RESUMEN
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition worldwide, demanding further investigation into its pathogenesis. Circular RNAs (circRNAs) are emerging as pivotal regulators in MASLD processes, yet their pathological implications in MASLD remain poorly understood. This study focused on elucidating the role of circular RNA ribonucleotide reductase subunit M2 (circRRM2) in MASLD progression. In this study, we used both in vitro and in vivo MASLD models using long-chain-free fatty acid (FFA)-treated hepatocytes and high-fat diet (HFD)-induced MASLD in mice, respectively. We determined the expression patterns of circRRM2, microRNA-142-5p (miR-142-5p), and neuregulin 1 (NRG1) in livers of MASLD-afflicted mice and MASLD hepatocytes by RT-qPCR. Dual-luciferase reporter assays verified the binding relationships among circRRM2, miR-142-5p, and NRG1. We conducted further analyses of their roles in MASLD hepatocytes and modulated circRRM2, miR-142-5p, and NRG1 expression in vitro by transfection. Our findings were validated in vivo. The results demonstrated reduced levels of circRRM2 and NRG1, along with elevated miR-142-5p expression in MASLD livers and hepatocytes. Overexpression of circRRM2 downregulated lipogenesis-related genes and decreased triglycerides accumulation in livers of MASLD mice. MiR-142-5p, which interacts with circRRM2, effectively counteracted the effects of circRRM2 in MASLD hepatocytes. Furthermore, NRG1 was identified as a miR-142-5p target, and its overexpression mitigated the regulatory impact of miR-142-5p on MASLD hepatocytes. In conclusion, circRRM2, via its role as a miR-142-5p sponge, upregulating NRG1, possibly influenced triglycerides accumulation in both in vitro and in vivo MASLD models.NEW & NOTEWORTHY CircRRM2 expression was downregulated in free fatty acid (FFA)-challenged hepatocytes and high-fat diet (HFD) fed mice. Overexpressed circular RNA ribonucleotide reductase subunit M2 (circRRM2) attenuated metabolic dysfunction-associated steatotic liver disease (MASLD) development by suppressing FFA-induced triglycerides accumulation. CircRRM2 targeted microRNA-142-5p (miR-142-5p), which served as an upstream inhibitor of neuregulin 1 (NRG1) and collaboratively regulated MASLD progression.
Asunto(s)
Dieta Alta en Grasa , Hepatocitos , MicroARNs , Neurregulina-1 , ARN Circular , Animales , MicroARNs/metabolismo , MicroARNs/genética , Ratones , Hepatocitos/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Masculino , Neurregulina-1/genética , Neurregulina-1/metabolismo , Ratones Endogámicos C57BL , Hígado Graso/metabolismo , Hígado Graso/genética , Humanos , Hígado/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Ribonucleósido Difosfato ReductasaRESUMEN
Brain-inspired neuromorphic computing and portable intelligent electronic products have received increasing attention. In the present work, nanocellulose-gated indium tin oxide neuromorphic transistors are fabricated. The device exhibits good electrical performance. Short-term synaptic plasticities were mimicked, including excitatory postsynaptic current, paired-pulse facilitation, and dynamic high-pass synaptic filtering. Interestingly, an effective linear synaptic weight updating strategy was adopted, resulting in an excellent recognition accuracy of â¼92.93% for the Modified National Institute of Standard and Technology database adopting a two-layer multilayer perceptron neural network. Moreover, with unique interfacial protonic coupling, anxiety disorder behavior was conceptually emulated, exhibiting "neurosensitization", "primary and secondary fear", and "fear-adrenaline secretion-exacerbated fear". Finally, the neuromorphic transistors could be dissolved in water, demonstrating potential in "green" electronics. These findings indicate that the proposed oxide neuromorphic transistors would have potential as implantable chips for nerve health diagnosis, neural prostheses, and brain-machine interfaces.
Asunto(s)
Óxidos , Transistores Electrónicos , Humanos , Encéfalo , Agua , Trastornos de AnsiedadRESUMEN
The neural system is a multifunctional perceptual learning system. Our brain can perceive different kinds of information to form senses, including touch, sight, hearing, and so on. Mimicking such perceptual learning systems is critical for neuromorphic platform applications. Here, an artificial tactile perceptual neuron is realized by utilizing electronic skins (E-skin) with oxide neuromorphic transistors, and this artificial tactile perceptual neuron successfully simulates biological tactile afferent nerves. First, the E-skin device is constructed using microstructured polydimethylsiloxane membranes coated with Ag/indium tin oxide (ITO) layers, exhibiting good sensitivities of â¼2.1 kPa-1 and fast response time of tens of milliseconds. Then, the chitosan-based electrolyte-gated ITO neuromorphic transistor is fabricated and exhibits high performance and synaptic responses. Finally, the integrated artificial tactile perceptual neuron demonstrates pressure excitatory postsynaptic current and paired-pulse facilitation. The artificial tactile perceptual neuron is featured with low energy consumption as low as â¼0.7 nJ. Moreover, it can mimic acute and chronic pain and nociceptive characteristics of allodynia and hyperalgesia in biological nociceptors. Interestingly, the artificial tactile perceptual neuron can employ "Morse code" pressure-interpreting scheme. This simple and low-cost approach has excellent potential for applications including but not limited to intelligent humanoid robots and replacement neuroprosthetics.