Bone marrow mesenchymal stem cells induce M2 microglia polarization through PDGF-AA/MANF signaling

BACKGROUND Bone marrow mesenchymal stem cells(BMSCs)are capable of shifting the microglia/macrophages phenotype from M1 to M2,contributing to BMSCsinduced brain repair.However,the regulatory mechanism of BMSCs on microglia/macrophages after ischemic stroke is unclear.Recent evidence suggests that mesencephalic astrocyte-derived neurotrophic factor(MANF)and plateletderived growth factor-AA(PDGF-AA)/MANF signaling regulate M1/M2 macrophage polarization.AIM To investigate whether and how MANF or PDGF-AA/MANF signaling influences BMSCs-mediated M2 polarization.METHODS We identified the secretion of MANF by BMSCs and developed transgenic BMSCs using a targeting small interfering RNA for knockdown of MANF expression.Using a rat middle cerebral artery occlusion(MCAO)model transplanted by BMSCs and BMSCs-microglia Transwell coculture system,the effect of BMSCsinduced downregulation of MANF expression on the phenotype of microglia/macrophages was tested by Western blot,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence.Additionally,microglia were transfected with mimics of miR-30a*,which inuenced expression of X-box binding protein(XBP)1,a key transcription factor that synergized with activating transcription factor 6(ATF6)to govern MANF expression.We examined the levels of miR-30a*,ATF6,XBP1,and MANF after PDGF-AA treatment in the activated microglia.RESULTS Inhibition of MANF attenuated BMSCs-induced functional recovery and decreased M2 marker production,but increased M1 marker expression in vivo or in vitro.Furthermore,PDGF-AA treatment decreased miR-30a*expression,had no influence on the levels of ATF6,but enhanced expression of both XBP1 and MANF.CONCLUSION BMSCs-mediated MANF paracrine signaling,in particular the PDGF-AA/miR-30a*/XBP1/MANF pathway,synergistically mediates BMSCs-induced M2 polarization.

Novel Polarization Control Approach to Long-Term Fiber-Optic Frequency Transfer

We demonstrate a novel polarization control system based on a gradient descent algorithm,applied to a 450-km optical frequency transfer link.The power of the out-loop beat note is retrieved by controlling the polarization state of the transferred signal,with a recovery time of 24 ms,thereby ensuring the long-term evaluation of the fiber link.As a result,data utilization is enhanced from 70%to 99%over a continuous measurement period of^12 h.A fractional transfer instability of 7.2×10^-20 is achieved at an integration time of 10000 s.This work lays the foundation for the comparison of a remote optical clock system via a long-haul optical fiber link.

T-cell and B-cell repertoire diversity are selectively skewed in children with idiopathic nephrotic syndrome revealed by high-throughput sequencing

Background Clinical studies suggest that the dysfunction of T cells and B cells may play an essential role in the pathogenesis of idiopathic nephrotic syndrome(INS),but laboratory evidence is lacking.Therefore,this study explored T-cell receptor(TCR)and B-cell receptor(BCR)profiling in children with idiopathic nephrotic syndrome.Methods High-throughput sequencing technology was used to profile the TCR and BCR repertoires in children with INS.Peripheral blood was collected from ten INS patients,including five vinculin autoantibody-positive patients and five vin-culin autoantibody-negative patients,before and after treatment.TCR and BCR libraries were constructed by 5'-RACE and sequenced by a DNBSEQ-T7 sequencer,and sequence analyses were performed using ReSeqTools,FastP,MiXCR,and VDJtools.Results The TRA(T-cell receptorα),TRG(T-cell receptor y),and IGH(immunoglobulin heavy chain)repertoires of the INS group were occupied by highly abundant clonotypes,whereas small clonotypes occupied the healthy group,especially TRA.A significant increase in the Shannon-Weaver index was observed for the TRA and TRG repertoires after treatment in vinculin autoantibody-negative patients,but a significant increase in the IGH repertoire after treatment was observed in vinculin autoantibody-positive patients.The frequency of some V-J pairs was significantly enriched in steroid-sensitive nephrotic syndrome patients.The usage frequency of the V and J genes was skewed in patients,which seemed not related to immunosuppressive therapy.However,after effective treatment,dynamic changes in the size of the individual clonotype were observed.Conclusion T-cell and B-cell immunity contribute to the pathogenesis of different INSs.

Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis:a prospective,comparative study

Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.