Brassinin Promotes the Degradation of Tie2 and FGFR1 in Endothelial Cells and Inhibits Triple-Negative Breast Cancer Angiogenesis

Brassinin, a phytoalexin derived from cruciferous vegetables, has been reported to exhibit anti-cancer activity in multiple cancer types. However, its effects on triple-negative breast cancer (TNBC) development and the underlying mechanisms have not been elucidated so far. In this study, we demonstrated in vitro that brassinin preferentially reduces the viability of endothelial cells (ECs) when compared to other cell types of the tumor microenvironment, including TNBC cells, pericytes, and fibroblasts. Moreover, brassinin at non-cytotoxic doses significantly suppressed the proliferation, migration, tube formation, and spheroid sprouting of ECs. It also efficiently inhibited angiogenesis in an ex-vivo aortic ring assay and an in-vivo Matrigel plug assay. Daily intraperitoneal injection of brassinin significantly reduced tumor size, microvessel density, as well as the perfusion of tumor microvessels in a dorsal skinfold chamber model of TNBC. Mechanistic analyses showed that brassinin selectively stimulates the degradation of Tie2 and fibroblast growth factor receptor 1 in ECs, leading to the down-regulation of the AKT and extracellular signal-regulated kinase pathways. These findings demonstrate a preferential and potent anti-angiogenic activity of brassinin, which may be the main mechanism of its anti-tumor action. Accordingly, this phytochemical represents a promising candidate for the future anti-angiogenic treatment of TNBC

Application of generalized equivalent uniform dose optimization in the treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy

Background and purpose: In the design of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma, the traditional dose-volume (DV) physical optimization method is compared with the combined use of the DV physical optimization method and the generalized equivalent uniform dose (gEUD) optimization. This study aimed to investigate dosimetry differences in radiotherapy planning for nasopharyngeal carcinoma using gEUD method, to explore the effect of different optimization methods on the protection of organ at risk (OAR) in IMRT planning. Methods: Fifty patients with nasopharyngeal carcinoma in Eye & ENT Hospital of Fudan University from 2019 to 2021 were randomly selected, and two optimization plans were used for each case at the same time for optimization calculation. Group A used the traditional DV physical optimization method, while group B combined DV optimization and gEUD optimization methods adopted, in which gEUD was selected as a=1, 2, 5, 10 and 20. We evaluated the results of OAR dose data obtained by using different optimization schemes and different a values. Results: The planned data of the two plans were compared and analyzed, and there was no statistically significant difference in the dosimetry index of the target area between groups (P>0.05). However, in terms of the protection of the parotid gland and oral cavity, the results of the optimization plan of group B were significantly better compared with group A. The a value of gEUD had more obvious influence on the average dose of the parotid gland and the oral cavity. Conclusion: In the radiotherapy plan for nasopharyngeal carcinoma, the combined use of physical optimization and biological optimization can not only meet the target dose requirements but also better protect the parotid gland, oral cavity and other endangered OAR

MicroRNAs in Tumor Endothelial Cells: Regulation, Function and Therapeutic Applications

Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an upto-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies

Clinical Findings in Patients With Persistent Positional Nystagmus: The Designation of “Heavy and Light Cupula”

Objective: Direction-changing positional nystagmus (DCPN) had been observed as persistent horizontal apogeotropic and was considered as “cupulolithiasis or heavy cupula. ” Recently, the concept of “light cupula” exhibiting persistent geotropic DCPN has been introduced. However, the light cupula is not systematically described, while the identification and diagnosis of “light cupula” should be improved. Here we investigated the underlying characteristics and therapeutic options designed to the “light” and “heavy” cupula, respectively; and summarized the clinical characteristics and therapeutic effect in the two groups.Methods: A total of 359 cases with vertigo and bilateral DCPN were found in the supine roll test. Only 25 patients with persistent DCPN were enrolled and followed up. According to the direction of nystagmus, we further divided the patients into “heavy cupula” (apogeotropic) and “light cupula” (geotropic) groups. We compared the incidence, characteristics of nystagmus and the efficacy of repositioning maneuver in the two groups.Results: Nine patients with persistent horizontal geotropic DCPN were confirmed as “light cupula,” other 16 patients with persistent horizontal ageotropic DCPN were confirmed as heavy cupula. All 25 patients had null plane; the mean value and standard deviation of the null plane in light cupula and heavy cupula was 25.67 ± 9.31° and 27.06 ± 6.29°, respectively. The mean value and standard deviation of the termination plane in light cupula was 28.78 ± 10.00°, and 30.25 ± 6.53° in heavy cupula. There was no statistical significance between the two groups. We found that the direction of evoked nystagmus in the supine position was toward the intact side in light cupula, while in heavy cupula, it was toward the lesion side. The null plane appeared on the lesion side. For light cupula patients, the effect was not obvious at Day-7 after the treatment, however, treatment for most heavy cupula patients were effective. All patients recovered after 30 days of treatment.Conclusion: The null plane is crucial in determining the lesion side for light or heavy cupula. Although the short-term therapeutic effect of the light cupula is not as promising as the effect seen in heavy cupula, the long-term prognosis in both groups is comparable; with all patients recovered after 30 days of treatment.Study design: This is a retrospective cohort study

Morphological changes in the cerebellum during aging: evidence from convolutional neural networks and shape analysis

The morphology and function of the cerebellum are associated with various developmental disorders and healthy aging. Changes in cerebellar morphology during the aging process have been extensively investigated, with most studies focusing on changes in cerebellar regional volume. The volumetric method has been used to quantitatively demonstrate the decrease in the cerebellar volume with age, but it has certain limitations in visually presenting the morphological changes of cerebellar atrophy from a three-dimensional perspective. Thus, we comprehensively described cerebellar morphological changes during aging through volume measurements of subregions and shape analysis. This study included 553 healthy participants aged 20–80 years. A novel cerebellar localized segmentation algorithm based on convolutional neural networks was utilized to analyze the volume of subregions, followed by shape analysis for localized atrophy assessment based on the cerebellar thickness. The results indicated that out of the 28 subregions in the absolute volume of the cerebellum, 15 exhibited significant aging trends, and 16 exhibited significant sex differences. Regarding the analysis of relative volume, only 11 out of the 28 subregions of the cerebellum exhibited significant aging trends, and 4 exhibited significant sex differences. The results of the shape analysis revealed region-specific atrophy of the cerebellum with increasing age. Regions displaying more significant atrophy were predominantly located in the vermis, the lateral portions of bilateral cerebellar hemispheres, lobules I-III, and the medial portions of the posterior lobe. This atrophy differed between sexes. Men exhibited slightly more severe atrophy than women in most of the cerebellar regions. Our study provides a comprehensive perspective for observing cerebellar atrophy during the aging process

Research on Energy Hierarchical Management and Optimal Control of Compound Power Electric Vehicle

In response to the challenges posed by the low energy utilization of single-power pure electric vehicles and the limited lifespan of power batteries, this study focuses on the development of a compound power system. This study constructs a composite power system, analyzes the coupling characteristics of multiple systems, and investigates the energy management and optimal control mechanisms. Firstly, a power transmission scheme is designed for a hybrid electric vehicle. Then, a multi-state model is established to assess the electric vehicle’s performance under complex working conditions and explore how these conditions impact system coupling. Next, load power is redistributed using the Haar wavelet theory. The super capacitor is employed to stabilize chaotic and transient components in the required power, with low-frequency components serving as input variables for the controller. Further, power distribution is determined through the application of fuzzy logic theory. Input parameters include the system’s power requirements, power battery status, and super capacitor state of charge. The result is the output of a composite power supply distribution factor. To fully exploit the composite power supply’s potential and optimize the overall system performance, a global optimization control strategy using the dynamic programming algorithm is explored. The optimization objective is to minimize power loss within the composite power system, and the optimal control is calculated through interpolation using the interp function. Finally, a comparative simulation experiment is conducted under UDDS cycle conditions. The results show that the composite power system improved the battery discharge efficiency and reduced the number of discharge cycles and discharge current of the power battery. Under the cyclic working condition of 1369 s, the state of charge of the power battery in the hybrid power system decreases from 0.9 to 0.69, representing a 12.5% increase compared to the single power system. The peak current of the power battery in the hybrid power system decreases by approximately 20 A compared with that in the single power system. Based on dynamic programming optimization, the state of charge of the power battery decreases from 0.9 to 0.724. Compared with that of the single power system, the power consumption of the proposed system increases by 25%, that of the hybrid power fuzzy control system increases by 14.2%, and that of the vehicle decreases by 14.7% after dynamic programming optimization. The multimode energy shunt relationship is solved through efficient and reasonable energy management and optimization strategies. The performance and advantages of the composite energy storage system are fully utilized. This approach provides a new idea for the energy storage scheme of new energy vehicles

Mucosa-associated lymphoid tissue of nasopharynx: A case report and literature review

Nasopharyngeal MALT lymphoma is a rare disease, with limited cases reported in the literature. To the best of our knowledge, there is no research detailing the treatment of nasopharyngeal MALT lymphoma. In this present paper, we report an unusual case of a 70-year-old female patient with nasopharyngeal MALT lymphoma. The patient was treated with radiotherapy alone. The detailed radiation therapy of the treatment was demonstrated. The patient is free of locally recurrent or distant disease at two years. Radiotherapy alone can be a helpful treatment for MALT lymphoma confined to the nasopharyngeal cavity

The Relationship between Physical Exercise and Negative Emotions in College Students in the Post-Epidemic Era: The Mediating Role of Emotion Regulation Self-Efficacy

Objective: To investigate the relationship between physical activity and negative emotions among college students in the post-epidemic era and determine if emotional regulation plays a mediating role between physical activity and negative emotions. Methods: 479 college students (293 males, 186 females, M = 19.94, SD = 1.25) who were under closed campus management during the epidemic period were surveyed using the physical activity rating scale (PARS-3), the self-assessment scale for anxiety (SAS), the self-esteem scale for depression (SDS), and the emotion regulation self-efficacy scale (RES). Results: (1) Physical activity, negative emotions, and emotion regulation self-efficacy among college students were significantly different by gender (p < 0.01). (2) Physical exercise was negatively correlated with anxiety and depression (r = −0.236, p < 0.01; r = −0.198, p < 0.01) and positively correlated with emotion regulation self-efficacy (r = 0.256, p < 0.01) in college students. (3) Emotion regulation self-efficacy was negatively correlated with anxiety and depression (r = −0.440, p < 0.01; r = −0.163, p < 0.01). (4) Emotion regulation self-efficacy also partially mediated the relationship between physical activity and negative emotions. Conclusion: (1) Physical activity in the post-epidemic era negatively predicted anxiety and depression in school-isolated college students. (2) Emotion regulation self-efficacy in the post-epidemic era partially mediates the relationship between physical activity and anxiety and depression

A Review of Target Recognition Technology for Fruit Picking Robots: From Digital Image Processing to Deep Learning

Machine vision technology has dramatically improved the efficiency, speed, and quality of fruit-picking robots in complex environments. Target recognition technology for fruit is an integral part of the recognition systems of picking robots. The traditional digital image processing technology is a recognition method based on hand-designed features, which makes it difficult to achieve better recognition as it results in dealing with the complex and changing orchard environment. Numerous pieces of literature have shown that extracting special features by training data with deep learning has significant advantages for fruit recognition in complex environments. In addition, to realize fully automated picking, reconstructing fruits in three dimensions is a necessary measure. In this paper, we systematically summarize the research work on target recognition techniques for picking robots in recent years, analyze the technical characteristics of different approaches, and conclude their development history. Finally, the challenges and future development trends of target recognition technology for picking robots are pointed out

Brassinin Promotes the Degradation of Tie2 and FGFR1 in Endothelial Cells and Inhibits Triple-Negative Breast Cancer Angiogenesis

Brassinin, a phytoalexin derived from cruciferous vegetables, has been reported to exhibit anti-cancer activity in multiple cancer types. However, its effects on triple-negative breast cancer (TNBC) development and the underlying mechanisms have not been elucidated so far. In this study, we demonstrated in vitro that brassinin preferentially reduces the viability of endothelial cells (ECs) when compared to other cell types of the tumor microenvironment, including TNBC cells, pericytes, and fibroblasts. Moreover, brassinin at non-cytotoxic doses significantly suppressed the proliferation, migration, tube formation, and spheroid sprouting of ECs. It also efficiently inhibited angiogenesis in an ex-vivo aortic ring assay and an in-vivo Matrigel plug assay. Daily intraperitoneal injection of brassinin significantly reduced tumor size, microvessel density, as well as the perfusion of tumor microvessels in a dorsal skinfold chamber model of TNBC. Mechanistic analyses showed that brassinin selectively stimulates the degradation of Tie2 and fibroblast growth factor receptor 1 in ECs, leading to the down-regulation of the AKT and extracellular signal-regulated kinase pathways. These findings demonstrate a preferential and potent anti-angiogenic activity of brassinin, which may be the main mechanism of its anti-tumor action. Accordingly, this phytochemical represents a promising candidate for the future anti-angiogenic treatment of TNBC