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
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
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
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
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
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
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
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 ...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.展开更多
The combination of hydrogen/deuterium(H/D)formaldehyde-based isotopic methyl labeling with solid-phase extraction and high-performance liquid chromatography–high resolution mass spectrometry(HPLC-HRMS)is a powerful a...The combination of hydrogen/deuterium(H/D)formaldehyde-based isotopic methyl labeling with solid-phase extraction and high-performance liquid chromatography–high resolution mass spectrometry(HPLC-HRMS)is a powerful analytical solution for nontargeted analysis of trace-level amino-containing chemicals in water samples.Given the huge amount of chemical information generated in HPLC-HRMS analysis,identifying all possible H/Dlabeled amino chemicals presents a significant challenge in data processing.To address this,we designed a streamlined data processing pipeline that can automatically extract H/D-labeled amino chemicals from the raw HPLC-HRMS data with high accuracy and efficiency.First,we developed a cross-correlation algorithm to correct the retention time shift resulting from deuterium isotopic effects,which enables reliable pairing of H-and D-labeled peaks.Second,we implemented several bioinformatic solutions to remove false chemical features generated by in-source fragmentation,salt adduction,and natural13C isotopes.Third,we used a data mining strategy to construct the AMINES library that consists of over 38,000 structure-disjointed primary and secondary amines to facilitate putative compound annotation.Finally,we integrated these modules into a freely available R program,HDPairFinder.R.The rationale of each module was justified and its performance tested using experimental H/D-labeled chemical standards and authentic water samples.We further demonstrated the application of HDPairFinder to effectively extract N-containing contaminants,thus enabling the monitoring of changes of primary and secondary N-compounds in authentic water samples.HDPairFinder is a reliable bioinformatic tool for rapid processing of H/D isotopic methyl labeling-based nontargeted analysis of water samples,and will facilitate a better understanding of N-containing chemical compounds in water.展开更多
The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immuno...The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.展开更多
Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive diso...Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.展开更多
Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and...Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.展开更多
Small peptides have attracted increasing attention for their unique features and diverse biological functions.Achieving rapid separation and accurate quantification,however,remains a challenge because of their low abu...Small peptides have attracted increasing attention for their unique features and diverse biological functions.Achieving rapid separation and accurate quantification,however,remains a challenge because of their low abundance and the co-existence of numerous structural isomers.In this study,we developed a novel approach using isotope chemical labeling for ultrasensitive determination of di/tripeptides in biological samples.We successfully synthesized a novel derivatization reagent,4-(2-(ethoxymethylene)-3-oxobutanamido)-N,N,N-trimethylbenzenaminium iodide(EOTMBA)as well as its deuterium-labeled isotope reagent(d_(3)-EOTMBA).A total of 97 small peptides,including 89 dipeptides and 8 tripeptides,could be completely derivatized in methanol within 1.5h at 60℃.After EOTMBA labeling,analysis of these di/tripeptides were achieved within 22 min by LC-MS/MS analysis.The method demonstrated 86.3%-113%accuracy and the limit of quantification ranged from 0.25 fmol/L to 5 nmol/L.Using this method,we achieved ultrasensitive and accurate quantification of di/tripeptides in 147 plasma,49 urine and 46 bile samples obtained from healthy individuals and patients with biliary tract diseases.The identified differential di/tripeptide biomarker panels showed promising diagnostic performance for patients with biliary tract cancer with area under the receiver operating curve values from 0.870 to 0.996.Furthermore,this method was successfully applied to quantify di/tripeptides in the extract of an animal-derived traditional Chinese medicine,Eupolyphaga sinensis Walker.These findings highlight the possible application of the analytical method in clinics and for the purposes of quality control of traditional Chinese medicines.展开更多
Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling a...Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling and fast photooxidation of proteins(FPOP),in conjunction with mass spectrometry(MS),to investigate structural modifications for the new class of immuno-oncological therapy known as bispecific antigen-binding biotherapeutics(BABB).The evaluated techniques unveiled subtle structural changes occurring at the amino acid residue level within the antigen-binding domain under both native and thermal stress conditions,which cannot be detected by conventional biophysical techniques,e.g.,near-ultraviolet circular dichroism(NUV-CD).The determined variations in labeling uptake under native and stress conditions,corroborated by binding assays,shed light on the binding effect,and highlighted the potential of covalent-labeling methods to effectively monitor conformational changes that ultimately influence the product quality.Our study provides a foundation for implementing the developed techniques in elucidating the inherent structural characteristics of novel therapeutics and their conformational stability.展开更多
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 structur...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.展开更多
BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emot...BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.展开更多
Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent...Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation.Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation.These labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ allocation.Furthermore,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of noncompliant.We argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to transplantation.For patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more drastic.Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.展开更多
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.
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.
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 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 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Supported by The Key Research and Development Program Projects of Shaanxi Province of China,No.S2023-YF-YBSF-0273Natural Science Foundation of Shaanxi Province of China,No.2022JQ-900.
文摘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.
基金supported by grants from the Natural Sciences and Engineering Research Council of Canada,Alberta Innovatesthe Canada Research Chairs Program。
文摘The combination of hydrogen/deuterium(H/D)formaldehyde-based isotopic methyl labeling with solid-phase extraction and high-performance liquid chromatography–high resolution mass spectrometry(HPLC-HRMS)is a powerful analytical solution for nontargeted analysis of trace-level amino-containing chemicals in water samples.Given the huge amount of chemical information generated in HPLC-HRMS analysis,identifying all possible H/Dlabeled amino chemicals presents a significant challenge in data processing.To address this,we designed a streamlined data processing pipeline that can automatically extract H/D-labeled amino chemicals from the raw HPLC-HRMS data with high accuracy and efficiency.First,we developed a cross-correlation algorithm to correct the retention time shift resulting from deuterium isotopic effects,which enables reliable pairing of H-and D-labeled peaks.Second,we implemented several bioinformatic solutions to remove false chemical features generated by in-source fragmentation,salt adduction,and natural13C isotopes.Third,we used a data mining strategy to construct the AMINES library that consists of over 38,000 structure-disjointed primary and secondary amines to facilitate putative compound annotation.Finally,we integrated these modules into a freely available R program,HDPairFinder.R.The rationale of each module was justified and its performance tested using experimental H/D-labeled chemical standards and authentic water samples.We further demonstrated the application of HDPairFinder to effectively extract N-containing contaminants,thus enabling the monitoring of changes of primary and secondary N-compounds in authentic water samples.HDPairFinder is a reliable bioinformatic tool for rapid processing of H/D isotopic methyl labeling-based nontargeted analysis of water samples,and will facilitate a better understanding of N-containing chemical compounds in water.
文摘The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.
基金the support from the National Natural Science Foundation of China (Nos.21974067, 22274073, 81971373 and 82001535)the National Key Research and Development Program of China (No.2018YFC1004700)+1 种基金Fundamental Research Funds for the Central Universities (Nos.020514380309,021414380502 and 2022300324)the State Key Laboratory of Analytical Chemistry for Life Science (Nos.5431ZZXM2305 and 5431ZZXM2204)。
文摘Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.
基金supported by Natural Science Foundation of Beijing Municipality(L212013)National Key Research and Development Program of China(No.2022YFA1206104)+2 种基金AI+Health Collaborative Innovation Cultivation Project(Z211100003521002)National Natural Science Foundation of China(81971718,82073786,81872809,U20A20412,81821004)Beijing Natural Science Foundation(7222020).
文摘Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.
基金financially supported in part by the National Natural Science Fund of China for Distinguished Young Scholars(No.81825023)National Natural Science Foundation of China(No.82003979)Natural Science Foundation of Shanghai(No.23ZR1459100)。
文摘Small peptides have attracted increasing attention for their unique features and diverse biological functions.Achieving rapid separation and accurate quantification,however,remains a challenge because of their low abundance and the co-existence of numerous structural isomers.In this study,we developed a novel approach using isotope chemical labeling for ultrasensitive determination of di/tripeptides in biological samples.We successfully synthesized a novel derivatization reagent,4-(2-(ethoxymethylene)-3-oxobutanamido)-N,N,N-trimethylbenzenaminium iodide(EOTMBA)as well as its deuterium-labeled isotope reagent(d_(3)-EOTMBA).A total of 97 small peptides,including 89 dipeptides and 8 tripeptides,could be completely derivatized in methanol within 1.5h at 60℃.After EOTMBA labeling,analysis of these di/tripeptides were achieved within 22 min by LC-MS/MS analysis.The method demonstrated 86.3%-113%accuracy and the limit of quantification ranged from 0.25 fmol/L to 5 nmol/L.Using this method,we achieved ultrasensitive and accurate quantification of di/tripeptides in 147 plasma,49 urine and 46 bile samples obtained from healthy individuals and patients with biliary tract diseases.The identified differential di/tripeptide biomarker panels showed promising diagnostic performance for patients with biliary tract cancer with area under the receiver operating curve values from 0.870 to 0.996.Furthermore,this method was successfully applied to quantify di/tripeptides in the extract of an animal-derived traditional Chinese medicine,Eupolyphaga sinensis Walker.These findings highlight the possible application of the analytical method in clinics and for the purposes of quality control of traditional Chinese medicines.
基金supported by Amgen Inc.,USA and the National Institutes of Health,USA(Grant Nos.:R01CA218500(ARI)and R35GM136421(ARI))。
文摘Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling and fast photooxidation of proteins(FPOP),in conjunction with mass spectrometry(MS),to investigate structural modifications for the new class of immuno-oncological therapy known as bispecific antigen-binding biotherapeutics(BABB).The evaluated techniques unveiled subtle structural changes occurring at the amino acid residue level within the antigen-binding domain under both native and thermal stress conditions,which cannot be detected by conventional biophysical techniques,e.g.,near-ultraviolet circular dichroism(NUV-CD).The determined variations in labeling uptake under native and stress conditions,corroborated by binding assays,shed light on the binding effect,and highlighted the potential of covalent-labeling methods to effectively monitor conformational changes that ultimately influence the product quality.Our study provides a foundation for implementing the developed techniques in elucidating the inherent structural characteristics of novel therapeutics and their conformational stability.
基金supported by National Key R&D Program of China(2021YFA1502803)the National Natural Science Foundation of China(NSFC)(21972066,91745202)+3 种基金NSFC-Royal Society Joint Program(21661130149)L.P.thanks the Royal Society and Newton Fund for a Royal Society-Newton Advanced Fellowshipsupported by the Research Funds for the Frontiers Science Centre for Critical Earth Material Cycling,Nanjing Universitya Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘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.
基金Supported by The National Natural Science Foundation of China,No.81871080the Key R&D Program of Jining(Major Program),No.2023YXNS004+2 种基金the National Natural Science Foundation of China,No.81401486the Natural Science Foundation of Liaoning Province of China,No.20170540276the Medicine and Health Science Technology Development Program of Shandong Province,No.202003070713.
文摘BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.
文摘Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation.Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation.These labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ allocation.Furthermore,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of noncompliant.We argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to transplantation.For patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more drastic.Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.
