Targeting cancer stem cells in drug discovery: Current state and future perspectives

In recent decades,cancer stem cells(CSCs)have been increasingly identified in many malignancies.CSC-related signaling pathways and their functions provide new strategies for treating cancer.The aberrant activation of related signaling pathways(e.g.,Wnt,Notch,and Hedgehog pathways)has been linked to multiple types of malignant tumors,which makes these pathways attractive targets for cancer therapy.CSCs display many characteristic features,such as self-renewal,differentiation,high tumorigenicity,and drug resistance.Therefore,there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication,survival,and differentiation.Notable crosstalk occurs among different signaling pathways and potentially leads to compensatory escape.Therefore,multitarget inhibitors will be one of the main methods to overcome the drug resistance of CSCs.Many small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials,and some inhibitors,such as vismodegib,sonidegib,and glasdegib,have been approved.Tumor cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo protein.The signal transducers and activators of transcription 3(STAT3)inhibitor BBI608 is being evaluated in a phase III trial for a variety of cancers.Structural derivatives of BBI608 are the main focus of STAT3 inhibitor development,which is another strategy for CSC therapy.In addition to the potential pharmacological inhibitors targeting CSCrelated signaling pathways,other methods of targeting CSCs are available,such as nano-drug delivery systems,mitochondrion targeting,autophagy,hyperthermia,immunotherapy,and CSC microenvironment targeting.In addition,we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.

Anode material NbO for Li-ion battery and its electrochemical properties

The NbO electrode materials were successfully synthesized by high-temperature solid-phase method using Nb powders and Nb2O5 powders as raw materials. The crystalline structure, morphology, and electrochemical properties of the obtained materials were characterized by X-ray diffi＇action （XRD）, scanning electron microscopy （SEM）, dynamic light scattering instrument （DLSA）, half- cell charge-discharge tests, and cyclic voltammetry （CV）. The reaction mechanism of lithium with NbO was inves- tigated by ex-situ XRD studies. The results show that material average Li storage voltage is nearly located at 1.6 V, and the lithium intercalation into NbO remains a single-phase process. For the first discharge, a capacity of 355 mAh·g^-1 is obtained at a current rate of 0.1C, and 293 mAh·g^-1is maintained after 50 cycles, whereas a capacity of 416 mAh·g^-1 is obtained at a current rate of 0.1C alter ball milling. And 380 mAh·g^-1 reversible capacity remains for the ball milling sample.

Electrochemical performance of Al_2O_3 pre-coated spinel LiMn_2O_4

Al_2O_3-coated spinel LiMn_2O_4 cathode materials, presintered LiMn_2O_4(P-LMO), and calcined LiMn_2O_4(C-LMO) were synthesized by chemical deposition and thermal treating method using presintered and calcined LiMn_2O_4 as precursors. The crystal structure, morphology,the thickness of the coating layer, and particle size of prepared samples were investigated by X-ray diffraction(XRD), scanning electron microscopy(SEM), high-resolution transmission electron microscopy(HRTEM), and Malvern instruments. The average particle size of P-LMO with like-spheres(0.3 μm) is much smaller than that of C-LMO(0.5 μm). The Al_2O_3 layer of P-LMO can effectively reduce the charge transfer resistance and inhibit the Mn dissolution. The electrochemical performance of P-LMO is better than that of C-LMO. It is found that the LiMn_2O_4 cathode materials have excellent electrochemical cyclability by coated 2 mol% Al_2O_3 at the surface of presintered material. The initial discharge capacity of the material with 2 mol% Al_2O_3-coated is 114.0 m Ah·g^(-1) at 0.1 C rate and 55 ℃, and the capacity retention is 87.3 % at 0.5 C rate.