Our study highlights the overactivated neddylation pathway in lung cancer development and as a promising therapeutic target.

Real-time sensing of nitric oxide (NO) in physiological environments is critically important in monitoring neurotransmission, inflammatory responses, cardiovascular systems, etc. Conventional approaches for NO detection relying on indirect colorimetric measurement or built with rigid and permanent materials cannot provide continuous monitoring and/or require additional surgical retrieval of the implants, which comes with increased risks and hospital cost. Herein, we report a flexible, biologically degradable and wirelessly operated electrochemical sensor for real-time NO detection with a low detection limit (3.97 nmol), a wide sensing range (0.01–100 μM), and desirable anti-interference characteristics. The device successfully captures NO evolution in cultured cells and organs, with results comparable to those obtained from the standard Griess assay. Incorporated with a wireless circuit, the sensor platform achieves continuous sensing of NO levels in living mammals for several days. The work may provide essential diagnostic and therapeutic information for health assessment, treatment optimization and postsurgical monitoring.

Purpose: Targeting the protein neddylation pathway has become an attractive anticancer strategy; however, the role of death receptor-mediated extrinsic apoptosis during treatment remained to be determined.Experimental Design: The activation of extrinsic apoptosis and its role in MLN4924 treatment of human esophageal squamous cell carcinoma (ESCC) were evaluated both in vitro and in vivo. The expression of the components of extrinsic apoptotic pathway was determined by immunoblotting analysis and downregulated by siRNA silencing for mechanistic studies.Results: Pharmaceutical or genetic inactivation of neddylation pathway induced death receptor 5 (DR5)-mediated apoptosis and led to the suppression of ESCC in murine models. Mechanistically, neddylation inhibition stabilized activating transcription factor 4 (ATF4), a Cullin-Ring E3 ubiquitin ligases (CRL) substrate. Transcription factor CHOP was subsequently transactivated by ATF4 and further induced the expression of DR5 to activate caspase-8 and induce extrinsic apoptosis. Moreover, the entire neddylation pathway was hyperactivated in ESCC and was negatively associated with patient overall survival.Conclusions: Our findings highlight a critical role of ATF4-CHOP-DR5 axis-mediated extrinsic apoptosis in neddylationtargeted cancer therapy and support the clinical investigation of neddylation inhibitors (e.g., MLN4924) for the treatment of ESCC, a currently treatment-resistant disease with neddylation hyperactivation.

Fibroblast growth factor (FGF) belongs to a large family of growth factors. FGFs use paracrine or endocrine signaling to mediate a myriad of biological and pathophysiological process, including angiogenesis, wound healing, embryonic development, and metabolism regulation. FGF drugs for the treatment of burn and ulcer wounds are now available. The recent discovery of the crucial roles of the endocrine-acting FGF19 subfamily in maintaining homeostasis of bile acid, glucose, and phosphate further extended the activity profile of this family. Here, the applications of recombinant FGFs for the treatment of wounds, diabetes, hypophosphatemia, the development of FGF receptor inhibitors as anti-neoplastic drugs, and the achievements of basic research and applications of FGFs in China are reviewed.

Ni3S2 nanosheets doped with tin (Sn) grown on nickel foam (Sn–Ni3S2/NF) through a facile hydrothermal process were found to be superior water-splitting electrocatalysts. As for overall water splitting (OWS), when the current density is 10 mA cm–2, the required voltage is only 1.46 V. Meanwhile, it exhibits a large current density property and long-time stability (>60 h current–time tests) for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). In order to reach the current densities of 100 and 1000 mA cm–2, Sn–Ni3S2/NF needs overpotentials of 0.17 and 0.57 V for HER, and 0.27 and 0.58 V for OER, respectively. The water-splitting property of Sn–Ni3S2/NF is much better than that of pure Ni3S2/NF or even 20 wt % Pt/C/NF and RuO2/NF. Furthermore, Sn–Ni3S2/NF showed a higher turnover frequency at different potentials, with ∼100% Faraday efficiency for both O2 and H2. The improved activity of Sn–Ni3S2/NF activity for water-splitting is attributed to the doping of Sn, which enhanced the intrinsic activity of Sn–Ni3S2/NF for OWS. This article not only provides a new efficient and stable catalyst for OWS, but also proposes an interface design principle for NF-based high-performance water-splitting materials.