Biology subjects

Li, S.-s.

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

3 recordsLinked to original sources

bioRxiv2023

Ulinastatin Ameliorates Cardiac Ischemia/Reperfusion Injury via Inhibiting the tissue kallikrein-kinin system

BackgroundEndothelial cells (ECs) are considered more sensitive to cardiac ischemia/reperfusion (I/R) injury compared to cardiomyocytes. However, current research is mainly focused on molecular mechanisms and preventive strategies targeting cardiomyocyte I/R injury, whereas insufficient attention is placed on protecting endothelial function. Methods and ResultsIn this study, we established an interlink among ulinastatin (UIT; a serine protease inhibitor), the kallikrein-kinin system (KKS), and EC injury in response to cardiac reperfusion for the first time, using in vitro and in vivo experiments, and bioinformatic analysis. Our data indicated that UTI affected I/R by inhibiting the activation of KKS and simultaneously down-regulating both bradykinin receptor 1 (Bdkrb1) and bradykinin receptor 2 (Bdkrb2) related signaling such as extracellularsignal-regulated kinase (ERK)/inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS), thereby reducing infarct size, attenuating inflammation and edema, and improving cardiac function and mortality. Interestingly, UIT significantly suppressed KLK1 activity but did not down-regulate the KKS in normal conditions, suggesting inhibition of KLK1 might be the crucial mechanism for UIT-induced cardioprotection in reperfusion injury. Moreover, knockdown of Bdkrb1 in reperfusion-induced cardiac endothelial cells (MCECs) injury significantly prevented ERK translocation into the nucleus, reducing apoptosis, junction disruption, and expression levels of cytokines, whereas Bdkrb2 deletion could not protect MCECs against I/R injury. ConclusionsOur findings imply that inhibition of KLK1/Bdkrb1 is a critical target for UIT in the treatment of reperfusion-induced cardiac endothelial inflammation, apoptosis, and leakage and might be a potential therapeutic strategy for cardiac reperfusion injury.

cell biology↗

bioRxiv2021

Selfee: Self-supervised Features Extraction of animal behaviors

Fast and accurately characterizing animal behaviors is crucial for neuroscience research. Deep learning models are efficiently used in laboratories for behavior analysis. However, it has not been achieved to use a fully unsupervised method to extract comprehensive and discriminative features directly from raw behavior video frames for annotation and analysis purposes. Here, we report a self-supervised feature extraction (Selfee) convolutional neural network with multiple downstream applications to process video frames of animal behavior in an end-to-end way. Visualization and classification of the extracted features (Meta-representations) validate that Selfee processes animal behaviors in a comparable way of human understanding. We demonstrate that Meta-representations can be efficiently used to detect anomalous behaviors that are indiscernible to human observation and hint in-depth analysis. Furthermore, time-series analyses of Meta-representations reveal the temporal dynamics of animal behaviors. In conclusion, we present a self-supervised learning approach to extract comprehensive and discriminative features directly from raw video recordings of animal behaviors and demonstrate its potential usage for various downstream applications.

neuroscience↗

bioRxiv2019

Sex differences in electrophysiological properties of mouse mPOA neurons revealed by in vitro whole-cell recordings

The medial preoptic area (mPOA) of the hypothalamus is sexually dimorphic and controls sexually dimorphic display of male mating and parental care. Yet, despite extensive characterization of sex differences in the mPOA, we know surprisingly little about whether or how male and female mPOA neurons differ electrophysiologically, which relate more directly to neuronal firing and behavioral pattern generation. In this study, we performed whole-cell patch clamp recordings of the mPOA in acute brain slices cut from virgin adult mice, and compared in total 29 electrophysiological parameters between male and female mPOA neurons. We find that resting membrane potential (Vm), input resistance (Rm), time constant ({tau}m), threshold (Vth) and minimum current (rheobase) required to generate an action potential differ significantly between male and female in a cell-type dependent manner. Nonetheless, there is little evidence for profuse sex differences in neuronal excitability, except for a higher probability of rebound neurons in males. Depletion of male gonadal hormones in adulthood partially de-masculinizes sexually dimorphic electrophysiological parameters, suggesting that some of these sex differences may establish during development. Furthermore, as a demonstration of the behavioral relevance of these sex differences, we show that pharmacologic blockage of currents mediated by T-type Ca2+ channel, which underlie rebound and tends to be larger in male mPOA neurons, result in behavioral deficits in male mating. In summary, we have identified key sex differences in electrophysiological properties of mPOA neurons that likely contribute to sexually dimorphic display of behaviors.\n\nSignificance StatementSex represents an important biological variable that impact an individuals behaviors, physiology and disease susceptibility. Indeed, sex differences in the nervous system manifest across many different levels and scales. Yet, throughout previous multifaceted investigations on sex differences in the brain, electrophysiological characterizations, which could potentially bridge cellular and molecular sex differences with sexually dimorphic brain functions and behaviors, remains scant. Here, focusing on an evolutionarily conserved sexually dimorphic nucleus, we investigated sex differences in electrophysiological properties of mPOA neurons and its modulation by gonadal hormones in adult males via in vitro whole-cell patch clamp. As a result, we identified novel sex differences in electrophysiological properties that likely contribute to sexually dimorphic display of behaviors and physiological functions.

neuroscience↗