Innovative Cyanine-Based Fluorescent Dye for Targeted Mitochondrial Imaging and Its Utility in Whole-Brain Visualization

Conducting in vivo brain imaging can be a challenging task due to the complexity of brain tissue and the strict requirements for safe and effective imaging agents. However, a new fluorescent dye called Cy5-PEG2 has been developed that selectively accumulates in mitochondria, enabling the visualization of these essential organelles in various cell lines. This dye is versatile and can be used for the real-time monitoring of mitochondrial dynamics in living cells. Moreover, it can cross the blood-brain barrier, making it a promising tool for noninvasive in vivo brain imaging. Based on the assessment of glial cell responses in the hippocampus and neocortex regions using GFAP and Iba1 biomarkers, Cy5-PEG2 seems to have minimal adverse effects on brain immune response or neuronal health. Therefore, this mitochondria-targeting fluorescent dye has the potential to advance our understanding of mitochondrial dynamics and function within the broader context of whole-brain physiology and disease progression. However, further research is needed to evaluate the safety and efficacy of Cy5-PEG2

Box-counting measure of metric spaces

In this paper, we introduce a new notion called the \emph{box-counting measure} of a metric space. We show that for a doubling metric space, an Ahlfors regular measure is always a box-counting measure; consequently, if $E$ is a self-similar set satisfying the open set condition, then the Hausdorff measure restricted to $E$ is a box-counting measure. We show two classes of self-affine sets, the generalized Lalley-Gatzouras type self-affine sponges and Bara\'nski carpets, always admit box-counting measures; this also provides a very simple method to calculate the box-dimension of these fractals. Moreover, among others, we show that if two doubling metric spaces admit box-counting measures, then the multi-fractal spectra of the box-counting measures coincide provided the two spaces are Lipschitz equivalent

Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification.

Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis, a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-Derived Extracellular Vesicles from Hypertensive Rats

Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt-Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased the mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, the mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications

Evaluation and correction of GPM satellite precipitation products during Typhoon "In-Fa" affecting Zhejiang

To understand and improve the performance and quality of Global Precipitation Measurement (GPM) satellite-derived precipitation products during the typhoon process, with gauge observations from ground meteorological stations, this study used the successive and optimal interpolation correction methods to correct the GPM precipitation products. The performance of GPM products (Version 6) before and after the correction at different time scales are evaluated with the products during the two landfalls of Typhon"In-Fa". Results show that the original GPM precipitation products fail to describe the strong rainfall center over the high terrain area, which significantly underestimates the precipitation by approximately 45%. This is mainly due to the underestimation of the large values in the northeast region of Zhejiang province. The analysis of precipitation classification inspection suggests that the uncorrected GPM satellite-derived products have good capability for light rain, but poor for other rainfall levels. After the successive and optimal interpolation correction, significant improvement can be found in the cumulative, daily, and hourly rainfall products. The products with successive correction are better, while the product with optimal interpolation slightly overestimates the actual precipitation. The corrected GPM products can not only describe the heavy precipitation center related to the terrain but also reflect heavy rainstorms and heavy precipitation with hourly rainfall intensity greater than 23 mm·h-1