Development of a prognostic nomogram and risk stratification system for upper thoracic esophageal squamous cell carcinoma

BackgroundThe study aimed to develop a nomogram model to predict overall survival (OS) and construct a risk stratification system of upper thoracic esophageal squamous cell carcinoma (ESCC).MethodsNewly diagnosed 568 patients with upper ESCC at Fujian Medical University Cancer Hospital were taken as a training cohort, and additional 155 patients with upper ESCC from Sichuan Cancer Hospital Institute were used as a validation cohort. A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS. The predictive power of nomogram model was evaluated by using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI).ResultsIn this study, multivariate analysis revealed that gender, clinical T stage, clinical N stage and primary gross tumor volume were independent prognostic factors for OS in the training cohort. The nomogram based on these factors presented favorable prognostic efficacy in the both training and validation cohorts, with concordance statistics (C-index) of 0.622, 0.713, and area under the curve (AUC) value of 0.709, 0.739, respectively, which appeared superior to those of the American Joint Committee on Cancer (AJCC) staging system. Additionally, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the nomogram presented better discrimination ability to predict survival than those of AJCC staging. Furthermore, decision curve analysis (DCA) of the nomogram exhibited greater clinical performance than that of AJCC staging. Finally, the nomogram fairly distinguished the OS rates among low, moderate, and high risk groups, whereas the OS curves of clinical stage could not be well separated among clinical AJCC stage.ConclusionWe built an effective nomogram model for predicting OS of upper ESCC, which may improve clinicians’ abilities to predict individualized survival and facilitate to further stratify the management of patients at risk

A pyroptosis-related gene signature for prognosis prediction in hepatocellular carcinoma

IntroductionHepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood.MethodsIn our study, clinical information and mRNA expression for 1076 patients with HCC were obtained from the five public cohorts. Pyroptotic clusters were generated by unsupervised clustering based on 40 pyroptosis-related genes (PRGs) in the TCGA and ICGC cohort. A pyroptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) regression according to differentially expressed genes (DEGs) of pyroptotic clusters. The signature was then tested in the validation cohorts (GES10142 and GSE14520) and subsequently validated in the CPTAC cohort (n=159) at both mRNA and protein levels. Response to sorafenib was explored in GSE109211.ResultsThree clusters were identified based on the 40 PRGs in the TCGA cohort. A total of 24 genes were selected based on DEGs of the above three pyroptotic clusters to construct the pyroptotic risk score. Patients with the high-risk score showed shorter overall survival (OS) compared to those with the low-risk score in the training set (P<0.001; HR, 3.06; 95% CI, 2.22-4.24) and the test set (P=0.008; HR, 1.61; 95% CI, 1.13-2.28). The predictive ability of the risk score was further confirmed in the CPTAC cohort at both mRNAs (P<0.001; HR, 2.99; 95% CI, 1.67-5.36) and protein levels (P<0.001; HR, 2.97; 95% CI 1.66-5.31). The expression of the model genes was correlated with immune cell infiltration, angiogenesis-related genes, and sensitivity to antiangiogenic therapy (P<0.05).DiscussionIn conclusion, we established a prognostic signature of 24 genes based on pyroptosis clusters for HCC patients, providing insight into the risk stratification of HCC

A Modified Location-Weighted Landscape Index to Evaluate Nutrient Retention in Agricultural Wetlands: A Case Study of the Honghe Hani Rice Terraces World Heritage Site

Understanding the influence of landscape patterns on the water quality of agricultural wetlands is critically important for their management and related decision-making. However, the question of how to quantify this objectively remains a challenge in the relevant scientific fields. In this study, the location-weighted landscape index (LWLI), a process-oriented indicator that integrates ecological processes with landscape patterns based on the source and sink theory, was modified into the SLWLI by assigning nutrient-based weights in the Honghe Hani Rice Terraces World Heritage Site (HHRT). The results indicate that the five watersheds are dominated by sink landscapes, representing 64 percent of the total area. Rice terraced fields were a composite “source–sink” landscape, and their areas in the five watersheds ranged from 4.82 to 20.40%. The nutrient retention function of the sink landscapes of total nitrogen (TN) ranged from 0.64 to 0.86, whereas the total phosphorus (TP) ranged from 0.72 to 0.82, showing good retention function in regard to both nutrients. The contribution rates of forest land and rice terraces to TN and TP retention were greater than 47.07 and 17.07%, respectively, which indicates their key regulation of the nutrient retention function, reducing the risk of water eutrophication and leading to optimized conservation. The vertical pattern of the HHRT plays an important role in nutrient retention function. The SLWLI is an effective index that can be used to assess nutrient retention function and to identify sink landscapes for regulating water pollution in agricultural wetlands

Analysis of Dynamics and Diversity of Microbial Community during Production of Germinated Brown Rice

Sprouts may be contaminated with different pathogenic and spoilage microorganisms, which lead far too easily to foodborne outbreaks. The elucidations of microbial profiles in germinated brown rice (BR) are important, but the changes in the microbial composition during germination are unknown. This study aimed to investigate the microbiota composition and to monitor the dominant microbial dynamics in BR during germination using both culture-independent and -dependent methods. BR samples (HLJ2 and HN) were collected from each stage of the germination processing. The populations of microbes (total viable counts, yeast/mold counts, Bacillus cereus, and Enterobacteriaceae) of two BR cultivars increased markedly with the prolongation of the germination time. High-throughput sequencing (HTS) showed that the germination process significantly influenced the microbial composition and reduced the microbial diversity. Similar microbial communities were observed between the HLJ2 and the HN samples, but with different microbial richness. The bacterial and fungal alpha diversity achieved the maximum for ungerminated samples and declined significantly after soaking and germination. During germination, Pantoea, Bacillus, and Cronobacter were the dominant bacterial genera, but Aspergillus, Rhizopus, and Coniothyrium dominated for the fungi in the BR samples. The predominance of harmful and spoilage microorganisms in BR during germination is mainly from contaminated seeds, which highlights the potential risk of foodborne illness from sprouted BR products. The results provide new insight into the microbiome dynamics of BR and may help to establish effective decontamination measures against pathogenic microorganisms during sprout production

Temp-Spatial Heterogeneity of Water Recharge and Its Stable Mechanisms of the Mountainous Rice Terraces in East Asia Monsoon Region

The paddy field water recharge system and the mechanism of its stability are key scientific issues related to reducing the threat to global food security and enhancing the well-being of humans. In this study, we sampled the field water, precipitation, and groundwater in the Hani terrace areas and measured the values of hydrogen and oxygen stable isotopes. The results indicated that precipitation and groundwater were the main sources of terrace water recharge in the Hani terrace area. Spatially, the terrace areas were divided into rain-fed terraces, which were mainly recharged by precipitation, and spring-fed terraces, where groundwater was the primary source of recharge. Temporally, there were two different recharge periods: the rain-fed season (>70% recharge from precipitation) and the spring-fed season (>30% recharge from groundwater). The temporally alternating recharge periods of the spring-fed and rain-fed seasons and the interconnected spatial distribution of rain-fed and spring-fed types were essential to maintain stable water sources in the Hani terraces. Meanwhile, the spatial heterogeneity of groundwater recharge and the timing of agricultural cultivation adjusted the system to some extent. Rice cultivation will be sustainable if the changes in monsoonal precipitation due to global climate change align with the anthropogenic agricultural cultivation cycle, including land preparation, planting, growing, and harvesting. This is the key reason that the mountainous rice cultivation systems of the Hani terraces have lasted for thousands of years under the influence of the East Asian monsoon

Ammonia nitrogen exposure caused structural damages to gill mitochondria of clam Ruditapes philippinarum

Ammonia nitrogen has been one of the key pollution indicators along the Chinese coastline for quite a few years. Our previous studies have proved that ammonia nitrogen is harmful for Ruditapes philippinarum clam in several aspects. Environmental concentrations of ammonia nitrogen were found to significantly decrease ATP contents and disturb ATP metabolism, in addition to reducing the potential across the mitochondrial membrane in clam gill tissues. Accordingly, mitochondrion is considered as one of the target organelles of ammonia nitrogen toxicity in clams. However, there is a lack of direct evidence to prove it. In order to reveal detail information of ammonia nitrogen toxicity on clam mitochondria and screen the related biomarker to indicate ammonia nitrogen pollution, mitochondrial parameters in gill tissues including swelling, mtDNA copy number and marker enzyme (succinic dehydrogenase, SDH) activity were measured after the clams were exposed to 0.1 mg/L and 0.5 mg/L ammonia nitrogen for 3 days and 21 days, respectively. Moreover, adverse effects of ammonia nitrogen exposure on clam mitochondrial ultra-structures, mitochondrial swelling and division were also discriminated under transmission electron microscope (TEM). Final results showed that ammonia nitrogen exposure to both concentrations significantly induced mitochondrial swelling, reduced the number of mitochondria and messed their normal structure, decreased the number of mtDNA copies and down-regulated SDH activity, all in a concentration and duration dependent manner. So, the present study helps us to better understand the structural damage of ammonia nitrogen on mitochondria in clam gill cells and provides fundamental data for ammonia nitrogen control in aquaculture

High glucose impairs cognitive function through inducing mitochondrial calcium overload in Treg cells

Summary: High glucose has been proved to impair cognitive function in type 2 diabetes, but the underlying mechanisms remain elusive. Here, we found that high glucose increased transcription factors’ SP1 O-GlcNAcylation in regulatory T (Treg) cells. Glycosylated SP1 further enhanced HDAC2 recruitment and histone deacetylation on Na+/Ca2+/Li+ exchanger (NCLX) promoter, which downregulated NCLX expression and led to mitochondrial calcium overload and oxidative damage, thereby promoting Treg cell dysfunction, M1 microglia polarization, and diabetes-associated cognitive impairment. Importantly, GLP-1 receptor agonist alleviated these deleterious effects via GLP-1-receptor-mediated upregulation of OGA and inhibition of SP1 O-GlcNAcylation in Treg cells. Our study highlighted a link between high-glucose-mediated SP1 O-GlcNAcylation and HDAC2/NCLX signaling in control of mitochondrial calcium concentrations in Treg cells. It also revealed a mechanism for linking Treg cell dysfunction and cognitive impairment in type 2 diabetes and provides an insight into the mechanism underlying the neuroprotective effects of GLP-1 receptor agonist

Digenetic inheritance of SLC12A3 and CLCNKB genes in a Chinese girl with Gitelman syndrome

Abstract Background Gitelman syndrome (GS) is an autosomal recessive disorder and mild variant of classic Bartter syndrome. The latter is caused by defects in the genes CLCNKB and/or CLCNKA (chloride voltage-gated channel Ka and Kb). Patients with GS usually have loss-of-function mutations in SLC12A3. No patient has been reported with compound heterozygous mutations in these genes. We report a girl with GS with a paternally inherited heterozygous mutation in SLC12A3, and maternally inherited heterozygous variants in both CLCNKB and CLCNKA. Case presentation In this report, we reported a female patient (8 y and 10 mo) who had growth retardation (111.8 cm, − 1.62 standard deviation height for age) and normal blood pressure, with persistent hypokalemia, hypomagnesemia, hypocalciuria, hypochloremic alkalosis, and elevated levels of plasma renin and aldosterone. Her younger brother, father, and paternal grandmother all had histories of mild low levels of plasma potassium (3.0–3.5 mmol/L), which were rectified by potassium-rich foods. The genomic DNA of the patient, younger brother, parents, and grandparents were screened for gene variations and pedigree analysis using trio whole exome sequencing (WES). The candidate variants were validated by Sanger sequencing. Protein-protein interaction analysis utilized the following databases: Biogrid, MINT, HPRD, STRING, IntAct, iRefIndex, and ppiTrim. The trio WES screening showed that the patient has paternally inherited SLC12A3 p.N359K, and maternally inherited CLCNKB p.L94I. The paternal grandmother and younger brother are both carriers of SLC12A3 p.N359K. According to the STRING database, SLC12A3 and CLCNKB proteins may interact or coexpress with proteins associated with GS. Conclusions Based on clinical phenotypes, genetic evidence of the pedigree, and previous reported studies, this case of GS indicates a digenetic inheritance of SLC12A3 and CLCNKB that resulted in renal tubular dysfunction perhaps, due to a genetic double-hit mechanism. The putative pathogenicity of the CLCNKB p.L94I variant requires confirmation

The Expression of Snail, Galectin-3, and IGF1R in the Differential Diagnosis of Benign and Malignant Pheochromocytoma and Paraganglioma

Objective. The aim of this study was to investigate the expression of Snail, galectin-3, and IGF1R in benign and malignant pheochromocytoma and paraganglioma (PPGL) and explore their role in the diagnosis of malignant PPGL. Methods. We retrospectively collected and analyzed surgical tumor tissue from 226 patients initially diagnosed with PPGL who underwent surgery from Jan. 2009 to Jan. 2016 at West China Hospital, Sichuan University. We observed and quantified the expression of Snail, galectin-3, and IGF1R in paraffin-embedded samples by immunohistochemical staining. Results. The significant difference in survival time among the three groups (benign PHEO, benign PGL, and potentially malignant PPGL) was compared by Kaplan-Meier survival analysis. The positive staining of Snail, galectin-3, and IGF1R in the benign PHEO group was significantly lower than that in the other three groups (P<0.001). The Kaplan-Meier survival plots indicated that the survival time of the patients with intense positive staining was significantly lower than that of the patients with weak positive staining. Conclusion. The intense expression of Snail, galectin-3, and IGF1R may be valuable indicators for the diagnosis of malignant PPGL