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Abstract IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.

Abstract Background Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. Methods The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA+ B cells. Results HCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8+ T lymphocyte activation was enhanced in the absence of IL-21R due to the reduction of immunosuppressive IgA+ B cells. Mechanistically, the IL-21R-STAT1-c-Jun/c-Fos regulatory axis was activated in MASH-driven HCC and thus promoted the transcription of Igha, resulting in the induction of IgA+ B cells. Conclusions IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy.

Background: The notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissues，contribute to excessive inflammation and necrosis, yet the precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from a disrupted lipid redox metabolism, is the focus of this investigation. Specifically, this study delves into the ferroptosis of Treg cells in the context of NEC and observes the protective effects exerted by vitamin E intervention, which aims to mitigate ferroptosis of Treg cells. Methods: To investigate the reduction of Treg cells in NEC intestine, we analyzed its association with ferroptosis from multiple angles. We constructed a mouse with a specific knockout of Gpx4 in Treg cells, aiming to examine the impact of Treg cell ferroptosis on NEC intestinal injury and localized inflammation. Ultimately, we employed vitamin E treatment to mitigate ferroptosis in NEC intestine's Treg cells, monitoring the subsequent amelioration in intestinal inflammatory damage. Results: The diminution of Treg cells in NEC is attributed to ferroptosis stemming from diminished GPX4 expression. Gpx4-deficient Treg cells exhibit impaired immunosuppressive function and are susceptible to ferroptosis. This ferroptosis of Treg cells exacerbates intestinal damage and inflammatory response in NEC. Notably, Vitamin E can inhibit the ferroptosis of Treg cells, subsequently alleviating intestinal damage and inflammation in NEC. Additionally, Vitamin E bolsters the anti-lipid peroxidation capability of Treg cells by upregulating the expression of GPX4. Conclusion: In the context of NEC, the ferroptosis of Treg cells represents a significant factor contributing to intestinal tissue damage and an exaggerated inflammatory response. GPX4 is pivotal for the viability and functionality of Treg cells. Vitamin E exhibits the capability to mitigate the ferroptosis of Treg cells, thereby enhancing their number and function, which plays a crucial role in mitigating intestinal tissue damage and inflammatory response in NEC.

Summary: Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.

Study region: The Heihe River source area in the Northeastern Qinghai-Tibetan Plateau, China. Study focus: Soil evaporation, which is a key process in soil water loss, is influenced by various environmental factors. However, the identification of its main drivers on a large scale in alpine mountains remains challenging due to sampling constraints. This study examined the spatial distribution of soil evaporation and control factors during the growing season in the Heihe River source area. New hydrological insights: The results indicated that soil evaporation, represented by lc-excess values, gradually increased from southeast to northwest, and then decreased, reaching a depth of 50 cm below the surface. Although the normalized difference vegetation index explained 54 % of the spatial variation in soil evaporation, the interaction between land surface temperature and soil water content (SWC) provided a more robust explanation. The soil evaporation losses exhibited the following pattern: cropland > grassland > forest land > shrubland. In forest land and shrubland, SWC and precipitation explained 68 % and 73.3 % of the spatial variations in soil evaporation, respectively. Grassland mainly relied on temperature and SWC, with 49.33 % of unexplained spatial variability by environmental factors. Meanwhile, the aridity index and aspect explained 45 % and 44.6 % of the spatial variations in cropland. These findings provided invaluable information for advancing our understanding of the ecohydrological processes in alpine mountains.

The Qinghai-Tibet Plateau (QTP) is critical for global carbon and nitrogen cycling and carbon sequestration because of its sensitive positive response to global warming. Although the factors affecting soil carbon and nitrogen in the sophisticated mountainous terrain of the QTP have been extensively investigated, the specific “direct” or “indirect” roles and their influence path remain unclear. In this study, the patterns of soil total carbon contents (STC) and soil total nitrogen contents (STN) were examined based on 445 soil samples collected from 89 plots in the Heihe River source region, northeastern QTP. The objective is to elucidate the interactions and driving mechanisms among climate, vegetation, geographical environmental factors, and soil properties for STC/STN. We found; (1) notable differences in STC/STN between altitudinal gradients and LULC types, exhibiting an overall increasing trend, followed by a decreasing trend with an increase in altitude; (2) the STC/STN in the 0–50 cm soil layer declined as soil depth increased, such that the distinctive “surface aggregation” characteristics were confirmed. In general, regions with higher soil total carbon densities (STCD) and soil total nitrogen densities (STND) were concentrated in the southeast of the watershed, whereas regions with lower densities were identified in the northwest. (3) Soil water content (SWC) and bulk density (BD) are critical in distributing STC/STN. Among the significant environmental factors influencing STC, SWC had the maximum direct path coefficient (0.42), suggesting a direct effect. Other factors, such as land-use and land-cover change (LULC), BD, pH, and normalized difference vegetation index (NDVI) affected the STC content via a wide variety of pathways. For STN, SWC (0.46), and pH (−0.2) showed direct path coefficients with magnitudes greater than the indirect path coefficients, suggesting direct effects. Moreover, NDVI, BD, and precipitation affected the STN through other factors. These findings provide insights into soil carbon and nitrogen dynamics in alpine soil under sophisticated mountainous terrain. They provide valuable support for studying soil carbon and nitrogen cycling, and for evaluating carbon and nitrogen stocks in cold regions.

Water conservation, a crucial ecological service in the Qinghai Plateau, has been affected by climate change and human activity, which has made it a focal point in the field of ecohydrology. This study aimed to analyze the spatiotemporal trends in water conservation in the Qinghai Plateau from 1990 to 2020 using the InVEST model. This study found that the average annual water conservation of the Qinghai Plateau is 31.72 mm, with a total volume of 226.6 × 108 m3. The trend of water conservation increased from the northwest to the southeast, with the Three-River Source, Eastern Agricultural, and Qilian Mountain regions being the focal points. Shrubs and forests had the highest average units of water conservation, whereas grasslands had the largest total water conservation. Meadows are a vegetation type suitable for protection to enhance water conservation. Water conservation is strongly correlated with precipitation and actual evapotranspiration. These results provide theoretical support for protecting and improving the water conservation in the Qinghai Plateau.

Elucidating the water surplus and loss of different vegetation landscapes in cold regions is important for the conservation and management of water resources in alpine inland rivers. As such, this study is to systematically reveal the water variation in different vegetation landscape zones of the alpine inland river basin, delineate its water resources protection zones, and propose its water resources management strategies. In addition, the study confirms that stable isotope and remote sensing techniques can quantify the variations of water surplus and loss in different vegetation zones of the Qinghai Lake Shaliu River basin, and identifies the alpine desert zone as an important water-producing zone, the alpine meadow zone as an important water storage zone, and the alpine steppe zone as the main water-consuming zone of the basin. At the same time, the alpine meadow zone was also the area with the strongest evapotranspiration. The variations of water surplus and loss in different vegetation zones depended significantly on elevation, and the quality of ecological environment profoundly affected the water holding capacity of the basin. Therefore, according to the variations of water surplus and loss in different vegetation zones of the basin, the alpine desert zone and the alpine meadow zone were the important water resources core protection areas for water production and storage in the basin, and the alpine steppe zone was the general water resources protection area in the basin. The results of this study indicated that the water resources management strategy of alpine inland river basin should be a composite model that improves the quality of ecological environment and combines core protection of water resources in the middle and upper reaches with effective management of water resources in the lower reaches.

The ecology of the Qilian Mountains has been seriously threatened by uncontrolled grazing and wasteland reclamation. This study examined the ecological changes on the southern slope of Qilian Mountains from the perspective of water conservation by classifying different clusters of water conservation functional areas to efficiently use limited human resources to tackle the water conservation protection problem. In this study, we used Integrate Valuation of Ecosystem Services and Tradeoffs (InVEST) model to estimate water conservation and analyzed the factors that influence the function. The results of this study include: (1) from 2000 to 2015, the water conservation of the southern slope of Qilian Mountains generally showed an increasing trend, and the total water conservation in 2015 increased by 42.18% compared with 2000. (2) Rainfall, fractional vegetation cover (FVC), and evapotranspiration have the most significant influence on the water conservation of study area. Among them, water conservation is positively correlated with rainfall and FVC (P ​

Understanding the evolving hydrological characteristics of landslide-induced barrier lakes is crucial for flood control, forecasting, early warning, and safety measures in reservoir areas. This study examines the changes in the hydrological characteristics of the Attabad landslide-dammed lake over the past decade after the occurrence of the landslide, focusing on lake area dynamics and sediment concentration. High-resolution satellite images from QuickBird, Pleiades, and WorldView2 over seven periods were analyzed. The findings indicate that the lake area has gradually decreased, with the center of mass shifting towards the lake dam, indicating a trend towards stability. The suspended sediment in the barrier lake is distributed in a strip running from north to south, then northeast to southwest, with the sediment concentration decreasing from the lake entrance to the dam and from the lake bank to the center. Over time, the average sediment concentration has decreased from 2010 to 2020, with higher concentrations in summer than in winter. Notably, during the 2017–2020 period, the lower-middle parts of the lake experienced a higher sediment concentration, while the dam area witnessed lower concentrations, thereby reducing the sediment impact on the dam. Furthermore, the sediment content in the middle of the dammed lake is relatively high, which may lead to the formation of a new dammed dam in the middle and the division of the original dammed lake into two smaller lakes, which will affect the stability of the dammed lake.

Summary: Amino acid (aa) metabolism is closely correlated with the pathogenesis of psoriasis; however, details on aa transportation during this process are barely known. Here, we find that SLC38A5, a sodium-dependent neutral aa transporter that counter-transports protons, is markedly upregulated in the psoriatic skin of both human patients and mouse models. SLC38A5 deficiency significantly ameliorates the pathogenesis of psoriasis, indicating a pathogenic role of SLC38A5. Surprisingly, SLC38A5 is almost exclusively expressed in dendritic cells (DCs) when analyzing the psoriatic lesion and mainly locates on the lysosome. Mechanistically, SLC38A5 potentiates lysosomal acidification, which dictates the cleavage and activation of TLR7 with ensuing production of pro-inflammatory cytokines such as interleukin-23 (IL-23) and IL-1β from DCs and eventually aggravates psoriatic inflammation. In summary, this work uncovers an auxiliary mechanism in driving lysosomal acidification, provides inspiring insights for DC biology and psoriasis etiology, and reveals SLC38A5 as a promising therapeutic target for treating psoriasis.

Summary: γδ T cells make key contributions to tissue physiology and immunosurveillance through two main functionally distinct subsets, γδ T1 and γδ T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular functional specialization; however, its role in γδ T cells remains less well understood. Here, we find that m6A methylation controls the functional specification of γδ T17 vs. γδ T1 cells. Mechanistically, m6A methylation prevents the formation of endogenous double-stranded RNAs and promotes the degradation of Stat1 transcripts, which converge to prevent over-activation of STAT1 signaling and ensuing inhibition of γδ T17. Deleting Mettl3, the key enzyme in the m6A methyltransferases complex, in γδ T cells reduces interleukin-17 (IL-17) production and ameliorates γδ T17-mediated psoriasis. In summary, our work shows that METTL3-mediated m6A methylation orchestrates mRNA stability and double-stranded RNA (dsRNA) contents to equilibrate γδ T1 and γδ T17 cells.

Aims: To investigate the safety of oral iron therapy in pregnant women with iron-deficiency anemia (IDA) in the real world. Methods: A retrospective analysis was performed on 1792 pregnant patients with IDA who received oral iron supplements from 12 hospitals in Shandong Province from 1 April to 31 June 2021; follow-up and adverse reactions were recorded. They were divided into six groups according to the treatment drugs. Results: The overall adverse reaction rate was 15.4%, and the main adverse reaction site was the digestive system. The incidence of all kinds of oral iron adverse reactions from high to low in order: compound ferrous sulfate and folic acid tablets (21.88%); iron proteinsuccinylate oral solution (20.90%); ferrous succinate tablets (19.76%); ferrous succinate sustained-release tablets (18.00%); iron polysaccharide complex capsule (12.06%); and iron dextran oral solution (6.94%). It was found that there was a significant difference in the incidence of adverse reactions among the six drugs ( p 0.05), but there was a significant difference in the incidence of adverse reactions in different gestational ages ( p

Study region: The Datong River source region in the Northeast Qinghai-Tibetan Plateau Study focus: Climate change and anthropogenic factors are the most important factors influencing runoff. Land use/land cover (LULC) is an important anthropogenic factor that has a significant impact on runoff changes. Quantifying runoff variation characteristics and determining the effect of changes in climate and LULC on runoff is important for water resource management and application. The mathematical statistics analysis and soil and water assessment tool (SWAT) were combined to perform a comprehensive analysis of runoff based on meteorological and hydrological data from the Datong River source area, and the effect of changes in climate and LULC on runoff was quantitatively calculated. New hydrological insights for the region: The results indicate that under the warm and humid climate, there was a slight change in the inter-annual runoff, while the distribution of runoff within the year was uneven due to the control of climate factors. Climate exhibited a positive driving effect on runoff, while LULC reduced the runoff and contributed 125% and − 25%, respectively, to the change in the runoff. Rainfall is the most important climatic factor influencing runoff change. It is recommended that the flood tragedy induced by short periods of high rainfall be taken into account during the process of water resource management in the basin.

In recent years, the ecological and environmental problems caused by mining in the Qilian Mountains have attracted considerable attention, and the government has carried out a number of comprehensive ecological environment remediation projects there, among which ecological restoration in the Qilian Mountain alpine mining area is an essential task. As a result, heavy metals have been studied in the soil of the Qilian Mountain alpine mining area. This can provide a scientific basis and data support for the establishment of a demonstration index for monitoring ecological environmental restoration in mining areas. In order to understand the content and contamination status of heavy metals in the soil surrounding the alpine mining area of Qilian Mountain, 56 soil samples were collected to determine the levels of eight heavy metals, including Cd, Hg, As, Pb, Cr, Cu, Zn, and Ni. The spatial distribution of heavy metals in the soil of the study area was analyzed based on a statistical approach. The single-factor pollution index (Pi), Nemerow comprehensive pollution index (PN), geoaccumulation index (Igeo), and potential ecological risk index (RI) were used to evaluate soil heavy metal pollution and potential ecological risk. Principal component analysis (PCA), positive matrix factorization (PMF) models, and geostatistical analysis were also used to investigate the source of heavy metals. The results show that the average Cd, As, Cr, Cu, Zn, and Ni content of the grassland soil around the mining area exceeds the soil background values in both Qinghai Lake Basin and Qinghai Province. The spatial distribution of the eight heavy metal elements in soil showed an island-like pattern, with high-value areas of each metal element appearing, indicating that human activities in the study area had negative effects on the soil environment. The value of the single pollution index showed that levels of Ni, Cd, Cu, Cr, Hg, and As pollution were low, while there was no Pb or Zn pollution. The Nemerow integrated pollution index had an average value of 1.39, indicating a slight pollution trend. The average values of Cr and Zn in the geoaccumulation index ranged from 0 to 1, indicating mild to moderate contamination in the studied region. The average value of the integrated ecological risk index in the study area was 135.43, which is in the intermediate ecological risk range. In descending order of size, the average ecological risk index of each heavy metal element was Hg > Cd> As > Ni > Cu > Pb > Cr > Zn. From the perspective of the spatial distribution pattern of ecological risk, the two high-value discriminants were in the western part of the study area, close to the mining area. Zn, Cu, Pb, and Cd in soils were mainly affected by human activity, while Cr and Ni were mainly affected by soil geochemistry. Cd is the main contaminant in the study area, and soil Cd contamination of the grassland in the study area must be considered.

Abstract. Metabolic change is associated with cell activities, such as signal transduction, cell differentiation, and cell cycle. In the pathogenesis of autoimmune diseases, abnormal activation of T cells is often accompanied by changes in their metabolism. Conversely, the changes of metabolites can also regulate the proliferation, differentiation, and function of T cells. As a bridge between innate and adaptive immune responses, γδ T cells have unique biological characteristics and functions. However, the immunometabolic mechanism of γδ T cells has been a novel field for research in recent years. In this review, we summarize the influence of metabolic pathways and nutrients on γδ T cell function, and metabolic features of γδ T cell subsets, which may provide new insights in interventions targeting γδ T cells in disease control.

Abstract Background Satellite cells (SCs) are critical to skeletal muscle regeneration. Inactivation of SCs is linked to skeletal muscle loss. Transferrin receptor 1 (Tfr1) is associated with muscular dysfunction as muscle‐specific deletion of Tfr1 results in growth retardation, metabolic disorder, and lethality, shedding light on the importance of Tfr1 in muscle physiology. However, its physiological function regarding skeletal muscle ageing and regeneration remains unexplored. Methods RNA sequencing is applied to skeletal muscles of different ages to identify Tfr1 associated to skeletal muscle ageing. Mice with conditional SC ablation of Tfr1 were generated. Between Tfr1SC/WT and Tfr1SC/KO (n = 6–8 mice per group), cardiotoxin was intramuscularly injected, and transverse abdominal muscle was dissected, weighted, and cryosectioned, followed by immunostaining, haematoxylin and eosin staining, and Masson staining. These phenotypical analyses were followed with functional analysis such as flow cytometry, tread mill, Prussian blue staining, and transmission electron microscopy to identify pathological pathways that contribute to regeneration defects. Results By comparing gene expression between young (2 weeks old, n = 3) and aged (80 weeks old, n = 3) mice among four types of muscles, we identified that Tfr1 expression is declined in muscles of aged mice (~80% reduction, P

Background Epidemiological surveys have revealed that low serum vitamin D level was correlated with increased risk of tumors. Dysfunctional T cells in patients with tumor are characterized as exhausted with high levels of immune checkpoint receptors (ICRs). However, whether the reduced level of vitamin D in patients with cancer correlates with cytotoxic T-cell exhaustion is unknown.Methods Periphery blood samples from 172 patients with non-small cell lung cancer (NSCLC) were prospectively collected. Patients with NSCLC received one course of intravenous docetaxel (75 mg/m2) followed by treatment with or without rocaltrol at a dose of 0.5–2.0 µg/day for total of 3 weeks. We performed phenotypical and functional analysis of T-cell through flow cytometry. Vitamin D receptor (VDR) knockout and overexpression CD8+ and Vδ2+ T cells were constructed using Cas9-gRNA targeted and overexpressing approaches to identify 1α,25(OH)2D3/VDR-mediated transcription regulation for ICRs or antitumor activity in T cells.Results We show that serum level of vitamin D is negatively correlated with expression of programmed cell death-1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), but positively correlated with CD28 expression on CD8+ and Vγ9Vδ2+ T cells in patients with NSCLC. 1α,25(OH)2D3, the active form of vitamin D, promotes the nuclear translocation of VDR, which binds to the promoter region of Pdcd1, Tim3, and Tigit genes and inhibits their expression. Besides, 1α,25(OH)2D3 pretreatment also promotes the methylation of CpG island in the promoter region of the Pdcd1 gene and increases H3K27 acetylation at the promoter region of the Cd28 gene, which leads to surface PD-1 downregulation and CD28 upregulation, respectively. We further reveal that VDR-mediated Ca2+ influx enhanced expression of Th1 cytokines via T-cell receptor activation. Functionally, 1α,25(OH)2D3 pretreated CD8+ T cells or Vγ9Vδ2+ T cells showed increased Th1 cytokine production and enhanced antitumor immunity. Finally, oral 1α,25(OH)2D3 could also decrease expression of PD-1, Tim-3, TIGIT and increase expression of CD28, resulting in cytokine production (associated with antitumor immunity) by cytotoxic T cells of patients with NSCLC.Conclusions Our findings uncover the pleiotropic effects of 1α,25(OH)2D3 in rescuing the exhausted phenotype of human cytotoxic T cells in patients with tumor and in promoting their antitumor immunity.Trial registration number ChiCTR2100051135.

This study discusses the impact of two different ecological restoration approaches on the distribution of soil particle size and organic carbon, expecting to provide references for research on the effects of ecological restoration on the soil carbon pool in alpine regions. By replacing the method of time sampling with spatial sampling, grasslands enclosed only in the growing season and woodlands enclosed all year round were respectively selected as the research objects. Through centrifugation, the soil samples were classified by grain size into sand (50–2000 μm), silt (2–50 μm), and clay (

Due to increased levels of human activity, various pollutants are frequently detected on the Tibetan Plateau, where the environment is extremely fragile and sensitive. Therefore, this study investigated the sources, pollution, and ecological risks of soil potentially toxic elements (PTEs) in different landscape areas within the Qaidam Basin in the northeastern part of the Qinghai–Tibet Plateau. The contents of seven PTEs (Cd, Cu, Pb, Zn, As, Cr, and Ni) in 32 topsoil samples (0–2 cm) were analyzed in different regions of the Qaidam Basin. The concentrations of As, Cd, Cr, Cu, Ni, Pb, and Zn were 10.4–29.9 mg/kg, 0.08–4.45 mg/kg, 19–66 mg/kg, 8.2–40 mg/kg, 11.7–30.8 mg/kg, 11.1–31.2 mg/kg, and 32–213 mg/kg, respectively. The correlation between Pb and Cd in unpopulated areas was 0.896 (p < 0.01). The correlations among Pb, Cd, and Zn in agricultural areas, among As, Cd, Cr, and Zn in saline lake areas, and among As, Cd, Cr, Cu, Ni, Pb, and Zn in residential areas were all greater than 0.65 (p < 0.05). The principal component analysis results showed that Pb and Cd in unpopulated areas, Pb, Cd, and Zn in agricultural areas, As, Cd, Cr, Zn, and Pb in saline lake areas, and As, Cd, Cr, Cu, Ni, Pb, and Zn in residential areas were affected by human activities (significant factor >0.70). Based on the geological accumulation index and single-factor pollution index results, the maximum Cd values were found to be 4.93 and 45.88, respectively; Cd was thus the most serious PTE pollutant. The comprehensive pollution index of Nemero showed that moderately and severely polluted areas accounted for 18.89% and 18.46% of the total area, respectively. The results of the potential risk index showed that very strong and strong ecological risk points together accounted for 18.8% of the total points. The spatial variations in PTE pollution and the potential ecological risk index had similar patterns; both increased from the unpopulated areas in the northeastern Qaidam Basin to Golmud city in the south-western Qaidam Basin. These results indicate that human activities negatively impacted the soil ecological environment in the Qaidam Basin during the rapid development of the economy and urbanization and that these negative impacts tended to spread to unpopulated areas. Therefore, it is necessary to emphasize the significant impacts of human activities on environmental quality and formulate preventive measures to reduce PTE pollution in the Qinghai–Tibet Plateau.

Evapotranspiration is an important process in the water budget of an ecosystem. Quantifying the components of evapotranspiration is of great significance in revealing the ecohydrological process of alpine inland river basins. In this study, the evapotranspiration fluxes in the Shaliu River basin were classified by hydrogen and oxygen stable isotope technology and remote sensing technology. The results showed the following: (1) The average value of soil fractional evaporation (E1) in the summer of 2018 and 2019 was 7.59 mm and 2.10 mm, respectively. (2) The average ratio of soil evaporation (Esoil) in the summer of 2018 was 48.82%, 68.11%, 54.99%, respectively. The average ratio of Esoil in the summer of 2019 was 66.86%, 57.50%, 55.53%, respectively. The average value of Esoil in the summer of 2018 and 2019 was 42.84 mm and 35.36 mm, respectively. (3) The average ratio of vegetation transpiration (T) in the summer of 2018 was 51.18%, 31.89%, and 45.01%, respectively. The average ratio of T in the summer of 2019 was 33.14%, 42.50%, and 44.47%, respectively. The average value of T in the summer of 2018 and 2019 was 32.59 mm and 26.23 mm, respectively. Obviously, the soil fractionation was stronger in the summer of 2018 than that in the summer of 2019. At the same time, both soil evaporation and plant transpiration in summer 2018 were higher than those in summer 2019, and soil evaporation in the Shaliu River basin was greater than plant transpiration in summer during the study period. The results of this study can provide data reference for mastering the eco-hydrological process of the Shaliu River basin.

Estimating accurately the vegetation water consumption (VWC) in the Qinghai Lake Basin (QLB) is conducive to the effective utilization and management of water resources in the QLB, which is of great significance to the construction of a national park in the QLB. We used Geographic Information System (GIS) technology and remote sensing (RS) technology based on potential evapotranspiration data to calculate the VWC in the QLB from 2000 to 2020, and analyzed the influencing factors of the VWC in the QLB from 2000 to 2020. The results showed that (1) the average value of the VWC in the QLB varied from 242.96 mm to 287.99 mm, the average value of the VWC was 267.07 mm, and the average value of the total VWC was 79.05 × 108 m3 from 2000 to 2020. (2) In terms of spatial variation of the VWC, the VWC in the QLB did not increase significantly from 2000 to 2014, however, the VWC in the QLB showed a significant increase from 2015 to 2020. (3) As the altitude gradient increases, the VWC in the QLB from 2000 to 2020 showed a significant downward trend with the increase in altitude. When the altitude increases by 100 m, the value of the VWC decreases by 13.47 mm from 2000 to 2014 and 22.8 mm from 2015 to 2020, respectively. (4) Exploring the influencing factors of the VWC in the QLB from 2000 to 2020, the results showed that the VWC was mainly affected by the average annual precipitation and normalized difference vegetation index (NDVI) from 2000 to 2014. It was mainly affected by the combined effects of annual temperature, precipitation, and vegetation coverage from 2015 to 2020. The VWC was mainly affected by the average annual temperature, precipitation, and vegetation coverage along the altitude gradient from 2000 to 2014. It was mainly affected by the average annual temperature and vegetation coverage in the QLB from 2015 to 2020. Obviously, vegetation coverage was the most important factor affecting the VWC regardless of spatial or altitude gradient variations.

As the “Asian Water Tower”, understanding the hydrological cycles in Qinghai Province and its interior is critical to the security of terrestrial ecosystems. Based on Moderate Resolution Imaging Spectroradiometer (MODIS)16 evapotranspiration (ET) remote sensing data, we used least squares regression, correlation analysis, and t-test to determine the temporal and spatial changes and trends of ET in Qinghai Province and its five ecological functional regions, located on the Qinghai–Tibet Plateau (Plateau) Western China from 2000 to 2020. In addition, we discussed the main factors affecting the changes of ET in different regions of Qinghai Province over the first two decades of the 21st century along spatial as well as altitudinal gradients. The results showed that: (1) the average annual ET in Qinghai Province was 496.56 mm/a, the highest ET value appeared in the southeast of the study area (684.08 mm/a), and the lowest ET value appeared in the Qaidam region in the northwest (110.49 mm/a); (2) the annual ET showed an increasing trend with a rate of 3.71 mm/a (p < 0.01), the place where ET decreased most was in the Three-River Source region (−8–0 mm/a) in the southwest of the study area, and the ET increased the most in the Hehuang region in the east of the study area (9–34 mm/a); (3) temperature (T) was the dominant ET change factor in Qinghai Province, accounting for about 65.27% of the region, followed by the normalized difference vegetation index (NDVI) and precipitation (P) for 62.52% and 55.41%, respectively; and (4) ET increased significantly by 2.84 mm/100 m with increasing altitude. The dominant factors changed from P to NDVI and T as the altitude increased. The research is of practical value for gaining insight into the regional water cycle process on the Plateau under climate change.

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of cirrhosis and major risk factors for hepatocellular carcinoma and liver-related death. Despite substantial clinical and basic research, the pathogenesis of obesity-related NAFLD remains poorly understood. In this study, we show that perforin can act as an immune regulator to prevent the progression of NAFLD. Aged perforin-deficient (Prf−/−) mice have increased lipid accumulation in the liver compared to WT mice. With high-fat diet (HFD) challenge, Prf−/− mice have increased liver weight, more severe liver damage, and increased liver inflammation when compared with WT controls. Mechanistic studies revealed that perforin specifically regulates intrinsic IFN-γ production in CD4 T cells, not CD8 T cells. We found that CD4 T cell depletion reduces liver injury and ameliorates the inflammation and metabolic morbidities in Prf−/− mice. Furthermore, improved liver characteristics in HFD Prf−/− and IFN-γR−/− double knockout mice confirmed that IFN-γ is a key factor for mediating perforin regulation of NAFLD progression. Overall, our findings reveal the important regulatory role perforin plays in the progression of obesity-related NAFLD and highlight novel strategies for treating NAFLD.

Urban wetlands, an important part of the urban ecosystem, play an important role in regional carbon cycles and the carbon balance. To analyze the CO2 source and sink effects of plateau urban wetlands, based on the data measured by an eddy covariance instrument, the temporal and spatial characteristics of CO2 flux and their influencing factors in the urban wetland of Xining City in the Qinghai Province of China during a warm season (July to September 2020) were studied. The results show that: (1) On the daily scale, the CO2 flux exhibited an obvious “U”-type variation, characterized by strong uptake in the daytime and weak emission at night, with an average daily flux of −0.05 mg·m−2·s−1. The CO2 uptake peak of the wetland took place at 13:00 (−0.62 mg·m−2·s−1), and the emission peak occurred at 23:30 (0.34 mg·m−2·s−1); (2) on the monthly scale, the CO2 flux of the wetland in the study period showed a net uptake each month. The flux increased month by month, and the maximum value occurred in September (−142.82 g·m−2·month−1); (3) from a spatial point of view, the river area showed a weak CO2 uptake (−0.07 ± 0.03 mg·m−2·s−1), while the artificial wetland area showed a strong CO2 uptake (−0.14 ± 0.03 mg·m−2·s−1). The former was significantly lower than the latter (p < 0.01); (4) the regression analysis results show that the CO2 flux was significantly correlated with PAR, VPD, Tsoil, and SWC (p < 0.01). The relationships between the flux and PAR, Tsoil, and SWC were rectangular hyperbola (y = 0.2304 − 2 × 10−3x/(0.9037 + 0.0022x), R2 = 0.64), exponential (y = 0.046exp(0.091x), R2 = 0.88), and quadratic (y = −0.0041x2 + 0.1784x − 1.6946, R2 = 0.83), respectively. Under the joint action of various environmental factors, the urban wetland ecosystem in plateau displayed a strong carbon sink function in warm seasons. This study can establish a data scaffold for the accurate estimation of carbon budget of this type of ecosystem.

A total of 30 late onset severe preeclampsia (LS-PE) patients and 30 early onset severe preeclampsia (ES-PE) patients were selected as Experimental group, and 30 normal pregnant were selected as Control group. Expression of S100 calcium-binding protein A8 (S100A8) mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect expression of S100A8 protein and inflammatory factors. Levels of uric acid (UA) and creatinine (CRE) were measured using an automatic biochemical analyzer. Urinary protein (UPRO) content was measured using biuret colorimetry. S100A8 levels were significantly higher in experimental groups than in control groups at mRNA and protein levels ( P

The identification of m6A demethylases and high-throughput sequencing analysis of methylated transcriptome corroborated m6A RNA epigenetic modification as a dynamic regulation process, and reignited its investigation in the past few years. Many basic concepts of cytogenetics have been revolutionized by the growing understanding of the fundamental role of m6A in RNA splicing, degradation and translation. In this review, we summarize typical features of methylated transcriptome in mammals, and highlight the ‘writers’, ‘erasers’ and ‘readers’ of m6A RNA modification. Moreover, we emphasize recent advances of biological functions of m6A and conceive the possible roles of m6A in the regulation of immune response and related diseases.

In the new era, there is an urgent need to further promote pairing assistance to Tibet, promote the simultaneous construction of a strong agriculture in China, and compose a Chinese-style modernization. Southern Tibet, located in the southeastern part of the Tibet Autonomous Region, includes Shannan City and Nyingchi City, is a region assisted by four provincial partners including Hubei Province. This paper introduces the agricultural environment in southern Tibet, studies its agricultural characteristics, and analyzes the main issues of its pairing assistance. Taking forging the strong consciousness of the Chinese national community as the main line, the paper explores strategies for promoting agricultural high-quality development in southern Tibet through pairing assistance to Tibet from the perspective of agricultural power, and proposes some strategies, such as inheriting agricultural cultural heritage, promoting the upgrading of modern seed industry, enhancing the characteristic advantages of highland barley (naked barley) and animal husbandry industries, and developing edible fungi and cold water fish industries. [ABSTRACT FROM AUTHOR]