Background:
MicroRNAs (miRNAs) are known to regulate the inflammatory response in various cell types. However, the ability of miRNAs to modulate dendritic cells (DCs) function for allergen ...immunotherapy is unclear.
Objective:
To assess the role of miR‐23b in the regulation of ovalbumin (OVA)‐induced DC differentiation and function and to investigate the related molecular mechanisms.
Methods:
Bone marrow‐derived dendritic cells (BMDCs) were generated from murine bone marrow progenitor cells and subsequently stimulated with OVA to examine the profile of miRNA expression. After transfection with miR‐23b reagents, DCs were evaluated for endocytic ability, surface marker expression, cytokine secretion and CD4+ T‐cell differentiation. The possible roles of the Notch and NF‐κB signalling pathways were also evaluated. Human monocyte‐derived dendritic cells (MDDCs) were similarly evaluated as well.
Results:
Significant upregulation of miR‐23b was observed in BMDCs pulsed with OVA. Following miR‐23b transfection, BMDCs showed decreased OVA uptake, increased IL‐10 production, decreased IL‐12 production and an enhanced capacity to promote FoxP3+ CD4+ T regulatory cells (Tregs) differentiation. In addition, inactivation of the Notch1 and NF‐κB signalling pathways were observed. Conversely, inhibition of miR‐23b in BMDCs resulted in the opposite effects. In human MDDCs, miRNA23b transfection similarly increased IL‐10 and decreased IL‐12 production, and that treated human MDDCs induced increased FoxP3+ CD4+ T cells.
Conclusion:
Our findings provide evidence that miR‐23b is capable of inducing tolerogenic DC activity and Treg responses in vitro through the inhibition of the Notch1 and NF‐κB signalling pathways; thus, miR‐23b might represent a therapeutic target for the management of allergic diseases.
•An unsteady model is proposed for osmotic energy conversion.•The variation of salt concentration during actual operation is considered.•The accuracy of model is verified by salinity-gradient power ...generation experiments.•A parallel encapsulation method is provided to enhance output power density.
Converting the salinity-gradient into electricity via ion migration in nanoconfined channels driven by the salt concentration gap between sea and river water is an important renewable energy utilization method. The osmotic energy conversion device is regarded as a power source with constant voltage output in the conventional constant voltage source (V-source) power equivalent circuit model, which is based on a steady state with constant concentration on both sides of the membrane. In this study, an unsteady equivalent capacitor–capacitor/resistor (C-CR) power equivalent circuit model is proposed to consider the salt concentration variation during actual operation. The maximum relative deviation of the calculated short circuit current between the C-CR power equivalent circuit model and the measured experimental data is 7.06%. The maximum relative deviation of the predicted maximum output power density between the C-CR power equivalent circuit model and the measured experimental data is less than 14.22%, while the corresponding maximum deviation for the V-source power equivalent circuit model has an error of 38.14%. A parallel encapsulation method by embedding graphene oxide membranes (GOMs) into polydimethylsiloxane (PDMS) is provided to offer an extended accessible area for ion transport to enhance the ion flux and output power density. This method reveals a linearly increased output power with the number of GOMs, which provides convenience for increasing output power. This work provides an effective way to design integrated osmotic energy conversion devices, which promotes the development of salinity-gradient-driven energy conversion systems.
Epileptic encephalopathies are severe epilepsy disorders with strong genetic bases. We performed targeted next‐generation sequencing (NGS) in 70 patients with epileptic encephalopathies. The likely ...pathogenicity of variants in candidate genes was evaluated by American College of Medical Genetics and Genomics (ACMG) scoring taken together with the accepted clinical presentation. Thirty‐three candidate variants were detected after population filtration and computational prediction. According to ACMG, 21 candidate variants, including 18 de novo variants, were assessed to be pathogenic/likely pathogenic with clinical concordance. Twelve variants were initially assessed as uncertain significance by ACMG, among which 3 were considered causative and 3 others were considered possibly causative after analysis of clinical concordance. In total, 24 variants were identified as putatively causative, among which 19 were novel findings. SCN1A mutations were identified in 50% of patients with Dravet syndrome. TSC1/TSC2 mutations were detected in 66.7% of patients with tuberous sclerosis. STXBP1 mutations were the main findings in patients with West syndrome. Mutations in SCN2A, KCNT1, KCNQ2 and CLCN4 were identified in patients with epileptic infantile with migrating focal seizures; among them, KCNQ2 and CLCN4 were first identified as potential causative genes. Only one CHD2 mutation was detected in patients with Lennox‐Gastaut syndrome. This study highlighted the utility of targeted NGS in genetic diagnoses of epileptic encephalopathies and a comprehensive evaluation of the pathogenicity of variants based on ACMG scoring and assessment of clinical concordance. Epileptic encephalopathies differ in genetic causes, and the genotype‐phenotype correlations would provide insights into the underlying pathogenic mechanisms.
We identified 24 causative mutations (19 novel) in a cohort of 70 EE patients and delineated new phenotype associated with CLCN4 and KCNQ2.
Secondary flux ropes are suggested to play important roles in energy dissipation and particle acceleration during magnetic reconnection. However, their generation mechanism is not fully understood. ...In this Letter, we present the first direct evidence that a secondary flux rope was generated due to the evolution of an electron vortex, which was driven by the electron Kelvin-Helmholtz instability in an ion diffusion region as observed by the Magnetospheric Multiscale mission. The subion scale (less than the ion inertial length) flux rope was embedded within the electron vortex, which contained a secondary electron diffusion region at the trailing edge of the flux rope. We propose that intense electron shear flow produced by reconnection generated the electron Kelvin-Helmholtz vortex, which induced a secondary reconnection in the exhaust of the primary X line and then led to the formation of the flux rope. This result strongly suggests that secondary electron Kelvin-Helmholtz instability is important for reconnection dynamics.
Abstract Whistler-mode waves have been extensively observed and investigated in terrestrial space. In this study, we present the dynamic response of whistler-mode waves to different solar wind ...conditions in the dayside terrestrial space based on Magnetospheric Multiscale (MMS) data. Statistical results show that the occurrence rate, amplitudes, and corresponding electron temperature anisotropy of whistler-mode waves increase with P sw in the dayside terrestrial space, which is attributed to the compression of magnetic fields in these magnetosheath and outer magnetosphere. Furthermore, whistler-mode waves under the southward interplanetary magnetic fields (IMFs) show a higher occurrence rate than that under the northward IMFs, mostly corresponding to T e ⊥ / T e ∥ > 1, and have a higher occurrence rate during quasi-radial IMFs. These results present that whistler-mode waves in these magnetosheath and outer magnetosphere are also modulated by the solar wind as clearly as the inner magnetosphere. This work advanced our understanding in the solar–terrestrial interaction.
The Magnetospheric Multiscale spacecraft encountered an electron diffusion region (EDR) in a symmetric reconnection in the Earth's magnetotail. The EDR contained a guide field of about 2 nT, which ...was 13% of the magnetic field in the inflow region, and its thickness was about 2 local electron inertial lengths. Intense energy dissipation, a super-Alfvénic electron jet, electron nongyrotropy, and crescent-shaped electron velocity distributions were observed in association with this EDR. These features are similar to those of the EDRs in asymmetric reconnection at the dayside magnetopause. Electrons gained about 50% of their energy from the immediate upstream to the EDR. Crescent electron distributions were seen at the boundary of the EDR, while highly curved magnetic field lines inside the EDR may have gyrotropized the electrons. The EDR was characterized by a parallel current that was carried by antiparallel drifting electrons that were probably accelerated by a parallel electric field along the guide field. These results reveal the essential electron physics of the EDR and provide a significant example of an EDR in symmetric reconnection with a weak guide field.
Magnetic holes have been widely observed in various space plasma systems. The origin of magnetic holes and their influence to background plasma are under debate. In this paper, we show a ...kinetic‐scale electron vortex magnetic hole in a nonideal region of an active X line, which was observed by the Magnetospheric Multiscale mission at the dayside magnetopause. Intense current and nonideal electric field in the electron frame were observed within the magnetic hole, which led to a strong energy dissipation. Thus, the electron vortex magnetic hole probably provided an additional energy dissipation channel besides the electron diffusion region adjacent to the hole. We suggest that magnetic reconnection provided favorable conditions for the formation of this kinetic‐scale magnetic hole and is an important source of magnetic holes in space plasma.
Key Points
First evidence for reconnection‐driven kinetic‐scale magnetic hole
The hole was associated with an electron vortex and was observed in the vicinity of an electron diffusion region
The hole probably provided an additional energy dissipation channel besides the electron diffusion region
ABSTRACT
We constrain the equation of state of quark stars within the Bayesian statistical approach using the mass and radius measurements of PSR J0030+0451 from NICER. Three types of bag models, ...with and without non-zero finite quark mass and/or superfluidity, are employed for quark stars made up with self-bound strange quark matter. We find the $90{{\ \rm per\ cent}}$ posterior credible boundary around the most probable values of the quark star maximum mass is $M_{\rm TOV}=2.38_{-0.23}^{+0.26}\, M_{\odot }$, within the model flexibility of the finite quark mass, the quark pairing gap, and the perturbative contribution from the one-gluon exchange. The radius of a canonical $1.4 \, M_{\odot }$ quark star is $R_{\rm 1.4}\sim 12.3\, {\rm km}$, smaller than the results based on neutron star models.
Energetic electrons have frequently been observed in small‐scale flux ropes. However, whether these energetic electrons were energized directly within the flux rope or not is unknown. In this paper, ...we present concrete evidence provided by the Magnetospheric Multiscale mission that a secondary flux rope provided strong acceleration for electrons expelled by the reconnection X line. We find that the energetic electron fluxes inside the ion‐scale flux rope were larger than those outside the flux rope. Electrons were adiabatically accelerated by betatron and Fermi mechanisms inside the flux rope. The highest energy electrons (>100 keV) were produced by betatron acceleration, whereas Fermi acceleration was unable to accelerate the electrons to high energy probably due to the finite distance of the acceleration region along the field‐aligned direction. These results confirm the essential role of ion‐scale flux ropes in producing energetic electrons.
Key Points
First quantitative evidence for adiabatic electron acceleration within ion‐scale flux rope
The most energetic electrons were produced by betatron acceleration inside the flux rope
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