis.The glycans identified in this study are expected to serve as potential biomarkers for the early diagnosis of CRC,offering valuable reference points for clinical diagnosis and treatment.
