Osteosarcoma (OS) is the most prevalent type of primary malignant bone cancer and currently lacks effective targeted treatments. Increasing evidence indicates that SOX2 overexpression is a primary driver of OS. By screening a small-molecule kinase inhibitor library, we identified AKT as a kinase essential for robust SOX2 expression in OS cells. AKT was found to be frequently overexpressed in OS and positively correlated with SOX2 protein levels. We demonstrated that AKT has no effect on SOX2 transcription but promotes SOX2 protein stability. Mechanistically, AKT binds to and phosphorylates SOX2 at T116, preventing SOX2 ubiquitination and proteasome-dependent degradation by ubiquitin E3 ligases UBR5 and STUB1. Moreover, we found that AKT-SOX2 axis is a significant modulator of cancer stemness and chemoresistance and that the combination of AKT inhibitor MK2206 and cisplatin resulted in a synergistic and potent inhibition of OS tumor growth in the PDX model. In conclusion, we identified a critical role for AKT in promoting SOX2 overexpression, tumor stemness, and chemoresistance in OS, and provided evidence that targeting AKT combined with chemotherapy may hold promise for treating refractory OS.

Accurate micro gas flow measurement is critical for medical ventilator calibration, environmental gas monitoring, and semiconductor manufacturing. Laminar flowmeters are widely employed in micro gas flow measurement applications owing to their inherent advantages of high linearity, the absence of moving components, and a broad measurement range. Nevertheless, due to the low measurement accuracy under micro gas flow caused by nonlinear errors and a relatively complex structure, traditional laminar flow measurement devices exhibit limitations in micro gas flow measurement scenarios. This study proposes a novel micro gas flow measurement method based on a single capillary laminar flow element, which simplifies the structure and enhances applicability in the field of micro gas flow. Through structural optimization with precise control of the capillary length–diameter ratios and theoretical error correction based on computational analysis, nonlinear errors were effectively reduced while improving the measurement accuracy in the field of micro gas flow. The proposed methodology was systematically validated through computational fluid dynamics simulations (ANSYS Fluent 2021 R1) and experimental investigations using a dedicated test platform. The experimental results show that the relative error of the measurement system within the full measurement range is less than ±0.6% (1–10 cm³/min; cm³/min means cubic centimeter per minute), and its accuracy is superior to 1% of reading (1% Rd) or 1.5% of reading (1.5% Rd) of conventional laminar flowmeters. The fitting curve of the flow rate versus the pressure difference derived from the measurement results maintains an excellent linear correlation (R² > 0.99), thus confirming that this method has practical application value in the field of micro gas flow measurement.

Francis turbine is a core energy conversion part and low frequency vibrations caused by unsteady vortex rope in the draft tube may damage the unit through resonance. Therefore, a more comprehensive assessment and monitoring of the status of Francis turbine is of great significance for unit stability. In this hydraulic machinery, mechanical impulses and hydraulic excitation are co-existing. The former manifests as a narrow low frequency band with high kurtosis, while the latter represents a wide high frequency band with energy associated with the vortex rope. Based on that, a novel method coined Convkurgram is proposed to suppress the extreme high kurtosis mechanical components and extract the hydraulic carrier wave efficiently. Besides, it takes multiple information frequency bands into consideration in case of contamination waves exist. Finally, the method is evaluated by means of actual vibration signals collected from the hydroelectric generating unit under normal and cavitation conditions. The results show the proposed method recognizes the characteristic frequency bands of mechanical components and hydraulic carriers as well as extracts the shaft frequency and blade passing frequency successfully.