The TET (ten-eleven translocation) family of α-ketoglutarate (α-KG)-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), ...5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of α-KG, linking 5mC oxidation to cancer development. We report here that the levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic and prostate cancers when compared with the matched surrounding normal tissues. Associated with the 5hmC decrease is the substantial reduction of the expression of all three TET genes, revealing a possible mechanism for the reduced 5hmC in cancer cells. The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development.
Background
B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet.
Objective
This study aims to ...investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy‐induced intestinal inflammation in mice.
Methods
The intestinal mucosa‐derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs.
Results
A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)‐β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti‐IgM antibody induced naive B cells to differentiate into the TGF‐β‐producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy‐induced intestinal Th2 pattern inflammation in mice.
Conclusions
CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy‐related Th2 pattern inflammation in mice.
This paper proposes a method for online estimating the rotor flux linkage and voltage-source inverter (VSI) nonlinearity of permanent magnet synchronous machine (PMSM) drives. Thermocouples are ...employed for measuring the temperature variation of the stator winding in order to obtain the actual value of stator winding resistance. An Adaline estimator is used for online estimation of distorted voltage Vdead due to VSI nonlinearity. Both are subsequently used for the estimation of the rotor flux linkage. The proposed method is experimentally validated on a PMSM drive system and shows good performance in tracking the variation of the rotor flux linkage and compensating the VSI nonlinearity.
Purpose
The function of B cells in papillary thyroid cancer (PTC) is controversial. The role of B-cell-related tertiary lymphoid structures (TLSs) is still unclear. Whether B cells exert their ...anti-tumor effect through forming TLS in PTC needs further investigation.
Methods
We detected the percentage of B cells in PTC tissues by multi-parameter flow cytometry. Paraffin-embedded tumor tissues of 125 PTC patients were collected and stained with Haematoxylin–Eosin (H&E) for inflammatory infiltration analysis in combination with clinical features. Multiplexed immunohistochemistry (mIHC) was performed to verify the TLSs in above inflammatory infiltration. Correlation of B cells and TLSs with prognosis was analyzed using the TCGA database.
Results
We observed that PTC patients with higher expression of B lineage cell genes had improved survival and the percentage of B cells in the PTC tumor tissues was variable. Moreover, PTC tumor tissues with more B cells were surrounded by immune cell aggregates of varying sizes. We furtherly confirmed the immune cell aggregates as TLSs with different maturation stages. By analyzing PTC data from TCGA database, we found the maturation stages of TLSs were associated with genders and clinical stages among PTC patients. Moreover, patients with high TLSs survived longer and had a better prognosis.
Conclusion
B cells are associated with the existence of TLSs which have different maturation stages in PTC. Both B cells and TLSs are associated with the survival rate of PTC. These observations indicate that the anti-tumor effects of B cells in PTC are associated with TLSs formation.
Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ...ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.
Background and aims
The function of interleukin (IL)‐10‐producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease‐activated receptor (PAR)‐2 has immunoregulatory ...functions. This study aimed to elucidate the role of PAR2 in the suppression of IL‐10 expression in peripheral B cells.
Methods
Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2‐like protein 12 (Bcl2L12) and IL‐10 in the B cells was analyzed. An AR mouse model was developed.
Results
We observed that the expression of IL‐10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL‐10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS‐induced IL‐10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12‐shRNA‐carrying liposomes reversed the capability of IL‐10 expression and the immunosuppressive function. Administration of Bcl2L12 shRNA‐carrying liposomes attenuated experimental AR in mice.
Conclusions
Activation of PAR2 inhibits the expression of IL‐10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA‐carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR.
In this paper, a novel sensorless control strategy with the injection of a high-frequency pulsating carrier signal into a stationary reference frame is proposed. Differing from the two most commonly ...used conventional high-frequency carrier signal injection methods, i.e., the injection of a rotating carrier voltage into a stationary reference frame and the injection of a pulsating carrier voltage into an estimated synchronous reference frame, the new proposed strategy injects a pulsating high-frequency carrier voltage into a stationary reference frame, which is as stable as the rotating carrier signal injection method. Then, the rotor position information can be retrieved from the carrier current response that is amplitude-modulated by the machine saliency, which is as simple as the pulsating carrier signal injection method. The signal demodulation process, the compensation of the cross-saturation effect, and magnetic polarity detection are also discussed and analyzed in detail. The experimental results on an interior permanent-magnet synchronous machine demonstrate that the new proposed strategy has a robust magnetic polarity detection and that it can achieve an accurate rotor position estimation with good steady-state performance and dynamic performance.
Cracks in solid-state materials are typically irreversible. Here we report electrically reversible opening and closing of nanoscale cracks in an intermetallic thin film grown on a ferroelectric ...substrate driven by a small electric field (~0.83 kV/cm). Accordingly, a nonvolatile colossal electroresistance on-off ratio of more than 10
is measured across the cracks in the intermetallic film at room temperature. Cracks are easily formed with low-frequency voltage cycling and remain stable when the device is operated at high frequency, which offers intriguing potential for next-generation high-frequency memory applications. Moreover, endurance testing demonstrates that the opening and closing of such cracks can reach over 10
cycles under 10-μs pulses, without catastrophic failure of the film.
We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of ...the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.
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