Cascade Catalytic Nanoparticles Selectively Alkalize Cancerous Lysosomes to Suppress Cancer Progression and Metastasis.

Lysosomes are critical in modulating the progression and metastasis for various cancers. There is currently an unmet need for lysosomal alkalizers that can selectively and safely alter the pH and inhibit the function of cancer lysosomes. Here an effective, selective, and safe lysosomal alkalizer is reported that can inhibit autophagy and suppress tumors in mice. The lysosomal alkalizer consists of an iron oxide core that generates hydroxyl radicals (•OH) in the presence of excessive H+ and hydrogen peroxide inside cancer lysosomes and cerium oxide satellites that capture and convert •OH into hydroxide ions. Alkalized lysosomes, which display impaired enzyme activity and autophagy, lead to cancer cell apoptosis. It is shown that the alkalizer effectively inhibits both local and systemic tumor growth and metastasis in mice. This work demonstrates that the intrinsic properties of nanoparticles can be harnessed to build effective lysosomal alkalizers that are both selective and safe.

Epidemiological characteristics and spatiotemporal clustering of scarlet fever in Liaoning Province, China, 2010-2019.

BACKGROUND: To explore the epidemiological characteristics and spatiotemporal distribution of scarlet fever in Liaoning Province, which could provide scientific evidence for the formulation and improvement of prevention and control strategies and measures. METHODS: Data on scarlet fever cases and population were obtained from the China Information System for Disease Control and Prevention in Liaoning Province between 2010 and 2019. We examined the spatial and spatiotemporal clusters of scarlet fever across Liaoning Province using the Moran's I, local indicators of spatial association, local Gi* hotspot statistics, and Kulldorff's retrospective space-time scan statistical analysis. RESULTS: Between 1st January 2010 and 31st December 2019, 46,652 cases of scarlet fever were reported in Liaoning Province, with an annual average incidence of 10.67 per 100,000. The incidence of scarlet fever had obvious seasonality with high incidence in early summer June and early winter December. The male-to-female ratio was 1.53:1. The highest incidence of cases occurred in 3-9 year old children. The most likely spatiotemporal cluster and the secondary clusters were detected in urban regions of Shenyang and Dalian, Liaoning Province. CONCLUSIONS: The incidence of scarlet fever has obvious spatiotemporal clustering, with the high-risk areas mainly concentrated in urban area of Shenyang and Dalian, Liaoning Province. Control strategies need to focus on high-risk season, high-risk areas and high-risk populations in order to reduce the incidence of scarlet fever.

Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice.

Diverse clustered protocadherins are thought to function in neurite morphogenesis and neuronal connectivity in the brain. Here, we report that the protocadherin alpha (Pcdha) gene cluster regulates neuronal migration during cortical development and cytoskeletal dynamics in primary cortical culture through the WAVE (Wiskott-Aldrich syndrome family verprolin homologous protein, also known as Wasf) complex. In addition, overexpression of proline-rich tyrosine kinase 2 (Pyk2, also known as Ptk2b, Cakß, Raftk, Fak2, and Cadtk), a non-receptor cell-adhesion kinase and scaffold protein downstream of Pcdhα, impairs cortical neuron migration via inactivation of the small GTPase Rac1. Thus, we define a molecular Pcdhα/WAVE/Pyk2/Rac1 axis from protocadherin cell-surface receptors to actin cytoskeletal dynamics in cortical neuron migration and dendrite morphogenesis in mouse brain.