Discovery of drug targets for heart failure with preserved and reduced ejection fraction
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PGRMC2 is a pressure-volume regulator critical for myocardial responses to stress in mice
Progesterone receptors are classified into nuclear and membrane-bound receptor families. Previous unbiased proteomic studies indicate a potential association between cardiac diseases and the progesterone receptor membrane-bound component-2 (PGRMC2); however, the role of PGRMC2 in the heart remains unknown. In this study, we use a heart-specific knockout (KO) mouse model (MyH6•Pgrmc2flox/flox) in which the Pgrmc2 gene was selectively deleted in cardiomyocytes. Here we show that PGRMC2 serves as a mediator of steroid hormones for rapid calcium signaling in cardiomyocytes to maintain cardiac contraction, sufficient stroke volume, and adequate cardiac output by regulating the cardiac pressure-volume relationship. The KO hearts from male and female mice exhibit an impairment in pressure-volume relationship. Under hypoxic conditions, this pressure-volume dysregulation progresses to congestive left and right ventricular failure in the KO hearts. Overall, we propose that PGRMC2 is a cardiac pressure-volume regulator to maintain normal cardiac physiology, especially during hypoxic stress.
Revealing the mechanism of cold metal transfer
Cold metal transfer (CMT) is a pioneering feeding system widely used in wire-arc additive manufacturing (WAAM) and welding. However, process optimisation remains challenging. Although CMT has been extensively applied in various industrial sectors, its underlying mechanism is poorly understood because of the complex physics of the interactions between the wire and molten material and the wire’s highly dynamic motion. To elucidate the complexity and features of CMT, we explore the dynamic behaviour and anatomy of molten materials during wire motions (withdrawal and dipping cycles) using high-speed photography at a timescale of microseconds. We reveal a crucial driving force in the melt pool and the frequent ejection of streams or particles during CMT. This study contributes to WAAM and welding by presenting the influential features of ultra-high-dynamics CMT and facilitating the progression of process optimisation.
A novel wearable device integrating ECG and PCG for cardiac health monitoring
The alarming prevalence and mortality rates associated with cardiovascular diseases have emphasized the urgency for innovative detection solutions. Traditional methods, often costly, bulky, and prone to subjectivity, fall short of meeting the need for daily monitoring. Digital and portable wearable monitoring devices have emerged as a promising research frontier. This study introduces a wearable system that integrates electrocardiogram (ECG) and phonocardiogram (PCG) detection. By ingeniously pairing a contact-type PZT heart sound sensing structure with ECG electrodes, the system achieves the acquisition of high-quality ECG and PCG signals. Notably, the signal-to-noise ratios (SNR) for ECG and PCG signals were measured at 44.13 dB and 30.04 dB, respectively, demonstrating the system’s remarkable stability across varying conditions. These collected signals were subsequently utilized to derive crucial feature values, including electromechanical delay (EMD), left ventricular ejection time (LVET), and pre-ejection period (PEP). Furthermore, we collected a dataset comprising 40 cases of ECG and PCG signals, enabling a comparative analysis of these three feature parameters between healthy individuals and coronary heart disease patients. This research endeavor presents a significant step forward in the realm of early, non-invasive, and intelligent monitoring of cardiovascular diseases, offering hope for earlier detection and more effective management of these life-threatening conditions.
Cross-species comparison reveals that Hmga1 reduces H3K27me3 levels to promote cardiomyocyte proliferation and cardiac regeneration
In contrast to adult mammalian hearts, the adult zebrafish heart efficiently replaces cardiomyocytes lost after injury. Here we reveal shared and species-specific injury response pathways and a correlation between Hmga1, an architectural non-histone protein, and regenerative capacity, as Hmga1 is required and sufficient to induce cardiomyocyte proliferation and required for heart regeneration. In addition, Hmga1 was shown to reactivate developmentally silenced genes, likely through modulation of H3K27me3 levels, poising them for a pro-regenerative gene program. Furthermore, AAV-mediated Hmga1 expression in injured adult mouse hearts led to controlled cardiomyocyte proliferation in the border zone and enhanced heart function, without cardiomegaly and adverse remodeling. Histone modification mapping in mouse border zone cardiomyocytes revealed a similar modulation of H3K27me3 marks, consistent with findings in zebrafish. Our study demonstrates that Hmga1 mediates chromatin remodeling and drives a regenerative program, positioning it as a promising therapeutic target to enhance cardiac regeneration after injury.
A phase III study comparing preservative-free latanoprost eye drop emulsion with preserved latanoprost in open-angle glaucoma or ocular hypertension
To evaluate the efficacy and safety of preservative-free latanoprost eye drop emulsion in reducing intraocular pressure (IOP) versus preserved latanoprost in open-angle glaucoma (OAG) or ocular hypertension (OHT).
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