The ion channels of endomembranes.

The endomembrane system consists of organellar membranes in the biosynthetic pathway [endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles] as well as those in the degradative pathway (early endosomes, macropinosomes, phagosomes, autophagosomes, late endosomes, and lysosomes). These endomembrane organelles/vesicles work together to synthesize, modify, package, transport, and degrade proteins, carbohydrates, and lipids, regulating the balance between cellular anabolism and catabolism. Large ion concentration gradients exist across endomembranes: Ca2+ gradients for most endomembrane organelles and H+ gradients for the acidic compartments. Ion (Na+, K+, H+, Ca2+, and Cl-) channels on the organellar membranes control ion flux in response to cellular cues, allowing rapid informational exchange between the cytosol and organelle lumen. Recent advances in organelle proteomics, organellar electrophysiology, and luminal and juxtaorganellar ion imaging have led to molecular identification and functional characterization of about two dozen endomembrane ion channels. For example, whereas IP3R1-3 channels mediate Ca2+ release from the ER in response to neurotransmitter and hormone stimulation, TRPML1-3 and TMEM175 channels mediate lysosomal Ca2+ and H+ release, respectively, in response to nutritional and trafficking cues. This review aims to summarize the current understanding of these endomembrane channels, with a focus on their subcellular localizations, ion permeation properties, gating mechanisms, cell biological functions, and disease relevance.

Non-invasive evaluation of endometrial microvessels via in vivo intrauterine photoacoustic endoscopy.

The endometrium microvessel system, responsible for supplying oxygen and nutrients to the embryo, holds significant importance in evaluating endometrial receptivity (ER). Visualizing this system directly can significantly enhance ER evaluation. Currently, clinical methods like Narrow-band hysteroscopy and Color Doppler ultrasound are commonly used for uterine blood vessel examination, but they have limitations in depth or resolution. Endoscopic Photoacoustic Imaging (PAE) has proven effective in visualizing microvessels in the digestive tract, while its adaptation to uterine imaging faces challenges due to the uterus's unique physiological characteristics. This paper for the first time that uses high-resolution PAE in vivo to capture a comprehensive network of endometrial microvessels non-invasively. Followed by continuous observation and quantitative analysis in the endometrial injury model, we further corroborated that PAE detection of endometrial microvessels stands as a valuable indicator for evaluating ER. The PAE system showcases its promising potential for integration into reproductive health assessments.

Saliency enhancement method for photoacoustic molecular imaging based on Grüneisen relaxation nonlinear effect.

Photoacoustic molecular imaging technology has a wide range of applications in biomedical research. In practical scenarios, both the probes and blood generate signals, resulting in the saliency of the probes in the blood environment being diminished, impacting imaging quality. Although several methods have been proposed for saliency enhancement, they inevitably suffer from moderate generality and detection speed. The Grüneisen relaxation (GR) nonlinear effect offers an alternative for enhancing saliency and can improve generality and speed. In this article, the excitation and detection efficiencies are optimized to enhance the GR signal amplitude. Experimental studies show that the saliency of the probe is enhanced. Moreover, the issue of signal aliasing is studied to ensure the accuracy of enhancement results in the tissues. In a word, the feasibility of the GR-based imaging method in saliency enhancement is successfully demonstrated in the study, showing the superiorities of good generality and detection speed.

Structural basis for sugar perception by Drosophila gustatory receptors.

Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.

In vivo endoscopic optical coherence elastography based on a miniature probe.

Optical coherence elastography (OCE) is a functional extension of optical coherence tomography (OCT). It offers high-resolution elasticity assessment with nanoscale tissue displacement sensitivity and high quantification accuracy, promising to enhance diagnostic precision. However, in vivo endoscopic OCE imaging has not been demonstrated yet, which needs to overcome key challenges related to probe miniaturization, high excitation efficiency and speed. This study presents a novel endoscopic OCE system, achieving the first endoscopic OCE imaging in vivo. The system features the smallest integrated OCE probe with an outer diameter of only 0.9 mm (with a 1.2-mm protective tube during imaging). Utilizing a single 38-MHz high-frequency ultrasound transducer, the system induced rapid deformation in tissues with enhanced excitation efficiency. In phantom studies, the OCE quantification results match well with compression testing results, showing the system's high accuracy. The in vivo imaging of the rat vagina demonstrated the system's capability to detect changes in tissue elasticity continually and distinguish between normal tissue, hematomas, and tissue with increased collagen fibers precisely. This research narrows the gap for the clinical implementation of the endoscopic OCE system, offering the potential for the early diagnosis of intraluminal diseases.