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The present study was set out to address the therapeutic efficacy of human adipose tissue stem cells derived extracellular vesicles (hADSC-Evs) in a mouse model of dry eye disease and to investigate the underlying mechanisms involved. hADSC-Evs eye drops were topically administered to mice that subjected to desiccating stress (DS). Clinical parameters of ocular surface damage were assessed with fluorescein staining, tear production and PAS staining. For in vitro studies, cell viability assay and TUNEL staining were performed in human corneal epithelial cells (HCECs) treated with hADSC-Evs under hyperosmotic media. In addition, immunofluorescent staining, Real-time PCR (qRT-PCR) and Western blots were used to evaluated NLRP3, ASC, caspase-1, and IL-1β expression levels. Compared with vehicle control mice, topical hADSC-Evs treated mice showed decreased corneal epithelial defects, increased tear production, decreased goblet cell loss, as well as reduced inflammatory cytokines production. In vitro, hADSC-Evs could protect HCECs against hyperosmotic stress-induced cell apoptosis. Mechanistically, hADSC-Evs treatment suppressed the DS induced rises in NLRP3 inflammasome formation, caspase-1 activation and IL-1β maturation. In conclusion, hADSC-Evs eye drops effectively suppress NLRP3 inflammatory response and alleviate ocular surface damage in dry eye disease. Dry eye disease (DED) is a highly prevalent ocular surface disorder in the world 1. It is estimated that more than 16 million adults are diagnosed DED in US, and the prevalence in Asia is even higher than in western countries 2,3. According to the reports of Dry Eye Workshop (DEWS II), DED is a multifactorial disease that characterized by loss of homeostasis of the tear film 4. The tear film instability causes symptoms of discomfort, itching, eye irritation, glare and blurry vision, leading to a reduction in quality of life. Although the pathogenesis of DED is not yet fully understood, mounting evidence showed that the "vicious cycle of inflammation", including tear film instability, tear hyperosmolarity, apoptosis of cornea/conjunctiva and elevated levels of pro-inflammatory cytokines, play a core driver in its initiation and progression 5,6. Accordingly, most of the treatments to date are focused on reducing inflammation and restoring normal tear film 7. Mesenchymal stem cells (MSCs) are self-renewing multipotent stromal cells that can be isolated from mesenchymal tissues such as bone marrow, adipose, umbilical cord, as well as other tissues 8. Due to their immunomodulatory and trophic characteristics, MSC-based therapeutic intervention has been explored in a variety of immune-mediated disorders, including dry eye disease 9-12. Although most of the results were promising, safety issues regarding MSC-based therapy are still a matter of concern. Extracellular vesicles, with nanosized diameter of 30-150 nm, are known as intercellular communication mediators by transferring various bioactive molecules (proteins, lipids and RNAs) 13. Recent studies revealed that MS...

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Background. Previous studies have suggested that teachers' frequent use of cognitive activation strategies in mathematics lessons is positively associated with students' mathematics achievement. Aims. This study aims to investigate the possible mediating role of mathematics selfefficacy in the association between cognitive activation and achievement in mathematics classrooms. Besides that, we explored the moderating role of students' socioeconomic status (SES) in the relationships between cognitive activation, mathematics self-efficacy, and mathematics achievement. Samples. This study employed data from a project of the National Assessment Center for Education Quality (NACEQ) in China. A sample with 8707 fourth-grade primary students and 129 mathematics teachers was analysed. Methods. The multi-level analysis was used in this study with students representing the level-1 units and teachers representing the level-2 units. Results. Based on a large-scale standard assessment and survey in China, this study showed that cognitive activation was positively related to mathematics performance overall. Mathematics self-efficacy played a vital mediating role in the association between cognitive activation and mathematics achievement. The indirect relationship between cognitive activation and mathematics achievement via mathematics self-efficacy was moderated by SES both at the student level and the teacher level. Conclusions. Our study suggests the importance of cognitively activating instruction, especially for students with lower SES and classes with lower average SES.

By evaluating the consistency of the Gassmann theory with various inclusion‐based effective medium theories, we investigate the impact of elastic interactions between ellipsoidal pores on the poroelasticity. To rule out any factors that can violate the Gassmann condition, other than elastic interactions, we first construct idealized models that contain only a single set of isolated, identical, and vertically aligned ellipsoidal pores. The numerical simulation suggests that the periodic distribution of ellipsoidal pores generate uniform pore pressure distribution, whereas random distribution of ellipsoidal pores generates heterogeneous pore pressure distributions. Then we analyze the precise conditions under which the underlying Gassmann relationship is valid for various inclusion‐based models. The results reveal the following: (1) Noninteracting effective medium theories are always consistent with the Gassmann prediction, simply because the elastic interactions are ignored. (2) The elastic interactions between randomly distributed pores cause heterogeneous pore pressure that violates the essential requirement of the Gassmann theory. The differential effective medium and self‐consistent approximation theories corresponding to this model thus are inconsistent with the Gassmann prediction. (3) The elastic interactions between periodically distributed pores cause uniform pore pressure; therefore, the Gassmann condition is fully satisfied. The T‐matrix approach explicitly takes into account such elastic interactions and thus is consistent with the Gassmann theory. It is interesting to notice that on top of other well‐known common types of heterogeneities, like pore structure or fluid heterogeneities, the distribution of pores and its associated elastic interactions can be a separate source of heterogeneity, and this makes Gassmann equations not valid anymore.

National Natural Science Foundation of China [10735090, 11005151]An inactivation mechanism study on A549 cancer cells by means of a dielectric barrier discharge plasma needle is presented. The neutral red uptake assay provides a quantitative estimation of cell viability after plasma treatment. Experimental results show that the efficiency of argon plasma for the inactivation process is very dependent on power and treatment time. A 27 W power and 120 s treatment time along with 900 standard cubic centimeter per minute Ar flow and a nozzle-to-sample separation of 3 mm are the best parameters of the process. According to the argon emission spectra of the plasma jet and the optical microscope images of the A549 cells after plasma treatment, it is concluded that the reactive species (for example, OH and O) in the argon plasma play a major role in the cell deactivation. (C) 2011 American Institute of Physics. [doi:10.1063/1.3553873

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Basement membrane (BM) is a thin layer of extracellular matrix that surrounds most animal tissues, serving as a physical barrier while allowing nutrient exchange. Although they have important roles in tissue structural integrity, physical properties of BMs remain largely uncharacterized, which limits our understanding of their mechanical functions. Here, we perform pressure-controlled inflation and deflation to directly measure the nonlinear mechanics of BMs in situ. We show that the BMs behave as a permeable, hyperelastic material whose mechanical properties and permeability can be measured in a model-independent manner. Furthermore, we find that BMs exhibit a remarkable nonlinear stiffening behavior, in contrast to the reconstituted Matrigel. This nonlinear stiffening behavior helps the BMs to avoid the snap-through instability (or structural softening) widely observed during the inflation of most elastomeric balloons and thus maintain sufficient confining stress to the enclosed tissues during their growth.