DLM-GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing.

The in vitro recapitulation of tumor microenvironment is of great interest to preclinical screening of drugs. Compared with culture of cell lines, tumor organ slices can better preserve the complex tumor architecture and phenotypic activity of native cells, but are limited by their exposure to fluid shear and gradual degradation under perfusion culture. Here, we established a decellularized liver matrix (DLM)-GelMA "sandwich" structure and a perfusion-based microfluidic platform to support long-term culture of tumor slices with excellent structural integrity and cell viability over 7 days. The DLM-GelMA was able to secrete cytokines and growth factors while providing shear protection to the tumor slice via the sandwich structure, leading to the preservation of the tumor microenvironment where immune cells (CD3, CD8, CD68), tumor-associated fibroblasts (α-SMA), and extracellular matrix components (collagen I, fibronectin) were well maintained. Furthermore, this chip presented anti-tumor efficacy at cisplatin (20 µM) on tumor patients, demonstrating our platform's efficacy to design patient-specific treatment regimens. Taken together, the successful development of this DLM-GelMA sandwich structure on the chip could faithfully reflect the tumor microenvironment and immune response, accelerating the screening process of drug molecules and providing insights for practical medicine.

Research Progress on Gene Synthesis and Anticancer and Lipid-lowering Mechanism of Monacolin K.

Monacolin K (MK), also known as lovastatin (LOV), is a secondary metabolite synthesized by Monascus in the later stage of fermentation and is the main component of functional red yeast rice (RYR). The structure of MK is similar to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), and it can competitively bind to 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMGCR), thus reducing the level of blood lipids. MK can affect the expression of MAPK, PI3K/AKT, and NF-κB pathway, prepare conjugates with other compounds, and enhance the sensitivity of cancer cells to chemotherapeutic drugs so as to induce apoptosis of acute myeloid leukemia, prostate cancer, breast cancer, lung cancer, gastric cancer, and liver cancer. Combined with the synthetic route of MK, this paper summarizes the latest lipid-lowering and anticancer mechanism of MK, and provides a reference for the application of MK in medicine.

Back-propagation neural network-based reconstruction algorithm for diffuse optical tomography.

Diffuse optical tomography (DOT) is a promising noninvasive imaging modality and is capable of providing functional characteristics of biological tissue by quantifying optical parameters. The DOT image reconstruction is ill-posed and ill-conditioned, due to the highly diffusive nature of light propagation in biological tissues and limited boundary measurements. The widely used regularization technique for DOT image reconstruction is Tikhonov regularization, which tends to yield oversmoothed and low-quality images containing severe artifacts. It is necessary to accurately choose a regularization parameter for Tikhonov regularization. To overcome these limitations, we develop a noniterative reconstruction method, whereby optical properties are recovered based on a back-propagation neural network (BPNN). We train the parameters of BPNN before DOT image reconstruction based on a set of training data. DOT image reconstruction is achieved by implementing a single evaluation of the trained network. To demonstrate the performance of the proposed algorithm, we compare with the conventional Tikhonov regularization-based reconstruction method. The experimental results demonstrate that image quality and quantitative accuracy of reconstructed optical properties are significantly improved with the proposed algorithm.