Biology subjects

Lee, S.-H.

Publications and source records attributed to Lee, S.-H..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Locomotion-dependent auditory gating to the parietal cortex mediates flexible multisensory decisions

Decision-making in mammals fundamentally relies on integrating multiple sensory inputs, with conflicting information resolved flexibly based on a dominant sensory modality. However, the neural mechanisms underlying state-dependent changes in sensory dominance remain poorly understood. Our study demonstrates that locomotion in mice shifts auditory-dominant decisions toward visual dominance during audiovisual conflicts. Using circuit-specific calcium imaging and optogenetic manipulations, we found that weakened visual representation in the posterior parietal cortex (PPC) leads to auditory-dominant decisions in stationary mice. Prolonged locomotion, however, promotes visual dominance by inhibiting auditory cortical neurons projecting to the PPC (ACPPC). This shift is mediated by secondary motor cortical neurons projecting to the auditory cortex (M2AC), which specifically inhibit ACPPC neurons without affecting auditory cortical projections to the striatum (ACSTR). Our findings reveal the neural circuit mechanisms underlying auditory gating to the association cortex depending on locomotion states, providing insights into the state-dependent changes in sensory dominance during multisensory decision-making.

animal behavior and cognition↗

bioRxiv2024

Formation of a giant unilocular vacuole via macropinocytosis-like process confers anoikis resistance

Cell survival in metazoans depends on cell attachment to the extracellular matrix (ECM) or to neighboring cells. Loss of such attachment triggers a type of programmed cell death known as anoikis, the acquisition of resistance to which is a key step in cancer development. The mechanisms underlying anoikis resistance remain unclear, however. The intracellular F-actin cytoskeleton plays a key role in sensing the loss of cell-ECM attachment, but how its disruption affects cell fate during such stress is not well understood. Here, we reveal a cell survival strategy characterized by the formation of a giant unilocular vacuole (GUVac) in the cytoplasm of the cells whose actin cytoskeleton is disrupted during loss of matrix attachment. Time-lapse imaging and electron microscopy showed that large vacuoles with a diameter of >500 nm accumulated early after inhibition of actin polymerization in cells in suspension culture, and that these vacuoles subsequently coalesced to form a GUVac. GUVac formation was found to result from a variation of a macropinocytosis-like process, characterized by the presence of inwardly curved membrane invaginations. This phenomenon relies on both F-actin depolymerization and the recruitment of septin proteins for micron-sized plasma membrane invagination. The vacuole fusion step during GUVac formation requires PI(3)P produced by VPS34 and PI3K-C2 on the surface of vacuoles. Furthermore, its induction after loss of matrix attachment conferred anoikis resistance. Our results thus show that the formation of a previously unrecognized organelle promotes cell survival in the face of altered actin and matrix environments.

cell biology↗

bioRxiv2024

Inositol polyphosphate multikinase regulates Th1 and Th17 cell differentiation by controlling Akt-mTOR signaling

Activated proinflammatory T helper (Th) cells, such as Th1 and Th17 cells, mediate immune responses against intra- and extra-cellular pathogens as well as cause the development of various autoimmune diseases. Inositol polyphosphate multikinase (IPMK) is a key enzyme essential for inositol phosphate and phosphoinositide metabolism, which is known to control major biological events such as growth; however, its role in the function of Th cells remains unclear. Here we show that the expression of IPMK is highly induced in distinct Th1 and Th17 subsets. Further, while conditional deletion of IPMK in CD4+ T cells is dispensable for Th2-dependent immune responses, both Th1- and Th17-mediated immune responses are markedly diminished when this enzyme is absent resulting in reduced resistance to Leishmania major infection and attenuation of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. In addition, IPMK-deficient naive CD4+ T cells display aberrant T cell activation and impaired differentiation into Th17 cells, which is associated with reduced activation of Akt, mechanistic target of rapamycin (mTOR), and STAT3. Mechanistically, IPMK as a phosphatidylinositol 3-kinase (PI3-kinase) controls the production of phosphatidylinositol (3,4,5)-trisphosphate, thereby promoting T cell activation, differentiation, and effector functions. Our findings suggest that IPMK acts as a critical regulator of Th1 and Th17 differentiation, highlighting the physiological importance of IPMK in Th1- and Th17-mediated immune homeostasis.

immunology↗

bioRxiv2024

Efficient value encoding through convergence of tactile and visual value information in the primate putamen

The processing of diverse sensory values by a limited number of basal ganglia neurons raises the question of whether each value is processed independently or combined as the number of neurons decreases from the cortex to downstream structures. Here, we discovered that tactile and visual values were partially converged in the primate putamen, enhancing its efficiency in encoding values while preserving modality information. Humans and monkeys performed tactile and visual value discrimination tasks. Notably, the human putamen selectively represented both tactile and visual values in fMRI scans. Single-unit electrophysiology further revealed that half of the individual neurons in the macaque putamen encoded both tactile and visual values, and the other half encoded each value separately. The bimodal value neurons enable more efficient value encoding using fewer neurons than the modality-selective value neurons. Our data suggest that the basal ganglia system uses modality convergence to efficiently encode values with limited resources.

neuroscience↗

bioRxiv2024

Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden

Clonal hematopoiesis of indeterminate potential (CHIP) allows estimation of clonal dynamics and documentation of somatic mutations in the hematopoietic system. Recent studies utilizing large cohorts of the general population and patients have revealed significant associations of CHIP burden with age and disease status, including in cancer and chronic diseases. An increasing number of cancer patients are treated with immune checkpoint inhibitors (ICI), but the association of ICI response in non-small cell lung cancer (NSCLC) patients with CHIP burden remains to be determined. We collected blood samples from 100 metastatic NSCLC patients before and after ICI for high-depth sequencing of the CHIP panel and 63 samples for blood single-cell RNA sequencing(scRNA-seq). Whole exome sequencing (WES) was performed in an independent replication cohort of 180 patients. The impact of CHIP status on the immunotherapy response was not significant. However, metastatic lung cancer patients showed higher CHIP prevalence (44/100 for patients vs 5/42 for controls; P = 0.01). In addition, lung squamous cell carcinoma patients showed increased burden of larger clones compared to lung adenocarcinoma patients (8/43 for LUSC vs 2/50 for LUAD; P = 0.04). Furthermore, single cell RNA-seq analysis of the matched patients showed significant enrichment of inflammatory pathways mediated by NF-B in myeloid clusters of the severe CHIP group. Our findings suggest minimal involvement of CHIP mutation and clonal dynamics during immunotherapy but a possible role of CHIP as an indicator of immunologic response in NSCLC patients.

genomics↗

bioRxiv2023

A Novel Pathway Implicated in Regulating Cognitive disfunction in a DrosophilaAlzheimer's Disease Model through Acer Inhibition and CG2233 Modulation

Alzheimers disease (AD) is a progressive neurodegenerative disorder, accounting for most dementia cases worldwide. Current therapies for AD have limited effectiveness in slowing disease progression or delivering a cure. As such, there is an immediate need for ongoing research and innovative strategies to tackle this multifaceted disease. Recently, several studies have implicated the renin-angiotensin system (RAS), known to regulate blood pressure, as a possible therapeutic target for AD. RAS-inhibiting drugs, including angiotensin-converting enzyme inhibitors (ACE-Is), have been shown to reduce the incidence and progression of AD. However, the literature describing their beneficial effects is inconsistent, with contradictory findings reporting no effects. How these drugs may function in AD remains poorly understood. Our previous work in Drosophila models expressing AD-related transgenes investigated the benefits of captopril, an ACE-I, and found it effectively rescued AD-related phenotypes including cognitive performance independent of A{beta}42 changes. Importantly, our study implicated Acer, a homolog of mammalian ACE, as a key player. In our current study, we demonstrate that the beneficial outcomes of Acer inhibition depend on preventing its catalytic activity and downstream target processing. We identify CG2233 as a prospective target and reveal its functional interaction with Acer. Furthermore, we show CG2233 is implicated in AD-related pathways in A{beta}42 expressing flies. Together, these findings provide a new avenue to study the role of ACE in AD. Significance StatementAD is a devastating neurodegenerative disorder with limited therapeutic success. Emerging research highlights the potential of inhibiting the renin-angiotensin system (RAS) in AD. Epidemiological findings and experimental studies have shown promising outcomes with RAS-targeting drugs including angiotensin-converting enzyme inhibitors (ACE-Is). Our previous work in Drosophila AD models revealed the efficacy of captopril, an ACE-I, in improving AD-related phenotypes. Moreover, we identified Acer as a key player in these mechanisms. Our current study further elucidates the role of Acer, identifies CG2233 as a potential target, and uncovers their functional interaction, shedding light on pathways relevant to AD phenotypes. This research underscores the significance of investigating ACE and ACE-I mechanisms in AD, offering potential innovative means for AD therapy.

neuroscience↗

bioRxiv2023

Kv4.2 regulates baseline synaptic strength by inhibiting R-type channel-mediated calcium signaling in the hippocampus

Kv4.2 channels, which mediate A-type K+ current, exert significant influence on synaptic input signals and synaptic plasticity in the principal cells of the hippocampus. While their influence on activity-dependent regulation of synaptic response is well-established, the impact of Kv4.2 channels on baseline synaptic strength remains elusive. To investigate this, we selectively inhibited postsynaptic Kv4.2 by introducing Kv4.2 antibodies into the hippocampal granule cells and evaluated its impact on the baseline synaptic transmission. Our results demonstrated that Kv4.2 inhibitions led to notable increase in the amplitude of AMPA receptor (AMPAR)-mediated synaptic currents, and this effect was in parallel with the Kv4.2 expression level at dendritic regions. This Kv4.2-dependent synaptic potentiation was effectively abolished by intracellular 10 mM BAPTA or block of R-type calcium channels (RTCC) and downstream signaling molecules including protein kinase A (PKA) and protein kinase C (PKC). Importantly, Kv4.2 inhibitions did not occlude further synaptic strengthening high frequency stimulation, suggesting that synaptic strength regulation by Kv4.2 s distinct from the mechanism of long-term potentiation. Our study highlights the role of Kv4.2 in regulating the baseline synaptic strength, where Kv4.2-mediated inhibition of RTCC is crucial.

neuroscience↗

bioRxiv2023

Genomic hypomethylation in cell-free DNA predicts responses to checkpoint blockade in lung and breast cancer

Genomic hypomethylation has recently been identified as a determinant of therapeutic responses to immune checkpoint blockade (ICB). However, tumor tissue is often unattainable, and tissue-based methylation profiling suffers from low tumor purity. In this study, we developed an assay named iMethyl to estimate the genomic hypomethylation status from cell-free DNA (cfDNA) as well as tissue by deep targeted sequencing of young LINE-1 elements with > 400,000 reads per sample. iMethyl was applied to a total of 653 ICB samples encompassing lung cancer (cfDNA n=167; tissue n=137; cfDNA early during treatment n=40), breast cancer (cfDNA n=91; tissue n=50; PBMC n=50; cfDNA at progression n=44), and ovarian cancer (tissue n=74). iMethyl-tissue had better predictive power than tumor mutation burden and PD-L1 expression. Furthermore, iMethyl-liquid predicted ICB responses accurately regardless of the tumor purity of tissue samples. iMethyl-liquid was also able to monitor therapeutic responses early during treatment (3 or 6 weeks after initiation of ICB) and detect progressive hypomethylation accompanying tumor progression. In conclusion, our method allows for reliable noninvasive prediction, early evaluation, and monitoring of clinical responses to ICB therapy.

cancer biology↗

bioRxiv2023

The defined TLR3 agonist, Nexavant, exhibits anti-cancer efficacy and potentiates anti-PD-1 antibody therapy by enhancing immune cell infiltration.

Nexavant has been reported as an alternative to the TLR3 agonist of Poly(I:C) and its derivatives. The physicochemical properties, signaling pathways, anti-cancer effects, and mechanisms of Nexavant were investigated. Nexavants distinct nature, compared to Poly(I:C), was evident through precise quantification, thermostability, and resistance to RNase A. Unlike Poly (I: C) which activates TLR3, RIG-I and MDA5, Nexavant stimulates the signaling through TLR3 and RIG-I but not MDA5. Intratumoral Nexavant treatment led to a unique immune response compared to Poly(I:C), immune cell infiltration, and suppression of tumor growth in various animal cancer models. Nexavant therapy outperformed anti-PD-1 antibody treatment in all tested models and showed a synergistic effect in combinational therapy, especially in well-defined cold tumor models. The effect was similar to Nivolumab in a humanized mouse model. Intranasal instillation of Nexavant recruited immune cells (NK, CD4+ T, CD8+ T) to the lungs, suppressing lung metastasis and improving animal survival. Our study highlighted Nexavants defined nature for clinical use, unique signaling pathways, and its potential as a standalone anti-cancer agent or in combination with anti-PD-1 antibody. Simple SummaryNexavant, a newly reported TLR3 agonist, has advantages over Poly(I:C) in quality control and pre-clinical efficacy. Here, we further investigated Nexavants physicochemical properties, downstream signaling pathways, anti-cancer efficacy, and mechanism of action. Nexavant was homogenous in solution, less sensitive to RNase A, and showed thermostability compared with Poly(I:C). Unlike Poly(I:C), the TLR3, RIGI, and MDA5 activator, Nexavant only activated TLR3 and RIG-I but not MDA5. Administration of Nexavant either by intratumoral or intranasal route suppressed tumor growth in various cancer models. Combination therapy with anti-PD-1 antibody exhibited synergistic tumor growth inhibition than the respective monotherapies. This study demonstrated that Nexavant could be more suitable for clinical use over Poly(I:C) and applied as an anti-cancer agent in the presence or absence of an anti-PD-1 antibody.

immunology↗

bioRxiv2023

A cerebellar disinhibitory circuit supports synaptic plasticity

How does the cerebellum learn how to control motion? The cerebellar motor learning critically depends on the long-term depression of the synapses between granule cells and Purkinje cells, which encode motor commands and inhibitory modifications to motor outputs, respectively, for simultaneous granule cell inputs and climbing fibre inputs, the latter of which encode the error signals1-3. However, recent studies have revealed that inhibitory inputs to Purkinje cells may disrupt long-term depression4-8, and it is not clear how long-term depression can occur without disruption. In search of a clue, we investigated the synaptic connectivity among the neurons reconstructed from serial electron microscopy images of the cerebellar molecular layer9,10. We discovered synapses between climbing fibres and a subset of inhibitory interneurons, which synapse onto the remaining interneurons, which in turn synapse onto Purkinje cells. Such connectivity redefines the interneuron types, which have been defined morphologically or molecularly11-13. Together with climbing fibres to Purkinje cell connections, those cell types form a feedforward disinhibitory circuit14. We argued that this circuit secures long-term depression by suppressing inhibition whenever climbing fibre input is provided and long-term depression needs to occur15, and we validated the hypothesis through a computational model. This finding implies a general principle of circuit mechanism in which disinhibition supports synaptic plasticity16,17.

neuroscience↗

bioRxiv2023

Molecular Basis of Kv1 Channel Downregulation and Its Epileptogenic Implications in Lgi1 Knock-out Mice

The Kv1 members (KCNA, Shaker) of the voltage-gated potassium channels are implicated in determining key functional neuronal properties from spike generation at axonal initial segments to the control of synaptic strength at nerve terminals. In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy (ADTLE), Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv1 remains unknown. In this study we analyse by immunofluorescence the detailed modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 expression levels. Moreover, we find that the downregulation of these Kv channels is associated with an important increase in bursting patterns. Finally, mass spectrometry uncovered key important modifications in the Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals.

neuroscience↗

bioRxiv2023

Robust prediction of patient outcomes with immune checkpoint blockade therapy for cancer using common clinical, pathologic, and genomic features

Despite the revolutionary impact of immune checkpoint blockade (ICB) in cancer treatment, accurately predicting patients responses remains elusive. We analyzed eight cohorts of 2881 ICB-treated patients across 18 solid tumor types, the largest dataset to date, examining diverse clinical, pathologic, and genomic features. We developed the LOgistic Regression-based Immunotherapy-response Score (LORIS) using a transparent, compact 6-feature logistic regression model. LORIS outperforms previous signatures in ICB response prediction and can identify responsive patients, even those with low tumor mutational burden or tumor PD-L1 expression. Importantly, LORIS consistently predicts both objective responses and short-term and long-term survival across most cancer types. Moreover, LORIS showcases a near-monotonic relationship with ICB response probability and patient survival, enabling more precise patient stratification across the board. As our method is accurate, interpretable, and only utilizes a few readily measurable features, we anticipate it will help improve clinical decision-making practices in precision medicine to maximize patient benefit.

cancer biology↗

bioRxiv2023

Decision-consistent bias mediated by drift dynamics of human visual working memory

Sensory evidence tends to be fleeting, often unavailable when we categorize or estimate world features. To overcome this, our brains sustain sensory information in working memory. Although keeping that information accurate while acting on it is vital, humans display two canonical biases: estimates are biased toward a few stimuli ("stimulus-specific bias") and prior decisions ("decision-consistent bias"). Integrative--especially neural mechanistic--accounts of these biases remain scarce. Here, we identify drift dynamics toward discrete attractors as a common source of both biases in orientation estimation, with decisions further steering memory states. Behavior and neuroimaging data reveal how these biases co-evolve through the decision-steered attractor dynamics. Task-optimized recurrent neural networks suggest neural mechanisms that enable categorical decisions to emerge from working memory for continuous stimuli while updating its trajectory, warping decision-consistent biases under stimulus-specific drift.

neuroscience↗

bioRxiv2023

Spatial correspondence in relative space regulates serial dependence

Our perception is often attracted to what we have seen before, a phenomenon called serial dependence. Serial dependence can help maintain a stable perception of the world, given the statistical regularity in the environment. If serial dependence serves this presumed utility, it should be pronounced when consecutive elements share the same identity when multiple elements spatially shift across successive views. However, such preferential serial dependence between identity-matching elements in dynamic situations has never been empirically tested. Here, we hypothesized that serial dependence between consecutive elements is modulated more effectively by the spatial correspondence in relative space than by that in absolute space because spatial correspondence in relative coordinates can warrant identity matching invariantly to changes in absolute coordinates. To test this hypothesis, we developed a task where two targets change positions in unison between successive views. We found that serial dependence was substantially modulated by the correspondence in relative coordinates, but not by that in absolute coordinates. Moreover, such selective modulation by the correspondence in relative space was also observed even for the serial dependence defined by previous non-target elements. Our findings are consistent with the view that serial dependence subserves object-based perceptual stabilization over time in dynamic situations.

animal behavior and cognition↗

bioRxiv2023

In vivo CRISPR screen identifies KRAS-induced COX-2 as a driver of immune evasion and immunotherapy resistance in lung cancer

Oncogenic KRAS impairs anti-tumour immune responses, but effective strategies to combine KRAS inhibitors and immunotherapies have so far proven elusive. In vivo CRISPR-Cas9 screening in an immunogenic murine lung cancer model identifies mechanisms by which oncogenic KRAS promotes immune evasion, most notably expression of immunosuppressive cyclooxygenase-2 (COX-2) in cancer cells. Oncogenic KRAS was a potent inducer of COX-2 in both mouse and human lung cancer which was suppressed using KRAS inhibitors. COX-2 acting via prostaglandin E2 (PGE2) promotes resistance to immune checkpoint blockade (ICB) in both mouse and human lung adenocarcinoma. Targeting COX-2/PGE2 remodelled the tumour microenvironment by inducing pro-inflammatory polarisation of myeloid cells and influx of activated cytotoxic CD8+ T cells, which increased the efficacy of ICB. Restoration of COX-2 expression contributed to tumour relapse after prolonged KRAS inhibition. We propose testing COX-2/PGE2 pathway inhibitors in combination with KRAS G12C inhibition or ICB in patients with KRAS-mutant lung cancer.

cancer biology↗

bioRxiv2023

Input-specific bi-directional regulation of CA3 pyramidal cell excitability: implication in sequential memory formation

Neuronal excitability is a key determinant for recruitment of a neuron to an ensemble. High-frequency mossy fiber (MF) inputs induce a prolonged increase in the excitability of a CA3 pyramidal cell (called long-term potentiation of intrinsic excitability, LTP-IE), thereby weak perforant pathway (PP) inputs can induce long-term potentiation at PP synapses (PP-LTP). However, sustained hyperexcitability is detrimental, and a mechanism to reverse this primed state is necessary. Here, we show that burst firings of CA3 pyramidal cells elicited by PP or recurrent synaptic inputs reverse the MF-induced LTP-IE. Moreover, the high-frequency PP inputs to MF-primed CA3 pyramidal cells induced not only PP-LTP but also restored the high excitability state. Labeling a neuronal ensemble using c-fos promoter in animals exposed to a novel context, we found most CA3 ensemble cells exhibited increased excitability, indicative of LTP-IE. Moreover, when the animals experienced novel contexts twice with an interval, a substantial subset of putative twice-activated CA3 ensemble cells exhibited reduced excitability, implying depotentiation of LTP-IE. We developed an in silico model based on these experimental results and found that MF-induced LTP-IE and its depotentiation are critical for association of orthogonal neuronal ensembles representing temporally discontiguous events. HighlightsO_LIIt is unknown how non-overlapping ensembles are linked in the hippocampal CA3 area. C_LIO_LIMossy fiber inputs prime CA3 pyramidal cells by enhancing dendritic excitability. C_LIO_LIPerforant pathway (PP) inputs to the primed cells induce synaptic strengthening. C_LIO_LIAt the same time, the high excitability state is restored by PP inputs. C_LIO_LIThis learning rule may play a key role in sequence learning in CA3 network. C_LI

neuroscience↗

bioRxiv2023

Boundary-updating as a source of history effect on decision uncertainty

When sorting a sequence of stimuli into binary classes, current choices are often negatively correlated with recent stimulus history. This phenomenon--dubbed the repulsive bias--can be explained by boundary updating, a process of shifting the class boundary to previous stimuli. This explanation implies that recent stimulus history can also influence "decision uncertainty," the probability of making incorrect decisions, since it depends on the location of the boundary. However, there have been no previous efforts to elucidate the impact of previous stimulus history on decision uncertainty. Here, from the boundary-updating process that accounts for the repulsive bias, we derived a prediction that decision uncertainty increases as current choices become more congruent with previous stimuli. We confirmed this prediction in behavioral, physiological, and neural correlates of decision uncertainty. Our work demonstrates that boundary updating offers a principled account of how previous stimulus history concurrently relates to choice bias and decision uncertainty.

neuroscience↗

bioRxiv2023

Static and dynamic analysis of in-vivo imaging for early-detection of lymphedema via near-infrared fluorescence indocyanine green lymphangiography

BackgroundNear-infrared fluorescence indocyanine green (NIRF-ICG) lymphangiography, a primary modality for detecting lymphedema, which is a disease due to lymphatic obstruction, enables real-time observations of lymphatic flow and reveals not only the spatial distribution of drainage (static analysis), but also information on the lymphatic contraction (dynamic analysis). MethodsWe have produced lymphatic obstruction models in upper limbs through the dissection of proximal lymph nodes (LNs) and radiation (dissection limbs). After the model formation during 1 week, the static and dynamic analysis using NIRF-ICG lymphangiography were performed for six weeks. The drainage pattern and leakage of lymph fluid were observed and time-domain signals of lymphatic contraction were measured in the distal lymph vessels. The obtained signals were converted to the frequency-domain spectrums using the signal processing. ResultsThe results of both static and dynamic analyses proved to be effective in accurately identify the extent of lymphatic disruption in the dissection limbs. The static analysis showed abnormal drainage patterns and an increased leakage of lymph fluid to the periphery of the vessels compared to the control limbs. Meanwhile, the waveforms were changed and the frequency of the contractile signals was increased by 58% in the dynamic analysis. Specifically, our findings revealed that regular lymphatic contractions, observed at a frequency range of 0.08 [~] 0.13 Hz in the control limbs, were absent in the dissection limbs. The contractile regularity was not fully restored until the end of the follow-up, indicating a persistent lymphatic disruption in the dissected limbs. ConclusionThe dynamic analysis was consistent with the static analysis, and it could detect the abnormalities of lymphatic circulation by observing the characteristics of signals without the need for a control group. As NIRF-ICG lymphangiography is currently used in clinical practice, our findings may be useful for the early detection of the lymphatic circulation problem.

bioengineering↗