Objective: High altitude is characterized by low oxygen pressure, resulting in multiple adaptive responses. Tibetans who have lived in the plateau for thousands of years have developed unique phenotypes, such as downregulation of the HIF pathway through EPAS1 and EGLN1 gene mutation. However, the changes of hemoglobin–oxygen affinity under hypoxia environment remain elusive. Methods: A blood cell analyzer and a blood oxygen analyzer were used to conduct routine blood tests and measure the oxygen affinity P₅₀ in in the Han population that rapidly entered the plateau (for 3–7 days), the plateau-acclimatized Han population (residing for 30 days on the plateau), the plateau Han population (more than 10 years on the plateau), and the Tibetan population. Results: The Han population that rapidly entered the plateau had increasing higher P₅₀ values, RBCs counts and hemoglobin (HGB) levels, while the acclimatized Han population, the plateau Han population and Tibetan all had significantly lower P₅₀ values. However, there were no significant differences in the RBCs counts and HGB levels between the plateau Han, Tibetan populations and the Han population of the plains. Discussion: The adaptability of the Tibetan and plateau Han populations to the plateau was mainly due to the strong affinity of HGB for oxygen, which provided sufficient oxygen for tissues and organs. Conclusions: The change of P₅₀ could be a feature of the adaptation to the plateau and to avoid altitude sickness, such as high-altitude polycythemia and dyspnea.

Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.Graphical Abstract