5-Bromo-2'-deoxyuridine labeling:historical perspectives,factors infiuencing the detection,toxicity,and its implications in the neurogenesis

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.

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

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.

A review of ^(17)O isotopic labeling techniques for solid-state NMR structural studies of metal oxides in lithium-ion batteries

Recent advances in utilizing ^(17)O isotopic labeling methods for solid-state nuclear magnetic resonance(NMR)investigations of metal oxides for lithium-ion batteries have yielded extensive insights into their structural and dynamic details.Herein,we commence with a brief introduction to recent research on lithium-ion battery oxide materials studied using ^(17)O solid-state NMR spectroscopy.Then we delve into a review of ^(17)O isotopic labeling methods for tagging oxygen sites in both the bulk and surfaces of metal oxides.At last,the unresolved problems and the future research directions for advancing the ^(17)O labeling technique are discussed.

Impaired implicit emotion regulation in patients with panic disorder:An event-related potential study on affect labeling

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.

Challenges with non-descriptive compliance labeling of end-stage renal disease patients in accessibility for renal transplantation

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.

Cerebral perfusion in patients with unilateral internal carotid artery occlusion by dual post-labeling delays arterial spin labeling imaging

BACKGROUND Global and regional cerebral blood flow(CBF)changes in patients with unilateral internal carotid artery occlusion(ICAO)are unclear when the dual post-labeling delays(PLD)arterial spin labeling(ASL)magnetic resonance imaging(MRI)technique is used.Manual delineation of regions of interest for CBF measurement is time-consuming and laborious.AIM To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique.METHODS Twenty hospitalized patients with ICAO and sex-and age-matched controls were included in the study.Regional CBF was measured by Dr.Brain's ASL software.The present study evaluated differences in global,middle cerebral artery(MCA)territory,anterior cerebral artery territory,and Alberta Stroke Program Early Computed Tomography Score(ASPECTS)regions(including the caudate nucleus,lentiform nucleus,insula ribbon,internal capsule,and M1-M6)and brain lobes(including frontal,parietal,temporal,and insular lobes)between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s.RESULTS When comparing CBF between ICAO patients and controls,the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s;the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s,and it was lower in 9 brain regions at PLD 2.5 s;the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s.The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s.The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions,whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions.The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s,and in M6 at PLD 2.5 s.CONCLUSION Unilateral ICAO results in hypoperfusion in the global and MCA territories,especially in the ASPECTS area.Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.

A rabies virus-based toolkit for efficient retrograde labeling and monosynaptic tracing

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.

TurboID Proximity Labeling of a Protocadherin Protein to Characterize Interacting Protein Complex

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.

Automated File Labeling for Heterogeneous Files Organization Using Machine Learning

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.

A Steganography Based on Optimal Multi-Threshold Block Labeling

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.

PartLabeling:A label management framework in 3D space

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.

Key Review Points on Cosmetic Labeling and Relevant Cases

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.

基于Yolov5的交通信号灯智能识别程序开发

交通信号检测是智能汽车识别交通环境的一项重要辅助技术,现有的算法能够解决单一交叉口环境下的信号检测问题,但需要在十字路口的复杂交通环境中提高算法的精度和干扰可靠性。文章以one-stage目标检测算法Yolov5的应用为研究基础,实现多场景下的交通信号灯自动检测与识别,使用Labeling进行图片标注,通过镜像、裁剪、反转、等运行增强数据集,不断地调参实验与迭代模型训练,目标检测精度达到80%。

近红外无创血糖浓度的Label Sensitivity算法和支持向量机回归

近红外光谱分析技术在生物医学工程领域具有广阔应用前景。无创且持续性地测量能实时监控人体血糖水平,给糖尿病患者带来极大便利性、提高生存质量、降低糖尿病并发症发生率具有很大的社会效益。无创血糖监测的想法提出较早,但仍然存在预测精度低、预测值与标签值相关性不高等难点,至今没有达到临床要求。近年来,光谱检测技术发展迅猛且机器学习技术在智能信息处理方面具有明显优势,两者结合可以有效提高人体无创血糖医学监测模型的精度和普适性。提出了一种标签敏感度算法(LS),并结合支持向量机方法建立了人体血糖含量预测模型。使用近红外光谱仪采集了4名志愿者食指处动态血液光谱数据(每名志愿者28组数据),并使用多元散射矫正(MSC)方法消除了部分光散射的影响。考虑血糖对不同波长光的吸收有差异,提出了基于血糖浓度标签差的特征波长挑选方法,并构建了标签敏感度支持向量机(LSSVR)预测模型。设计实验,对比该模型与偏最小二乘回归(PLSR)和区分度支持向量机(FSSVR)算法。结果表明,LS算法的最佳特征波长数为32,经特征波长选择后的LSSVR表现最佳,其均方误差降低至0.02 mmol·L^(-1),明显优于全谱段PLSR模型,血糖浓度的预测值与标签值的相关系数提升至99.8%,预测值全部位于可容许误差的克拉克网格A区内。LSSVR模型的优异表现为早日实现血糖的无创监测提供了新思路。

Semantic role labeling based on conditional random fields

Due to the fact that semantic role labeling （SRL） is very necessary for deep natural language processing, a method based on conditional random fields （CRFs） is proposed for the SRL task. This method takes shallow syntactic parsing as the foundation, phrases or named entities as the labeled units, and the CRFs model is trained to label the predicates＇ semantic roles in a sentence. The key of the method is parameter estimation and feature selection for the CRFs model. The L-BFGS algorithm was employed for parameter estimation, and three category features： features based on sentence constituents, features based on predicate, and predicate-constituent features as a set of features for the model were selected. Evaluation on the datasets of CoNLL-2005 SRL shared task shows that the method can obtain better performance than the maximum entropy model, and can achieve 80. 43 % precision and 63. 55 % recall for semantic role labeling.

Label Recovery and Trajectory Designable Network for Transfer Fault Diagnosis of Machines With Incorrect Annotation

The success of deep transfer learning in fault diagnosis is attributed to the collection of high-quality labeled data from the source domain.However,in engineering scenarios,achieving such high-quality label annotation is difficult and expensive.The incorrect label annotation produces two negative effects:1)the complex decision boundary of diagnosis models lowers the generalization performance on the target domain,and2)the distribution of target domain samples becomes misaligned with the false-labeled samples.To overcome these negative effects,this article proposes a solution called the label recovery and trajectory designable network(LRTDN).LRTDN consists of three parts.First,a residual network with dual classifiers is to learn features from cross-domain samples.Second,an annotation check module is constructed to generate a label anomaly indicator that could modify the abnormal labels of false-labeled samples in the source domain.With the training of relabeled samples,the complexity of diagnosis model is reduced via semi-supervised learning.Third,the adaptation trajectories are designed for sample distributions across domains.This ensures that the target domain samples are only adapted with the pure-labeled samples.The LRTDN is verified by two case studies,in which the diagnosis knowledge of bearings is transferred across different working conditions as well as different yet related machines.The results show that LRTDN offers a high diagnosis accuracy even in the presence of incorrect annotation.

Does Green Food Certification promote agri-food export quality?Evidence from China

The construction of a food certification system plays a vital role in upgrading export quality, which previous studies have largely overlooked. We match China's industry-level data of Green Food Certification with its HS6-digit export data of agri-food products to quantify the impact of Green Food Certification on export quality. We identify the significant and positive effect of Green Food Certification on export quality. The 2SLS estimation based on instrumental variables and a range of robustness checks confirm the validity and robustness of the benchmark conclusions. Further analysis discloses that Green Food Certification improves export quality by raising agricultural production efficiency and brand premiums. Heterogeneity analysis shows that the effect of Green Food Certification varies across regions, notably improving the quality of agri-food products exported to developed regions and regions with high levels of import supervision. Furthermore, among various product types, Green Food Certification significantly improves the export quality of primary products and products vulnerable to non-tariff measures. The above findings could guide the future development of agri-food quality certification systems, potentially leading to a transformation and promotion of the agri-food trade.

Folate-conjugated Fe_3O_4 nanoparticles for in vivo tumor labeling

Highly biocompatible superparamagnetic Fe3O4 nanoparticles were synthesized by amide of folic acid （FA） ligands and the NH2-group onto the surface of Fe3O4 nanoparticles. The as-synthesized folate-conjugated Fe3O4 nanoparticles were characterized by X-ray diffraction diffractometer, transmission electron microscope, FT-IR spectrometer, vibrating sample magnetometer, and dynamic light scattering instrument. The in vivo labeling effect of folate-conjugated Fe3O4 nanoparticles on the hepatoma cells was investigated in tumor-bearing rat. The results demonstrate that the as-prepared nanoparticles have cubic structure of Fe3O4 with a particle size of about 8 nm and hydrated diameter of 25.7 nm at a saturation magnetization of 51 A·m2/kg. These nanoparticles possess good physiological stability, low cytotoxicity on human skin fibroblasts and negligible effect on Wistar rats at the concentration as high as 3 mg/kg body mass. The folate-conjugated Fe3O4 nanoparticles could be effectively mediated into the human hepatoma Bel 7402 cells through the binding of folate and folic acid receptor, enhancing the signal contrast of tumor tissue and surrounding normal tissue in MRI imaging. It is in favor of the tumor cells labeling, tracing, magnetic resonance imaging （MRI） target detection and magnetic hyperthermia.

Influence of ear tags on the results of body composition analysis in mice

Background:The aim of this study was to investigate the influence of marking meth-ods on the outcomes of body composition analysis and provide guidance for the se-lection of marking methods in mouse body composition analysis.Methods:Male C57BL/6J mice aged 6 weeks were randomly assigned for pre-and post-ear tagging measurements.The body composition of the mice was measured using a small animal body composition analyzer,which provided measurements of the mass of fat,lean,and free fluid.Then,the mass of fat,lean and free fluid to body weight ratio was gained.Further data analysis was conducted to obtain the range and coeffi-cient of variation in body composition measurements for each mouse.The distribution of fat and lean tissue in the mice was also analyzed by comparing the fat-to-lean ratio.Results:(1)The mass of all body composition components in the ear tagging group was significantly lower than that in the control group.(2)There was a significant in-crease in the range and coefficient of variation of body composition measurements between the ear tagging group and the control group.(3)The fat-to-lean ratio in the ear tagging group was significantly lower than that in the control group.Conclusions:Ear tagging significantly lowered the results of body composition analy-sis in mice and higher the results of measurement error.Therefore,ear tagging should be avoided as much as possible when conducting body composition analysis experi-ments in mice.

Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight

Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.