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Cardiac arrhythmias are a primary contributor to sudden cardiac death, a major unmet medical need. Because right ventricular (RV) dysfunction increases the risk for sudden cardiac death, we examined responses to RV stress in mice. Among immune cells accumulated in the RV after pressure overload-induced by pulmonary artery banding, interfering with macrophages caused sudden death from severe arrhythmias. We show that cardiac macrophages crucially maintain cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions. Amphiregulin (AREG) produced by cardiac macrophages is a key mediator that controls connexin 43 phosphorylation and translocation in cardiomyocytes. Deletion of Areg from macrophages led to disorganization of gap junctions and, in turn, lethal arrhythmias during acute stresses, including RV pressure overload and β-adrenergic receptor stimulation. These results suggest that AREG from cardiac resident macrophages is a critical regulator of cardiac impulse conduction and may be a useful therapeutic target for the prevention of sudden death. Cardiac immune cells play various roles in the maintenance of homeostasis and diseases in the heart. Here the authors show that cardiac resident macrophages are a critical regulator of cardiac impulse conduction through amphiregulin production, contributing to the prevention of sudden death.

The blood–brain barrier (BBB) has hampered the efficiency of nanoparticle delivery into the brain via conventional strategies. The widening of BBB tight junctions via focused ultrasound (FUS) offers a promising approach for enhancing the delivery of nanoparticles into the brain. However, there is currently an insufficient understanding of how nanoparticles pass through the opened BBB gaps. Here we investigated the size-dependence of nanoparticle delivery into the brain assisted by FUS-induced BBB opening, using gold nanoparticles (AuNPs) of 3, 15, and 120 nm diameter. For 3- and 15-nm AuNPs, FUS exposure significantly increased permeation across an in vitro BBB model by up to 9.5 times, and the permeability was higher with smaller diameter. However, in vivo transcranial FUS exposure in mice demonstrated that smaller particles were not necessarily better for delivery into the brain. Medium-sized (15 nm) AuNPs showed the highest delivery efficiency (0.22% ID), compared with 3- and 120-nm particles. A computational model suggested that this optimum size was determined by the competition between their permeation through opened BBB gaps and their excretion from blood. Our results would greatly contribute to designing nanoparticles for their delivery into the brain for the treatment of central nervous system diseases.

Ultrashort burst laser pulses serve as powerful tools for precise laser processing, broadband ultrafast spectroscopy, and high-speed laser-scanning microscopy. However, the performance of conventional burst pulse generators is limited by constraints in the pulse time interval variability, pulse energy variability, pulse number variability, and overall system complexity. Here, we present a compact burst pulse generator that offers a broad tuning range for pulse time intervals, along with control over the number of pulses and pulse energies within the burst. It consists of four mirrors, two of which are parallel to each other, and outputs pulses that are equally spaced both temporally and spatially. We demonstrated the generation of a burst laser pulse by shaping a single ultrashort laser pulse into six pulses with time intervals ranging from femtoseconds to nanoseconds. The pulse time intervals and energies were consistent with theoretical results.

Frequency- and time-domain Brillouin scattering spectroscopy are powerful tools to read out the mechanical properties of complex systems in material and life sciences. Indeed, coherent acoustic phonons in the time-domain method offer superior depth resolution and a stronger signal than incoherent acoustic phonons in the frequency-domain method. However, it does not allow multichannel detection and, therefore, falls short in signal acquisition speed. Here, we present Brillouin scattering spectroscopy that spans the time and frequency domains to allow the multichannel detection of Brillouin scattering light from coherent acoustic phonons. Our technique maps the time-evolve Brillouin oscillations at the instantaneous frequency of a chromatic-dispersed laser pulse. The spectroscopic heterodyning of Brillouin oscillations in the frequency domain enhances the signal acquisition speed by at least 100-fold over the time-domain method. As a proof of concept, we imaged heterogeneous thin films and biological cells over a wide bandwidth with nanometer depth resolution. We, therefore, foresee that our approach catalyzes future phonon spectroscopy toward real-time mechanical imaging.

Ultrasound is an innovative physical modality allowing non-invasive and reversible modulation of neural circuit activity in the brain with high spatial resolution. Despite growing interest in clinical applications, the safe and effective use of ultrasound neuromodulation has been limited by a lack of understanding of the physical mechanisms underlying its effects. Here, we demonstrate acoustic frequency-dependent physical effects that underlie ultrasound neuromodulation, where cavitation and radiation forces are the dominant sources of low- and high-frequency stimulation, respectively. We used 39.5 kHz and 500 kHz acoustic frequencies to stimulate cultured neural and glial cells, excised from rat cortex, to study acoustic frequency-dependent neural responses. We demonstrate increased evoked responses due to increased cavitation activity at the 39.5 kHz acoustic frequency. In contrast, notable cavitation activity was not detected at 500 kHz despite detection of evoked responses. Our work highlights the dependence of ultrasound neuromodulation on acoustic frequencies, with different physical effects underlying cell responses to low and high sub-MHz acoustic frequency ranges. Competing Interest Statement The authors have declared no competing interest.