Background Accumulating evidence shows that microRNA-210 (miR-210) holds great promise to improve angiogenesis for brain tissue repair after cerebral ischemia. However, safe and efficient delivery of miR-210 via intravenous administration is still a challenge. In the past decade, exosomes have emerged as a novel endogenous delivery system. Here, c(RGDyK) peptide is conjugated to exosomes, and they are loaded with cholesterol-modified miR-210 (RGD-exo:miR-210). Results In a transient middle cerebral artery occlusion (MCAO) mouse model, the RGD-exo:miR-210 targets the lesion region of the ischemic brain after intravenous administration, resulting in an increase in miR-210 at the site. Furthermore, RGD-exo:miR-210 are administered once every other day for 14 days, and the expressions of integrin β 3 , vascular endothelial growth factor (VEGF) and CD34 are significantly upregulated. The animal survival rate is also enhanced. Conclusions These results suggest a strategy for the targeted delivery of miR-210 to ischemic brain and provide an angiogenic agent for the treatment of ischemic stroke. Electronic supplementary material The online version of this article (10.1186/s12951-019-0461-7) contains supplementary material, which is available to authorized users.

The growth of B cell receptor (BCR) microclusters upon antigen stimulation drives B cell activation. Here, we show that PI3K-mediated PIP production is required for the growth of BCR microclusters. This growth is likely inhibited by PTEN and dependent on its plasma membrane binding and lipid phosphatase activities. Mechanistically, we find that PIP-dependent recruitment and activation of a guanine nucleotide exchange factor, Dock2, is required for the sustained growth of BCR microclusters through remodeling of the F-actin cytoskeleton. As a consequence, Dock2 deficiency significantly disrupts the structure of the B cell immunological synapse. Finally, we find that primary B cells from systemic lupus erythematosus (SLE) patients exhibit more prominent BCR and PI3K microclusters than B cells from healthy controls. These results demonstrate the importance of a PI3K- and PTEN-governed PIP and PIP equilibrium in regulating the activation of B cells through Dock2-controlled growth of BCR microclusters.

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Green, environment friendly, and sustainable biomass-based adhesive has been considered as an optimum alternative of petroleum-derived adhesive, yet poor water resistance restricts their advancement and popularization to a large extent. Herein, a hyperbranched cross-linking cellulose-based adhesive with a synergistic effect of covalent bonds and secondary bonds (mainly include hydrogen bond and hydrophobic effect) is synthesized based on the Maillard reaction between dialdehyde cellulose (DAC) and polyamines. The active aldehyde sites on the DAC skeleton anchor the amino group to form covalent bonds consuming a large number of hydrophilic groups, the remaining aliphatic segments of polyamines criss-cross to knit a hydrophobic network and endow the adhesive the ability to resist water erosion; integrant-exposed hydrophilic groups form intermolecular hydrogen bonds preferentially after curing and clustering due to the agglomeration effect of cellulose, which reduces the opportunity of forming hydrogen bonds with water molecules. The outstanding water resistance is manifested in two aspects: (1) the dry lap shear strength of modified adhesive increased from 1.47 to 3.29 MPa, making increments of 123.8% compared with the original DAC adhesive, the re-dry strength after 3 h of immersion in water of 63 °C or boiling achieved a breakthrough from 0 to 2.27 and 2.36 MPa; (2) the modified adhesive has a higher residual rate (above 77%) and a lower moisture absorption value (less than 22.2%) compared with the neat DAC adhesive (49 and 26.6%). The work provides an underlying approach to prepare wood adhesive with excellent bonding performance and eminent water resistance based on green and cheap raw materials and simple cooking chemistry.

The job-shop scheduling problem (JSSP) is a challenging scheduling and optimization problem in the industry and engineering, which relates to the work efficiency and operational costs of factories. The completion time of all jobs is the most commonly considered optimization objective in the existing work. However, factories focus on both time and cost objectives, including completion time, total tardiness, advance time, production cost, and machine loss. Therefore, this article first time proposes a many-objective JSSP that considers all these five objectives to make the model more practical to reflect the various demands of factories. To optimize these five objectives simultaneously, a novel multiple populations for multiple objectives (MPMO) frameworkbased genetic algorithm (GA) approach, called MPMOGA, is proposed. First, MPMOGA employs five populations to optimize the five objectives, respectively. Second, to avoid each population only focusing on its corresponding single objective, an archive sharing technique (AST) is proposed to store the elite solutions collected from the five populations so that the populations can obtain optimization information about the other objectives from the archive. This way, MPMOGA can approximate different parts of the entire Pareto front (PF). Third, an archive update strategy

In light of the decreasing immune protection against symptomatic SARS-CoV-2 infection after initial vaccinations and the now dominant immune-evasive Omicron variants, ‘booster’ vaccinations are regularly performed to restore immune responses. Many individuals have received a primary heterologous prime-boost vaccination with long intervals between vaccinations, but the resulting long-term immunity and the effects of a subsequent ‘booster’, particularly against Omicron BA.1, have not been defined. We followed a cohort of 23 young adults, who received a primary heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, over a 7-month period and analysed how they responded to a BNT162b2 ‘booster’. We show that already after the primary heterologous vaccination, neutralization titers against Omicron BA.1 are recognizable but that humoral and cellular immunity wanes over the course of half a year. Residual responsive memory T cells recognized spike epitopes of the early SARS-CoV-2 B.1 strain as well as the Delta and BA.1 variants of concern (VOCs). However, the remaining antibody titers hardly neutralized these VOCs. The ‘booster’ vaccination was well tolerated and elicited both high antibody titers and increased memory T cell responses against SARS-CoV-2 including BA.1. Strikingly, in this young heterologously vaccinated cohort the neutralizing activity after the ‘booster’ was almost as potent against BA.1 as against the early B.1 strain. Our results suggest that a ‘booster’ after heterologous vaccination results in effective immune maturation and potent protection against the Omicron BA.1 variant in young adults.

Broomcorn millet ( Panicum miliaceum L.) is one of the oldest domesticated crops and has been grown in arid and semiarid areas in China since 10,000 cal. BP. However, limited information is available about how bacterial communities within the rhizosphere of different broomcorn millet cultivars respond to drought stress. Here, we characterized the changes in the rhizobacterial assemblages of two broomcorn millet cultivars, namely, P. miliaceum cv. HeQu Red (HQR) and P. miliaceum YanLi 10 (YL10), from the jointing stage to the grain filling stage after they were exposed to a short-term drought stress treatment at the seedling stage. Drought significantly inhibited the growth of both cultivars, but the effect on YL10 was higher than that on HQR, indicating that the drought tolerance of HQR was greater than that of YL10. Proteobacteria (33.8%), Actinobacteria (21.0%), Acidobacteria (10.7%), Bacteroidetes (8.2%), Chloroflexi (6.3%), Gemmatimonadetes (5.9%), Firmicutes (3.5%), Verrucomicrobia (2.9%), and Planctomycetes (2.7%) were the core bacterial components of broomcorn millet rhizosphere as suggested by 16S rDNA sequencing results. The diversity and composition of bacterial rhizosphere communities substantially varied at different developmental stages of broomcorn millet. As the plants matured, the richness and evenness of the rhizobacterial community significantly decreased. Principal coordinate analysis showed that the structure of the bacterial rhizosphere community changed notably only at the flowering stage between the two cultivars, suggesting a stage-dependent effect. Although drought stress had no significant effect on the diversity and structure of the bacterial rhizosphere community between the two cultivars, differential responses to drought was found in Actinobacteria and Acinetobacter , Lysobacter , Streptomyces , and Cellvibrio . The relative abundance of Actinobacteria and Lysobacter , Streptomyces , and Cellvibrio in the YL10 rhizosphere was stimulated by the drought treatment compared with that in the HQR rhizosphere, whereas the opposite effect was found in Acinetobacter . Our results suggested that the effects of cultivars on bacterial rhizosphere communities were highly dependent on plant developmental stage, reflecting the genetic variations in the two broomcorn millet cultivars.

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