No abstract

Dasatinib treatment is approved as first-line therapy for chronic myeloid leukemia. However, pulmonary hypertension (PH) is a highly morbid and often fatal side-effect of dasatinib, characterized by progressive pulmonary vascular remodeling. Melatonin exerts strong antioxidant capacity against the progression of cardiovascular system diseases. The present work aimed to investigate the effect of melatonin on dasatinib-aggravated hypoxic PH and explore its possible mechanisms. Dasatinib-aggravated rat experimental model of hypoxic PH was established by utilizing dasatinib under hypoxia. The results indicated that melatonin could attenuate dasatinib-aggravated pulmonary pressure and vascular remodeling in rats under hypoxia. Additionally, melatonin attenuated the activity of XO, the content of MDA, the expression of NOX4, and elevated the activity of CAT, GPx, and SOD, the expression of SOD2, which were caused by dasatinib under hypoxia. In vitro, dasatinib led to decreased LDH activity and production of NO in human pulmonary microvascular endothelial cells (HPMECs), moreover increased generation of ROS, and expression of NOX4 both in HPMECs and primary rat pulmonary arterial smooth muscle cells (PASMCs) under hypoxia. Dasatinib up-regulated the expression of cleaved caspase-3 and the ratio of apoptotic cells in HPMECs, and also elevated the percentage of S phase and the expression of Cyclin D1 in primary PASMCs under hypoxia. Melatonin ameliorated dasatinib-aggravated oxidative damage and apoptosis in HPMECs, meanwhile reduced oxidative stress level, proliferation, and repressed the stability of HIF1-α protein in PASMCs under hypoxia. In conclusion, melatonin significantly attenuates dasatinib-aggravated hypoxic PH by inhibiting pulmonary vascular remodeling in rats. The possible mechanisms involved protecting endothelial cells and inhibiting abnormal proliferation of smooth muscle cells. Our findings may suggest that melatonin has potential clinical value as a therapeutic approach to alleviate dasatinib-aggravated hypoxic PH.

Hypoxic pulmonary hypertension (HPH) is a progressive cardiopulmonary system disease characterized by pulmonary vascular remodeling. Its occurrence and progression are closely related to oxidative stress. Lycopene, extracted from red vegetables and fruits, exhibits a particularly high antioxidant capacity that is beneficial for cardiovascular diseases. Nevertheless, the role and mechanism of lycopene in HPH remain unknown. Here, we found that lycopene reversed the elevated right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary vascular remodeling induced by hypoxia in rats. In vitro, lycopene caused lower proliferation and migration of PASMCs, with higher apoptosis. Consistent with the antiproliferative result of lycopene on hypoxic PASMCs, the hippo signaling pathway associated with cell growth was activated. Furthermore, lycopene reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) activity in the lungs and serum of rats under hypoxia conditions. The expression of NOX4 in the lungs was also significantly decreased. Hypoxic PASMCs subjected to lycopene showed decreased reactive oxygen species (ROS) production and NOX4 expression. Importantly, lycopene repressed HIF-1α expression both in the lungs and PASMCs in response to hypoxia in the absence of a significant change of HIF-1α mRNA. Compared with 2ME2 (a HIF-1α inhibitor) alone treatment, lycopene treatment did not significantly change PASMC proliferation, NOX4 expression, and ROS production after 2ME2 blocked HIF-1α, suggesting the inhibitory effect of lycopene on HIF-1α-NOX4-ROS axis and the targeted effect on HIF-1α. After CHX blocked protein synthesis, lycopene promoted the protein degradation of HIF-1α. MG-132, a proteasome inhibitor, notably reversed the decrease in HIF-1α protein level induced by lycopene in response to hypoxia. Therefore, lycopene suppressed hypoxia-induced oxidative stress through HIF-1α-NOX4-ROS axis, thereby alleviating HPH. Our findings will provide a new research direction for clinical HPH therapies.

Serious stains on the surface of photovoltaic modules will affect the efficiency of power generation and may cause fire. Therefore, the cleaning must be clean and thorough. If the dead corner is left, it may cause “hot spot effect” and other serious consequences. The effect of photovoltaic module surface fouling on power generation efficiency is quite significant. Firstly, the surface turbidity affects the light transmission rate, and then affects the radiation amount accepted by the module surface; secondly, the dirt adheres to the surface of the panel and forms shadow, which produces hot spot effect in the local part of the PV module, thus causing damage to the PV panel, affecting the power generation rate and shortening the life of the PV panel. This process will aggravate the aging of the battery panel, reduce the output, and even cause a fire in serious cases. Photovoltaic cleaning robot is a new thing. In recent years, it has been highly concerned by the majority of photovoltaic power plant owners and photovoltaic enterprises. Photovoltaic cleaning robots can not only tell stories. However, it is necessary to realize the unattended periodic cleaning, intelligent dust removal and snow removal of photovoltaic modules through low cost and high reliability, and improve the efficiency of cleaning dust on the surface of photovoltaic panels by using intelligent cleaning robots, and thoroughly remove the dust and dirt on the surface of photovoltaic panels, so as to improve the power generation efficiency. Extend the service life of photovoltaic power station. This is a real practical photovoltaic cleaning robot[1].

Aristolochic acid (AA) and its derivatives, isolated from the Aristolochiaceae plant family, are a group of nitrophenanthrene carboxylic acids (Balachandran et al., 2005;Yang et al., 2013). Applications prepared from Aristolochiaceae plants, including AA, have been used for the treatment of diverse diseases, such as arthritis, gout, rheumatism, hypertension, urinary tract infection, and festering wounds (Debelle et al., 2008;Anger et al., 2020). However, these applications are reported to be nephrotoxic. Aristolochic acid nephropathy (AAN) is a common nephropathy caused by AA (Chen et al., 2012;Wang et al., 2015). In AAN, most patients rapidly deteriorate to end-stage renal disease (ESRD) (Luciano and Perazella, 2015). Patients with AAN exhibit increased serum creatinine (Scr), severe anemia, rapid tubulointerstitial injury, loss of renal proximal tubules, and tubule atrophy (Priestap et al., 2012). Recently, AA has been shown to cause acute kidney