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
Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown rem...Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.展开更多
This paper addresses the diagnosability analysis problem under external malicious attacks of a networked discrete event system modeled by labeled Petri net.In particular,we focus on a stealthy replacement attack to al...This paper addresses the diagnosability analysis problem under external malicious attacks of a networked discrete event system modeled by labeled Petri net.In particular,we focus on a stealthy replacement attack to alter or corrupt the observation of the system,in which the transition labels are replaced by others or empty string,and its attack stealthiness requires that the corrupted observations should be contained in the behavior of system.The aim of this work is,from an attacker viewpoint,to design a stealthy replacement attack for violating the diagnosability of system.To this end,we first build a new structure,called complete unfolded verifier,with the notion of a predefined elementary unsound path that leads to the violation of diagnosability,which is used to enumerate all the potential attacked paths to be transformed into elementary unsound ones.Then an optimal attack synthesis problem in terms of minimum energy cost is formulated by determining whether an elementary unsound path is generated via solving a set of integer nonlinear programming problems.Finally,we show that the nonlinear programming problems can be transformed into integer linear programming problems by introducing additional linear constraints.Examples are used to illustrate the proposed attack strategy.展开更多
TP-5 and Thy(1, synthesized by solid phase synthesis, have the effect to restrain the formation of superoxide anion in xanthine oxidase system in vitro. The formations of lipid peroxide in several organs (such as live...TP-5 and Thy(1, synthesized by solid phase synthesis, have the effect to restrain the formation of superoxide anion in xanthine oxidase system in vitro. The formations of lipid peroxide in several organs (such as liver, brain and thymus) of the mice treated with TP-5, TP-5(R, active fragment of Thy(1 and active fragment of Thy(1(R of 10 (g(kg(d-1 for 10 d were decreased. That means these peptides possess the capability of antioxidezation.展开更多
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
The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid ...The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid syntheses of aromatic scaffolds that contains deuterium remain an important yet elusive task.State-of-the-art approaches mainly relied on the transition metal-catalyzed C-H deuteration via the assistance of directing groups(DGs),which often suffered from over-deuteration and lengthy step counts required for installation and/or removal of DG.Herein,we report a generalizable synthetic linchpin strategy for the facile preparation of the ortho-deuterated aromatic core.Through capture of aryne-derived 1,3-zwitterion with heavy water,we synthesized an array of ortho-deuterated aryl sulfonium salts.These novel linchpins not only participated the transition metal catalyzed cross-coupling reaction as nucleophiles,but also served as aryl radical reservoirs under photochemical or electrochemical conditions,enabling facile and precise access to structurally diverse deuterated aromatics.Moreover,we have disclosed a novel EDA complex enabled direct arylation of phosphines under visible-light irradiation,further expanding the utility of our platform approach.展开更多
Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.S...Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.Standard classification methods fail to address these dual challenges,limiting their real-world performance.In this paper,a novel,three-phase training framework is proposed that learns a robust ordinal classifier directly from noisy labels.The approach synergistically combines a rank-based ordinal regression backbone with a cooperative,semi-supervised learning strategy to dynamically partition the data into clean and noisy subsets.A hybrid training objective is then employed,applying a supervised ordinal loss to the clean set.The noisy set is simultaneously trained using a dualobjective that combines a semi-supervised ordinal loss with a parallel,label-agnostic contrastive loss.This design allows themodel to learn fromthe entire noisy subset while using contrastive learning to mitigate the risk of error propagation frompotentially corrupt supervision.Extensive experiments on a new,large-scale,multi-site clinical dataset validate our approach.Themethod achieves state-of-the-art performance with 80.71%accuracy and a 76.86%F1-score,significantly outperforming existing approaches,including a 2.26%improvement over the strongest baseline method.This work provides not only a robust solution for a practical medical imaging problem but also a generalizable framework for other tasks plagued by noisy ordinal labels.展开更多
The coil-to-globule transition of thermally sensitive linear poly（N-isopropylacrylamide） （PNIPAM） labeled with dansyl group is induced by 1.54 μm laser pulses （widths10 ns）. The dansyl group is used to follow t...The coil-to-globule transition of thermally sensitive linear poly（N-isopropylacrylamide） （PNIPAM） labeled with dansyl group is induced by 1.54 μm laser pulses （widths10 ns）. The dansyl group is used to follow the transition kinetics because its fluorescence intensity is very sensitive to its micro-environment. As the molar ratio of NIPAM monomer to dansyl group increases from 110 to 300, the effect of covalently attached dansyl fluorophores on the transition decreases. In agreement with our previous study in which we used 8-anilino- l-naphthalensulfonic acid ammonium salt free in water as a fluorescent probe, the current study reveals that the transition has two distinct stages with two characteristic times, namely, Tfast≈0.1 ms, which can be attributed to the nucleation and formation of some ＂pearls＂ （locally contracting segments） on the chain, and tslow≈0.5 ms, which is related to the merging and coarsening of the ＂pearls＂.Tfast is independent of the PNIPAM chain length over a wide range （Mw=2.8× 10^6-4.2 × 10^7 g/mol）. On the other hand, Tslow only slightly increases with the chain length.展开更多
It is difficult to build accurate model for measurement noise covariance in complex backgrounds. For the scenarios of unknown sensor noise variances, an adaptive multi-target tracking algorithm based on labeled random...It is difficult to build accurate model for measurement noise covariance in complex backgrounds. For the scenarios of unknown sensor noise variances, an adaptive multi-target tracking algorithm based on labeled random finite set and variational Bayesian （VB） approximation is proposed. The variational approximation technique is introduced to the labeled multi-Bernoulli （LMB） filter to jointly estimate the states of targets and sensor noise variances. Simulation results show that the proposed method can give unbiased estimation of cardinality and has better performance than the VB probability hypothesis density （VB-PHD） filter and the VB cardinality balanced multi-target multi-Bernoulli （VB-CBMeMBer） filter in harsh situations. The simulations also confirm the robustness of the proposed method against the time-varying noise variances. The computational complexity of proposed method is higher than the VB-PHD and VB-CBMeMBer in extreme cases, while the mean execution times of the three methods are close when targets are well separated.展开更多
Objective To explore the migration of transplanted neural stem cells co-labeled with superparamagnetic iron oxide （SPIO） and bromodeoxyuridine （Brdu） using the 4.7T MR system and to study the cell differentiation ...Objective To explore the migration of transplanted neural stem cells co-labeled with superparamagnetic iron oxide （SPIO） and bromodeoxyuridine （Brdu） using the 4.7T MR system and to study the cell differentiation with immuno-histochemical method in ischemic rats. Methods Rat neural stem cells （NSCs） co-labelled with SPIO mediated by poly-L-lysine and bromodeoxyuridine （BrdU） were transplanted into the unaffected side of rat brain with middle cerebral artery occlusion （MCAO）. At weeks 1, 2, 3, 4, 5, and 6 after MCAO, migration of the labelled cells was monitored by MRI. At week 6 the rats were killed and their brain tissue was cut according to the migration site of transplanted ceils indicated by MRI and subjected to Prussian blue staining and immunohistochemical staining to observe the migration and differentiation of the transplanted NSCs. Results Three weeks after transplantation, the linear hypointensity area derived from the migration of labelled NSCs was observed by MRI in the corpus callosum adjacent to the injection site. Six weeks after the transplantation, the linear hypointensity area was moved toward the midline along the corpus callosum. MRI findings were confirmed by Prussian blue staining and immunohistochemical staining of the specimen at week 6 after the transplantation. Flourescence co-labelled immunohistochemical methods demonstrated that the transplanted NSCs could differentiate into astrocytes and neurons. Conclusion MRI can monitor the migration of SPIO-labelled NSCs after transplantation in a dynamical and non-invasive manner. NSCs transplanted into ischemic rats can differentiate into astrocytes and neurons during the process of migration.展开更多
Leguminous crops play a vital role in enhancing crop yield and improving soil fertility. Therefore, it can be used as an organic N source for improving soil fertility. The purpose of this study was to(i) quantify the ...Leguminous crops play a vital role in enhancing crop yield and improving soil fertility. Therefore, it can be used as an organic N source for improving soil fertility. The purpose of this study was to(i) quantify the amounts of N derived from rhizodeposition, root and above-ground biomass of peanut residue in comparison with wheat and(ii) estimate the effect of the residual N on the wheat-growing season in the subsequent year. The plants of peanut and wheat were stem fed with 15 N urea using the cotton-wick method at the Wuqiao Station of China Agricultural University in 2014. The experiment consisted of four residue-returning strategies in a randomized complete-block design:(i) no return of crop residue(CR0);(ii) return of above-ground biomass of peanut crop(CR1);(iii) return of peanut root biomass(CR2); and(iv) return of all residue of the whole peanut plant(CR3). The 31.5 and 21% of the labeled 15 N isotope were accumulated in the above-ground tissues(leaves and stems) of peanuts and wheat, respectively. N rhizodeposition of peanuts and wheat accounted for 14.91 and 3.61% of the BG15 N, respectively. The 15 N from the below-ground 15 N-labeled of peanuts were supplied 11.3, 5.9, 13.5, and 6.1% of in the CR0, CR1, CR2, and CR3 treatments, respectively. Peanut straw contributes a significant proportion of N to the soil through the decomposition of plant residues and N rhizodeposition. With the current production level on the NCP, it is estimated that peanut straw can potentially replace 104 500 tons of synthetic N fertilizer per year. The inclusion of peanut in rotation with cereal can significantly reduce the use of N fertilizer and enhance the system sustainability.展开更多
Objective Doubly labeled water （DLW） method is the gold standard for measuring total energy expenditure （TEE）. We used this method to measure TEE in Chinese young men. Methods Sixteen healthy young men age 23±...Objective Doubly labeled water （DLW） method is the gold standard for measuring total energy expenditure （TEE）. We used this method to measure TEE in Chinese young men. Methods Sixteen healthy young men age 23±1 recruited. TEE was measured by the DLW method, by indirect calorimetry. We also conducted 24-h estimate energy requirements of the subjects. years with body mass index 22.0±1.4 kg/m2 were and basal energy expenditure （BEE） was determined activity, energy balance and factorial approach to Results TEE of subjects by DLW method was 9.45±0.57 M J/day （2258±180 kcal/day）. The 24-h activity was 10.80±0.33 M J/day （2582±136 kcal/day）. The energy requirement, derived from energy balance observations, was 9.93±1.32 M J/day （2373±315 kcal/day）. The BEE of 6.65±0.28 M J/day （1589±67 kcal/day）, calculated by the adjusted Schofield equation, was significantly higher （P〈O.O01） than that measured by indirect calorimetry, 5.99-±0.66 M J/day （1433-±158 kcal/day）. The TEE derived from the factorial approach was 10.31-±0.43 M J/day （2463±104 kcal/day）. Conclusion The TEE of Chinese young men measured by the DLW method was about 10% lower than the current recommended nutrient intake （RNI）, suggesting that the RNI for Chinese men maybe overestimated. Further studies are warranted to determine the value of the estimated energy requirement.展开更多
AIM To determine whether Hb3 and its fragment F(ab')2 have practical value in radioimmunoimaging of colorectal cancer.METHODS Intact Hb3 was purified by hydroxylapatite chromatography. The fragment F(ab')2 was...AIM To determine whether Hb3 and its fragment F(ab')2 have practical value in radioimmunoimaging of colorectal cancer.METHODS Intact Hb3 was purified by hydroxylapatite chromatography. The fragment F(ab')2 was prepared by cold digestion and purified as intact Hb3. Hb3 and its fragment F(ab')2 were labeled with 99mTc by direct labeling method using SnCl2 as reducing agent. The radioactive doses ranged from 15 to 40 mCi. The imaging was accomplished by single photon emission computered tomograph (SPECT) with imaging time ranging from 2.5 to 48 hours. In this study, 10 patients were selected. Among them, 7 were administered with intact Hb3, and 3 with F(ab')2 fragment. All the patients were diagnosed as having colorectal adenocarcinoma.RESULTS After purification, intact Hb3 and its fragment F(ab')2 were fit for radioimmunoimaging. The percentage of labeling of 99mTc to Hb3 or F(ab')2 was 80.6%-91.5%. Among the 10 patients, 3 of 7 patients administered with intact Hb3 had positive scans, the other 4 had negative scans, and 2 of 3 patients administered with F(ab')2 had positive scans, the other 1 had negative scans.CONCLUSION The results showed that both intact Hb3 and its F(ab')2 have some practical value in radioimmunoimaging of colorectal cancer, and the effects of imaging with F(ab')2 was better than that with intact Hb3.展开更多
Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correl...Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,^(68)Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer ^(68)Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.展开更多
A rapid and sensitive fluorescence labeling method was developed and validated for the microanalysis of a sulfated polysaccharide drug,namely propylene glycol alginate sodium sulfate(PSS), in rat plasma. Fluorescein i...A rapid and sensitive fluorescence labeling method was developed and validated for the microanalysis of a sulfated polysaccharide drug,namely propylene glycol alginate sodium sulfate(PSS), in rat plasma. Fluorescein isothiocyanate(FITC) was selected to label PSS, and 1, 6-diaminohexane was used to link PSS and FITC in order to prepare FITC-labeled PSS(F-PSS) through a reductive amination reaction. F-PSS was identified by UV-Vis, FT-IR and 1H-NMR spectrum. The cell stability and cytotoxicity of F-PSS were tested in Madin-Darby canine kidney(MDCK) cells. The results indicated that the labeling efficiency of F-PSS was 0.522% ± 0.0248% and the absolute bioavailability was 8.39%. F-PSS was stable in MDCK cells without obvious cytotoxicity. The method was sensitive and reliable; it showed a good linearity, precision, recovery and stability. The FITC labeling method can be applied to investigating the absorption and metabolism of PSS and other polysaccharides in biological samples.展开更多
Direct labeling of virus particles is a powerful tool for the visualization of virus–cell interaction events. However, this technique involves the chemical modification of viral proteins that affects viral biological...Direct labeling of virus particles is a powerful tool for the visualization of virus–cell interaction events. However, this technique involves the chemical modification of viral proteins that affects viral biological properties. Here we describe an alternative approach of influenza virus labeling that utilizes Function-Spacer-Lipid(FSL) constructs that can be gently inserted into the virus membrane. We assessed whether labeling with fluorescent(fluo-Ad-DOPE) or biotin-labeled(biot-CMG2-DOPE) probes has any deleterious effect on influenza virus hemagglutinin(HA) receptor specificity, neuraminidase(NA) activity, or replicative ability in vitro. Our data clearly show that neither construct significantly affected influenza virus infectivity or viral affinity to sialyl receptors. Neither construct influenced the NA activities of the influenza viruses tested, except the A/Puerto Rico/8/34(H1N1) strain. Our data indicate that lipid labeling provides a powerful tool to analyze influenza virus infection in vitro.展开更多
The accuracy of laser-induced breakdown spectroscopy(LIBS) quantitative method is greatly dependent on the amount of certified standard samples used for training. However, in practical applications, only limited stand...The accuracy of laser-induced breakdown spectroscopy(LIBS) quantitative method is greatly dependent on the amount of certified standard samples used for training. However, in practical applications, only limited standard samples with labeled certified concentrations are available. A novel semi-supervised LIBS quantitative analysis method is proposed, based on co-training regression model with selection of effective unlabeled samples. The main idea of the proposed method is to obtain better regression performance by adding effective unlabeled samples in semisupervised learning. First, effective unlabeled samples are selected according to the testing samples by Euclidean metric. Two original regression models based on least squares support vector machine with different parameters are trained by the labeled samples separately, and then the effective unlabeled samples predicted by the two models are used to enlarge the training dataset based on labeling confidence estimation. The final predictions of the proposed method on the testing samples will be determined by weighted combinations of the predictions of two updated regression models. Chromium concentration analysis experiments of 23 certified standard high-alloy steel samples were carried out, in which 5 samples with labeled concentrations and 11 unlabeled samples were used to train the regression models and the remaining 7 samples were used for testing. With the numbers of effective unlabeled samples increasing, the root mean square error of the proposed method went down from 1.80% to 0.84% and the relative prediction error was reduced from 9.15% to 4.04%.展开更多
In the field of medical images,pixel-level labels are time-consuming and expensive to acquire,while image-level labels are relatively easier to obtain.Therefore,it makes sense to learn more information(knowledge)from ...In the field of medical images,pixel-level labels are time-consuming and expensive to acquire,while image-level labels are relatively easier to obtain.Therefore,it makes sense to learn more information(knowledge)from a small number of hard-to-get pixel-level annotated images to apply to different tasks to maximize their usefulness and save time and training costs.In this paper,using Pixel-Level Labeled Images forMulti-Task Learning(PLDMLT),we focus on grading the severity of fundus images for Diabetic Retinopathy(DR).This is because,for the segmentation task,there is a finely labeled mask,while the severity grading task is without classification labels.To this end,we propose a two-stage multi-label learning weakly supervised algorithm,which generates initial classification pseudo labels in the first stage and visualizes heat maps at all levels of severity using Grad-Cam to further provide medical interpretability for the classification task.A multitask model framework with U-net as the baseline is proposed in the second stage.A label update network is designed to alleviate the gradient balance between the classification and segmentation tasks.Extensive experimental results show that our PLDMLTmethod significantly outperforms other stateof-the-art methods in DR segmentation on two public datasets,achieving up to 98.897%segmentation accuracy.In addition,our method achieves comparable competitiveness with single-task fully supervised learning in the DR severity grading task.展开更多
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.
基金supported by the grants provided by Zhuhai People's Hospital,China(Grant No.:2021KYQD-03)the National Natural Science Foundation of China(Grant No.:22176016).
文摘Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.
基金supported in part by the IN2CCAM Project that had received funding from the European Union’s Horizon Europe research and Innovation Programme(101076791).
文摘This paper addresses the diagnosability analysis problem under external malicious attacks of a networked discrete event system modeled by labeled Petri net.In particular,we focus on a stealthy replacement attack to alter or corrupt the observation of the system,in which the transition labels are replaced by others or empty string,and its attack stealthiness requires that the corrupted observations should be contained in the behavior of system.The aim of this work is,from an attacker viewpoint,to design a stealthy replacement attack for violating the diagnosability of system.To this end,we first build a new structure,called complete unfolded verifier,with the notion of a predefined elementary unsound path that leads to the violation of diagnosability,which is used to enumerate all the potential attacked paths to be transformed into elementary unsound ones.Then an optimal attack synthesis problem in terms of minimum energy cost is formulated by determining whether an elementary unsound path is generated via solving a set of integer nonlinear programming problems.Finally,we show that the nonlinear programming problems can be transformed into integer linear programming problems by introducing additional linear constraints.Examples are used to illustrate the proposed attack strategy.
文摘TP-5 and Thy(1, synthesized by solid phase synthesis, have the effect to restrain the formation of superoxide anion in xanthine oxidase system in vitro. The formations of lipid peroxide in several organs (such as liver, brain and thymus) of the mice treated with TP-5, TP-5(R, active fragment of Thy(1 and active fragment of Thy(1(R of 10 (g(kg(d-1 for 10 d were decreased. That means these peptides possess the capability of antioxidezation.
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supported by the National Natural Science Foundation of China (Nos.22271010 and 21702013)。
文摘The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid syntheses of aromatic scaffolds that contains deuterium remain an important yet elusive task.State-of-the-art approaches mainly relied on the transition metal-catalyzed C-H deuteration via the assistance of directing groups(DGs),which often suffered from over-deuteration and lengthy step counts required for installation and/or removal of DG.Herein,we report a generalizable synthetic linchpin strategy for the facile preparation of the ortho-deuterated aromatic core.Through capture of aryne-derived 1,3-zwitterion with heavy water,we synthesized an array of ortho-deuterated aryl sulfonium salts.These novel linchpins not only participated the transition metal catalyzed cross-coupling reaction as nucleophiles,but also served as aryl radical reservoirs under photochemical or electrochemical conditions,enabling facile and precise access to structurally diverse deuterated aromatics.Moreover,we have disclosed a novel EDA complex enabled direct arylation of phosphines under visible-light irradiation,further expanding the utility of our platform approach.
文摘Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.Standard classification methods fail to address these dual challenges,limiting their real-world performance.In this paper,a novel,three-phase training framework is proposed that learns a robust ordinal classifier directly from noisy labels.The approach synergistically combines a rank-based ordinal regression backbone with a cooperative,semi-supervised learning strategy to dynamically partition the data into clean and noisy subsets.A hybrid training objective is then employed,applying a supervised ordinal loss to the clean set.The noisy set is simultaneously trained using a dualobjective that combines a semi-supervised ordinal loss with a parallel,label-agnostic contrastive loss.This design allows themodel to learn fromthe entire noisy subset while using contrastive learning to mitigate the risk of error propagation frompotentially corrupt supervision.Extensive experiments on a new,large-scale,multi-site clinical dataset validate our approach.Themethod achieves state-of-the-art performance with 80.71%accuracy and a 76.86%F1-score,significantly outperforming existing approaches,including a 2.26%improvement over the strongest baseline method.This work provides not only a robust solution for a practical medical imaging problem but also a generalizable framework for other tasks plagued by noisy ordinal labels.
文摘The coil-to-globule transition of thermally sensitive linear poly（N-isopropylacrylamide） （PNIPAM） labeled with dansyl group is induced by 1.54 μm laser pulses （widths10 ns）. The dansyl group is used to follow the transition kinetics because its fluorescence intensity is very sensitive to its micro-environment. As the molar ratio of NIPAM monomer to dansyl group increases from 110 to 300, the effect of covalently attached dansyl fluorophores on the transition decreases. In agreement with our previous study in which we used 8-anilino- l-naphthalensulfonic acid ammonium salt free in water as a fluorescent probe, the current study reveals that the transition has two distinct stages with two characteristic times, namely, Tfast≈0.1 ms, which can be attributed to the nucleation and formation of some ＂pearls＂ （locally contracting segments） on the chain, and tslow≈0.5 ms, which is related to the merging and coarsening of the ＂pearls＂.Tfast is independent of the PNIPAM chain length over a wide range （Mw=2.8× 10^6-4.2 × 10^7 g/mol）. On the other hand, Tslow only slightly increases with the chain length.
基金supported by the National High Technology Research and Development Program of China (No.2014AA7014061)the National Natural Science Foundation of China (No.61501484)
文摘It is difficult to build accurate model for measurement noise covariance in complex backgrounds. For the scenarios of unknown sensor noise variances, an adaptive multi-target tracking algorithm based on labeled random finite set and variational Bayesian （VB） approximation is proposed. The variational approximation technique is introduced to the labeled multi-Bernoulli （LMB） filter to jointly estimate the states of targets and sensor noise variances. Simulation results show that the proposed method can give unbiased estimation of cardinality and has better performance than the VB probability hypothesis density （VB-PHD） filter and the VB cardinality balanced multi-target multi-Bernoulli （VB-CBMeMBer） filter in harsh situations. The simulations also confirm the robustness of the proposed method against the time-varying noise variances. The computational complexity of proposed method is higher than the VB-PHD and VB-CBMeMBer in extreme cases, while the mean execution times of the three methods are close when targets are well separated.
基金the National Natural Science Foundation of China, No. 30300093, 30570628, 30770751
文摘Objective To explore the migration of transplanted neural stem cells co-labeled with superparamagnetic iron oxide （SPIO） and bromodeoxyuridine （Brdu） using the 4.7T MR system and to study the cell differentiation with immuno-histochemical method in ischemic rats. Methods Rat neural stem cells （NSCs） co-labelled with SPIO mediated by poly-L-lysine and bromodeoxyuridine （BrdU） were transplanted into the unaffected side of rat brain with middle cerebral artery occlusion （MCAO）. At weeks 1, 2, 3, 4, 5, and 6 after MCAO, migration of the labelled cells was monitored by MRI. At week 6 the rats were killed and their brain tissue was cut according to the migration site of transplanted ceils indicated by MRI and subjected to Prussian blue staining and immunohistochemical staining to observe the migration and differentiation of the transplanted NSCs. Results Three weeks after transplantation, the linear hypointensity area derived from the migration of labelled NSCs was observed by MRI in the corpus callosum adjacent to the injection site. Six weeks after the transplantation, the linear hypointensity area was moved toward the midline along the corpus callosum. MRI findings were confirmed by Prussian blue staining and immunohistochemical staining of the specimen at week 6 after the transplantation. Flourescence co-labelled immunohistochemical methods demonstrated that the transplanted NSCs could differentiate into astrocytes and neurons. Conclusion MRI can monitor the migration of SPIO-labelled NSCs after transplantation in a dynamical and non-invasive manner. NSCs transplanted into ischemic rats can differentiate into astrocytes and neurons during the process of migration.
基金supported by the National Natural Science Foundation of China(31671640)the Special Fund for Agro-scientific Research in the Public Interest,China(201503121-11)the National Key Research and Development Program of China(2016YFD0300205-01)
文摘Leguminous crops play a vital role in enhancing crop yield and improving soil fertility. Therefore, it can be used as an organic N source for improving soil fertility. The purpose of this study was to(i) quantify the amounts of N derived from rhizodeposition, root and above-ground biomass of peanut residue in comparison with wheat and(ii) estimate the effect of the residual N on the wheat-growing season in the subsequent year. The plants of peanut and wheat were stem fed with 15 N urea using the cotton-wick method at the Wuqiao Station of China Agricultural University in 2014. The experiment consisted of four residue-returning strategies in a randomized complete-block design:(i) no return of crop residue(CR0);(ii) return of above-ground biomass of peanut crop(CR1);(iii) return of peanut root biomass(CR2); and(iv) return of all residue of the whole peanut plant(CR3). The 31.5 and 21% of the labeled 15 N isotope were accumulated in the above-ground tissues(leaves and stems) of peanuts and wheat, respectively. N rhizodeposition of peanuts and wheat accounted for 14.91 and 3.61% of the BG15 N, respectively. The 15 N from the below-ground 15 N-labeled of peanuts were supplied 11.3, 5.9, 13.5, and 6.1% of in the CR0, CR1, CR2, and CR3 treatments, respectively. Peanut straw contributes a significant proportion of N to the soil through the decomposition of plant residues and N rhizodeposition. With the current production level on the NCP, it is estimated that peanut straw can potentially replace 104 500 tons of synthetic N fertilizer per year. The inclusion of peanut in rotation with cereal can significantly reduce the use of N fertilizer and enhance the system sustainability.
基金supported by the projects of National Natural Science Foundation of China (No.30771811)the National Technology Research and Development Program in the Eleventh Five-Year Plan of China(No.2008BAI58B01)
文摘Objective Doubly labeled water （DLW） method is the gold standard for measuring total energy expenditure （TEE）. We used this method to measure TEE in Chinese young men. Methods Sixteen healthy young men age 23±1 recruited. TEE was measured by the DLW method, by indirect calorimetry. We also conducted 24-h estimate energy requirements of the subjects. years with body mass index 22.0±1.4 kg/m2 were and basal energy expenditure （BEE） was determined activity, energy balance and factorial approach to Results TEE of subjects by DLW method was 9.45±0.57 M J/day （2258±180 kcal/day）. The 24-h activity was 10.80±0.33 M J/day （2582±136 kcal/day）. The energy requirement, derived from energy balance observations, was 9.93±1.32 M J/day （2373±315 kcal/day）. The BEE of 6.65±0.28 M J/day （1589±67 kcal/day）, calculated by the adjusted Schofield equation, was significantly higher （P〈O.O01） than that measured by indirect calorimetry, 5.99-±0.66 M J/day （1433-±158 kcal/day）. The TEE derived from the factorial approach was 10.31-±0.43 M J/day （2463±104 kcal/day）. Conclusion The TEE of Chinese young men measured by the DLW method was about 10% lower than the current recommended nutrient intake （RNI）, suggesting that the RNI for Chinese men maybe overestimated. Further studies are warranted to determine the value of the estimated energy requirement.
文摘AIM To determine whether Hb3 and its fragment F(ab')2 have practical value in radioimmunoimaging of colorectal cancer.METHODS Intact Hb3 was purified by hydroxylapatite chromatography. The fragment F(ab')2 was prepared by cold digestion and purified as intact Hb3. Hb3 and its fragment F(ab')2 were labeled with 99mTc by direct labeling method using SnCl2 as reducing agent. The radioactive doses ranged from 15 to 40 mCi. The imaging was accomplished by single photon emission computered tomograph (SPECT) with imaging time ranging from 2.5 to 48 hours. In this study, 10 patients were selected. Among them, 7 were administered with intact Hb3, and 3 with F(ab')2 fragment. All the patients were diagnosed as having colorectal adenocarcinoma.RESULTS After purification, intact Hb3 and its fragment F(ab')2 were fit for radioimmunoimaging. The percentage of labeling of 99mTc to Hb3 or F(ab')2 was 80.6%-91.5%. Among the 10 patients, 3 of 7 patients administered with intact Hb3 had positive scans, the other 4 had negative scans, and 2 of 3 patients administered with F(ab')2 had positive scans, the other 1 had negative scans.CONCLUSION The results showed that both intact Hb3 and its F(ab')2 have some practical value in radioimmunoimaging of colorectal cancer, and the effects of imaging with F(ab')2 was better than that with intact Hb3.
基金support from the National Natural Science Foundation of China(Grant No.:22076069)the Natural Science Foundation of Jiangsu Province(Grant No.:BK20201135)+1 种基金the Major Scientific Research Project of Jiangsu Commission of Health(Grant No.:ZDA2020007)the Science Technology and Development Project of Wuxi(Grant No.:Y20212013).
文摘Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,^(68)Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer ^(68)Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
基金supported in part by programs of Qingdao Science and Technology Project (11-2-3-73-jh)Shandong Science and Technology Project (2011GSF 11815)Special Fund for Marine Scientific Research in the Public Interest (201005024)
文摘A rapid and sensitive fluorescence labeling method was developed and validated for the microanalysis of a sulfated polysaccharide drug,namely propylene glycol alginate sodium sulfate(PSS), in rat plasma. Fluorescein isothiocyanate(FITC) was selected to label PSS, and 1, 6-diaminohexane was used to link PSS and FITC in order to prepare FITC-labeled PSS(F-PSS) through a reductive amination reaction. F-PSS was identified by UV-Vis, FT-IR and 1H-NMR spectrum. The cell stability and cytotoxicity of F-PSS were tested in Madin-Darby canine kidney(MDCK) cells. The results indicated that the labeling efficiency of F-PSS was 0.522% ± 0.0248% and the absolute bioavailability was 8.39%. F-PSS was stable in MDCK cells without obvious cytotoxicity. The method was sensitive and reliable; it showed a good linearity, precision, recovery and stability. The FITC labeling method can be applied to investigating the absorption and metabolism of PSS and other polysaccharides in biological samples.
基金partially(NVB) supported by RAS Presidium Grant "Molecular and Cell Biology"
文摘Direct labeling of virus particles is a powerful tool for the visualization of virus–cell interaction events. However, this technique involves the chemical modification of viral proteins that affects viral biological properties. Here we describe an alternative approach of influenza virus labeling that utilizes Function-Spacer-Lipid(FSL) constructs that can be gently inserted into the virus membrane. We assessed whether labeling with fluorescent(fluo-Ad-DOPE) or biotin-labeled(biot-CMG2-DOPE) probes has any deleterious effect on influenza virus hemagglutinin(HA) receptor specificity, neuraminidase(NA) activity, or replicative ability in vitro. Our data clearly show that neither construct significantly affected influenza virus infectivity or viral affinity to sialyl receptors. Neither construct influenced the NA activities of the influenza viruses tested, except the A/Puerto Rico/8/34(H1N1) strain. Our data indicate that lipid labeling provides a powerful tool to analyze influenza virus infection in vitro.
基金supported by National Natural Science Foundation of China (No. 51674032)
文摘The accuracy of laser-induced breakdown spectroscopy(LIBS) quantitative method is greatly dependent on the amount of certified standard samples used for training. However, in practical applications, only limited standard samples with labeled certified concentrations are available. A novel semi-supervised LIBS quantitative analysis method is proposed, based on co-training regression model with selection of effective unlabeled samples. The main idea of the proposed method is to obtain better regression performance by adding effective unlabeled samples in semisupervised learning. First, effective unlabeled samples are selected according to the testing samples by Euclidean metric. Two original regression models based on least squares support vector machine with different parameters are trained by the labeled samples separately, and then the effective unlabeled samples predicted by the two models are used to enlarge the training dataset based on labeling confidence estimation. The final predictions of the proposed method on the testing samples will be determined by weighted combinations of the predictions of two updated regression models. Chromium concentration analysis experiments of 23 certified standard high-alloy steel samples were carried out, in which 5 samples with labeled concentrations and 11 unlabeled samples were used to train the regression models and the remaining 7 samples were used for testing. With the numbers of effective unlabeled samples increasing, the root mean square error of the proposed method went down from 1.80% to 0.84% and the relative prediction error was reduced from 9.15% to 4.04%.
文摘In the field of medical images,pixel-level labels are time-consuming and expensive to acquire,while image-level labels are relatively easier to obtain.Therefore,it makes sense to learn more information(knowledge)from a small number of hard-to-get pixel-level annotated images to apply to different tasks to maximize their usefulness and save time and training costs.In this paper,using Pixel-Level Labeled Images forMulti-Task Learning(PLDMLT),we focus on grading the severity of fundus images for Diabetic Retinopathy(DR).This is because,for the segmentation task,there is a finely labeled mask,while the severity grading task is without classification labels.To this end,we propose a two-stage multi-label learning weakly supervised algorithm,which generates initial classification pseudo labels in the first stage and visualizes heat maps at all levels of severity using Grad-Cam to further provide medical interpretability for the classification task.A multitask model framework with U-net as the baseline is proposed in the second stage.A label update network is designed to alleviate the gradient balance between the classification and segmentation tasks.Extensive experimental results show that our PLDMLTmethod significantly outperforms other stateof-the-art methods in DR segmentation on two public datasets,achieving up to 98.897%segmentation accuracy.In addition,our method achieves comparable competitiveness with single-task fully supervised learning in the DR severity grading task.
