The Qinghai–Tibet Plateau is one of the regions most strongly affected by climate change. The climate feedback of the distribution of plateau pika, a key species, is closely related to the trophic structure of the plateau ecosystem and the development of agriculture and animal husbandry on the plateau. In order to understand the impact of future climate change on the suitable distribution area of plateau pika, potential suitable distribution areas of Plateau pika were predicted using the MaxEnt model under three climate scenarios (SSP 1-2.6, SSP 2-4.5, and SSP 5-8.5) in the near term (2021–2040) and medium term (2041–2060). The predictions were found to be highly accurate with AUC values of 0.997 and 0.996 for the training and test sets. The main results are as follows: (1) The precipitation of the wettest month (BIO 16), mean diurnal range (BIO 2), slope, elevation, temperature seasonality (BIO 4), and annual mean temperature (BIO 1) were the main influencing factors. (2) In the historical period, the total suitable distribution area of Plateau pika in the Qinghai–Tibet Plateau accounted for 29.90% of the total area at approximately 74.74 × 10⁴ km², concentrated in the eastern and central areas of the Qinghai–Tibet Plateau. (3) The total suitable distribution area of pika exhibited an expansion trend under SSP 1-2.6 and SSP 2-4.5 in the near term (2021–2040), and the expansion area was concentrated in the eastern and central parts of the Qinghai–Tibet Plateau. The expansion area was the largest in Qinghai Province, followed by Sichuan Province and Tibet. In contrast, the suitable distribution area shrank in the Altun Mountains, Xinjiang. Under SSP 5-8.5 in the near term and all scenarios in the medium term (2041–2060), the suitable distribution area of Plateau pika decreased to different degrees. The shrinkage area was concentrated at the margin of the Qaidam Basin, central Tibet, and the Qilian Mountains in the east of Qinghai Province. (4) Plateau pika migrated toward the east or southeast on the Qinghai–Tibet Plateau under the three climate scenarios. Under most of the scenarios, the migration distance was longer in the medium term than in the near term.

Background: To investigate venous thromboembolism (VTE) in hospitalized patients with severe high altitude pulmonary edema (HAPE), we performed a single center retrospective study to evaluate its clinical characteristics, prognosis, and potential thromboprophylaxis strategies in a large referral and treatment center in plateau regions. Methods: We studied a total of 18 patients with severe HAPE from January 1, 2012 to December 31, 2021. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities and cardiac ultrasound, and computed tomographic pulmonary angiography (CTPA) variables were obtained, and comparisons were made between groups with and without VTE. Results: Of the 18 patients hospitalized with severe HAPE (age 43 (range, 34–54) years, 14 [77.8%] men), 7 patients developed VTE (38.9%), including 5 with deep vein thrombosis (DVT) and pulmonary embolism (PE), 2 of whom had DVT only. Eighteen patients are all firstly rapid ascent to high altitudes which the mean altitude was 3700 m (3656–4050 m). Compared with patients who did not have VTE, patients with VTE had a longer time in hospital (13 [11, 19] versus 9 [7, 12]; P = 0.027), respiratory failure (6 [85.7%] versus 2 [18.2%]; P = 0.013), the shortened APTT (21.50 [19.00, 27.50] versus 26.30 [24.80, 30.10]; P = 0.044) and the higher level of D-dimer (7.81 [4.62, 9.60] versus 2.90 [1.75, 3.37]; P = 0.003). The proportion of thromboprophylaxis is too low in our cohort which 2 of 18 (11.1%) patients were given VTE prophylaxis. There was no statistically significant difference between the VTE and non-VTE groups (0 [0.0%] versus 2 [18.2%]; P = 0.497). Conclusions: The prevalence of VTE is high in hospitalized patients with severe high altitude pulmonary edema (HAPE). Prophylaxis for venous thromboembolism may be protective in severe HAPE patients after admission. Our data seem to suggest that VTE is probably an additional prognostic factors in patients with severe HAPE.

Background: Pulmonary metabolic dysfunction can cause lung tissue injury. There is still no ideal drug to protect against hypoxia-induced lung injury, therefore, the development of new drugs to prevent and treat hypoxia-induced lung injury is urgently needed. We aimed to explore the ameliorative effects and molecular mechanisms of vitamin D3 (VD3) on hypoxia-induced lung tissue injury. Methods: Sprague–Dawley (SD) rats were randomly divided into three groups: normoxia, hypoxia, and hypoxia + VD3. The rat model of hypoxia was established by placing the rats in a hypobaric chamber. The degree of lung injury was determined using hematoxylin and eosin (H&E) staining, lung water content, and lung permeability index. Transcriptome data were subjected to differential gene expression and pathway analyses. In vitro, type II alveolar epithelial cells were co-cultured with hepatocytes and then exposed to hypoxic conditions for 24 h. For VD3 treatment, the cells were treated with low and high concentrations of VD3. Results: Transcriptome and KEGG analyses revealed that VD3 affects the complement and coagulation cascade pathways in hypoxia-induced rats, and the genes enriched in this pathway were Fgb/Fga/LOC100910418. Hypoxia can cause increases in lung edema, inflammation, and lung permeability disruption, which are attenuated by VD3 treatment. VD3 weakened the complement and coagulation cascade in the lung and liver of hypoxia-induced rats, characterized by lower expression of fibrinogen alpha chain (Fga), fibrinogen beta chain (Fgb), protease-activated receptor 1 (PAR1), protease-activated receptor 3 (PAR3), protease-activated receptor 4 (PAR4), complement (C) 3, C3a, and C5. In addition, VD3 improved hypoxic-induced type II alveolar epithelial cell damage and inflammation by inhibiting the complement and coagulation cascades. Furthermore, VD3 inhibited hypoxia-induced autophagy in vivo and in vitro, which was abolished by the mitophagy inducer, carbonyl cyanide-m-chlorophenylhydrazone (CCCP). Conclusion: VD3 alleviated hypoxia-induced pulmonary edema by inhibiting the complement and coagulation cascades and autophagy pathways.

The evolution and current distribution of species on the Qinghai-Tibet Plateau have been significantly impacted by historical occurrences, including the uplift of the plateau and the Quaternary climate upheaval. As a remnant species, the plateau pika (Ochotona curzoniae) is a great model for researching historical events. In this study, 302 samples from 42 sample sites were utilized to analyze the impact of historical events on the evolution and distribution pattern of plateau pikas. The genetic diversity, patterns of differentiation, and historical dynamics of the plateau pika were investigated using molecular markers that included four mitochondrial genes (COI, D-loop, Cytb, and 12S rRNA) and three nuclear genes (GHR, IRBP, and RAG1). The results showed that: (1) The genetic diversity of the plateau pika was high in the Tibetan Plateau (H_d = 0.9997, π = 0.01205), and the plateau pika evolved into five lineages that occupied different geographical areas, with lineage 1 (Group 1) in the south of the Yarlung Zangbo River, lineage 2 (Group 2) in the hinterland of the plateau, lineage 3 (Group 3) in the northeastern part of the plateau, lineage 4 (Group 4) in the Hengduan Mountains, and lineage 5 (Group 5) in the eastern part of the plateau. (2) The gene flow among the five lineages was low, and the differentiation level was high (N_m < 0.25; Fst > 0.25), indicating that the geographical barriers between the five lineages, such as the Yarlung Zangbo River, the Qaidam-Ghuong-Guide Basin, and the Lancang River, effectively promoted the population differentiation of the plateau pika. (3) The plateau pika first spread from the Hengduan Mountains to the entire Qinghai-Tibet Plateau and then conducted small-scale migration and dispersal in several refuges across the plateau in response to climate changes during the glacial and interglacial periods. (4) Except for Group 1 and Group 4, all the other populations exhibited a rapid expansion between 0.06 and 0.01 Mya, but the expansion was considerably delayed or halted by the effects of climate change during the last glacial maximum (0.02 Mya). Overall, the plateau pika on the Qinghai-Tibet Plateau exhibits high genetic diversity, and topographic obstacles, including mountains, valleys, and basins, created by the uplift of the plateau and climatic changes since the Quaternary period have played an important role in the differentiation and historical dynamics of the plateau pika population.

High altitude pulmonary edema (HAPE) is a serious threat to the physical and mental health of people who quickly enter high plateaus, deserves more attention and in-depth research. In our study, through the detection of various physiological indexes and other phenotypes in a HAPE rat model, the HAPE group showed a significant decrease in oxygen partial pressure and oxygen saturation, and a significant increase in pulmonary artery pressure and lung tissue water content. The lung histomorphology showed characteristics such as pulmonary interstitial thickening and inflammatory cell infiltration. We applied quasi-targeted metabolomics to compare and analyze the components of metabolites in arterial–veinous blood in control rats and HAPE rats. Using kyoto Encyclopedia of Genes Genomes (KEGG) enrichment analysis and two machine algorithms, we speculate that after hypoxic stress and comparing arterial blood and venous blood products in rats, the metabolites were richer, indicating that normal physiological activities, such as metabolism and pulmonary circulationhad a greater impact after hypoxic stress; D-mannose^DOWN, oxidized glutathione^DOWN, glutathione disulfide^DOWN, and dehydrocholic acid^DOWN in arterial blood play key roles in predicting the occurrence of HAPE; in venous blood, L-leucine^DOWN, L-thyroxine^DOWN, and cis-4-hydroxy- D-proline^DOWN may have key roles, which can be considered biomarkers of HAPE. This result provides a new perspective for the further diagnosis and treatment of plateau disease and lays a strong foundation for further research.

Background: Diabetic kidney disease (DKD), a major complication of type 2 diabetes mellitus (T2DM), is the leading cause of end-stage renal disease (ESRD). Recently, the innate immune system, particularly neutrophils and the process of NET formation, has garnered significant attention for its role in the progression of T2DKD in patients with T2DM. However, the underlying mechanism remains unclear.Methods: We employed single-cell LacNAc sequencing (scLacNAc-seq) to characterize immune cell populations, glycosylation patterns, and functional alterations in peripheral blood mononuclear cells (PBMCs), focusing on low-density granulocytes (LDGs), from patients with T2DM and T2DKD versus healthy controls (HC). In vitro cultures of primary human neutrophils under high glucose and high glucose plus serum from patients with T2DKD were used to assess NET formation via myeloperoxidase (MPO) detection. Plasma levels of reactive oxygen species (ROS), CXCL8, CXCR2, MPO, and neutrophil elastase (NE) were quantified by ELISA.Results: Patients with T2DM and T2DKD showed increased LDG counts and glycosylation abundance in FOLR3- and PI3-expressing subclusters. Functional enrichment analysis of overlapping differentially expressed genes (DEGs) and subclusters revealed enrichment in NET formation pathways. In vitro studies promoted NET release, as evidenced by reduced intracellular MPO and elevated supernatant MPO under hyperglycemic conditions. Plasma ROS, CXCL8, CXCR2, MPO, and NE levels were elevated in patients with T2DM and T2DKD than in HCs. Furthermore, enhanced interactions between neutrophils and mononuclear phagocytes (MPs), primarily mediated by the CXCL8/CXCR2 axis, were observed.Conclusion: This study identifies immunological alterations in T2DM and T2DKD, implicating neutrophil-mediated inflammation and NET formation in T2DKD progression. Correlative data suggest that targeting ROS and the CXCL8/CXCR2 pathway may represent potential therapeutic directions, though preclinical validation is warranted.