Microcurrent-Mediated Modulation of Myofibroblasts for Cardiac Repair and Regeneration.

Cardiovascular diseases are a significant cause of illness and death worldwide, often resulting in myofibroblast differentiation, pathological remodeling, and fibrosis, characterized by excessive extracellular matrix protein deposition. Treatment options for cardiac fibrosis that can effectively target myofibroblast activation and ECM deposition are limited, necessitating an unmet need for new therapeutic approaches. In recent years, microcurrent therapy has demonstrated promising therapeutic effects, showcasing its translational potential in cardiac care. This study therefore sought to investigate the effects of microcurrent therapy on cardiac myofibroblasts, aiming to unravel its potential as a treatment for cardiac fibrosis and heart failure. The experimental design involved the differentiation of primary rat cardiac fibroblasts into myofibroblasts. Subsequently, these cells were subjected to microcurrent (MC) treatment at 1 and 2 µA/cm2 DC with and without polarity reversal. We then investigated the impact of microcurrent treatment on myofibroblast cell behavior, including protein and gene expression, by performing various assays and analyses comparing them to untreated myofibroblasts and cardiac fibroblasts. The application of microcurrents resulted in distinct transcriptional signatures and improved cellular processes. Gene expression analysis showed alterations in myofibroblast markers, extracellular matrix components, and pro-inflammatory cytokines. These observations show signs of microcurrent-mediated reversal of myofibroblast phenotype, possibly reducing cardiac fibrosis, and providing insights for cardiac tissue repair.

High-Resolution "Magic"-Field Spectroscopy on Trapped Polyatomic Molecules.

Rapid progress in cooling and trapping of molecules has enabled first experiments on high-resolution spectroscopy of trapped diatomic molecules, promising unprecedented precision. Extending this work to polyatomic molecules provides unique opportunities due to more complex geometries and additional internal degrees of freedom. Here, this is achieved by combining a homogeneous-field microstructured electric trap, rotational transitions with minimal Stark broadening at a"magic" offset electric field, and optoelectrical Sisyphus cooling of molecules to the low millikelvin temperature regime. We thereby reduce Stark broadening on the J=5←4 (K=3) transition of formaldehyde at 364 GHz to well below 1 kHz, observe Doppler-limited linewidths down to 3.8 kHz, and determine the magic-field line position with an uncertainty below 100 Hz. Our approach opens a multitude of possibilities for investigating diverse polyatomic molecule species.

Fast, precise, and widely tunable frequency control of an optical parametric oscillator referenced to a frequency comb.

Optical frequency combs (OFCs) provide a convenient reference for the frequency stabilization of continuous-wave lasers. We demonstrate a frequency control method relying on tracking over a wide range and stabilizing the beat note between the laser and the OFC. The approach combines fast frequency ramps on a millisecond timescale in the entire mode-hop free tuning range of the laser and precise stabilization to single frequencies. We apply it to a commercially available optical parametric oscillator (OPO) and demonstrate tuning over more than 60 GHz with a ramping speed up to 3 GHz/ms. Frequency ramps spanning 15 GHz are performed in less than 10 ms, with the OPO instantly relocked to the OFC after the ramp at any desired frequency. The developed control hardware and software are able to stabilize the OPO to sub-MHz precision and to perform sequences of fast frequency ramps automatically.

Optoelectrical Cooling of Polar Molecules to Submillikelvin Temperatures.

We demonstrate direct cooling of gaseous formaldehyde (H2CO) to the microkelvin regime. Our approach, optoelectrical Sisyphus cooling, provides a simple dissipative cooling method applicable to electrically trapped dipolar molecules. By reducing the temperature by 3 orders of magnitude and increasing the phase-space density by a factor of ∼10(4), we generate an ensemble of 3×10(5) molecules with a temperature of about 420 µK, populating a single rotational state with more than 80% purity.

Rotational Cooling of Trapped Polyatomic Molecules.

Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH_{3}F) by optically pumping the population of 16 M sublevels in the rotational states J=3, 4, 5 and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby generating a translationally cold (≈30 mK) and nearly pure state ensemble of about 10^{6} molecules. Our scheme is extendable to larger sets of initial states, other final states, and a variety of molecule species, thus paving the way for internal-state control of ever-larger molecules.

Sisyphus cooling of electrically trapped polyatomic molecules.

Polar molecules have a rich internal structure and long-range dipole-dipole interactions, making them useful for quantum-controlled applications and fundamental investigations. Their potential fully unfolds at ultracold temperatures, where various effects are predicted in many-body physics, quantum information science, ultracold chemistry and physics beyond the standard model. Whereas a wide range of methods to produce cold molecular ensembles have been developed, the cooling of polyatomic molecules (that is, with three or more atoms) to ultracold temperatures has seemed intractable. Here we report the experimental realization of optoelectrical cooling, a recently proposed cooling and accumulation method for polar molecules. Its key attribute is the removal of a large fraction of a molecule's kinetic energy in each cycle of the cooling sequence via a Sisyphus effect, allowing cooling with only a few repetitions of the dissipative decay process. We demonstrate the potential of optoelectrical cooling by reducing the temperature of about one million CH(3)F molecules by a factor of 13.5, with the phase-space density increased by a factor of 29 (or a factor of 70 discounting trap losses). In contrast to other cooling mechanisms, our scheme proceeds in a trap, cools in all three dimensions and should work for a large variety of polar molecules. With no fundamental temperature limit anticipated down to the photon-recoil temperature in the nanokelvin range, we expect our method to be able to produce ultracold polyatomic molecules. The low temperatures, large molecule numbers and long trapping times of up to 27 seconds should allow an interaction-dominated regime to be attained, enabling collision studies and investigation of evaporative cooling towards a Bose-Einstein condensate of polyatomic molecules.

Chemosensory anxiety signals augment the startle reflex in humans.

The aim of the present study was to investigate whether chemosensory anxiety signals can activate behavioral withdrawal systems in humans. Twelve male university students donated their axillary sweat in two situations: right before an oral academic examination (anxiety condition) and during ergometric training (exercise condition). Subjective ratings revealed that the odor donors experienced significantly more anxiety and less pleasure during the anxiety condition than during the exercise condition. Seven subjects (three females) participated in the psychophysiological experiment. The chemosensory stimuli from pooled sweat samples of the donors, and from unused cotton pads (pad condition) were presented via a constant-flow olfactometer. Acoustic startle probes (100 dB (A)) were delivered during and between the presentations of the chemosensory stimuli. Only three subjects were able to discriminate the chemosensory stimuli of the human sweat samples from room air. However, the startle reflex amplitude (EMG of the eyeblink response) recorded in the context of chemosensory anxiety signals was increased, as compared to the amplitude recorded in the context of chemosensory stimuli from either exercise (p = 0.018) or cotton pad (p = 0.012). It is concluded that chemosensory anxiety signals may pre-attentively prime defensive behavior.

Positive emotional priming of facial affect perception in females is diminished by chemosensory anxiety signals.

Chemosensory communication of anxiety is a common phenomenon in vertebrates and improves perceptual and responsive behaviour in the perceiver in order to optimize ontogenetic survival. A few rating studies reported a similar phenomenon in humans. Here, we investigated whether subliminal face perception changes in the context of chemosensory anxiety signals. Axillary sweat samples were taken from 12 males while they were waiting for an academic examination and while exercising ergometric training some days later. 16 subjects (eight females) participated in an emotional priming study, using happy, fearful and sad facial expressions as primes (11.7 ms) and neutral faces as targets (47 ms). The pooled chemosensory samples were presented before and during picture presentation (920 ms). In the context of chemosensory stimuli derived from sweat samples taken during the sport condition, subjects judged the targets significantly more positive when they were primed by a happy face than when they were primed by the negative facial expressions (P = 0.02). In the context of the chemosensory anxiety signals, the priming effect of the happy faces was diminished in females (P = 0.02), but not in males. It is discussed whether, in socially relevant ambiguous perceptual conditions, chemosensory signals have a processing advantage and dominate visual signals or whether fear signals in general have a stronger behavioural impact than positive signals.