The delivery of miR-21a-5p by extracellular vesicles induces microglial polarization via the STAT3 pathway following hypoxia-ischemia in neonatal mice

Extracellular vesicles(EVs)from mesenchymal stromal cells(MSCs)have previously been shown to protect against brain injury caused by hypoxia-ischemia(HI).The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs.However,the underlying mechanisms have not previously been determined.In this study,we induced oxygen-glucose deprivation in BV-2 cells(a microglia cell line),which mimics HI in vitro,and found that treatment with MSCs-EVs increased the cell viability.The treatment was also found to reduce the expression of pro-inflammatory cytokines,induce the polarization of microglia towards the M2 phenotype,and suppress the phosphorylation of selective signal transducer and activator of transcription 3(STAT3)in the microglia.These results were also obtained in vivo using neonatal mice with induced HI.We investigated the potential role of miR-21a-5p in mediating these effects,as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway.We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells,which had been lowered following oxygen-glucose deprivation.When the level of miR-21a-5p in the MSCs-EVs was reduced,the effects on microglial polarization and STAT3 phosphorylation were reduced,for both the in vitro and in vivo HI models.These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p,which induces microglial M2 polarization by targeting STAT3.

CLE25 peptide regulates phloem initiation in Arabidopsis through a CLERK-CLV2 receptor complex

The phloem, located within the vascular system, is critical for delivery of nutrients and signaling molecules throughout the plant body. Although the morphological process and several factors regulating phloem differentiation have been reported, the molecular mechanism underlying its initiation remains largely unknown. Here, we report that the small peptide-coding gene, CLAVATA 3 (CLV3)/EMBEYO SURROUNDING REGION 25 (CLE25), the expression of which begins in provascular initial cells of 64-cell-staged embryos, and continues in sieve element-procambium stem cells and phloem lineage cells, during postembryonic root development, facilitates phloem initiation in Arabidopsis. Knockout of CLE25 led to delayed protophloem formation, and in situ expression of an antagonistic CLE25G6T peptide compromised the fate-determining periclinal division of the sieve element precursor cell and the continuity of the phloem in roots. In stems of CLE25G6T plants the phloem formation was also compromised, and procambial cells were over-accumulated. Genetic and biochemical analyses indicated that a complex, consisting of the CLE-RESISTANT RECEPTOR KINASE (CLERK) leucinerich repeat (LRR) receptor kinase and the CLV2 LRR receptor- like protein, is involved in perceiving the CLE25 peptide. Similar to CLE25, CLERK was also expressed during early embryogenesis. Taken together, our findings suggest that CLE25 regulates phloem initiation in Arabidopsis through a CLERK-CLV2 receptor complex.

Catalyst-controlled diastereoselective ring-opening formal [3+2]-cycloadditions of arylvinyl oxirane 2,2-diesters with cyclic N-sulfonyl imines

A diastereoselectivity-controllable formal[3+2]-cycloaddition of arylvinyl oxirane 2,2-diesters with cyclic N-sulfonyl imines is developed,affording the corresponding tricyclic oxazolidine derivatives in moderate to excellent yields with excellent diastereoselectivities in the presence of palladium(0)or scandium(III)triflate.This protocol allows selective synthesis of diastereomers of tricyclic oxazolidine derivatives under switchable and mild conditions.Further transformations of the obtained products were conducted by removing ester groups and arylvinyl moieties.

Molecular mechanisms and therapeutic strategies of vulnerable atherosclerotic plaques

Vulnerable atherosclerotic plaque rupture lead-ing to thrombosis is the major cause of acute coronary syndrome(ACS).Studies on the pathophysiologic mechanism of both ACS and plaque stabilizing treatment are driving the development of animal models of vulnerable plaque.In our laboratory,we established animal models of plaque rupture and thrombosis in rabbits and mice that are similar to human plaque rupture.Potential mechanisms involved in plaque vulnerability were studied from the inflammation-immunity,proliferation-apoptosis,oxidative stress and biomechanics aspects.Imaging markers and biomarkers were used to detect vulnerable plaques,including high frequency duplex ultrasound,intravascular ultrasound(IVUS),intravascular ultrasound elastography,magnetic resonance imaging(MRI)and inflammatory markers.Effective gene and drug strategies to treat vulnerable plaques were explored.