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The drying process is a significant step in the manufacturing process of enteric hard capsules, which affects the physical and chemical properties of the capsules. Thus, the drying characteristics of plant-based enteric hard capsules were investigated at a constant air velocity of 2 m/s in a bench scale hot-air dryer under a temperature range of 25 to 45 °C and relative humidity of 40 to 80%. Results indicate that the drying process of the capsules mainly occur in a falling-rate period, implying that moisture transfer in the capsules is governed by internal moisture diffusion rate. High temperature and low relative humidity reduce drying time but increase the drying rate of the capsules. Investigation results of the mechanical properties and storage stability of the capsules, however, reveal that a fast drying rate leads to plant-based enteric hard capsules of low quality. Scanning electron microscopy further demonstrates that more layered cracks appear in capsules produced under a faster drying rate. The Page model yielded the best fit for describing thin-layer drying of the capsules based on the coefficient of determination and reduced chi-square. Moreover, it was established that the effective moisture diffusivity of the capsules increases with an increase in drying temperature or reduction in relative humidity.

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.

Using plant-based polysaccharide gels to produce hard capsules is a novel application of this technology in the medicinal field, which has garnered significant attention. However, the current manufacturing technology, particularly the drying process, limits its industrialization. The work herein employed an advanced measuring technique and a modified mathematical model to get more insight into the drying process of the capsule. Low field magnetic resonance imaging (LF-MRI) technique is adopted to reveal the distribution of moisture content in the capsule during drying. Furthermore, a modified mathematical model is developed by considering the dynamic variation of the effective moisture diffusivity (Deff) according to Fick’s second law, which enables accurate prediction of the moisture content of the capsule with a prediction accuracy of ±15%. The predicted Deff ranges from 3 × 10−10 to 7 × 10−10 m2·s−1, which has an irregular variation with a time extension. Moreover, as temperature increases or relative humidity decreases, there is an increased acceleration of moisture diffusion. The work provides a fundamental understanding of the drying process of the plant-based polysaccharide gel, which is crucial for enhancing the industrial preparation of the HPMC-based hard capsules.

The biological effects and regulatory mechanisms of low-dose and low-dose-rate radiation are still rather controversial. Therefore, in this study we investigated the effects of low-dose-rate radiation on zebrafish neurodevelopment and the role of miRNAs in radiation-induced neurodevelopment. Zebrafish embryos received prolonged gamma-ray irradiation (0 mGy/h, 0.1 mGy/h, 0.2 mGy/h, 0.4 mGy/h) during development. Neurodevelopmental indicators included mortality, malformation rate, swimming speed, as well as the morphology changes of the lateral line system and brain tissue. Additionally, spatiotemporal expression of development-related miRNAs (dre-miR-196a-5p, dre-miR-210-3p, dre-miR-338) and miRNA processing enzymes genes (Dicer and Drosha) were assessed by qRT-PCR and whole mount in situ hybridization (WISH). The results revealed a decline in mortality, malformation and swimming speed, with normal histological and morphological appearance, in zebrafish that received 0.1 mGy/h; however, increased mortality, malformation and swimming speed were observed, with pathological changes, in zebrafish that received 0.2 mGy/h and 0.4 mGy/h. The expression of miRNA processing enzyme genes was altered after irradiation, and miRNAs expression was downregulated in the 0.1 mGy/h group, and upregulated in the 0.2 mGy/h and 0.4 mGy/h groups. Furthermore, ectopic expression of dre-miR-210-3p, Dicer and Drosha was also observed in the 0.4 mGy/h group. In conclusion, the effect of low-dose and low-dose-rate radiation on neurodevelopment follows the threshold model, under the regulation of miRNAs, excitatory effects occurred at a dose rate of 0.1 mGy/h and toxic effects occurred at a dose rate of 0.2 mGy/h and 0.4 mGy/h.