•VNS may be effective in treating a wider range of brain diseases.•VNS can exert its effect through the anti-inflammatory and central mechanisms.•The liver, spleen, gut, and brain are involved in the ...anti-inflammatory mechanisms.•The central mechanisms are related to monoamine, GABA, BDNF-TrkB, CBF and functional connectivity of brain regions.
Brain diseases, including neurodegenerative, cerebrovascular and neuropsychiatric diseases, have posed a deleterious threat to human health and brought a great burden to society and the healthcare system. With the development of medical technology, vagus nerve stimulation (VNS) has been approved by the Food and Drug Administration (FDA) as an alternative treatment for refractory epilepsy, refractory depression, cluster headaches, and migraines. Furthermore, current evidence showed promising results towards the treatment of more brain diseases, such as Parkinson’s disease (PD), autistic spectrum disorder (ASD), traumatic brain injury (TBI), and stroke. Nonetheless, the biological mechanisms underlying the beneficial effects of VNS in brain diseases remain only partially elucidated. This review aims to delve into the relevant preclinical and clinical studies and update the progress of VNS applications and its potential mechanisms underlying the biological effects in brain diseases.
Safety is the lifeline of tourism development. The article's goal is to examin how Chinese tourists perceive risk when travelling aboard.
In order to create the initial corpus, this study first uses ..."outbound tourism"as the key word to crawl the question and answer (hereinafter referred to as "Q & A") data from 4 Chinese online travel operator platforms, then preprocesses the "Q & A" data in Python. Secondly, after being extracted, the feature words are converted into the word vector model using the word vector method based on neural network language model. Finally, the word vectors are clustered and classified.
It is found that there are six dimensions of risk perception of Chinese tourists' outbound tourism, namely traffic risk, planning risk, service risk, communication risk, financial risk and functional risk.
Important and practical information for government and tourism enterprises is provided to accurately grasp the risk perception of Chinese tourists' outbound tourism and continuously improve the supply of tourism risk information.
Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate ...abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF signaling promotes cystine uptake and biosynthesis of glutathione (GSH) to protect fibroblasts from ferroptosis. Lastly, low dose IKE together with etanercept, a TNF antagonist, induce ferroptosis in fibroblasts and attenuate arthritis progression in the CIA model. Our results thus imply that the combination of TNF inhibitors and ferroptosis inducers may serve as a potential candidate for RA therapy.
We are presenting an electrochemical immunosensor for the determination of Galectin-3 (Gal-3), a biomarker of heart failure. A glassy carbon electrode (GCE) was modified with a film of a composite ...made from the N-doped graphene nanoribbons immobilized Fe-based-Metal-organic frameworks deposited with Au nanoparticles (N-GNRs-Fe-MOFs@AuNPs). Primary antibody against Gal-3 (Gal-3-Ab1) was immobilized on the Au nanoparticles on the surface of the modified GCE which then was blocked with bovine serum albumin. Signal amplification is crucial for obtaining low detection limits in biosensors. Here, a relatively simple and ultrasensitive sandwich-type electrochemical immunosensor based on novel signal generation and amplification was developed for the determination of Gal-3. A kind of novel redox-active species, AuPt-Methylene blue (MB) (AuPt-MB) nanocomposites, was synthesized by a one-pot method for the first time. Wherein, MB as a kind of the electron transfer mediators in an amperometric biosensor is responsible for electron production and signal amplification. The rod-like AuPt-MB nanohybrids displayed uniform morphology and good electrochemical activity and can combine with the second antibodies against Gal-3 (Gal-3-Ab2). And the AuPt-MB-Ab2 coupled with the N-GNRs-Fe-MOFs@AuNPs-Ab1 to form the sandwich type format that can greatly enhance the biosensor's sensitivity. Under optimal conditions, the designed immunosensor exhibited a linear concentration range from 100fgmL−1 to 50ngmL−1, with a low detection limit of 33.33fgmL−1 (S/N = 3) for Gal-3 in spiked serum. Additionally, the designed immunosensor showed acceptable selectivity, reproducibility and stability. The satisfactory results in analyzing human serum samples indicated potential application promising in monitoring biomarkers.
•A novel sandwich-type electrochemical immunosensor for the detection of galectin-3 was designed at the first time.•The N-GNRs-Fe-MOF@AuNPs was first used in the immunosensor as substrate platform.•AuPt-MB was first synthesized and applied as signal probe.
Research and development on the technologies of locating the mobile (wireless) phone caller have been rapidly gaining momentum around the world. Once these technologies are mature enough to be ...deployed, they will have significant impact on automotive telematics and modern public transit systems. In this paper, we discuss why locating mobile phones becomes a hot topic among telecommunications giants, what technologies are being studied and standardized, when we are going to see the actual deployment, and what services they may provide? We then consider its potential impact on future intelligent transportation systems, including telematics and public transit systems. Many of us have already recognized how important a role the communications systems play in modern transportation. In the near future, if every mobile phone is able to determine its location, advances in our current transportation systems become inevitable.
Elucidation of both the molecular composition and organization of the ocular lens is a prerequisite to understand its development, function, pathology, regenerative capacity, as well as to model lens ...development and disease using in vitro differentiation of pluripotent stem cells. Lens is comprised of the anterior lens epithelium and posterior lens fibers, which form the bulk of the lens. Lens fibers differentiate from lens epithelial cells through cell cycle exit-coupled differentiation that includes cellular elongation, accumulation of crystallins, cytoskeleton and membrane remodeling, and degradation of organelles within the central region of the lens. Here, we profiled spatiotemporal expression dynamics of both mRNAs and non-coding RNAs from microdissected mouse nascent lens epithelium and lens fibers at four developmental time points (embryonic E day 14.5, E16.5, E18.5, and P0.5) by RNA-seq. During this critical time window, multiple complex biosynthetic and catabolic processes generate the molecular and structural foundation for lens transparency. Throughout this developmental window, 3544 and 3518 genes show consistently and significantly greater expression in the nascent lens epithelium and fibers, respectively. Comprehensive data analysis confirmed major roles of FGF-MAPK, Wnt/β-catenin, PI3K/AKT, TGF-β, and BMP signaling pathways and revealed significant novel contributions of mTOR, EIF2, EIF4, and p70S6K signaling in lens formation. Unbiased motif analysis within promoter regions of these genes with consistent expression changes between epithelium and fiber cells revealed an enrichment for both established (e.g. E2Fs, Etv5, Hsf4, c-Maf, MafG, MafK, N-Myc, and Pax6) transcription factors and a number of novel regulators of lens formation, such as Arntl2, Dmrta2, Stat5a, Stat5b, and Tulp3. In conclusion, the present RNA-seq data serves as a comprehensive reference resource for deciphering molecular principles of normal mammalian lens differentiation, mapping a full spectrum of signaling pathways and DNA-binding transcription factors operating in both lens compartments, and predicting novel pathways required to establish lens transparency.
•New RNA-seq datasets to analyze maturation of nascent lens epithelium and lens fibers.•Identification of coordinated differentiation processes in mouse embryonic lenses.•Resource to study gene regulatory networks that govern lens morphogenesis.•Unbiased data analyses confirm and reveal novel lens signaling pathways.•Data source for comprehensive analysis for gene loss-of-function mouse lens studies.
The Nested Air Quality Prediction Model System （NAQPMS） was used to investigate the temporal and spatial variations of PM2.5 over tropospheric central eastern China in January 2013. The impact of ...regional transport and its implications on pollu- tion prevention and control were also examined. Comparison between simulated and observed PM2.5 showed NAQPMS was able to reproduce the evolution of PM2.5 during heavy haze episodes. The results indicated that regional transport of PM2.5 played an important role in regional haze episodes in the city cluster including Hebei, Beijing and Tianjin （HBT）. The cross-city clusters transport outside HBT and transport among cities inside HBT contributed 20%-35% and 26%-35% of PM2.5 as compared with local emission, in HBT respectively. To meet the Air Quality Standards for Grade II, 90%, 90% and 65% of emissions would have to be cut down in Hebei, Tianjin and Beijing, if non-control strategy was taken in the surround- ing city clusters of HBT. This implicated that control of emissions in one city cluster is not sufficient to reduce regional haze events, and joint efforts among city clusters are essential. Besides regional transports, two-way feedback between bounda- ry-layer evolution and PM2.5 also significantly contributed to the formation of heavy hazes, which contributed 30% of monthly average PM2.5 concentration in HBT.
The crystalline silicon (c-Si) based technologies occupy 95% market share in the global photovoltaic (PV) production capacity. The conversion efficiency of silicon heterojunction (SHJ) solar cell in ...mass production has gone beyond 23%. The most pressing challenge hindering the industrial scale expansion of SHJ solar cell currently is the relatively high production cost as compared to the PERC (passivated emitter and rear cell) product. The low temperature silver paste utilized in the SHJ cell process accounts significantly for about 30% of the total processing cost due to its large consumption. Copper plating is of great current interest to silicon heterojunction application, which has a high potential to cut down the cost and improve cell efficiency by the remarkably reduced shading loss, increased electrode conduction and fill factor. However, there are still some critical issues need to be systematically optimized and proven for mass production. Selectively-deposited seed layer and stripping-free plating resist are the key factors to simplify the plating process. This paper gives a detailed look into the development of copper metallization for SHJ solar cell. Plating process involving seed layer formation and patterning methods are explicated. The process simplification and reliability are discussed aiming at its employment in industrial production.
Autophagy plays an important role in causing inflammatory responses initiated by environmental pollutants and respiratory tract infection.
We sought to investigate the role of cockroach ...allergen–induced excessive activation of autophagy in allergic airway inflammation and its underlying molecular mechanisms.
Environmental allergen–induced autophagy was investigated in the primary human bronchial epithelial cells (HBECs) and lung tissues of asthmatic mouse model and patients. The role of autophagy in asthma development was examined by using autophagy inhibitor 3-methyladenine in an asthma mouse model. Furthermore, the involvements of reactive oxygen species (ROS) and oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) signaling in regulating autophagy during asthma were examined in allergen-treated HBECs and mouse model.
Cockroach allergen activated autophagy in HBECs and in the lung tissues from asthmatic patients and mice. Autophagy inhibitor 3-methyladenine significantly attenuated airway hyperresponsiveness, TH2-associated lung inflammation, and ROS generation. Mechanistically, we demonstrated a pathological feedforward circuit between cockroach allergen–induced ROS and autophagy that is mediated through CaMKII oxidation. Furthermore, transgenic mice with ROS-resistant CaMKII MM-VVδ showed attenuation of TH2-associated lung inflammation and autophagy. Mitochondrial ox-CaMKII inhibition induced by adenovirus carrying mitochondrial-targeted inhibitor peptide CaMKIIN suppresses cockroach allergen–induced autophagy, mitochondrial dysfunction, mitophagy, and cytokine production in HBECs. Finally, mitochondrial CaMKII inhibition suppressed the expression of one of the key ubiquitin-binding autophagy receptors, optineurin, and its recruitment to fragmented mitochondria. Optineurin knockdown inhibited cockroach allergy–induced mitophagy.
Our data suggest a previously uncovered axis of allergen-ROS-ox-CaMKII-mitophagy in the development of allergic airway inflammation and asthma.
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Pyroptosis, a newly discovered form of programmed cell death, is characterized by cell swelling, the protrusion of large bubbles from the plasma membrane and cell lysis. This death pathway is ...mediated by the pore formation of gasdermin D (GSDMD), which is activated by human caspase-1/caspase-4/caspase-5 (or mouse caspase-1/caspase11), and followed with the releasing of both cell contents and proinflammatory cytokines. Pyroptosis was initially found to function as an innate immune effector mechanism to facilitate host defense against pathogenic microorganisms, and subsequent studies revealed that pyroptosis also plays an eventful role in inflammatory immune diseases and tumor resistance. Recent studies have also shown that pyroptosis is involved in the initiation, the progression and complications of atherosclerosis. Here, we provide an overview of the role of pyroptosis in atherosclerosis by focusing on three important participating cells: ECs, macrophages, and SMCs. In addition, we also summarized drugs and stimuli that regulate the progression of atherosclerosis by influencing cell pyroptosis.
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