Multi-level decisions for addressing trade-off in the cross-regional water-environment-agriculture interactive system under constraint of water ecological carrying capacity.

The complex-enhanced hierarchical relationship among multiple stakeholders in the water-environment-agriculture interactive system has been overlooked. This study develops a leader-follower-enhanced framework (named as FCMLP) that integrates variable-weight combination prediction model, multi-level programming, and fuzzy credibility constrained programming, which can effectively address the above problems under uncertainties. Five water ecological carrying capacity (WECC) statuses are treated as a critical constraint into the modeling framework to improve the accuracy of decision-making. An interactive fuzzy satisfaction algorithm is advanced for solving this multi-level problem, in which COD discharge minimization, economic benefits maximization, and grain yield maximization are taken as the upper-, middle-, and lower-level goals, respectively. The framework is applied to plan the cross-regional water-environment-agriculture interactive system in the Beijing-Tianjin-Hebei and Yangtze River Economic Belt. Solutions reveal that increased WECC status and credibility level would decrease 1.40%-1.74%, 0.71%-9.61%, and 1.63%-2.26% of water resources allocation, COD emissions, and economic benefits, respectively. Crop area and grain yield would dramatically decline by 4.13%-4.46% and 4.03%-4.67% when a credibility level increases from 0.8 to 1, respectively. The overall satisfactory degree would range from 0.58 to 0.70, which illustrates interactive decision-making process of multiple stakeholders. Significant differences can be observed in the optimized schemes of water resources allocation and environmental-economic-agricultural performances among various models. The amounts of allocated water resources, pollutant discharge, and economic output from the FCMLP model would be respectively 11.30%-13.45%, 14.90%-15.21%, and 73.12%-73.48% higher than those from the environment- and agriculture-oriented schemes, yet 13.81%, 32.05%, and 15.29% lower than those from the economy-oriented scheme. Some water adaptability countermeasures are given for ensuring the scientific operation of the South-to-North Water Transfer Project and alleviating conflicts between water source and receiving areas. Further exploration of the optimization scheme of water-environment-energy-agriculture system driven by climate change is still required for guaranteeing the dynamic balance of regional resources.

Association of T-cell receptor repertoires and arterial stiffness in patients with essential hypertension.

BACKGROUND: Abnormal immune responses, particularly T-cell activity, are linked to vascular complications in hypertension, but mechanisms remain unknown. Our study aims to explore the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and T-cell receptor (TCR) repertoires in essential hypertension patients, focusing on understanding the role of T cells in the development of arterial stiffness in this population. METHODS: The study included 301 essential hypertension patients and 48 age-matched normotensive controls. Essential hypertension patients were stratified into high (baPWV ≥1400 cm/s, n = 213) and low (baPWV <1400 cm/s, n = 88) baPWV groups. High-throughput sequencing analyzed peripheral TCRß repertoires. RESULTS: Significant TCRß repertoire differences were observed between essential hypertension and normotensive groups, as well as between high and low baPWV essential hypertension subgroups. Specifically, patients in the high baPWV group exhibited notable variations in the utilization of specific TCR beta joining (TRBJ) and variable (TRBV) genes compared to the low baPWV group. These alterations were accompanied by reduced TCRß diversity (represented by diversity 50 s), increased percentages of the largest TCRß clones, and a higher number of TCRß clones exceeding 0.1%. The presence of specific TCRß clones was detected in both groups. Furthermore, reduced diversity 50s and elevated percentages of the largest TCRß clones were independently correlated with baPWV, emerging as potential risk factors for increased baPWV in essential hypertension patients. CONCLUSION: TCR repertoires were independently associated with arterial stiffness in patients with essential hypertension, implicating a potential role for dysregulated T-cell responses in the pathogenesis of arterial stiffness in this patient population.Trial registration: ChiCTR2100054414.

Reduced Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients With Essential Hypertension and Subclinical Carotid Atherosclerosis.

BACKGROUND: It has long been hypothesized that the abnormal immune responses contribute to the essential hypertension (EH) and its subclinical target organ damage (STOD). However, the mechanism is unclear. This study aimed at exploring the potential association with abnormal T-cell responses and EH, STOD, and early atherosclerosis in patients with EH. METHODS: This cross-sectional study included 146 patients with EH and 73 age-matched normotensive individuals. The expressed peripheral TCR (T-cell receptor) ß repertoire was analyzed by high through-put sequencing. RESULTS: The TCRß repertoires of the patients with EH were significantly different, with significantly elevated certain TCR beta variable (TRBV) and joint (TRBJ) gene usages, significantly reduced TCRß diversity indexes (diversity 50s) and numbers of total TCRß clonal types, significantly elevated percentages of the biggest TCRß clones and numbers of clones accounting >0.1% sequences, compared with those in the normotensive controls. Decreased diversity 50s and increased biggest TCRß clone percentages were independently correlated with carotid intima-media thickness and subclinical carotid atherosclerosis (SCA) in the patients with EH. Moreover, the diversity 50s were further significantly reduced and the biggest TCRß clone percentages were significantly increased in the patients with EH with SCA (n=89) comparing to the patients with EH/patients without SCA (n=57), and in patients with EH/SCA with carotid plaque (n=22) comparing to patients with EH/SCA/patients without carotid plaque (n=67). Importantly, specific TCRß clones were identified in different subgroups of the patients with EH. CONCLUSIONS: These results reveal that abnormal T-cell responses may play important roles in the progression of EH and its SCA, especially the formation of carotid plaque. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100054414.

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is the most prevalent sleep disturbance that affects approximately 936 million people worldwide and leads to extensively increased incidence of cardiovascular disease, metabolic syndrome, neurological disorders, and traffic accidents. Severe OSA patients suffer a significantly higher risk of complications and worse comorbidity outcomes. Notwithstanding, with inadequate access to contact diagnosis based on polysomnography (PSG), numerous patients with severe sleep apnea have not been diagnosed, especially during the pandemic. Moreover, how the T cell immunity is impaired in OSA remains largely unknown. Methods: We primarily investigated the T cell receptor (TCR) repertoires of 50 patients with severe OSA, 23 patients with mild-to-moderate OSA, 23 patients without OSA, and 157 healthy individuals, from their peripheral blood. Firstly, we compared the clinical characteristics, blood cell counts, the ratio of neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and CD4+/CD8+T cell count between groups. Then, we compared the diversity, clonotypes, unique VJ alleles in patients with different disease severity. Furthermore, by identifying a series of disease-associated amino acid sequences, we employed a repeated hold-out machine learning strategy to explore the optimal algorithm for calculating the TCR repertoire characteristic Index (OSA-TCI). We further confirmed its relation with clinical features by linear regression analysis. Moreover, in followup of severe OSA patients who accepted adherent non-invasive ventilation, we assessed the changes of TCR repertoires, OSA-TCI, ESS, NLR, PLR, and CD4+/CD8+T after therapy. Results: We found an unexpected increase in diversity and clonotypes in the TCR repertoire of OSA patients. Furthermore, we successfully developed a novel indicator termed OSA-TCI to summarize the unique repertoire alteration, which provided 90% of sensitivity and 87% of specificity in distinguishing severe OSA. In rationalization, OSA-TCI was found correlated to AHI, BMI, hemoglobin, N1, N2 percentage of sleep, snoring, smoking and lowest oxygen saturation, but only independently related to AHI (R = 0.603) and smoking (R = 0.22). Finally, we observed OSA-TCI in the eight severe patients decreased significantly after home noninvasive ventilation for three months during follow-up, consistently in line with the TCR repertoire improvement. In contrast, NLR, PLR, and the ratio of CD4+/CD8+T cell count were found useless to diagnose and therapeutic surveillance of severe OSA. Conclusions: Our study is the first to unveil the TCR repertoire alteration in OSA, indicates possible insidious autoimmune mechanisms underlying OSA, and suggests that TCR repertoires serve as a convenient peripheral blood biomarker for OSA assessment without long-time contact and facility/instrument occupation. It may shed light on future diagnostic, immunological, pathophysiological, and prognostic research on OSA.