Biology subjects

Shi, Z.

Publications and source records attributed to Shi, Z..

At least 91 records · Page 5Linked to original sources

bioRxiv2024

How to measure functional connectivity using resting-state fMRI? A comprehensive empirical exploration of different connectivity metrics

BackgroundFunctional connectivity in the context of functional magnetic resonance imaging is typically quantified by Pearso[n]s or partial correlation between regional time series of the blood oxygenation level dependent signal. However, a recent interdisciplinary methodological work proposes more than 230 different metrics to measure similarity between different types of time series. ObjectiveHence, we systematically evaluated how the results of typical research approaches in functional neuroimaging vary depending on the functional connectivity metric of choice. We further explored which metrics most accurately detect neural decline induced by age and malignant brain tumors, aiming to initiate a debate on how best assessing brain connectivity in functional neuroimaging research. MethodsWe addressed both research questions using four independent neuroimaging datasets, comprising multimodal data from a total of 1187 individuals. We analyzed resting-state functional sequences to calculate functional connectivity using 20 representative metrics from four distinct mathematical domains. We further used T1- and T2-weighted images to compute regional brain volumes, diffusion-weighted imaging data to build structural connectomes, and pseudo-continuous arterial spin labeling to measure regional brain perfusion. ResultsFirst, our results demonstrate that the results of typical functional neuroimaging approaches differ fundamentally depending on the functional connectivity metric of choice. Second, we show that correlational and distance metrics are most appropriate to cover neural decline induced by age. In this context, partial correlation performs worse than other correlational metrics. Third, our findings suggest that the FC metric of choice depends on the utilized scanning parameters, the regions of interest, and the individual investigated. Lastly, beyond the major objective of this study, we provide evidence in favor of brain perfusion measured via pseudo-continuous arterial spin labeling as a robust neural entity mirroring age-related neural and cognitive decline. ConclusionOur empirical evaluation supports a recent theoretical functional connectivity framework. Future functional imaging studies need to comprehensively define the study-specific theoretical property of interest, the methodological property to assess the theoretical property, and the confounding property that may bias the conclusions.

neuroscience↗

bioRxiv2024

Distractor-response binding influences visual search

Intertrial priming effects in visual search and action control suggest the involvement of binding and retrieval processes. However, the role of distractor-response binding (DRB) in visual search has been largely overlooked, and the specific processing stage within the functional architecture of attentional guidance where the DRB occurs remains unclear. To address these gaps, we implemented two search tasks, where participants responded based on a separate feature from the one defining the target. We kept the target dimension consistent across trials while varying the color and shape of the distractor. Moreover, we either repeated or randomized the target position in different sessions. Our results revealed a pronounced response priming, a difference between trials where the response changed vs. repeated: they were stronger when distractor features or the target position were repeated than they varied. Furthermore, the distractor feature priming, a difference between the distractor features repetition and switch, was contingent on the target position, suggesting that DRB likely operates at late stages of target identification and response selection. These insights affirm the presence of DRB during visual search and support the framework of binding and retrieval in action control as a basis for observed intertrial priming effects related to distractor features. Public significance statementThis study investigated inter-trial effects within visual search tasks and uncovered significant evidence for the role of distractor-response binding. This phenomenon involves linking a response in a given trial to the perceptual features (e.g. color and shape) of non-target items. Crucially, the study revealed that this distractor-response binding effect depends on whether the target location is repeated nearly repeated, suggesting that the retrieval of a previous response occurs at the later stages of target identification or response selection, even though non-target features likely are identified at an earlier stage.

neuroscience↗

bioRxiv2024

Opposing Motor Memories in the Direct and Indirect Pathways of the Basal Ganglia

Loss of dopamine neurons causes motor deterioration in Parkinsons disease patients. We have previously reported that in addition to acute motor impairment, the impaired motor behavior is encoded into long-term memory in an experience-dependent and task-specific manner, a phenomenon we refer to as aberrant inhibitory motor learning. Although normal motor learning and aberrant inhibitory learning oppose each other and this is manifested in apparent motor performance, in the present study, we found that normal motor memory acquired prior to aberrant inhibitory learning remains preserved in the brain, suggesting the existence of independent storage. To investigate the neuronal circuits underlying these two opposing memories, we took advantage of the RNA-binding protein YTHDF1, an m6A RNA methylation reader involved in the regulation of protein synthesis and learning/memory. Conditional deletion of Ythdf1 in either D1 or D2 receptor-expressing neurons revealed that normal motor memory is stored in the D1 (direct) pathway of the basal ganglia, while inhibitory memory is stored in the D2 (indirect) pathway. Furthermore, fiber photometry recordings of GCaMP signals from striatal D1 (dSPN) and D2 (iSPN) receptor-expressing neurons support the preservation of normal memory in the direct pathway after aberrant inhibitory learning, with activities of dSPN predictive of motor performance. Finally, a computational model based on activities of motor cortical neurons, dSPN and iSPN neurons, and their interactions through the basal ganglia loops supports the above observations. These findings have important implications for novel approaches in treating Parkinsons disease by reactivating preserved normal memory, and in treating hyperkinetic movement disorders such as chorea or tics by erasing aberrant motor memories.

neuroscience↗

bioRxiv2024

CAMKV Kinase Signaling Is a Novel Therapeutic Avenue with Prognostic Relevance in Neuroblastoma

Neuroblastoma (NB) can be a highly aggressive malignancy in children. However, the precise mechanisms driving NB tumorigenesis remain elusive. This study revealed the critical role of CREB phosphorylation in NB cell proliferation. By employing a CRISPR-Cas9 knockout screen targeting calcium/calmodulin-dependent protein kinase (CaMK) family members, we identified the CaM kinase-like vesicle-associated (CAMKV) protein as a kinase that mediates direct phosphorylation of CREB to promote NB cell proliferation. CAMKV was found to be a transcriptional target of MYCN/MYC in NB cells. CAMKV knockout and knockdown effectively suppressed NB cell proliferation and tumor growth both in vitro and in vivo. Bioinformatic analysis revealed that high CAMKV expression is significantly correlated with poor patient survival. High-risk NB frequently had high CAMKV protein levels by Immunohistochemical staining. Integrated transcriptomic and proteomic analyses of CAMKV knockdown cells unveiled downstream targets involved in CAMKV-regulated phosphorylation and signaling pathways, many of which are linked to neural development and cancer progression. We identified small molecule inhibitors targeting CAMKV and further demonstrated the efficacy of one inhibitor in suppressing NB tumor growth and prolonging the survival of mice bearing xenografted tumors. These findings reveal a critical role for CAMKV kinase signaling in NB growth and identified CAMKV kinase as a potential therapeutic target and prognostic marker for patients with NB.

cancer biology↗

bioRxiv2024

Characterization of the SARS-CoV-2 BA.5 Variants in H11-K18-hACE2 Hamsters

This study aims to comprehensively characterize the SARS-CoV-2 BA.5 variants using K18 hACE2 transgenic mice and golden hamsters as model organisms. Previous research on SARS-CoV-2 has utilized both mouse and hamster models, leading to conflicting results concerning the viruss lethality. In our study, the finding suggests that H11-K18 hACE2 golden hamsters closely mimic the disease progression observed in human COVID-19 cases caused by BA.5 variants, demonstrating consistent severity and symptoms comparable to severe infections. Additionally, hamsters exhibit heightened respiratory viral replication, accurately reflecting the clinical viral kinetics observed in humans. The study emphasizes the critical importance of selecting an appropriate animal model for SARS-CoV-2 research, while also providing robust support for the hypothesis that BA.5 variants contribute to fatal outcomes in COVID-19 cases. These findings highlight the pivotal role of the golden hamster model in advancing our understanding of the pathogenic mechanisms underlying SARS-CoV-2 variants, as well as in the development of targeted therapeutic strategies. Significance StatementOur research work explores groundbreaking insights that could reshape our understanding of COVID-19 and pave the way for targeted therapies. We use golden hamster models to express the possibility of different animal models could contribute to human diseases. We hope this finding could clarify some conflicts existed, and help further development of medication for COVID.

immunology↗

bioRxiv2024

Distinct Sequential Effects in Space and Time: Repulsion in Direction Judgments and Attraction in Time Reproduction

Our current perception and decision-making are shaped by recent experiences, a phenomenon known as serial dependence. While serial dependence is well-documented in visual perception and has been recently explored in time perception, their functional similarities across non-temporal and temporal domains remain elusive, particularly in relation to task relevance and working memory load. To address this, we designed a unified experimental paradigm using coherent motion stimuli to test both direction and time reproduction. The direction and time tasks were randomly mixed across trials. Additionally, we introduced pre-cue versus post-cue settings in separate experiments to manipulate working memory load during the encoding phase. We found attractive biases in time reproduction but repulsive biases in direction estimation. Notably, the temporal attraction was more pronounced when the preceding task was also time-related. In contrast, the direction repulsion remained unaffected by the nature of the preceding task. Additionally, both attractive and repulsive biases were enhanced by the post-cue compared to the pre-cue. Our findings suggest that opposing sequential effects in non-temporal and temporal domains may originate from different processing stages linked to sensory adaptation and post-perceptual processes involving working memory.

neuroscience↗

bioRxiv2024

Vaping and smoking cue reactivity in young adult electronic cigarette users who have never smoked combustible cigarettes: a functional neuroimaging study

IntroductionThe rapid growth in the use of electronic cigarettes (e-cigarettes) among young adults who have never smoked combustible cigarettes is concerning, as it raises the potential for chronic vaping and nicotine addiction. A key characteristic of drug addiction is the elevated neural response to conditioned drug-related cues (i.e., cue reactivity). Generalized reactivity to both vaping and smoking cues may signify an increased risk for smoking initiation in non- smoking vapers. In this study, we used functional magnetic resonance imaging (fMRI) to evaluate brain responses to vaping and smoking cues in young adult never-smoking vapers. MethodsSixty-six young adult never-smoking vapers underwent functional MRI while viewing visual cues pertaining to vaping, smoking, and nicotine-unrelated unconditioned reward (i.e., food). A priori region-of-interest analysis combined with exploratory whole-brain analysis was performed to characterize neural reactivity to vaping and smoking cues in comparison to food cues. ResultsThe medial prefrontal cortex and the posterior cingulate cortex, regions that play a key role in drug cue reactivity, showed significantly increased neural response to vaping cues compared to food cues. The posterior cingulate cortex additionally showed increased neural responses to smoking cues compared to food cues. ConclusionsDespite never having smoked combustible cigarettes, young adult vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems associated with cue reactivity. The findings shed light on the mechanisms underlying nicotine addiction and smoking initiation risk in this critical population and may contribute to the development of science-based interventions and regulatory measures in the future. IMPLICATIONSThe escalating vaping prevalence among US never-smoking young adults is alarming, due to its potential ramifications for nicotine addiction development. Nicotine addiction is characterized by elevated neural response to conditioned nicotine-related cues. Using functional neuroimaging, we showed that young adult non-smoking vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems previously associated with cue reactivity. Such cross-reactivity to both types of nicotine cues may serve as the mechanism underlying nicotine addiction and smoking initiation risk in this population. Our findings may contribute to the development of science-based interventions and regulatory measures addressing the vaping epidemic.

neuroscience↗

bioRxiv2024

Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of ZNRF3/RNF43 stimulates cell growth and tumorigenesis through upregulated EGFR signaling. Together, these data highlight ZNRF3 and RNF43 as novel E3 ubiquitin ligases of EGFR and establish the inactivation of ZNRF3/RNF43 as a driver of increased EGFR signaling, ultimately promoting cancer progression. This discovery establishes a connection between two fundamental signaling pathways, EGFR and WNT, at the level of cytoplasmic membrane receptors, uncovering a novel mechanism underlying the frequent co-activation of EGFR and WNT signaling in development and cancer.

cancer biology↗

bioRxiv2024

Ultrasound-Driven Programmable Artificial Muscles

Muscular systems1, the fundamental components of mobility in animals, have sparked innovations across technological and medical fields2,3. Yet artificial muscles suffer from dynamic programmability, scalability, and responsiveness due to complex actuation mechanisms and demanding material requirements. Here, we introduce a design paradigm for artificial muscles, utilizing >10,000 microbubbles with targeted ultrasound activation. These microbubbles are engineered with precise dimensions that correspond to distinct resonance frequencies. When stimulated by a sweeping-frequency ultrasound, microbubble arrays in the artificial muscle undergo selective oscillations and generate distributed point thrusts, enabling the muscle to achieve programmable deformation with remarkable attributes: a high compactness of [~]3,000 microbubbles/mm{superscript 2}, a low weight of 0.047 mg/mm2, a substantial force intensity of [~]1.21 N/mm2, and fast response (sub-100 ms during gripping). Moreover, they offer good scalability (from micro- to -centimeter scale), exceptional compliance, and many degrees of freedom. We support our approach with a theoretical model and demonstrate applications spanning flexible organism manipulation, conformable robotic skins for adding mobility to static objects and conformally attach to ex vivo porcine organs, and biomimetic stingraybots for propulsion within ex vivo biological environments. The customizable artificial muscles could offer both immediate and long-term impact on soft robotics, wearable technologies, haptics, and biomedical instrumentation.

bioengineering↗

bioRxiv2023

Learning regular cross-trial shifts of the target location in serial search involves awareness: an eye-tracking study

People can learn, and utilize, not only static but also dynamic (cross-trial) regularities in the positioning of target items in parallel, pop-out visual search. However, while static target-location learning also works in serial search, acquiring dynamic regularities seems prevented by the demands imposed by item-by-item scanning. Also, questions have been raised regarding a role of explicit awareness for utilizing (at least) dynamic regularities to optimize performance. The present study re-investigated whether dynamic regularities may be learned in serial search when regular shifts of the target location occur frequently, and whether such learning would correlate with awareness of the dynamic rule. To this end, we adopted the same regularity used by Yu et al. (2023) to demonstrate dynamic learning in parallel search: a cross-trial shift of the target location in, e.g., clockwise direction within a circular array in 80% of the trials, which was compared to irregular shifts in the opposite (e.g., counterclockwise; 10%) or some other, random direction (10%). The results showed that [2/3] of participants learned the dynamic regularity, with their performance gains correlating with awareness: the more accurately they estimated how likely the target shifted in the frequent direction, the greater their gains. Importantly, part of the gains accrued already early during search: a large proportion of the very first and short-latency eye movements was directed to the predicted location, whether or not the target appeared there. We discuss whether this rule-driven behavior is causally mediated by conscious control. (248 words).

neuroscience↗

bioRxiv2023

scHiCyclePred: a deep learning framework for predicting cell cycle phases from single-cell Hi-C data using multi-scale interaction information

While scRNA-seq offers gene expression snapshots, it misses the spatial context of chromatin organization crucial for cell cycle regulation. Single-cell Hi-C, capturing chromatins three-dimensional (3D) architecture, fills this void, revealing interactions between genomic regions that transcript-only data might overlook. We introduce scHiCyclePred, a model that utilizes single-cell Hi-Cs multi-scale interaction data to predict cell cycle phases by extracting chromatins 3D features. This fusion-prediction model integrates three feature sets into a unified vector. Remarkably, scHiCyclePred outperforms methods like NAGANO and CIRCLET and traditional machine learning techniques across various metrics. Our insights into 3D chromatin dynamics during the cell cycle further underscore its utility. By offering a more comprehensive view of cell cycle dynamics through chromatin structure, scHiCyclePred stands to significantly advance our understanding in cellular biology and holds potential to catalyze breakthroughs in disease research. Access scHiCyclePred at github.com/HaoWuLab-Bioinformatics/scHiCyclePred.

bioinformatics↗

bioRxiv2023

Revisiting the Kuleshov effect with authentic films: A behavioral and fMRI study

As a fundamental film theory, montage theory posits that film editing significantly influences the viewers perception. The Kuleshov effect, a central concept in montage theory, proposes that the emotional interpretation of neutral facial expressions is influenced by the accompanying emotional scene in a face-scene-face sequence. However, concerns persist regarding the validity of previous studies, often employing inauthentic film materials like static images, leaving the question of its existence in authentic films unanswered. This study addresses these concerns by utilizing authentic films in two experiments. In Experiment 1, multiple film clips were captured under the guidance of a professional film director and seamlessly integrated into authentic film sequences. A total of 59 participants viewed these face-scene-face film sequences and were tasked with rating the valence of neutral faces. The findings revealed that the interpretation of emotion in neutral faces is significantly influenced by the accompanying fearful or happy scene, eliciting perceptions of negative or positive emotion from the neutral face. These results affirm the existence of the Kuleshov effect within authentic film sequences. In Experiment 2, 31 participants engaged in a similar task under functional magnetic resonance imaging (fMRI). The results revealed neural correlates supporting the existence of the Kuleshov effect at a neural level. These correlates include the cuneus, precuneus, hippocampus, parahippocampal gyrus, post cingulate gyrus, orbitofrontal cortex, fusiform gyrus, and insula. These findings also underscore the contextual framing inherent in the Kuleshov effect. By seamlessly integrating film theory and cognitive neuroscience experiments, this comprehensive study provides robust evidence supporting the existence of the Kuleshov effect. It significantly enhances our understanding of film editing and its profound impact on viewers perception.

neuroscience↗

bioRxiv2023

Aftereffects of Delay Adaptation in Visual and Tactile Duration Reproduction

Brief actions involve multiple temporal cues that may not always synchronize, and in basic action-effect relationships, the effect is often delayed. How the brain incorporates delays across modalities in a sensorimotor duration reproduction remains unclear. To investigate this, we conducted two experiments on duration reproduction with delayed sensory feedback. Participants reproduced durations in either visual (Experiment 1) or tactile (Experiment 2) modalities. In the adaptation phase, a contingent sensory feedback, either visual or tactile, was delayed by 150 ms in one session and synchronized in the control session, with accuracy feedback provided after each trial. In the testing phase, random action-effect delays (0-150 ms) were introduced and accuracy feedback was removed. The findings revealed that accuracy feedback effectively recalibrated motor time but did not eliminate the delay. Without accuracy feedback, tactile reproduction relied more on the tactile feedback than on motor time, resulting in greater lengthening of motor reproduction compared to the visual feedback. These findings suggest that temporal delay adaptation is influenced by accuracy feedback and sensorimotor integration, with sensorimotor reliability assigning a higher weight to the tactile than the visual modality.

neuroscience↗

bioRxiv2023

Alternative splicing expands the antiviral IFITM repertoire in Chinese horseshoe bats

The interferon response is shaped by the evolutionary arms race between hosts and the pathogens they carry. The human interferon-induced transmembrane protein (IFITM) family consists of three antiviral IFITM genes that arose by gene duplication, they restrict virus entry and are key players of the interferon response. Yet, little is known about IFITMs in other mammals. Here, we identified an IFITM gene in Chinese horseshoe bat, a natural host of SARS-coronaviruses, that is alternatively spliced to produce two IFITM isoforms. These bat IFITMs have conserved structures in vitro and differential antiviral activities against influenza A virus and coronaviruses including SARS- and MERS-coronavirus. In parallel with human IFITM1-3, the bat IFITM isoforms localize to distinct cellular compartments. Further analysis of IFITM repertoires in 205 mammals reveals that alternative splicing is a ubiquitous strategy for IFITM diversification, albeit less widely adopted than gene duplication. These findings showcase an example of convergent evolution where species-specific selection pressures led to expansion of the IFITM family through multiple means, underscoring the importance of IFITM diversity as a component of innate immunity.

microbiology↗

bioRxiv2023

The saccade-induced temporal attentional gradient: Duration compression of the post-saccadic second event

Rapid eye movements can distort our perception of time, as evidenced by the phenomenon of Chronostasis, where the first event following a saccade appears to last longer than it actually does. Despite extensive research on this phenomenon, the effect of saccades on sequential post-saccadic events, beyond the first one, has never been investigated. To address this, in the present study we compared the subjective estimates of the time of first and second post-saccadic events (with fixation conditions as controls). We found saccadic eye movements not only to affect the perceived duration of the first post-saccadic event (Chronostasis), but also that of the second event. Specifically, when the second event immediately following the first event, it was subjectively compressed. When the second event was used as the (constant) reference interval, Chronostasis was enhanced. Remarkably, the compression effect persisted even when potential "attentional-blink"-induced processes, that might affect timing at the transition from the first to the second event, were eliminated. To explain our findings, we propose that saccades induce a transient temporal attentional gradient that results in an overestimation of the first and an underestimation of the second interval when the two intervals are temporally (near-) contiguous.

neuroscience↗

bioRxiv2023

Homologs of SD6 and ICE2 from rice may be involved in regulation of ABA in woody perennial buds

The availability of ABA, a central component in the regulation of the dormancy cycle in grapevine buds, is controlled by coordinated and opposite regulation of NCED and ABA8OX expression, as shown during natural dormancy release and following treatment with Hydrogen Cyanamide (HC). This implies the existence of a shared regulatory entity, which serves as an upstream switch. A molecular switch for integrated and opposite regulation of NCED and ABA8OX was recently described in rice, involving a pair of bHLH transcription factors (OsSD6-OsICE2) that directly regulate ABA8OX3 expression and indirectly regulate NCED2 expression, by direct regulation of the expression of the NCED repressor OsbHLH048. Here, we tested whether expression of the Vitis homologs of the rice SD6 and ICE2 are regulated by dormancy release stimuli, and whether the direction of regulation agrees with that of ABA8OX. Treatment with two independent stimuli of bud break (HC and hypoxia), as well as natural dormancy release, resulted in upregulation of OsSD6 homologs and down regulation of OsICE2 homologs, in agreement with the rice model. In unexpected contrast, the homolog of OsbHLH048 was down-regulated. Our results suggest a grapevine model in which (1) the homologs of OsSD6 and OsICE2 act as direct activators and repressors of ABA8OX3 expression, as for rice, (2) they have opposed effects on the expression of an OsbHLH048 homolog, which serves as direct activator of NCED expression, as for Arabidopsis, and (3) together they act as a switch that allows removal of ABA repression, followed by meristem reactivation and bud break. HIGHLIGHTA molecular switch for integrated and opposite regulation of NCED and ABA8OX in rice seeds, operated by three bHLH transcription factors, is conserved in grapevine buds and regulates dormancy release

developmental biology↗

bioRxiv2023

CSTA: A Biomarker Regulating Esophageal Stricture Epithelial Barrier, Potential Medication Target

Esophageal strictures resulting from ESD/EMR in the esophagus are distressing, with uncertain causes and treatments due to epithelial barrier dysfunction. We explored cystatin A (CSTA) as a novel biomarker for the esophageal epithelial barrier. CSTA regulates the barrier and is influenced by tacrolimus (FK506). Analyzing biopsy samples by proteomics, we identified CSTA as an esophageal epithelial biomarker. Knocking down CSTA reduced responsiveness to triamcinolone acetonide (TA) and lowered expression of proteins related to cell-cell junctions and barrier function during inflammation. These findings suggest that down-regulate CSTA weakens tight junctions and the esophageal barrier, leading to strictures. Notably, FK506 showed promise in rescuing CSTA-knockdown cells by increasing the expression of proteins related to cell-cell junctions and barrier function. This highlights FK506 as a potential therapy for esophageal strictures in patients with CSTA mutations.

cell biology↗

bioRxiv2023

Theranostic multifunctional lipid nanoparticles containing curcumin for integrated imaging and stabilizing vulnerable atherosclerotic plaques through an "eat-me" signal

BACKGROUNDCurcumin has emerged as a promising candidate capable of polarization of macrophages, which promote the stability of atherosclerotic plaque. Nevertheless, a notable limitation lies in the non-specific nature of curcumins targeting. The present study endeavors to harness multifunctional lipid nanoparticles (MLNPs), which could both facilitate imaging and achieve targeted delivery of curcumin specifically to inflammatory macrophages, to effectively counteract vulnerable plaque and mitigate the risk of ischemic events. METHODSThe term "MLNPs", for targeted delivery of curcumin using multimodal imaging techniques including single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), refers to a new type of nanoparticle designed to specifically target and modulate macrophages with phagocytic function. These nanoparticles are cholesteryl-9-carboxynonanoate-(125I-iron oxide nanoparticle/Cur)-lipid-coated nanoparticles [9-CCN-(125I-ION/Cur)-LNPs], which carry hybrid imaging agents. These agents are combinations of 125I-ION and lipids that contain phagocytic "eat-me" signals, which induces macrophages to swallow MLNPs. RESULTSThe accumulation of the devised 9-CCN-(125I-ION/Cur)-LNPs on the unstable plaque of animal models in vivo was accurately reflected and lesions were highlighted by both SPECT and MRI. The intense radioactive signals on SPECT images facilitated the identification and quantification of the target lesion, while MRI based on ION particles facilitated the visualization of the focal localization and volumetry of atherosclerotic plaque. The targeted distribution of the unstable plaque in the rabbit aorta was further confirmed by ex vivo planar images of nuclide and Prussian blue staining for ION. Additionally, 9-CCN-(125I-ION/Cur)-LNPs were found to specifically and effectively bind to the pro-inflammatory M1 macrophages present in the unstable plaque, resulting in the accumulation of radionuclide and hypointensity on T2W images. CONCLUSIONSThe 9-CCN-(125I-ION/Cur)-LNPs demonstrated remarkable capability in the delivery of both 125I-ION and curcumin to macrophages, ultimately resulting in M1-M2 macrophage polarization, which may offer valuable insights into addressing unstable atherosclerotic plaque.

neuroscience↗