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In JoVE (1)
Other Publications (24)
- Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology
- The Journal of Physical Chemistry. B
- Langmuir : the ACS Journal of Surfaces and Colloids
- Circulation Research
- Lung Cancer (Amsterdam, Netherlands)
- Journal of Cancer Research and Clinical Oncology
- Immunopharmacology and Immunotoxicology
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Circulation
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- Journal of the American Chemical Society
- Experimental Lung Research
- Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
- Immunopharmacology and Immunotoxicology
- Bioorganic & Medicinal Chemistry Letters
- Journal of the American Chemical Society
- Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
- Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi
- Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
- Macromolecular Rapid Communications
- Nanoscale Research Letters
- Bioconjugate Chemistry
- Circulation. Arrhythmia and Electrophysiology
- American Journal of Physiology. Heart and Circulatory Physiology
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Articles by Wenwen Li in JoVE
JoVE Bioengineering
Multiparameter Optisk Kartläggning av Langendorff-perfusion Kanin hjärta
Department of Biomedical Engineering, Washington University in St. Louis
Den här artikeln beskrivs grundläggande rutiner för optisk kartläggning experiment i Langendorff-perfusion kanin hjärta med panoramautsikt bildsystem, och de dubbla (spänning och kalcium) avbildning modalitet.
Other articles by Wenwen Li on PubMed
[Clone of M2 Autoantigens from Human Sources and Evaluation of Measurement of M2 Autoantibodies in Diagnosis of Primary Biliary Cirrhosis]
To evaluate the value of measurement of M2 autoantibodies in diagnosis of primary biliary cirrhosis (PBS).
Magnetic Carbon Nanotubes: Synthesis by Electrostatic Self-assembly Approach and Application in Biomanipulations
Magnetic multiwalled carbon nanotubes (MWNTs) were facilely prepared by the electrostatic self-assembly approach. Poly(2-diethylaminoethyl methacrylate) (PDEAEMA) was covalently grafted onto the surfaces of MWNTs by MWNT-initiated in situ atom transfer radical polymerization (ATRP) of 2-diethylaminoethyl methacrylate (DEAEMA). The PDEAEMA-grafted MWNTs were quaternized with methyl iodide (CH(3)I), resulting in cationic polyelectrolyte-grafted MWNTs (MWNT-PAmI). Magnetic iron oxide (Fe(3)O(4)) nanoparticles were loaded onto the MWNT surfaces by electrostatic self-assembling between MWNT-PAmI and Fe(3)O(4), affording magnetic nanotubes. The assembled capability of the nanoparticles can be adjusted to some extent by changing the feed ratio of Fe(3)O(4) to MWNT-PAmI. The obtained magnetic nanotubes were characterized with TEM, EDS, STEM, and element mapping analyses. TEM and EDS measurements confirmed the nanostructures and the components of the resulting nanoobjects. The magnetic nanotubes were assembled onto sheep red blood cells in a phosphate buffer solution, forming magnetic cells. The blood cells attached with or without magnetic nanotubes can be selectively manipulated in a magnetic field. These results promise a general and efficient strategy to magnetic nanotubes and the fascinating potential of such magnetic nanoobjects in applications of bionanoscience and technology.
Efficiently Stabilized Spherical Vaterite CaCO3 Crystals by Carbon Nanotubes in Biomimetic Mineralization
Carbon nanotubes were used to induce the formation of spherical vaterite crystals and stabilize the metastable crystals in the biomimetic mineralization of CaCO3 for the first time. It was found that carboxyl-functionalized multiwalled/single-walled carbon nanotubes (MWNT-COOH/SWNT-COOH) can favor the formation of spherical vaterite crystals and stabilize the crystals. In the presence of CNT-COOH, CaCO3 vaterite crystals with diameters of ca. 1-7 microm coated and embedded with the carbon nanotubes (CNTs) were obtained in 30 min by adding Na2CO3 aqueous solution to the aqueous solution of CaCl2. The spherical vaterite crystals covered by the carboxylic CNTs can exist stably in water for a week. Carboxylic-polymer-functionalized CNTs can also facilitate the formation of spherical vaterite crystals, whereas the formed crystals completely transformed into thermodynamically stable calcite crystals in water within 10 h. "Offline" TEM observations of the mineralization process of CaCO3 in the presence of CNT-COOH or pristine CNTs revealed the stability mechanism of vaterite crystals with carboxylic CNTs. The crystals nucleate at the carboxyl groups of CNT-COOH, grow around the CNTs, and finally form spherical vaterite crystals embedded and covered by the CNTs. The strong interaction between CNT-COOH and crystals together with the strong mechanical strength of CNTs stabilizes the formed vaterite crystals and makes them difficult to dissolve in water. These findings announce that nanomaterials could strongly influence the mineralization of biomineralization matters, which may help us prepare novel biomaterials and bionanomaterials.
Enhanced Transmural Fiber Rotation and Connexin 43 Heterogeneity Are Associated with an Increased Upper Limit of Vulnerability in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy
Human hypertrophic cardiomyopathy, characterized by cardiac hypertrophy and myocyte disarray, is the most common cause of sudden cardiac death in the young. Hypertrophic cardiomyopathy is often caused by mutations in sarcomeric genes. We sought to determine arrhythmia propensity and underlying mechanisms contributing to arrhythmia in a transgenic (TG) rabbit model (beta-myosin heavy chain-Q403) of human hypertrophic cardiomyopathy. Langendorff-perfused hearts from TG (n=6) and wild-type (WT) rabbits (n=6) were optically mapped. The upper and lower limits of vulnerability, action potential duration (APD) restitution, and conduction velocity were measured. The transmural fiber angle shift was determined using diffusion tensor MRI. The transmural distribution of connexin 43 was quantified with immunohistochemistry. The upper limit of vulnerability was significantly increased in TG versus WT hearts (13.3+/-2.1 versus 7.4+/-2.3 V/cm; P=3.2e(-5)), whereas the lower limits of vulnerability were similar. APD restitution, conduction velocities, and anisotropy were also similar. Left ventricular transmural fiber rotation was significantly higher in TG versus WT hearts (95.6+/-10.9 degrees versus 79.2+/-7.8 degrees; P=0.039). The connexin 43 density was significantly increased in the mid-myocardium of TG hearts compared with WT (5.46+/-2.44% versus 2.68+/-0.77%; P=0.024), and similar densities were observed in the endo- and epicardium. Because a nearly 2-fold increase in upper limit of vulnerability was observed in the TG hearts without significant changes in APD restitution, conduction velocity, or the anisotropy ratio, we conclude that structural remodeling may underlie the elevated upper limit of vulnerability in human hypertrophic cardiomyopathy.
CpG Island Methylator Phenotype Involving Tumor Suppressor Genes Located on Chromosome 3p in Non-small Cell Lung Cancer
CpG island methylator phenotype (CIMP) involving methylation abnormalities of tumor suppressor gene (TSG) on short arm of chromosome 3 (chromosome 3p) has not been so far epigenetically elucidated in non-small cell lung cancer (NSCLC). Using methylation-specific PCR (MSP) method, we examined methylation profiles for eight TSGs harbored in chromosome 3p in 60 NSCLC tissues and 60 paired normal tissues as well as 11 normal blood samples. CIMP positive is referred to having four or more than four synchronously methylated genes per sample. Consequently, 59 of 60 (98.3%) NSCLC presented promoter methylation of at least one gene while only one malignant tumor showed no methylation of any of eight genes. The frequency of promoter methylation for eight genes explored ranged from 12% for hMLH1 to 67% for RASSF1A given that of VHL (none) was not considered. Interestingly, CIMP+ was found in 56.7% (34/60) of NSCLC, and in 6.7% (4/60) of paired normal tissues and 0% (0/11) of normal blood samples, respectively; CIMP- was present in 43.3% (26/60) of NSCLC, 93.3% (56/60) of paired normal tissues, and 100% (11/11) of normal blood samples, respectively. The data suggest that CIMP status was significantly associated with NSCLC, paired normal tissues and normal blood samples (P<0.001). In addition, there appeared to be a significant association between CIMP status and survival prognosis of NSCLC (P=0.0166). In the present study, for the first time, we shed light on the presence of chromosome 3p-specific CIMP, which might play an important role in tumorigenesis of NSCLC.
Infrequently Methylated Event at Sites -362 to -142 in the Promoter of TGF Beta R1 Gene in Non-small Cell Lung Cancer
Many malignant tumor cells, including non-small cell lung cancer (NSCLC) cells, are frequently resistant to transforming growth factor beta (TGF-beta)-mediated signal transduction. This refractory response might be due to reduced/loss expression of the TGF-beta receptor 1 (TGF beta R1). However, little was known about connection between inactivation of the TGF beta R1 gene and the presence of CpG methylated promoter in NSCLC.
Immunoregulatory and Anti-tumor Effects of Polysaccharopeptide and Astragalus Polysaccharides on Tumor-bearing Mice
The aim of this study was to determine whether polysaccharopeptide (PSP) and Astragalus polysaccharides (APS) can be combined together as a new complex prescription (PSP + APS) for aiding adriamycin (AMD) chemotherapy. Ehrlich's ascites carcinoma (EAC) was used to establish a solid tumor model in Kunming mice. Immunocytochemical and immunohistochemical analysis were employed to detect the immunoregulatory and anti-tumor effects of EAC bearing mice after 30 days of administration with PSP and APS. PSP and PSP + APS could significantly increase the percentage of CD3(+) and CD4(+) T-lymphocytes, the ratio of CD4(+)/CD8(+), and the expression of IL-2/IL-2R in spleen and Bax in tumor tissue, but led to a diminution of Bcl-2 and CDK4 in tumor tissue compared with those of control group. In addition, PSP +APS could restore the immunological effects against AMD-induced immunosuppression, such as the subset of leukomonocyte, the expression of IL-2/IL-2R in the spleen, and the thymus index. These findings suggest that the immunomodulatory and anti-cancer effects of this new formula (PSP+APS) were better than those of PSP alone, and also could resist immunosuppression induced by AMD.
Panoramic Imaging Reveals Basic Mechanisms of Induction and Termination of Ventricular Tachycardia in Rabbit Heart with Chronic Infarction: Implications for Low-voltage Cardioversion
Sudden cardiac death due to arrhythmia in the settings of chronic myocardial infarction (MI) is an important clinical problem. Arrhythmic risk post-MI continues indefinitely even if heart failure and acute ischemia are not present due to the anatomic substrate of the scar and border zone (BZ) tissue.
Resolution of Established Cardiac Hypertrophy and Fibrosis and Prevention of Systolic Dysfunction in a Transgenic Rabbit Model of Human Cardiomyopathy Through Thiol-sensitive Mechanisms
Cardiac hypertrophy, the clinical hallmark of hypertrophic cardiomyopathy (HCM), is a major determinant of morbidity and mortality not only in HCM but also in a number of cardiovascular diseases. There is no effective therapy for HCM and generally for cardiac hypertrophy. Myocardial oxidative stress and thiol-sensitive signaling molecules are implicated in pathogenesis of hypertrophy and fibrosis. We posit that treatment with N-acetylcysteine, a precursor of glutathione, the largest intracellular thiol pool against oxidative stress, could reverse cardiac hypertrophy and fibrosis in HCM.
Multiple Monophasic Shocks Improve Electrotherapy of Ventricular Tachycardia in a Rabbit Model of Chronic Infarction
We previously showed that the cardioversion threshold (CVT) for ventricular tachycardia (VT) is phase dependent when a single monophasic shock (1MP) is used.
Star Polymers Via Cross-linking Amphiphilic Macroinitiators by AGET ATRP in Aqueous Media
Amphiphilic star polymers with low polydispersity (PDI) and high molecular weight were synthesized by an activator generated by electron transfer atom transfer radical polymerization (AGET ATRP) in aqueous dispersed media using a simple "arm-first" method and linear block copolymers poly(ethylene oxide)-b-polystyrene (PEO-PS-Cl) as arm precursors. The amphiphilic block copolymers PEO-PS-Cl with halogen chain-end functionality formed micelles in water and then were cross-linked by the divinyl cross-linkers. Due to the formation of cross-linker swollen micelles before the polymerization was initiated, star-star or star-linear chain reactions were not required for the star formation. The suppressed star-star coupling reactions resulted in the formation of star polymers with low PDI (M(w)/M(n) < 1.1) but still high molecular weight (over 1000 kg/mol).
Infrequently Methylated Event at Sites -181 to -9 Within the 5' CpG Island of E-cadherin in Non-small Cell Lung Cancer
Epigenetic silencing of E-cadherin via aberrant methylation has been investigated in various human tumors, whereas evidence for elucidating mechanism underlying reduction of E-cadherin mRNA remains unclear in non-small cell lung cancer (NSCLC). The authors previously found that reduction of E-cadherin mRNA or protein expression has been frequently observed in NSCLC. In this study, the authors explore the contribution of E-cadherin methylation to the development and progression of NSCLC. The authors directly performed the bisulfite DNA sequencing to examine CpG methylation within the 5' CpG island of E-cadherin in 35 tumor and paired normal tissue specimens from patients with primary NSCLC. Then, the authors measured the level of E-cadherin mRNA by real-time quantitative polymerase chain reaction (PCR) analysis. Despite of reduction in E-cadherin mRNA by 65.7% (23/35) and presence of methylation by 28.6% (10/35) in tumors, the authors found no association of reduction of E-cadherin mRNA level with methylation of 19 sites from -181 to -9 bp located upstream from the translation start of E-cadherin in NSCLC. In conclusion, the authors provide no evidence for the presence of aberrant methylation sites of E-cadherin in tumors from patients with NSCLC, which can explain decrease of E-cadherin mRNA. Decrease in E-cadherin mRNA may be regulated by methylation-independent pathways in NSCLC.
Somatosensory-evoked Potentials and Cortical Activities Evoked by Magnetic Stimulation on Acupoint in Human
Two acupuncture manipulations are clinically used: manual manipulation and electrical acupuncture. There is little published on the EEG changes during magnetic stimulation on an acupuncture site. In this study, EEG data in response to magnetic stimulation on HeGu (LI 4) acupoint were measured to determine whether magnetic acupoint stimulation might modulate ongoing EEG or not. Eighteen healthy volunteers (13 male, 5 female) 20 to 35 years old were chosen in this experiment, with consent obtained before the study. The highest evoked potential was recorded in FCZ electrode, at about 140-170 ms (P150) after acupoint stimulation, but not mock point stimulation. Comparison of the somatosensory-evoked potentials in response to acupoint stimulation and mock point stimulation showed that P150 was specific to acupoint stimulation. With regard to the location of P150 in the human brain, we suggest that magnetic stimulation on HeGu acupoint would affect specific brain areas compared with the mock point. The difference in the anatomical structure of acupoint and non-acupoint may explain the specific acupoint-brain correlation, and P150 may be a characteristic activation in response to acupoint afferent.
Immunomodulatory Effects of Polysaccharopeptide (PSP) in Human PBMC Through Regulation of TRAF6/TLR Immunosignal-transduction Pathways
Polysaccharopeptide (PSP) was extracted from Coriolus versicolor, and has been proved to be a valuable adjuvant for the combination with chemotherapy or radiotherapy in the treatment of various cancers. Objective: To understand the mechanism of PSP on immunomodulation, we examined gene expression and cytokine secretion associated with immunosignal-transduction signaling in human peripheral blood mononuclear cells (PBMCs).
Synthesis and Anti-tumor Activities of Methyl 2-O-aryl-6-O-aryl'-D-glucopyranosides
A synthetic method of introducing bulky aryl groups at the 2-O- and 6-O-positions on glucopyranosides was developed. A total of 37 new compounds of this class were obtained successfully. These compounds were tested on several tumor cell lines by MTT assays, and some of them exhibited encouraging inhibitory activities. The most potent compound, CAB-SHZH-27, exhibited EC(50) values of 14, 12, and 10 micromol/L on A549, MDA-MB-231 and HeLa cells, respectively. A preliminary structure-activity relationship analysis indicates that the two free hydroxyl groups on the D-glucose core are indispensable for the biological activities of this class of compounds, and the aryl group at the 6-O-position has a more obvious impact than the one at the 2-O-position. An interesting 'on-off' mechanism of this class of compounds was also observed in our MTT assays, which remains to be explored.
Dual-reactive Surfactant Used for Synthesis of Functional Nanocapsules in Miniemulsion
Dual-functional amphiphilic block copolymers, alpha-azido-omega-2-chloroisobutyrate-poly(oligo(ethylene oxide) monomethyl ether methacrylate)-b-poly(n-butyl methacrylate), prepared by atom-transfer radical polymerization were used as dual-reactive surfactants (i.e., macroinitiators for a miniemulsion copolymerization of a monovinyl monomer and divinyl cross-linker as well as surfactants with latent functionality). Because of the amphiphilic nature of the block copolymers used as surfactant/initiators, the polymerization was initiated at the oil-water interface, with polymer chains slowly growing inward in a controlled manner after activation by the catalyst. Polymeric nanocapsules with cross-linked shells and the latent azido functionality were obtained. Introduction of various degradable cross-linking agents into the system resulted in the formation of nanocapsules that were cleaved under specific conditions. The preserved latent alpha-terminal azido groups in the dual-reactive surfactant were utilized to attach a fluorescent dansyl probe and/or atom-transfer radical polymerization initiators to grow linear polymer chains forming an additional shell covalently connected to the nanocapsules.
CpG Island Methylator Phenotype Involving Chromosome 3p Confers an Increased Risk of Non-small Cell Lung Cancer
This study aims to explore the association of CpG island methylator phenotype (CIMP) involving tumor suppressor genes on short arm of chromosome 3 (3p) with increased risk of non-small cell lung cancer (NSCLC).
[Expression, Purification and Activity Analyses of Three Bcl-2 Family Proteins]
Bcel-2 family proteins (Bcl-x(L), Bcl-2, Mel-1 etc.) are key regulators of some life processes, including apoptosis and autophagy. They are currently considered as promising targets for developing new anti-tumor therapies. In our study, the human Bcl-2/Bcl-x(L) chimeric gene and the human/mouse Mel-1 chimeric gene were designed and cloned, and the prokaryotic expression vectors for expressing glutathione S-transferase (GST) fusion proteins and histidine tag fusion proteins were constructed respectively. These two proteins as well as the GST-Bcl-x(L) fusion protein were all successfully expressed in E. coli and subsequently purified. In addition, we measured the binding of these Bcl-2 family proteins to the Bid BH3 peptide by fluorescence polarization-based assay. The dissociation constants (Kd) obtained by us were in general agreement with the data reported in literature. The Kd values of all three proteins with or without the GST tag were almost identical. All these results validate the biological functions of these Bcl-2 family proteins obtained by us. These proteins can be used in the experimental screening of small-molecule regulators of Bcl-2 family proteins in vitro.
Destructive Power Dynamics of Alpha-theta Oscillations Via Spike and Wave in CA3
The power dynamics of alpha-theta oscillations via inter-ictal spikes and waves (SWs) in CA3 is investigated by means of Hilbert transform and the statistical method based on CA3 channel of LFP(Local Field Potention) data sampled on total 6 rats in resting with sniffing and of iEEG data on total 10 patients in quiet wakefulness. The comparison of alpha-theta power is done between the inter-ictal groups and control groups. It is concluded that the inter-ictal SWs can disrupt the power of alpha-theta oscillations, leading to the decreased power after SW. Because the alpha-theta oscillations are related with the cognition, it is estimated that the inter-ictal SWs can negatively affecte the cognitive function during the inter-ictal dynamics, although the alpha-theta power will be recoverable in some days after injections, even exceed over the power level before injections.
Uniform PEO Star Polymers Synthesized in Water Via Free Radical Polymerization or Atom Transfer Radical Polymerization
Amphiphilic star shaped polymers with poly(ethylene oxide) (PEO) arms and cross-linked hydrophobic core were synthesized in water via either conventional free radical polymerization (FRP) or atom transfer radical polymerization (ATRP) techniques using a simple "arm-first" method. In FRP, PEO based macromonomers (MM) were used as arm precursors, which were then cross-linked by divinylbenzene (DVB) using 2,2'-azoisobutyronitrile (AIBN). Uniform star polymers (Mw/Mn < 1.2) were achieved through adjustment of the ratio of PEO MM, DVB, and AIBN. While in case of ATRP, both PEO MM, and PEO based macroinitiator (MI) were used as arm precursors with ethylene glycol diacrylate as cross-linker. Even more uniform star polymers with less contamination by low MW polymers were obtained, as compared to the products synthesized by FRP.
Ag Nanoparticles/PPV Composite Nanofibers with High and Sensitive Opto-electronic Response
ABSTRACT: The novel Ag nanoparticles/poly(p-phenylene vinylene) [PPV] composite nanofibers were prepared by electrospinning. The transmission electron microscope image shows that the average diameter of composite fibers is about 500 nm and Ag nanoparticles are uniformly dispersed in the PPV matrix with an average diameter of about 25 nm. The Fourier transform infrared spectra suggest that there could be a coordination effect to a certain extent between the Ag atom and the π system of PPV, which is significantly favorable for the dissociation of photoexcitons and the charge transfer at the interface between the Ag nanoparticle and the PPV. The Au top electrode device of the single Ag/PPV composite nanofiber exhibits high and sensitive opto-electronic responses. Under light illumination of 5.76 mW/cm2 and voltage of 20 V, the photocurrent is over three times larger than the dark current under same voltage, which indicates that this kind of composite fiber is an excellent opto-electronic nanomaterial.
Direct DNA Conjugation to Star Polymers for Controlled Reversible Assemblies
Polymer biomolecule hybrids represent a powerful class of highly customizable nanomaterials. Here, we report star-polymer conjugates with DNA using a "ligandless" Cu(I) promoted azide-alkyne cycloaddition click reaction. The multivalency of the star-polymer architecture allows for the concomitant conjugation of other molecules along with the DNA, and the conjugation method provides control over the DNA orientation. The star-polymer DNA nanoparticles are shown to assemble into higher-order nanoassemblies through hybridization. Further, we show that the DNA strands can be utilized in controlled disassembly of the nanostructures.
Low-energy Multistage Atrial Defibrillation Therapy Terminates Atrial Fibrillation with Less Energy Than a Single Shock
Implantable device therapy of atrial fibrillation (AF) is limited by pain from high-energy shocks. We developed a low-energy multistage defibrillation therapy and tested it in a canine model of AF.
The Role of Dynamic Instability and Wavelength in Arrhythmia Maintenance As Revealed by Panoramic Imaging with Blebbistatin Vs. 2,3-butanedione Monoxime
Unlike other excitation-contraction uncouplers, blebbistatin has few electrophysiological side effects and has gained increasing acceptance as an excitation-contraction uncoupler in optical mapping experiments. However, the possible role of blebbistatin in ventricular arrhythmia has hitherto been unknown. Furthermore, experiments with blebbistatin and 2,3-butanedione monoxime (BDM) offer an opportunity to assess the contribution of dynamic instability and wavelength of impulse propagation to the induction and maintenance of ventricular arrhythmia. Recordings of monophasic action potentials were used to assess effects of blebbistatin in Langendorff-perfused rabbit hearts (n = 5). Additionally, panoramic optical mapping experiments were conducted in rabbit hearts (n = 7) that were sequentially perfused with BDM, then washed out, and subsequently perfused with blebbistatin. The susceptibility to arrhythmia was investigated using a shock-on-T protocol. We found that 1) application of blebbistatin did not change action potential duration (APD) restitution; 2) in contrast to blebbistatin, BDM flattened APD restitution curve and reduced the wavelength; and 3) incidence of sustained arrhythmia was much lower under blebbistatin than under BDM (2/123 vs. 23/99). While arrhythmias under BDM were able to stabilize, the arrhythmias under blebbistatin were unstable and terminated spontaneously. In conclusion, the lower susceptibility to arrhythmia under blebbistatin than under BDM indicates that blebbistatin has less effects on arrhythmia dynamics. A steep restitution slope under blebbistatin is associated with higher dynamic instability, manifested by the higher incidence of not only wave breaks but also wave extinctions. This relatively high dynamic instability leads to the self-termination of arrhythmia because of the sufficiently long wavelength under blebbistatin.
