Cinnamaldehyde causes developmental neurotoxicity in zebrafish via the oxidative stress pathway that is rescued by astaxanthin.

Toxicology studies provide a reliable dose range for the use of compounds. Zebrafish show unique advantages in toxicology research. Cinnamaldehyde (Cin) is one of the main active compounds isolated from Cinnamon trees and other species of the genus Cinnamomum. In this study, we investigated the developmental neurotoxicity of cinnamaldehyde in zebrafish and preliminarily explored its underlying mechanism. Cinnamaldehyde causes developmental neurotoxicity in zebrafish, as evidenced by the damage to ventricular structures, eye malformations, shortened body length, trunk curvature, decreased neuronal fluorescence, and pericardial oedema. Moreover, it can induce abnormal behaviour and gene expression in zebrafish. After treatment with the oxidative stress inhibitor astaxanthin, the behaviour and abnormal gene expression were reversed. All of these data demonstrated that the developmental neurotoxicity of cinnamaldehyde might be attributed to oxidative stress. In addition, this study also confirmed that zebrafish is a reliable model for toxicity studies.

TMT-based quantitative proteomics analysis reveals the role of Notch signaling in FAdV-4-infected LMH cell.

Fowl adenovirus serotype 4 (FAdV-4) is recognized as a pathogen that causes hydropericardium syndrome. Irrespective of the pathway used by the virus to invade the chicken, the pathological characteristics of the disease include degeneration and necrosis of hepatocytes, formation of intranuclear inclusions, as well as inflammatory cell infiltration. Liver dysfunction constitutes one of the critical factors leading to death. Therefore, it is vital to investigate the virus-mediated severe pathological liver damage to further understand the pathogenesis of FAdV-4. Here, proteomics, a tandem mass tag (TMT)-based approach to directly analyze protein expression, was used to determine the protein expression during FAdV-4 proliferation in leghorn male hepatoma (LMH) cells. We identified 177 differentially expressed proteins associated with various biological processes and pathways. The functional enrichment analysis revealed that FAdV-4 could downregulate some signaling pathways in LMH cells, including NOD-like receptor signaling, RIG-I-like receptor signaling, NF-κB signaling, TNF signaling pathway, and Notch signaling, FoxO signaling, PI3K-Akt signaling, and autophagy. The results of proteomics screening suggested an association between FAdV-4 infection and Notch signaling in LMH in vitro, indicating that Notch signaling regulated the expression of inflammatory cytokines and interferons but not viral replication in LMH cells. These data contributed to the understanding of the immunopathogenesis and inflammopathogenesis of FAdV-4 infection and also provided valuable information for the further analysis of the molecular mechanisms underlying viral pathogenesis.

Association analysis of risk genes identified by SCHEMA with schizophrenia in the Chinese Han population.

BACKGROUND: Schizophrenia is a chronic brain disorder. Previously, the Schizophrenia Exome Sequencing Meta-analysis consortium identified 10 highest risk genes related to schizophrenia. This study aimed to analyze the relationship between the 10 highest risk genes identified by the SCHEMA and schizophrenia in a Chinese population. METHODS: A total of 225 variants in 10 genes were screened in a Chinese population of 6836 using a customized array. All variants were annotated through the Variant Effect Predictor tool, and the functional impacts of missense variants were assessed based on sorting intolerant from tolerant and PolyPhen-2 scores. The SHEsisPlus tool was used to analyze the association between risk genes and schizophrenia at the locus and gene levels. RESULTS: At the locus level, no missense variants significantly related to schizophrenia were found, but we detected three missense variants that appeared only in cases, including TRIO p. Arg1185Gln, RB1CC1 p. Arg1514Cys, and HERC1 p. Val4517Leu. At the gene level, five genes (TRIO, RB1CC1, HERC1, GRIN2A, and CACAN1G) with more than one variant analyzed were kept for the gene-level association analysis. Only the association between RB1CC1 and schizophrenia reached a significant level (OR = 1.634; 95% CI, 1.062-2.516; P = 0.025). CONCLUSION: In this study, we determined that RB1CC1 might be a risk gene for schizophrenia in the Chinese population. Our results provide new evidence for recognizing the correlation of these risk genes with the Chinese schizophrenia population.

FAdV-4 induce autophagy via the endoplasmic reticulum stress-related unfolded protein response.

Hydropericardium syndrome caused by the fowl adenovirus serotype 4 (FAdV-4) is prevalent disease in China with a high mortality rate. Many studies have demonstrated some viral infections to induce stress in the endoplasmic reticulum (ER). When the ER stress exceeds or persists, it activates autophagy, eventually triggering the onset of diseases. However, no report has ever stated FAdV-4 infection to induce ER stress-mediated autophagy. Previous studies have identified FAdV-4 infection in triggering autophagy in the hepatocytes; however, the underlying mechanism of this induction remains unknown. This study investigated the mechanism of ER stress-mediated autophagy induced by FAdV-4 infection. Here, ER stress was found to be triggered by FAdV-4 infection, as evident from the increased expression of the ER stress marker glucose-regulated protein 78, and the dilated morphology of the ER. Three pathways linked with the unfolded protein response (UPR) were found to be triggered in the hepatocellular carcinoma cell line, which included the PKR-like ER protein kinase (PERK), transcription factor 6, and inositol-requiring enzyme 1 (IRE1) pathways, respectively. Additionally, our results demonstrated that autophagy is involved in the PERK-eukaryotic initiation factor 2 subunit - C/EBP homologous protein and IRE1-c-Jun-N-terminal kinase pathways. Furthermore, treatment with the small interfering RNAs, or specific chemical inhibitors for the two pathways were found to reduce the interfering activity and could suppress the FAdV-4 replication. Collectively, these results developed new insight into the mechanisms of FAdV-4-induced autophagy by activating the ER stress-related UPR pathway and provided the experimental bases and novel ideas for developing antiviral drugs.

A Combined Tie-Fastening Method for the Reusable Surgical Gown with Two Neck Tie Belts to Improve Wearing Comfort.

The reusable surgical gowns made of slippery materials have the tendency to slip down as they are being worn. The rear neck tie(s) can sometimes loosen, and this causes the surgical gown to slip down somewhat, making the surgical staff members feel uncomfortable. If the gowns have two rear neck ties with a tendency of loosening and allowing the gowns to slip down, the surgical staff members feel more uncomfortable when there is only one tie loosening but the other tie is tethering. To fasten the neck ties of the surgical gown with two neck tie belts, we propose a simplified method of fastening the two sets of tie belts together as one tie, instead of fastening them separately. The object of this study is to evaluate this combined tying method for its ability to secure the gown and its wearing comfort. We enrolled five volunteers to evaluate the tie loosening condition of the reusable surgical gowns with two sets of rear neck tie belts after a series of upper limb motion exercises while wearing and not wearing the X-ray protective apron beneath the gown. The amount of uppermost rear neck cloth edge separation was recorded before and after the exercise. We also evaluated the wearing comfort of five enrolled operating surgeons for comparing the original and this modified tying method while wearing and not wearing the X-ray protective apron. In the results, we found that combined tying tends to have significantly more rear gown separation (0.94 cm) than separate tying (0.27 cm) after vigorous upper extremities exercise. However, during the actual performance of the surgeries, the rear neck tie(s) loosening and wearing discomfort of the combined tying method was significantly less than using the separate tying method (loosening: 0% vs. 30%) (discomfort: 0% vs. 35%) while the X-ray protective apron was not worn. For reusable surgical gowns that have two rear neck ties, we suggest the two sets of rear neck ties could be fastened together as one combined tie in routine surgical practice. With this, tying could be performed easier and faster, and wearing comfort could be improved.

Extra-articular Corrective Osteotomy With Bone Grafting to Achieve Lengthening and Regain Alignment for Distal Radius Fracture Malunion.

Surgical correction of the distal radius fracture malunion is challenging because of the 3-dimensional deformity. We propose a method by using the Kapandji intrafocal pinning in corrective osteotomy for treatment of the distal radius fracture malunion to facilitate the alignment correction while using the bone graft to restore the radial length. The surgery was started with the osteotomy from a volar approach, and the osteotomy gap was expanded gradually. Then, allobone grafting was performed to maintain the corrected radial length. We used the Kapandji intrafocal pinning dorsally to provide dorsal supporting force and radially to correct the radial inclination. Finally, a volar plate was used to buttress and push the distal fragment to fit as to regain the correct volar tilt. We enrolled 10 patients of distal radius fracture malunion with a mean age of 59.3 years. All patients had bone healing within 3 months after surgery. The mean lengthened distance was 5 mm. The radial inclination and volar tilt could be corrected with improved functional results.