Dysregulated VEGF/VEGFR-2 Signaling and Plexogenic Lesions in the Embryonic Lungs of Chickens Predisposed to Pulmonary Arterial Hypertension.

Plexiform lesions are a hallmark of pulmonary arterial hypertension (PAH) in humans and are proposed to stem from dysfunctional angioblasts. Broiler chickens (Gallus gallus) are highly susceptible to PAH, with plexiform-like lesions observed in newly hatched individuals. Here, we reported the emergence of plexiform-like lesions in the embryonic lungs of broiler chickens. Lung samples were collected from broiler chickens at embryonic day 20 (E20), hatch, and one-day-old, with PAH-resistant layer chickens as controls. Plexiform lesions consisting of CD133+/vascular endothelial growth factor receptor type-2 (VEGFR-2)+ angioblasts were exclusively observed in broiler embryos and sporadically in layer embryos. Distinct gene profiles of angiogenic factors were observed between the two strains, with impaired VEGF-A/VEGFR-2 signaling correlating with lesion development and reduced arteriogenesis. Pharmaceutical inhibition of VEGFR-2 resulted in enhanced lesion development in layer embryos. Moreover, broiler embryonic lungs displayed increased activation of HIF-1α and nuclear factor erythroid 2-related factor 2 (Nrf2), indicating a hypoxic state. Remarkably, we found a negative correlation between lung Nrf2 activation and VEGF-A and VEGFR-2 expression. In vitro studies indicated that Nrf2 overactivation restricted VEGF signaling in endothelial progenitor cells. The findings from broiler embryos suggest an association between plexiform lesion development and impaired VEGF system due to aberrant activation of Nrf2.

Synergistic effect of organic matter-floc size-bound water and multifactorial quantitative model of optimal reagent demand in sewage sludge conditioning process prior to dewatering.

The high amount of densely hydrated organic substance present in sewage sludge impedes its filterability, thus restricting sludge disposal. Although chemical conditioning can facilitate filtration, the diverse sludge properties complicate the quantitative control of conditioning process. Investigating how to accurately quantify the optimal reagent demand (ORD) based on the critical physicochemical properties of the target sludge is an effective way to address the current issue. This study focused on the sewage and stockpiled sludge with varying properties, and their ORD under different chemical conditioning. The results showed that organic content, floc size, and bound water synergistically influenced conditioning process. The quantitative models were established between their coupling indicators and ORD, with coupling indicators including the ratio of organic content to floc size, the ratio of flow viscosity to floc size, and the ratio of the product of organic content and bound water to floc size. The linear correlation of the coupling indicator with ORD was higher than that of the traditional single-factor indicator. Furthermore, the inherent filterability of the sludge was somewhat separate from the adjustability of its filtration. A "dual-system" impact model was proposed to characterized the conditioning and filtration processes. These results provide theoretical guidance for the quantitative regulation of conditioning and filtration processes of sludge with complex characteristics.