Polyhexamethylene guanidine accelerates the macrophage foamy formation mediated pulmonary fibrosis.

Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-ß1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.

Septic serum mediates inflammatory injury in human umbilical vein endothelial cells via reactive oxygen species, mitogen activated protein kinases and nuclear factor­κB.

Sepsis­induced blood vessel dysfunction is mainly caused by microvascular endothelial cell injury. However, the mechanism underlying sepsis­induced endothelial cell injury remains unclear. The present study hypothesized that sepsis­induced inflammatory injury of endothelial cells may be the first step of endothelial barrier dysfunction. Therefore, the present study aimed to uncover the mechanism underlying the inflammatory effects of sepsis. A rat model of cecal ligation and puncture­induced sepsis was established, and septic serum was collected. Subsequently, human umbilical vein endothelial cells (HUVECs) were treated with the isolated septic or normal serum. HUVEC viability was assessed using a Cell Count Kit­8 assay. Furthermore, transmission electron microscopy and reverse transcription­quantitative PCR (RT­qPCR) analysis were carried out to observe the cell morphology and determine the mRNA expression levels in septic serum­induced HUVECs. The protein expression levels were evaluated by western blot analysis, and the secretion of the inflammatory factors interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α was determined by ELISA. Additionally, reactive oxygen species (ROS) generation and nuclear factor (NF)­κB nuclear translocation were observed under a fluorescence microscope. The results of the present study demonstrated that HUVEC viability was significantly decreased following 12­ or 24­h treatment with septic serum. In addition, chromatin condensation, mitochondrial vacuolization and endoplasmic reticulum degranulation were observed following treatment with septic serum. Furthermore, the secretion levels of IL­1ß, IL­6 and TNF­α were increased in septic serum­stimulated HUVECs. Septic serum treatment also enhanced superoxide anion generation, promoted extracellular signal regulated kinase 1/2 (ERK1/2), N­terminal kinase (JNK) and p38 mitogen­activated protein kinase (p38) phosphorylation, and increased NF­κB levels in the nuclei of HUVECs. Finally, pre­treatment of HUVECs with the antioxidant N­acetylcysteine, the ERK1/2 inhibitor PD98059, the p38 inhibitor SB203580, the JNK inhibitor SP610025 or the NF­κB inhibitor pyrrolidine dithiocarbamate restored the septic serum­induced IL­1ß, IL­6 and TNF­α expression. In conclusion, the results of the current study suggested that the septic serum­induced endothelial cell injury may be mediated by increasing ROS generation, activation of mitogen­activated protein kinases and NF­κB translocation.

Development and validation of a photobioreactor for uniform distribution of light intensity along the optical path based on numerical simulation.

A theoretical approach was followed to optimize the design of a cylindrical photobioreactor for wastewater treatment based on algal culture. In particular, the problem of uneven light distribution that impairs algal growth was minimized by optimizing the area of uniform illumination distribution for a bioreactor design that can be enlarged without affecting its performance. The theoretical analysis was based on modeled simulations to determine the best configuration and illumination mode. The Monte Carlo method was used to simulate the illumination distribution inside the bioreactor, and the relationships between the width of the area with uniform illumination and related parameters were explored. Based on these theoretical considerations and predictions, an actual experimental photobioreactor was built containing a working area (where culture of Chlorella pyrenoidosa was enabled) and a catchment area for effluent. The performance of this bioreactor was tested with synthetic wastewater as a substrate. The light distribution was found to be relatively uniform inside the bioreactor, supporting excellent algal growth and resulting in maximum removal rates of 84.41% for total nitrogen, 99.73% for total phosphorus, 85.03% for NH4+-N, and 75.94% for chemical oxygen demand (COD) over a period of 32 days of operation. The presented approach provides new insights for improving the efficiency and scalability of photobioreactors and promotes their development for wastewater treatment and resource utilization.

Effect of Potassium Chlorate on the Treatment of Domestic Sewage by Achieving Shortcut Nitrification in a Constructed Rapid Infiltration System.

A constructed rapid infiltration (CRI) system is a new type of sewage biofilm treatment technology, but due to its anaerobic zone it lacks the carbon sources and the conditions for nitrate retention, and its nitrogen removal performance is very poor. However, a shortcut nitrification–denitrification process presents distinctive advantages, as it saves oxygen, requires less organic matter, and requires less time for denitrification compared to conventional nitrogen removal methods. Thus, if the shortcut nitrification–denitrification process could be applied to the CRI system properly, a simpler, more economic, and efficient nitrogen removal method will be obtained. However, as its reaction process shows that the first and the most important step of achieving shortcut nitrification–denitrification is to achieve shortcut nitrification, in this study we explored the feasibility to achieve shortcut nitrification, which produces nitrite as the dominant nitrogen species in effluent, by the addition of potassium chlorate (KClO3) to the influent. In an experimental CRI test system, the effects on nitrogen removal, nitrate inhibition, and nitrite accumulation were studied, and the advantages of achieving a shortcut nitrification–denitrification process were also analysed. The results showed that shortcut nitrification was successfully achieved and maintained in a CRI system by adding 5 mM KClO3 to the influent at a constant pH of 8.4. Under these conditions, the nitrite accumulation percentage was increased, while a lower concentration of 3 mM KClO3 had no obvious effect. The addition of 5mM KClO3 in influent presumably inhibited the activity of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB), but inhibition of nitrite-oxidizing bacteria (NOB) was so strong that it resulted in a maximum nitrite accumulation percentage of up to over 80%. As a result, nitrite became the dominant nitrogen product in the effluent. Moreover, if the shortcut denitrification process will be achieved in the subsequent research, it could save 60.27 mg CH3OH per litre of sewage in the CRI system compared with the full denitrification process.