Administration of exosomes derived from mesenchymal stromal cells (MSCs) could improve some neurologic conditions by transferring functional biomolecules to recipient cells. Furthermore, exosomes ...from hypoxic progenitor cells exerted better therapeutic effects in organ injury through specific cargoes. However, there are no related reports about whether exosomes derived from MSCs or hypoxia‐preconditioned MSCs (PC‐MSCs) could prevent memory deficits in Alzheimer disease (AD). In this study, the exosomes derived from MSCs or PC‐MSCs were systemically administered to transgenic APP/PS1 mice. The expression of miR‐21 in MSCs was significantly increased after hypoxic treatment. Injection of exosomes from normoxic MSCs could rescue cognition and memory impairment according to results of the Morris water maze test, reduced plaque deposition, and Aβ levels in the brain; could decrease the activation of astrocytes and microglia; could down‐regulate proinflammatory cytokines (TNF‐α and IL‐1β); and could up‐regulate anti‐inflammatory cytokines (IL‐4 and ‐10) in AD mice, as well as reduce the activation of signal transducer and activator of transcription 3 (STAT3) and NF‐κB. Compared to the group administered exosomes from normoxic MSCs, in the group administered exosomes from PC‐MSCs, learning and memory capabilities were significantly improved; the plaque deposition and Aβ levels were lower, and expression of growth‐associated protein 43, synapsin 1, and IL‐10 was increased; and the levels of glial fibrillary acidic protein, ionized calcium‐binding adaptor molecule 1, TNF‐α, IL‐1β, and activation of STAT3 and NF‐κB were sharply decreased. More importantly, exosomes from PC‐MSCs effectively increased the level of miR‐21 in the brain of AD mice. Additionally, replenishment of miR‐21 restored the cognitive deficits in APP/PS1 mice and prevented pathologic features. Taken together, these findings suggest that exosomes from PC‐MSCs could improve the learning and memory capabilities of APP/PS1 mice, and that the underlying mechanism may lie in the restoration of synaptic dysfunction and regulation of inflammatory responses through regulation of miR‐21.—Cui, G.‐H., Wu, J., Mou, F.‐F., Xie, W.‐H., Wang, F.‐B., Wang, Q.‐L., Fang, J., Xu, Y.‐W., Dong, Y.‐R., Liu, J.‐R., Guo, H.‐D. Exosomes derived from hypoxia‐preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J. 32, 654–668 (2018). www.fasebj.org
Aims
Gastric hypersensitivity (GHS) is a characteristic pathogenesis of functional dyspepsia (FD). DNA methyltransferase 1 (DNMT1) and acid‐sensing ion channel 1 (ASIC1) are associated with GHS ...induced by prenatal maternal stress (PMS). The aim of this study was to investigate the mechanism of DNMT1 mediating the analgesic effect of folic acid (FA) on PMS‐induced GHS.
Methods
GHS was quantified by electromyogram recordings. The expression of DNMT1, DNMT3a, DNMT3b, and ASIC1 were detected by western blot, RT‐PCR, and double‐immunofluorescence. Neuronal excitability and proton‐elicited currents of dorsal root ganglion (DRG) neurons were determined by whole‐cell patch clamp recordings.
Results
The expression of DNMT1, but not DNMT3a or DNMT3b, was decreased in DRGs of PMS rats. FA alleviated PMS‐induced GHS and hyperexcitability of DRG neurons. FA also increased DNMT1 and decreased ASIC1 expression and sensitivity. Intrathecal injection of DNMT1 inhibitor DC‐517 attenuated the effect of FA on GHS alleviation and ASIC1 downregulation. Overexpression of DNMT1 with lentivirus not only rescued ASIC1 upregulation and hypersensitivity, but also alleviated GHS and hyperexcitability of DRG neurons induced by PMS.
Conclusions
These results indicate that increased DNMT1 contributes to the analgesic effect of FA on PMS‐induced GHS by reducing ASIC1 expression and sensitivity.
The present study has shown that FA alleviates PMS‐induced GHS through increasing DNMT1 and decreasing ASIC1, respectively, and blocking DNMT1 attenuate the effect of FA on GHS and ASIC1 expression. These findings suggest that DNMT1 mediates the analgesic effect of FA on GHS through downregulating ASIC1 and may be a therapeutic target for the treatment of visceral pain.
Conducting polymers, such as the p-doped poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), have enabled the development of an array of opto- and bio-electronics devices. However, ...to make these technologies truly pervasive, stable and easily processable, n-doped conducting polymers are also needed. Despite major efforts, no n-type equivalents to the benchmark PEDOT:PSS exist to date. Here, we report on the development of poly(benzimidazobenzophenanthroline):poly(ethyleneimine) (BBL:PEI) as an ethanol-based n-type conductive ink. BBL:PEI thin films yield an n-type electrical conductivity reaching 8 S cm
, along with excellent thermal, ambient, and solvent stability. This printable n-type mixed ion-electron conductor has several technological implications for realizing high-performance organic electronic devices, as demonstrated for organic thermoelectric generators with record high power output and n-type organic electrochemical transistors with a unique depletion mode of operation. BBL:PEI inks hold promise for the development of next-generation bioelectronics and wearable devices, in particular targeting novel functionality, efficiency, and power performance.
This paper proposes a resilient controller for DC microgrid to achieve current sharing and voltage restoration under discrete-time false data injection (FDI) and denial-of-service (DoS) attacks. ...Switching and impulsive signals are used to model the dynamic system of DC microgrid under DoS and FDI. To deal with the cyber attacks, a combined error of current and voltage is proposed and a switching secondary controller is designed. Based on the stability analysis method on hybrid systems, we establish a sufficient condition for selecting control parameters in relation to the average dwell time of FDI attack and the normal communication rate under DoS attack. Furthermore, an adaptive gain based control scheme is proposed to relax the requirement on knowledge of the cyber attacks in control parameter design. The utility of the results is illustrated through case studies on a tested DC microgrid.
Inferior charge transport in insulating and bulk discharge products is one of the main factors resulting in poor cycling stability of lithium-oxygen batteries with high overpotential and large ...capacity decay. Here we report a two-step oxygen reduction approach by pre-depositing a potassium carbonate layer on the cathode surface in a potassium-oxygen battery to direct the growth of defective film-like discharge products in the successive cycling of lithium-oxygen batteries. The formation of defective film with improved charge transport and large contact area with a catalyst plays a critical role in the facile decomposition of discharge products and the sustained stability of the battery. Multistaged discharge constructing lithium peroxide-based heterostructure with band discontinuities and a relatively low lithium diffusion barrier may be responsible for the growth of defective film-like discharge products. This strategy offers a promising route for future development of cathode catalysts that can be used to extend the cycling life of lithium-oxygen batteries.
The in situ tracking of the pyrolysis of a binary molecular cluster Zn7(μ3‐CH3O)6(L)6ZnLCl22 is presented with one brucite disk and two mononuclear fragments (L=mmimp: ...2‐methoxy‐6‐((methylimino)‐methyl)phenolate) to porous carbon using TG‐MS from 30 to 900 °C. Following up the spilled gas product during the decomposed reaction of zinc cluster along the temperature rising, and in conjunction with XRD, SEM, BET and other materials characterization, where three key steps were observed: 1) cleavage of the bulky external ligand; 2) reduction of ZnO and 3) volatilization of Zn. The real‐time‐dependent phase‐sequential evolution of the remaining products and the processing of pore forming template transformation are proposed simultaneously. The porous carbon structure featuring a uniform nano‐sized pore distribution synthesized at 900 °C with the highest surface area of 1644 m2 g−1 and pore volume of 0.926 cm3 g−1 exhibits the best known capacitance of 662 F g−1 at 0.5 A g−1.
Supercharged: The in situ pyrolysis and real‐time progressive phase evolution of a binary zinc molecular cluster are tracked. The supercapacitive porous carbon, which is obtained under 900 °C, has a record capacitance of 662 F g−1 at 0.5 A g−1.
As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused more than 6,000,000 infected persons and 360,000 deaths globally. Previous studies revealed pregnant women with COVID-19 had similar ...clinical manifestations to nonpregnant women. However, little is known about the outcome of neonates born to infected women.
In this retrospective study, we studied 29 pregnant women with COVID-19 infection delivered in 2 designated general hospitals in Wuhan, China between January 30 and March 10, 2020, and 30 neonates (1 set of twins). Maternal demographic characteristics, delivery course, symptoms, and laboratory tests from hospital records were extracted. Neonates were hospitalized if they had symptoms (5 cases) or their guardians agreed to a hospitalized quarantine (13 cases), whereas symptom-free neonates also could be discharged after birth and followed up through telephone (12 cases). For hospitalized neonates, laboratory test results and chest X-ray or computed tomography (CT) were extracted from hospital records. The presence of antibody of SARS-CoV-2 was assessed in the serum of 4 neonates. Among 29 pregnant COVID-19-infected women (13 confirmed and 16 clinical diagnosed), the majority had higher education (56.6%), half were employed (51.7%), and their mean age was 29 years. Fourteen women experienced mild symptoms including fever (8), cough (9), shortness of breath (3), diarrhea (2), vomiting (1), and 15 were symptom-free. Eleven of 29 women had pregnancy complications, and 27 elected to have a cesarean section delivery. Of 30 neonates, 18 were admitted to Wuhan Children's Hospital for quarantine and care, whereas the other 12 neonates discharged after birth without any symptoms and had normal follow-up. Five hospitalized neonates were diagnosed as COVID-19 infection (2 confirmed and 3 suspected). In addition, 12 of 13 other hospitalized neonates presented with radiological features for pneumonia through X-ray or CT screening, 1 with occasional cough and the others without associated symptoms. SARS-CoV-2 specific serum immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in 4 neonates and 2 were positive. The limited sample size limited statistical comparison between groups.
In this study, we observed COVID-19 or radiological features of pneumonia in some, but not all, neonates born to women with COVID-19 infection. These findings suggest that intrauterine or intrapartum transmission is possible and warrants clinical caution and further investigation.
Chinese Clinical Trial Registry, ChiCTR2000031954 (Maternal and Perinatal Outcomes of Women with coronavirus disease 2019 (COVID-19): a multicenter retrospective cohort study).
This paper studies the current sharing problem of a dc microgrid using the hybrid dynamic control method. The hybrid dynamic controller framework is established including a continuous-time part and a ...discrete-time part, where the former part eliminates the voltage deviation of the dc bus and the latter part ensures the current sharing accuracy of the dc microgrid. The proposed distributed hybrid secondary controller not only guarantees a high accuracy of current sharing but also maintains the voltage regulation at the dc bus. Different from most existing methods, it only utilizes the sampling output current information of neighbors at the discrete time instants, which greatly reduces the communication burden. Under the framework of stability analysis on the closed-loop system, the proposed hybrid dynamic controller achieves both current sharing and voltage regulation if the average interacted interval of the discrete time interaction satisfies a bounded constraint. Besides, a detailed parameter design of the controller is provided. Finally, simulation and experimental tests are presented to demonstrate the effectiveness of the proposed method.
Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease (IBD) characterized by complicated and relapsing inflammation in the gastrointestinal tract. SM934 is a water-soluble ...artemisinin analogue that shows anti-inflammatory and immuno-regulatory effects. In this study, we investigated the effects of SM934 on UC both in vivo and in vitro. A mouse model of colitis was established in mice by oral administration of 5% dextran sulfate sodium (DSS). SM934 (3, 10 mg/kg per day, ig) was administered to the mice for 10 days. After the mice were sacrificed, colons, spleens and mesenteric lymph nodes (MLNs) were collected for analyses. We showed that SM934 administration restored DSS-induced body weight loss, colon shortening, injury and inflammation scores. Furthermore, SM934 administration significantly decreased the disease activity index (DAI), histopathological scores, and myeloperoxidase (MPO) activities in colonic tissues. Moreover, SM934 administration dose-dependently decreased the mRNA and protein levels of DSS-induced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the percentage of macrophages and neutrophils in colon tissues. The effects of SM934 on LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages were examined in vitro. Treatment with SM934 (0.8, 8, 80 μmol/L) dose-dependently decreased the production of pro-inflammatory mediators in LPS-stimulated RAW264.7 cells and THP-1-derived macrophages via inhibiting activation of the NF-κB signaling. Our results reveal the protective effects of SM934 on DSS-induced colitis can be attributed to its suppressing effects on neutrophils and macrophages and its inhibitory role in the NF-κB signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.
The structure and dynamics in SE Tibet are the key to understand the tectonic evolution of the Tibetan Plateau. In this study we determined high-resolution P-wave seismic images in the upper mantle ...and transition zone in SE Tibet by jointly inverting the travel-time residuals of local events and the relative travel-time residuals of teleseismic events recorded by very dense seismic stations. We revealed a high-velocity body in the upper mantle beneath South China that represents the root of the Yangtze Craton. The high-velocity body extends in the entire Yangtze Craton at 300–450 km depths, but it is constrained just beneath the Sichuan Basin and surrounded by extensive low-velocity zones to the southwest at 65–250 km depths. We propose that the Yangtze Craton is destructed laterally by the mantle flow extruded from the Tibetan Plateau. We obtain a low-velocity column in the upper mantle under the Tengchong volcano as well as the visible high-velocity bodies in the upper mantle and transition zone below the low-velocity column. The images suggest that the Tengchong volcano is closely related to the subduction of the Burma plate and caused by the dehydration of the subducted slab. The present study reveals unprecedented details of the mantle structures beneath SE Tibet and provides new insights into the geodynamics of the Tibetan Plateau and its interaction with the stable Yangtze Craton.
•Southeastward mantle flow exists in the upper mantle under SE Tibet.•Yangtze Craton is destructed laterally by the upper-mantle extrusion.•Tengchong volcano is related to the subduction of the Burman plate.
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