Background Ferroptosis is a novel form of regulated cell death that plays a critical role in tumorigenesis. The purpose of this study was to establish a ferroptosis-associated gene (FRG) signature ...and assess its clinical outcome in gastric cancer (GC). Methods Differentially expressed FRGs were identified using gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were performed to construct a prognostic signature. The model was validated using an independent GEO dataset, and a genomic-clinicopathologic nomogram integrating risk scores and clinicopathological features was established. Results An 8-FRG signature was constructed to calculate the risk score and classify GC patients into two risk groups (high- and low-risk) according to the median value of the risk score. The signature showed a robust predictive capacity in the stratification analysis. A high-risk score was associated with advanced clinicopathological features and an unfavorable prognosis. The predictive accuracy of the signature was confirmed using an independent GSE84437 dataset. Patients in the two groups showed different enrichment of immune cells and immune-related pathways. Finally, we established a genomic-clinicopathologic nomogram (based on risk score, age, and tumor stage) to predict the overall survival (OS) of GC patients. Conclusions The novel FRG signature may be a reliable tool for assisting clinicians in predicting the OS of GC patients and may facilitate personalized treatment.
Aim
Nitrogen (N) and phosphorus (P) are two major limiting factors in terrestrial ecosystems. Excessive N applications alter ecosystem functions by causing nutrient imbalances with P. Yet, little is ...known about why and how the balance between N and P regulates soil multifunctionality –the simultaneous provision of multiple soil functions–.
Methods
We explored how P additions regulated the responses of soil multifunctionality to different levels of N fertilization (10, 20, 40 g N m
−2
yr
−1
) using a mesocosm experiment in a temperate grassland in China.
Results
Nitrogen alone and P addition increased multifunctionality at rate of ≤10 and 20 g N m
−2
yr
−1
, respectively. However, the magnitude of positive effects decreased with N additions over this level. P additions increased multifunctionality resistance to N at low rate of ≤10 g m
−2
yr
−1
compared to higher N levels. Soil N:P stoichiometry and plant diversity played dominant roles in regulating soil multifunctionality.
Conclusions
We found that a balanced combination of N and P additions (20:10) can help maintain the highest multifunctionality in this temperate grassland. The results provide new insights that through P addition, we could better manage soil multifunctionality and increase its resistance to expected fertilization scenarios (≤ 10 g m
−2
yr
−1
).
Nitrogen (N) fertilization due to N deposition, N in manure from grazing livestock and direct input to soil by humans are impacting our terrestrial ecosystems globally. However, to date, our ...understanding of how artificial gradients of N fertilization indirectly affect phosphorus (P) availability by altering the rates and interrelationships of multiple structural and functional attributes of terrestrial ecosystems is still limited.
Here, we conducted a 3‐year field experiment to evaluate the direct and indirect effects of multiple level of N addition on a wide range of ecosystem structural and functional attributes associated with >20 plant, soil and microbial variables in a semi‐arid grassland.
We found that N fertilization can have multiple cascading effects on ecosystem structures and functions. These cascading events ultimately result in the activation of multiple biologically driven mechanisms to promote P availability (e.g. increased soil organic P mineralization, plant phosphorus resorption, enzymatic and genetic processes of phosphatase). The increasing phosphatase production and its functional gene expression, and decreasing plant and microbial biomass might imply important shifts in the carbon‐use strategies of plants and microbes allocating more resources to high‐C consuming enzymatic and genetic processes and less in plant and microbial biomass. Nitrogen addition decreases fungal community biomass which suggests the decoupling of key symbiotic plant–fungal relationships for nutrient acquirement.
Overall, our study advances our understanding of how and why N fertilization simultaneously influences multiple structural and functional attributes, ultimately accelerating phosphorus cycle in terrestrial ecosystems.
抽象的
氮肥的使用正在显著影响全球的陆地生态系统，其中氮的来源包括：氮沉降、放牧家畜的粪肥和直接人为的土壤输入。但是，迄今为止，我们对模拟的氮肥梯度如何通过改变陆地生态系统的多种结构和功能属性的大小和相互关系而间接影响磷的可利用性的理解还十分有限。我们开展了为期三年的野外控制实验研究评估多个水平的氮添加对超过20个与植物、土壤和微生物相关的生态系统结构和功能指标的直接和间接影响。研究结果表明氮肥的使用对多种生态系统结构和功能产生级联影响。氮添加的级联效应最终激活多种生物驱动机制提高磷的可利用性，例如：提高有机磷矿化速率、植物磷的重吸收效率和激活磷酸酶相关的酶和基因过程。磷酸酶的产量和其功能基因表达的增加，而植物和微生物生物量的减少可能表明：植物和微生物碳利用策略的改变，即分配更多的碳给高能耗的酶和基因过程，减少对植物和微生物生物量的分配。此外，氮添加显著降低了真菌群落的生物量，结果表明关键的植物‐真菌共生关系发生了解耦合。总之，我们的研究加强了氮肥如何和为什么同时影响多种陆地生态系统的结构和功能属性，最终提高生态系统的磷循环的理解。
A free Plain Language Summary can be found within the Supporting Information of this article.
A free plain Language Summary can be found within the Supporting Information of this article.
An increasing number of studies have investigated the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in various types of cancer. The present meta-analysis was designed to investigate its ...prognostic value of pretreatment LMR in pancreatic cancer (PC).
An integrated meta-analysis was conducted and eligible studies were recruited by a systematic search in MEDLINE, EMBASE, and Cochrane databases. The association between LMR and survival outcomes and clinicopathological features were analyzed in PC patients.
A total of 10 studies (11 cohorts) comprising 2557 patients were included in this meta-analysis. The result demonstrated that low LMR could predict unfavorable overall survival(OS) (HR: 0.60, 95% confidence interval CI: 0.50–0.71, p < 0.001) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR: 0.43, 95% CI: 0.20–0.94, p = 0.03). Moreover, low LMR was also positively correlated with male patients, CA199, and TNM stage.
This study suggested that low pretreatment LMR was associated with advanced clinicopathological features and poor prognosis as a predicative factor in patients with PC.
•Several studies have investigated the prognostic value of the LMR in various types of cancer.•We investigated its prognostic value of pretreatment LMR in PC.•The results showed that low LMR could predict unfavorable OS and DFS/RFS.•We therefore conclude that low pretreatment LMR was associated with advanced clinicopathological features and poor prognosis as a predicative factor in patients with PC.
Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function of circRNAs in gastric cancer (GC) are still ...unknown. Here, we aimed to determine the regulatory mechanism of circRNAs in GC.
Expression profiles of circRNAs were downloaded from four Gene Expression Omnibus (GEO) microarray datasets. Expression profiles of miRNAs and mRNAs were collected from The Cancer Genome Atlas (TCGA) database. We used the robust rank aggregation method to identify differentially expressed circRNAs (DEcircRNAs) and a ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Functional and pathway enrichment analyses were performed and interactions between proteins were predicted using Cytoscape. Aa subnetwork regulatory module was built using the MCODE plugin.
A total of eight DEcircRNAs, 240 DEmiRNAs, and 4578 DEmRNAs were identified. The circRNA-miRNA-mRNA network was constructed based on seven circRNAs, 33 miRNAs, 69 mRNAs in GC. GO and KEGG pathway analysis indicated DEmRNAs might be associated with GC onset and progression. A PPI network was established and four hub genes (MCM4, KIF23, MCM8, and NCAPD2) were determined from the network. Then a circRNA-miRNA-hub gene subnetwork was constructed based on the four DEcircRNAs, three DEmiRNAs, and four DEmRNAs.
Our findings provide a deeper understanding the circRNA-related competing endogenous RNA regulatory mechanism in GC pathogenesis.
Recently, the lymphocyte-to-monocyte ratio (LMR) has been reported to be a prognostic factor in multiple malignancies. The current study was designed to assess the prognostic value of pretreatment ...LMR in gastric cancer (GC).
MEDLINE, EMBASE, Cochrane, and CNKI databases were searched until April 2017. Eligible articles were defined as studies assessing the prognostic role of pretreatment LMR in GC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were calculated using fixed-effects or random-effects models.
A total of six studies comprising 4908 patients were included in the study. Pooled results showed that low LMR was significantly associated with decreased OS (HR: 0.66, 95% confidence interval CI: 0.54–0.82, p < .001), but not with poor DFS/RFS (HR: 0.71, 95% CI: 0.38–1.32, p = .004). The unfavorable prognostic impact of low LMR on OS was observed in patients of different disease stages and cut-off values. Moreover, low LMR was significantly related to age (>median), gender (male), CEA (>5 ng/ml), tumor size (>3 cm), TNM stage (III-IV), lymph node metastasis, and distant metastasis.
Low pretreatment LMR may be a significant prognostic biomarker for poor OS in patients with GC.
•The lymphocyte-to-monocyte ratio (LMR) has been reported to be a prognostic factor in multiple malignancies.•We firstly assess the prognostic value of pretreatment LMR in gastric cancer (GC).•Pooled results showed that low LMR was significantly associated with decreased OS, but not with poor DFS/RFS.•Low LMR was significantly related to age, gender, CEA, tumor size, TNM stage, lymph node metastasis, and distant metastasis.
Vault RNAs (vtRNAs) are small noncoding RNAs and highly expressed in many eukaryotes. Here, we identified vtRNA2‐1 as a novel regulator of the intestinal barrier via interaction with RNA‐binding ...protein HuR. Intestinal mucosal tissues from patients with inflammatory bowel diseases and from mice with colitis or sepsis express increased levels of vtRNAs relative to controls. Ectopically expressed vtRNA2‐1 decreases the levels of intercellular junction (IJ) proteins claudin 1, occludin, and E‐cadherin and causes intestinal epithelial barrier dysfunction in vitro, whereas vtRNA2‐1 silencing promotes barrier function. Increased vtRNA2‐1 also decreases IJs in intestinal organoid, inhibits epithelial renewal, and causes Paneth cell defects ex vivo. Elevating the levels of tissue vtRNA2‐1 in the intestinal mucosa increases the vulnerability of the gut barrier to septic stress in mice. vtRNA2‐1 interacts with HuR and prevents HuR binding to claudin 1 and occludin mRNAs, thus decreasing their translation. These results indicate that vtRNA2‐1 impairs intestinal barrier function by repressing HuR‐facilitated translation of claudin 1 and occludin.
Synopsis
Vault RNAs (vtRNAs) are small noncoding RNAs, and their levels increase in intestinal mucosa from patients with IBD. vtRNA2‐1 disrupts intestinal epithelial barrier function by decreasing intercellular junctions via interaction with HuR.
vtRNA2‐1 inhibits expression of claudin 1, occludin, and E‐cadherin posttranscriptionally.
vtRNA2‐1 impairs intestinal epithelial renewal and causes Paneth cell defects ex vivo.
Elevating tissue vtRNA2‐1 levels increases vulnerability of gut barrier to septic stress in mice.
vtRNA2‐1 interacts with HuR and prevents HuR binding to mRNAs.
Vault RNAs (vtRNAs) are small noncoding RNAs, and their levels increase in intestinal mucosa from patients with IBD. vtRNA2‐1 disrupts intestinal epithelial barrier function by decreasing intercellular junctions via interaction with HuR.
Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that form covalently closed circles. Although circRNAs influence many biological processes, little is known about their role in ...intestinal epithelium homeostasis. We surveyed circRNAs required to maintain intestinal epithelial integrity and identified circular homeodomain-interacting protein kinase 3 (circHIPK3) as a major regulator of intestinal epithelial repair after acute injury.
Intestinal mucosal tissues were collected from mice exposed to cecal ligation and puncture for 48 hours and patients with inflammatory bowel diseases and sepsis. We isolated primary enterocytes from the small intestine of mice and derived intestinal organoids. The levels of circHIPK3 were silenced in intestinal epithelial cells (IECs) by transfection with small interfering RNAs targeting the circularization junction of circHIPK3 or elevated using a plasmid vector that overexpressed circHIPK3. Intestinal epithelial repair was examined in an in vitro injury model by removing part of the monolayer. The association of circHIPK3 with microRNA 29b (miR-29b) was determined by biotinylated RNA pull-down assays.
Genome-wide profile analyses identified ∼300 circRNAs, including circHIPK3, differentially expressed in the intestinal mucosa of mice after cecal ligation and puncture relative to sham mice. Intestinal mucosa from patients with inflammatory bowel diseases and sepsis had reduced levels of circHIPK3. Increasing the levels of circHIPK3 enhanced intestinal epithelium repair after wounding, whereas circHIPK3 silencing repressed epithelial recovery. CircHIPK3 silencing also inhibited growth of IECs and intestinal organoids, and circHIPK3 overexpression promoted intestinal epithelium renewal in mice. Mechanistic studies revealed that circHIPK3 directly bound to miR-29b and inhibited miR-29 activity, thus increasing expression of Rac1, Cdc42, and cyclin B1 in IECs after wounding.
In studies of mice, IECs, and human tissues, our results indicate that circHIPK3 improves repair of the intestinal epithelium at least in part by reducing miR-29b availability.
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Circular RNA circHIPK3 enhances intestinal epithelial repair and promotes mucosal growth by reducing microRNA 29b activity, but its levels decrease in patients with inflammatory bowel disease.
Introduction. A growing number of studies have explored the association between the pretreatment lymphocyte-to-monocyte ratio (LMR) and survival outcomes in various cancers. However, its prognostic ...significance on bladder cancer remains inconsistent. The aim of this meta-analysis was to evaluate the prognostic value of pretreatment LMR in bladder cancer. Methods. The MEDLINE, EMBASE, Cochrane Library, and CNKI databases were comprehensively searched for relevant studies. A meta-analysis of overall survival (OS), recurrence-free survival (RFS), or cancer-specific survival (CSS) clinicopathological features was conducted. Results. Nine studies containing 5,638 cancer patients were analyzed in this meta-analysis. Patients with high LMR tended to have favourable OS (HR: 0.63, 95% CI: 0.50-0.80, P<0.001), RFS (HR: 0.59, 95% CI: 0.38-0.91, P=0.017), and CSS (HR: 0.76, 95% CI: 0.70-0.83, P<0.001). Moreover, low LMR was highly correlated with age (≥60), differentiation (low), T stage (III-IV), lymph node metastasis (yes), and concomitant Cis (yes). Conclusion. Pretreatment LMR might be a useful predictor of survival outcomes in patients with bladder cancer.
•C sequestration and mineralization showed negative correlations at 0–10 cm layer.•Macro-aggregates (>2 mm) were the main carriers of SOC sequestration.•No-till improved C stock in macro-aggregates ...due to less mineralization.•Straw returning increased C concentration due to low mineralization quotient.
Understanding the process of soil organic carbon (SOC) sequestration and mineralization in aggregates is pertinent to mitigate climate change and minimize risks of soil degradation. Thus, soil samples were obtained after a 10-year field experiment to identify the influences of tillage on aggregate-associated SOC sequestration and mineralization in the North China Plain (NCP). Four tillage practices investigated were as follows: no-till with straw retention (NTS, conservation tillage), rotary tillage with straw incorporation (RTS), conventional tillage with straw incorporation (CTS), and conventional tillage with straw removal (CT). Significantly negative correlations were observed between SOC concentration and potentially mineralized carbon in aggregates under different treatments for the 0–10 cm soil layer. The large macro-aggregates (>2 mm) with the highest proportion of size distribution represented the major pool of SOC stock (47.3–51.2%) and mineralization amount (38.2–43.6%) in the 0–30 cm layer, followed by that in the small macro-aggregates (0.25–2 mm), regardless of tillage practices. However, the mineralization quotient (mineralization per unit SOC concentration) of macro-aggregates (>0.25 mm) was lower than that for the other size classes. The NTS enhanced the macro-aggregate formation in the 0–20 cm layer and associated SOC concentration in the 0–10 cm layer. Furthermore, NTS decreased total potential mineralization in the 0–30 cm layer compared with the other tillage practices, attributed to decrease in the large macro-aggregates (30.0–51.4%) with low particulate organic carbon (POC) concentration. The NTS with low straw inputs had higher incremental efficiency with straw incorporation than that in the RTS and CTS by 45.0% and 13.5%, respectively (P < 0.05). Overall, the higher proportion of macro-aggregates recorded under NTS decreased carbon mineralization, and consequently, increased incremental efficiency with straw incorporation, and improved SOC sequestration in the surface soil layer in the NCP.
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