Biology subjects

Li, S.-M.

Publications and source records attributed to Li, S.-M..

4 recordsLinked to original sources

bioRxiv2026

Methodologies for Manipulating Cardiomyocyte Physiology: In Vitro and In Vivo Perspectives

Cardiac tissue is primarily made up of cardiomyocytes, which are regulated by the autonomic nervous system. We have used and developed approaches such as patch clamping and electrical stimulation-combined calcium imaging, computer modeling, optogenetics and chemogenetics combining with video-based Short-Time Fourier transformation (STFT) method to study the physiological activities of cardiomyocytes. The action potential of cardiomyocytes was found to be synchronized with calcium signals, which can be grouped into two categories by STFT. A mathematical model was developed to simulate the changes in electrical activities within cardiomyocytes caused by energy depletion, especially for 2-deoxy-D-glucose (2DG) treatment. Optogenetic and chemogenetics tools, such as ChR2(H134R), OptoXR-{beta}2AR and hM3Dq accelerated beating, while GR, ACR1 and hM4Di inhibited cardiomyocytes beating. A video-based STFT method was developed to visualize the beating frequency during these manipulations. An in vitro co-culture method was developed to study the relationship between sympathetic neuronal firing and calcium dynamics in cardiomyocytes. In vivo, electrocardiograph (ECG) measurements showed that Clozapine N-oxide (CNO) caused heart rates increasement in cTnT-hM3Dq virus injected mouse. However, it had no impact on cTnT-hM4Di virus injected mouse. This study provides comprehensive methodologies for studying cardiomyocyte physiology and manipulating heart rates in vitro and in vivo.

cell biology↗

bioRxiv2026

Optogenetic Regulation of Mitochondrial Function to Modulate Cell Death

Cell death is a critical process involved in physiological and pathological conditions, including neurodegenerative diseases and cancer. This study explores the use of optogenetic techniques to induce cell death by employing light sensitive proteins. By manipulating mitochondrial function with light-sensitive proteins, we investigated three distinct strategies: 1) inhibiting oxidative phosphorylation through Gloeobacter rhodopsin-mediated alkalization, 2) inducing mitochondrial depolarization with reverse proton-pumping rhodopsins (RPPR) and anion-conducting channelrhodopsins, and 3) generating reactive oxygen species (ROS) using mitochondria-targeted miniSOG. Our findings highlight the potential of optogenetic approaches to induce cell death, offering promising avenues for therapeutic interventions in diseases characterized by aberrant cell survival.

cell biology↗

bioRxiv2025

Tryptophanol, a novel auxin analog found in marine diatoms, enhances nitrogen assimilation

Diatoms exhibit superior competitive capacity in nitrogen assimilation, largely contributing to their growth, although the mechanisms underpinning their success have not been completely understood. Here, a non-ribosomal peptide synthase-like (PtNRPS1, with an unusual domain structure A-T-R1-R2) gene was found to play a vital role in short-term nitrogen assimilation in the marine diatom Phaeodactylum tricornutum. In vitro biochemical assays and in vivo overexpression confirmed that PtNRPS1 catalyzed two sequential two-electron reductions of L-tryptophan to tryptophanol. Tryptophanol exhibits high structural and functional similarities to indole-3-acetic acid (IAA), the most typical phytohormone auxin. Surprisingly, the effective concentration of tryptophanol was lower than that of IAA by as much as 2-5 orders of magnitude for P. tricornutum. Compared with the action of IAA, a distinct molecular mode for tryptophanol was revealed by transcriptomic analysis, resulting mainly in enhanced short-term nitrogen assimilation, which was also confirmed by the elevated nitrogen uptake rates determined by stable-isotope tracking. Finally, global distribution of PtNRPS1 homologues from stramenopiles was found to be positively correlated with the abundance of genes involved in nitrogen assimilation pathways. Overall, our study provides evidence of an auxin-like derivative synthesized by an NRPS in a diatom. We speculate that tryptophanol may accelerate nitrogen assimilation, conferring advantages in the competition for nitrogen in the ocean.

plant biology↗

bioRxiv2024

Mitochondrial DNA Release and Activation of the cGAS-STING Pathway in Lethal Stx12 Knockout Mice

STX12 (syntaxin12 or syntaxin13), a member of the SNARE protein family, plays a crucial role in intracellular vesicle transport and membrane fusion. Our previous research has demonstrated that Stx12 knockout mice exhibit perinatal lethality with iron deficiency anemia. Despite its importance, the comprehensive physiological and pathological mechanism of STX12 remain largely unknown. Here, we uncover that STX12 deficiency causes the depolarization of mitochondrial membrane potential in zebrafish embryos and mouse embryonic fibroblasts. Additionally, the loss of STX12 decreases levels of mitochondrial complex subunits, accompanying mitochondrial DNA (mtDNA) release and activating cGAS-STING pathway and Type I interferon pathway in the lung tissue of Stx12-/- mice. Additionally, we have observed a substantial increase in cytokines and neutrophil infiltration within the lung tissues of Stx12 knockout mice, indicating a severe inflammation, which could be a contributing factor for Stx12-/-mortality. Various interventions have failed to rescue the lethal phenotype, suggesting that systemic effects may contribute to lethality. Further research is warranted to elucidate potential intervention strategies. Overall, our findings uncover the critical role of STX12 in maintaining mitochondrial function and mtDNA stability in pulmonary cells, and reveal that STX12 depletion results in pulmonary mtDNA release and activates mtDNA-dependent innate immunity.

molecular biology↗