Research progress in the treatment of bladder cancer based on nanotechnology

Bladder cancer is the most common malignant tumor in the urinary system. Currently, the clinical treatment options for bladder cancer mainly include surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, photodynamic therapy, combination therapy, etc. The conventional treatment and administration strategies for bladder cancer primarily depend on the tumor stage and the extent of metastasis. However, in the process of non-surgical treatment, drugs lack specificity and targeting. Once the dosage is improperly controlled, drugs will damage normal cells when attacking cancer cells, which will lead to poor efficacy and multiple side effects. Nanomedicine is an emerging interdisciplinary field that utilizes nanomaterials and technologies in nanomedicine to provide disruptive technologies for traditional treatments, with advantages such as targeted delivery and high efficiency with low toxicity. Many nanotechnologies have become hot topics in clinical research in the field of medicine. Functionalized nanoparticles can actively or passively target specific cells within target organs, such as bladder cancer cells, by altering their surface properties, thereby enhancing drug delivery precision, reducing damage to normal cells, and improving treatment efficacy. This article provides an overview of the progress in classical and novel treatment approaches to bladder cancer, with a particular focus on the potential applications and future development directions of nanotechnology in the treatment of bladder cancer, providing important reference for personalized therapy and clinical translation in bladder cancer

Mechanical stiffness promotes skin fibrosis through Piezo1-mediated arginine and proline metabolism

Abstract The increased mechanics of fibrotic skin tissue continuously regulate fibroblast functions such as survival and differentiation. Although all these processes consume metabolites, it is unclear whether and how cells adapt their metabolic activity to increased matrix stiffness. Here, we show that transferring mouse dermal fibroblasts from soft to stiff substrates causes an up-regulation of arginine and proline metabolism. Increased matrix stiffness stimulates the expression and activity of key metabolic enzymes, leading to the synthesis of L-proline, a major source of collagen. In addition, the novel mechanosensitive channel Piezo1 was identified as a key regulator of arginine and proline metabolism in fibroblasts under increased stiffness. Consistently, targeting Piezo1 to dermal fibroblasts in vivo effectively reduces fibrosis and arginine-proline metabolism in mouse skin. Therefore, mechanical stiffness is a critical environmental cue for fibroblast metabolism and skin fibrosis progression

Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2/Wnt11-CCL24 positive feedback loop

Abstract Skin fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) caused by fibrotic disorders of the skin. In recent years, ECM stiffness has emerged as a prominent mechanical cue that precedes skin fibrosis and drives its progression by promoting fibroblasts activation. However, how stiffness influences fibroblasts activation for skin fibrosis progression remains unknown. Here, we report a positive feedback loop mediated by the mechanosensitive ion channel Piezo1 and aberrant tissue mechanics in driving skin fibrosis. Piezo1 is upregulated in fibrotic skin in both humans and mice. Piezo1 knockdown dermal fibroblasts lose their fibroproliferative phenotypes despite being grown on a stiffer substrate. We show that Piezo1 acts through the Wnt2/Wnt11 pathway to mechanically induce secretion of C-C motif chemokine ligand 24 (CCL24, also known as eotaxin-2), a potent cytokine associated with fibrotic disorders. Importantly, adeno-associated virus (AAV)-mediated Piezo1 knockdown ameliorated the progression of skin fibrosis and skin stiffness in mice. Overall, increased matrix stiffness promotes skin fibrosis through the inflammatory Piezo1-Wnt2/Wnt11-CCL24 pathway. In turn, a stiffer skin microenvironment increases Piezo1 expression to exacerbate skin fibrosis aggression. Therefore, targeting Piezo1 represents a strategy to break the positive feedback loop between fibroblasts mechanotransduction and aberrant tissue mechanics in skin fibrosis

Dynamics of cutaneous atmospheric oxygen uptake in response to mechanical stretch revealed by optical fiber microsensor

Skin expands and regenerates in response to mechanical stretch. This important homeostasis process is critical for skin biology and can be exploited to generate extra skin for reconstructive surgery. Atmospheric oxygen uptake is important in skin homeostasis. However, whether and how cutaneous atmospheric oxygen uptake changes during mechanical stretch remains unclear, and relevant research tools to quantify oxygen flux are limited. Herein, we used the scanning micro-optrode technique (SMOT), a non-invasive self-referencing optical fiber microsensor, to achieve real-time measurement of cutaneous oxygen uptake from the atmosphere. An in vivo mechanical stretch-induced skin expansion model was established, and an in vitro Flexcell Tension system was used to stretch epidermal cells. We found that oxygen influx of skin increased dramatically after stretching for 1 to 3 days and decreased to the non-stretched level after 7 days. The enhanced oxygen influx of stretched skin was associated with increased epidermal basal cell proliferation and impaired epidermal barrier. In conclusion, mechanical stretch increases cutaneous oxygen uptake with spatial-temporal characteristics, correlating with cell proliferation and barrier changes, suggesting a fundamental mechanistic role of oxygen uptake in the skin in response to mechanical stretch. Optical fiber microsensor-based oxygen uptake detection provides a non-invasive approach to understand skin homeostasis

Effects of aeration rate on maturity and gaseous emissions during sewage sludge composting

This study investigated effects of aeration rate (AR) on maturity and gaseous emissions during sewage sludge composting, sewage sludge and corn stalks as the bulking agent were co-composted at different ARs (0.1, 0.2, 0.3 L·kg−1 dry matter (DM)·min−1). The thermophilic phase for the low and moderate AR treatments was able meet sanitation requirements, but too short to meet sanitation requirements in the high AR treatment. The high AR treatment was significantly different from the other treatments, and had the lowest electrical conductivity and highest E4/E6(absorbance ratio of wavelength 465 and 665 nm). The AR influences the nitrogen variations; high AR compost had the highest NH4+-N content and lowest NOx−-N content. The AR was the main factor influencing compost stability, but the AR had little impact on pH and the germination index. The moderate AR treatment had the highest NH3 emissions during composting, while the low AR treatment had the highest CH4 and N2O emissions. Based on our comprehensive investigation, the recommended AR for sludge composting is 0.2 L·kg−1 DM·min−1

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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