Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals utilized in various industrial settings and include products such as flame retardants, artificial film-forming foams, cosmetics, and non-stick cookware, among others. Epidemiological studies suggest a link between increased blood PFAS levels and prostate cancer incidence, but the mechanism through which PFAS impact cancer development is unclear. To investigate the link between PFAS and prostate cancer, we evaluated the impact of metabolic alterations resulting from a high-fat diet combined with PFAS exposure on prostate tumor progression. We evaluated in vivo prostate cancer xenograft models exposed to perfluorooctane sulfonate (PFOS), a type of PFAS compound, and different diets to study the effects of PFAS on prostate cancer progression and metabolic activity. Metabolomics and transcriptomics were used to understand the metabolic landscape shifts upon PFAS exposure. We evaluated metabolic changes in benign or tumor cells that lead to epigenomic reprogramming and altered signaling, which ultimately increase tumorigenic risk and tumor aggressiveness. Our studies are the first in the field to provide new and clinically relevant insights regarding novel metabolic and epigenetic states as well as to support the future development of effective preventative and therapeutic strategies for PFAS-induced prostate cancers. Our findings enhance understanding of how PFAS synergize with high-fat diets to contribute to prostate cancer development and establish an important basis to mitigate PFAS exposure.

Estrogen receptor-positive (ER+) metastatic tumors contribute to nearly 70% of breast cancer-related deaths. Most patients with ER+ metastatic breast cancer (MBC) undergo treatment with the estrogen receptor antagonist fulvestrant (Fulv) as standard-of-care. Yet, among such patients, metastasis in the liver is associated with reduced overall survival compared to other metastasis sites. The factors underlying the reduced responsiveness of liver metastases to ER-targeting agents remain unknown, impeding the development of more effective treatment approaches to improve outcomes for patients with ER+ liver metastases. We therefore evaluated site-specific changes in MBC cells and determined the mechanisms through which the liver metastatic niche specifically influences ER+ tumor metabolism and drug resistance. We characterized ER activity of MBC cells both in vitro, using a novel system of tissue-specific extracellular matrix hydrogels representing the stroma of ER+ tumor metastatic sites (liver, lung and bone), and in vivo, in liver and lung metastasis mouse models. ER+ metastatic liver tumors and MBC cells grown in liver hydrogels displayed upregulated expression of glucose metabolism enzymes in response to Fulv. Furthermore, differential ERα activity, but not expression, was detected in liver hydrogels. In vivo, increased glucose metabolism led to increased glycogen deposition in liver metastatic tumors, while a fasting-mimicking diet increased efficacy of Fulv treatment to reduce the metastatic burden. Our findings identify a novel mechanism of endocrine resistance driven by the liver tumor microenvironment. Implications: These results may guide the development of dietary strategies to circumvent drug resistance in liver metastasis, with potential applicability in other metastatic diseases.

Coronary microvascular disease (CMD) is a common form of heart disease in postmenopausal women. It is not due to plaque formation but dysfunction of microvessels that feed the heart muscle. The majority of the patients do not receive a proper diagnosis, are discharged prematurely and must go back to the hospital with persistent symptoms. Because of the lack of diagnostic biomarkers, in the current study, we focused on identifying novel circulating biomarkers of CMV that could potentially be used for developing a diagnostic test. We hypothesized that plasma metabolite composition is different for postmenopausal women with no heart disease, CAD, or CMD. A total of 70 postmenopausal women, 26 healthy individuals, 23 individuals with CMD and 21 individuals with CAD were recruited. Their full health screening and tests were completed. Basic cardiac examination, including detailed clinical history, additional disease and prescribed drugs, were noted. Electrocardiograph, transthoracic echocardiography and laboratory analysis were also obtained. Additionally, we performed full metabolite profiling of plasma samples from these individuals using gas chromatography-mass spectrometry (GC–MS) analysis, identified and classified circulating biomarkers using machine learning approaches. Stearic acid and ornithine levels were significantly higher in postmenopausal women with CMD. In contrast, valine levels were higher for women with CAD. Our research identified potential circulating plasma biomarkers of this debilitating heart disease in postmenopausal women, which will have a clinical impact on diagnostic test design in the future.

We address the problem of privately communicating audio messages to multiple listeners in a reverberant room using a set of loudspeakers. We propose two methods based on emitting noise. In the first method, the loudspeakers emit noise signals that are appropriately filtered so that after echoing along multiple paths in the room, they sum up and descramble to yield distinct meaningful audio messages only at specific focusing spots, while being incoherent everywhere else. In the second method, adapted from wireless communications, we project noise signals onto the nullspace of the MIMO channel matrix between the loudspeakers and listeners. Loudspeakers reproduce a sum of the projected noise signals and intended messages. Again because of echoes, the MIMO nullspace changes across different locations in the room. Thus, the listeners at focusing spots hear intended messages, while the acoustic channel of an eavesdropper at any other location is jammed. We show, using both numerical and real experiments, that with a small number of speakers and a few impulse response measurements, audio messages can indeed be communicated to a set of listeners while ensuring negligible intelligibility elsewhere.

We describe a private audio messaging system that uses echoes to unscramble messages at a few predetermined locations in a room. The system works by splitting the audio into short chunks and emitting them from different loudspeakers. The chunks are filtered so that as they echo around the room, they sum to noise everywhere except at a few chosen focusing spots where they exactly reproduce the intended messages. Unlike in the case of standard personal audio zones, the proposed method renders sound outside the focusing spots unintelligible. Our method essentially depends on echoes: the room acts as a mixing system such that at given points we get the desired output. Finally, we only require a modest number of loudspeakers and only a few impulse response measurements at points where the messages should be delivered. We demonstrate the effectiveness of the proposed method via objective quantitative metrics as well as informal listening experiments in a real room.