The conductive hydrogels always suffered from high internal friction, large hysteresis, and low capability of accurately predicting physical deformation, which seriously restricted their application ...in smart wearable devices. To address these problems, solvent molecules are directionally inserted into the polymer molecule chains via bridge effect to effectively reduce the molecular internal friction. Moreover, swelling is also combined to eliminate the temporary entanglements in the hydrogel system. The cooperation between the bridge and swollen effect endows the prepared polyacrylamide (PAM)/laponite/H3BO3/ethylene glycol (Eg) organohydrogel (PLBOH) ultralow hysteresis (1.38%, ε = 100%), ultrafast response (≈10 ms), and high linearity in the whole‐strain‐range (R2 = 0.996) with a great sensitivity (GF = 2.68 at the strain range of 0–750%). Meanwhile, the prepared PL10B30OH exhibits long‐term stability, excellent stretchability, and low dissipated energy. Furthermore, the assembled triboelectric nanogenerator (TENG) displays an outstanding energy harvesting performance with an output voltage of 200 V with the size of 20 mm × 20 mm. The assembled strain sensors can monitor the small strain of facial expressions and large strain of human movements, indicating the tremendous applications in self‐powered intelligent and flexible wearable electronics under harsh environmental conditions.
An innovative method is developed to prepare the hydrogel via bridge effect to directionally insert solvent molecules into the hydrogel, which effectively acts as lubricate to reduce the molecular internal friction. The developed hydrogel exhibits ultralow‐hysteresis, ultrafast‐response, and whole‐strain‐range linearity contributed by the special molecular structure, which also holds great potential in flexible wearable devices.
Sustained cardiac hypertrophy accompanied by maladaptive cardiac remodelling represents an early event in the clinical course leading to heart failure. Maladaptive hypertrophy is considered to be a ...therapeutic target for heart failure. However, the molecular mechanisms that regulate cardiac hypertrophy are largely unknown.
Here we show that a circular RNA (circRNA), which we term heart-related circRNA (HRCR), acts as an endogenous miR-223 sponge to inhibit cardiac hypertrophy and heart failure. miR-223 transgenic mice developed cardiac hypertrophy and heart failure, whereas miR-223-deficient mice were protected from hypertrophic stimuli, indicating that miR-223 acts as a positive regulator of cardiac hypertrophy. We identified ARC as a miR-223 downstream target to mediate the function of miR-223 in cardiac hypertrophy. Apoptosis repressor with CARD domain transgenic mice showed reduced hypertrophic responses. Further, we found that a circRNA HRCR functions as an endogenous miR-223 sponge to sequester and inhibit miR-223 activity, which resulted in the increase of ARC expression. Heart-related circRNA directly bound to miR-223 in cytoplasm and enforced expression of HRCR in cardiomyocytes and in mice both exhibited attenuated hypertrophic responses.
These findings disclose a novel regulatory pathway that is composed of HRCR, miR-223, and ARC. Modulation of their levels provides an attractive therapeutic target for the treatment of cardiac hypertrophy and heart failure.
The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid‐brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels ...in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.
Degeneration of dopaminergic neurons is a most common age‐related disorder in the central nervous system. A break‐through idea using electromagnetized nanoparticles to mediate neural plasticity and recover the functions of degenerative dopaminergic neurons in the midbrain of a Parkinson's disease animal model is conceived. A significant advance in remote and regenerative cell therapy of the neurodegenerative diseases is thus provided.
Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be ...a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biological functions and have been extensively investigated in past years.
We identified miR-489 and lncRNAs (cardiac hypertrophy related factor, CHRF) from hypertrophic cardiomyocytes. Here, we tested the hypothesis that miR-489 and CHRF can participate in the regulation of cardiac hypertrophy in vivo and in vitro.
A microarray was performed to analyze miRNAs in response to angiotensin II treatment, and we found miR-489 was substantially reduced. Enforced expression of miR-489 in cardiomyocytes and transgenic overexpression of miR-489 both exhibited reduced hypertrophic response on angiotensin II treatment. We identified myeloid differentiation primary response gene 88 (Myd88) as a miR-489 target to mediate the function of miR-489 in cardiac hypertrophy. Knockdown of Myd88 in cardiomyocytes and Myd88-knockout mice both showed attenuated hypertrophic responses. Furthermore, we explored the molecular mechanism by which miR-489 expression is regulated and found that an lncRNA that we named CHRF acts as an endogenous sponge of miR-489, which downregulates miR-489 expression levels. CHRF is able to directly bind to miR-489 and regulate Myd88 expression and hypertrophy.
Our present study reveals a novel cardiac hypertrophy regulating model that is composed of CHRF, miR-489, and Myd88. The modulation of their levels may provide a new approach for tackling cardiac hypertrophy.
Inflammasomes are a class of cytosolic protein complexes. They act as cytosolic innate immune signal receptors to sense pathogens and initiate inflammatory responses under physiological and ...pathological conditions. The NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18, which are mediated by caspase-1, and secretes mature forms of these mediators from cells to promote the further inflammatory process and oxidative stress. Simultaneously, cells undergo pro-inflammatory programmed cell death, termed pyroptosis. The danger signals for activating NLRP3 inflammasome are very extensive, especially reactive oxygen species (ROS), which act as an intermediate trigger to activate NLRP3 inflammasome, exacerbating subsequent inflammatory cascades and cell damage. Vascular endothelium at the site of inflammation is actively involved in the regulation of inflammation progression with important implications for cardiovascular homeostasis as a dynamically adaptable interface. Endothelial dysfunction is a hallmark and predictor for cardiovascular ailments or adverse cardiovascular events, such as coronary artery disease, diabetes mellitus, hypertension, and hypercholesterolemia. The loss of proper endothelial function may lead to tissue swelling, chronic inflammation, and the formation of thrombi. As such, elimination of endothelial cell inflammation or activation is of clinical relevance. In this review, we provided a comprehensive perspective on the pivotal role of NLRP3 inflammasome activation in aggravating oxidative stress and endothelial dysfunction and the possible underlying mechanisms. Furthermore, we highlighted the contribution of noncoding RNAs to NLRP3 inflammasome activation-associated endothelial dysfunction, and outlined potential clinical drugs targeting NLRP3 inflammasome involved in endothelial dysfunction. Collectively, this summary provides recent developments and perspectives on how NLRP3 inflammasome interferes with endothelial dysfunction and the potential research value of NLRP3 inflammasome as a potential mediator of endothelial dysfunction.
Abnormal mitochondrial fission participates in the pathogenesis of many diseases. Long non-coding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the ...regulation of mitochondrial network is unclear. Here we report that a lncRNA, named cardiac apoptosis-related lncRNA (CARL), can suppress mitochondrial fission and apoptosis by targeting miR-539 and PHB2. The results show that PHB2 is able to inhibit mitochondrial fission and apoptosis. miR-539 is responsible for the dysfunction of PHB2 and regulates mitochondrial fission and apoptosis by targeting PHB2. Further, we show that CARL can act as an endogenous miR-539 sponge that regulates PHB2 expression, mitochondrial fission and apoptosis. Our present study reveals a model of mitochondrial fission regulation that is composed of CARL, miR-539 and PHB2. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.
Areca nut (AN) is used for traditional herbal medicine and social activities in several countries. It was used as early as about A.D. 25-220 as a remedy. Traditionally, AN was applied for several ...medicinal functions. However, it was also reported to have toxicological effects. In this review article, we updated recent trends of research in addition to acquire new knowledge about AN. First, the history of AN usage from ancient years was described. Then, the chemical components of AN and their biological functions was compared; arecoline is an especially important compound in AN. AN extract has different effects caused by different components. Thus, the dual effects of AN with pharmacological and toxicological effects were summarized. Finally, we described perspectives, trends and challenges of AN. It will provide the insight of removing or modifying the toxic compounds of AN extractions for enhancing their pharmacological activity to treat several diseases in future applications.
Oxidative stress is mainly caused by intracellular reactive oxygen species (ROS) production, which is highly associated with normal physiological homeostasis and the pathogenesis of diseases, ...particularly ocular diseases. Autophagy is a self-clearance pathway that removes oxidized cellular components and regulates cellular ROS levels. ROS can modulate autophagy activity through transcriptional and posttranslational mechanisms. Autophagy further triggers transcription factor activation and degrades impaired organelles and proteins to eliminate excessive ROS in cells. Thus, autophagy may play an antioxidant role in protecting ocular cells from oxidative stress. Nevertheless, excessive autophagy may cause autophagic cell death. In this review, we summarize the mechanisms of interaction between ROS and autophagy and their roles in the pathogenesis of several ocular diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and optic nerve atrophy, which are major causes of blindness. The autophagy modulators used to treat ocular diseases are further discussed. The findings of the studies reviewed here might shed light on the development and use of autophagy modulators for the future treatment of ocular diseases.
DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its ...anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg
· d
) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.
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