Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay.

BACKGROUND: More than half of the colorectal cancer (CRC) patients will develop liver metastasis that underlies the cancer mortality. In the hepatic tumor microenvironment, the interplay between CRC cells and hepatic stellate cells (HSCs), and the activation of HSCs to become carcinoma-associated fibroblasts (CAFs) will further promote the cancer development. Nevertheless, the critical signaling molecule that involved in these processes remains unknown, which hinders the development of effective therapeutic agents for the treatment of metastatic CRC (mCRC). METHODS: Conditioned medium system and co-cultured system were used to examine the interplay between CRC cells and HSCs. Luminex liquid suspension chip detection and enzyme-linked immunosorbent assay were used to screen for the mediators in the conditioned medium that facilitated the CRC-HSCs interplay and HSCs-to-CAFs differentiation. Cell and animal models were used to examine whether brevilin A inhibited CRC liver metastasis via the VEGF-IL6-STAT3 axis. RESULTS: In the CRC-HSCs interplay, CRC promoted HSCs-to-CAFs differentiation by releasing vascular endothelial growth factor (VEGF); and HSCs released interleukin 6 (IL6) that activated signal transducer and activator of transcription 3 (STAT3) in the CRC and hence increased the cancer metastatic potential. The functions of the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay were further validated by VEGF recombinant protein and IL6 neutralizing antibody. More importantly, brevilin A, an active compound isolated from Centipeda minima (L.) A. Br. et Aschers, targeted the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay, hence significantly inhibited colorectal liver metastasis and cancer growth both in vitro and in vivo. CONCLUSIONS: We are the first to demonstrate brevilin A possesses potent anti-mCRC effect by targeting the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay. Our findings not only support the development of brevilin A as a novel therapeutic agent for mCRC treatment, but also pave the path for the development of other VEGF-IL6-STAT3 targeting therapeutic strategies.

Off-axis three-mirror freeform systems design based on improved W-W differential equations.

Design of an off-axis system using the Wassermann-Wolf (W-W) differential equations can effectively eliminate the spherical aberration and coma problem; however, it is complicated and time consuming to calculate the discrete point coordinates on the freeform mirror surfaces due to multiple numbers of reference system transformation in the design process. This paper presents an improved W-W-differential-equations-based design method for off-axis three-mirror freeform systems. First, to reduce the number of coordinate transformations, a geometric relationship between different optical rays in an off-axis system is established using the distance between the central points of adjacent mirrors. Second, a three-dimensional rotation matrix is used to associate the optical paths passing through adjacent mirrors in different reference coordinate systems, and new simplified W-W differential equations based on the ray vectors are constructed. The experimental results show that our method can easily and effectively design off-axis three-mirror freeform systems with different parameters and structures, and the designed systems have good imaging quality.

A new segment method for pulmonary artery and vein.

Accurate differentiation between pulmonary arteries and veins (A/V) holds pivotal importance in the realm of diagnosing and treating pulmonary ailments. This study presents a new approach that leverages grayscale differences between A/V. Distinctions are measured using median and mean grayscale values within the vessel area. Initially, adherent regions are removed based on vessel structure. The trunk regions are segmented using gray level information near the heart region of the lung boundary. Incorrectly segmented vessels are corrected based on connectivity. For distal lung vessels, a similar distance field is established using a graph-cut method. Experimental results show the algorithm's superior segmentation accuracy, achieving 97.26% compared to the CNN-based average accuracy of 91.67%. Error branches are more concentrated, aiding subsequent manual and automatic correction. This demonstrates the algorithm's effective segmentation of pulmonary A/V.