Non-enzymatic chitinase-3 like-protein-1 (CHI3L1) belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid, and is regulated by extracellular matrix changes, cytokines, growth factors, drugs, and stress. CHI3L1 is synthesized and secreted by a multitude of cells including macrophages, neutrophils, synoviocytes, chondrocytes, fibroblast-like cells, smooth muscle cells, and tumor cells. It plays a major role in tissue injury, inflammation, tissue repair, and remodeling responses. CHI3L1 has been strongly associated with diseases including asthma, arthritis, sepsis, diabetes, liver fibrosis, and coronary artery disease. Moreover, following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line, CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models. To date, interleukin-13 receptor subunit alpha-2, transmembrane protein 219, galectin-3, chemo-attractant receptor-homologous 2, and CD44 have been identified as CHI3L1 receptors. CHI3L1 signaling plays a critical role in cancer cell growth, proliferation, invasion, metastasis, angiogenesis, activation of tumor-associated macrophages, and Th2 polarization of CD4+ T cells. Interestingly, CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis. This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis, then posits investigational strategies for targeted therapies.

An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem cells (MSCs) has been shown to be related to various human metabolic diseases, such as obesity and osteoporosis; however, the underlying mechanisms remain elusive. We found that the interaction between osteopontin (OPN), an arginine-glycine-aspartate-containing glycoprotein, and integrin αv/β1 plays a critical role in the lineage determination of MSCs. Although OPN is a well established marker during osteogenesis, its role in MSC differentiation is still unknown. Our study reveals that blockade of OPN function promoted robust adipogenic differentiation, while inhibiting osteogenic differentiation. Re-expression of OPN restored a normal balance between adipogenesis and osteogenesis in OPN-/- MSCs. Retarded bone formation by OPN-/- MSCs was also verified by in vivo implantation with hydroxyapatite-tricalcium phosphate (HA-TCP), a bone-forming matrix. The role of extracellular OPN in MSC differentiation was further demonstrated by supplementation and neutralization of OPN. Blocking well-known OPN receptors integrin αv/β1 but not CD44, also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin αv/β1. Consistent with these in vitro results, OPN-/- mice had a higher fat to total body weight ratio than did wild-type mice. Therefore, our study demonstrates a novel role for OPN-integrin αv/β1 in regulating MSC differentiation.

Aqueous batteries (ABs) have attracted increasing attention because of their inherent safety and low cost. Nevertheless, hydrogen evolution reaction (HER) at the anode presents severe challenges for stable and safe operation of ABs. Instead of passivating the anode surface to hinder HER kinetics, a novel design strategy is proposed here to suppress the HER via alternating its thermodynamics pathway. By adding a hydrogen bond acceptor, dimethyl sulfoxide (DMSO), the onset potential of HER can be delayed by as much as 1.0 V (on titanium mesh). Spectral characterization and molecular dynamics simulation confirm that the formation of hydrogen bonds between DMSO and water molecules can reduce the water activity, thereby suppressing the HER. This strategy has proven to be universal in expanding the electrochemical window of aqueous electrolytes. For instance, unconventional V 2+ ↔V 3+ redox processes in Na 3 V 2 (PO 4 ) 3 (-1.2 V versus Ag/AgCl) and highly stable Zn plating/stripping processes can be realized in ABs.