This research investigated the relation between individual differences in inhibitory control and emotion regulation. Preschool children (
N
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53) ages 4–6 (
M
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5; 0) were assessed on brief batteries ...of inhibitory control of prepotent responses and emotion regulation. Individual differences in inhibitory control were significantly correlated with children's ability to regulate their emotions. This relation held up even after controlling for age and verbal ability, and persisted for both Emotion Understanding and “online” control of emotional expressions that were negative (Disappointing Gift) or positive (Secret Keeping). Parent report of children's self-control and emotion regulation corroborated the behavioral results. These findings suggest that executive control of attention, action, and emotion are skills that develop in concert in the preschool period. However, there was also evidence of a quadratic relation in which emotion regulation was optimal at intermediate levels of inhibition, highlighting the interplay of both cognitive control and temperament in socio-emotional functioning.
Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs), induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using ...colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4
T-cell response. Similarly, genetically depleting MФs in myeloma-bearing MM
mice retarded myeloma growth in vivo. Furthermore, the combination of CSF1R blockade and chemotherapy such as bortezomib or melphalan displayed an additive therapeutic efficacy against established myeloma. Finally, a fully human CSF1R blocking mAb, similar to its murine counterpart, was able to inhibit the differentiation, proliferation and survival of human MФs. Thus, this study provides the first direct in vivo evidence that MΦs and MAMs are indeed important for myeloma development and progression. Our results also suggest that targeting MAMs by CSF1R blocking mAbs may be promising methods to (re)sensitize myeloma cells to chemotherapy and promote anti-myeloma immune responses in patients.
T cell trafficking into tumors depends on a "match" between chemokine receptors on effector cells (e.g., CXCR3 and CCR5) and tumor-secreted chemokines. There is often a chemokine/chemokine receptor ..."mismatch", with tumors producing minute amounts of chemokines, resulting in inefficient targeting of effectors to tumors. We aimed to alter tumors to produce higher levels of CXCL11, a CXCR3 ligand, to attract more effector cells following immunotherapy. Mice bearing established subcutaneous tumors were studied. In our first approach, we used modified chimeric antigen receptor (CAR)-transduced human T cells to deliver CXCL11 (CAR/CXCL11) into tumors. In our second approach, we intravenously (iv) administered a modified oncolytic vaccinia virus (VV) engineered to produce CXCL11 (VV.CXCL11). The effect of these treatments on T cell trafficking into the tumors and anti-tumor efficacy after subsequent CAR T cell injections or anti-tumor vaccines was determined. CAR/CXCL11 and VV.CXCL11 significantly increased CXCL11 protein levels within tumors. For CAR/CXCL11, injection of a subsequent dose of CAR T cells did not result in increased intra-tumoral trafficking, and appeared to decrease the function of the injected CAR T cells. In contrast, VV.CXCL11 increased the number of total and antigen-specific T cells within tumors after CAR T cell injection or vaccination and significantly enhanced anti-tumor efficacy. Both approaches were successful in increasing CXCL11 levels within the tumors; however, only the vaccinia approach was successful in recruiting T cells and augmenting anti-tumor efficacy. VV.CXCL11 should be considered as a potential approach to augment adoptive T cell transfer or vaccine immunotherapy.
Abstract
We presented observations of PSRs J0614+2229 and J1938+2213 using the Five-hundred-meter Aperture Spherical radio Telescope. PSR J0614+2229 shows two distinct emission states, in which the ...emission of state A occurs earlier than that of state B in longitude. The phase offset between the average pulse profile peaks of the two states is about 1.°05. The polarization properties of the average pulse profile of the two states are different with different linear position angle swings. We found that the emission becomes brighter during the transition between the two states, which has never been seen in other mode-changing pulsars before. PSR J1938+2213 appears to consist of a weak emission state superposed by brighter burst emissions. The weak state is always present and the energy of the strongest pulse in the burst state is about 57 times larger than that of the average pulse energy. The polarization properties of the two states are also different, and orthogonal polarization modes can be seen only in the burst state, rather than both states. Our results suggest that, for the two pulsars, the emissions of the two states may be generated in different regions in the pulsar magnetosphere.
Summary The May 2008 earthquake in Wenchuan drew attention to the important but largely unrecognised public-health problem of injury-related mortality and morbidity in China. Injuries account for ...more than 10% of all deaths and more than 30% of all potentially productive years of life lost due to premature mortality in China. Traffic-related injuries (mainly among cyclists and pedestrians), suicide, drowning, and falls account for 79% of all injury deaths. Rural injury death rates are double those of urban rates and male rates are double those of female rates. Despite an 81% increase in the traffic-related mortality from 1987 to 2006—associated with rapid motorisation—the overall injury mortality decreased by 17%, largely due to a surprising (and unexplained) 57% reduction in the suicide rate. Low-cost prevention measures that are most likely to produce large reductions in injury deaths include enforcement of laws for drinking and driving and for seat belt and helmet use, restriction of access to the most potent pesticides, and teaching children to swim. China needs to improve monitoring of fatal and non-fatal injuries, promote intersectoral collaboration, build institutional capacities, and, most importantly, mobilise community support and political will for investment in prevention.
Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in ...schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5-1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P < 0.01) or CYP2C19 *2/*3 genotype (P < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P < 0.01) or 2 (P < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 - β) = 0.8486 at type I level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy.
The cytotoxicity of cadmium (Cd) induced autophagy and apoptosis in MES-13 cells was determined by flow cytometry. Autophagy was also assessed by formation of autophagosomes and processing of LC3. ...Pharmacological inhibition of autophagy resulted in increased of cell viability, suggesting autophagy plays a role in cell death in Cd-treated mesangial cells. Cd also induced a rapid elevation in cytosolic calcium (Ca²⁺i ), and modulation of Ca²⁺i via treatment with IP ₃R inhibitor or knockdown of calcineurin resulted in a change in the proportion of cell death, suggesting that the release of calcium from the ER plays a crucial role in Cd-induced cell death. Inhibition of Cd-induced ERK activation by PD 98059 suppressed Cd-induced autophagy, and BAPTA-AM eliminated activation of ERK. BAPTA-AM also inhibited Cd-induced mitochondrial depolarization and activation of caspases. These findings demonstrated that Cd induces both autophagy and apoptosis through elevation of Ca²⁺i, followed by Ca²⁺-ERK and Ca²⁺-mitochondria-caspase signaling pathways.
Objective: To evaluate the clinical efficacy and safety of iguratimod for the treatment of primary Sjögren's syndrome (pSS) and explore its possible mechanism of action.
Method: We conducted a ...randomized, placebo-controlled clinical trial in 66 pSS patients. Patients were randomized in a 2:1 ratio to receive oral iguratimod for 24 weeks or matching placebo. The primary endpoint was the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI). Secondary endpoints included mental discomfort visual analogue scale (VAS) score, patient global assessment (PGA), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test values, unstimulated whole salivary flow, erythrocyte sedimentation rate (ESR), and immunoglobulin G (IgG). The proportions of B cells in peripheral blood and levels of serum B-cell activating factor (BAFF) were measured at baseline and week 24 in the iguratimod group. All adverse events were recorded during the trial period.
Results:ESSPRI improved more in the iguratimod than in the placebo group (p = 0.016). Mental discomfort VAS score, PGA, Schirmer's test, ESR, and IgG also improved more in the iguratimod than in the placebo group (all p < 0.05). Adverse events were reported 13.6% of the iguratimod group. Levels of BAFF and proportions of plasma cells in patients decreased significantly after iguratimod treatment. The proportions of peripheral plasma cells had positive correlations with both serum IgG and BAFF.
Conclusion: Iguratimod improved some dryness symptoms and disease activity in pSS patients, and reduced the level of BAFF and percentage of plasma cells over 24 weeks. Iguratimod seems to be an effective and safe treatment for pSS.
This study reports a relation between electron flux modulations and chorus emissions by using correlation analysis. On April 18, 2017, Arase observed an enhancement of electron fluxes and ...intensification of banded chorus emissions at the same time. A result of the analysis shows that both the upper‐band and lower‐band chorus emissions have good correlations with field‐aligned electron fluxes that satisfy their resonance conditions. This indicates simultaneous interactions with both the emission bands and electrons, resulting in electron pitch‐angle scattering toward the magnetic field direction. In addition, low‐energy electron fluxes in the perpendicular direction also show positive correlations with the chorus intensities, probably because the chorus emissions are modulated by a fluctuation of perpendicular low‐energy electron fluxes.
Plain Language Summary
Scientists have believed that pulsating auroras in the polar regions originate in precipitating electrons that are caused by a wave‐particle interaction in the magnetosphere. Recent observational studies show direct evidence that chorus waves near the magnetic equator scatter local magnetospheric electrons, which are then streaming along the field line down to the ionosphere to generate aurora pulsation in response to modulation of the chorus emissions. Chorus waves usually have two distinct frequency bands, that is, upper band and lower band, but it had not been investigated that how two emission bands interact with electrons. In this study, we analyzed Arase satellite's observation data and identified good correlations between field‐aligned electron fluxes and intensities of the upper‐band and lower‐band emissions. This result indicates that pitch‐angle scattering of electrons takes place by both chorus emission bands simultaneously.
Key Points
Arase observed intense banded chorus emissions near the magnetic equator simultaneously with an electron flux enhancement
Parallel electron fluxes show good correlations with intensities of both the upper‐band and the lower‐band chorus waves
The positive correlation indicates pitch‐angle scattering of electrons by the chorus waves toward the magnetic field direction
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