In eukaryotic cells, lysosomes are digestive centers where biological macromolecules are degraded by phagocytosis and autophagy, thereby maintaining cellular self-renewal capacity and energy supply. Lysosomes also serve as signaling hubs to monitor the intracellular levels of nutrients and energy by acting as platforms for the assembly of multiple signaling pathways, such as mammalian target of rapamycin complex 1 (mTORC1) and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK). The structural integrity and functional balance of lysosomes are essential for cell function and viability. In fact, lysosomal damage not only disrupts intracellular clearance but also results in the leakage of multiple contents, which pose great threats to the cell by triggering cell death pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The collapse of lysosomal homeostasis is reportedly critical for the pathogenesis and development of various diseases, such as tumors, neurodegenerative diseases, cardiovascular diseases, and inflammatory diseases. Lysosomal quality control (LQC), comprising lysosomal repair, lysophagy, and lysosomal regeneration, is rapidly initiated in response to lysosomal damage to maintain lysosomal structural integrity and functional homeostasis. LQC may be a novel but pivotal target for disease treatment because of its indispensable role in maintaining intracellular homeostasis and cell fate.
To make up for the insufficiency and instability of contact dispensers that are used for fluid dispensing in microelectronic packaging, a noncontact jetting dispenser driven by a piezostack actuator is introduced in this paper. After describing the structural components and operating principle of the dispensing mechanism, a fluid model is presented to discuss the dynamic properties of the fluid and analyze the key parameters of the proposed dispenser. The ANSYS simulation software is used to design the displacement amplifier, which is an important component of the dispenser. The maximum displacement output of 323 µm is obtained by optimizing. Subsequently, the dynamic behavior of the displacement amplifier is measured by an optical displacement sensor. The displacement change with the driving voltage amplitude and frequency is also investigated; the maximum displacement is 320 µm, and the error between the simulation and the measurement result is just 0.75%. In order to verify the practicality of dispenser, experiments are conducted to examine the effects of the driving voltage, backpressure, working temperature, and distance between the nozzle and the collector on the jetting performance and droplet diameter. The dispenser can dispense droplets uniformly and steadily. Its maximum jetting frequency is 65 Hz, and droplets of 1.07-mm diameter are produced by a stainless steel nozzle of 0.25-mm diameter in the experimental study, with the variation of the droplet diameter being within ±2%.
Transcription factor EB (TFEB) is a member of the microphthalmia-associated transcription factor/transcription factor E (MiTF/TFE) family and critically involved in the maintenance of structural integrity and functional balance of multiple cells. In this review, we described the effects of post-transcriptional modifications, including phosphorylation, acetylation, SUMOylation, and ubiquitination, on the subcellular localization and activation of TFEB. The activated TFEB enters into the nucleus and induces the expressions of targeted genes. We then presented the role of TFEB in the biosynthesis of multiple organelles, completion of lysosome-autophagy pathway, metabolism regulation, immune, and inflammatory responses. This review compiles existing knowledge in the understanding of TFEB regulation and function, covering its essential role in response to cellular stress. We further elaborated the involvement of TFEB dysregulation in the pathophysiological process of various diseases, such as the catabolic hyperactivity in tumors, the accumulation of abnormal aggregates in neurodegenerative diseases, and the aberrant host responses in inflammatory diseases. In this review, multiple drugs have also been introduced, which enable regulating the translocation and activation of TFEB, showing beneficial effects in mitigating various disease models. Therefore, TFEB might serve as a potential therapeutic target for human diseases. The limitation of this review is that the mechanism of TFEB-related human diseases mainly focuses on its association with lysosome and autophagy, which needs deep description of other mechanism in diseases progression after getting more advanced information.
Tactile pressure sensing over a wide operation range (>1 MPa) is challenging for a variety of applications in fields such as aviation, oceanography, and biomedicine. Recently, innovative strategies have been utilized to improve the performances of tactile sensors using specially designed structures, dielectric layers, and electrodes. Here, a hierarchical structural design based on ionic gel films has been utilized to build iontronic pressure sensors with ultrahigh sensitivities and broad operation ranges. Sculptured patterns made by a controlled CO 2 laser scanning process have been produced on polyimide films to achieve two kinds of protrusion structures for high specific surface areas and strength to withstand high pressure. The iontronic sensor has been constructed by adding two screen-printed electrodes of high surface areas to achieve an ultrahigh sensitivity of 2593 kPa −1 and a wide pressure range from 0 Pa to 3.36 MPa. The prototype device also has a fast response and recovery time of 26 and 13 ms, respectively, and an excellent mechanical durability in the endurance test of over 2700 repeated loading and unloading cycles under a pressure of 1 MPa. Several application examples have been demonstrated, including the detection of physiological signals on human volunteers, the feedback control of intelligent robots, the grasping operation of underwater soft grippers, and the environmental wind-speed monitoring. As such, this work demonstrates a versatile and economical methodology to produce high-performance flexible sensors for various potential applications.
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