title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=210 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Multifaceted roles of cGAS-STING pathway in the lung cancer: from mechanisms to translation link: https://peerj.com/articles/18559 last-modified: 2024-11-22 description: Lung cancer (LC) remains one of the most prevalent and lethal malignancies globally, with a 5-year survival rate for advanced cases persistently below 10%. Despite the significant advancements in immunotherapy, a substantial proportion of patients with advanced LC fail to respond effectively to these treatments, highlighting an urgent need for novel immunotherapeutic targets. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has gained prominence as a potential target for improving LC immunotherapy due to its pivotal role in enhancing anti-tumor immune responses, augmenting tumor antigen presentation, and promoting T cell infiltration. However, emerging evidence also suggests that the cGAS-STING pathway may have pro-tumorigenic effects in the context of LC. This review aims to provide a comprehensive analysis of the cGAS-STING pathway, including its biological composition, activation mechanisms, and physiological functions, as well as its dual roles in LC and the current and emerging LC treatment strategies that target the pathway. By addressing these aspects, we intend to highlight the potential of the cGAS-STING pathway as a novel immunotherapeutic target, while also considering the challenges and future directions for its clinical application. creator: Mingming Wei creator: Qingzhou Li creator: Shengrong Li creator: Dong Wang creator: Yumei Wang uri: https://doi.org/10.7717/peerj.18559 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2024 Wei et al. title: Serum neuron-specific enolase (NSE) is associated with the overall survival of colorectal cancer: a retrospective study link: https://peerj.com/articles/18617 last-modified: 2024-11-22 description: BackgroundSerum neuron-specific enolase (NSE) had been associated with survival of several cancers. However, its prognostic significance for colorectal cancer (CRC) has not been effectively discussed. We aimed to investigate the relationship between baseline serum NSE and the overall survival (OS) of colorectal adenocarcinoma (CRAD) patients.MethodsA retrospective study had been conducted by including 564 histopathology confirmed CRAD patients between January 2013 and December 2018 from Yunnan Provincial Cancer hospital, China. Cox proportional hazards model was used to estimate the crude and adjusted associations between serum NSE measured at diagnosis and the OS of the patients. Restricted cubic spline (RCS) was further applied to delineate dose-response trend of the NSE-OS association.ResultsAfter controlling for possible confounding factors, baseline serum NSE was significantly associated with OS in CRAD: when dichotomizing by the median, patients with higher baseline serum NSE (NSE >= 12.93 ng/mL) were observed a worse prognosis (hazard ratio, HR: 1.82, 95% CI [1.30–2.55], p < 0.01). Stratified analysis by tumor stage revealed a stronger NSE-OS association in advanced CRAD patients. RCS disclosed a prominent dose-response relationship in NSE-OS association for all CRAD patients: along with the increase of baseline serum NSE, the adjusted HR of CRAD patients increased gradually. This dose-response trend is also evident in advanced stage CRAD patients, but not in early stage CRAD patients.ConclusionsSerum NSE measured at diagnosis might be a useful prognostic indicator for CRAD, especially for advanced stage patients. creator: Junwei Peng creator: Jie Ma creator: Jian Lu creator: Hailiang Ran creator: Zhongqin Yuan creator: Hai Zhou creator: Yunchao Huang creator: Yuanyuan Xiao uri: https://doi.org/10.7717/peerj.18617 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2024 Peng et al. title: Estimation and prediction of water conservation in the upper reaches of the Hanjiang River Basin based on InVEST-PLUS model link: https://peerj.com/articles/18441 last-modified: 2024-11-21 description: With the gradual prominence of global water shortage and other problems, evaluating and predicting the impact of land use change on regional water conservation function is of great reference significance for carrying out national spatial planning and environmental protection, and realizing land intelligent management. We first analyzed 8,416 remote sensing images in the upper reaches of the Hanjiang River Basin (URHRB) by GEE platform and obtained the land use and land cover (LULC) results of fours periods. Through our field investigation, the accuracy of remote sensing image interpretation is obviously higher than that of other comprehensive LULC classification results. Then, through the coupling of InVEST-PLUS model, not only the results of URHRB water conservation from 1990 to 2020 were calculated and the accuracy was assessed, but also the LULC results and water conservation of URHRB under different development scenarios in 2030 were predicted. The results showed as follows: From 1990 to 2020, the forest area of URHRB increased by 7152.23 km2, while the area of cropland, shrub and grassland decreased by 3220.35 km2, 1414.72 km2 and 3385.39 km2, respectively. The InVEST model reliably quantifies the water yield and water conservation of URHRB. In the past 30 years, the total amount of water-saving in China has shown a trend of increasing first and then decreasing. From the perspective of vegetation types, URHRB forest land is the main body of water conservation, with an average annual water conservation depth of 653.87 mm and an average annual water conservation of 472.10×108 m3. Under the ecological protection scenario of the URHRB in 2030, the maximum water conservation in the basin is 574.92×108 m3, but compared with the water conservation in 2010, there is still a gap of 116.28×108 m3. Therefore, through the visualization analysis of the LULC changes of URHRB and water conservation function, it is found that the land and resources department should pay attention to the LULC changes of water sources and adjust the territorial spatial planning in time to cope with the huge water conservation gap in the future. creator: Pengtao Niu creator: Zhan Wang creator: Jing Wang creator: Yi Cao creator: Peihao Peng uri: https://doi.org/10.7717/peerj.18441 license: https://creativecommons.org/licenses/by-nc/4.0 rights: ©2024 Niu et al. title: Development and validation of a simple clinical nomogram for predicting infectious diseases in pediatric kidney transplantation recipients: a retrospective study link: https://peerj.com/articles/18454 last-modified: 2024-11-21 description: To construct and verify an easy-to-use nomogram for predicting the risk of infectious diseases in pediatric kidney transplant recipients. Clinical data of hospitalized pediatric kidney transplant recipients were retrospectively analyzed. Meaningful variables identified from the multivariate stepwise logistic regression analysis were used to construct the nomogram. Internal validation was performed using Bootstrap resampling 1,000 times. The nomogram was evaluated using calibration, decision and receiver operating characteristic (ROC) curves. A total of 297 pediatric kidney transplant recipients were included (164 infected, 133 non-infected). Multivariate stepwise regression analysis identified white blood cell count (WBC), lymphocyte to monocyte ratio (MLR), platelet to neutrophil ratio (PNR), red cell distribution width-standard deviation (RDW-SD), and albumin (ALB) as significant predictors of postoperative infection. The nomogram, based on the five indicators, showed strong discrimination ability (AUC = 0.756; 95% CI [0.702–0.811]), with a sensitivity of 88.0% and a specificity of 54.3%. The calibration curve and decision curve further demonstrated good consistency and clinical practicality between the predicted and actual values. WBC, MLR, PNR, RDW-SD, and ALB are effective indicators for predicting postoperative infection in pediatric kidney transplant recipients. The nomogram constructed from these indicators can effectively predict and evaluate the early risk of infection in these patients. creator: Li Li creator: Meng Fu creator: Changshan Wang creator: Yuxin Pei creator: Lizhi Chen creator: Liping Rong creator: Yuanyuan Xu creator: Zhilang Lin creator: Yuanquan Qiu creator: Xiaoyun Jiang creator: Mengjie Jiang uri: https://doi.org/10.7717/peerj.18454 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Li et al. title: The diagnostic utility of glycosaminoglycans (GAGs) in the early detection of cancer: a systematic review link: https://peerj.com/articles/18486 last-modified: 2024-11-21 description: BackgroundGlycosaminoglycans (GAGs) are a family of polysaccharides found abundantly in the extracellular matrix (ECM) of tissues. Research has indicated that the dysregulation of ECM, including changes and disruptions in GAGs, contributes to various cancer hallmarks such as metabolic reprogramming, persistent growth signals, immunosuppression, angiogenesis, tumor invasion, and metastasis.ObjectiveThis systematic review aims to evaluate the diagnostic accuracy of GAGs, including heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA), in early detection of cancer.MethodFour databases (PubMed, Scopus, EBSCO, and Ovid) were searched for studies in English within the last 15 years, involving at least 50 human participants. Using a two-stage process: identification and screening, 11 articles were selected and critically appraised using Critical Appraisal Skills Programme (CASP) checklists and Newcastle-Ottawa Scale (NOS) appropriate for each study design.ResultEleven studies met the inclusion criteria, encompassing various cancers like renal cell carcinoma (RCC), upper GI cancer (UGI), ovarian cancer, prostate cancer, breast cancer, lung cancer, colorectal cancer and oral cancer. Methodological quality was assessed using two established tools, with no studies exhibiting a high risk of bias. Heparan sulfate levels showed diagnostic potential in renal cancer with a maximum accuracy of 98.9%, achieving 94.7% specificity and 100% sensitivity. Chondroitin sulfate disaccharides emerged as a promising diagnostic marker in ovarian cancer and showed potential as diagnostic markers in renal cancer. However, there were no statistically significant differences in urinary chondroitin sulfate levels between patients and controls in prostate cancer. In breast cancer, hyaluronic acid showed moderate accuracy (AUC = 0.792) in distinguishing metastatic from non-metastatic disease, and a composite score incorporating multiple markers, including HA, showed even higher accuracy (AUC = 0.901) in detecting metastatic breast cancer. HA demonstrated moderate diagnostic accuracy for UGI cancers. Serum HA levels were significantly elevated in patients with oral cancer and pleural malignant mesothelioma and associated with tumor progression in patients with lung cancer. Elevated low molecular weight form of hyaluronan (~6 k Da HA) levels were found in colorectal cancer tissues.ConclusionGAGs hold potential as early cancer detection biomarkers. Further validation with larger, diverse populations is needed to validate their diagnostic accuracy and clinical utility. creator: Sarah Douglah creator: Reem Khalil creator: Reem Kanaan creator: Moza Almeqbaali creator: Nada Abdelmonem creator: Marc Abdelmessih creator: Yousr Khairalla creator: Natheer H. Al-Rawi uri: https://doi.org/10.7717/peerj.18486 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2024 Douglah et al. title: Single-cell data revealed the function of natural killer cells and macrophage cells in chemotherapy tolerance in acute myeloid leukemia link: https://peerj.com/articles/18521 last-modified: 2024-11-21 description: BackgroundAcute myeloid leukemia (AML) is highly prevalent and heterogeneous among adult acute leukemias. Current chemotherapeutic approaches for AML often face the challenge of drug resistance, and AML immune cells play an important role in the regulation of AML drug resistance. Thus, it is of key significance to explore the regulatory mechanisms of immune cells in AML to alleviate chemotherapy resistance in AML.MethodsBased on AML single-cell transcriptomic data, this study revealed the differences in the expression of immune cell subpopulations and marker genes in AML patients in the complete remission group (CR) compared to AML patients in the non-complete remission group (non-CR) after chemotherapy. Functional enrichment by clusterprofiler revealed the regulatory functions of differentially expressed genes (DEGs) in AML. AUCell enrichment scores were used to assess the immunoregulatory functions of immune cells. Pseudotime analysis was used to construct immune cell differentiation trajectories. CellChat was used for cellular communication analysis to elucidate the interactions between immune cells. Survival analysis with the R package “survival” revealed the role of immune cell marker genes on AML prognosis. Finally, the wound healing and trans-well assay were performed.ResultsSingle-cell clustering analysis revealed that NK/T cells and macrophage cells subpopulations were significantly higher in non-CR AML patients than in CR AML. AUCell enrichment analysis revealed that FCAR+ and FCGR3A+ macrophages were significantly more active in the non-CR group and correlated with processes regulating cellular energy metabolism and immune cell activity. Differentially expressed NK cell marker genes between CR and non-CR groups mainly included HBA1, S100A8, and S100A9, which were associated with cancer drug resistance regulation, these marker genes of (FCAR, FCGR3A, PREX1, S100A8 and S100A9) were upregulated in human chronic myeloid leukemia cells (HAP1) and silencing of S100A8 affected migration and invasion of HAP1 cells. In particular, the differentiation pathways of macrophages and NK cells in non-CR differed from those of patients in the CR group. Cellular communication analyses showed that ligand-receptor pairs between NK cells and macrophage cells mainly included HLA-E-KLRK1, HLA-E-KLRC1, HLA-E-CD94:NKG2A, CLEC2B-KLRB1. In addition, LGALS9-CD45, CCL3L1- CCR1, CCL3-CCR1 between these two immune cells mainly regulate secreted signaling to mediate AML progression. Marker genes in NK/T cells and macrophage cells were significantly associated with AML prognosis.ConclusionThis study reveals the potential role of NK cells and macrophages in AML chemoresistance through the analysis of single-cell RNA sequencing data. This provides new ideas and insights into the key mechanisms of immune cells in AML treatment. creator: Jing Gao creator: Xueqian Yan creator: Dan Fan creator: Yuanchun Li uri: https://doi.org/10.7717/peerj.18521 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Gao et al. title: The ecological niche characteristics and interspecific associations of plant species in the alpine meadow of the Tibetan Plateau affected plant species diversity under nitrogen addition link: https://peerj.com/articles/18526 last-modified: 2024-11-21 description: BackgroundPlant species diversity is of great significance to maintain the structure and function of the grassland ecosystem. Analyzing community niche and interspecific associations is crucial for understanding changes in plant species diversity. However, there are few studies on the response of plant species diversity, species niche characteristics, and interspecific relationships to nitrogen addition in alpine meadows on the Qinghai-Tibet Plateau.MethodsThis study investigates the effects of different levels of nitrogen addition (0, 15, 30, 45, and 60 g N m−2) on plant species diversity, functional group importance values, niche width, niche overlap, and interspecific associations in an alpine meadow.Results1) Compared with the control (CK), the Shannon-Weiner index and species richness index significantly increased by 11.36% and 30.77%, respectively, with nitrogen addition at 30 g N m−2, while both indices significantly decreased by 14.48% and 23.08%, respectively, at 60 g N m−2. As nitrogen addition increased, the importance value of grasses showed an upward trend, whereas the importance value of sedges showed a decline. 2) The niche width of Poa pratensis L., Elymus nutans Griseb., and Stipa purpurea Griseb. are increased with higher nitrogen addition. As nitrogen addition increases, the niche overlap values also show a rising trend. At 60 g N m−2, the overall community association in the alpine meadow exhibited a significant negative correlation. These findings suggest that grasses exhibit strong ecological adaptability under high nitrogen addition and gain a competitive advantage in spatial competition, increasing their niche width. Moreover, as nitrogen levels increase, the importance values of grasses rise significantly, and their ecological characteristics become more similar, resulting in reduced niche overlap among plant species. Furthermore, high nitrogen addition intensifies interspecific competition between grasses, sedges, and forbs, disrupting the original balance and reducing species diversity. These insights provide a valuable understanding of changes in species diversity and competitive dynamics in alpine meadow plant communities under high nitrogen addition. creator: Xuemei Xiang creator: Ke Jia De creator: Weishan Lin creator: Tingxu Feng creator: Fei Li creator: Xijie Wei uri: https://doi.org/10.7717/peerj.18526 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2024 Xiang et al. title: Abnormal hypothalamic functional connectivity and serum arousal-promoting neurotransmitters in insomnia disorder patients: a pilot study link: https://peerj.com/articles/18540 last-modified: 2024-11-21 description: ObjectiveThe present study aimed to investigate the functional connectivity (FC) of the anterior and posterior hypothalamus with the whole brain in insomnia disorder (ID) patients. Additionally, we explored the relationship between FC values and serum levels of arousal-promoting neurotransmitters (orexin-A and histamine) in ID patients.MethodsThis study enrolled 30 ID patients and 30 age- and gender-matched healthy controls. Resting-state functional magnetic resonance imaging (RS-fMRI) was employed to assess the FC of the anterior and posterior hypothalamus with the whole brain. Serum concentrations of orexin-A and histamine were measured using enzyme-linked immunosorbent assay (ELISA). Moreover, Spearman correlation analysis was conducted to investigate the relationship between FC values and serum levels of arousal-promoting neurotransmitters in ID patients.ResultsOur findings showed decreased FC between the posterior hypothalamus and several brain regions including the bilateral orbital superior frontal gyrus, the bilateral angular gyrus, the right anterior cingulate cortex, the left precuneus, and the right medial superior frontal gyrus in ID patients. Additionally, decreased FC was observed between the anterior hypothalamus and the right anterior cingulate cortex among ID patients. Compared to the healthy controls, ID patients showed significantly elevated serum concentrations of orexin-A and histamine. Furthermore, we identified a positive correlation between the FC of the right medial superior frontal gyrus with posterior hypothalamus and histamine levels in ID patients.ConclusionID patients exhibited aberrant FC in brain regions related to sleep-wake regulation, particularly involving the default mode network and anterior cingulate cortex, which may correlate with the peripheral levels of histamine. These findings contribute to our understanding of the potential neuroimaging and neurohumoral mechanism underlying ID patients. creator: Jingjing Lin creator: Zhenye Luo creator: Mei Fan creator: Yaxi Liu creator: Xian Shi creator: Yixian Cai creator: Zhiyun Yang creator: Liting Chen creator: Jiyang Pan uri: https://doi.org/10.7717/peerj.18540 license: https://creativecommons.org/licenses/by-nc/4.0 rights: © 2024 Lin et al. title: Health-related quality of life and its associated factors among Chinese seasonal retired migrants in Hainan link: https://peerj.com/articles/18574 last-modified: 2024-11-21 description: BackgroundSeasonal retired migrants are mainly retired or semiretired people who migrate to warmer areas during the winter and then return to their original homes in the following year. Despite its increasing popularity, the evidence concerning the health status of Chinese seasonal retired migrants is controversial. Although some studies have shown that seasonal retired migrants have better health status, other studies note that migrants are driven involuntarily by health concerns and that their mental health suffers during migration. The objective of this study was to provide quantified evidence on the health-related quality of life (HRQoL) of seasonal retired migrants in China and to identify potential factors associated with HRQoL.MethodsThis was a community-based cross-sectional study of seasonal retired migrants who lived in Wuzhishan, Hainan during the winter. The Chinese version of the EuroQol 5-Dimension 5-Level (EQ-5D-5L) was used to assess participants’ HRQoL. Data on demographic and behavioral characteristics, body mass index, and the presence of chronic diseases were collected using a self-administered survey. Logistic regressions were used to explore the factors associated with responses in each dimension of the EQ-5D-5L descriptive system, and a multiple linear regression model was used to explore the factors associated with EuroQol visual analogue scale (EQ-VAS) scores.ResultsA total of 992 participants (female: 56.5%) were enrolled in the current study, with a mean age of 67.87 ± 6.98 years. Most participants reported problems in the pain/discomfort dimension (16.7%), followed by the anxiety/depression dimension (8.3%). Few participants reported problems in the first three dimensions of the EQ-5D-5L: mobility (5.4%), usual activities (2.0%), and self-care (1.2%). The median EQ-VAS score was 84 (interquartile range: 80–89). The regression results indicated that poor sleep quality, the presence of chronic diseases, and low-level physical activity were important factors that were negatively associated with multiple dimensions of the EQ-5D-5L. In addition, the EQ-VAS score was negatively associated with age, the presence of chronic diseases, poor sleep quality, and low-level physical activity.ConclusionThis study revealed that Chinese seasonal retired migrants have high HRQoL. In addition, this study revealed that sleep quality and physical activity are correlated with multiple dimensions of the EQ-5D-5L descriptive system and EQ-VAS. Therefore, lifestyle interventions related to sleep quality and physical activity are essential for improving HRQoL among Chinese seasonal retired migrants. creator: Sikun Chen creator: Tianchang Li creator: Lingjun Wang creator: Shigong Wang creator: Lin Ouyang creator: Jiwei Wang creator: Dayi Hu creator: Jinming Yu uri: https://doi.org/10.7717/peerj.18574 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Chen et al. title: Correlation between pre-operative VE-cadherin and DLL4 and the maturation after primary arteriovenous fistula in uremic patients link: https://peerj.com/articles/18356 last-modified: 2024-11-20 description: AimsUremic patients require dialysis to replace the declined kidney function, and arteriovenous fistula (AVF) is a commonly used dialysis access route. Our study aimed to explore vascular endothelial cells cadherin (VE-cadherin) and Delta-like ligand 4 (DLL4) expression in uremic patients undergoing primary AVF surgery and their correlation with AVF maturation.MethodsWe conducted a prospective study that included n = 55 voluntary uremic patients receiving their initial AVF procedure for renal replacement therapy, subjects were divided into a mature group and a failure group based on whether the AVF matured within 3 months post-operatively. We analyzed the association of VE-cadherin and DLL4 with AVF maturation by examining their expression levels in serum and the endothelium of cephalic veins.ResultsPre-operative serum VE-cadherin, in the mature group measured 125.07 (106.77–167.65) ng/L, and DLL4 was 92.78 (83.83–106.72) pg/mL, while the failure group had VE-cadherin at 95.40 (79.03–107.16) ng/L (P = 0.001), and DLL4 at 60.42 (43.98–80.15) pg/mL with a statistical significant; (P = 0.002), binary logistic regression analysis indicated a significant association between cephalic vein diameter, VE-cadherin, DLL4 levels, and AVF immaturity (P = 0.024, P = 0.014 respectively). Immunohistochemical staining showed slightly higher VE-cadherin levels in the mature group than in the failure group (P = 0.366). DLL4 was primarily located in the cell membrane and cytoplasm, concentrated in the inner membrane, with significantly higher levels in the mature group compared to the failure group (P = 0.027).ConclusionThe failure group exhibited lower levels of VE-cadherin and DLL4 in serum and vascular tissue, these results suggest that VE-cadherin and DLL4 might play pivotal regulatory roles in the onset and the progression of fistula immaturity, potentially serving as promising targets for future interventions. creator: Huanhuan Yin creator: Yifan Tang creator: Yanping Wang creator: Yousuf Abdulkarim Waheed creator: Disheng Wang creator: Dong Sun uri: https://doi.org/10.7717/peerj.18356 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2024 Yin et al.