Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms.

Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1ß and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.

Effect of High Altitude Environment on Pharmacokinetic and Pharmacodynamic of Warfarin in Rats.

BACKGROUND: High altitude environment affects the pharmacokinetic (PK) parameters of drugs and the PK parameters are an important theoretical basis for guiding the rational clinical use of drugs. Warfarin is an oral anticoagulant of the coumarin class commonly used in clinical practice, but it has a narrow therapeutic window and wide individual variation. However, the effect of high altitude environment on PK and pharmacodynamic (PD) of warfarin is unclear. OBJECTIVE: The objective of this study is to investigate the effect of a high altitude environment on PK and PD of warfarin in rats. METHOD: Rats were randomly divided into plain group and high altitude group and blood samples were collected through the orbital venous plexus after administration of 2 mg/kg warfarin. Warfarin concentrations in plasma samples were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and PK parameters were calculated by the non-compartment model using WinNonlin 8.1 software. Meanwhile, the expression of PXR, P-gp and CYP2C9 in liver tissues was also determined by western blotting. The effect of high altitude environment on PD of warfarin was explored by measuring activated partial thromboplastin time (APTT) and prothrombin time (PT) values and then calculated international normalized ratio (INR) values based on PT. RESULTS: Significant changes in PK behaviors and PD of warfarin in high altitude-rats were observed. Compared with the plain-rats, the peak concentration (Cmax) and the area under the plasma concentration-time curve (AUC) increased significantly by 50.9% and 107.46%, respectively. At the same time, high altitude environment significantly inhibited the expression of PXR, P-gp and CYP2C9 in liver tissues. The results of the PD study showed that high altitude environments significantly prolonged PT, APTT and INR values. CONCLUSION: High altitude environment inhibited the metabolism and increased the absorption of warfarin in rats and increased the effect of anticoagulant effect, suggesting that the optimal dose of warfarin for patients at high altitude should be reassessed.

Disrupted gut microbiota aggravates spatial memory dysfunction induced by high altitude exposure: A link between plateau environment and microbiome-gut-brain axis.

Approximately 400 million people work and live in high-altitude areas and suffer from memory dysfunction worldwide. Until now, the role of the intestinal flora in plateau-induced brain damage has rarely been reported. To address this, we investigated the effect of intestinal flora on spatial memory impairment induced by high altitudes based on the microbiome-gut-brain axis theory. C57BL/6 mice were divided into three groups: control, high-altitude (HA), and high-altitude antibiotic treatment (HAA) group. The HA and HAA groups were exposed to a low-pressure oxygen chamber that simulated an altitude of 4000 m above sea level (m. a. s.l.) for 14 days, with the air pressure in the chamber set at 60-65 kPa. The results showed that spatial memory dysfunction induced by the high-altitude environment was aggravated by antibiotic treatment, manifesting as lowered escape latency and hippocampal memory-related proteins (BDNF and PSD-95). 16 S rRNA sequencing showed a remarkable separation of the ileal microbiota among the three groups. Antibiotic treatment exacerbated the reduced richness and diversity of the ileal microbiota in mice in the HA group. Lactobacillaceae were the main target bacteria and were significantly reduced in the HA group, which was exacerbated by antibiotic treatment. Meanwhile, reduced intestinal permeability and ileal immune function in mice exposed high-altitude environment was also aggravated by antibiotic treatment, as indicated by the lowered tight junction proteins and IL-1ß and IFN-γ levels. Furthermore, indicator species analysis and Netshift co-analysis revealed that Lactobacillaceae (ASV11) and Corynebacteriaceae (ASV78, ASV25, and ASV47) play important roles in high-altitude exposure-induced memory dysfunction. Interestingly, ASV78 was negatively correlated with IL-1ß and IFN-γ levels, indicating that ASV78 may be induced by reduced ileal immune function, which mediates high-altitude environment exposure-induced memory dysfunction. This study provides evidence that the intestinal flora is effective in preventing brain dysfunction caused by exposure to high-altitude environments, suggesting a relationship between the microbiome-gut-brain axis and altitude exposure.

Physical Properties and Hydration Characteristics of Low-Heat Portland Cement at High-Altitude.

High-altitude environments are characterized by low air pressures and temperature variations. Low-heat Portland cement (PLH) is a more energy-efficient alternative to ordinary Portland cement (OPC); however, the hydration properties of PLH at high altitudes have not been previously investigated. Therefore, in this study, the mechanical strengths and levels of the drying shrinkage of PLH mortars under standard, low-air-pressure (LP), and low-air-pressure and variable-temperature (LPT) conditions were evaluated and compared. In addition, the hydration characteristics, pore size distributions, and C-S-H Ca/Si ratio of the PLH pastes under different curing conditions were explored using X-ray diffraction (XRD), thermogravimetric analysis (TG), scanning electron microscopy (SEM), and mercury intrusion porosimetry (MIP). Compared with that of the PLH mortar cured under the standard conditions, the compressive strength of the PLH mortar cured under the LPT conditions was higher at an early curing stage but lower at a later curing stage. In addition, drying shrinkage under the LPT conditions developed rapidly at an early stage but slowly at a later stage. Moreover, the characteristic peaks of ettringite (AFt) were not observed in the XRD pattern after curing for 28 d, and AFt transformed into AFm under the LPT conditions. The pore size distribution characteristics of the specimens cured under the LPT conditions deteriorated, which was related to water evaporation and micro-crack formation at low air pressures. The low pressure hindered the reaction between belite and water, which contributed to a significant change in the C-S-H Ca/Si ratio in the early curing stage in the LPT environment.

Diet and high altitude strongly drive convergent adaptation of gut microbiota in wild macaques, humans, and dogs to high altitude environments.

Animal gut microbiota plays an indispensable role in host adaptation to different altitude environments. At present, little is known about the mechanism of animal gut microbiota in host adaptation to high altitude environments. Here, we selected wild macaques, humans, and dogs with different levels of kinship and intimate relationships in high altitude and low altitude environments, and analyzed the response of their gut microbiota to the host diet and altitude environments. Alpha diversity analysis found that at high altitude, the gut microbiota diversity of wild macaques with more complex diet in the wild environments is much higher than that of humans and dogs with simpler diet (p < 0.05), and beta diversity analysis found that the UniFrac distance between humans and dogs was significantly lower than between humans and macaques (p < 0.05), indicating that diet strongly drive the convergence of gut microbiota among species. Meanwhile, alpha diversity analysis found that among three subjects, the gut microbiota diversity of high altitude population is higher than that of low altitude population (ACE index in three species, Shannon index in dog and macaque and Simpson index in dog, p < 0.05), and beta diversity analysis found that the UniFrac distances among the three subjects in the high altitude environments were significantly lower than in the low altitude environments (p < 0.05). Additionally, core shared ASVs analysis found that among three subjects, the number of core microbiota in high altitude environments is higher than in low altitude environments, up to 5.34 times (1,105/207), and the proportion and relative abundance of the core bacteria types in each species were significantly higher in high altitude environments than in low altitude environments (p < 0.05). The results showed that high altitude environments played an important role in driving the convergence of gut microbiota among species. Furthermore, the neutral community model trial found that the gut microbiota of the three subjects was dispersed much more at high altitude than at low altitude, implying that the gut microbiota convergence of animals at high altitudes may be partly due to the microbial transmission between hosts mediated by human activities.

Mountain spa rehabilitation improved health of patients with post-COVID-19 syndrome: pilot study.

European Association of Spa Rehabilitation (ESPA) recommends spa rehabilitation for patients with post-COVID-19 syndrome. We tested the hypothesis that a high-altitude environment with clean air and targeted spa rehabilitation (MR - mountain spa rehabilitation) can contribute to the improving platelet mitochondrial bioenergetics, to accelerating patient health and to the reducing socioeconomic problems. Fifteen healthy volunteers and fourteen patients with post-COVID-19 syndrome were included in the study. All parameters were determined before MR (MR1) and 16-18 days after MR (MR2). Platelet mitochondrial respiration and OXPHOS were evaluated using high resolution respirometry method, coenzyme Q10 level was determined by HPLC, and concentration of thiobarbituric acid reactive substances (TBARS) as a parameter of lipid peroxidation was determined spectrophotometrically. This pilot study showed significant improvement of clinical symptoms, lungs function, and regeneration of reduced CI-linked platelet mitochondrial respiration after MR in patients with post-COVID-19 syndrome. High-altitude environment with spa rehabilitation can be recommended for the acceleration of recovery of patients with post-COVID-19 syndrome.

Highland adaptation of birds on the Qinghai-Tibet Plateau via gut microbiota.

Highland birds evolve multiple adaptive abilities to cope with the harsh environments; however, how they adapt to the high-altitude habitats via the gut microbiota remains understudied. Here we integrated evidences from comparative analysis of gut microbiota to explore the adaptive mechanism of black-necked crane, a typical highland bird in the Qinghai-Tibet Plateau. Firstly, the gut microbiota diversity and function was compared among seven crane species (one high-altitude species and six low-altitude species), and then among three populations of contrasting altitudes for the black-necked crane. Microbiota community diversity in black-necked crane was significantly lower than its low-altitude relatives, but higher microbiota functional diversity was observed in black-necked crane, suggesting that unique bacteria are developed and acquired due to the selection pressure of high-altitude environments. The functional microbial genes differed significantly between the low- and high-altitude black-necked cranes, indicating that altitude significantly impacted microbial communities' composition and structure. Adaptive changes in microbiota diversity and function are observed in response to high-altitude environments. These findings provide us a new insight into the adaptation mechanism to the high-altitude environment for birds via the gut microbiota. KEY POINTS: • The diversity and function of gut microbiota differed significantly between the low- and high-altitude crane species. • Black-necked crane adapts to the high-altitude environment via specific gut microbiota. • Altitude significantly impacted microbial communities' composition and structure.

[Application and research of smart wearable devices for heart and brain diseases related to high altitude].

Smart wearable devices play an increasingly important role in physiological monitoring and disease prevention because they are portable, real-time, dynamic and continuous.The popularization of smart wearable devices among people under high-altitude environment would be beneficial for the prevention for heart and brain diseases related to high altitude. The current review comprehensively elucidates the effects of high-altitude environment on the heart and brain of different population and experimental subjects, the characteristics and applications of different types of wearable devices, and the limitations and challenges for their application. By emphasizing their application values, this review provides practical reference information for the prevention of high-altitude disease and the protection of life and health.

Application and research of smart wearable devices for heart and brain diseases related to high altitude / 生物医学工程学杂志

Smart wearable devices play an increasingly important role in physiological monitoring and disease prevention because they are portable, real-time, dynamic and continuous.The popularization of smart wearable devices among people under high-altitude environment would be beneficial for the prevention for heart and brain diseases related to high altitude. The current review comprehensively elucidates the effects of high-altitude environment on the heart and brain of different population and experimental subjects, the characteristics and applications of different types of wearable devices, and the limitations and challenges for their application. By emphasizing their application values, this review provides practical reference information for the prevention of high-altitude disease and the protection of life and health.

Cirbp-PSD95 axis protects against hypobaric hypoxia-induced aberrant morphology of hippocampal dendritic spines and cognitive deficits.

Hypobaric hypoxia (HH) is a typical characteristic of high altitude environment and causes a spectrum of pathophysiological effects, including headaches, gliovascular dysfunction and cognitive retardation. Here, we sought to understand the mechanisms underlying cognitive deficits under HH exposure. Our results showed that hypobaric hypoxia exposure impaired cognitive function and suppressed dendritic spine density accompanied with increased neck length in both basal and apical hippocampal CA1 region neurons in mice. The expression of PSD95, a vital synaptic scaffolding molecule, is down-regulated by hypobaric hypoxia exposure and post-transcriptionally regulated by cold-inducible RNA-binding protein (Cirbp) through 3'-UTR region binding. PSD95 expressing alleviates hypoxia-induced dendritic spine morphology changes of hippocampal neurons and memory deterioration. Moreover, overexpressed Cirbp in hippocampus rescues HH-induced abnormal expression of PSD95 and attenuates hypoxia-induced dendritic spine injury and cognitive retardation. Thus, our findings reveal a novel mechanism that Cirbp-PSD-95 axis appears to play an essential role in HH-induced cognitive dysfunction in mice.

Identification of the molecular mechanisms underlying brisket disease in Holstein heifers via microbiota and metabolome analyses.

Brisket disease (BD) is common among Holstein heifers in high-altitude environments, and this disease may result in serious economic loss. At present, no effective treatment is available for brisket disease. In this study, liver and cecum samples were collected from five heifers with BD and five healthy heifers (HH) for analyses of the metabolome and microbiota. The mean pulmonary arterial pressure and systolic blood pressure were significantly higher in BD heifers, whereas the average breathing rate, blood oxygen saturation, and glucose level were significantly lower in BD group than in the HH group. Further, 16S rDNA data showed that the abundance of Firmicutes was significantly lower and that of Bacteroidetes was significantly higher in BD group than in the HH group. At the genus level, the BD group heifers harbored fewer Ruminococcaceae and Lachnospiraceae than the HH group. Several metabolites, including beta-D-fructose, D-ribose, 1,4-beta-D-glucan, sucrose, and glucose-6-phosphate were present at low levels in BD heifers. Moreover, the mean pulmonary arterial pressure was negatively correlated with beta-D-fructose (r = - 0.74; P = 0.013), D-ribose (r = - 0.72; P = 0.018), and acetyl-tyrosine-ethyl-ester (r = - 0.71; P = 0.022). We also found that mean pulmonary arterial pressure was negatively correlated with most of the genera, including those in the families of Lachnospiraceae and Ruminococcaceae. In summary, the decreased levels of metabolites and microbial genera might affect BD by limiting the energy supply. This study may help us better understand the role of the microbiota in BD and provide new insights into the management of feeding to decrease the rate of BD in Holstein dairy cows in the Qinghai-Tibetan plateau.

Characterisation of the gut microbial community of rhesus macaques in high-altitude environments.

BACKGROUND: The mammal intestinal microbiota is involved in various physiological processes and plays a key role in host environment adaption. However, for non-human primates (NHPs), little is known about their gut microbial community in high-altitude environments and even less about their adaption to such habitats. We characterised the gut microbial community of rhesus macaques from multiple high-altitude environments and compared it to those of low-altitude populations. RESULTS: We collected faecal samples of rhesus macaques from four high-altitude populations (above 3000 m) and three low-altitude populations (below 500 m). By calculating the alpha diversity index, we found that high-altitude populations exhibited a higher diversity. Statistical analysis of beta diversity indicated significant differences between high- and low-altitude populations. Significant differences were also detected at the phylum and family levels. At the phylum level, the high-altitude gut microbial community was dominated by Firmicutes (63.42%), while at low altitudes, it was dominated by Bacteroidetes (47.4%). At the family level, the high-altitude population was dominated by Ruminococcaceae (36.2%), while the low-altitude one was dominated by Prevotellaceae (39.6%). Some families, such as Christensenellaceae and Rikenellaceae, were consistently higher abundant in all high-altitude populations. We analysed the overlap of operational taxonomic units (OTUs) in high-altitude populations and determined their core OTUs (shared by all four high-altitude populations). However, when compared with the low-altitude core OTUs, only 65% were shared, suggesting a divergence in core OTUs. Function prediction indicated a significant difference in gene copy number of 35 level-2 pathways between high- and low-altitude populations; 29 of them were higher in high altitudes, especially in membrane transport and carbohydrate metabolism. CONCLUSIONS: The gut microbial community of high-altitude rhesus macaques was significantly distinct from that of low-altitude populations in terms of diversity, composition and function. High-altitude populations were dominated by Firmicutes and Ruminococcace, while in low-altitude populations, Bacteroidetes and Prevotellaceae were dominant. The difference in gut microbiota between these two populations may be caused by differences in host diet, environmental temperature and oxygen pressure. These differentiated gut microbial microorganisms may play a critical role in the adaptive evolution of rhesus macaques to high-altitude environments.

Recent progress of high-altitude environment impact on the eyes / 中华实验眼科杂志

High-altitude environment has its unique characteristics,which can cause a variety of acute and chronic mountain sicknesses.With increasing human activities at high altitude,the impact of high altitude exposure on human body has become a hotspot.Hypobaric hypoxia,strong breeze,strong radiation and excess ultraviolet exposure can induce pathophysiological changes in human body and eyes.Individual difference exists in response to high-altitude environment.In order to provide ideas for further study on the mechanisms of ocular changes at high altitude,this article reviewed the characteristics of high-altitude environment and their impact on the eyes,including visual function (vision,color vision,visual field and visual electrophysiology),intraocular pressure,ocular structures (tear film,conjunctiva,cornea,pupil,lens and fundus) and ocular treatments.

Development of high altitude stretcher / 医疗卫生装备

Objective To develop a new type of stretcher to meet the needs of medical evacuation in high altitude region. Methods The stretcher was composed of a bearing plate, a protective shield, a control unit and external accessories. An enclosed space was formed by the shield and plate,and there were an air inlet and outlet in the shield to regulate the pressure and oxygen content in the space. An electric blanket was put on the plate, which was combined with the control unit to execute dynamic monitoring and control of the temperature and oxygen content in the shield.Results The stretcher enhanced the casualty safety during transport so that the effect of high altitude on casualty conditions could be decreased effectively. Conclusion The stretcher can be used for casualty transport in high-altitude conditions while reduce the casualty riks.

Pathophysiologic Determination of Frostbite Under High Altitude Environment Simulation in Sprague-Dawley Rats.

OBJECTIVES: Pathophysiologic changes of frostbite have been postulated but rarely understood, especially the changes caused by chilly high altitude environment. Therefore, we investigated the pathophysiologic changes of high altitude frostbite (HAF) caused by cold and hypoxia. METHODS: Forty Sprague-Dawley rats were randomly divided into 5 equal groups, namely, control, superficial HAF (S-HAF), partial-thickness HAF (PT-HAF), full-thickness HAF (FT-HAF), and partial-thickness normal frostbite (PT-NF) groups. The S-HAF, PT-HAF, and FT-HAF groups were fed under hypobaric hypoxic conditions simulating an altitude of 5000 m. Then, the PT-NF, S-HAF, PT-HAF, and FT-HAF models were constructed by controlling the duration of the direct freezing by liquid nitrogen. Animal vital signs were measured after the operation, and histopathologic changes were observed after routine hematoxylin and eosin staining. In addition, the microcirculation of frostbite tissues was monitored and compared by contrast ultrasonography during wound healing. RESULTS: The S-HAF, PT-HAF, and FT-HAF groups showed significant differences in the microcirculatory and histopathologic changes in the various tissue layers (P < .05). In addition, combined cold and hypoxia caused more damage to frostbite tissue than pure cold. The circulation recovery of HAF models was significantly slower relative to NF models (P < .05). CONCLUSIONS: A safe and reproducible HAF model was proposed. More important, pathophysiologic determination of HAF provided the foundation and potential for developing novel and effective frostbite therapies.

De novo transcriptome characterization of the ghost moth, Thitarodes pui, and elevation-based differences in the gene expression of its larvae.

Thitarodes pui larvae are the hosts of a medicinal fungus, Ophiocordyceps sinensis, and are naturally distributed at an altitude of 4100-4650 m on Segrila Mountain of the Tibetan Plateau. Here, we conducted transcriptome profiling of T. pui larvae based on the Illumina high-throughput sequencing platform. Subsequently, we explored elevation-based differences of T. pui by comparing gene expression profiles between larvae at high-altitude (natural conditions) and larvae exposed to short-term (2months) low-altitude conditions. A total of 105,935,208 clean reads were assembled into 70,048 unigenes with a mean length of 639 bp. All unigenes were searched against public databases, with 51.26% unigenes being successfully annotated in the NR, SWISS-PROT, EuKaryotic Orthologous Groups (KOG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genome (KEGG) databases. A total of 11,846 unigenes were functionally classified into 239 KEGG pathways. Metabolism was the most represented pathway, with 4271 unigenes (36.05%). Using the transcriptome data as a reference, 629 (311 up-regulated/318 down-regulated) genes were differentially expressed by low-altitude larvae when compared with those of high-altitude larvae. The most significantly differentially expressed genes were annotated in the processes of carbohydrate metabolism, lipid metabolism, and respiration. This report provides valuable information about the T. pui transcriptome for future genomic studies, including how gene expression is altered in larvae reared at different elevations.