Ultrahigh Effective Diffusion in Oxide by Engineering the Interfacial Transporter Channels.

Mass storage and removal in solids always play a vital role in technological applications such as modern batteries and neuronal computations. However, they were kinetically limited by the slow diffusional process in the lattice, which made it challenging to fabricate applicable conductors with high electronic and ionic conductivities at room temperature. Here, we proposed an acid solution/WO3/ITO sandwich structure and achieved ultrafast H transport in the WO3 layer by interfacial job-sharing diffusion, which means the spatially separated transport of the H+ and e- in different layers. From the color change of WO3, the effective diffusion coefficient (Deff) was estimated, dramatically increasing ≤106 times and overwhelming values from previous reports. The experiments and simulations also revealed the universality of extending this approach to other atoms and oxides, which could stimulate systematic studies of ultrafast mixed conductors in the future.

Structure of rosettes in the zona glomerulosa of human adrenal cortex.

Recent studies in mouse models have demonstrated that the multi-cellular rosette structure of the adrenal zona glomerulosa (ZG) is crucial for aldosterone production by ZG cells. However, the rosette structure of human ZG has remained unclear. The human adrenal cortex undergoes remodeling during aging, and one surprising change is the occurrence of aldosterone-producing cell clusters (APCCs). It is intriguing to know whether APCCs form a rosette structure like normal ZG cells. In this study, we investigated the rosette structure of ZG in human adrenal with and without APCCs, as well as the structure of APCCs. We found that glomeruli in human adrenal are enclosed by a laminin subunit ß1 (lamb1)-rich basement membrane. In slices without APCCs, each glomerulus contains an average of 11 ± 1 cells. In slices with APCCs, each glomerulus in normal ZG contains around 10 ± 1 cells, while each glomerulus in APCCs has significantly more cells (average of 22 ± 1). Similar to what was observed in mice, cells in normal ZG or in APCCs of human adrenal formed rosettes through ß-catenin- and F-actin-rich adherens junctions. The cells in APCCs form larger rosettes through enhanced adherens junctions. This study provides, for the first time, a detailed characterization of the rosette structure of human adrenal ZG and shows that APCCs are not an unstructured cluster of ZG cells. This suggests that the multi-cellular rosette structure may also be necessary for aldosterone production in APCCs.

Prostaglandin E2 increases migration and proliferation of human glioblastoma cells by activating transient receptor potential melastatin 7 channels.

Recent studies showed that both prostaglandin E2 (PGE2) and transient receptor potential melastatin 7 (TRPM7) play important roles in migration and proliferation of human glioblastoma cells. In this study, we tested the association between PGE2 and TRPM7. We found that PGE2 increased TRPM7 currents in HEK293 and human glioblastoma A172 cells. The PGE2 EP3 receptor antagonist L-798106 abrogated the PGE2 stimulatory effect, while EP3 agonist 17-phenyl trinor prostaglandin E2 (17-pt-PGE2) mimicked the effect of PEG2 on TRPM7. The TRPM7 phosphotransferase activity-deficient mutation, K1646R had no effect on PGE2 induced increase of TRPM7 currents. Inhibition of protein kinase A (PKA) activity by Rp-cAMP increased TRPM7 currents. TRPM7 PKA phosphorylation site mutation S1269A abolished the PGE2 effect on TRPM7 currents. PGE2 increased both mRNA and membrane protein expression of TRPM7 in A172 cells. Knockdown of TRPM7 by shRNA abrogated the PGE2 stimulated migration and proliferation of A172 cells. Blockage of TRPM7 with 2-aminoethoxydiphenyl borate (2-APB) or NS8593 had a similar effect as TRPM7-shRNA. In conclusion, our results demonstrate that PGE2 activates TRPM7 via EP3/PKA signalling pathway, and that PGE2 enhances migration and proliferation of human glioblastoma cells by up-regulation of the TRPM7 channel.

Regulation of aldosterone production by ion channels: From basal secretion to primary aldosteronism.

Aldosterone is produced by zona glomerulosa (ZG) cells of the adrenal cortex and plays a key role in balancing water and electrolytes levels. Autonomous overproduction of aldosterone leads to primary aldosteronism (PA), which is the most common form of secondary endocrine hypertension. Recently, significant progress has been made towards understanding the genetic basis of PA, where increasing clinical evidence suggests that mutations in ion channels appear to be the major cause of aldosterone-producing adenomas. In this review, we focused on potassium and calcium channels that regulate aldosterone secretion, and their roles in the pathology of PA. Because potassium and calcium channels are differentially expressed in ZG cells in different species of mammals, the limitations of published studies are also discussed.

GDF-15 enhances intracellular Ca2+ by increasing Cav1.3 expression in rat cerebellar granule neurons.

GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-ß superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K(+) currents and Kv2.1 α subunit expression through TßRII (TGF-ß receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca(2+) concentration ([Ca(2+)]i) in response to membrane depolarization, as determined by Ca(2+) imaging. Whole-cell current recordings indicated that GDF-15 increased the inward Ca(2+) current (ICa) without altering steady-state activation of Ca(2+) channels. Treatment with nifedipine, an inhibitor of L-type Ca(2+) channels, abrogated GDF-15-induced increases in [Ca(2+)]i and ICa The GDF-15-induced increase in ICa was mediated via up-regulation of the Cav1.3 α subunit, which was attenuated by inhibiting Akt/mTOR and ERK (extracellular-signal-regulated kinase) pathways and by pharmacological inhibition of Src-mediated TßRII phosphorylation. Given that Cav1.3 is not only a channel for Ca(2+) influx, but also a transcriptional regulator, our data confirm that GDF-15 induces protein expression via TßRII and activation of a non-Smad pathway, and provide novel insight into the mechanism of GDF-15 function in neurons.

Role of voltage-gated calcium channels in the regulation of aldosterone production from zona glomerulosa cells of the adrenal cortex.

Zona glomerulosa cells (ZG) of the adrenal gland constantly integrate fluctuating ionic, hormonal and paracrine signals to control the synthesis and secretion of aldosterone. These signals modulate Ca2+ levels, which provide the critical second messenger to drive steroid hormone production. Angiotensin II is a hormone known to modulate the activity of voltage-dependent L- and T-type Ca2+ channels that are expressed on the plasma membrane of ZG cells in many species. Because the ZG cell maintains a resting membrane voltage of approximately -85 mV and has been considered electrically silent, low voltage-activated T-type Ca2+ channels are assumed to provide the primary Ca2+ signal that drives aldosterone production. However, this view has recently been challenged by human genetic studies identifying somatic gain-of-function mutations in L-type CaV 1.3 channels in aldosterone-producing adenomas of patients with primary hyperaldosteronism. We provide a review of these assumptions and challenges, and update our understanding of the state of the ZG cell in a layer in which native cellular associations are preserved. This updated view of Ca2+ signalling in ZG cells provides a unifying mechanism that explains how transiently activating CaV 3.2 channels can generate a significant and recurring Ca2+ signal, and how CaV 1.3 channels may contribute to the Ca2+ signal that drives aldosterone production.

Leukotriene B4 Inhibits L-Type Calcium Channels via p38 Signaling Pathway in Vascular Smooth Muscle Cells.

BACKGROUND/AIMS: Arachidonic acid (AA) and its metabolites are important endogenous lipid messengers. In this study, we test the effect of Leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of AA, on L-type calcium channels in A7r5 rat aortic vascular smooth muscle cells. METHODS: L-type calcium channel currents were recorded by a patch-clamp technique. The mRNA expression of CaV1.2 was determined by Real-time RT-PCR. The protein expression of CaV1.2 and p38 activity was determined by Western blot analysis. RESULTS: LTB4 inhibits L-type channel currents in A7r5 cells in a dose-and time- dependent manner. LTB4 reduced the mRNA/protein expression of CaV1.2 channels in A7r5 cells. BLT1 receptor antagonist LY29311 abrogated the inhibitory effect of LTB4, while BLT2 receptor antagonist LY255283 had no effect. 5Z-7-oxozeaenol and SB203580, which block TAK1 and p38 kinase respectively, abrogated the LTB4 inhibitory effect on L-type calcium channels. LTB4 increased p38 activity in A7r5 cells. Blockage of Src, PI3K, JNK and NF-x03BA;B kinase had no effects on LTB4 inhibition of L-type calcium channel currents in A7r5 cells. CONCLUSION: We conclude that LTB4 inhibits L-type calcium channels through BLT1-TAk1-p38 signaling pathway. The LTB4 inhibitory effect on L-type calcium channels may be involved in its pathological processes such as atherosclerosis.

PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway.

AIMS: PGE2 is one of the most abundant prostanoids in mammalian tissues, but its effect on neuronal receptors has not been well investigated. This study examines the effect of PGE2 on GABAA receptor currents in rat cerebellar granule neurons. METHODS: GABAA currents were recorded using a patch-clamp technique. Cell surface and total protein of GABAA ß1/2/3 subunits was carried out by Western blot analysis. RESULTS: Upon incubation of neurons with PGE2 (1 µM) for 60 minutes, GABAA currents were significantly potentiated. This PGE2-driven effect could be blocked by PKC or CaMKII inhibitors as well as EP1 receptor antagonist, and mimicked by PMA or EP1 receptor agonist. Furthermore, Western blot data showed that PGE2 did not increase the total expression level of GABAA receptors, but significantly increased surface levels of GABAA ß1/2/3 subunits after 1 h of treatment. Consistently, both PKC and CaMKII inhibitors were able to reduce PGE2-induced increases in cell surface expression of GABAA receptors. CONCLUSION: Activation of either the PKC or CaMKII pathways by EP1 receptors mediates the PGE2-induced increase in GABAA currents. This suggests that upregulation of postsynaptic GABAA receptors by PGE2 may have profound effects on cerebellar functioning under physiological and pathological conditions.

Caspase-3 modulates regenerative response after stroke.

Stroke is a leading cause of long-lasting disability in humans. However, currently there are still no effective therapies available for promoting stroke recovery. Recent studies have shown that the adult brain has the capacity to regenerate neurons after stroke. Although this neurogenic response may be functionally important for brain repair after injury, the mechanisms underlying stroke-induced neurogenesis are not known. Caspase-3 is a major executioner and has been identified as a key mediator of neuronal death in the acute stage of stroke. Recently, however, accumulating data indicate that caspase-3 also participates in various biological processes that do not cause cell death. Here, we show that cleaved caspase-3 was increased in newborn neuronal precursor cells (NPCs) in the subventricular zone (SVZ) and the dentate gyrus during the period of stroke recovery, with no evidence of apoptosis. We observed that cleaved caspase-3 was expressed by NPCs and limited its self-renewal without triggering apoptosis in cultured NPCs from the SVZ of ischemic mice. Moreover, we revealed that caspase-3 negatively regulated the proliferation of NPCs through reducing the phosphorylation of Akt. Importantly, we demonstrated that peptide inhibition of caspase-3 activity significantly promoted the proliferation and migration of SVZ NPCs and resulted in a significant increase in subsequent neuronal regeneration and functional recovery after stroke. Together, our data identify a previously unknown caspase-3-dependent mechanism that constrains stroke-induced endogenous neurogenesis and should revitalize interest in targeting caspase-3 for treatment of stroke.

Differential roles of the C and N termini of Orai1 protein in interacting with stromal interaction molecule 1 (STIM1) for Ca2+ release-activated Ca2+ (CRAC) channel activation.

The entry of extracellular Ca(2+), which is mediated by Ca(2+) release-activated Ca(2+) (CRAC) channels, is essential for T cell activation and the normal functioning of other immune cells. Although the molecular components of CRAC channels, the Orai1 pore-forming subunit and the STIM1-activating subunit have been recently identified, the gating mechanism by which Orai1 channels conduct Ca(2+) entry upon Orai1-STIM1 interaction following Ca(2+) store release remains elusive. Herein, we show that C-terminal truncations or point mutations prevented Orai1 from binding to STIM1 and subsequent channel opening. In contrast, an Orai1 mutant with an N-terminal truncation interacted with but failed to be activated by STIM1. Moreover, Orai1 channels with C-terminal disruption, but not N-terminal truncation, could be gated by fused functional domains of STIM1. Interestingly, the channel activities of Orai1 mutants carrying either an N-terminal or a C-terminal truncation were restored by a methionine mutation at the putative gating hinge, the conserved Gly-98 site in the first transmembrane segment (TM1) of Orai1. Collectively, these results support a stepwise gating mechanism of STIM1-operated Orai1 channels; the initial binding between STIM1 and the C terminus of Orai1 docks STIM1 onto the N terminus of Orai1 to initiate conformational changes of the pore-lining TM1 helix of Orai1, leading to the opening of the channel.

Glucocorticoids modulate neural activity via a rapid non-genomic effect on Kv2.2 channels in the central nervous system.

Glucocorticoids are primary stress hormones that exert neuronal effects via both genomic and non-genomic signaling pathways. However, their rapid non-genomic effects and underlying mechanisms on neural activities remain elusive. In the present study, we investigated the rapid non-genomic effect of glucocorticoids on Kv2.2 channels in cultured HEK293 cells and acute brain slices including cortical pyramidal neurons and calyx-type synapses in the brain stem. We found that cortisol, the endogenous glucocorticoids, rapidly increased Kv2.2 currents by increasing the single-channel open probability in Kv2.2-expressing HEK293 cells through activation of the membrane-associated glucocorticoid receptor. Bovine serum albumin-conjugated dexamethasone, a membrane-impermeable agonist of the glucocorticoid receptor, could mimic the effect of cortisol on Kv2.2 channels. The cortisol-increased Kv2.2 currents were induced by activation of the extracellular signal-regulated protein kinase (ERK) 1/2 kinase, which could be inhibited by U0126, an antagonist of the ERK signaling pathway. In layer 2 cortical pyramidal neurons and the calyx of Held synapses, cortisol suppressed the action potential firing frequency during depolarization and reduced the successful rate upon high-frequency stimulation by activating Kv2.2 channels. We further examined the postsynaptic responses and found that cortisol did not affect the mEPSC and evoked EPSC, but increased the activity-dependent synaptic depression induced by a high-frequency stimulus train. In conclusion, glucocorticoids can rapidly activate Kv2.2 channels through membrane-associated glucocorticoid receptors via the ERK1/2 signaling pathway, suppress presynaptic action potential firing, and inhibit synaptic transmission and plasticity. This may be a universal mechanism of the glucocorticoid-induced non-genomic effects in the central nervous system.

Neuritin activates insulin receptor pathway to up-regulate Kv4.2-mediated transient outward K+ current in rat cerebellar granule neurons.

Neuritin is a new neurotrophic factor discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin also plays multiple roles in the process of neural development and synaptic plasticity. The receptors for binding neuritin and its downstream signaling effectors, however, remain unclear. Here, we report that neuritin specifically increases the densities of transient outward K(+) currents (I(A)) in rat cerebellar granule neurons (CGNs) in a time- and concentration-dependent manner. Neuritin-induced amplification of I(A) is mediated by increased mRNA and protein expression of Kv4.2, the main α-subunit of I(A). Exposure of CGNs to neuritin markedly induces phosphorylation of ERK (pERK), Akt (pAkt), and mammalian target of rapamycin (pmTOR). Neuritin-induced I(A) and increased expression of Kv4.2 are attenuated by ERK, Akt, or mTOR inhibitors. Unexpectedly, pharmacological blockade of insulin receptor, but not the insulin-like growth factor 1 receptor, abrogates the effect of neuritin on I(A) amplification and Kv4.2 induction. Indeed, neuritin activates downstream signaling effectors of the insulin receptor in CGNs and HeLa. Our data reveal, for the first time, an unanticipated role of the insulin receptor in previously unrecognized neuritin-mediated signaling.

Multiphysical Field Modulated VO2 Device for Information Encryption.

In the information explosion society, information security is highly demanded in the practical application, which raised a surge of interest in designing secure and reliable information transmission channels based on the inherent properties of emerging devices. Here, an innovative strategy to achieve the data encryption and reading during the data confidential transmission based on VO2 device is proposed. Owing to the specific insulator-to-metal transition property of VO2 , the phase transitions between the insulator and metallic states are modulated by the combination of electric field, temperature, and light radiation. These external stimulus-induced phase diagram is directly associated with the defined VO2 device, which are applicable for control the "0" or "1" electrical logic state for the information encryption. A prototype device is fabricated on an epitaxial VO2 film, which displayed a unique data encryption function with excellent stability. The current study not only demonstrated a multiphysical field-modulated VO2 device for information encryption, but also supplied some clues for functional devices applications in other correlated oxide materials.

A machine learning-based PET/CT model for automatic diagnosis of early-stage lung cancer.

Objective: The aim of this study was to develop a machine learning-based automatic analysis method for the diagnosis of early-stage lung cancer based on positron emission tomography/computed tomography (PET/CT) data. Methods: A retrospective cohort study was conducted using PET/CT data from 187 cases of non-small cell lung cancer (NSCLC) and 190 benign pulmonary nodules. Twelve PET and CT features were used to train a diagnosis model. The performance of the machine learning-based PET/CT model was tested and validated in two separate cohorts comprising 462 and 229 cases, respectively. Results: The standardized uptake value (SUV) was identified as an important biochemical factor for the early stage of lung cancer in this model. The PET/CT diagnosis model had a sensitivity and area under the curve (AUC) of 86.5% and 0.89, respectively. The testing group comprising 462 cases showed a sensitivity and AUC of 85.7% and 0.87, respectively, while the validation group comprising 229 cases showed a sensitivity and AUC of 88.4% and 0.91, respectively. Additionally, the proposed model improved the clinical discrimination ability for solid pulmonary nodules (SPNs) in the early stage significantly. Conclusion: The feature data collected from PET/CT scans can be analyzed automatically using machine learning techniques. The results of this study demonstrated that the proposed model can significantly improve the accuracy and positive predictive value (PPV) of SPNs at the early stage. Furthermore, this algorithm can be optimized into a robotic and less biased PET/CT automatic diagnosis system.

Continuous Photothermal and Radiative Cooling Energy Harvesting by VO2 Smart Coatings with Switchable Broadband Infrared Emission.

Extensive use of renewable and clean energy is one of the promising ways to solve energy/environmental problems and promote the sustainable development of our society. As inexhaustible energy sources, the photothermal (PT) and radiative cooling (RC) energy from the sun and outer space have recently attracted tremendous interest. However, these two kinds of energy utilization have distinctly opposite spectral properties, especially in the infrared range, making it extremely difficult to integrate these two energy harvesting modes within a fixed device for continuous energy collection. Thus, in the current study, we have proposed a spectrally self-adaptive broadband absorber/emitter (SSBA/E) based on vanadium dioxide (VO2), a typical phase transition material, to achieve continuous energy harvesting via collecting solar thermal energy in PT mode during the day and obtaining cool energy in wide-band RC mode at night. Experimental results show that owing to the phase transition property of the VO2 layer, these two energy collection modes can be adaptively switched. Specifically, the VO2-based device shows a broadband infrared emissivity modulation from 0.21 to 0.75 and low critical temperatures (58.4 and 49.2 °C) during the phase transition, leading to continuous energy harvesting with high efficiency. Due to the broadband infrared emission, the RC maximum power of the SSBA/E device was estimated to be 58 W m-2. The proposed VO2 smart coatings are also applicable for many other applications such as thermal management of spacecraft, infrared camouflage, or adaptive optical devices.

Cholesterol enhances neuron susceptibility to apoptotic stimuli via cAMP/PKA/CREB-dependent up-regulation of Kv2.1.

Cholesterol is a major component of membrane lipid rafts. It is more abundant in the brain than in other tissues and plays a critical role in maintaining brain function. We report here that a significant enhancement in apoptosis in rat cerebellar granule neurons (CGNs) was observed upon incubation with 5mM K(+) /serum free (LK-S) medium. Cholesterol enrichment further potentiated CGN apoptosis incubated under LK-S medium. On the contrary, cholesterol depletion using methyl-beta-cyclodextrin protected the CGNs from apoptosis induced by LK-S treatment. Cholesterol enrichment, however, did not induce apoptosis in CGNs that have been incubated with 25mM K(+) /serum medium. Mechanistically, increased I(K) currents and DNA fragmentation were found in CGNs incubated in LK-S, which was further potentiated in the presence of cholesterol. Cholesterol-treated CGNs also exhibited increased cAMP levels and up-regulation of Kv2.1 expression. Increased levels of activated form of PKA and phospho-CREB further supported activation of the cAMP/PKA pathway upon treatment of CGNs with cholesterol-containing LK-S medium. Conversely, inhibition of PKA or small G protein Gs abolished the increase in I(K) current and the potentiation of Kv2.1 expression, leading to reduced susceptibility of CGNs to LK-S and cholesterol-induced apoptosis. Our results demonstrate that the elevation of membrane cholesterol enhances CGN susceptibility to apoptotic stimuli via cAMP/PKA/CREB-dependent up-regulation of Kv2.1. Our data provide new evidence for the role of cholesterol in eliciting neuronal cell death.

Enhanced Contrast of WO3-Based Smart Windows by Continuous Li-Ion Insertion and Metal Electroplating.

The electrochromic WO3 smart window based on an aqueous electrolyte shows an excellent liquid/solid interface and thus can achieve a fast electrochromic response, while the aqueous electrolyte has a limited electrochemical window, which probably induces the H+ reduction and degrades the practical application. Here, we propose a strategy to modify the traditional Li+ acidic aqueous electrolyte by adding some selective inert metal ions, which not only improve the electrochromic performance but also avoid the possible production of hydrogen bubbles due to the broadened electrochemical window. Furthermore, reversible electroplating of inert metal ions will occur, leading to an enhanced optical transmission change of up to 77.5% at 500 nm and 70.4% at 700 nm. This combination of Li-ion insertion and metal electroplating in the ESW device makes it superior to all of the previous reports. The device also demonstrates high stability and high electrochromic efficiency after 1000 cycles. The current study not only emphasizes the rational design for aqueous electrolytes but also demonstrates a practical way to realize an excellent electrochromic window for practical applications.

Protein Kinase C Controls the Excitability of Cortical Pyramidal Neurons by Regulating Kv2.2 Channel Activity.

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.

Honokiol Reduces Mitochondrial Dysfunction and Inhibits Apoptosis of Nerve Cells in Rats with Traumatic Brain Injury by Activating the Mitochondrial Unfolded Protein Response.

This study was designed to determine the effects and underlying mechanism of honokiol (HNK) on traumatic brain injury (TBI). A rat TBI model was constructed using the modified Feeney free-fall percussion method and treatment with HNK via intraperitoneal injection. The brain tissues of the rats in each group were assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay to detect the level of neuronal apoptosis. Western blots were used to detect the expression levels of apoptosis-related proteins (Bcl-2 and Bax), and ELISAs were used to measure the levels of pro-inflammatory cytokines (IL-18 and IL-1ß) and the activity of caspase-1. In addition, the mitochondrial membrane potential, reactive oxygen species (ROS), and adenosine 5'-triphosphate (ATP) were also measured. Western blots and qRT-PCRs were used to determine the relative expression levels of the mitochondrial unfolded protein response (UPRmt)-related proteins and mRNAs. Based on the experimental results, treatment with HNK was associated with a decrease in the number of TUNEL-positive cells, downregulated Bax expression levels, elevated Bcl-2 expression levels, and inhibition of neuronal apoptosis in the brain tissue of TBI rats. HNK also suppressed neuroinflammation by decreasing IL-1ß and IL-18 levels and caspase-1 activity. Additionally, HNK lowered the mitochondrial membrane potential and ROS levels, increased ATP levels, and improved mitochondrial dysfunction in neural cells. Furthermore, in the investigation of the mechanism of HNK on TBI, we observed that HNK could activate UPRmt by upregulating the mRNA and protein expression levels of HSPA9, CLPP, and HSP60 in the brain tissues of TBI rats. Collectively, HNK reduced mitochondrial dysfunction, inhibited the apoptosis of nerve cells, and attenuated inflammation in the brains of TBI rats. The protective effect of HNK may be achieved through the activation of UPRmt.

Enhanced Pd/a-WO3 /VO2 Hydrogen Gas Sensor Based on VO2 Phase Transition Layer.

The utilization of clean hydrogen energy is becoming more feasible for the sustainable development of this society. Considering the safety issues in the hydrogen production, storage, and utilization, a sensitive hydrogen sensor for reliable detection is essential and highly important. Though various gas sensor devices are developed based on tin oxide, tungsten trioxide, or other oxides, the relatively high working temperature, unsatisfactory response time, and detection limitation still affect the extensive applications. In the current study, an amorphous tungsten trioxide (a-WO3 ) layer is deposited on a phase-change vanadium dioxide film to fabricate a phase transition controlled Pd/a-WO3 /VO2 hydrogen sensor for hydrogen detection. Results show that both the response time and sensitivity of the hydrogen sensor are improved greatly if increasing the working temperature over the transition temperature of VO2 . Theoretical calculations also reveal that the charge transfer at VO2 /a-WO3 interface becomes more pronounced once the VO2 layer transforms to the metal state, which will affect the migration barrier of H atoms in a-WO3 layer and thus improve the sensor performance. The current study not only realizes a hydrogen sensor with ultrahigh performance based on VO2 layer, but also provides some clues for designing other gas sensors with phase-change material.