Proinflammatory Th17 cells and CD4(+)CD25(+) regulatory T (Treg) cells are two newly identified T lymphocyte subsets, which have opposite effects on autoimmunity and inflammation. To assess the Th17/Treg pattern and cytokine microenvironment in peripheral blood of patients with RA, we included 66 RA patients and 20 healthy volunteers. Of all these subjects, peripheral Th17 and Treg frequencies were analyzed by flow cytometry (FCM) and the plasma levels of interleukin (IL)-17, 23, 6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 were detected by ELISA. The results demonstrated that RA patients revealed an obvious increase in peripheral Th17 frequencies and levels of Th17-related cytokines (IL-17, IL-23, IL-6, TNF-α) while a significant decrease in Treg frequencies and Treg-related cytokine (TGF-β1) levels when compared with healthy people. Our study indicated that development of RA is associated with peripheral Th17/Treg imbalance and characterized by a proinflammatory cytokine microenvironment, which supports continuing generation of Th17 cells.
Macroautophagy/autophagy plays an important role against pathogen infection in mammals and plants. However, little has been known about the role of autophagy in the interactions of insect vectors with the plant viruses, which they transmit. Begomoviruses are a group of single-stranded DNA viruses and are exclusively transmitted by the whitefly Bemisia tabaci in a circulative manner. In this study, we found that the infection of a begomovirus, tomato yellow leaf curl virus (TYLCV) could activate the autophagy pathway in the Middle East Asia Minor 1 (MEAM1) species of the B. tabaci complex as evidenced by the formation of autophagosomes and ATG8-II. Interestingly, the activation of autophagy led to the subsequent degradation of TYLCV coat protein (CP) and genomic DNA. While feeding the whitefly with 2 autophagy inhibitors (3-methyladenine and bafilomycin A 1 ) and silencing the expression of Atg3 and Atg9 increased the viral load; autophagy activation via feeding of rapamycin notably decreased the amount of viral CP and DNA in the whitefly. Furthermore, we found that activation of whitefly autophagy could inhibit the efficiency of virus transmission; whereas inhibiting autophagy facilitated virus transmission. Taken together, these results indicate that TYLCV infection can activate the whitefly autophagy pathway, which leads to the subsequent degradation of virus. Furthermore, our report proves that an insect vector uses autophagy as an intrinsic antiviral program to repress the infection of a circulative-transmitted plant virus. Our data also demonstrate that TYLCV may replicate and trigger complex interactions with the insect vector.
Nature-inspired actuators that can be driven by various stimuli are an emerging application in mobile microrobotics and microfluidics. In this study, a soft and multiple-environment-adaptive robotic platform with ferromagnetic particles impregnated in silicon-based polymer is adopted to fabricate microrobots for minimally invasive locomotion and control interaction with their environment. As an intelligent structure of platform, the change of its bending, deformation, and flapping displacement is rapid, reversible, and continuously controllable with sweeping and multicycle magnetic actuation. The bending angle of the soft platform (0.2 mm in thickness and 8.5 mm in length) can be deflected up to almost 90° within 2.7 s. Experiments demonstrated that the flexible platform of human skin-like material in various shapes, that is, flowerlike shapes, can transport a cargo to targeted area in air and a variety of liquids. It indicates excellent magnetic-actuation ability and good controllability. The results may be helpful in developing a magnetic-driven carrying platform, which can be operated like a human finger to manipulate biological objects such as single cells, microbeads, or embryos. Especially, it is likely to be used in harsh chemical and physical circumstances.
BackgroundFollicular helper T (Tfh) cells are specialized in helping B lymphocytes, which play a central role in autoimmune diseases that have a major B cell component, such as in rheumatoid arthritis (RA). Follicular regulatory T (Tfr) cells control the over-activation of Tfh and B cells in germinal centers. Dysregulation of Tfh cells and Tfr cells has been reported to be involved in the pathogenesis of some autoimmune diseases. However, the balance of Tfh and Tfr cells, and their roles in the development and progression of RA are still not clear.MethodsIn this study, we enrolled 44 patients with RA (20 patients with active RA and 24 patients with inactive RA) and 20 healthy controls, and analyzed the frequencies of circulating Tfh and Tfr cells, expression of programmed death-1 (PD-1), inducible co-stimulator (ICOS), intracellular IL-21, and pSTAT3 in Tfh cells, and serum levels of IL-6. The correlation among these parameters and that of Tfh or Tfr cells with disease activity were also analyzed.ResultsPatients with RA (especially active RA) had higher frequencies of Tfh cells, but lower percentages of Tfr cells, thereby resulting in elevated ratios of Tfh/Tfr. Expression levels of PD-1 and IL-21 in Tfh cells were higher in patients with RA than in healthy subjects, while no difference in ICOS expression was observed between patients and controls. Both pSTAT3 expression and serum IL-6 levels increased in patients with RA, and positive correlation between them was observed. Additionally, pSTAT3 expression was positively correlated with Tfh cell frequency. The Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) was negatively correlated with Tfr cell frequency, but was positively correlated with both Tfh/Tfr ratio and PD-1 expression.ConclusionsResults demonstrated that enhanced IL-6/pSTAT3 signaling may contribute to promotion of Tfh cells, consequently skewing the ratio of Tfh to Tfr cells, which may be crucial for disease progression in RA.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1690-0) contains supplementary material, which is available to authorized users.
Background
There has been no large-scale examination of the association between types of childhood abuse and personality disorders (PDs) in China using standardised assessment tools and the DSM-IV diagnostic criteria. Hence, this study aimed to explore the relationship between retrospective reports of various types of childhood maltreatments and current DSM-IV PDs in a clinical population in China, Shanghai.
Method
1402 subjects were randomly sampled from the Shanghai Psychological Counselling Centre. PDs were assessed using the Personality Diagnostic Questionnaire (PDQ4+). Participants were also interviewed using the Structured Clinical Interview (SCID-II). The Child Trauma Questionnaire (CTQ) was used to assess childhood maltreatment in five domains (emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect).
Results
According to Pearson's correlations, childhood maltreatment had a strong association with most PDs. Subsequently using partial correlations, significant relationships were also demonstrated between Cluster-B PDs and all the traumatic factors except physical neglect. A strongest positive correlation was found between Cluster-B PD and CTQ total scores (r=.312, p <.01). Using the Kruskal-Wallis rank sum test, significant differences in 4 groups of subjects (Cluster-A PD, Cluster-B PD, Cluster-C PD and Non-PD) in terms of emotional abuse (χ2 = 34.864, p <.01), physical abuse (χ2 = 14.996, p <.05), sex abuse (χ2 = 9.211, p <.05), and emotional neglect (χ2 = 17.987, p <.01) were found. Stepwise regression analysis indicated that emotional abuse and emotional neglect were predictive for Cluster-A PD and Cluster-B PD, and sexual abuse was highly predictive for Cluster-B PD, only emotional neglect was predictive for Cluster-C PD.
Conclusion
Early traumatic experiences are strongly related to the development of PDs. The effects of childhood maltreatment in the three clusters of PDs are different. Childhood trauma has the most significant impact on Cluster-B PD.
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