Pristimerin suppresses AIM2 inflammasome by modulating AIM2-PYCARD/ASC stability via selective autophagy to alleviate tendinopathy.

Macroautophagy/autophagy plays an important role in regulating cellular homeostasis and influences the pathogenesis of degenerative diseases. Tendinopathy is characterized by tendon degeneration and inflammation. However, little is known about the role of selective autophagy in tendinopathy. Here, we find that pristimerin (PM), a quinone methide triterpenoid, is more effective in treating tendinopathy than the first-line drug indomethacin. PM inhibits the AIM2 inflammasome and alleviates inflammation during tendinopathy by promoting the autophagic degradation of AIM2 through a PYCARD/ASC-dependent manner. A mechanistic study shows that PM enhances the K63-linked ubiquitin chains of PYCARD/ASC at K158/161, which serves as a recognition signal for SQSTM1/p62-mediated autophagic degradation of the AIM2-PYCARD/ASC complex. We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC. Finally, PM treatment in vivo generates an effect comparable to inflammasome deficiency in alleviating tendinopathy. Taken together, these findings demonstrate that PM alleviates the progression of tendinopathy by modulating AIM2-PYCARD/ASC stability via SQSTM1/p62-mediated selective autophagic degradation, thus providing a promising autophagy-based therapeutic for tendinopathy.Abbreviations: 3-MA: 3-methyladenine; AIM2: absent in melanoma 2; AT: Achilles tenotomy; ATP: adenosine triphosphate; BMDMs: bone marrow-derived macrophages; CHX: cycloheximide; Col3a1: collagen, type III, alpha 1; CQ: chloroquine; Cys: cysteine; DARTS: drug affinity responsive target stability; DTT: dithiothreitol; DUB: deubiquitinase; gDNA: genomic DNA; GSH: glutathione; His: histidine; IL1B/IL-1ß: interleukin 1 beta; IND: indomethacin; IP: immunoprecipitation; LPS: lipopolysaccharide; MMP: mitochondrial membrane potential; NLRP3: NLR family, pyrin domain containing 3; PM: pristimerin; PYCARD/ASC: PYD and CARD domain containing; SN: supernatants; SOX9: SRY (sex determining region Y)-box 9; SQSTM1: sequestosome 1; Tgfb: transforming growth factor, beta; TIMP3: tissue inhibitor of metalloproteinase 3; TNMD: tenomodulin; TRAF6: TNF receptor-associated factor 6; Ub: ubiquitin; USP50: ubiquitin specific peptidase 50; WCL: whole cell lysates.

A Microporous Hydrogen Bonded Organic Framework for Highly Selective Separation of Carbon Dioxide over Acetylene.

The separation of acetylene (C2 H2 ) from carbon dioxide (CO2 ) is a very important but challenging task due to their similar molecular dimensions and physical properties. In terms of porous adsorbents for this separation, the CO2 -selective porous materials are superior to the C2 H2 -selective ones because of the cost- and energy-efficiency but have been rarely achieved. Herein we report our unexpected discovery of the first hydrogen bonded organic framework (HOF) constructed from a simple organic linker 2,4,6-tri(1H-pyrazol-4-yl)pyridine (PYTPZ) (termed as HOF-FJU-88) as the highly CO2 -selective porous material. HOF-FJU-88 is a two-dimensional HOFs with a pore pocket of about 7.6 Å. The activated HOF-FJU-88 takes up a high amount of CO2 (59.6 cm3 g-1 ) at ambient conditions with the record IAST selectivity of 1894. Its high performance for the CO2 /C2 H2 separation has been further confirmed through breakthrough experiments, in situ diffuse reflectance infrared spectroscopy and molecular simulations.

A space-sacrificed pyrolysis strategy for boron-doped carbon spheres with high supercapacitor performance.

Targeting the potential application of morphological carbon in electrode materials, a space-sacrificed pyrolysis strategy was applied for the preparation of boron-doped carbon spheres (B-CSs), using commercial triphenyl borate (TPB) as carbon and boron co-source. The unique structure of TPB play an important role in the sacrificed space, and has notable effect on the surface area of B-CSs. The as prepared B-CSs possess a high surface area and boron content with uniform boron atoms distribution and high surface polarity, which contributes to the improvement of pseudo-capacitance. The sizes, specific surface areas, and boron contents of B-CSs can be easily regulated by varying the experimental parameters. The optimal sample has a boron content of 1.38 at%, surface area of 560 m2 g-1 and specific capacitance of 235F g-1. We can believe that this work would provide a flexible and extensible preparation technique of B-CSs for electrochemical applications.