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Neddylation, a type of protein post-translational modification that links the ubiquitin-like protein NEDD8 to substrate proteins, can be involved in various significant cellular processes and generate multiple biological effects. Currently, the best-characterized substrates of neddylation are the Cullin protein family, which is the core subunit of the Cullin-RING E3 ubiquitin ligase complex and controls many important biological processes by promoting ubiquitination and subsequent degradation of various key regulatory proteins. The normal or abnormal process of protein neddylation in the central nervous system can lead to a series of occurrences of normal functions and the development of diseases, providing an attractive, reasonable, and effective targeted therapeutic strategy. Therefore, this study reviews the phenomenon of neddylation in the central nervous system and summarizes the corresponding substrates. Finally, we provide a detailed description of neddylation involved in CNS diseases and treatment methods that may be used to regulate neddylation for the treatment of related diseases.

Secretory pathway kinase or kinase-like proteins (SPKKPs) are effective in the lumen of the endoplasmic reticulum (ER), Golgi apparatus (GA), and extracellular space. These proteins are involved in secretory signaling pathways and are distinctive from typical protein kinases. Various reports have shown that SPKKPs regulate the tumorigenesis and progression of human cancer via the phosphorylation of various substrates, which is essential in physiological and pathological processes. Emerging evidence has revealed that the expression of SPKKPs in human cancers is regulated by multiple factors. This review summarizes the current understanding of the contribution of SPKKPs in tumorigenesis and the progression of immunity. With the epidemic trend of immunotherapy, targeting SPKKPs may be a novel approach to anticancer therapy. This study briefly discusses the recent advances regarding SPKKPs.

A survey of mycotoxin contamination in feed commodities in China was performed and the regional differences of mycotoxin contamination in new season corn was assessed during January 2020–November 2020 in this research. 1,610 samples were analyzed for the major mycotoxins, namely aflatoxins, zearalenone (ZEN), trichothecenes type B, fumonisins (FUM), fusariotoxin T-2 (T-2) and ochratoxin A (OTA) using methods of liquid chromatography—tandem mass spectrometry and enzyme linked immunosorbent assay. Generally, aflatoxins occurred in 16% of all samples, and ZEN, trichothecenes type B and FUM were more prevalent with positive rates of 47, 72, and 63%, respectively. T2 and OTA were rarely detected. In new season corn, samples were also seriously contaminated with ZEN, trichothecenes type B, and FUM at positive rates of 47, 76, and 79%, respectively, and their averages of positives were 112, 735, and 3,811 μg/kg, respectively. The patterns of mycotoxin occurrence showed distinct regional trends in new season corn samples. Samples from Shandong province were highly contaminated with FUM, while special attention should be paid to aflatoxins in Anhui and Jiangsu provinces of East China. The contents of trichothecenes type B and ZEN from northern to southern provinces showed downward trends. In new season corm, co-occurrence of mycotoxins was widespread, and combinations of ZEN, trichothecenes type B, and FUM were frequently observed in this study. Trichothecenes type B and ZEN concentrations showed a positive correlation coefficient of 0.294, suggesting that toxicological interactions of these toxins deserve attention.

In this research, we performed a large-scale survey of mycotoxin contamination in several feed commodities and assessed regional differences in mycotoxin occurrence in maize across China in 2021. Concentrations of aflatoxins, zearalenone (ZEN), fumonisins, and trichothecenes type B were analyzed in 2,643 raw material and compound feed samples collected from eight provinces. Generally, trichothecenes type B, fumonisins, and ZEN were most prevalent and detected in averages of positive concentrations at 1,167, 1,623, and 204 μg/kg, respectively. In the new season maize, samples were also seriously infested with trichothecenes type B, fumonisins, and ZEN, and their averages of positive concentrations were 1,302, 2,518, and 225 μg/kg, respectively. Wheat was commonly contaminated with trichothecenes type B and ZEN, and the highest concentration levels of trichothecenes type B, fumonisins, and ZEN were all detected in the samples from maize by-products. Among the different geographical regions, distinct trends were observed in new season maize. Samples from Shandong province were highly contaminated with trichothecenes type B, fumonisins, and ZEN, while special attention should be paid to aflatoxins and fumonisins in Anhui and Jiangsu provinces in East China. In addition, the present survey showed that compound feeds and raw materials are commonly contaminated by multiple mycotoxins. Trichothecenes type B and ZEN concentrations were correlated significantly in this survey.

Diabetic neuropathic pain (DNP) and major depressive disorder (MDD) are common complications of diabetes mellitus and mutually affect each other. As a member of the ATP-gated ion channel family, P2X7 receptor is associated with the transduction of pain signal and the onset of depression. The aim of this study was to investigate the effects of dihydromyricetin (DHM) on rats with comorbid DNP and MDD. After the comorbid model was established, rat behavior changes were monitored by measuring the mechanical withdrawal threshold, thermal withdrawal latency, sugar water preference, immobility time in the forced-swim test, and open-field test parameters. The expressions of P2X7 receptor in the dorsal root ganglia (DRGs), spinal cord, and hippocampus were assessed by quantitative real-time PCR, Western blotting, and double immunofluorescence. We found that hyperalgesia, allodynia, and depressive behaviors of rats with comorbid DNP and MDD were relieved by treatment with DHM or application of a short-hairpin RNA for P2X7 receptor. The expression levels of P2X7, phosphorylated extracellular signal–regulated kinase 1/2, tumor necrosis factor α, and interleukin 1ß were increased in the DRGs, spinal cord, and hippocampus of rats in the model group but restored after DHM or P2X7 short-hairpin RNA treatment. In conclusion, P2X7 receptor in the DRGs, spinal cord, and hippocampus participates in the transduction of DNP and MDD signals. DHM seems to relieve comorbid DNP and MDD by reducing the expression of P2X7 receptor in the DRGs, spinal cord, and hippocampus and may be an effective new drug for the treatment of patients with both DNP and MDD.