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Oxidative stress is involved in the pathogenesis of Alzheimer’s disease (AD), which is linked to reactive oxygen species (ROS), lipid peroxidation, and neurotoxicity. Emerging evidence suggests a role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a major source of antioxidant response elements in AD. The molecular mechanism of oxidative stress and ferroptosis in astrocytes in AD is not yet fully understood. Here, we aimed to investigate the mechanism by which Nrf2 regulates the ferroptosis of astrocytes in AD. We found decreased expression of Nrf2 and upregulated expression of the ROS marker NADPH oxidase 4 (NOX4) in the frontal cortex from patients with AD and in the cortex of 3×Tg mice compared to wildtype mice. We demonstrated that Nrf2 deficiency led to ferroptosis-dependent oxidative stress-induced ROS with downregulated heme oxygenase-1 and glutathione peroxidase 4 and upregulated cystine glutamate expression. Moreover, Nrf2 deficiency increased lipid peroxidation, DNA oxidation, and mitochondrial fragmentation in mouse astrocytes (mAS, M1800-57). In conclusion, these results suggest that Nrf2 deficiency promotes ferroptosis of astrocytes involving oxidative stress in AD.

Erectile dysfunction (ED) is a common and difficult to treat disease, and has a high incidence rate worldwide. As a marker of vascular disease, ED usually occurs in cardiovascular disease, 2–5 years prior to cardiovascular disease events. The extracellular matrix (ECM) network plays a crucial role in maintaining cardiac homeostasis, not only by providing structural support, but also by promoting force transmission, and by transducing key signals to intracardiac cells. However, the relationship between ECM and ED remains unclear. To help fill this gap, we profiled single-cell RNA-seq (scRNA-seq) to obtain transcriptome maps of 82,554 cavernous single cells from ED and non-ED samples. Cellular composition of cavernous tissues was explored by uniform manifold approximation and projection. Pseudo-time cell trajectory combined with gene enrichment analysis were performed to unveil the molecular pathways of cell fate determination. The relationship between cavernous cells and the ECM, and the changes in related genes were elucidated. The CellChat identified ligand-receptor pairs (e.g., PTN-SDC2, PTN-NCL, and MDK-SDC2) among the major cell types in the cavernous tissue microenvironment. Differential analysis revealed that the cell type-specific transcriptomic changes in ED are related to ECM and extracellular structure organization, external encapsulating structure organization, and regulation of vasculature development. Trajectory analysis predicted the underlying target genes to modulate ECM (e.g., COL3A1, MDK, MMP2, and POSTN). Together, this study highlights potential cell–cell interactions and the main regulatory factors of ECM, and reveals that genes may represent potential marker features of ED progression.

Cellulose nanocrystals (CNCs) extracted from sisal by acid hydrolysis were used to prepare the film with a chiral nematic phase structure by evaporation-induced self-assembly method. The effects of different acid reaction times on the morphology of sisal CNCs and the optical and mechanical properties of CNC films were investigated. Transmission electron microscopy (TEM), surface charge, and scanning electron microscopy (SEM) analysis showed that as the reaction time of acid hydrolysis increased from 30 to 90 min, the surface charge of CNCs increased from 0.116 to 0.285 mmol g −1 and the average length decreased from 193.6 to 100.1 nm. Sisal CNCs can self-assemble to form the film with a chiral nematic phase structure by the evaporation-inducing method. The combination of the above two aspects resulted in an increase and then a decrease in the helical pitch of CNC films. UV–Vis spectra and polarized light (POM) analysis of the CNC films revealed that the change in helical pitch can affect the color change of CNC films from blue to red and then to yellow-green. The effects of different reaction times on the nanomechanical and macroscopic mechanical properties of CNC films are reported. At the reaction time of 60 min, the macroscopic mechanical properties of the CNC film were good with a tensile strength of 43.59 MPa. This research could provide a good option for the extraction and application of sisal CNCs and create higher value-added products of sisal.

It is anticipated that the rapid development of the Internet of Things (IoT) will improve the quality of human life. Nonetheless, large amounts of data need to be replicated, stored, processed, and shared, posing formidable challenges to communication bandwidth and information security. Herein, it is reported that polyimide (PI) threshold‐switching memristors exhibit Gaussian conductance and randomly set voltage distribution with nonideal properties to create a compression and encryption engine with a single chip. The Gaussian conductance distribution is used to achieve compressed sensing (CS) to integrate encryption into compression, and the spontaneous formation of the one‐time‐sampling measurement matrix satisfies absolute security. Moreover, the bitstreams generated by randomly distributed set voltages are used to diffuse the ciphertext from CS to improve security. The engine is shown to be secure even if the eavesdropper knows both the plaintext and the corresponding ciphertext. It has compression performance advantages that take both efficiency and security into account. In addition, due to the superior high temperature and mechanical properties of PI, the engine can continue to function normally in harsh environments. Herein, an excellent solution is offered for ensuring the efficiency and security of IoT. All‐in‐one compression and encryption engines with one‐time‐only keys constructed from flexible polyimide memristors are achieved, enabling the integration of compression and encryption. The one‐time‐only keys are formed spontaneously to implement compression and diffusion without programming operations, enabling the engine to satisfy perfect security and resist chosen‐plaintext attacks (CPA). An excellent solution is provided for high efficiency and security application.

Background The pathogenesis of Alzheimer's disease (AD) remains incompletely elucidated, and there is a notable deficiency in effective and safe therapeutic interventions. The influence of brain matrix viscoelasticity on the progression of AD has frequently been underestimated. It is imperative to elucidate these overlooked pathogenic factors and to innovate novel therapeutic strategies for AD. Gastrodin, a bioactive constituent derived from the traditional Chinese medicinal herb Gastrodia elata, exhibits a range of pharmacological properties, notably in the enhancement of neural function. Nevertheless, the underlying mechanisms of its action remain insufficiently elucidated. Consequently, this study seeks to examine the therapeutic effects and underlying mechanisms of gastrodin in the context of AD, with particular emphasis on its potential influence on the viscoelastic properties of the brain matrix. Methods This study employs a range of methodologies, including the Morris water maze test, Y‐maze spontaneous alternation test, atomic force microscopy (AFM), immunofluorescence, transmission electron microscopy, molecular docking, and Cellular Thermal Shift Assay (CETSA), to demonstrate that gastrodin mitigates tau pathology by modulating FERMT2, thereby reversing the deterioration of mechanical viscoelasticity in the brain. Results Gastrodin administration via gavage has been demonstrated to mitigate cognitive decline associated with AD, attenuate the hyperphosphorylation of tau protein in the hippocampus and cortex, and ameliorate synaptic damage. Additionally, gastrodin was observed to counteract the reduction in brain matrix viscoelasticity in 3xTg‐AD mice, as evidenced by the upregulation of extracellular matrix components pertinent to viscoelasticity, notably collagen types I and IV. Furthermore, molecular docking and CETSA revealed a strong binding affinity between gastrodin and FERMT2. Gastrodin treatment resulted in a reduction of FERMT2 fluorescence intensity, which is selectively expressed in astrocytes. Additionally, gastrodin contributed to the restoration of the blood–brain barrier (BBB) and modulated the expression levels of inflammatory mediators interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and matrix metallopeptidase 8 (MMP8). Conclusion Gastrodin treatment has the potential to mitigate tau pathology, thereby enhancing learning and memory in AD mouse models. This effect may be mediated through the modulation of cerebral mechanical viscoelasticity via the mechanosensor FERMT2, which facilitates the restoration of synaptic structure and function. This process is potentially linked to the maintenance of BBB integrity and the modulation of inflammatory factor release. Gastrodin reduces tau hyperphosphorylation in 3xTg‐AD mice, reverses decreased brain matrix viscoelasticity, and remodels ECM components by targeting the Alzheimer's risk gene FERMT2, primarily in astrocytes. It binds to FERMT2, inhibiting its expression, which leads to ECM remodeling, restored matrix viscoelasticity, and blood–brain barrier recovery. Gastrodin also modifies neuroinflammatory factors such as TNF‐α, IL‐6, and MMP8.

As an important receptor located in the skin, a nociceptor is capable of detecting noxious stimuli and sending warning signals to the central nervous system to avoid tissue damage, thus inspiring the development of artificial nociceptors for electronic receptors. Recently, memristors have attracted increasing attention for developing artificial nociceptors due to the simplicity of the artificial nociceptive system. However, the realization of artificial nociceptors with biocompatibility and biodegradability in a single memristive device remains a challenge. Herein, a fully biocompatible and biodegradable threshold switching (TS) memristor consisting of W/MgO/Mg/W configuration was proposed as an artificial nociceptor. The device showed unidirectional TS characteristics with stable electrical performance under bending conditions. Critical nociceptor behaviors, including threshold, relaxation, no adaptation, allodynia, and hyperalgesia, were successfully demonstrated in the memristive nociceptor. Meanwhile, an optoelectronic nociceptor system was built by the integration of a photoresistor and the memristor. Importantly, the devices transferred on a biodegradable polyvinyl acetate substrate as physically transient electronics could completely dissolve in deionized water, simulating the decomposition of skin necrosis. This study provides a novel route toward developing fully biocompatible and biodegradable artificial nociceptors for promising applications in implantable and wearable electronics and secure bio-integrated systems.

Alzheimers disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to have neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in myricetin protective effect on the toxicity induced by the Aβ42 oligomer. Neuronal SH-SY5Y cells were pretreated with myricetin before incubation with Aβ42 oligomer. The levels of pre- and post-synaptic proteins, mitochondrial division and fusion proteins, glycogen synthase kinase-3β (GSK-β) and extracellular regulated kinase (ERK) 1/2 were assessed by Western blotting. Flow cytometry assays for mitochondrial membrane potential (JC1) and reactive oxidative stress, as well immunofluorescence staining for lipid peroxidation (4-HNE) and DNA oxidation (8-OHdG), were performed. We found that myricetin prevented Aβ42 oligomer-induced tau phosphorylation and the reduction in pre/postsynaptic proteins. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation induced by the Aβ42 oligomer. Moreover, myricetin prevented the Aβ42 oligomer-induced reduction in mitochondrial fusion proteins (mitofusin-1, mitofusin-2), fission protein (dynamin-related protein 1) phosphorylation, and mitochondrial membrane potential via the associated GSK-3β and ERK 1/2 signaling pathways. In conclusion, this study provides new insight into the neuroprotective mechanism of myricetin against Aβ42 oligomer-induced toxicity.Competing Interest StatementThe authors have declared no competing interest.

Abnormal amyloid-β (Aβ) abnormal accumulation and oxidative stress play important roles in Alzheimer′ disease (AD). Quercetin has been reported to possess antioxidant and anti-inflammatory properties, and thus of therapeutic interests for neurodegenerative disorders. In the present study, we aimed to characterize the mechanisms by which quercetin exerts neuroprotective effects in murine neuroblastoma N2a cells stably expressing human Swedishh mutant amyloid precursor protein (APP). Quercetin treatment exhibited low cytoxicity, attenuated APP expression and APP-induced oxidative neurotoxicity in N2a/APP cells. We found that quercetin effected via the down-regulation of phospho-extracellular signal regulated protein kinase (p-ERK1/2) pathway and up-regulation of phospho-protein kinase B (p-AKT) pathway in N2a/APP cells. In addition, quercetin ameliorated the elevated levels of reactive oxygen species using DCFH-DA flow-cytometry in N2a/APP cells, lipid peroxidation using (4-HNE), and DNA oxidation (8-OHdG assays). Quercetin ameliorated the loss of mitochondrial membrane potential using JC-1 fluorescence assay in N2a/APP cells in a dose-dependent mannor. In conclusion, we domenstrated the neuroprotective effects of quercetin against the APP expression induced oxidative neurotoxicity, impairment of mitochondrial function and oxidative stress through inactivation of the ERK1/2 signaling pathway and activation of AKT signaling pathways. Competing Interest Statement The authors have declared no competing interest.

Oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD), which is linked to reactive oxygen species (ROS), lipid peroxidation, and neurotoxicity. Emerging evidence suggests a role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a major source of antioxidant response elements in AD. The molecular mechanism of oxidative stress and ferroptosis in astrocytes in AD has not yet been fully understood. Here, we aim to investigate the mechanism by which Nrf2 regulates the ferroptosis of astrocytes in AD. Postmortem frontal cortex tissues from patients with AD and nondemented controls and brain tissue from the 3xTg AD mouse model and wild-type mice (10 months old) were used. Immunofluorescence staining for Nrf2, the ROS marker NADPH oxidase 4 (NOX4), and GFAP was performed. We further induced Nrf2 deficiency in mouse astrocytes by using RNAi and assessed the changes in ROS, ferroptosis, lipid peroxidation, and mitochondrial dysfunction by using western blotting and immunofluorescence staining. We found decreased expression of Nrf2 and upregulated expression of NOX4 in the frontal cortex from patients with AD and cortex of 3xTg mice compared to control groups. We demonstrated that Nrf2 deficiency led to ferroptosis-dependent oxidative stress-induced ROS with downregulated heme oxygenase-1 and glutathione peroxidase 4 and upregulated cystine glutamate expression. Moreover, Nrf2 deficiency increased lipid peroxidation, DNA oxidation, and the mitochondrial fragmentation in mouse astrocytes. In conclusion, these results suggest that Nrf2 promotes ferroptosis of astrocytes involving oxidative stress in AD.Competing Interest StatementThe authors have declared no competing interest.