Abnormal downregulation of 10‐formyltetrahydrofolate dehydrogenase promotes the progression of oral squamous cell carcinoma by activating PI3K/Akt/Rb pathway

Abstract Background 10‐formyltetrahydrofolate dehydrogenase (ALDH1L1) is a major folate enzyme, which is usually underexpressed in malignant tumors and competes with tumors for the same folate substrate. However, the specific role and mechanisms of ALDH1L1 in oral squamous cell carcinoma (OSCC) remainsobscure. Methods The expression level of ALDH1L1 in paired OSCC tissues and adjacent noncancerous tissues were detected by quantitative realtime PCR, Western blot and immunohistochemistry. The relationship between ALDH1L1 expression and clinical characteristics was analyzed. Besides, CCK8, EdU staining, colony formation, wound healing, transwell invasion, apoptosis, cell cycle assays and nude mice tumor bearing experiments were employed to assess the role of ALDH1L1 in OSCC. To explore the underlying mechanisms of these effects, cell cycle‐related markers were examined. Results In this study, we revealed that ALDH1L1 expression was significantly reduced in OSCC, and its downregulation was associated with the malignancy of the tumor and poor prognosis of patients. In vivo and in vitro experiments, downregulation of ALDH1L1 in OSCC significantly inhibited the occurrence of NADP+‐dependent catalytic reactions and facilitated tumor cell growth, migration, invasion, survival, cell cycle progression, and xenograft tumor growth. On the contrary, re‐expression of ALDH1L1 plays a similar role to anti‐folate therapy, promoting NADPH production and suppressing the progression of OSCC. Furthermore, ALDH1L1 overexpressing obviously inhibited the expression of PI3K, p‐Akt, CDK2, CDK6, Cyclin D1, Cyclin D3, and Rb in OSCC cells, and promoted the expression of p27. LY294002 and 740 Y‐P were used to confirm the inhibitory effects of ALDH1L1 on OSCC progression through PI3K/Akt/Rb pathway. Conclusion Our findings highlight the clinical value of ALDH1L1 as a prognostic marker and the potential of a new target for anti‐folate therapy

Knowledge of Chinese dentists on HPV, their willingness and barriers to recommend HPV vaccination to patients

Objective: This study aimed to assess the knowledge of Chinese dentists on human papilloma virus (HPV), their willingness and factors prevention them from recommending patients for HPV vaccination, and to identify ways through which dentists can acquire HPV-related knowledge. Methods: This was a cross-sectional study based on Chinese dentists. The anonymous self-filled questionnaire method was used to collect demographic information of participants, their knowledge of HPV, willingness and barriers to recommending HPV vaccines to patients, and the strategies they can adopt to obtain HPV-related knowledge. Results: A total of 517 dentists completed the questionnaire, and 89.94% of dentists were willing to recommend HPV vaccination to patients. Participants aged 30–39 years, male dentists and dentist-in-charge had relatively lower knowledge scores than other groups. Besides, participants aged 30–39 years, working in private hospitals, and practicing in Southern China had a lower willingness to recommend HPV vaccination to patients. Recommending HPV vaccination to patients is not within the scope of practicing dentists, and concerns about the safety of the HPV vaccine were found to be the main barriers preventing its recommendation. Notably, 97.87% of dentists were eager to acquire HPV-related knowledge, and agreed for the first time to enroll in relevant educational courses. Conclusion: Chinese dentists had expressed a strong desire to recommend HPV vaccines to patients, even though their knowledge of HPV was scanty. Therefore, measures to improve their understanding of HPV vaccines and eliminate barriers suppressing their willingness to recommend HPV vaccines are urgently needed

Nonlinear vibration analysis of fiber reinforced composite cylindrical shells with partial constrained layer damping treatment

This research proposes a novel analytical model capable of accurately predicting the strain-dependent characteristics of fiber reinforced composite shells (FRCSs) with partial constrained layer damping (CLD) treatment by considering the nonlinearities of fiber reinforced composite and viscoelastic materials simultaneously. The nonlinear material properties are represented based on Jones-Nelson nonlinear theory, energy-based strain energy method, and complex modulus method. Then, the governing equations of motion for FRCSs are developed via Ritz method, and the identification procedure of nonlinear fitting parameters is also presented. By taking a T300 carbon fiber/epoxy resin cylindrical shell with partial CLD patches as an example, a series of experiments are carried out to validate the proposed modeling approach. Finally, the effects of material properties on nonlinear vibration behaviors of FRCSs covered with partial CLD patches are evaluated. Comparisons show that the proposed nonlinear model is more accuracy than that without considering strain dependence, where the maximum errors between the proposed model and measured data for natural frequencies, damping ratios and resonant response are 6.9%, 11.3%, and 11.2%, respectively.</p