Efficacy of c-Met inhibitor for advanced prostate cancer

<p>Abstract</p> <p>Background</p> <p>Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer.</p> <p>Methods</p> <p>We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression.</p> <p>Results</p> <p>We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration.</p> <p>Conclusions</p> <p>The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.</p

Queer In AI: A Case Study in Community-Led Participatory AI

We present Queer in AI as a case study for community-led participatory design in AI. We examine how participatory design and intersectional tenets started and shaped this community's programs over the years. We discuss different challenges that emerged in the process, look at ways this organization has fallen short of operationalizing participatory and intersectional principles, and then assess the organization's impact. Queer in AI provides important lessons and insights for practitioners and theorists of participatory methods broadly through its rejection of hierarchy in favor of decentralization, success at building aid and programs by and for the queer community, and effort to change actors and institutions outside of the queer community. Finally, we theorize how communities like Queer in AI contribute to the participatory design in AI more broadly by fostering cultures of participation in AI, welcoming and empowering marginalized participants, critiquing poor or exploitative participatory practices, and bringing participation to institutions outside of individual research projects. Queer in AI's work serves as a case study of grassroots activism and participatory methods within AI, demonstrating the potential of community-led participatory methods and intersectional praxis, while also providing challenges, case studies, and nuanced insights to researchers developing and using participatory methods.Comment: To appear at FAccT 202

ZMIZ1 Preferably Enhances the Transcriptional Activity of Androgen Receptor with Short Polyglutamine Tract

The androgen receptor (AR) is a ligand-induced transcription factor and contains the polyglutamine (polyQ) tracts within its N-terminal transactivation domain. The length of polyQ tracts has been suggested to alter AR transcriptional activity in prostate cancer along with other endocrine and neurologic disorders. Here, we assessed the role of ZMIZ1, an AR co-activator, in regulating the activity of the AR with different lengths of polyQ tracts as ARQ9, ARQ24, and ARQ35 in prostate cancer cells. ZMIZ1, but not ZMIZ2 or ARA70, preferably augments ARQ9 induced androgen-dependent transcription on three different androgen-inducible promoter/reporter vectors. A strong protein-protein interaction between ZMIZ1 and ARQ9 proteins was shown by immunoprecipitation assays. In the presence of ZMIZ1, the N and C-terminal interaction of the ARQ9 was more pronounced than ARQ24 and ARQ35. Both Brg1 and BAF57, the components of SWI/SNF complexes, were shown to be involved in the enhancement of ZMIZ1 on AR activity. Using the chromatin immunoprecipitation assays (ChIP), we further demonstrated a strong recruitment of ZMIZ1 by ARQ9 on the promoter of the prostate specific antigen (PSA) gene. These results demonstrate a novel regulatory role of ZMIZ1 in modulating the polyQ tract length of AR in prostate cancer cells

Application of Triboelectric Nanogenerator in Fluid Dynamics Sensing: Past and Future

The triboelectric nanogenerator (TENG) developed by Z. L. Wang’s team to harvest random mechanical energy is a promising new energy source for distributed sensing systems in the new era of the internet of things (IoT) and artificial intelligence (AI) for a smart world. TENG has many advantages that make it suitable for a wide range of applications, including energy harvesting, environmental protection, wearable electronics, robotics, and self-powered sensors. Sensing as an important part of TENG applications is gradually expanding, with the in-depth study of TENG sensing in its working principle, material selection, processing technology, system integration, surface treatment, and back-end algorithms by researchers. In industry and academia, fluid dynamics sensing for liquid and air is urgently needed but lacking. In particular, local fluid sensing is difficult and limited to traditional sensors. Fortunately, with advantages for ordinary TENGs and TENGs as fluid dynamics sensors, fluid dynamics sensing can be better realized. Therefore, the paper summarizes the up-to-date work on TENGs as fluid dynamics sensors, discusses the advantages of TENGs as fluid dynamics sensors in-depth, and, most importantly, aims to explore possible new key areas to help guide the future direction of TENG in fluid dynamics sensing by addressing the key challenges

Polyarylcyanation of Diyne: A One-Pot Three-Component Convenient Route for <i>In Situ</i> Generation of Polymers with AIE Characteristics

A facile, one-pot, three-component polymerization route for <i>in situ</i> generation of polymers with aggregation-induced emission (AIE) characteristics was developed. The polycoupling of dibromoarenes, internal diynes and potassium ferrocyanide was catalyzed by palladium acetate and sodium bicarbonate and proceeded smoothly in dimethylacetamide under nitrogen at 120 °C, producing poly­(triphenylacrylonitrite)­s (PTPANs) with high weight-average molecular weights of up to 223000 in high yields of up to 84%. This polymerization method enjoys the remarkable advantages of high reaction rate and efficiency and broad monomer scope. Model reaction was carried out to aid the structure characterization and property investigation of the obtained polymers. All the polymers show remarkable thermal stability, losing merely 5% of their weight at high temperature of up to 513 °C. They are soluble in common organic solvents and their spin-coated thin films exhibit high refractive indices (1.6482–1.7682). Thanks to the triphenylethene chromophore <i>in situ</i> generated during the polymerization, all the polymers are AIE-active and show strong light emission in the solid state. While UV irradiation of the polymer thin films in air through upper masks photo-oxidizes the exposed parts and quenches their light emission, the unexposed parts remain emissive. Two-dimensional fluorescent patterns with good resolution are thus generated

Polyarylcyanation of Diyne: A One-Pot Three-Component Convenient Route for <i>In Situ</i> Generation of Polymers with AIE Characteristics

A facile, one-pot, three-component polymerization route for <i>in situ</i> generation of polymers with aggregation-induced emission (AIE) characteristics was developed. The polycoupling of dibromoarenes, internal diynes and potassium ferrocyanide was catalyzed by palladium acetate and sodium bicarbonate and proceeded smoothly in dimethylacetamide under nitrogen at 120 °C, producing poly­(triphenylacrylonitrite)­s (PTPANs) with high weight-average molecular weights of up to 223000 in high yields of up to 84%. This polymerization method enjoys the remarkable advantages of high reaction rate and efficiency and broad monomer scope. Model reaction was carried out to aid the structure characterization and property investigation of the obtained polymers. All the polymers show remarkable thermal stability, losing merely 5% of their weight at high temperature of up to 513 °C. They are soluble in common organic solvents and their spin-coated thin films exhibit high refractive indices (1.6482–1.7682). Thanks to the triphenylethene chromophore <i>in situ</i> generated during the polymerization, all the polymers are AIE-active and show strong light emission in the solid state. While UV irradiation of the polymer thin films in air through upper masks photo-oxidizes the exposed parts and quenches their light emission, the unexposed parts remain emissive. Two-dimensional fluorescent patterns with good resolution are thus generated