The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immuno...The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.展开更多
Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and...Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.展开更多
BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emot...BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.展开更多
Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent...Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation.Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation.These labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ allocation.Furthermore,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of noncompliant.We argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to transplantation.For patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more drastic.Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.展开更多
Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for th...Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic inputs.Although several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination.These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.展开更多
File labeling techniques have a long history in analyzing the anthological trends in computational linguistics.The situation becomes worse in the case of files downloaded into systems from the Internet.Currently,most ...File labeling techniques have a long history in analyzing the anthological trends in computational linguistics.The situation becomes worse in the case of files downloaded into systems from the Internet.Currently,most users either have to change file names manually or leave a meaningless name of the files,which increases the time to search required files and results in redundancy and duplications of user files.Currently,no significant work is done on automated file labeling during the organization of heterogeneous user files.A few attempts have been made in topic modeling.However,one major drawback of current topic modeling approaches is better results.They rely on specific language types and domain similarity of the data.In this research,machine learning approaches have been employed to analyze and extract the information from heterogeneous corpus.A different file labeling technique has also been used to get the meaningful and`cohesive topic of the files.The results show that the proposed methodology can generate relevant and context-sensitive names for heterogeneous data files and provide additional insight into automated file labeling in operating systems.展开更多
Hiding secret data in digital images is one of the major researchfields in information security.Recently,reversible data hiding in encrypted images has attracted extensive attention due to the emergence of cloud servi...Hiding secret data in digital images is one of the major researchfields in information security.Recently,reversible data hiding in encrypted images has attracted extensive attention due to the emergence of cloud services.This paper proposes a novel reversible data hiding method in encrypted images based on an optimal multi-threshold block labeling technique(OMTBL-RDHEI).In our scheme,the content owner encrypts the cover image with block permutation,pixel permutation,and stream cipher,which preserve the in-block correlation of pixel values.After uploading to the cloud service,the data hider applies the prediction error rearrangement(PER),the optimal threshold selection(OTS),and the multi-threshold labeling(MTL)methods to obtain a compressed version of the encrypted image and embed secret data into the vacated room.The receiver can extract the secret,restore the cover image,or do both according to his/her granted authority.The proposed MTL labels blocks of the encrypted image with a list of threshold values which is optimized with OTS based on the features of the current image.Experimental results show that labeling image blocks with the optimized threshold list can efficiently enlarge the amount of vacated room and thus improve the embedding capacity of an encrypted cover image.Security level of the proposed scheme is analyzed and the embedding capacity is compared with state-of-the-art schemes.Both are concluded with satisfactory performance.展开更多
The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the de...The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the development of the neuron synapse. Hence, research on its protein interactome is key to understanding its functionality and specific properties. A newly discovered biotin ligase, TurboID, is a proximity labeler that is designed to be able to label and observe transmembrane proteins, something that previous methods struggled with. The TurboID method is verified in HEK293T cells and primary cultured mouse cortical neurons. Results have proven the validity of the TurboID method in observing PCDH9-interacting proteins.展开更多
Interpreted the latest cosmetic labeling requirements one by one from the basic principles on labels,content, positions, preceded terms and so on;analyzed the relevant cases, so as to help cosmetic manufacturers and o...Interpreted the latest cosmetic labeling requirements one by one from the basic principles on labels,content, positions, preceded terms and so on;analyzed the relevant cases, so as to help cosmetic manufacturers and operation enterprises to deeply understand the latest requirements on cosmetics labeling after the promulgation of the new regulations.展开更多
Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate d...Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate domain-specific design requirements,while at the same time satisfying aesthetic and functional principles of good design,can be a daunting task even for skilled visual designers.Presenting the annotations in 3D object space instead of projection space,allows for the preservation of spatial and depth cues.This results in stable layouts in dynamic environments,since the annotations are anchored in 3D space.Results In this paper we make two major contributions.First,we propose a technique for managing the layout and rendering of annotations in Virtual/Augmented Reality scenarios by manipulating the annotations directly in 3D space.For this,we make use of Artificial Potential Fields and use 3D geometric constraints to adapt them in 3D space.Second,we introduce PartLabeling:an open source platform in the form of a web application that acts as a much-needed generic framework allowing to easily add labeling algorithms and 3D models.This serves as a catalyst for researchers in this field to make their algorithms and implementations publicly available,as well as ensure research reproducibility.The PartLabeling framework relies on a dataset that we generate as a subset of the original PartNet dataset consisting of models suitable for the label management task.The dataset consists of 10003D models with part annotations.展开更多
To evaluate the reliability of three dimensional spiral fast spin echo pseudo-continuous arterial spin labeling(3D pc-ASL)in measuring cerebral blood flow(CBF)with different post-labeling delay time(PLD)in the resting...To evaluate the reliability of three dimensional spiral fast spin echo pseudo-continuous arterial spin labeling(3D pc-ASL)in measuring cerebral blood flow(CBF)with different post-labeling delay time(PLD)in the resting state and the right finger taping state.Methods 3D pc-ASL and three dimensional T1-weighted fast spoiled gradient recalled echo(3D T1-FSPGR)sequence were applied to eight healthy subjects twice at the same time each day for one week interval.ASL data acquisition was performed with post-labeling delay time(PLD)1.5 seconds and 2.0 seconds in the resting state and the right finger taping state respectively.CBF mapping was calculated and CBF value of both the gray matter(GM)and white matter(WM)was automatically extracted.The reliability was evaluated using the intraclass correlation coefficient(ICC)and Bland and Altman plot.Results ICC of the GM(0.84)and WM(0.92)was lower at PLD 1.5 seconds than that(GM,0.88;WM,0.94)at PLD 2.0 seconds in the resting state,and ICC of GM(0.88)was higher in the right finger taping state than that in the resting state at PLD 1.5 seconds.ICC of the GM and WM was 0.71 and 0.78 for PLD 1.5 seconds and PLD 2.0 seconds in the resting state at the first scan,and ICC of the GM and WM was 0.83 and 0.79 at the second scan,respectively.Conclusion This work demonstrated that 3D pc-ASL might be a reliable imaging technique to measure CBF over the whole brain at different PLD in the resting state or controlled state.展开更多
As a robust platform for genome editing,CRISPR/Cas9 is currently being explored for engineering biology or therapeutics,yet means for quantitative detection of Cas9 proteins remain to be fully realized.Here,we express...As a robust platform for genome editing,CRISPR/Cas9 is currently being explored for engineering biology or therapeutics,yet means for quantitative detection of Cas9 proteins remain to be fully realized.Here,we expressed Cas9 proteins and developed a novel detection method that traced Cas9 based on radiolabeled iodine.Through optimizing the reaction conditions of reaction time,temperature and cycles,we obtained ^(125)I-Cas9 of high labeling yield.The prepared ^(125)I-Cas9 was stable in various media and preserved excellent genome editing efficiency.Thus,our strategy provides a convenient and efficient tool for further tracing biological behaviors of Cas9 proteins in living systems.展开更多
A k-L(2,1)-labeling for a graph G is a function such that whenever and whenever u and v are at distance two apart. The λ-number for G, denoted by λ(G), is the minimum k over all k-L(2,1)-labelings of G. In this pape...A k-L(2,1)-labeling for a graph G is a function such that whenever and whenever u and v are at distance two apart. The λ-number for G, denoted by λ(G), is the minimum k over all k-L(2,1)-labelings of G. In this paper, we show that for or 11, which confirms Conjecture 6.1 stated in [X. Li, V. Mak-Hau, S. Zhou, The L(2,1)-labelling problem for cubic Cayley graphs on dihedral groups, J. Comb. Optim. (2013) 25: 716-736] in the case when or 11. Moreover, we show that? if 1) either (mod 6), m is odd, r = 3, or 2) (mod 3), m is even (mod 2), r = 0.展开更多
For a graph having no isolated vertex, a function is called an edge product cordial labeling of graph G, if the induced vertex labeling function defined by the product of labels of incident edges to each vertex is suc...For a graph having no isolated vertex, a function is called an edge product cordial labeling of graph G, if the induced vertex labeling function defined by the product of labels of incident edges to each vertex is such that the number of edges with label 0 and the number of edges with label 1 differ by at most 1 and the number of vertices with label 0 and the number of vertices with label 1 also differ by at most 1. In this paper, we discuss edge product cordial labeling for some cycle related graphs.展开更多
Arterial spin labeling(ASL) is a magnetic resonance imaging technique for measuring tissue perfusion using a freely diffusible intrinsic tracer.As compared with other perfusion techniques,ASL offers several advantages...Arterial spin labeling(ASL) is a magnetic resonance imaging technique for measuring tissue perfusion using a freely diffusible intrinsic tracer.As compared with other perfusion techniques,ASL offers several advantages and is now available for routine clinical practice in many institutions.Its noninvasive nature and ability to quantitatively measure tissue perfusion make ASL ideal for research and clinical studies.Recent technical advances have increased its sensitivity and also extended its potential applications.This review focuses on some basic knowledge of ASL perfusion,emerging techniques and clinical applications in neuroimaging.展开更多
Objective: To explore the correlation between the spectral computed tomography(CT) imaging parameters and the Ki-67 labeling index in lung adenocarcinoma.Methods: Spectral CT imaging parameters [iodine concentrations ...Objective: To explore the correlation between the spectral computed tomography(CT) imaging parameters and the Ki-67 labeling index in lung adenocarcinoma.Methods: Spectral CT imaging parameters [iodine concentrations of lesions(ICLs) in the arterial phase(ICLa)and venous phase(ICLv), normalized IC in the aorta(NICa/NICv), slope of the spectral HU curve(λHUa/λHUv)and monochromatic CT number enhancement on 40 keV and 70 keV images(CT40 keVa/v, CT70keVa/v)] in 34 lung adenocarcinomas were analyzed, and common molecular markers, including the Ki-67 labeling index, were detected with immunohistochemistry. Different Ki-67 labeling indexes were measured and grouped into four grades according to the number of positive-stained cells(grade 0, ≤1%;1%<grade 1≤10%;10%<grade 2≤30%;and grade 3, >30%). One-way analysis of variance(ANOVA) was used to compare the four different grades, and the Bonferroni method was used to correct the P value for multiple comparisons. A Spearman correlation analysis was performed to further research a quantitative correlation between the Ki-67 labeling index and spectral CT imaging parameters.Results: CT40keVa, CT40 keVv, CT70keVa and CT70keVv increased as the grade increased, and CT70keVa and CT70keVv were statistically significant(P<0.05). These four parameters and the Ki-67 labeling index showed a moderate positive correlation with lung adenocarcinoma nodules. ICL, NIC and λHU in the arterial and venous phases were not significantly different among the four grades.Conclusions: The spectral CT imaging parameters CT40keVa, CT40keVv, CT70keVa and CT70keVv gradually increased with Ki-67 expression and showed a moderate positive correlation with lung adenocarcinomas.Therefore, spectral CT imaging parameter-enhanced monochromatic CT numbers at 70 keV may indicate the extent of proliferation of lung adenocarcinomas.展开更多
Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological pro...Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not...BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not been fully elucidated to date.Some studies proved lower cerebral blood flow(CBF) in the hippocampus was associated with poor executive function and memory in T2DM.Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor(VEGF) expression and CBF changes in humans and animal models.In this study,we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional(3D) arterial spin labeling(3D-ASL) and VEGF expression in the hippocampus.AIM To assess the correlation between CBF(measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.METHODS Forty Sprague-Dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.RESULTS The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.CONCLUSION Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.展开更多
The limited labeled sample data in the field of advanced security threats detection seriously restricts the effective development of research work.Learning the sample labels from the labeled and unlabeled data has rec...The limited labeled sample data in the field of advanced security threats detection seriously restricts the effective development of research work.Learning the sample labels from the labeled and unlabeled data has received a lot of research attention and various universal labeling methods have been proposed.However,the labeling task of malicious communication samples targeted at advanced threats has to face the two practical challenges:the difficulty of extracting effective features in advance and the complexity of the actual sample types.To address these problems,we proposed a sample labeling method for malicious communication based on semi-supervised deep neural network.This method supports continuous learning and optimization feature representation while labeling sample,and can handle uncertain samples that are outside the concerned sample types.According to the experimental results,our proposed deep neural network can automatically learn effective feature representation,and the validity of features is close to or even higher than that of features which extracted based on expert knowledge.Furthermore,our proposed method can achieve the labeling accuracy of 97.64%~98.50%,which is more accurate than the train-then-detect,kNN and LPA methodsin any labeled-sample proportion condition.The problem of insufficient labeled samples in many network attack detecting scenarios,and our proposed work can function as a reference for the sample labeling tasks in the similar real-world scenarios.展开更多
文摘The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.
基金supported by Natural Science Foundation of Beijing Municipality(L212013)National Key Research and Development Program of China(No.2022YFA1206104)+2 种基金AI+Health Collaborative Innovation Cultivation Project(Z211100003521002)National Natural Science Foundation of China(81971718,82073786,81872809,U20A20412,81821004)Beijing Natural Science Foundation(7222020).
文摘Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.
基金Supported by The National Natural Science Foundation of China,No.81871080the Key R&D Program of Jining(Major Program),No.2023YXNS004+2 种基金the National Natural Science Foundation of China,No.81401486the Natural Science Foundation of Liaoning Province of China,No.20170540276the Medicine and Health Science Technology Development Program of Shandong Province,No.202003070713.
文摘BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.
文摘Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation.Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation.These labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ allocation.Furthermore,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of noncompliant.We argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to transplantation.For patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more drastic.Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.
基金supported by the National Natural Science Foundation of China,Nos.32100899(to KZL),31830035(to FQX),31771156(to FQX),21921004(to FQX)the National Science and Technology Innovation 2030,No.2021ZD0201003(to FQX)+2 种基金the Key-Area Research and Development Program of Guangdong Province,No.2018B030331001(to FQX)the Strategic Priority Research Program of the Chinese Academy of Sciences,No.XDB32030200(to FQX)the Shenzhen Key Laboratory of Viral Vectors for Biomedicine,No.ZDSYS20200811142401005(to FQX)。
文摘Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic inputs.Although several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination.These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.
文摘File labeling techniques have a long history in analyzing the anthological trends in computational linguistics.The situation becomes worse in the case of files downloaded into systems from the Internet.Currently,most users either have to change file names manually or leave a meaningless name of the files,which increases the time to search required files and results in redundancy and duplications of user files.Currently,no significant work is done on automated file labeling during the organization of heterogeneous user files.A few attempts have been made in topic modeling.However,one major drawback of current topic modeling approaches is better results.They rely on specific language types and domain similarity of the data.In this research,machine learning approaches have been employed to analyze and extract the information from heterogeneous corpus.A different file labeling technique has also been used to get the meaningful and`cohesive topic of the files.The results show that the proposed methodology can generate relevant and context-sensitive names for heterogeneous data files and provide additional insight into automated file labeling in operating systems.
基金the Ministry of Science and Technology of Taiwan,Grant Number MOST 110-2221-E-507-003.
文摘Hiding secret data in digital images is one of the major researchfields in information security.Recently,reversible data hiding in encrypted images has attracted extensive attention due to the emergence of cloud services.This paper proposes a novel reversible data hiding method in encrypted images based on an optimal multi-threshold block labeling technique(OMTBL-RDHEI).In our scheme,the content owner encrypts the cover image with block permutation,pixel permutation,and stream cipher,which preserve the in-block correlation of pixel values.After uploading to the cloud service,the data hider applies the prediction error rearrangement(PER),the optimal threshold selection(OTS),and the multi-threshold labeling(MTL)methods to obtain a compressed version of the encrypted image and embed secret data into the vacated room.The receiver can extract the secret,restore the cover image,or do both according to his/her granted authority.The proposed MTL labels blocks of the encrypted image with a list of threshold values which is optimized with OTS based on the features of the current image.Experimental results show that labeling image blocks with the optimized threshold list can efficiently enlarge the amount of vacated room and thus improve the embedding capacity of an encrypted cover image.Security level of the proposed scheme is analyzed and the embedding capacity is compared with state-of-the-art schemes.Both are concluded with satisfactory performance.
文摘The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the development of the neuron synapse. Hence, research on its protein interactome is key to understanding its functionality and specific properties. A newly discovered biotin ligase, TurboID, is a proximity labeler that is designed to be able to label and observe transmembrane proteins, something that previous methods struggled with. The TurboID method is verified in HEK293T cells and primary cultured mouse cortical neurons. Results have proven the validity of the TurboID method in observing PCDH9-interacting proteins.
文摘Interpreted the latest cosmetic labeling requirements one by one from the basic principles on labels,content, positions, preceded terms and so on;analyzed the relevant cases, so as to help cosmetic manufacturers and operation enterprises to deeply understand the latest requirements on cosmetics labeling after the promulgation of the new regulations.
文摘Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate domain-specific design requirements,while at the same time satisfying aesthetic and functional principles of good design,can be a daunting task even for skilled visual designers.Presenting the annotations in 3D object space instead of projection space,allows for the preservation of spatial and depth cues.This results in stable layouts in dynamic environments,since the annotations are anchored in 3D space.Results In this paper we make two major contributions.First,we propose a technique for managing the layout and rendering of annotations in Virtual/Augmented Reality scenarios by manipulating the annotations directly in 3D space.For this,we make use of Artificial Potential Fields and use 3D geometric constraints to adapt them in 3D space.Second,we introduce PartLabeling:an open source platform in the form of a web application that acts as a much-needed generic framework allowing to easily add labeling algorithms and 3D models.This serves as a catalyst for researchers in this field to make their algorithms and implementations publicly available,as well as ensure research reproducibility.The PartLabeling framework relies on a dataset that we generate as a subset of the original PartNet dataset consisting of models suitable for the label management task.The dataset consists of 10003D models with part annotations.
基金Supported by the Foundation for Medical and Health Sci&Tech Innovation Project of Sanya(2016YW37)the Special Financial Grant from China Postdoctoral Science Foundation(2014T70960)
文摘To evaluate the reliability of three dimensional spiral fast spin echo pseudo-continuous arterial spin labeling(3D pc-ASL)in measuring cerebral blood flow(CBF)with different post-labeling delay time(PLD)in the resting state and the right finger taping state.Methods 3D pc-ASL and three dimensional T1-weighted fast spoiled gradient recalled echo(3D T1-FSPGR)sequence were applied to eight healthy subjects twice at the same time each day for one week interval.ASL data acquisition was performed with post-labeling delay time(PLD)1.5 seconds and 2.0 seconds in the resting state and the right finger taping state respectively.CBF mapping was calculated and CBF value of both the gray matter(GM)and white matter(WM)was automatically extracted.The reliability was evaluated using the intraclass correlation coefficient(ICC)and Bland and Altman plot.Results ICC of the GM(0.84)and WM(0.92)was lower at PLD 1.5 seconds than that(GM,0.88;WM,0.94)at PLD 2.0 seconds in the resting state,and ICC of GM(0.88)was higher in the right finger taping state than that in the resting state at PLD 1.5 seconds.ICC of the GM and WM was 0.71 and 0.78 for PLD 1.5 seconds and PLD 2.0 seconds in the resting state at the first scan,and ICC of the GM and WM was 0.83 and 0.79 at the second scan,respectively.Conclusion This work demonstrated that 3D pc-ASL might be a reliable imaging technique to measure CBF over the whole brain at different PLD in the resting state or controlled state.
基金supported by the National Key Research and Development Program(No.2016YFA0400902)the Ministry of Science and Technology of China(Nos.2012CB825805,2012CB932600)+3 种基金the National Natural Science Foundation of China(Nos.11675251 and 11275251)Shanghai Rising-Star Program(No.14QA1404400)Distinguished Scientist Fellowship Program of King Saud Universitythe Youth Innovation Promotion Association of CAS(No.2016236)
文摘As a robust platform for genome editing,CRISPR/Cas9 is currently being explored for engineering biology or therapeutics,yet means for quantitative detection of Cas9 proteins remain to be fully realized.Here,we expressed Cas9 proteins and developed a novel detection method that traced Cas9 based on radiolabeled iodine.Through optimizing the reaction conditions of reaction time,temperature and cycles,we obtained ^(125)I-Cas9 of high labeling yield.The prepared ^(125)I-Cas9 was stable in various media and preserved excellent genome editing efficiency.Thus,our strategy provides a convenient and efficient tool for further tracing biological behaviors of Cas9 proteins in living systems.
文摘A k-L(2,1)-labeling for a graph G is a function such that whenever and whenever u and v are at distance two apart. The λ-number for G, denoted by λ(G), is the minimum k over all k-L(2,1)-labelings of G. In this paper, we show that for or 11, which confirms Conjecture 6.1 stated in [X. Li, V. Mak-Hau, S. Zhou, The L(2,1)-labelling problem for cubic Cayley graphs on dihedral groups, J. Comb. Optim. (2013) 25: 716-736] in the case when or 11. Moreover, we show that? if 1) either (mod 6), m is odd, r = 3, or 2) (mod 3), m is even (mod 2), r = 0.
文摘For a graph having no isolated vertex, a function is called an edge product cordial labeling of graph G, if the induced vertex labeling function defined by the product of labels of incident edges to each vertex is such that the number of edges with label 0 and the number of edges with label 1 differ by at most 1 and the number of vertices with label 0 and the number of vertices with label 1 also differ by at most 1. In this paper, we discuss edge product cordial labeling for some cycle related graphs.
文摘Arterial spin labeling(ASL) is a magnetic resonance imaging technique for measuring tissue perfusion using a freely diffusible intrinsic tracer.As compared with other perfusion techniques,ASL offers several advantages and is now available for routine clinical practice in many institutions.Its noninvasive nature and ability to quantitatively measure tissue perfusion make ASL ideal for research and clinical studies.Recent technical advances have increased its sensitivity and also extended its potential applications.This review focuses on some basic knowledge of ASL perfusion,emerging techniques and clinical applications in neuroimaging.
基金supported by National Natural Science Foundation of China (No. 91959116)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX 201803)+1 种基金“Beijing Hospitals Authority” Ascent Plan (No. DFL20191103)National Key R&D Program of China (No. 2017YFC1309101, 2017YFC1309104).
文摘Objective: To explore the correlation between the spectral computed tomography(CT) imaging parameters and the Ki-67 labeling index in lung adenocarcinoma.Methods: Spectral CT imaging parameters [iodine concentrations of lesions(ICLs) in the arterial phase(ICLa)and venous phase(ICLv), normalized IC in the aorta(NICa/NICv), slope of the spectral HU curve(λHUa/λHUv)and monochromatic CT number enhancement on 40 keV and 70 keV images(CT40 keVa/v, CT70keVa/v)] in 34 lung adenocarcinomas were analyzed, and common molecular markers, including the Ki-67 labeling index, were detected with immunohistochemistry. Different Ki-67 labeling indexes were measured and grouped into four grades according to the number of positive-stained cells(grade 0, ≤1%;1%<grade 1≤10%;10%<grade 2≤30%;and grade 3, >30%). One-way analysis of variance(ANOVA) was used to compare the four different grades, and the Bonferroni method was used to correct the P value for multiple comparisons. A Spearman correlation analysis was performed to further research a quantitative correlation between the Ki-67 labeling index and spectral CT imaging parameters.Results: CT40keVa, CT40 keVv, CT70keVa and CT70keVv increased as the grade increased, and CT70keVa and CT70keVv were statistically significant(P<0.05). These four parameters and the Ki-67 labeling index showed a moderate positive correlation with lung adenocarcinoma nodules. ICL, NIC and λHU in the arterial and venous phases were not significantly different among the four grades.Conclusions: The spectral CT imaging parameters CT40keVa, CT40keVv, CT70keVa and CT70keVv gradually increased with Ki-67 expression and showed a moderate positive correlation with lung adenocarcinomas.Therefore, spectral CT imaging parameter-enhanced monochromatic CT numbers at 70 keV may indicate the extent of proliferation of lung adenocarcinomas.
基金supported by the National Natural Science Foundation of China(No.314 008 55)the Technological Innovation Incubator Program from Henan University of Technology(No.201 518)the Introduced Postdoctoral Talents of Henan University of Technology(No.150 199)
文摘Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.
基金Supported by The Endocrine Clinical Medical Center of Yunnan ProvinceNo.ZX20190202+2 种基金the Fund of the Diabetic Innovation Team in Yunnan Province,No.2019HC002the Special Joint Fund from Yunnan Provincial Department of Science and Technology and Kunming Medical University,Kunming,Yunnan,China,No.2018FE001(-267)the SKY Image Research Fund,China,No. Z-2014-07-2003-12。
文摘BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not been fully elucidated to date.Some studies proved lower cerebral blood flow(CBF) in the hippocampus was associated with poor executive function and memory in T2DM.Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor(VEGF) expression and CBF changes in humans and animal models.In this study,we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional(3D) arterial spin labeling(3D-ASL) and VEGF expression in the hippocampus.AIM To assess the correlation between CBF(measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.METHODS Forty Sprague-Dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.RESULTS The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.CONCLUSION Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.
基金partially funded by the National Natural Science Foundation of China (Grant No. 61272447)National Entrepreneurship & Innovation Demonstration Base of China (Grant No. C700011)Key Research & Development Project of Sichuan Province of China (Grant No. 2018G20100)
文摘The limited labeled sample data in the field of advanced security threats detection seriously restricts the effective development of research work.Learning the sample labels from the labeled and unlabeled data has received a lot of research attention and various universal labeling methods have been proposed.However,the labeling task of malicious communication samples targeted at advanced threats has to face the two practical challenges:the difficulty of extracting effective features in advance and the complexity of the actual sample types.To address these problems,we proposed a sample labeling method for malicious communication based on semi-supervised deep neural network.This method supports continuous learning and optimization feature representation while labeling sample,and can handle uncertain samples that are outside the concerned sample types.According to the experimental results,our proposed deep neural network can automatically learn effective feature representation,and the validity of features is close to or even higher than that of features which extracted based on expert knowledge.Furthermore,our proposed method can achieve the labeling accuracy of 97.64%~98.50%,which is more accurate than the train-then-detect,kNN and LPA methodsin any labeled-sample proportion condition.The problem of insufficient labeled samples in many network attack detecting scenarios,and our proposed work can function as a reference for the sample labeling tasks in the similar real-world scenarios.
