Site-specific protein labeling plays important roles in drug discovery and illuminating biological processes at the molecular level.However,it is challenging to label proteins with high specificity while not affecting...Site-specific protein labeling plays important roles in drug discovery and illuminating biological processes at the molecular level.However,it is challenging to label proteins with high specificity while not affecting their structures and biochemical activities.Over the last few years,a variety of promising strategies have been devised that address these challenges including those that involve introduction of small-size peptide tags or unnatural amino acids(UAAs),chemical labeling of specific protein residues,and affinity-driven labeling.This review summarizes recent developments made in the area of site-specific protein labeling utilizing genetically encoding-and chemical-based methods,and discusses future issues that need to be addressed by researchers in this field.展开更多
Semantic segmentation is a core task in computer vision that allows AI models to interact and understand their surrounding environment. Similarly to how humans subconsciously segment scenes, this ability is crucial fo...Semantic segmentation is a core task in computer vision that allows AI models to interact and understand their surrounding environment. Similarly to how humans subconsciously segment scenes, this ability is crucial for scene understanding. However, a challenge many semantic learning models face is the lack of data. Existing video datasets are limited to short, low-resolution videos that are not representative of real-world examples. Thus, one of our key contributions is a customized semantic segmentation version of the Walking Tours Dataset that features hour-long, high-resolution, real-world data from tours of different cities. Additionally, we evaluate the performance of open-vocabulary, semantic model OpenSeeD on our own custom dataset and discuss future implications.展开更多
In 2012, Ponraj et al. defined a concept of k-product cordial labeling as follows: Let f be a map from V(G)to { 0,1,⋯,k−1 }where k is an integer, 1≤k≤| V(G) |. For each edge uvassign the label f(u)f(v)(modk). f is c...In 2012, Ponraj et al. defined a concept of k-product cordial labeling as follows: Let f be a map from V(G)to { 0,1,⋯,k−1 }where k is an integer, 1≤k≤| V(G) |. For each edge uvassign the label f(u)f(v)(modk). f is called a k-product cordial labeling if | vf(i)−vf(j) |≤1, and | ef(i)−ef(j) |≤1, i,j∈{ 0,1,⋯,k−1 }, where vf(x)and ef(x)denote the number of vertices and edges respectively labeled with x (x=0,1,⋯,k−1). Motivated by this concept, we further studied and established that several families of graphs admit k-product cordial labeling. In this paper, we show that the path graphs Pnadmit k-product cordial labeling.展开更多
The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their bin...The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of 125I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically 125I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).展开更多
Nanoclays have large specific surface area,good adsorption properties,and biocompatibility that have great potential for drug delivery applications[1].Evaluating the in vivo metabolic pathways of nanoclays can help to...Nanoclays have large specific surface area,good adsorption properties,and biocompatibility that have great potential for drug delivery applications[1].Evaluating the in vivo metabolic pathways of nanoclays can help to understand their pharmacodynamic sites and the toxicological effects caused by their in vivo retention time[2].展开更多
Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(R...Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(Reiter and Leroux,2017;Wallmeier et al.,2020).To date,over 180 ciliopathy-associated genes have been identified(Reiter and Leroux,2017),yet the underlying mechanisms remain poorly understood.展开更多
Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxi...Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxidative damage and microvascular permeability in ALI.Accurate detection of ONOO^(−)would facilitate early diagnosis and intervention in ALI.Near-infrared fluorescence(NIRF)probes offer new solutions due to their sensitivity,depth of tissue penetration,and imaging capabilities.However,the developed ONOO^(−)fluorescent probes face problems such as interference from other reactive oxygen species and easy intracellular diffusion.To address these issues,we introduced an innovative self-immobilizing NIRF probe,DCI2F-OTf,which was capable of monitoring ONOO^(−)in vitro and in vivo.Importantly,leveraging the high reactivity of the methylene quinone(QM)intermediate,DCI2F-OTf was able to covalently label proteins in the presence of ONOO^(−),enabling in situ imaging.In mice models of ALI,DCI2F-OTf enabled real-time imaging of ONOO^(−)levels and found that ONOO^(−)was tightly correlated with the progression of ALI.Our findings demonstrated that DCI2F-OTf was a promising chemical tool for the detection of ONOO^(−),which could help to gain insight into the pathogenesis of ALI and monitor treatment efficacy.展开更多
This paper is concerned with design-ing symbol labeling for a low-density parity-check(LDPC)-coded delayed bit-interleaved coded modu-lation(DBICM)scheme in a two-way relay channel(TWRC).We first present some properti...This paper is concerned with design-ing symbol labeling for a low-density parity-check(LDPC)-coded delayed bit-interleaved coded modu-lation(DBICM)scheme in a two-way relay channel(TWRC).We first present some properties of symbol labeling within a phase shift keying(PSK)modula-tion.These properties reduce the candidate labeling search space.Based on this search space,we take DBICM capacity as the cost function and propose a general method for optimizing symbol labeling by em-ploying the differential evolution algorithm.Numeri-cal results show that our labeling obtains a signal-to-noise ratio(SNR)gain up to 0.45 dB with respect to Gray labeling.展开更多
Background:Rabies virus(RABV)-derived neuronal tracing tools are extensively applied in retrograde tracing due to their strict retrograde transsynaptic transfer property and low neurotoxicity.However,the RABV infectio...Background:Rabies virus(RABV)-derived neuronal tracing tools are extensively applied in retrograde tracing due to their strict retrograde transsynaptic transfer property and low neurotoxicity.However,the RABV infection and expression of fluorescence products would be gradually cleared while the infected neurons still survive,a phenomenon known as non-cytolytic immune clearance(NCLIC).This phenomenon introduced the risk of fluorescence loss and led to the omission of a subset of neurons that should be labeled,thereby interfering in the analysis of tracing results.Methods:To compensate for the fluorescence loss problem,in this study,we developed a novel marker footprints(MF)mouse,involving a Cre recombinase-dependent red fluorescent reporter system and systemic expression of glycoprotein(G)and ASLV-A receptor(TVA).Using this mouse model combined with the well-developed RABV-EnvA-ΔG-GFP-Cre viral tool,we developed a novel green-to-red spectral labeling strategy.Results:Neurons in the MF mouse could be co-labeled with green fluorescence from the very quick expression of the viral tool and with red fluorescence from the relatively slow expression of the neuron itself,so neurons undergoing NCLIC with green fluorescence loss could be relabeled red.Furthermore,newly infected neurons could be labeled green and other neurons could be labeled yellow due to the temporal expression difference between the two fluorescent proteins.Conclusions:This is the first polysynaptic retrograde tracing labeling strategy that could label neurons using spectral fluorescence colors with only one injection of the viral tool,enabling its application in recognizing the labeling sequence of neurons in brain regions and enhancing the spatiotemporal resolution of neuronal tracing.展开更多
Liquid-liquid phase separation(LLPS)of proteins and nucleic acids is a common phenomenon in cells that underlies the formation of membraneless organelles.Although the macroscopic behavior of biomolecular coacervates h...Liquid-liquid phase separation(LLPS)of proteins and nucleic acids is a common phenomenon in cells that underlies the formation of membraneless organelles.Although the macroscopic behavior of biomolecular coacervates has been elucidated by microscopy,the detailed dynamic properties of proteins/peptides during the LLPS process remain poorly characterized.Here,site-directed spin labeling-electron paramagnetic resonance(SDSL-EPR)spectroscopy was employed to characterize the dynamic properties of a minimal model LLPS system consisting of positively charged peptides and RNA.The degree of phase separation,indicated by broadening of the EPR spectrum of the spin-labeled peptide due to slow molecular tumbling,was monitored by EPR.In addition,three distinct populations with varying molecular motion during LLPS,featuring different spectral lineshapes,were identified.These populations included a fast motion component(Ⅰ),a slower motion component(Ⅱ)associated with peptides in the dispersed phase and an immobile component(Ⅲ)observed in the dense phase.With gradual titration of the peptides to RNA,the EPR spectrum gradually shifted,refiecting changes in the populations of the components.Together,SDSL-EPR method not only provides new insights into the dynamic behavior of biomolecules during LLPS,but also offers a sensitive method for biomolecular phase separation processes at the molecular level.展开更多
Digital twin technology is revolutionizing personalized healthcare by creating dynamic virtual replicas of individual patients.This paper presents a novel multi-modal architecture leveraging digital twins to enhance p...Digital twin technology is revolutionizing personalized healthcare by creating dynamic virtual replicas of individual patients.This paper presents a novel multi-modal architecture leveraging digital twins to enhance precision in predictive diagnostics and treatment planning of phoneme labeling.By integrating real-time images,electronic health records,and genomic information,the system enables personalized simulations for disease progression modeling,treatment response prediction,and preventive care strategies.In dysarthric speech,which is characterized by articulation imprecision,temporal misalignments,and phoneme distortions,existing models struggle to capture these irregularities.Traditional approaches,often relying solely on audio features,fail to address the full complexity of phoneme variations,leading to increased phoneme error rates(PER)and word error rates(WER).To overcome these challenges,we propose a novel multi-modal architecture that integrates both audio and articulatory data through a combination of Temporal Convolutional Networks(TCNs),Graph Convolutional Networks(GCNs),Transformer Encoders,and a cross-modal attention mechanism.The audio branch of the model utilizes TCNs and Transformer Encoders to capture both short-and long-term dependencies in the audio signal,while the articulatory branch leverages GCNs to model spatial relationships between articulators,such as the lips,jaw,and tongue,allowing the model to detect subtle articulatory imprecisions.A cross-modal attention mechanism fuses the encoded audio and articulatory features,enabling dynamic adjustment of the model’s focus depending on input quality,which significantly improves phoneme labeling accuracy.The proposed model consistently outperforms existing methods,achieving lower Phoneme Error Rates(PER),Word Error Rates(WER),and Articulatory Feature Misclassification Rates(AFMR).Specifically,across all datasets,the model achieves an average PER of 13.43%,an average WER of 21.67%,and an average AFMR of 12.73%.By capturing both the acoustic and articulatory intricacies of speech,this comprehensive approach not only improves phoneme labeling precision but also marks substantial progress in speech recognition technology for individuals with dysarthria.展开更多
Self-labeling protein (SLP) tags, such as HaloTag, have gained considerable interest as advanced tools for live cell labeling. However, the chloroalkane-based substrates that can be directly used for protein labeling ...Self-labeling protein (SLP) tags, such as HaloTag, have gained considerable interest as advanced tools for live cell labeling. However, the chloroalkane-based substrates that can be directly used for protein labeling are limited. Here, we report two bioorthogonal small molecule linkers, chloroalkane-tetrazine (CA-Tz) and chloroalkane-azide (CA-N3), which can penetrate cell membranes and facilitate click chemistry-based labeling in live cells. We compare their labeling capability using two clickable silicon rhodamine dyes (SiR-PEG_(3)-TCO and SiR-PEG_(4)-DBCO). Confocal imaging results demonstrate that using CA-Tz and SiR-PEG_(3)-TCO dye exhibits superior intracellular labeling with low nonspecific signals. We subsequently compared the photostability of SiR dyes with that of green fluorescent proteins (mEmerald). Total internal reflection fluorescence (TIRF) imaging indicates that SiR dyes exhibit superior photostability under identical excitation conditions, making them suitable for long-term cell imaging. Furthermore, SiR dyes labeling also shows high structure retention for the fourth-order super-resolution optical fluctuation imaging (SOFI) compared to fluorescent proteins. This study presents clickable HaloTag linkers as effective tools for live cell labeling and imaging, highlighting the high-quality labeling of chloroalkane linkers and clickable dyes for live cell imaging.展开更多
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 ...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.展开更多
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 n...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.展开更多
Objective To evaluate the reliability of three dimensional spiral fast spin echo pseudo-continuous arterial spin labeling(3 D pc-ASL) in measuring cerebral blood flow(CBF) with different post-labeling delay time(PLD) ...Objective To evaluate the reliability of three dimensional spiral fast spin echo pseudo-continuous arterial spin labeling(3 D 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 3 D pc-ASL and three dimensional T1-weighted fast spoiled gradient recalled echo(3 D 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 3 D 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
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
Sparse labeling of neurons contributes to uncovering their morphology, and rapid expression of a fluorescent protein reduces the experiment range. To achieve the goal of rapid and sparse labeling of neurons in vivo, w...Sparse labeling of neurons contributes to uncovering their morphology, and rapid expression of a fluorescent protein reduces the experiment range. To achieve the goal of rapid and sparse labeling of neurons in vivo, we established a rapid method for depicting the fine structure of neurons at 24 h post-infection based on a mutant viruslike particle of Semliki Forest virus. Approximately 0.014 fluorescent focus-forming units of the mutant virus-like particle transferred enhanced green fluorescent protein into neurons in vivo, and its affinity for neurons in vivo was stronger than for neurons in vitro and BHK21(baby hamster kidney) cells. Collectively, the mutant virus-likeparticle provides a robust and convenient way to reveal the fine structure of neurons and is expected to be a helper virus for combining with other tools to determine their connectivity. Our work adds a new tool to the approaches for rapid and sparse labeling of neurons in vivo.展开更多
Neural stem cells were labeled with superparamagnetic iron oxide （SPIO） and tracked by MRI in vitro and in vivo after implantation, Rat neural stem cells were labeled with SPIO combined with PLL by the means of rece...Neural stem cells were labeled with superparamagnetic iron oxide （SPIO） and tracked by MRI in vitro and in vivo after implantation, Rat neural stem cells were labeled with SPIO combined with PLL by the means of receptor-mediated endocytosis. Prussian blue staining and electron microscopy were conducted to identify the iron particles in these neural stem cells. SPIO-labeled cells were tracked by 4.7T MRI in vivo and in vitro after implantation, The subjects were divided into 5 groups, including 5× 10^5 labeled cells cultured for one day after labeling, 5 × 10^5 same phase unlabeled cells, cell culture medium with 25μg Fe/mL SPIO, cell culture medium without SPIO and distilled water. MR/scanning sequences included TIWI, T2WI and T2＊WI. R2 and R2＊ of labeled cells were calculated. The results showed： （1） Neural stem cells could be labeled with SPIO and labeling efficiency was 100%. Prussian blue staining showed numerous blue-stained iron particles in the cytoplasm; （2） The average percentage change of signal intensity of labeled cells on TIWI in 4.7T MRI was 24.06%, T2WI 50.66% and T2＊WI 53.70% respectively; （3） T2 of labeled cells and unlabeled cells in 4.7T MRI was 516 ms and 77 ms respectively, R2 was 1.94 s^-1 and 12.98 s^-1 respectively, and T2＊ was 109 ms and 22.9 ms, R2＊ was 9.17 s^-1 and 43.67 s^-1 respectively; （4） Remarkable low signal area on T2WI and T2＊WI could exist for nearly 7 weeks and then disappeared gradually in the left brain transplanted with labeled cells, however no signal change in the right brain implanted with unlabeled cells. It was concluded that neural stem cells could be labeled effectively with SPIO. R2 and R2＊ of labeled cells were increased obviously. MRI can be used to track labeled cells in vitro and in vivo.展开更多
基金supported by the National Key R&D Program of China(No.2021YFC2103600)the National Natural Science Foundation of China(Nos.22278224,22478191)+1 种基金the Project of Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the State Key Laboratory of Materials Oriented Chemical Engineering(No.KL21-08)。
文摘Site-specific protein labeling plays important roles in drug discovery and illuminating biological processes at the molecular level.However,it is challenging to label proteins with high specificity while not affecting their structures and biochemical activities.Over the last few years,a variety of promising strategies have been devised that address these challenges including those that involve introduction of small-size peptide tags or unnatural amino acids(UAAs),chemical labeling of specific protein residues,and affinity-driven labeling.This review summarizes recent developments made in the area of site-specific protein labeling utilizing genetically encoding-and chemical-based methods,and discusses future issues that need to be addressed by researchers in this field.
文摘Semantic segmentation is a core task in computer vision that allows AI models to interact and understand their surrounding environment. Similarly to how humans subconsciously segment scenes, this ability is crucial for scene understanding. However, a challenge many semantic learning models face is the lack of data. Existing video datasets are limited to short, low-resolution videos that are not representative of real-world examples. Thus, one of our key contributions is a customized semantic segmentation version of the Walking Tours Dataset that features hour-long, high-resolution, real-world data from tours of different cities. Additionally, we evaluate the performance of open-vocabulary, semantic model OpenSeeD on our own custom dataset and discuss future implications.
文摘In 2012, Ponraj et al. defined a concept of k-product cordial labeling as follows: Let f be a map from V(G)to { 0,1,⋯,k−1 }where k is an integer, 1≤k≤| V(G) |. For each edge uvassign the label f(u)f(v)(modk). f is called a k-product cordial labeling if | vf(i)−vf(j) |≤1, and | ef(i)−ef(j) |≤1, i,j∈{ 0,1,⋯,k−1 }, where vf(x)and ef(x)denote the number of vertices and edges respectively labeled with x (x=0,1,⋯,k−1). Motivated by this concept, we further studied and established that several families of graphs admit k-product cordial labeling. In this paper, we show that the path graphs Pnadmit k-product cordial labeling.
基金Institutional support was provided by the project of the Czech Academy of Sciences,Czech Republic(to the Institute of Organic Chemistry and Biochemistry)(Project No.:RVO 61388963)This work was supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases(Programme EXCELES)funded by the European Union's Next Generation EU(Project No.:LX22NPO5104)the Czech Science Foundation,Czech Republic(Grant No.:23-05805S).
文摘The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of 125I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically 125I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).
基金supported by National Key Research and Development Program of China(Grant No.:2023YFF0716000)National Natural Science Foundation of China(Grant No.:82071965)+1 种基金Major plan of Jointly Constructed Project by the Science and Technology Department of the State Administration of Traditional Chinese Medicine and the Zhejiang Provincial Administration of Traditional Chinese Medicine,China(Grant No.:GZY-ZJ-KJ-24025)Zhejiang Provincial Natural Science Foundation of China(Grant No.:LQ23H180005).
文摘Nanoclays have large specific surface area,good adsorption properties,and biocompatibility that have great potential for drug delivery applications[1].Evaluating the in vivo metabolic pathways of nanoclays can help to understand their pharmacodynamic sites and the toxicological effects caused by their in vivo retention time[2].
基金supported by grants from the National Key Research and Development Program of China(2019YFA0802704)the National Natural Science Foundation of China(31771620)+2 种基金the Natural Science Foundation of Chongqing,China(CSTB2022NSCQMSX1424)Research Startup Fund of Southwest University(SWU117064)Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention&Henan Key Laboratory of Population Defects Prevention(ZD202302)。
文摘Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(Reiter and Leroux,2017;Wallmeier et al.,2020).To date,over 180 ciliopathy-associated genes have been identified(Reiter and Leroux,2017),yet the underlying mechanisms remain poorly understood.
基金supported by the National Natural Science Foundation of China(Nos.22264013,21961010)Hainan Province Science and Technology Special Fund(Nos.ZDYF2021SHFZ219,ZDYF2022SHFZ037)+4 种基金Special Funds of S&T Cooperation and Exchange Projects of Shanxi Province(No.202204041101040)Natural Science Research Talent Project of Hainan Medical University(No.JBGS202101)Postgraduate Innovative Research Project of Hainan(No.Qhys2021-384)Hainan Province Clinical Medical Center(2021)Project for Functional Materials and Molecular Imaging Science Innovation Group of Hainan Medical University.
文摘Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxidative damage and microvascular permeability in ALI.Accurate detection of ONOO^(−)would facilitate early diagnosis and intervention in ALI.Near-infrared fluorescence(NIRF)probes offer new solutions due to their sensitivity,depth of tissue penetration,and imaging capabilities.However,the developed ONOO^(−)fluorescent probes face problems such as interference from other reactive oxygen species and easy intracellular diffusion.To address these issues,we introduced an innovative self-immobilizing NIRF probe,DCI2F-OTf,which was capable of monitoring ONOO^(−)in vitro and in vivo.Importantly,leveraging the high reactivity of the methylene quinone(QM)intermediate,DCI2F-OTf was able to covalently label proteins in the presence of ONOO^(−),enabling in situ imaging.In mice models of ALI,DCI2F-OTf enabled real-time imaging of ONOO^(−)levels and found that ONOO^(−)was tightly correlated with the progression of ALI.Our findings demonstrated that DCI2F-OTf was a promising chemical tool for the detection of ONOO^(−),which could help to gain insight into the pathogenesis of ALI and monitor treatment efficacy.
文摘This paper is concerned with design-ing symbol labeling for a low-density parity-check(LDPC)-coded delayed bit-interleaved coded modu-lation(DBICM)scheme in a two-way relay channel(TWRC).We first present some properties of symbol labeling within a phase shift keying(PSK)modula-tion.These properties reduce the candidate labeling search space.Based on this search space,we take DBICM capacity as the cost function and propose a general method for optimizing symbol labeling by em-ploying the differential evolution algorithm.Numeri-cal results show that our labeling obtains a signal-to-noise ratio(SNR)gain up to 0.45 dB with respect to Gray labeling.
基金Hubei Natural Science Foundation of China,Grant/Award Number:2024AFB593。
文摘Background:Rabies virus(RABV)-derived neuronal tracing tools are extensively applied in retrograde tracing due to their strict retrograde transsynaptic transfer property and low neurotoxicity.However,the RABV infection and expression of fluorescence products would be gradually cleared while the infected neurons still survive,a phenomenon known as non-cytolytic immune clearance(NCLIC).This phenomenon introduced the risk of fluorescence loss and led to the omission of a subset of neurons that should be labeled,thereby interfering in the analysis of tracing results.Methods:To compensate for the fluorescence loss problem,in this study,we developed a novel marker footprints(MF)mouse,involving a Cre recombinase-dependent red fluorescent reporter system and systemic expression of glycoprotein(G)and ASLV-A receptor(TVA).Using this mouse model combined with the well-developed RABV-EnvA-ΔG-GFP-Cre viral tool,we developed a novel green-to-red spectral labeling strategy.Results:Neurons in the MF mouse could be co-labeled with green fluorescence from the very quick expression of the viral tool and with red fluorescence from the relatively slow expression of the neuron itself,so neurons undergoing NCLIC with green fluorescence loss could be relabeled red.Furthermore,newly infected neurons could be labeled green and other neurons could be labeled yellow due to the temporal expression difference between the two fluorescent proteins.Conclusions:This is the first polysynaptic retrograde tracing labeling strategy that could label neurons using spectral fluorescence colors with only one injection of the viral tool,enabling its application in recognizing the labeling sequence of neurons in brain regions and enhancing the spatiotemporal resolution of neuronal tracing.
基金supported by the National Natural Science Foundation of China(No.21927814)the National Key Research and Development Program of China(Nos.2019YFA0405600,2019YFA0706900,2021YFA1200104,2022YFC3400500)+2 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(Nos.XDB0540200,XDB37040201)Plans for Major Provincial Science&Technology Projects(No.202303a07020004)the Youth Innovation Promotion Association,CAS(No.2022455)。
文摘Liquid-liquid phase separation(LLPS)of proteins and nucleic acids is a common phenomenon in cells that underlies the formation of membraneless organelles.Although the macroscopic behavior of biomolecular coacervates has been elucidated by microscopy,the detailed dynamic properties of proteins/peptides during the LLPS process remain poorly characterized.Here,site-directed spin labeling-electron paramagnetic resonance(SDSL-EPR)spectroscopy was employed to characterize the dynamic properties of a minimal model LLPS system consisting of positively charged peptides and RNA.The degree of phase separation,indicated by broadening of the EPR spectrum of the spin-labeled peptide due to slow molecular tumbling,was monitored by EPR.In addition,three distinct populations with varying molecular motion during LLPS,featuring different spectral lineshapes,were identified.These populations included a fast motion component(Ⅰ),a slower motion component(Ⅱ)associated with peptides in the dispersed phase and an immobile component(Ⅲ)observed in the dense phase.With gradual titration of the peptides to RNA,the EPR spectrum gradually shifted,refiecting changes in the populations of the components.Together,SDSL-EPR method not only provides new insights into the dynamic behavior of biomolecules during LLPS,but also offers a sensitive method for biomolecular phase separation processes at the molecular level.
基金funded by the Ongoing Research Funding program(ORF-2025-867),King Saud University,Riyadh,Saudi Arabia.
文摘Digital twin technology is revolutionizing personalized healthcare by creating dynamic virtual replicas of individual patients.This paper presents a novel multi-modal architecture leveraging digital twins to enhance precision in predictive diagnostics and treatment planning of phoneme labeling.By integrating real-time images,electronic health records,and genomic information,the system enables personalized simulations for disease progression modeling,treatment response prediction,and preventive care strategies.In dysarthric speech,which is characterized by articulation imprecision,temporal misalignments,and phoneme distortions,existing models struggle to capture these irregularities.Traditional approaches,often relying solely on audio features,fail to address the full complexity of phoneme variations,leading to increased phoneme error rates(PER)and word error rates(WER).To overcome these challenges,we propose a novel multi-modal architecture that integrates both audio and articulatory data through a combination of Temporal Convolutional Networks(TCNs),Graph Convolutional Networks(GCNs),Transformer Encoders,and a cross-modal attention mechanism.The audio branch of the model utilizes TCNs and Transformer Encoders to capture both short-and long-term dependencies in the audio signal,while the articulatory branch leverages GCNs to model spatial relationships between articulators,such as the lips,jaw,and tongue,allowing the model to detect subtle articulatory imprecisions.A cross-modal attention mechanism fuses the encoded audio and articulatory features,enabling dynamic adjustment of the model’s focus depending on input quality,which significantly improves phoneme labeling accuracy.The proposed model consistently outperforms existing methods,achieving lower Phoneme Error Rates(PER),Word Error Rates(WER),and Articulatory Feature Misclassification Rates(AFMR).Specifically,across all datasets,the model achieves an average PER of 13.43%,an average WER of 21.67%,and an average AFMR of 12.73%.By capturing both the acoustic and articulatory intricacies of speech,this comprehensive approach not only improves phoneme labeling precision but also marks substantial progress in speech recognition technology for individuals with dysarthria.
基金funded by the National Natural Science Foundation of China (Nos. 62235007 and 22204070)the National Key Research and Development Program (No. 2020YFA0909000)+2 种基金Guangdong Provincial Key Laboratory of Advanced Biomaterials (No. 2022B1212010003)Shenzhen Science and Technology Innovation Project (Nos. KQTD20170810111314625, SGDX20211123114002003 and JCYJ20210324115807021)Shenzhen Bay Laboratory (No. SZBL2021080601002).
文摘Self-labeling protein (SLP) tags, such as HaloTag, have gained considerable interest as advanced tools for live cell labeling. However, the chloroalkane-based substrates that can be directly used for protein labeling are limited. Here, we report two bioorthogonal small molecule linkers, chloroalkane-tetrazine (CA-Tz) and chloroalkane-azide (CA-N3), which can penetrate cell membranes and facilitate click chemistry-based labeling in live cells. We compare their labeling capability using two clickable silicon rhodamine dyes (SiR-PEG_(3)-TCO and SiR-PEG_(4)-DBCO). Confocal imaging results demonstrate that using CA-Tz and SiR-PEG_(3)-TCO dye exhibits superior intracellular labeling with low nonspecific signals. We subsequently compared the photostability of SiR dyes with that of green fluorescent proteins (mEmerald). Total internal reflection fluorescence (TIRF) imaging indicates that SiR dyes exhibit superior photostability under identical excitation conditions, making them suitable for long-term cell imaging. Furthermore, SiR dyes labeling also shows high structure retention for the fourth-order super-resolution optical fluctuation imaging (SOFI) compared to fluorescent proteins. This study presents clickable HaloTag linkers as effective tools for live cell labeling and imaging, highlighting the high-quality labeling of chloroalkane linkers and clickable dyes for live cell imaging.
基金The National Natural Science Foundation of China(No60663004)the PhD Programs Foundation of Ministry of Educa-tion of China (No20050007023)
文摘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.
基金Project(2011JQ028)supported by the Fundamental Research Funds for the Central Universities,ChinaProjects(2008SK3114,2010SK3113)supported by Hunan Provincial Science&Technology Plan,China+2 种基金Project(B2007086)supported by Science&Research Funds of Hunan Health Department,ChinaProject(12JJ5057)supported by Natural Science Foundation of Hunan Province,ChinaProjects(XCX1119,XCX12073)supported by University Students Innovative Experiment Plan Project of Hunan Agricultural University,China
文摘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.
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Objective To evaluate the reliability of three dimensional spiral fast spin echo pseudo-continuous arterial spin labeling(3 D 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 3 D pc-ASL and three dimensional T1-weighted fast spoiled gradient recalled echo(3 D 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 3 D 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.
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(31771197,31830035 and 91732304)the National Basic Research Development Program(973 Program)of China(2015CB755600)+2 种基金the Strategic Priority Research Program(B)Chinese Academy of Sciences,China(XDBS01030200)the Major Research Plan of the National Natural Science Foundation of China(91632303)
文摘Sparse labeling of neurons contributes to uncovering their morphology, and rapid expression of a fluorescent protein reduces the experiment range. To achieve the goal of rapid and sparse labeling of neurons in vivo, we established a rapid method for depicting the fine structure of neurons at 24 h post-infection based on a mutant viruslike particle of Semliki Forest virus. Approximately 0.014 fluorescent focus-forming units of the mutant virus-like particle transferred enhanced green fluorescent protein into neurons in vivo, and its affinity for neurons in vivo was stronger than for neurons in vitro and BHK21(baby hamster kidney) cells. Collectively, the mutant virus-likeparticle provides a robust and convenient way to reveal the fine structure of neurons and is expected to be a helper virus for combining with other tools to determine their connectivity. Our work adds a new tool to the approaches for rapid and sparse labeling of neurons in vivo.
基金This project was supported by a grant from National Natural Sciences Youth Foundation of China (30300093).
文摘Neural stem cells were labeled with superparamagnetic iron oxide （SPIO） and tracked by MRI in vitro and in vivo after implantation, Rat neural stem cells were labeled with SPIO combined with PLL by the means of receptor-mediated endocytosis. Prussian blue staining and electron microscopy were conducted to identify the iron particles in these neural stem cells. SPIO-labeled cells were tracked by 4.7T MRI in vivo and in vitro after implantation, The subjects were divided into 5 groups, including 5× 10^5 labeled cells cultured for one day after labeling, 5 × 10^5 same phase unlabeled cells, cell culture medium with 25μg Fe/mL SPIO, cell culture medium without SPIO and distilled water. MR/scanning sequences included TIWI, T2WI and T2＊WI. R2 and R2＊ of labeled cells were calculated. The results showed： （1） Neural stem cells could be labeled with SPIO and labeling efficiency was 100%. Prussian blue staining showed numerous blue-stained iron particles in the cytoplasm; （2） The average percentage change of signal intensity of labeled cells on TIWI in 4.7T MRI was 24.06%, T2WI 50.66% and T2＊WI 53.70% respectively; （3） T2 of labeled cells and unlabeled cells in 4.7T MRI was 516 ms and 77 ms respectively, R2 was 1.94 s^-1 and 12.98 s^-1 respectively, and T2＊ was 109 ms and 22.9 ms, R2＊ was 9.17 s^-1 and 43.67 s^-1 respectively; （4） Remarkable low signal area on T2WI and T2＊WI could exist for nearly 7 weeks and then disappeared gradually in the left brain transplanted with labeled cells, however no signal change in the right brain implanted with unlabeled cells. It was concluded that neural stem cells could be labeled effectively with SPIO. R2 and R2＊ of labeled cells were increased obviously. MRI can be used to track labeled cells in vitro and in vivo.
