Prevention of Chemotherapy-Induced Peripheral Neuropathy by Inhibiting C-X-C Motif Chemokine Receptor 2.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major drawback in the use of chemotherapeutic agents for patients with cancer. Although studies have investigated a broad number of molecules that might be related to CIPN, the differences in the chemokine pathways between various chemotherapeutic agents, such as vincristine and oxaliplatin, which are some of the most widely used treatments, have not been fully elucidated. We confirmed that the administration (intraperitoneal injections for seven days) of vincristine (0.1 mg/kg) and oxaliplatin (3 mg/kg) induced pain by using the von Frey behavioral test. Subsequent applications with vincristine and oxaliplatin led to mechanical allodynia that lasted more than one week from the fifth day. After the induction of mechanical allodynia, the mRNA expression of CXCR2, CXCL1, CXCL3, and CXCL5 was examined in the dorsal root ganglia (DRG) and spinal cord of the CIPN models. As a result, the mRNA expression of CXCR2 robustly increased in the lumbar spinal cord in the oxaliplatin-treated mice. Next, to evaluate the involvement of CXCR2 in CIPN, reparixin, a CXCR1/2 inhibitor, was administered intrathecally or intraperitoneally with vincristine or oxaliplatin and was further verified by treatment with ruxolitinib, which inhibits Janus kinase 2 downstream of the CXCR1/2 pathway. Reparixin and ruxolitinib blocked oxaliplatin-induced allodynia but not vincristine-induced allodynia, which suggests that CXCR2-related pathways are associated with the development of oxaliplatin-induced neuropathy. Together with the above results, this suggests that the prevention of oxaliplatin-induced neuropathy by CXCR2 inhibition can lead to successful chemotherapy, and it is important to provide appropriate countermeasures against CIPN development for each specific chemotherapeutic agent.

Data on the predictions of plant redistribution under interplays among climate change, land-use change, and dispersal capacity.

The future distribution data of Pittosporum tobira, Raphiolepis indica var. umbellata, Neolitsea sericea, Ilex integra, and Eurya emarginata were acquired from the MigClim, a GIS-based (hybrid) cellular automation model, modeling and the traditional SDM modeling using BioMod2. The current SDM projections, the traditional SDM predictions, which were assumed the climate-change-only, and model validation were performed using BioMod2 with 686 presence/absence data for each plant species. The MigClim predictions were performed under the combination of two climate change scenarios (RCP 4.5 and RCP 8.5), two land-use change scenarios (SSP1 and SSP3), and four dispersal scenarios (no dispersal, short-distance dispersal, long-distance dispersal, and full dispersal). For the MigClim predictions, the initial distribution map was produced by coupling the current land-use map with the ensemble SDM predictions for each plant. The future habitat suitability map was predicted by coupling the land-use prediction with the SDM predictions under RCP 4.5 and RCP 8.5. For the land-use map, the future land-use maps were predicted under SSP1 and SSP3 using the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) Scenario Generator tool, and the land-use categories were classified into two classes, namely barrier and non-barrier. The degree of dispersal for each species was calculated using a negative exponential function, where the coefficients were 0.005 (∼1 km) and 0.0005 (∼10 km). The future expansion of range was predicted through dispersal simulations of 80 times from 1990 to 2070. The prediction and analyzed data provide essential information and insight for understanding the climate change effects on the warm-adapted plants in interactions with land-use change and the dispersal process. These data can be used for detecting restoration areas for increasing connectivity among habitats, establishing protected areas, and developing environmental policies related to restoration and conservation.

Effects of side-chain interdigitation on stability: an environmentally, electrically, and thermally stable semiconducting polymer.

A polymeric semiconductor, poly(3,6-dihexyl-[2,2']bi[thieno[3,2-b]thiophene]) (PDHTT), was synthesized and tested as an active layer in organic thin film transistors (OTFTs). This semiconductor showed considerable potential for use in commercial electronic devices because of its superior characteristics, particularly its good stability. PDHTT-based OTFTs exhibited high stability in air, retaining their initial performance after exposure to 70% relative humidity for 50 days; they were also stable under repeated electrical stress and even after exposure to temperatures as high as 250 °C. We attribute the remarkable stability of PDHTT OTFTs to the relatively low highest occupied molecular orbital (5.1 eV) level of the polymer and its highly interdigitated structure in the thin film state.