Expressions of CXCL12/CXCR4 in Oral Premalignant and Malignant Lesions

Objective. The chemokine receptor CXCR4 and its ligand CXCL12 have been suggested to play important roles in the initiation or progression of cancers. The goal of the present study was to investigate alterations of CXCL12/CXCR4 in oral premalignant lesions and oral squamous cell carcinoma (OSCC). Methods. In 13 normal oral epithelia, 24 dysplastic oral leukoplakia (OLK), and 40 OSCC specimens, expressions of CXCL12 and CXCR4 were evaluated by immunohistochemistry. Results. CXCR4 was expressed in 37.5% of OLK and 60% of OSCC. CXCL12 was detected in 50% of OLK and 62.5% of OSCC. In OLK, CXCR4 positive ratio showed no significant difference from normal epithelia, but the CXCL12 positive ratio was significantly higher. Significant relationship between CXCL12 and CXCR4 was found both in OLK and OSCC. Conclusion. Our results indicated that CXCL12/CXCR4 axis may play roles from early steps of oral malignant transformation and contribute to the progress of oral carcinogenesis

Crosstalk of RNA methylation writers defines tumor microenvironment and alisertib resistance in breast cancer

BackgroundThe five major RNA methylation modifications (m6A, m1A, m6Am, m5C, and m7G) exert biological roles in tumorigenicity and immune response, mediated mainly by “writer” enzymes. Here, the prognostic values of the “writer” enzymes and the TCP1 role in drug resistance in breast cancer (BC) were explored for further therapeutic strategies.MethodsWe comprehensively characterized clinical, molecular, and genetic features of subtypes by consensus clustering. RNA methylation modification “Writers” and related genes_risk (RMW_risk) model for BC was constructed via a machine learning approach. Moreover, we performed a systematical analysis for characteristics of the tumor microenvironment (TME), alisertib sensitivity, and immunotherapy response. A series of experiments in vitro were carried out to assess the association of TCP1 with drug resistance.ResultsOne “writer” (RBM15B) and two related genes (TCP1 and ANKRD36) were identified for prognostic model construction, validated by GSE1456, GSE7390, and GSE20685 cohorts and our follow-up data. Based on the patterns of the genes related to prognosis, patients were classified into RMW_risk-high and RMW_risk-low subtypes. Lower RMW_Score was associated with better overall survival and the infiltration of immune cells such as memory B cells. Further analysis revealed that RMW_Score presented potential values in predicting drug sensitivity and response for chemo- and immunotherapy. In addition, TCP1 was confirmed to promote BC alisertib-resistant cell proliferation and migration in vitro.ConclusionRMW_Score could function as a robust biomarker for predicting BC patient survival and therapeutic benefits. This research revealed a potential TCP1 role regarding alisertib resistance in BC, providing new sights into more effective therapeutic plans

Dynamics Analysis of Unbalanced Motorized Spindles Supported on Ball Bearings

This paper presents an improved dynamic model for unbalanced high speed motorized spindles. The proposed model includes a Hertz contact force model which takes into the internal clearance and an unbalanced electromagnetic force model based on the energy of the air magnetic field. The nonlinear characteristic of the model is analysed by Lyapunov stability theory and numerical analysis to study the dynamic properties of the spindle system. Finally, a dynamic operating test is carried out on a DX100A-24000/20-type motorized spindle. The good agreement between the numerical solutions and the experimental data indicates that the proposed model is capable of accurately predicting the dynamic properties of motorized spindles. The influence of the unbalanced magnetic force on the system is studied, and the sensitivities of the system parameters to the critical speed of the system are obtained. These conclusions are useful for the dynamic design of high speed motorized spindles

Bearing Fault Feature Extraction Method Based on Enhanced Differential Product Weighted Morphological Filtering

Aimed at the problem of fault characteristic information bearing vibration signals being easily submerged in some background noise and harmonic interference, a new algorithm named enhanced differential product weighted morphological filtering (EDPWMF) is proposed for bearing fault feature extraction. In this method, an enhanced differential product weighted morphological operator (EDPWO) is first constructed by means of infusing the differential product operation and weighted operation into four basic combination morphological operators. Subsequently, aiming at the disadvantage of the parameter selection of the structuring element (SE) of EDPWO depending on artificial experience, an index named fault feature ratio (FFR) is employed to automatically determine the flat SE length of EDPWO and search for the optimal weighting correlation factors. The fault diagnosis results of simulation signals and experimental bearing fault signals show that the proposed method can effectively extract bearing fault feature information from raw bearing vibration signals containing noise interference. Moreover, the filtering result obtained by the proposed method is better than that of traditional morphological filtering methods (e.g., AVG, STH and EMDF) through comparative analysis. This study provides a reference value for the construction of advanced morphological analysis methods

The Effect of Heat Source Path on Thermal Evolution during Electro-Gas Welding of Thick Steel Plates

In recent years, the shipbuilding industry has experienced a growing demand for tighter control and higher strength requirements in thick steel plate welding. Electro-gas welding (EGW) is a high heat input welding method, widely used to improve the welding efficiency of thick plates. Modelling the EGW process of thick steel plates has been challenging due to difficulties in accurately depicting the heat source path movement. An EGW experiment on 30 mm thickness E36 steel plates was conducted in this study. A semi-ellipsoid heat source model was implemented, and its movement was mathematically expressed using linear, sinusoidal, or oscillate-stop paths. The geometry of welding joints, process variables, and steel composition are taken from industrial scale experiments. The resulting thermal evolutions across all heat source-path approaches were verified against experimental observations. Practical industrial recommendations are provided and discussed in terms of the fusion quality for E36 steel plates with a heat input of 157 kJ/cm. It was found that the oscillate-stop heat path predicts thermal profile more accurately than the sinusoidal function and linear heat path for EGW welding of 30 mm thickness and above. The linear heat path approach is recommended for E36 steel plate thickness up to 20 mm, whereas maximum thickness up to 30 mm is appropriate for sinusoidal path, and maximum thickness up to 35 mm is appropriate for oscillate-stop path in EGW welding, assuming constant heat input

Flavonoid extract Kushenol a exhibits anti‐proliferative activity in breast cancer cells via suppression of PI3K/AKT/mTOR pathway

Abstract Background Kushenol A is natural flavonoid extract discovered in recent years, with potential anti‐tumor activity. Its role in breast cancer is poorly understood. Methods To investigate biological function of Kushenol A in breast cancer (BC), Cell Counting Kit‐8 assay, colony formation assay, flow cytometry, western blotting, qPCR analysis, and xenograft mouse model were performed. Results We found that Kushenol A treatment reduced proliferative capability and induced G0/G1 phase cell cycle arrest and apoptosis of BC cells in a concentration‐dependent manner. Besides, Kushenol A treatment contributed to the upregulation of apoptosis‐related and cell cycle‐associated genes. In nude mice, Kushenol A administration repressed BC xenograft tumor growth. Mechanistically, phosphorylation levels of AKT and mTOR were markedly attenuated in Kushenol A‐treated BC cells; however, there were no significant differences in total AKT and mTOR expressions. Moreover, PI3K inhibitor combined with Kushenol A exhibited synergistic inhibitory activity on cell proliferation. Conclusions Taken together, our findings suggested that Kushenol A suppressed BC cell proliferation by modulating PI3K/AKT/mTOR signaling pathway. Kushenol A may be a promising therapeutic drug for treating BC

The Power Setting of Focused Ultrasound for the Palliative Treatment of Advanced Pancreatic Cancer: A Study in an Ex Vivo Bovine Liver

High-intensity focused ultrasound (HIFU) ablation has been widely used in advanced pancreatic cancer in recent years. In numerous studies, HIFU has been shown to be safe, effective, and practicable, but there are a few HIFU-related adverse effects. The patients’ discomfort during therapy increased proportionally with increasing delivered energy and pain levels seemed to be independent of the dose of anesthetic or sedation. If the power used in therapy is too high, the temperature of the target area will rise rapidly, and the boiling and cavitation make the shape of the necrosis area difficult to control. In recent years, moderate-intensity focused ultrasound (MIFU) has also been shown to heat the tumor locally for palliative treatment. Choosing the appropriate power and effectively controlling the tissue temperature until reaching the threshold for thermal necrosis are of great significance for ensuring the safety of palliative treatment. In this study, an infrared temperature measurement experimental system was set up to measure the temperature rise at different power in an ex vivo bovine liver. It was found that when the acoustic intensity of the focused ultrasound was lower than the cavitation threshold (within the range of the MIFU), the temperature of the tissue kept rising at a steady rate and could still reach the thermal damage threshold temperature within tens of seconds. The results showed that the temperature induced by the MIFU was almost entirely dependent on the thermal effect, and the temperature of the tissue at the end of sonication was linearly related to the power. Finally, this study considered the effect of blood perfusion on the temperature for the application of focused ultrasound in the palliative treatment of advanced pancreatic cancer with the goal of providing a reference for the application of focused ultrasound in the palliative treatment of advanced pancreatic cancer

Feasibility and efficacy of ultrasound-guided high-intensity focused ultrasound of breast fibroadenoma

AbstractObjective This nonrandomized prospective clinical trial aimed to assess the efficacy, safety and follow-up outcomes of ultrasound-guided high-intensity focused ultrasound (USgHIFU) surgery in patients with breast fibroadenoma.Methods With the approval of the institutional ethics committee and written informed consent, a total of 113 patients diagnosed with breast fibroadenoma by core-needle biopsy in our hospital were recruited. USgHIFU surgery was performed under local anesthesia. Contrast-enhanced ultrasound (CEUS) or contrast-enhanced MRI (CEMRI) was performed to evaluate the nonperfused volume (NPV). The patients were followed up with physical examination and ultrasound imaging.Results The clinical outcome of 85 patients with 147 fibroadenomas with a follow-up time of more than 3 months was analyzed in this study. Fifty-two patients had one lesion, twenty-one patients had two lesions and twelve patients had more than two lesions. During USgHIFU, the median localization time for all fibroadenomas was 3 (interquartile range: 1, 5) min, and the median treatment time was 9 (interquartile range: 5, 15) min. Under local anesthesia, all the patients tolerated the treatment well. No serious epidermal burns were observed in any of the patients. Based on CEUS or CEMRI imaging evaluation, the median NPV ratio was 100% (interquartile range: 79.2%, 116.8%). The VRR were 26.77 ± 50.05%, 50.22 ± 42.01% and 72.74 ± 35.39% at 3–6 months, 6–12 months and >12 months, respectively, which showed significant statistical difference (p < .001).Conclusion Ultrasound-guided HIFU surgery is an effective and safe noninvasive alternative technique for the treatment of breast fibroadenoma

Sigma‐1 receptor attenuates osteoclastogenesis by promoting ER‐associated degradation of SERCA2

Abstract Sigma‐1 receptor (Sigmar1) is a specific chaperone located in the mitochondria‐associated endoplasmic reticulum membrane (MAM) and plays a role in several physiological processes. However, the role of Sigmar1 in bone homeostasis remains unknown. Here, we show that mice lacking Sigmar1 exhibited severe osteoporosis in an ovariectomized model. In contrast, overexpression of Sigmar1 locally alleviated the osteoporosis phenotype. Treatment with Sigmar1 agonists impaired both human and mice osteoclast formation in vitro. Mechanistically, SERCA2 was identified to interact with Sigmar1 based on the immunoprecipitation‐mass spectrum (IP‐MS) and co‐immunoprecipitation (co‐IP) assays, and Q615 of SERCA2 was confirmed to be the critical residue for their binding. Furthermore, Sigmar1 promoted SERCA2 degradation through Hrd1/Sel1L‐dependent ER‐associated degradation (ERAD). Ubiquitination of SERCA2 at K460 and K541 was responsible for its proteasomal degradation. Consequently, inhibition of SERCA2 impeded Sigmar1 deficiency enhanced osteoclastogenesis. Moreover, we found that dimemorfan, an FDA‐approved Sigmar1 agonist, effectively rescued bone mass in various established bone‐loss models. In conclusion, Sigmar1 is a negative regulator of osteoclastogenesis, and activation of Sigmar1 by dimemorfan may be a potential treatment for osteoporosis in clinical practice