Visualizing Subcellular Enrichment of Glycogen in Live Cancer Cells by Stimulated Raman Scattering

Glycogen, a branched glucose polymer, helps regulate glucose homeostasis through immediate storage and release of glucose. Reprogramming of glycogen metabolism has recently been suggested to play an emerging role in cancer progression and tumorigenesis. However, regulation of metabolic rewiring for glycogen synthesis and breakdown in cancer cells remains less understood. Despite the availability of various glycogen detection methods, selective visualization of glycogen in living cells with high spatial resolution has proven to be highly challenging. Here, we present an optical imaging strategy to visualize glycogen in live cancer cells with minimal perturbation by combining stimulated Raman scattering microscopy with metabolic incorporation of deuterium-labeled glucose. We revealed the subcellular enrichment of glycogen in live cancer cells and achieved specific glycogen mapping through distinct spectral identification. Using this method, different glycogen metabolic phenotypes were characterized in a series of patient-derived BRAF mutant melanoma cell lines. Our results indicate that cell lines manifesting high glycogen storage level showed increased tolerance to glucose deficiency among the studied melanoma phenotypes. This method opens up the possibility for noninvasive study of complex glycogen metabolism at subcellular resolution and may help reveal new features of glycogen regulation in cancer systems

Visualizing Subcellular Enrichment of Glycogen in Live Cancer Cells by Stimulated Raman Scattering

Glycogen, a branched glucose polymer, helps regulate glucose homeostasis through immediate storage and release of glucose. Reprogramming of glycogen metabolism has recently been suggested to play an emerging role in cancer progression and tumorigenesis. However, regulation of metabolic rewiring for glycogen synthesis and breakdown in cancer cells remains less understood. Despite the availability of various glycogen detection methods, selective visualization of glycogen in living cells with high spatial resolution has proven to be highly challenging. Here, we present an optical imaging strategy to visualize glycogen in live cancer cells with minimal perturbation by combining stimulated Raman scattering microscopy with metabolic incorporation of deuterium-labeled glucose. We revealed the subcellular enrichment of glycogen in live cancer cells and achieved specific glycogen mapping through distinct spectral identification. Using this method, different glycogen metabolic phenotypes were characterized in a series of patient-derived BRAF mutant melanoma cell lines. Our results indicate that cell lines manifesting high glycogen storage level showed increased tolerance to glucose deficiency among the studied melanoma phenotypes. This method opens up the possibility for noninvasive study of complex glycogen metabolism at subcellular resolution and may help reveal new features of glycogen regulation in cancer systems

Void Lensing in Cubic Galileon Gravity

Weak lensing studies via cosmic voids are a promising probe of Modified Gravity (MG). Excess surface mass density (ESD) is widely used as a lensing statistic in weak lensing research. In this paper, we use the ray-tracing method to study the ESD around voids in simulations based on Cubic Galileon (CG) gravity. With the compilation of N-body simulation and ray-tracing method, changes in structure formation and deflection angle resulting from MG can both be considered, making the extraction of lensing signals more realistic. We find good agreements between the measurement and theoretical prediction of ESD for CG gravity. Meanwhile, the lensing signals are much less affected by the change of the deflection angle than the change of the structure formation, indicating a good approximation of regarding ESD (statistics) as the projection of 3D dark matter density field. Finally, we demonstrate that it is impossible to distinguish CG and General Relativity in our simulation, however, in the next-generation survey, thanks to the large survey area and the increased galaxy number density, detecting the differences between these two models is possible. The methodology employed in this paper that combines N-body simulation and ray-tracing method can be a robust way to measure the lensing signals from simulations based on the MGs, and especially on that which significantly modifies the deflection angle.Comment: 14 pages, 9 figure

The molecular clouds in a section of the third Galactic quadrant: observational properties and chemical abundance ratio between CO and its isotopologues

We compare the observational properties between $^{12}$CO, $^{13}$CO, and C$^{18}$O and summarize the observational parameters based on 7069 clouds sample from the Milky Way Imaging Scroll Painting (MWISP) CO survey in a section of the third Galactic quadrant. We find that the $^{13}$CO angular area ($A_{\rm ^{13}CO}$) generally increases with that of $^{12}$CO ($A_{\rm ^{12}CO}$), and the ratio of $A_{\rm ^{13}CO}$ to $A_{\rm ^{12}CO}$ is 0.38 by linear fitting. We find that the $^{12}$CO and $^{13}$CO flux are tightly correlated as $F_{\rm ^{13}CO}~=~0.17~ F_{\rm ^{12}CO}$ with both fluxes calculated within the $^{13}$CO-bright region. This indicates that the abundance $X_{\rm ^{13}CO}$ is a constant to be 6.5$^{+0.1}_{-0.5}$ $\times 10^{-7}$ for all samples under assumption of local thermodynamic equilibrium (LTE). Additionally, we observed that the X-factor is approximately constant in large sample molecular clouds. Similarly, we find $F_{\rm C^{18}O}~=~0.11~F_{\rm ^{13}CO}$ with both fluxes calculated within C$^{18}$O-bright region, which indicates that the abundance ratios ${X_{\rm ^{13}CO}/X_{\rm C^{18}O}}$ stays the same value 9.7$^{+0.6}_{-0.8}$ across the molecular clouds under LTE assumption. The linear relationships of $F_{\rm ^{12}CO}$ vs. $F_{\rm ^{13}CO}$ and $F_{\rm ^{13}CO}$ vs. $F_{\rm C^{18}O}$ hold not only for the $^{13}$CO-bright region or C$^{18}$O-bright region, but also for the entire molecular cloud scale with lower flux ratio. The abundance ratio ${X_{\rm ^{13}CO}/X_{\rm C^{18}O}}$ inside clouds shows a strong correlation with column density and temperature. This indicates that the ${X_{\rm ^{13}CO}/X_{\rm C^{18}O}}$ is dominated by a combination of chemical fractionation, selectively dissociation, and self-shielding effect inside clouds.Comment: 11 pages, 16 figures, 1 table, accepted by A

ChimpACT: A Longitudinal Dataset for Understanding Chimpanzee Behaviors

Understanding the behavior of non-human primates is crucial for improving animal welfare, modeling social behavior, and gaining insights into distinctively human and phylogenetically shared behaviors. However, the lack of datasets on non-human primate behavior hinders in-depth exploration of primate social interactions, posing challenges to research on our closest living relatives. To address these limitations, we present ChimpACT, a comprehensive dataset for quantifying the longitudinal behavior and social relations of chimpanzees within a social group. Spanning from 2015 to 2018, ChimpACT features videos of a group of over 20 chimpanzees residing at the Leipzig Zoo, Germany, with a particular focus on documenting the developmental trajectory of one young male, Azibo. ChimpACT is both comprehensive and challenging, consisting of 163 videos with a cumulative 160,500 frames, each richly annotated with detection, identification, pose estimation, and fine-grained spatiotemporal behavior labels. We benchmark representative methods of three tracks on ChimpACT: (i) tracking and identification, (ii) pose estimation, and (iii) spatiotemporal action detection of the chimpanzees. Our experiments reveal that ChimpACT offers ample opportunities for both devising new methods and adapting existing ones to solve fundamental computer vision tasks applied to chimpanzee groups, such as detection, pose estimation, and behavior analysis, ultimately deepening our comprehension of communication and sociality in non-human primates.Comment: NeurIPS 202

Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells

Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies

Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells

Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies

Efficient Depolymerization of Cellulosic Paper Towel Waste Using Organic Carbonate Solvents

Efficient depolymerization of lignocellulosic biomass is a prerequisite for sugar production and its subsequent upgradation to fuels and chemicals. Organic carbonate solvents, i.e., propylene carbonate (PC), ethylene carbonate (EC), and dimethyl carbonate (DMC), which are low in toxicity and biodegradable, were investigated as "green"co-solvents (PC/H2O, EC/H2O, DMC/H2O, solvent ratio 1:1) for depolymerization of cellulosic paper towel waste. PC/H2O and EC/H2O enhanced the depolymerization of paper towel waste and improved the total sugar yield (up to ∼25 C mol %) compared to H2O only (up to ∼11 C mol %) under mild reaction conditions (130 °C, 20 min). The higher performance of PC/H2O and EC/H2O can be attributed to higher availability of reactive protons in the catalytic system that facilitates efficient acid hydrolysis of recalcitrant cellulosic fibers. Moreover, a substantial buildup of in-vessel pressure by CO2 release during the microwave-assisted reaction because of decomposition of PC or EC might have accelerated the conversion of paper towel wastes. PC and EC are prospective solvents for lignocellulosic biomass conversion considering their green features and notable catalytic performance, which have a good potential for substituting conventional organic solvents such as dimethyl sulfoxide (DMSO) and tetrahydrofuran (THF) that are often considered hazardous in terms of health, safety, and environmental implications