Standard treatment for metastatic prostate cancer (CaP) prevents ligand-activation of androgen receptor (AR). Despite initial remission, CaP progresses while relying on AR. AR transcriptional output controls CaP behavior and is an alternative therapeutic target, but its molecular regulation is poorly understood. Here, we show that action of activated AR partitions into fractions that are controlled preferentially by different coregulators. In a 452-AR-target gene panel, each of 18 clinically relevant coregulators mediates androgen-responsiveness of 0–57% genes and acts as a coactivator or corepressor in a gene-specific manner. Selectivity in coregulator-dependent AR action is reflected in differential AR binding site composition and involvement with CaP biology and progression. Isolation of a novel transcriptional mechanism in which WDR77 unites the actions of AR and p53, the major genomic drivers of lethal CaP, to control cell cycle progression provides proof-of-principle for treatment via selective interference with AR action by exploiting AR dependence on coregulators.

We have developed a user-friendly nomogram that uses easily recognized variables to calculate the likelihood of upgrade for ADH. The nomogram could assist the treating surgeon in decision-making, particularly when the patient is at risk for surgical intervention.

Background Trust in science meaningfully contributes to our understanding of people’s belief in misinformation and their intentions to take actions to prevent COVID-19. However, no experimental research has sought to intervene on this variable to develop a scalable response to the COVID-19 infodemic. Objective Our study examined whether brief exposure to an infographic about the scientific process might increase trust in science and thereby affect belief in misinformation and intention to take preventive actions for COVID-19. Methods This two-arm, parallel-group, randomized controlled trial aimed to recruit a US representative sample of 1000 adults by age, race/ethnicity, and gender using the Prolific platform. Participants were randomly assigned to view either an intervention infographic about the scientific process or a control infographic. The intervention infographic was designed through a separate pilot study. Primary outcomes were trust in science, COVID-19 narrative belief profile, and COVID-19 preventive behavioral intentions. We also collected 12 covariates and incorporated them into all analyses. All outcomes were collected using web-based assessment. Results From January 22, 2021 to January 24, 2021, 1017 participants completed the study. The intervention slightly improved trust in science (difference-in-difference 0.03, SE 0.01, t1000=2.16, P=.031). No direct intervention effect was observed on belief profile membership, but there was some evidence of an indirect intervention effect mediated by trust in science (adjusted odds ratio 1.06, SE 0.03, 95% CI 1.00-1.12, z=2.01, P=.045) on membership in the “scientific” profile compared with the others. No direct nor indirect effects on preventive behaviors were observed. Conclusions Briefly viewing an infographic about science appeared to cause a small aggregate increase in trust in science, which may have, in turn, reduced the believability of COVID-19 misinformation. The effect sizes were small but commensurate with our 60-second, highly scalable intervention approach. Researchers should study the potential for truthful messaging about how science works to serve as misinformation inoculation and test how best to do so. Trial Registration NCT04557241; https://clinicaltrials.gov/ct2/show/NCT04557241 International Registered Report Identifier (IRRID) RR2-10.2196/24383

BackgroundDeveloping an ideal wound dressing that meets the multiple demands of good biocompatibility, an appropriate porous structure, superior mechanical property and excellent antibacterial activity against drug-resistant bacteria is highly desirable for clinical wound care. Biocompatible thermoplastic polyurethane (TPU) membranes are promising candidates as a scaffold; however, their lack of a suitable porous structure and antibacterial activity has limited their application. Antibiotics are generally used for preventing bacterial infections, but the global emergence of drug-resistant bacteria continues to cause social concerns.ResultsConsequently, we prepared a flexible dressing based on a TPU membrane with a specific porous structure and then modified it with a biomimetic polydopamine coating to prepare in situ a nano-silver (NS)-based composite via a facile and eco-friendly approach. SEM images showed that the TPU/NS membranes were characterized by an ideal porous structure (pore size: ~ 85 μm, porosity: ~ 65%) that was decorated with nano-silver particles. ATR-FITR and XRD spectroscopy further confirmed the stepwise deposition of polydopamine and nano-silver. Water contact angle measurement indicated improved surface hydrophilicity after coating with polydopamine. Tensile testing demonstrated that the TPU/NS membranes had an acceptable mechanical strength and excellent flexibility. Subsequently, bacterial suspension assay, plate counting methods and Live/Dead staining assays demonstrated that the optimized TPU/NS2.5 membranes possessed excellent antibacterial activity against P. aeruginosa, E. coli, S. aureus and MRSA bacteria, while CCK8 testing, SEM observations and cell apoptosis assays demonstrated that they had no measurable cytotoxicity toward mammalian cells. Moreover, a steady and safe silver-releasing profile recorded by ICP-MS confirmed these results. Finally, by using a bacteria-infected (MRSA or P. aeruginosa) murine wound model, we found that TPU/NS2.5 membranes could prevent in vivo bacterial infections and promote wound healing via accelerating the re-epithelialization process, and these membranes had no obvious toxicity toward normal tissues.ConclusionBased on these results, the TPU/NS2.5 nanocomposite has great potential for the management of wounds, particularly for wounds caused by drug-resistant bacteria.