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Rational application of N fertilizer is essential for maintaining the long-term productivity of Moso bamboo forests. Microbial activity is a crucial indicator of soil quality. Changes in soil nutrient resources due to N addition can lead to microbial nutrient limitations, thereby impeding the maintenance of soil quality. Currently, there is limited research on the effects of N application on microbial nutrient limitations in Moso bamboo forest soils. To examine the changes in extracellular enzyme activity and microbial nutrient limitations in Moso bamboo forest soils following N application, we conducted an N application experiment in northern Guizhou. The findings revealed that the N3 treatment (726 kg·N·hm−2·yr−1) significantly reduced β-glucosidase (BG) activity by 27.61% compared to the control group (no fertilization). The N1 (242 kg·N·hm−2·yr−1), N2 (484 kg·N·hm−2·yr−1), and N3 treatments notably increased the activities of leucine aminopeptidase (LAP) and N-acetyl-β-D-glucosidase (NAG) by 11.45% to 15.79%. Acid phosphatase (ACP) activity remained unaffected by fertilization. N application treatments significantly decreased the C:Ne and C:Pe ratios, while the N:Pe ratio was less influenced by N fertilizer application. Scatter plots and vector characteristics of enzyme activity stoichiometry suggested that microorganisms in the study area were limited by C and N, and N fertilizer application reduced the vector length and increased the vector angle, indicating that N application alleviated the C and N limitation of microorganisms in Moso bamboo forests. Redundancy Analysis (RDA) demonstrated that microbial biomass phosphorus (MBP) was the most critical factor affecting extracellular enzyme activity and stoichiometry. Furthermore, Random Forest Regression analysis identified MBP and the N:Pm ratio as the most significant factors influencing microbial C and N limitation, respectively. The study demonstrated that N application modulates the microbial nutrient acquisition strategy by altering soil nutrient resources in Moso bamboo forests. Formulating fertilizer application strategies based on microbial nutrient requirements is more beneficial for maintaining soil quality and sustainably managing Moso bamboo forests. Additionally, our study offers a theoretical reference for understanding carbon cycling in bamboo forest ecosystems in the context of substantial N inputs. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underlying vascular inflammation and associated inflammatory vascular diseases are not well defined. Here we show that endothelial intracellular adenosine and its key regulator adenosine kinase (ADK) play important roles in vascular inflammation. Pro-inflammatory stimuli lead to endothelial inflammation by increasing endothelial ADK expression, reducing the level of intracellular adenosine in endothelial cells, and activating the transmethylation pathway through increasing the association of ADK with S-adenosylhomocysteine (SAH) hydrolase (SAHH). Increasing intracellular adenosine by genetic ADK knockdown or exogenous adenosine reduces activation of the transmethylation pathway and attenuates the endothelial inflammatory response. In addition, loss of endothelial ADK in mice leads to reduced atherosclerosis and affords protection against ischemia/reperfusion injury of the cerebral cortex. Taken together, these results demonstrate that intracellular adenosine, which is controlled by the key molecular regulator ADK, influences endothelial inflammation and vascular inflammatory diseases.The molecular mechanisms underlying vascular inflammation are unclear. Here the authors show that pro-inflammatory stimuli lead to endothelial inflammation by increasing adenosine kinase expression, and that its knockdown in endothelial cells inhibits atherosclerosis and cerebral ischemic injury in mice.

The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine-metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased the levels of intracellular adenosine in human endothelial cells. Knockdown (KD) of ADK elevated intracellular adenosine, promoted proliferation, migration, and angiogenic sprouting in human endothelial cells. Additionally, mice deficient in endothelial ADK displayed increased angiogenesis as evidenced by the rapid development of the retinal and hindbrain vasculature, increased healing of skin wounds, and prompt recovery of arterial blood flow in the ischemic hindlimb. Mechanistically, hypomethylation of the promoters of a series of pro-angiogenic genes, especially for VEGFR2 in ADK KD cells, was demonstrated by the Infinium methylation assay. Methylation-specific PCR, bisulfite sequencing, and methylated DNA immunoprecipitation further confirmed hypomethylation in the promoter region of VEGFR2 in ADK-deficient endothelial cells. Accordingly, loss or inactivation of ADK increased VEGFR2 expression and signaling in endothelial cells. Based on these findings, we propose that ADK downregulation-induced elevation of intracellular adenosine levels in endothelial cells in the setting of hypoxia is one of the crucial intrinsic mechanisms that promote angiogenesis.

Anti–vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A (Adora2a), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury–induced CNV or mice with a deficiency in the very low–density lipoprotein receptor), we found that deletion of Adora2a either globally or specifically in endothelial cells reduced subretinal fibrosis independently of angiogenesis. We showed that Adora2a-dependent endothelial-to-mesenchymal transition contributed to the development of subretinal fibrosis in mice with laser injury–induced CNV. Deficiency of Adora2a in cultured mouse and human choroidal endothelial cells suppressed induction of the endothelial-to-mesenchymal transition. A metabolomics analysis of cultured human choroidal endothelial cells showed that ADORA2A knockdown with an siRNA reversed the increase in succinate because of decreased succinate dehydrogenase B expression under fibrotic conditions. Pharmacological inhibition of ADORA2A with a small-molecule KW6002 in both mouse models recapitulated the reduction in subretinal fibrosis observed in mice with genetic deletion of Adora2a. ADORA2A inhibition may be a therapeutic approach to treat subretinal fibrosis associated with nAMD. Editor's summary: Retinal fibrosis reversal age-related macular degeneration (AMD) is driven by neovascularization and is associated with subretinal fibrosis. Working in mice with genetically induced AMD or with a laser-induced retinal injury, Yang et al. show that deleting the gene encoding adenosine receptor 2A (Adora2a) prevented subretinal fibrosis in both mouse models. Specifically, deleting Adora2a in endothelial cells was sufficient to reverse subretinal fibrosis by preventing endothelial-to-mesenchymal transition. In human choroidal endothelial cells, the authors showed that endothelial-to-mesenchymal transition was associated with succinate accumulation due to decreased succinate dehydrogenase subunit B expression. Treatment with an ADORA2A antagonist reversed subretinal fibrosis in both mouse models, suggesting that targeting ADORA2A in endothelial cells could be a therapeutic strategy to treat AMD. —Brandon Berry [ABSTRACT FROM AUTHOR]

Background: Single‐cell transcriptomics has revolutionised our understanding of the cellular composition of the tumour microenvironment (TME) in nasopharyngeal carcinoma (NPC). Despite this progress, a key limitation of this technique has been its inability to capture epithelial/tumour cells, which has hindered further investigation of tumour heterogeneity and immune escape in NPC. Methods: In this study, we aimed to address these limitations by analysing the transcriptomics and spatial characteristics of NPC tumour cells at single‐cell resolution using scRNA/snRNA‐seq and imaging mass cytometry techniques. Results: Our findings demonstrate multiple patterns of immune escape mechanisms in NPC, including the loss of major histocompatibility complex (MHC) molecules in malignant cells, induction of epithelial–mesenchymal transition in fibroblast‐like malignant cells and the use of hyperplastic cells in tumour nests to protect tumour cells from immune infiltration. Additionally, we identified, for the first time, a CD8+ natural killer (NK) cell cluster that is specific to the NPC TME. Conclusions: These findings provide new insights into the complexity of NPC immune landscape and may lead to novel therapeutic strategies for this disease. [ABSTRACT FROM AUTHOR]

The China Fusion Engineering Test Reactor (CFETR), a superconducting magnetic confinement tokamak fusion reactor, will develop a high-performance torus cryopump to pump torus plasma exhaust gas. The inlet valve is one of the key components of the cryopump, and it is used to isolate the cryopump from the plasma for regeneration, to control the pumping speed of the cryopump, and to operate as a pressure relief valve in case of a failure, such as the cryopipe breaking inside the cryopump chamber. This paper presents a novel inlet valve. Ensuring that the design of the inlet valve meets the above requirements will be a challenge. In order to verify the reliability of the inlet valve, its critical components are analyzed and optimized by the Finite Element Method. The effect of the stroke of the inlet valve on pumping performance is then estimated by the Monte Carlo Method, and the pressure profile in the whole flow field is studied to predict the cryopump's behavior. Finally, the seismic capacity of the optimized inlet valve is analyzed, and the mechanical performance of the inlet valve is shown to meet CFETR design criteria. These design and analysis results will provide technical support and references for the development of the CFETR torus cryopump. [ABSTRACT FROM AUTHOR]