SPAG5 deficiency activates autophagy to reduce atherosclerotic plaque formation in ApoE-/- mice.

BACKGROUND: Autophagy, as a regulator of cell survival, plays an important role in atherosclerosis (AS). Sperm associated antigen 5 (SPAG5) is closely associated with the classical autophagy pathway, PI3K/Akt/mTOR signaling pathway. This work attempted to investigate whether SPAG5 can affect AS development by regulating autophagy. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low density lipoprotein (ox-LDL) to induce cell damage. ApoE-/- mice were fed a Western diet to establish an AS mouse model. Haematoxylin and eosin (H&E) staining and Oil Red O staining evaluated the pathological changes and in lipid deposition in aortic tissues. CCK-8 and flow cytometry detected cell proliferation and apoptosis. Immunohistochemistry, Enzyme linked immunosorbent assay, qRT-PCR and western blotting assessed the levels of mRNA and proteins. RESULTS: Ox-LDL treatment elevated SPAG5 expression and the expression of autophagy-related proteins, LC3-I, LC3-II, Beclin-1, and p62, in HUVECs. GFP-LC3 dots were increased in ox-LDL-treated HUVECs and LPS-treated HUVECs. SPAG5 knockdown reversed both ox-LDL and LPS treatment-mediated inhibition of cell proliferation and promotion of apoptosis in HUVECs. SPAG5 silencing further elevated autophagy and repressed the expression of PI3K, p-Akt/Akt, and p-mTOR/mTOR in ox-LDL-treated HUVECs. 3-MA (autophagy inhibitor) treatment reversed SPAG5 silencing-mediated increase of cell proliferation and decrease of apoptosis in ox-LDL-treated HUVECs. In vivo, SPAG5 knockdown reduced atherosclerotic plaques in AS mice through activating autophagy and inhibiting PI3K/Akt/mTOR signaling pathway. CONCLUSION: This work demonstrated that SPAG5 knockdown alleviated AS development through activating autophagy. Thus, SPAG5 may be a potential target for AS therapy.

General Model for Predicting Response of Gas-Sensitive Materials to Target Gas Based on Machine Learning.

Gas sensors play a crucial role in various industries and applications. In recent years, there has been an increasing demand for gas sensors in society. However, the current method for screening gas-sensitive materials is time-, energy-, and cost-consuming. Consequently, an imperative exists to enhance the screening efficiency. In this study, we proposed a collaborative screening strategy through integration of density functional theory and machine learning. Taking zinc oxide (ZnO) as an example, the responsiveness of ZnO to the target gas was determined quickly on the basis of the changes in the electronic state and structure before and after gas adsorption. In this work, the adsorption energy and electronic and structural characteristics of ZnO after adsorbing 24 kinds of gases were calculated. These computed features served as the basis for training a machine learning model. Subsequently, various machine learning and evaluation algorithms were utilized to train the fast screening model. The importance of feature values was evaluated by the AdaBoost, Random Forest, and Extra Trees models. Specifically, charge transfer was assigned importance values of 0.160, 0.127, and 0.122, respectively, ranking as the highest among the 11 features. Following closely was the d-band center, which was presumed to exert influence on electrical conductivity and, consequently, adsorption properties. With 5-fold cross-validation using the Extra Tree accuracy, the 24-sample data set achieved an accuracy of 88%. The 72-sample data set achieved an accuracy of 78% using multilayer perceptron after 5-fold cross-validation, with both data sets exhibiting low standard deviations. This verified the accuracy and reliability of the strategy, showcasing its potential for rapidly screening a material's responsiveness to the target gas.

Clinicopathological analysis of 18 cases of secretory carcinoma of the salivary glands.

Background/purpose: Secretory carcinoma (SC) is a rare salivary gland tumor that featured by ETV6::NTRK3 gene fusion, and was included in the WHO Classification of Head and Neck Tumors since 2017. Nevertheless, the description of SCs by WHO is still vague. This study examined 18 SC cases by using both histomorphology and molecular pathology for diagnostic determination, especially immunohistochemical features of SCs. Materials and methods: Based on WHO characteristics, 18 patients with SC admitted between 2001 and 2022 were included in this study. Main histomorphological patterns, FISH analyses of the ETV6::NTRK3 gene fusion, and immunohistochemical analyses of S100, mammaglobin, DOG1, ADFP, CA6 and Ki-67 were performed. Results: Among the 18 SC patients, the median age of onset was 39.22 years. Grossly, the average tumor size in 2.96 cm with various texture from soft to tough. The majority patients were positive for S100, mammaglobin, and negative for DOG1, except for one patient negative for S100 (Case 18). All patients were positive for ADFP, and the majority patients were negative for CA6, except for Case 9. Two cases were found recurrence, and the tumor were found both in parotid gland with local invasion. Conclusion: Combined with the results of previous studies, we proposed that the combination of all five markers, S100, mammaglobin, DOG1, ADFP and CA6, could contribute more to differential diagnosis of SCs with other salivary carcinomas, especially with AciCC. The prognosis of SCs is optimistic in most cases, but larger patient cohort and long-term follow-up are still needed.

The clinical implication and translational research of OSCC differentiation.

BACKGROUND: The clinical value and molecular characteristics of tumor differentiation in oral squamous cell carcinoma (OSCC) remain unclear. There is a lack of a related molecular classification prediction system based on pathological images for precision medicine. METHODS: Integration of epidemiology, genomics, experiments, and deep learning to clarify the clinical value and molecular characteristics, and develop a novel OSCC molecular classification prediction system. RESULTS: Large-scale epidemiology data (n = 118,817) demonstrated OSCC differentiation was a significant prognosis indicator (p < 0.001), and well-differentiated OSCC was more chemo-resistant than poorly differentiated OSCC. These results were confirmed in the TCGA database and in vitro. Furthermore, we found chemo-resistant related pathways and cell cycle-related pathways were up-regulated in well- and poorly differentiated OSCC, respectively. Based on the characteristics of OSCC differentiation, a molecular grade of OSCC was obtained and combined with pathological images to establish a novel prediction system through deep learning, named ShuffleNetV2-based Molecular Grade of OSCC (SMGO). Importantly, our independent multi-center cohort of OSCC (n = 340) confirmed the high accuracy of SMGO. CONCLUSIONS: OSCC differentiation was a significant indicator of prognosis and chemotherapy selection. Importantly, SMGO could be an indispensable reference for OSCC differentiation and assist the decision-making of chemotherapy.

Carcinosarcoma of the deep lobe of the parotid gland in the parapharyngeal region: A case report.

BACKGROUND: Salivary carcinosarcoma is an extremely rare tumor containing both malignant epithelial and mesenchymal constituents. This article reports a rare case of carcinosarcoma with salivary duct carcinoma and osteosarcoma as the tumor components. The clinicopathological characteristics, treatment, and prognosis are discussed in conjunction with the literature. CASE SUMMARY: A 48-year-old man presented with a complaint of a mass in the right parotid region. Osteosarcoma was first considered for assessment by fine-needle aspiration cytology. Physical examination revealed a mass measuring approximately 4 cm × 3.5 cm × 3 cm. The mass, the whole lobe of the right parotid gland, and the right mandible were completely removed during surgery. Postoperative histopathology confirmed carcinosarcoma of the salivary gland. CONCLUSION: A definite diagnosis of salivary gland carcinosarcoma can only be obtained after complete surgical resection.

TIM-3/Galectin-9 and CD160 expression in salivary adenoid cystic carcinoma.

OBJECTIVE: Investigating T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), Galectin 9 (Gal-9), CD160 expression and tumor-infiltrating lymphocytes (TILs) and correlation with clinicopathological characteristics of salivary adenoid cystic carcinoma (SACC). METHODS: Sixty cases of SACC were detected by immunohistochemical staining to evaluate TIM-3, Gal-9, and CD160 expression and analyze the correlation between TIM-3, Gal-9, CD160 expression and clinicopathologic features by rank-sum test. The association of TILs with TIM-3, Gal-9, and CD160 expression in SACC stromal was done by Chi-square test. RESULTS: TIM-3 and CD160 overexpression were correlated with recurrence of SACC (p = 0.029, p = 0.007, respectively). High Gal-9 expression was correlated with pathological classification (p = 0.018). The average percentage of TILs was 18.2% in SACC and most of TILs were more likely to occur in minor salivary glands (p = 0.038). Pairwise positive correlations were observed between the expression of TIM-3, Gal-9, and CD160 in tumor cells as well as in TILs, respectively. CONCLUSION: Low density of TILs was characteristic of the SACC microenvironment, with upregulation of TIM-3, Gal-9, and CD160 all occurring. However, TIM-3, Gal-9, and CD160 expression in the stromal dependent on the number of TILs represent potential therapeutic targets in SACC.

Transcription factor-target gene regulatory network analysis in human lung adenocarcinoma.

Background: Transcription factors (TFs) play a crucial role in the occurrence and progression of lung adenocarcinoma (LUAD), and targeting TFs is an important direction for treating LUAD. However, targeting a single TF often fails to achieve satisfactory therapeutic outcomes. Furthermore, the regulatory TF-target gene networks involved in the development of LUAD is complex and not yet fully understood. Methods: In this study, we performed RNA sequencing (RNA-seq) to analyze the transcriptome profile of human LUAD tissues and matched adjacent nontumor tissues. We selected the differentially expressed TFs, performed enrichment analysis and survival curve analysis, and predicted the regulatory networks of the top differential TFs with their target genes. Finally, alternative splicing analyses were also performed. Results: We found that TFs GRHL3, SIX1, SIX2, SPDEF, and ETV4 were upregulated, while TAL1, EPAS1, SOX17, NR4A1, and EGR3 were significantly downregulated in LUAD tissues compared to normal tissues. We propose a potential GRHL3-CDH15-Wnt-ß-catenin pro-oncogenic signaling axis and a potential TAL1-ADAMTS1-vascular antioncogenic signaling axis. In addition, we found that alternative splicing of intron retention (IR), approximate IR (XIR), multi-IR (MIR), approximate MIR (XMIR), and approximate alternative exon ends (XAE) showed abnormally increased frequencies in LUAD tissues. Conclusions: These findings revealed a novel TF-target gene regulatory axis related to tumorigenesis and provided potential therapeutic targets and mechanisms for LUAD.

Primordial odontogenic tumour: a case report.

Odontogenic primary tumor is a rare benign odontogenic tumor in the maxillofacial area. A case of odontogenic primary basal tumor is reported. The clinicopathological features and treatment principles are discussed in the literature.

Expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia and leukoplakia cancerization with spicy diet in Chengdu.

OBJECTIVES: To investigate the expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia (OLK) and OLK cancerization who have aspicy diet in Chengdu. METHODS: Thirtypatients with OLK andspicy diet and 15 patients with OLK without spicy diet in Chengdu were divided into three groups: hyperplastic OLK (OLK-), OLK with mild to moderate dysplasia (OLK+), and severe dysplastic  OLK or oral squamous cell carcinoma (OSCC) transforming from OLK (OLK++/OSCC). The expression of Ki-67, Cyclin D1, P53, and P16 were detected by immunohistochemistry and statistically analyzed. RESULTS: The expression of Ki-67 and P53 in patients with or without spicy diet in the OLK+and OLK++/OSCC groups were stronger than that of the OLK- group (P<0.05). The OLK++/OSCC group showed a higher expression of Cyclin D1 and lower expression of P16 than the OLK- group (P<0.05). The expression of Ki-67, Cyclin D1, P53, and P16 in patients with spicy diet and without spicy diet had no substantial difference. The expression of Ki-67 and Cyclin D1 showed a positive correlation (r=0.439, P=0.015). CONCLUSIONS: Spicy diet did not have an influence on the expression of Ki-67, Cyclin D1, P53, and P16 in patients with OLK and OSCC. The expression of Ki-67, Cyclin D1, and P53 increased with the development of OLK, whereas P16 showed opposite expression trend.