Depression-related Testosterone Deficiency is Linked to Reduced Cholesterol Levels in Leydig Cells of CUMS Mice.

Testosterone deficiency in humans can be caused by depressive symptoms; however, the causes of this deficiency are incompletely understood. This study demonstrates that male mice with depression-like symptoms due to chronic unpredictable mild stress (CUMS) show reduced serum testosterone levels and disrupted sexual behaviors. However, the observed testosterone reductions were not caused by apoptosis of Leydig cells. Oil red O staining revealed that lipid droplets were dramatically decreased in Leydig cells, suggesting that defects in cholesterol uptake might be related to testosterone-deficiency in depression-like mice. To investigate the potential mechanism, lipid homeostasis was examined by liquid chromatography tandem mass spectrometry. The results revealed that higher levels of sphingomyelins (SM 8:0;2O/28:1, 18:0;2O/22:2, 33:0;3O, 33:1;2O) were linked to decreased cholesterol levels. Further investigation indicated that testosterone biosynthesis from cholesterol in Leydig cells was impaired by downregulation of Ldlr, SR-BI, LHR, and P450scc. Elevated levels of interferon signaling associated pathways in depression-like mice testes may also contribute to decreased testosterone level. Taken together, these findings provide a novel understanding of male reproductive problems under psychological stress and suggest that cholesterol uptake might be a causal factor in reduced testosterone production in depression-like mice.

Racial and Ethnic Differences in Initiation and Discontinuation of Antiarrhythmic Medications in Management of Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with considerable morbidity and mortality. Timely management and treatment are critical in alleviating AF disease burden. There is significant heterogeneity in patterns of AF care. It is unclear whether there are racial and ethnic differences in treatment of AF following antiarrhythmic drug (AAD) prescription. Methods: Using the Optum Clinformatics Data Mart-Socioeconomic Status database from January, 2009, through March, 2022, multivariable logistic regression techniques were used to examine the impact of race and ethnicity on rate of AAD initiation, as well as receipt of catheter ablation within two years of initiation. We compared AAD discontinuation rate by race and ethnicity groups using Cox regression models. Log-rank analyses were used to examine the rate of AF-related hospitalization. Results: Among 143,281 patients identified with newly diagnosed AF, 30,019 patients (21%) were initiated on an AAD within 90 days. Patients identified as Non-Hispanic Black (NHB) were significantly less likely to receive an AAD compared to Non-Hispanic White patients (NHW) (Odds Ratio [OR] 0.90, 95% confidence interval [CI] 0.85-0.94). Compared to NHW, Hispanic (Hazard Ratio [HR] 1.08, 95% CI 1.02-1.14) and Asian patients (HR 1.17, 95% CI 1.06-1.29) have a higher rate of AAD discontinuation. Following AAD initiation, NHB patients were significantly more likely to have an AF-related hospitalization (p < 0.01). However, NHB patients were significantly less likely to receive ablation compared to NHW (HR 0.83, 95% CI 0.70-0.97), and less likely to change AAD (p < 0.01). Conclusion: Patients identified as NHB are 10% less likely to receive an AAD for treatment of newly diagnosed AF. Compared to NHW, Hispanic and Asian patients were more likely to discontinue AAD treatment. Once initiated on an AAD, NHB patients were significantly more likely to have an AF -related hospitalization, but were 17% less likely to receive ablation compared to NHW patients. The etiology of, and interventions to reduce, these disparities require further investigation.

Facilitating Interskin Communication in Artificial Polymer Systems through Liquid Transfer.

Chemical communication is a ubiquitous process in nature, and it has sparked interest in the development of electric-sense-based robotic perception systems with chemical components. Here, a novel liquid crystal polymer is introduced that combines the transferring, receiving, and sensing of chemical signals, providing a new principle to achieve chemical communication in robotic systems. This approach allows for the transfer of cargo between two polymer coatings, and the transfer can be monitored through an electrical signal. Additionally, cascade transfer can be achieved through this approach, as the transfer of cargo is not limited to only two coatings, but can continue from the second to a third coating. Furthermore, the two coatings can be infused with different reagents, and upon exchange, a reaction takes place to generate the desired species. The novel method of chemical communication that is developed presents a notable improvement in embodied perception. This advancement facilitates human-robot and robot-robot interactions and enhances the ability of robots to efficiently and accurately perform complex tasks in their environment.

Novel 4-Aryl-4H-chromene derivative displayed excellent in vivo anti-glioblastoma efficacy as the microtubule-targeting agent.

In this study, a series of novel 4-Aryl-4H-chromene derivatives (D1-D31) were designed and synthesized by integrating quinoline heterocycle to crolibulin template molecule based on the strategy of molecular hybridization. One of these compounds D19 displayed positive antiproliferative activity against U87 cancer cell line (IC50 = 0.90 ± 0.03 µM). Compound D19 was verified as the microtubule-targeting agent through downregulating tubulin related genes of U87 cells, destroying the cytoskeleton of tubulins and interacting with the colchicine-binding site to inhibit the polymerization of tubulins by transcriptome analysis, immune-fluorescence staining, microtubule dynamics and EBI competition assays as well as molecular docking simulations. Moreover, compound D19 induced G2/M phase arrest, resulted in cell apoptosis and inhibited the migration of U87 cells by flow cytometry analysis and wound healing assays. Significantly, compound D19 dose-dependently inhibited the tumor growth of orthotopic glioma xenografts model (GL261-Luc) and effectively prolonged the survival time of mice, which were extremely better than those of positive drug temozolomide (TMZ). Compound D19 exhibited potent in vivo antivascular activity as well as no observable toxicity. Furthermore, the results of in silico simulation studies and P-gp transwell assays verified the positive correlation between compound D19's Blood-Brain Barrier (BBB) permeability and its in vivo anti-GBM activity. Overall, compound D19 can be used as a promising anti-GBM lead compound for the treatment of glioblastoma.

Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men.

Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities.