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.

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。

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.

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.

In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides

Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)^(-/-)mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with medicinal effects.

Predicting Acute Mountain Sickness Using Regional Sea-Level Cerebral Blood Flow

Objective To investigate the role of sea-level cerebral blood flow(CBF)in predicting acute mountain sickness(AMS)using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL).Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging(MRI)including 3D-pCASL at sea level.The CBF values of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),posterior cerebral artery(PCA),and posterior inferior cerebellar artery(PICA)territories and the laterality index(LI)of CBF were compared between the AMS and non-AMS groups.Statistical analyses were performed to determine the relationship between CBF and AMS,and the predictive performance was assessed using receiver operating characteristic(ROC)curves.Results The mean cortical CBF in women(81.65±2.69 mL/100 g/min)was higher than that in men(74.35±2.12 mL/100 g/min)(P<0.05).In men,the cortical CBF values in the bilateral ACA,PCA,PICA,and right MCA were higher in patients with AMS than in those without.Cortical CBF in the right PCA best predicted AMS(AUC=0.818).In women,the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of 0.753.Conclusion Although the mechanism and prediction of AMS are quite complicated,higher cortical CBF at sea level,especially the CBF of the posterior circulatory system,may be used for prediction in male volunteers using non-invasive 3D-pCASL.

Carbon allocation in Picea jezoensis:Adaptation strategies of a non-treeline species at its upper elevation limit

Understanding the physiological adaptations of non-treeline trees to environmental stress is important to understand future shifts in species composition and distribution of current treeline ecotone.The aim of the present study was to elucidate the mechanisms of the formation of the upper elevation limit of non-treeline tree species,Picea jezoensis,and the carbon allocation strategies of the species on Changbai Mountain.We employed the^(13)C in situ pulse labeling technique to trace the distribution of photosynthetically assimilated carbon in Picea jezoensis at different elevational positions(tree species at its upper elevation limit(TSAUE,1,700 m a.s.l.)under treeline ecotone;tree species at a lower elevation position(TSALE,1,400 m a.s.l.).We analyzed^(13)C and the non-structural carbohydrate(NSC)concentrations in various tissues following labeling.Our findings revealed a significant shift in carbon allocation in TSAUE compared to TSALE.There was a pronounced increase inδ^(13)C allocation to belowground components(roots,soil,soil respiration)in TSAUE compared to TSALE.Furthermore,the C flow rate within the plant-soil-atmosphere system was faster,and the C residence time in the plant was shorter in TSAUE.The trends indicate enhanced C sink activity in belowground tissues in TSAUE,with newly assimilated C being preferentially directed there,suggesting a more conservative C allocation strategy by P.jezoensis at higher elevations under harsher environments.Such a strategy,prioritizing C storage in roots,likely aids in withstanding winter cold stress at the expense of aboveground growth during the growing season,leading to reduced growth of TSAUE compared to TSALE.The results of the present study shed light on the adaptive mechanisms governing the upper elevation limits of non-treeline trees,and enhances our understanding of how non-treeline species might respond to ongoing climate change.

Learning about good nutrition with the 5-color front-of-package label"Nutri-Score":an experimental study

The Nutri-Score is a 5-color front-of-pack nutrition label designed to provide consumers with an easily understandable guideline to the healthiness of food products.The impact that the Nutri-Score may have on consumers'choices is unclear since different experimental paradigms have found vastly different effect sizes.In the present study,we have investigated how student participants change a hypothetical personal 1-daydietary plan after a learning phase during which they learn about the Nutri-Scores of the available food items.Participants were instructed to compose a healthy diet plan in order that the question of whether the NutriScore would improve their ability to compose a healthy dietary plan could be investigated,independent of the question of whether they would apply this knowledge in their ordinary lives.We found a substantial(Cohen's d=0.86)positive impact on nutritional quality(as measured by the Nutrient Profiling System score of the Food Standards Agency)and a medium-sized(Cohen's d=0.43)reduction of energy content.Energy content reduction was larger for participants who had initially composed plans with higher energy content.The results suggest that the Nutri-Score has the potential to guide consumers to healthier food choices.It remains unclear,however,whether this potential will be reflected in real-life dietary choices.

Reliability of Three Dimentional Pseudo-continuous Arterial Spin Labeling:A Volumetric Cerebral Perfusion Imaging with Different Post-labeling Time and Functional State in Health Adults

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.