The tubular endolysosomal network is a quality control system that ensures the proper delivery of internalized receptors to specific subcellular destinations in order to maintain cellular homeostasis. Although retromer was originally described in yeast as a regulator of endosome-to-Golgi receptor recycling, mammalian retromer has emerged as a central player in endosome-to-plasma membrane recycling of a variety of receptors. Over the past decade, information regarding the mechanism by which retromer facilitates receptor trafficking has emerged, as has the identification of numerous retromer-associated molecules including the WASH complex, sorting nexins (SNXs) and TBC1d5. Moreover, the recent demonstration that several SNXs can directly interact with retromer cargo to facilitate endosome-to-Golgi retrieval has provided new insight into how these receptors are trafficked in cells. The mechanism by which SNX17 cargoes are recycled out of the endosomal system was demonstrated to involve a retromer-like complex termed the retriever, which is recruited to WASH positive endosomes through an interaction with the COMMD/CCDC22/CCDC93 (CCC) complex. Lastly, the mechanisms by which bacterial and viral pathogens highjack this complex sorting machinery in order to escape the endolysosomal system or remain hidden within the cells are beginning to emerge. In this review, we will highlight recent studies that have begun to unravel the intricacies by which the retromer and associated molecules contribute to receptor trafficking and how deregulation at this sorting domain can contribute to disease or facilitate pathogen infection.

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Digital light processing (DLP) is one of the additive manufacturing (AM) technologies suitable for preparation of high-performance ceramics. The present study provided an optimized formula to fabricate osteoinductive calcium phosphate (CaP) ceramics with high precision and controllable three-dimensional (3D) structure. Among the four surfactants, monoalcohol ethoxylate phosphate was the best one to modify the CaP powders for preparing the photocurable slurry with high solid loading and good spreading ability. By testing the photopolymerization property of the 60 wt % solid loading slurry, the appropriate processing parameters including the slice thickness (50 μm), exposure intensity (10.14 mW/cm2), and exposure time (8 s) were set to perform the 3D printing of the ceramic green body in the DLP system. After the debinding and sintering, the final CaP ceramics were acquired. The stereomicroscope and SEM observation confirmed the high precision of the ceramics. The average compressive strength of the ceramics with 64.5% porosity reached 9.03 MPa. On only soaking in simulated body fluid for 1 day, an even layer of apatite formed on the ceramic surface. The cell culture confirmed that the ceramics could allow the good attachment, growth, and proliferation of murine bone marrow mesenchymal stem cells. After implantation into the dorsal muscles of beagle dogs for 3 months, abundant blood vessels and obvious ectopic bone formation were observed clearly by the histological evaluation. Therefore, with good bioactivity and osteoinductivity as well as high precision and adjustable mechanical strength, the 3D printed CaP ceramics in the DLP system could have good potential in customized bone-repairing applications.

Antithrombotic therapy has become an important goal for the treatment of ischemic disorders such as cerebral ischemia. Our recent studies found that Z-ligustilide (LIG), a characterized 3-n-alkylphthalide constituent of Radix Angelica sinensis essential oil, exerted signiˆcant neuroprotection against cerebral ischemic damage in several animal models. The present study evaluated the antithrombotic activity of LIG and its eŠect on platelet aggregation and coagulation time. LIG (10 or 40 mg/kg) was intragastrically administered to rats once daily for 3 days. Our results showed that LIG signiˆcantly and dose-dependently reduced arterial thrombus weight in an arteriovenous shunt thrombosis in rats and platelet aggregation induced by adenosine diphosphate in rats ex vivo. Meanwhile, LIG at 10 or 40 mg/kg had no signiˆcant eŠect on coagulation time, including activated partial thromboplastin time and prothrombin time, in rats ex vivo. The present study demonstrated for theˆrst time that LIG may exert e‹cient antithrombotic activity through inhibition of platelet aggregation, without eŠecting coagulation time of peripheral blood. These data, together with the previously reported neuroprotective eŠects of LIG on cerebral ischemia, suggest that the antithrombotic activity of LIG may contribute to its potential for the treatment of ischemic diseases, including ischemic stroke.

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There is a high prevalence of vitamin D and calcium insufficiency in pregnant women and neonates in Chengdu even when mothers are compliant with prenatal vitamin supplementation. Supplementation is needed to improve maternal and neonatal vitamin D and calcium nutrition.

Nanostructured calcium phosphate (CaP) ceramics could impair osteoclastic differentiation and function. A deep understanding of surface structure-modulated osteoclastogenesis may help us disclose mechanism of CaP-involved osteoinduction.

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