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Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. Recent studies demonstrate that TSP1 is highly expressed in adipose tissue (AT) and positively associated with AT inflammation and insulin resistance (IR). In this study, the contribution of different cellular sources of TSP1 to obesity-induced metabolic complications is determined by using mice with either adipocyte or myeloid/macrophage-specific deletion of TSP1 in a diet-induced obese model. The results demonstrated that neither adipocyte nor myeloid/macrophage-specific deletion of TSP1 affected the development of long-term high-fat diet-induced obesity. Adipocyte-specific deletion of TSP1 did not protect mice from obesity-induced inflammation and IR. On the contrary, obese mice with myeloid/macrophage loss of TSP1 had reduced macrophage accumulation in AT, which was accompanied with reduced inflammation and improved glucose tolerance and insulin sensitivity compared with obese control mice. Reduced macrophage-derived-TGF-β1 signaling and adipose tissue fibrosis were also observed in long-term high-fat-fed mice with myeloid/macrophage-specific TSP1 deletion. Moreover, in vitro experiments demonstrated an autocrine effect of TSP1-mediated TGF-β activation in macrophages in obesity. Collectively this study highlights the critical contribution of myeloid/macrophage-derived TSP1 to obesity-associated chronic inflammation and IR, which may serve as a new therapeutic target for metabolic disease.

process due to the aggressivity (e.g., electroporation or sonication methods), low yield, or poor controllability of traditional methods. [2,3] In addition, because the separation process from donor cells involves cumbersome processing steps, the weakened or lost function of exosomes in this process is difficult to be enhanced or compensated in the process of engineering. [4] In this work, the concept of "independent module/cascading function" is proposed for the controllable construction of engineered exosomes, that is, nanosized artificial module with specific functions is synthesized independently, and then selectively and controllably combined with natural exosome module in a "one-by-one" way to construct engineered exosome. The concept of "independent module" is not limited by the activity conditions of exosomes, so as to greatly enrich the preparation methods and types of artificial modules. Meantime, based on the selective and controllable combination technology between different modules, this method can effectively protect the integrity of exosome membrane structure and the activity of functional proteins and nucleic acids on membrane surface. "Cascading function" refers to endowing exosomes with new functions through rich design of artificial modules, and meeting the complex requirements of disease treatment through cascading effect, so as to play a remarkable therapeutic effect.In addition, this kind of engineered exosomes is applied to the treatment of Parkinson's disease (PD), aiming to solve the challenges of precise targeting and complex needs of PD treatment, of which the pathogenesis is complex and involves many factors and there is no effective method to completely cure it. [5] Up to now, the pathogenesis of PD can be summarized as the following process: nuclear gene mutation of dopaminergic neurons inhibits the normal hydrolysis of α-synuclein (α-syn) and promotes its aggregation in mitochondria, producing high concentration of reactive oxygen species (ROS), which further leads to enhanced expression of inducible nitric oxide synthase (iNOS) and neuroinflammation, and destroys itself and its surrounding neuronal cells. [6] Exosomes derived from stem cells have the potential to promote tissue repair and nerve regeneration, and have the ability to penetrate the blood-brain barrier Current exosome engineering methods usually lead to the damage of exosome morphology and membrane, which cannot meet the complex needs of disease treatment. Herein, the concept of an "independent module/cascading function" is proposed to construct an engineered exosome nanotherapy platform including an independent artificial module and a natural module. The artificial module with movement/chemotaxis function is first synthesized, and then it is controllably combined with the natural exosome module with "one by one" mode through a "differentiated" modification method. The whole process can not only maintain the activity of the natural exosome module, but also endows it with motion ability, so as to realize the purpose of...

hoc test or Dunnett's T3 post hoc test was used in one-way ANOVA. p < 0.05 was considered statistically significant (*p < 0.05).

No abstract

ALCELL lignin has been employed as a coupling agent in oil palm empty fruit bunch (EFB)–polypropylene (PP) composites. The lignin has been chemically modified with hexamethylene diisocyanate (HMDI). Evidence for the reaction between HMDI and lignin has been observed by using Fourier transform infrared (FTIR) analysis. The effect of lignin as a coupling agent on the flexural properties has been studied. The results show that the HMDI‐modified lignin is able to impart greater compatibility between EFB and PP. This is reflected in the greater flexural strength shown by the composites with HMDI‐modified lignin than those with the unmodified lignin. Scanning electron microscopy studies show that HMDI‐modification of lignin results in a better blending and compatibility between lignin and PP matrix. The glass transition temperature of lignin increases as the level of HMDI modification is increased. © 2001 Society of Chemical Industry

ALCELL lignin has been employed as a coupling agent in empty fruit bunch fiber (EFBF)-polypropylene (PP) composites. The lignin has been chemically modified with toluene diisocyanate (TDI) to various weight loadings. The evidence of the reaction between TDI and lignin has been observed by using Fourier transform infrared (FTIR) analysis. The effect of lignin as a coupling agent on mechanical properties has been studied. The results show that the TDI-modified lignin is able to impart greater compatibility between EFBF and PP. This is reflected in the greater mechanical properties shown by the composites with TDI-modified lignin than in those with the unmodified lignin. Scanning electron microscopy (SEM) studies showed that TDI modification of lignin resulted in a better blending and compatibility between lignin and PP matrix. The glass-transition temperature of the lignin increases as the WPG is increased.

No abstract