As an organophosphorus ester, tri-ortho-cresyl phosphate (TOCP) has been widely used in agriculture and industry. It is reported that TOCP can induce organophosphate-induced delayed neuropathy (OPIDN) in sensitive animal and human species. However, the exact molecular mechanisms underlying TOCP-induced neurotoxicity are still unknown. In this study, we found that TOCP could induce autophagy by activating protein kinase C alpha (PKCα) signaling in neuroblastoma SK-N-SH cells. PKCα activators could positively regulate TOCP-induced autophagy by increasing the expression levels of neighbor BRCA1 gene protein 1 (NBR1), LC3 and P62 autophagic receptor protein. Furthermore, PKCα activation impaired the ubiquitin-proteasome system (UPS), resulting in inhibition of proteasome activity and accumulation of ubiquitinated proteins. UPS dysfunction could stimulate autophagy to serve as a compensatory pathway, which contributed to the accumulation of the abnormally hyperphosphorylated tau proteins and degradation of impaired proteins of the MAP 2 and NF-H families in neurodegenerative disorders. K E Y W O R D S autophagy, OPIDN, protein kinase C alpha, tri-ortho-cresyl phosphate, ubiquitin-proteasome system 1 | INTRODUCTION As an organophosphorus ester, tri-ortho-cresyl phosphate (TOCP) has been widely used as a flame retardant, lubricant, plasticizer and jet oil additive (Craig & Barth, 1999). This organophosphorus ester is capable of inducing delayed neuropathy (OPIDN) in human species and other sensitive animals (Xu et al., 2017). In 1930, Jamaica ginger caused a large-scale outbreak of TOCP-induced delayed neuropathy, affecting approximately 40 000 Americans (Morgan, 1982; Morgan & Tulloss, 1976). During the twentieth century, 60 000 people may have developed TOCP-induced delayed neuropathy because of the contamination of beverages or food by industrial products (Latimer, 1962). However, the exact molecular mechanisms underlying TOCP-induced neurotoxicity are still unknown. Autophagy is an important process for the elimination of wornout organelles and aggregated proteins, which may be involved in regulating many cellular functions, including cell metabolism, survival and differentiation (Codogno & Meijer, 2005; Gautam, Shravage, & Baehrecke, 2012). Studies reported that TOCP could induce Abbreviations: LC3, microtubule-associated protein 1 light chain; MgOAc, magnesium acetate; NBR 1, neighbor BRCA1 gene protein 1; OPIDN, organophosphate-induced delayed neuropathy; p-PKCα, phospho-protein kinase C alpha; PKCα, protein kinase C alpha; PMA, phorbol myristate acetate; SP, staurosporine; TOCP, tri-ortho-cresyl phosphate; UPS, ubiquitin-proteasome system.

Aryl hydrocarbon receptor nuclear translocator protein 2 (ARNT2), a member of the basic helix-loop-helix superfamily of transcription factors, may serve a vital role in neuronal survival and cell proliferation via formation of heterodimers with hypoxia-inducible factor-1α. Previous studies indicated that ARNT2 levels were elevated in the brains of ischemic rats; however, the involvement of ARNT2 in post-stroke depression (PSD) rats is not well understood. Therefore, the present study aimed to investigate the levels of ARNT2 in the hippocampi of PSD rats, and to clarify the potential association between ARNT2 and behavioral performance. A PSD rat model was established by middle cerebral artery occlusion (MCAO) followed by a 4-week chronic unpredictable mild stress (CUMS) regimen. A sucrose preference test and open field test (OFT) were conducted, and body weight was measured. In addition, reverse transcription-polymerase chain reaction and immunohistochemistry were performed to measure ARNT expression. Results indicated that MCAO+CUMS rats had lower weight gain, consumed less sucrose and moved less compared with controls. Furthermore, the mRNA and protein levels of ARNT in MCAO+CUMS rats were increased compared with in controls. The sucrose preference index and horizontal movement distance in the OFT were positively correlated with ARNT mRNA level. Thus, from these findings it was suggested that ARNT2 may be positively associated with improvement of cognitive impairment, and therefore may be a potential target in PSD treatment.

Spark plasma sintering (SPS) tests were designed using the Taguchi method to create high‐performance composites consisting of 60 wt% TiB2, 30 wt% TiC, and 10 wt% Ti. The effects of SPS parameters on the microstructure and mechanical properties of TiB2‐TiC‐TiB composites were systematically investigated. Additionally, the evolution of phase and microstructure during the densification of the composites was analyzed in detail. It has been demonstrated that composites can achieve a high relative density of 99.8%, a hardness of 22.2 GPa, a strength of 739 MPa, and a fracture toughness of 7.07 MPa m1/2, as well as a dense structure and small grain size. These properties can be obtained by sintering at a temperature of 1500°C, a pressure of 50 MPa, and a holding time of 5 min. Sintering temperature is the primary factor that promotes the densification of the composite and influences its relative density, grain size, and morphology. Holding time and sintering pressure are relatively minor factors, but they play important roles at different stages of the sintering process.