Background
Diabetes can result in pathological changes to enteric nervous system. Our aim was to test the dynamic changes of enteric neurons and identify the role of enteric glial cells (EGCs) in ...regulating enteric neuron expression in diabetic rats.
Methods
A single injection of streptozotocin (STZ) was used to establish diabetic rats. Animals were randomly distributed into diabetic 1‐, 4‐, 8‐, and 16‐week groups, as well as age‐matched control groups. The PGP9.5‐ and glial fibrillary acidic protein (GFAP)‐immunopositive cells were quantified by immunohistochemistry. The protein levels of PGP9.5, ChAT, nNOS, S‐100β, and c‐fos were determined by western blotting. The levels of nerve growth factor (NGF), neurotrophin 3 (NT‐3), and glial cell‐derived neurotrophic factor (GDNF) were tested by ELISA.
Key Results
An increase in blood glucose and a decrease in body weight were observed following STZ administration. PGP9.5 expression did not change in the diabetic ileum. However, ChAT increased after 16 weeks, and nNOS decreased after 8 and 16 weeks in the ilea of diabetic rats. The absence of degeneration of enteric neurons during the acute stage of the disease could be the consequence of the up‐regulation of GFAP, S‐100β, and c‐fos. Moreover, the content of NGF, NT‐3, and GDNF in the ileum increased by varying degrees after 1 and/or 4 weeks of diabetes. Using 2 co‐culture models of EGCs and SH‐SY5Y cells in a high glucose condition, the supportive role of EGCs was further confirmed.
Conclusions & Inferences
Enteric glial cell activation can protect enteric neurons from damage due to diabetes in the acute stage of the disease, in part via the promotion of neurotrophin release.
Diabetes can result in pathological changes to the enteric nervous system. However, the dynamic changes of enteric neurons and the role of EGCs in regulating enteric neuron expression in rats with diabetes have not been elucidated.
We found that EGC activation protected enteric neurons from damage due to diabetes in the acute stage of the disease, in part via the promotion of neurotrophin release.
The protective effect of EGCs in diabetic neuropathy provides further direction on disease intervention in humans.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The corrosion behavior of type 316 stainless steel in simulated anode environment for proton exchange membrane fuel cell (PEMFC), i.e., dilute hydrochloric acid solutions bubbled with pure hydrogen ...gas at 80
°C, was investigated by using electrochemical measurement techniques. The main purpose is to offer some fundamental information for the use of stainless steels as bipolar plate material for PEMFC. Both polarization curve and electrochemical impedance spectroscopy (EIS) measurements illustrate that 316 stainless steel cannot passivate spontaneously in the simulated environments. The absorbed (and/or adsorbed) hydrogen atoms from cathodic corrosion reactions on the steel surface may deteriorate the passivity and corrosion resistance. The oxidation of these hydrogen atoms gives rise to a second current peak in the anodic polarization curve, and the current increases with immersion time. EIS spectra also reveal that a porous corrosion product layer formed on the steel surface during the active dissolution in the test solutions. 316 stainless steel exhibits the similar corrosion behavior in sulfate ions containing dilute hydrochloric acid solution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The feasibility of LiZnPO
4
(LZP) ceramic prepared by a solid-state reaction method for low-temperature co-fired ceramic application was investigated. Dense ceramic with 94.37% relative density was ...obtained when the ceramic was sintered at 850 °C for 4 h. The LZP ceramic sintered at 850 °C for 4 h possessed a relative permittivity (ε
r
) of 5.3 and high quality factor (Q ×
f
) of 28,496 GHz (at 12.9 GHz) with a temperature coefficient of resonant frequency (τ
f
) of −80.4 ppm/°C. The relatively large negative τ
f
value was reduced by adding TiO
2
into LZP ceramics. The microstructure, microwave dielectric properties and cofiring compatibility with silver of LZP–TiO
2
composites were discussed. The composite with 0.17 volume fraction of TiO
2
sintered at 950 °C for 4 h shows ε
r
= 10.0, Q ×
f
= 10,025 GHz, τ
f
= +1.6 ppm/°C. The LZP-TiO
2
composite was chemically compatible with the commonly used electrode material silver.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The heavy rare-earth GdFeO3-type RFeO3 (R = Dy, Ho and Er) orthoferrites (space group Pnma, N 62) show spin reorientation transition characterized by a turning point on the magnetization curves. The ...basic Arrott plots curves showing positive slopes confirm the second-order nature of the spin reorientation and the transition temperature TSR is estimated to be ∼45 K, ∼53 K and ∼94 K for DyFeO3, HoFeO3 and ErFeO3, respectively. In addition, magnetic entropy change −ΔSM of the three samples is calculated to be 11.4, 9.8 and 7.4 J kg−1 K−1 at 10 K and 50 kOe, respectively. The field sensitive antiferromagnetic state and competitive magnetocaloric performances in RFeO3 have been attracting considerable interest for the possible applications in spintronic devices.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The first licensed dengue vaccine, CYD-TDV (Dengvaxia) is efficacious in seropositive individuals, but increases the risk for severe dengue in seronegative persons about two years after ...administration of the first dose. For countries considering the introduction of Dengvaxia, WHO recommends a pre-vaccination screening strategy whereby only persons with evidence of a past dengue infection would be vaccinated. Policy-makers need to consider the risk-benefit of vaccination strategies based on such screening tests, the optimal age to introduce the vaccine, communication and implementation strategies. To address these questions, the Global Dengue and Aedes-transmitted diseases Consortium (GDAC) organized a 3-day workshop in January 2019 with country representatives from Asia and Latin America.
The meeting discussions highlighted many challenges in introducing Dengvaxia, in terms of screening test characteristics, costs of such tests combined with a 3-dose schedule, logistics, achieving high coverage rates, vaccine confidence and communication; more challenges than for any other vaccine introduction programme. A screening test would require a high specificity to minimize individual risk, and at the same time high sensitivity to maximize individual and population benefit. The underlying seroprevalence dependent positive predictive value is the best indicator for an acceptable safety profile of a pre-vaccination screening strategy. The working groups discussed many possible implementation strategies. Addressing the bottlenecks in school-based vaccine introduction for Dengvaxia will also benefit other vaccines such as HPV and booster doses for tetanus and pertussis. Levels of public trust are highly variable and context specific, and understanding of population perceptions and concerns is essential to tailor interventions, monitor and mitigate risks.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
SOX2 (Sry-related high-mobility box SOX-2) is a transcription factor, which is essential for maintaining the cancer cell stemness. However, the role of microRNAs targeting SOX2 in cancer cell ...stemness remains unclear. We examined the effect of miR-590-5p, which targeted SOX2, on the breast cancer cell stemness and metastasis.
We predicted and screened microRNA targeting SOX2, and further investigated the regulatory role of miR-590-5p on the level of SOX2 with Western blot, luciferase reporting assay and qRT-PCR analysis. Flow cytometry was performed to detect the effect of miR-590-5p on the breast cancer stem cell population with ALDEFLUOR Assay. We inoculated the breast cancer cells transfected with or without miR-590-5p to NOD/SCID mice to detect the tumorigenicity in vivo. Finally, forty-nine pairs of breast cancer samples and adjacent noncancerous tissues were obtained, and immunohistochemistry (IHC) with SOX2 antibody and qRT-PCR assay were used to quantify the expression of miR-590-5p in breast cancer samples.
miR-590-5p significantly downregulated the SOX2 protein expression, and inhibition of miR-590-5p increased SOX2 expression. The luciferase reporter assay indicated that miR-590-5p decreased the SOX2 3'UTR (3' untranslated region) reporter activity but not the luciferase activity of the mutant reporter, in which the binding sites for miR-590-5p were mutated. ALDEFLUOR Assay showed that miR-590-5p significantly decreased breast cancer stem cells population. NOD/SCID nude mice experiments indicated that miR-590-5p significantly inhibited tumorigenicity of breast cancer cells. IHC assay and qRT-PCR suggested that miR-590-5p expression was downregulated in breast cancer patients, and negatively correlated with SOX2.
miR-590-5p inhibited breast cancer cell stemness through targeting SOX2. Our study indicated that miR-590-5p might be a useful strategy for breast cancer treatment.
Neuromodulatory dopamine (DA) acts as an essential signaling molecule in the central nervous system (CNS), and its dysfunction has been implicated in neurological disorders such as Parkinson's ...disease and schizophrenia. Due to its inherent redox properties, DA can be detected electrochemically by monitoring changes in current as the molecule is oxidized. Many electrode materials for electrochemical detection have been developed to monitor DA, but properties such as sensitivity and specificity must be optimized. We describe a conducting polymer (CP) nanocomposite of poly(3,4-ethylendioxythiophene) (PEDOT) doped with GO nanosheets, and report its superior DA detection performance over bare glassy carbon electrode (GCE) substrates. The GO/PEDOT electrode exhibits favorable electrical properties such as lowered impedance and increased charge storage capacity. The nanocomposite demonstrates improved sensitivity to the oxidation of DA at its surface. Meanwhile, interference from competing analyte, ascorbic acid (AA), is minimized. Mechanistic studies indicate that electrostatic interactions drive the increased sensitivity toward DA, and improved electrocatalysis of AA oxidation by the nanocomposite enables the selective discrimination of DA signals from those of AA. The described performance of the GO/PEDOT nanocomposite accentuates its promise for improving detection capabilities of electrochemical biosensors for the accurate and reliable detection of DA signals in biological samples.
Among high-grade brain tumors, glioblastoma is particularly difficult to treat, in part due to its highly infiltrative nature which contributes to the malignant phenotype and high mortality in ...patients. In order to better understand the signaling pathways underlying glioblastoma invasion, we performed the first large-scale CRISPR-Cas9 loss of function screen specifically designed to identify genes that facilitate cell invasion. We tested 4,574 genes predicted to be involved in trafficking and motility. Using a transwell invasion assay, we discovered 33 genes essential for invasion. Of the 11 genes we selected for secondary testing using a wound healing assay, 6 demonstrated a significant decrease in migration. The strongest regulator of invasion was mitogen-activated protein kinase 4 (MAP4K4). Targeting of MAP4K4 with single guide RNAs or a MAP4K4 inhibitor reduced migration and invasion in vitro. This effect was consistent across three additional patient derived glioblastoma cell lines. Analysis of epithelial-mesenchymal transition markers in U138 cells with lack or inhibition of MAP4K4 demonstrated protein expression consistent with a non-invasive state. Importantly, MAP4K4 inhibition limited migration in a subset of human glioma organotypic slice cultures. Our results identify MAP4K4 as a novel potential therapeutic target to limit glioblastoma invasion.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The pathophysiology of aortic stenosis shares many similarities with atherosclerosis and skeletal bone formation. Using non-invasive imaging, we compared aortic valve calcification and inflammation ...activity with that measured in atherosclerosis and bone.
Positron emission and computed tomography was performed using 18F-sodium fluoride (18F-NaF, calcification) and 18F-fluorodeoxyglucose (18F-FDG, inflammation) in 101 patients with calcific aortic valve disease (81 aortic stenosis and 20 aortic sclerosis). Calcium scores and positron emission tomography tracer activity (tissue-to-background ratio; TBR) were measured in the aortic valve, coronary arteries, thoracic aorta, and bone. Over 90% of the cohort had coexistent calcific atheroma, yet correlations between calcium scores were weak or absent (valve vs. aorta r(2) = 0.015, P = 0.222; valve vs. coronaries r(2) = 0.039, P = 0.049) as were associations between calcium scores and bone mineral density (BMD vs. valve r(2) = 0.000, P = 0.766; vs. aorta r(2) = 0.052, P = 0.025; vs. coronaries r(2) = 0.016, P = 0.210). 18F-NaF activity in the valve was 28% higher than in the aorta (TBR: 2.66 ± 0.84 vs. 2.11 ± 0.31, respectively, P < 0.001) and correlated more strongly with the severity of aortic stenosis (r(2) = 0.419, P < 0.001) than 18F-NaF activity outwith the valve (valve vs. aorta r(2) = 0.167, P < 0.001; valve vs. coronary arteries r(2) = 0.174, P < 0.001; valve vs. bone r(2) = 0.001, P = 0.806). In contrast, 18F-FDG activity was lower in the aortic valve than the aortic atheroma (TBR: 1.56 ± 0.21 vs. 1.81 ± 0.24, respectively, P < 0.001) and more closely associated with uptake outwith the valve (valve vs. aorta r(2) = 0.327, P < 0.001).
In patients with aortic stenosis, disease activity appears to be determined by local calcific processes within the valve that are distinct from atherosclerosis and skeletal bone metabolism.
•The microstructure and micro-damage were investigated at the FOD crater.•The residual stress was depicted by Johnson-Cook model and failure criterions.•The conditional probability density ...distributions were plotted in three dimensions.•The modified Kitagawa-Takahashi diagram was established with FOD defects.
High-speed railway axles are seriously threaten by external flying objects. Foreign object damage (FOD) on 25CrMo4 or EA4T axle steel specimens was then prepared by a compressed-gas gun. The microstructure and micro-damage at the crater were investigated by scanning electron microscopy, electron backscattered diffraction, transmission electron microscopy and nano-indentation. To correlate the FOD to the fatigue crack resistance, residual stress distribution due to FOD was also simulated by calibrating the Johnson-Cook constitutive equation and associated failure criterion in experiments. Besides the significant uncertainty of fatigue crack initiations from the FOD-induced micro-damage, residual stress and microstructure change, those FODed specimens also present a significantly lower fatigue strength than those at the absence of FOD. Furthermore, a higher impact velocity on the specimens appears to produce lower fatigue endurance. Finally, a modified Kitagawa-Takahashi diagram was established to combine the fatigue strength with FOD defects, which can be used in the fatigue resistance evaluation of high-speed railway axles.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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