Single inorganic–organic hybrid nanowires with ambipolar photoresponse

We report for the first time single nanowires (NWs) with ambipolar (positive/negative) photoresponse that changes sign depending on the illumination wavelength. The single NWs were grown by the meniscus-guided method using inorganic (ZnO nanoparticles)–organic (PEDOT:PSS) hybrid materials. The ambipolar photoresponse of the single NWs enabled us to develop an unprecedented spectrum-discriminating NW photodetector array

Light propagation in conjugated polymer nanowires decoupled from a substrate

Light-emitting conjugated polymer nanowires are vertically grown and remotely manipulated into a freestanding straight or curved structure in three-dimension. This approach enabled us to eliminate substrate coupling, a critical issue in nanowire photonics in the past decade. We for the first time accomplished characterization of propagation and bending losses of nanowires completely decoupled from a substrate

Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer

Obesity is recognized as a significant risk factor for ovarian cancer, with accumulating evidence highlighting its impact on disease progression and chemoresistance. This review synthesizes current research elucidating the link between obesity-induced lysosomal dysfunction and ovarian cancer chemoresistance. Epidemiological studies consistently demonstrate a positive correlation between body mass index (BMI) and ovarian cancer risk, attributed in part to the predilection of epithelial ovarian cancer cells for adipose tissue, particularly the omentum. Adipokines released from the omentum contribute to cancer-associated characteristics, including energy supply to cancer cells. Moreover, obesity-induced alterations in lysosomal function have been implicated in systemic inflammation and lipid metabolism dysregulation, further exacerbating cancer progression. Lysosomes play a crucial role in drug resistance, as evidenced by studies demonstrating their involvement in mediating resistance to chemotherapy in ovarian cancer cells. Recent findings suggest that pharmacological inhibition of lysosomal calcium channels sensitizes drug-resistant ovarian cancer cells to cisplatin treatment, highlighting the therapeutic potential of targeting lysosomal dysfunction in obesity-related chemoresistance. This review underscores the importance of understanding the multifaceted roles of lysosomes in obesity-related drug resistance and their implications for the development of targeted therapeutic interventions in ovarian cancer management

Lipidomics Analysis Unravels Aberrant Lipid Species and Pathways Induced by Zinc Oxide Nanoparticles in Kidney Cells

Zinc oxide nanoparticles (ZnO NPs) are widely used in versatile applications, from high technology to household products. While numerous studies have examined the toxic gene profile of ZnO NPs across various tissues, the specific lipid species associated with adverse effects and potential biomarkers remain elusive. In this study, we conducted a liquid chromatography-mass spectrometry based lipidomics analysis to uncover potential lipid biomarkers in human kidney cells following treatment with ZnO NPs. Furthermore, we employed lipid pathway enrichment analysis (LIPEA) to elucidate altered lipid-related signaling pathways. Our results demonstrate that ZnO NPs induce cytotoxicity in renal epithelial cells and modulate lipid species; we identified 64 lipids with a fold change (FC) > 2 and p p < 0.05 in HK2 cells post-treatment with ZnO NPs. Notably, the altered lipids between control HK2 cells and those treated with ZnO NPs were associated with the sphingolipid, autophagy, and glycerophospholipid pathways. This study unveils novel potential lipid biomarkers of ZnO NP nanotoxicity, representing the first lipidomic profiling of ZnO NPs in human renal epithelial cells

Light propagation in conjugated polymer nanowires decoupled from a substrate

Light-emitting conjugated polymer nanowires are vertically grown and remotely manipulated into a freestanding straight or curved structure in three-dimension. This approach enabled us to eliminate substrate coupling, a critical issue in nanowire photonics in the past decade. We for the first time accomplished characterization of propagation and bending losses of nanowires completely decoupled from a substrate. © 2014 the Partner Organisations.Link_to_subscribed_fulltex

The Effects of High Fat Diet-Induced Stress on Olfactory Sensitivity, Behaviors, and Transcriptional Profiling in Drosophila melanogaster

High-fat diet (HFD) often causes obesity and it has detrimental effects on the sensory system. In particular, sensory-mediated responses are crucial for maintaining energy balance, as they are involved in a metabolic regulation; however, there is still no clear explanation about the relationship between HFD-induced stress and sensory system. To gain insight on how HFD-induced stress affects olfactory sensitivity and behavioral responses, we have used a Drosophila melanogaster model for olfactory and nutrient-related signaling and accessed physiological, behavioral, and transcriptional changes. We demonstrated that lifespan and climbing ability in HFD-treated flies decreased and that olfactory sensitivity and behavioral responses to odorants were changed. Olfactory sensitivity to eight of ten odorants after 14 days on HFD treatment were reduced, while behavioral attraction was increased to benzaldehyde in flies that were treated with HFD. This behavioral and physiological modification in HFD-treated flies for 14 days was accompanied by a significant decrease in DmOrco gene expression in a peripheral olfactory organ, suggesting that is could be involved in the action of metabolic and sensory signal. Gene expression profiles of antennae showed significant differences on the olfactory receptors, odorant-binding proteins, and insulin signaling. Our results suggested that olfactory sensitivity and behavioral responses to HFD-induced stress are mediated through olfactory and nutrient-related signaling pathways

Zinc oxide nanoparticles trigger autophagy-mediated cell death through activating lysosomal TRPML1 in normal kidney cells

Zinc oxide nanoparticles (ZnO NPs) have been widely used in various materials including sunscreens, cosmetics, over-the-counter topical skin products, and pigments. As traces of the used ZnO NPs have been found in the kidney, it is crucial to uncover their potential risks. The aim of this study is to elucidate detrimental effects of ZnO NPs and the molecular mechanism behind their renal toxicity. Cytotoxic effects were measured by MTT assay after HK2 cells were exposed to ZnO NPs for 24 h and IC50 value was determined. ROS and intracellular Zn2+ levels were detected by flow cytometry, and localization of Zn2+ and lysosome was determined by confocal microscopy. Occurrence of autophagy and detection of autophagic flux were determined by Western blot and confocal microscopy, respectively. We performed unpaired student t test for two groups, and one-way ANOVA with Tukey’s post hoc for over three groups. ZnO NPs induced cell death in human renal proximal tubule epithelial cells, HK2. Cytosolic Zn2+ caused autophagy-mediated cell death rather than apoptosis. Cytosolic Zn2+ processed in lysosome was released by TRPML1, and inhibition of TRPML1 significantly decreased autophagic flux and cell death. The findings of this study suggest that ZnO NPs strongly induce autophagy-mediated cell death in human kidney cells. Controlling TRPML1 can be potentially used to prevent the kidney from ZnO NPs-induced toxicity

Discovery of 2‑((<i>R</i>)‑4-(2-Fluoro-4-(methylsulfonyl)phenyl)-2-methylpiperazin-1-yl)‑<i>N</i>‑((1<i>R</i>,2<i>s</i>,3<i>S</i>,5<i>S</i>,7<i>S</i>)‑5-hydroxyadamantan-2-yl)pyrimidine-4-carboxamide (SKI2852): A Highly Potent, Selective, and Orally Bioavailable Inhibitor of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)

A series of picolinamide- and pyrimidine-4-carboxamide-based inhibitors of 11β-hydroxysteroid dehydrogenase type 1 was synthesized and evaluated to optimize the lead compound <b>9</b>. The combination of the replacement of a pyridine ring of <b>9</b> with a pyrimidine ring and the introduction of an additional fluorine substituent at the 2-position of the phenyl ring resulted in the discovery of a potent, selective, and orally bioavailable inhibitor, <b>18a</b> (SKI2852), which demonstrated no CYP and PXR liabilities, excellent PK profiles across species, and highly potent and sustainable PD activity. Repeated oral administration of <b>18a</b> significantly reduced blood glucose and HbA1c levels and improved the lipid profiles in <i>ob</i>/<i>ob</i> mice. Moreover, the HbA1c-lowering effect of metformin was synergistically enhanced in combination with <b>18a</b>