Humanized mouse models: A valuable platform for preclinical evaluation of human cancer.

Animal models are routinely employed to assess the treatments for human cancer. However, due to significant differences in genetic backgrounds, traditional animal models are unable to meet bioresearch needs. To overcome this restriction, researchers have generated and optimized immunodeficient mice, and then engrafted human genes, cells, tissues, or organs in mice so that the responses in the model mice could provide a more reliable reference for treatments. As a bridge connecting clinical application and basic research, humanized mice are increasingly used in the preclinical evaluation of cancer treatments, particularly after gene interleukin 2 receptor gamma mutant mice were generated. Human cancer models established in humanized mice support exploration of the mechanism of cancer occurrence and provide an efficient platform for drug screening. However, it is undeniable that the further application of humanized mice still faces multiple challenges. This review summarizes the construction approaches for humanized mice and their existing limitations. We also report the latest applications of humanized mice in preclinical evaluation for the treatment of cancer and point out directions for future optimization of these models.

Chimeric Antigen Receptor-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.

Distant metastasis and primary tumor relapse are the two main hurdles to the success of surgical treatment for cancer patients. Circulating tumor cells (CTCs) and incomplete surgical resection are the primary cause of distant metastasis and local recurrence of tumors, respectively. Chimeric antigen receptor (CAR)-modified T cells target residual carcinomas and CTCs hold the potential to inhibit primary recurrence and reduce tumor metastasis, but the experimental evidence is lacking. Here, we developed a surgery-induced tumor metastasis model in immunocompetent mice to investigate the efficacy of CAR-T cells therapy in preventing metastasis and local recurrence. We observed that subcutaneous tumor resection has induced a large number of CTCs intravasated into circulation. EpCAM-specific CAR-T was effective in clearing CTCs following surgical removal of the tumor. This resulted in less pulmonary metastasis and longer survival in mice when compared to mice treated with surgery followed by Mock-T cells infusion. In addition, the local relapse was obviously inhibited at the surgical site followed by EpCAM-CAR-T cell treatment. This study demonstrated that CAR-T cell therapy can be an adjuvant treatment following surgery to prevent tumor metastasis and inhibit primary tumor relapse for cancer patients.

Co-infusion of CAR T cells with aAPCs expressing chemokines and costimulatory ligands enhances the anti-tumor efficacy in mice.

Chimeric antigen receptor-modified T (CAR-T) cell therapy has shown curable efficacy for treating hematological malignancies, while in solid tumors, the immunosuppressive microenvironment causes poor activation, expansion and survival of CAR-T cells, accounting mainly for the unsatisfactory efficacy. The artificial antigen-presenting cells (aAPCs) have been used for ex vivo expansion and manufacturing of CAR-T cells. Here, we constructed a K562 cell-based aAPCs expressing human epithelial cell adhesion molecule (EpCAM), chemokines (CCL19 and CCL21) and co-stimulatory molecular ligands (CD80 and 4-1BBL). Our data demonstrated that the novel aAPCs enhanced the expansion, and increased the immune memory phenotype and cytotoxicity of CAR-T cells recognizing EpCAM, in vitro. Of note, co-infusion CAR-T and aAPC enhances the infiltration of CAR-T cells in solid tumors, which has certain potential for the treatment of solid tumors Moreover, IL-2-9-21, a cytokine cocktail, prevents CAR-T cells from entering the state of exhaustion prematurely after continuous antigen engagement and boosts the anti-tumor activity of CAR-T cells co-infused with aAPCs. These data provide a new strategy to enhance the therapeutic potential of CAR-T cell therapy for the treatment of solid tumors.

Ultrahigh Nitrogen Content Carbon Nanosheets for High Stable Sodium Metal Anodes.

Sodium metal, with a high theoretical specific capacity of 1165 mAh g-1 , is the ultimate anode for sodium batteries, yet how to deal with the inhomogeneous and dendritic sodium deposition and the infinite relative dimension change of sodium metal anodes during sodium depositing/stripping is still challenging. Here, a facile fabricated sodiuphilic 2D N-doped carbon nanosheets (N-CSs) are proposed as sodium host material for sodium metal batteries (SMBs) to prevent dendrite formation and eliminate volume change during cycling. Revealing from combined in situ characterization analyses and theoretical simulations, the high nitrogen content and porous nanoscale interlayer gaps of the 2D N-CSs can not only concede dendrite-free sodium stripping/depositing but also accommodate the infinite relative dimension change. Furthermore, N-CSs can be easily process into N-CSs/Cu electrode via traditional commercial battery electrode coating equipment that pave the way for large-scale industrial applications. On account of the abundant nucleation sites and sufficient deposition space, N-CSs/Cu electrodes demonstrate a superior cycle stability of more than 1500 h at a current density of 2 mA cm-2 with a high coulomb efficiency of more than 99.9% and ultralow nucleation overpotential, which enable reversible and dendrites-free SMBs and shed light on further development of SMBs with even higher performance.

The complete mitogenome of Pareuchiloglanis sichuanensis (Siluriformes: Sisoridae).

Pareuchiloglanis sichuanensis is an endemic fish species in the upper reaches of the Yangtze River. In the present study, the complete mitochondrial genome of P. sichuanensis was analyzed. The mitochondrial genome, consisting of 16,774 base pairs (bp), included 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a non-coding control region. The phylogenetic tree showed that P. sichuanensis was closely related to P. anteanalis. These results provid the useful information for further studies on taxonomic status, molecular systematics, and stock evaluation.