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Hypoxia-inducible factors (HIFs) are one of the primary transcription factors regulating oxygen balance, and their stability is determined by the hydroxylation state of the prolyl hydroxylase domain (PHD) that is sensitive to oxygen. In recent years, studies have shown that HIFs-prolyl hydroxylases (PHDs) oxygen-sensing pathway is involved in the process of cellular ferroptosis. Ferroptosis, a new type of cell death, different from necrosis, apoptosis, necrotizing apoptosis, and pyroptosis, is essentially a programmed death caused by the accumulation of iron-dependent lipid peroxides in cells. This paper focuses on the role and mechanism of the HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis involved in nerve diseases, tumors, lung injury, and chemical nerve damage from three aspects of iron metabolism, lipid metabolism, and glutathione (GSH) synthesis/metabolism. This review will provide a theoretical basis and new ideas for the development of novel drugs targeting the HIFs-PHDs oxygen-sensing pathway and capable of regulating ferroptosis for the treatment of diseases related to ferroptosis such as nervous system diseases and tumors.

The Dawu well field, one of the largest in China, supplies most of the water for the Zibo City urban area in Shandong Province. The field yields 522,400–535,400 m3/d from an aquifer in fractured karstic Middle Ordovician carbonate rocks. Much of the recharge to the aquifer is leakage of surface water from Zihe Stream, the major drainage in the area. Installation of the Taihe Reservoir in 1972 severely reduced the downstream flow in Zihe Stream, resulting in a marked reduction in the water table in the Dawu field. Since 1994, following the installation of a recharge station on Zihe Stream upstream from the well field that injects water from the Taihe Reservoir into the stream, the groundwater resources of the field have recovered. An average of 61.2×103 m3/d of groundwater, mostly from the Ordovician aquifer, is pumped from the Heiwang iron mine, an open pit in the bed of Zihe Stream below the Taihe Reservoir. A stepwise regression equation, used to evaluate the role of discharge from the reservoir into the stream, confirms that reservoir water is one of the major sources of groundwater in the mine.

Boshan is an industrial city in the center of Shandong Province where ground water is the only source for the urban water supply. The major water resource is fracture-karst water in the middle Ordovician carbonate rocks. Based on the hydrogeologic investigation and mapping in this area, the authors studied the geologic and hydrogeologic settings, the major pollution sources and the pathways of contamination, the principal contaminants, and their spatial distribution in ground water. The ground-water quality has also been estimated by the fuzzy mathematic method. The geostatistical method, such as the kriging method, was taken to simulate spatial distribution of the contaminants. The grey system method was adopted to forecast future contamination. An attempt at the remediation of Cr{sup 6+} contamination in fracture-karst water was also discussed. Finally, some proposals for the protection of the ground-water environment in Boshan District are offered.