Carbon fiber (CF) is a potential microwave absorption (MA) material due to the strong dielectric loss. Nevertheless, owing to the high conductivity, poor impedance matching of carbon-based materials results in limited MA performance. How to solve this problem and achieve excellent MA performance remains a principal challenge. Herein, taking full advantage of CF and excellent impedance matching of bimetallic metal-organic frameworks (MOF) derivatives layer, an excellent microwave absorber based on micron-scale 1D CF and NiCoMOF (CF@NiCoMOF-800) is developed. After adjusting the oxygen vacancies of the bimetallic MOF, the resultant microwave absorber presented excellent MA properties including the minimum reflection loss (RLmin ) of -80.63 dB and wide effective absorption bandwidth (EAB) of 8.01 GHz when its mass percent is only 5 wt.% and the thickness is 2.59 mm. Simultaneously, the mechanical properties of the epoxy resin (EP)-based coating with this microwave absorber are effectively improved. The hardness (H), elastic modulus (E), bending strength, and compressive strength of CF@NiCoMOF-800/EP coating are 334 MPa, 5.56 GPa, 82.2 MPa, and 135.8 MPa, which is 38%, 15%, 106% and 53% higher than EP coating. This work provides a promising solution for carbon materials achieving excellent MA properties and mechanical properties.
The peelable microwave absorption (MA) coating with reversible adhesion for stable presence on substrates and easy release without any residuals is highly desired in temporary electromagnetic protection, which can quickly enter and disengage the electromagnetic protection state according to the real-time changeable harsh surroundings. On the contrary, with the incorporation of abundant absorbent to achieve excellent MA ability, the tunable adhesion and sufficient cohesion are extremely challenging to fulfill the above requirement. The reported peelable coatings still have problems in controlling adhesion/cohesion strength and coating release, facing substantial residuals after peeling even using complex chemical modification or abundant additives. Herein, a peelable MA coating based on the block characteristics of polar and nonpolar segments of poly(styrene-(ethylene-co-butylene)-styrene) (SEBS) is successfully developed. The polyaniline-decorated carbon nanotube as a microwave absorber plays a positive influence on the adhesion/cohesion of the coating due to bonding interaction. The competitive effective absorption bandwidth (EAB) of 8.8 GHz and controllable yet reversible adhesion release on various substrates and complex surfaces have been achieved. The reusability endows peelable MA coating with 93% retention of EAB even after ten coating-peeling cycles. The coating with excellent chemical and adhesion stability can effectively protect substrates from salt/acid/alkali corrosion, showing over 98% retention of EAB even after 8 h of accelerated corrosion. Our peelable MA coating via a general yet reliable approach provides a prospect for temporary electromagnetic protection.
The coexistence of spin-orbit coupling and piezoelectricity in a single material may have potential application in multifunctional devices, including spintronics, nanorobotics and piezotronics. Spin-orbit coupling provides a new means to manipulate electron's spin without an additional external magnetic field, while piezoelectricity refers to the interplay between mechanical stresses and electric polarization. Using first-principles calculations, the structural, electronic, optical, spin, and piezoelectric properties of the Janus Ge2XY (X ≠ Y = P, As, Sb, and Bi) monolayers were systematically investigated. All the Ge2XY are energetically and dynamically stable in the α phase. At the GW level, Ge2AsSb, Ge2AsBi, and Ge2SbBi have direct fundamental band gaps of 0.65, 0.64, and 0.91 eV. At the GW + BSE level, their optical gaps are 0.42, 0.45, and 0.63 eV, and the optical absorption coefficients can reach about 10-5 cm-1 in the infrared light region, which reveals that they have potential for application in infrared photodetectors. For Ge2PBi, Ge2AsBi, and Ge2SbBi containing the heavy Bi element, the lowermost conduction band and uppermost valence band have large spin splitting along the M-K and K-Γ lines, and the bands near the Fermi level possess Rashba spin splitting at the Γ point. Ge2PBi and Ge2SbBi have both large in-plane piezoelectric coefficients d11 (-0.75 and -3.18 pm V-1) and out-of-plane piezoelectric coefficients d31 (0.37 and 0.30 pm V-1). Our findings are helpful to understand the mechanism of the spin-orbit physics and piezoelectricity of Janus Ge2XY monolayers and guide experiments in exploring novel multifunctional materials.
The impedance matching performance of carbon nanotubes (CNTs) can be effectively enhanced by developing a uniform magnetic impedance matching layer, which can take on critical significance in achieving the desirable microwave absorption (MA) performance. To obtain a uniform coating of Nickel (Ni) nanoparticles on CNTs, several methods have been developed (e.g., the γ-irradiation technique, electroless deposition, as well as microwave welding method). However, the intricate and complicated conditions of the above-mentioned methods limit their wide application. Therefore, controlling the distribution of Ni nanoparticles with the aid of a concise and effective method remains a great challenge. Herein, in view of the uniform dispersion effect of polyvinylpyrrolidone (PVP) on CNTs and its complexation with Ni ions, uniform coating of Ni nanoparticles on CNTs is well developed after it is introduced in the hydrothermal process. The prepared Ni/CNTs composites exhibited excellent MA performance in comparison with those of reported Ni/CNTs composites for the ideal impedance matching performance and microwave attenuation ability. When the filler content was only 15 wt%, the minimum reflection loss (RLmin) reached -39.5 dB, and the effective bandwidth (EB) with RL < -10 dB reached 5.2 GHz at the thickness of 1.15 mm. A scalable strategy of regulating the distribution of Ni nanoparticles and preparing a lightweight microwave absorber based on CNTs was developed in this study, which can serve as a vital guideline for preparing novel MA composite materials.
Polyimide (PI) foam with excellent microwave absorption (MA) performance and desirable compressive strength is highly critical and in demand in the structural MA components. Although the satisfactory MA performance of the present PI-based MA foams has been achieved by employing diverse methods, the relatively low compressive strength (â¼KPa) restricted them from use as structural MA foams in practical application. Herein, isocyanate acid was introduced to the backbone of PI resin, which not only increased the PI backbone polarity and strength as rigid chain segment, but also served as a self-foaming component. The porous structure of PI foams was readily regulated by adjusting the water and carbon nanotube (CNT) filler contents of precursor dispersion. As a result of the improved polarity of the PI backbone resulted from the isocyanate group and high dielectric loss of CNT, the high compressive strength of 7.04 MPa and impressive MA property of the resultant PI foam with a low CNT loading ratio of 1.5 wt % were achieved, which were much higher than those reported previously. Especially, the effective absorption bandwidth (EAB) (RL < -10 dB) was up to 10.7 GHz (at the thickness of 3 mm), covering the C, X, and Ku bands simultaneously. Meanwhile, the EAB of the as-prepared PI foam retained 9.3 and 9.7 GHz even after being subjected to liquid nitrogen (-196 °C) and high temperature (300 °C) treatments due to the desirable stability of PI. In addition, the excellent thermal insulation resulted from the pores structure and low filler content was achieved, where the top surface only presented 60 °C after placing on 300 °C platform for 30 min. The high compressive strength, impressive MA property, and thermal insulation endowed the resultant CNT/PI foam with great potential application as structural MA foam in a harsh service environment.
Spring viremia of carp virus (SVCV) is a severe infectious pathogen that causes high rates of mortality in cyprinids and other fish species. Despite numerous investigations of SVCV infection, the underlying molecular mechanisms remain poorly understood. In this study, we found that the SVCV matrix protein (SVCV-M) played an inhibitory role in the host interferon (IFN) response by targeting the MAVS/TRAF3 signaling axis, thereby uncovering a previously unrecognized mechanism of SVCV escape from host innate antiviral immunity. Mechanistically, SVCV-M was located at the mitochondria independent of MAVS, which allowed SVCV-M to build an arena for competition with the MAVS platform. A microscale thermophoresis assay showed that SVCV-M had a high affinity for TRAF3, as indicated by a lower equilibrium dissociation constant (KD) value than that of MAVS with TRAF3. Therefore, the association of MAVS with TRAF3 was competitively impaired by SVCV-M in a dose-dependent manner. Accordingly, SVCV-M showed a potent ability to inhibit the K63-linked polyubiquitination of TRAF3. This inhibition was accompanied by the impairment of the IFN response, as shown by the marked decline in IFN-φ1-promoter (pro) luciferase reporter activity. By constructing truncated TRAF3 and SVCV-M proteins, the RING finger, zinc finger, and coiled-coil domains of TRAF3 and the hydrophobic-pocket-like structure formed by the α2-, α3-, and α4-helices of SVCV-M may be the major target and antagonistic modules responsible for the protein-protein interaction between the TRAF3 and SVCV-M proteins. These findings highlighted the intervention of SVCV-M in host innate immunity, thereby providing new insights into the extensive participation of viral matrix proteins in multiple biological activities. IMPORTANCE The matrix protein of SVCV (SVCV-M) is an indispensable structural element for nucleocapsid condensation and virion formation during viral morphogenesis, and it connects the core nucleocapsid particle to the outer membrane within the mature virus. Previous studies have emphasized the architectural role of SVCV-M in viral construction; however, the potential nonstructural functions of SVCV-M in viral replication and virus-host interactions remain poorly understood. In this study, we identified the inhibitory role of the SVCV-M protein in host IFN production by competitively recruiting TRAF3 from the MAVS signaling complex and impairing TRAF3 activation via inhibition of K63-linked polyubiquitination. This finding provided new insights into the regulatory role of SVCV-M in host innate immunity, which highlighted the broader functionality of rhabdovirus matrix protein apart from being a structural protein. This study also revealed a previously unrecognized mechanism underlying SVCV immune evasion by inhibiting the IFN response by targeting the MAVS/TRAF3 signaling axis.
Carps , Rhabdoviridae Infections/veterinary , Rhabdoviridae/physiology , Adaptor Proteins, Signal Transducing/metabolism , Animals , Immunity, Innate , Interferons/metabolism , Rhabdoviridae Infections/immunology , TNF Receptor-Associated Factor 3/genetics , TNF Receptor-Associated Factor 3/metabolism , Viral Matrix Proteins/metabolism , Viremia/veterinary
Retinoic acid-inducible gene I (RIG-I) is an important cytosolic pattern recognition receptor crucial for sensing RNA virus infection and initiating innate immune responses. However, the participation of RIG-I in cellular development under physiological conditions remains limited. In this study, the regulatory role of RIG-I in embryonic hematopoiesis was explored in a zebrafish model. Results showed that rig-I was ubiquitously expressed during embryogenesis at 24 h postfertilization (hpf). A defect in RIG-I remarkably disrupted the emergence of primitive hematopoietic precursors and subsequent myeloid and erythroid lineages. In contrast, RIG-I deficiency did not have an influence on the generation of endothelial precursors and angiogenesis and the development of mesoderm and adjacent tissues. The alteration in these phenotypes was confirmed by whole-mount in situ hybridization with lineage-specific markers. In addition, immunostaining and TUNEL assays excluded the abnormal proliferation and apoptosis of hematopoietic precursors in RIG-I-deficient embryos. Mechanistically, RIG-I regulates primitive hematopoiesis through downstream IFN signaling pathways, as shown by the decline in ifnφ2 and ifnφ3 expression, along with rig-I knockdown, and rescue of the defects of hematopoietic precursors in RIG-I-defective embryos after administration with ifnφ2 and ifnφ3 mRNAs. Additionally, the defects of hematopoietic precursors in RIG-I morphants could be efficiently rescued by the wild-type RIG-I but could not be restored by the RNA-binding-defective RIG-I with site mutations at the RNA-binding pocket, which are essential for association with RNAs. This finding suggested that endogenous RNAs may serve as agonists to activate RIG-I-modulated primitive hematopoiesis. This study revealed the functional diversity of RIG-I under physiological conditions far beyond that previously known.
Zebrafish Proteins , Zebrafish , Animals , Embryonic Development , Hematopoiesis/genetics , RNA , Zebrafish/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism
BACKGROUND: The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce. METHODS: We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated. RESULTS: Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively. CONCLUSIONS: The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.
Dementia , Rural Population , Child , China/epidemiology , Cross-Sectional Studies , Dementia/epidemiology , Humans , Prevalence , Risk Factors , Urban Population
Composites based on a shape-memory polymer doped with conductive particles are considered as soft actuators for artificial muscles and robots. Low-voltage actuating is expected to reduce equipment requirement and safety hazards, which requires a highly conductive particle content but weakens the reversible deformation. The spatial distribution of the conductive particle is key to decreasing the actuating voltage and maintaining the reversible deformation. Herein, an approach of fabricating a low-voltage actuator that can perform various biomimetic locomotions by spraying and hot pressing is reported. Carbon nanotubes (CNTs) are enriched inside the surface layer of poly(ethylene-co-vinyl acetate) (EVA) to form a high-density conductive network without degradation of the reversible deformation. The bilayer CNT/EVA actuator exhibits a reversible transformation of more than 10% even with 100 cycles, which requires an applied voltage of just 15 V. Taking advantage of the reprogrammability of the CNT/EVA actuator and reversible shift between the different shapes, different biomimetic locomotions (sample actuator, gripper, and walking robot) are demonstrated without any additional mechanical components. A scheme combining the electrical properties and the shape-memory effect provides a versatile strategy to fabricate low-voltage-actuated polymeric actuators, providing inspiration in the development of electrical soft actuators and biomimetic devices.
[Figure: see text].
Calcium Signaling , Membrane Proteins/metabolism , Myocytes, Cardiac/metabolism , Ryanodine Receptor Calcium Release Channel/genetics , Tachycardia, Ventricular/genetics , Action Potentials , Animals , Binding Sites , Cells, Cultured , HEK293 Cells , Humans , Mice , Mice, Inbred C57BL , Mutation , Myocytes, Cardiac/physiology , Myocytes, Cardiac/ultrastructure , Protein Binding , Ryanodine Receptor Calcium Release Channel/chemistry , Ryanodine Receptor Calcium Release Channel/metabolism , Tachycardia, Ventricular/metabolism , Tachycardia, Ventricular/pathology
Excellent electromagnetic interference (EMI) shielding ability, light weight, and good heat resistance are highly required for practical applications of EMI shielding materials, such as in areas of aerospace, aircraft, and automobiles. Herein, a lightweight and robust carbon nanotube (CNT)/polyimide (PI) foam was developed for efficient and heat-resistant EMI shielding. Thanks to poly(vinyl pyrrolidone) (PVP) as a surfactant that not only promotes the uniform dispersion of CNTs to form perfect CNT conductive networks but also can be removed in situ during the polymerization process, the density of resultant CNT/PI foam is only 32.1 mg·cm-3, and the EMI shielding effectiveness (EMI SE) is up to 41.1 dB, which represents one of the highest EMI SE values compared to previously reported polymer-based foams. The CNT/PI foam also achieves the absorption coefficient (A) of up to 82.3%, which is very impressive in CNT/polymer foams at comparable EMI SE levels. The PI matrix endows the foam with excellent heat resistance. The as-prepared CNT/PI foam presents a higher EMI SE than 35 dB even after being subjected to the flame of an alcohol burner. Moreover, the compressive strength and compressive modulus are up to 240.9 and 323.9 kPa. These results indicate its certain application potential in the harsh requirement of aeronautics and aerospace industries as a highly efficient and lightweight EMI shielding material.
The NLR family pyrin domain containing 3 (NLRP3) inflammasome is one of the best-characterized inflammasomes in humans and other mammals. However, knowledge about the NLRP3 inflammasome in nonmammalian species remains limited. Here, we report the molecular and functional identification of an NLRP3 homolog (DrNLRP3) in a zebrafish (Danio rerio) model. We found that DrNLRP3's overall structural architecture was shared with mammalian NLRP3s. It initiates a classical inflammasome assembly for zebrafish inflammatory caspase (DrCaspase-A/-B) activation and interleukin 1ß (DrIL-1ß) maturation in an apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)-dependent manner, in which DrNLRP3 organizes DrASC into a filament that recruits DrCaspase-A/-B by homotypic pyrin domain (PYD)-PYD interactions. DrCaspase-A/-B activation in the DrNLRP3 inflammasome occurred in two steps, with DrCaspase-A being activated first and DrCaspase-B second. DrNLRP3 also directly activated full-length DrCaspase-B and elicited cell pyroptosis in a gasdermin E (GSDME)-dependent but ASC-independent manner. These two events were tightly coordinated by DrNLRP3 to ensure efficient IL-1ß secretion for the initiation of host innate immunity. By knocking down DrNLRP3 in zebrafish embryos and generating a DrASC-knockout (DrASC-/-) fish clone, we characterized the function of the DrNLRP3 inflammasome in anti-bacterial immunity in vivo The results of our study disclosed the origin of the NLRP3 inflammasome in teleost fish, providing a cross-species understanding of the evolutionary history of inflammasomes. Our findings also indicate that the NLRP3 inflammasome may coordinate inflammatory cytokine processing and secretion through a GSDME-mediated pyroptotic pathway, uncovering a previously unrecognized regulatory function of NLRP3 in both inflammation and cell pyroptosis.
Cytoskeletal Proteins/metabolism , Inflammasomes/metabolism , Interleukin-1beta/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , Receptors, Estrogen/metabolism , Zebrafish Proteins/metabolism , Zebrafish/metabolism , Animals , Caspases/metabolism , HEK293 Cells , Humans , Mice , Protein Aggregates , Receptors, Estrogen/chemistry , Zebrafish Proteins/chemistry
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, resulted from the silencing of the Fmr1 gene and the subsequent loss of fragile X mental retardation protein (FMRP). Spine dysgenesis and cognitive impairment have been extensively characterized in FXS; however, the underlying mechanism remains poorly understood. As an important regulator of spine maturation, intercellular adhesion molecule 5 (ICAM5) mRNA may be one of the targets of FMRP and involved in cognitive impairment in FXS. Here we show that in Fmr1 KO male mice, ICAM5 was excessively expressed during the late developmental stage, and its expression was negatively correlated with the expression of FMRP and positively related with the morphological abnormalities of dendritic spines. While in vitro reduction of ICAM5 normalized dendritic spine abnormalities in Fmr1 KO neurons, and in vivo knockdown of ICAM5 in the dentate gyrus rescued the impaired spatial and fear memory and anxiety-like behaviors in Fmr1 KO mice, through both granule cell and mossy cell with a relative rate of 1.32 ± 0.15. Furthermore, biochemical analyses showed direct binding of FMRP with ICAM5 mRNA, to the coding sequence of ICAM5 mRNA. Together, our study suggests that ICAM5 is one of the targets of FMRP and is implicated in the molecular pathogenesis of FXS. ICAM5 could be a therapeutic target for treating cognitive impairment in FXS.SIGNIFICANCE STATEMENT Fragile X syndrome (FXS) is characterized by dendritic spine dysgenesis and cognitive dysfunctions, while one of the FMRP latent targets, ICAM5, is well established for contributing both spine maturation and learning performance. In this study, we examined the potential link between ICAM5 mRNA and FMRP in FXS, and further investigated the molecular details and pathological consequences of ICAM5 overexpression. Our results indicate a critical role of ICAM5 in spine maturation and cognitive impairment in FXS and suggest that ICAM5 is a potential molecular target for the development of medication against FXS.
Cognitive Dysfunction/metabolism , Dendritic Spines/metabolism , Fragile X Syndrome/metabolism , Gene Expression Regulation/physiology , Membrane Glycoproteins/metabolism , Nerve Tissue Proteins/metabolism , Animals , Cognitive Dysfunction/genetics , Dendritic Spines/pathology , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/complications , Fragile X Syndrome/genetics , Male , Mice , Mice, Knockout , Neurogenesis/genetics
Spinal cord injury (SCI) is a devastating neurological condition that results in progressive tissue loss, secondary to vascular dysfunction and inflammation. Lack of effective pharmacotherapies for SCI is mainly attributable to an incomplete understanding of its pathogenesis. Stimulator of interferon gene (Sting), also known as Transmembrane protein 173 (TMEM173), activates the type I interferon-regulated innate immune response, playing crucial role in modulating inflammation. However, the mechanism underlying Sting activation in SCI is still unclear. Here, we reported that Sting functioned as a positive regulator of SCI. Sting expression was increased in the injured spinal cord samples of SCI mice, along with significantly up-regulated levels of pro-inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6. Suppressing Sting expression in lipopolysaccharide-incubated mouse microglia markedly reduced the activation of nuclear factor-κB (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways, as illustrated by the decreased phosphorylation of IKKß, IκBα, NF-κB/p65, p38, ERK1/2 and JNK. Furthermore, LPS-stimulated release of pro-inflammatory cytokines in microglial cells was also reversed by Sting knockdown. In contrast, LPS-induced inflammation was further accelerated in microglial cells with Sting over-expression through potentiating NF-κB and MAPKs signaling. Mechanistically, Sting directly interacted with the TANK-binding kinase 1 (TBK1), thus promoting its phosphorylation and the activation of down-streaming NF-κB and MAPKs signaling pathways. Notably, the effects of Sting on SCI progression were verified in mice. Consistently, Sting knockout alleviated inflammatory response and facilitated recovery after SPI in mice through blocking TBK1 activation and subsequent NF-κB and MAPKs phosphorylation. In summary, our findings may provide a novel strategy for prevention and treatment of SCI by targeting Sting.
Inflammation/metabolism , Inflammation/pathology , Membrane Proteins/metabolism , Microglia/metabolism , Microglia/pathology , Protein Serine-Threonine Kinases/metabolism , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology , Animals , Cell Line , Cytokines/metabolism , Enzyme Activation , Inflammation Mediators , Lipopolysaccharides , MAP Kinase Signaling System/drug effects , Male , Mice, Inbred C57BL , NF-kappa B/metabolism , Protein Binding
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic arrhythmia that manifests syncope or sudden death in children and young adults under stress conditions. CPVT patients often present bradycardia and sino-atrial node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN function in two CPVT families and in a novel knock-in (KI) mouse model carrying the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate. Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was slower in KI mouse SAN preparations than in WT, without any significant alteration in the "funny" current (If ). The L-type Ca2+ current was reduced in KI SAN cells in a [Ca2+]i-dependent way, suggesting that bradycardia was due to disrupted crosstalk between the "voltage" and "Ca2+" clock, and the mechanisms of pacemaking was induced by aberrant spontaneous RyR2- dependent Ca2+ release. This finding was consistent with a higher Ca2+ leak during diastolic periods produced by long-lasting Ca2+ sparks in KI SAN cells. Our results uncover a mechanism for the CPVT-causing RyR2 N-terminal mutation R420Q, and they highlight the fact that enhancing the Ca2+ clock may slow the heart rhythm by disturbing the coupling between Ca2+ and voltage clocks.
