New insights into the occurrence of continuous cropping obstacles in pea (Pisum sativum L.) from soil bacterial communities, root metabolism and gene transcription.

BACKGROUND: Continuous cropping is a significant obstacle to sustainable development in the pea (Pisum sativum L.) industry, but the underlying mechanisms of this remain unclear. In this study, we used 16 S rDNA sequencing, transcriptomics, and metabolomics to analyze the response mechanism of roots and soil bacteria to continuous cropping and the relationship between soil bacteria and root phenotypes of different pea genotypes (Ding wan 10 and Yun wan 8). RESULTS: Continuous cropping inhibited pea growth, with a greater effect on Ding wan 10 than Yun wan 8. Metabolomics showed that the number of differentially accumulated metabolites (DAMs) in pea roots increased with the number of continuous cropping, and more metabolic pathways were involved. Transcriptomics revealed that the number of differentially expressed genes (DEGs) increased with the number of continuous cropping. Continuous cropping altered the expression of genes involved in plant-pathogen interaction, MAPK signal transduction, and lignin synthesis pathways in pea roots, with more DEGs in Ding wan 10 than in Yun wan 8. The up-regulated expression of genes in the ethylene signal transduction pathway was evident in Ding wan 10. Soil bacterial diversity did not change, but the relative abundance of bacteria significantly responded to continuous cropping. Integrative analysis showed that the bacteria with significant relative abundance in the soil were strongly associated with the antioxidant synthesis and linoleic acid metabolism pathway of pea roots under continuous cropping once. Under continuous cropping twice, the bacteria with significant relative abundance changes were strongly associated with cysteine and methionine metabolism, fatty acid metabolism, phenylpropanoid biosynthesis, terpenoid backbone biosynthesis, linoleic acid, and amino sugar and nucleotide sugar metabolism. CONCLUSION: Ding wan 10 was more sensitive to continuous cropping than Yun wan 8. Continuous cropping times and pea genotypes determined the differences in root metabolic pathways. There were common metabolic pathways in the two pea genotypes in response to continuous cropping, and the DEGs and DAMs in these metabolic pathways were strongly associated with the bacteria with significant changes in relative abundance in the soil. This study provides new insights into obstacles to continuous cropping in peas.

CsBPC2 is essential for cucumber survival under cold stress.

Cold stress affects the growth and development of cucumbers. Whether the BPC2 transcription factor participates in cold tolerance and its regulatory mechanism in plants have not been reported. Here, we used wild-type (WT) cucumber seedlings and two mutant Csbpc2 lines as materials. The underlying mechanisms were studied by determining the phenotype, physiological and biochemical indicators, and transcriptome after cold stress. The results showed that CsBPC2 knockout reduced cucumber cold tolerance by increasing the chilling injury index, relative electrical conductivity and malondialdehyde (MDA) content and decreasing antioxidant enzyme activity. We then conducted RNA sequencing (RNA-seq) to explore transcript-level changes in Csbpc2 mutants. A large number of differentially expressed genes (1032) were identified and found to be unique in Csbpc2 mutants. However, only 489 down-regulated genes related to the synthesis and transport of amino acids and vitamins were found to be enriched through GO analysis. Moreover, both RNA-seq and qPT-PCR techniques revealed that CsBPC2 knockout also decreased the expression of some key cold-responsive genes, such as CsICE1, CsCOR413IM2, CsBZR1 and CsBZR2. These results strongly suggested that CsBPC2 knockout not only affected cold function genes but also decreased the levels of some key metabolites under cold stress. In conclusion, this study reveals for the first time that CsBPC2 is essential for cold tolerance in cucumber and provides a reference for research on the biological function of BPC2 in other plants.

Changes of gut microbiota and short chain fatty acids in patients with Peutz-Jeghers syndrome.

Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future.

CsBPC2 is a key regulator of root growth and development.

BASIC PENTACYSTEINE (BPCs) transcription factors are important regulators of plant growth and development. However, the regulatory mechanism of BPC2 in roots remains unclear. In our previous study, we created Csbpc2 cucumber mutants by the CRISPR/Cas9 system, and our studies on the phenotype of Csbpc2 mutants showed that the root growth was inhibited compared with wide-type (WT). Moreover, the surface area, volume and number of roots decreased significantly, with root system architecture changing from dichotomous branching to herringbone branching. Compared with WT, the leaf growth of the Csbpc2 mutants was not affected. However, the palisade and spongy tissue were significantly thinner, which was not beneficial for photosynthesis. The metabolome of root exudates showed that compared with WT, amino acids and their derivatives were significantly decreased, and the enriched pathways were mainly regulated by amino acids and their derivatives, indicating that knockout of CsBPC2 mainly affected the amino acid content in root exudates. Importantly, transcriptome analysis showed that knockout of CsBPC2 mainly affected root gene expression. Knockout of CsBPC2 significantly reduced the gene expression of gibberellins synthesis. However, the expression of genes related to amino acid synthesis, nitrogen fixation and PSII-related photosynthesis increased significantly, which may be due to the effect of knocking out CsBPC2 on gibberellins synthesis, resulting in the inhibition of seedling growth, thus forming negative feedback regulation. Generally, we showed for the first time that BPC2 is a key regulator gene of root growth and development, laying the foundation for future mechanisms of BPC2 regulation in roots.

Association between uveitis onset and economic development in mainland China.

BACKGROUND: Economic prosperity has fostered numerous changes that may translate into better or worse outcomes across all domains of health. This study aims to explore the associations of economic development with uveitis onset in mainland China. METHODS: We used Poisson regression with generalized estimated equations to quantify the associations of per capita gross domestic product (GDP) with uveitis onset in 31 provinces of mainland China from 2006 to 2017. We further estimated the effects mediated by economic growth on the temperature-uveitis and PM2.5-uveitis associations established in our previous studies. RESULTS: A total of 12,721 uveitis patients from 31 provinces of mainland China were studied. Overall, every 10,000 Chinese yuan ($ 1491.278, 2006-2017) increase in per capita GDP, with no weighted value or weighted by population, corresponded to 1.85% (95% confidence interval, 1.19-2.52%) and 1.43% (95% confidence interval, 0.37-2.51%) lnRR decrease in the uveitis onsets. Stratified analysis showed this negative association between per capita GDP and uveitis onset, only existed in male patients (P < .001), individuals aged 20-50 years (P < 0 .05), non-infectious uveitis, uveitis with systemic disease, and Bechet's disease (all P < 0 .05). Moreover, the increased per capita GDP, if above the national level, could reinforce both temperature-uveitis and PM2.5-uveitis association (both P < 0.001). CONCLUSIONS: The findings suggest that economic development is negatively associated with uveitis onset. However, it may facilitate the uveitis onset mediated by both increased temperature and PM2.5 exposure if the per capita GDP is above national level.

The pro-inflammatory effect of triglyceride on human CD4+ T cells and experimental autoimmune uveitis.

Aberrant lipid metabolism plays a role in inflammation and progression of autoimmune diseases but the definite mechanism remains unclear. In this study we investigate lipidomic profiles in Behçet's disease (BD) and the role of triglyceride (TAG) in the pathogenesis of autoimmune uveitis. Lipidomics revealed a distinct lipid metabolite profile including increased TAG metabolites in plasma of active BD patients. TAG could stimulate the proliferation, IL-17 and IFN-γ expression by CD4+ T cells and Th1, Th17 cell differentiation in vitro, but did not influence neutrophils. A922500 inhibited the TAG generation, ameliorated the EAU severity, decreased Th17 frequency and IL-17 expression by CD4+ T cells in vivo. The proteomocis analysis showed an up-regulation of apoptosis-related protein, Pik3r2, in CD4+ T cells from A922500-treated mice. In conclusion, TAG can stimulate human CD4+ T cells and the inhibition of its generation could significantly ameliorate EAU activity in association with down-regulated Th17 cell response.

Average corticosteroid dose and risk for HBV reactivation and hepatitis flare in patients with resolved hepatitis B infection.

OBJECTIVES: Corticosteroids remain the mainstay of treatment for rheumatic diseases but can cause hepatitis B virus (HBV) reactivation in patients with resolved HBV infection. Risk assessment and stratification are needed to guide the management of these patients before corticosteroid therapy. METHODS: We prospectively enrolled patients with negative hepatitis B surface antigen positive Anti-hepatitis B core status with or without corticosteroid use and determined corticosteroid exposure by calculating cumulative dose and time-weighted average daily dose of prednisone. The primary outcome was the time to a composite of HBV reactivation, hepatitis flare or severe hepatitis. RESULTS: Among 1303 participants, the median of cumulative dose and time-weighted average dose of prednisone used in this cohort was 3000 mg (IQR: 300-6750 mg) and 15 mg/day (IQR: 10-20 mg/day), respectively. In multivariable analyses, cumulative dose showed inverted V-shaped relationship with primary events, which peaked at a cumulative dose of 1506 mg (HR: 3.72; 95% CI, 1.96 to 7.08). Quartiles of time-weighted average dose were independently associated with a monotonic increase in event risk (HR per quartile increase: 2.15; 95% CI, 1.56 to 2.98), reaching an HR of 49.48 (95% CI, 6.24 to 392.48) in the top quartile. The incidence of primary outcome was 16.67 per 100 person-years in the top quartile of time-weighted average dose (Q4>20 mg/day). Other quartiles all had an incidence of primary outcome less than 10 per 100 person-years. CONCLUSION: Patients with time-weighted average prednisone dose greater than 20 mg/day would be classified as the high risk for HBV reactivation or hepatitis flare. Prophylactic Anti-HBV therapy may be needed for these high-risk patients. TRIAL REGISTRATION NUMBER: ChiCTR1900023955.

Risk for uveitis relapse after COVID-19 vaccination.

OBJECTIVES: Several studies suggested that coronavirus disease 2019 (COVID-19) vaccination may lead to uveitis, a vision-threatening condition often associated with a variety of autoimmune or autoinflammatory diseases. This study aims to explore factors that influence the risk of uveitis relapse after COVID-19 vaccination to guide the prevention of disease. METHODS: Uveitis relapse was evidenced by worsening activity of intraocular inflammation (e.g. anterior chamber cells, vitreous haze) as defined by the Standardization of Uveitis Nomenclature Working Group. Time to uveitis relapse since the administration of each dose of COVID-19 vaccine was compared across participants with modifiable variables. RESULTS: The primary analysis included 438 non-COVID-19 participants with 857 doses of COVID-19 vaccine administered in total. The median age was 41 years (interquartile range, 30 to 51), and 57.3% were female. A total of 39 episodes of uveitis relapse events occurred in 34 patients after the receipt of a dose of COVID-19 vaccine within 30 days. The median time to relapse after vaccination was 5 days (interquartile range, 1 to 14). Concomitant use of systemic glucocorticoids at the time of vaccination was independently associated with a decrease in risk of relapse after vaccination (HR, 0.23 [95% CI, 0.07-0.74]; P value = 0.014). There was a trend in attenuating the risk of relapse with increasing prednisone dose from none to less than 20 mg per day and then to 20 mg per day or greater (P value for trend = 0.029). CONCLUSIONS: Concomitant treatment with systemic glucocorticoids for uveitis at the time of COVID-19 vaccination was associated with a dose-dependent lower risk of uveitis relapse after vaccination.

Evaluation of sensitivity and specificity of diagnostic criteria for Behçet's disease in the absence of a gold standard.

OBJECTIVE: The performance of existing diagnostic criteria for Behçet's disease (BD) is usually evaluated by comparison with expert opinions, which may be limited by misclassification and disagreement among experts. We aim to evaluate these criteria in the absence of a gold standard. METHODS: We obtained two datasets involving possible BD and other mimickers from a uveitis registry using case-cohort and nested case-control analyses, respectively. With a Bayesian inference approach, the sensitivity and specificity of International Study Group (ISG) and International Criteria for Behçet's Disease (ICBD) criteria were simultaneously estimated when true BD state was unknown. RESULTS: A total of 2440 and 2224 participants were included in case-cohort and nested case-control analyses, respectively. In case-cohort analysis, with scores of ≥4 for BD diagnosis, ICBD criteria showed higher sensitivity (median 97.6%; 95% credible interval 96.9, 98.2) than ISG criteria (median 90.0%; 95% credible interval 88.8, 91.2) but had lower specificity (median 90.8%; 95% credible interval 89.4, 92.1) than ISG criteria (median 98.8%; 95% credible interval 98.3, 99.3). With scores of ≥5 for diagnosis, ICBD criteria demonstrated higher sensitivity (median 97.5%; 95% credible interval 96.8, 98.1) and specificity (median 99.6%; 95% credible interval 99.3, 99.8) than the sensitivity (median 92.3%; 95% credible interval 91.2, 93.3) and specificity (median 98.8%; 95% credible interval 98.2, 99.2) for ISG criteria. The highest diagnostic consistency was observed between ISG criteria and ICBD criteria with scores of ≥5 for diagnosis (Kappa = 0.999; P < 0.001). Nested case-control analysis showed similar results. CONCLUSION: ICBD criteria showed optimum discriminatory properties in sensitivity and specificity with scores of ≥5 for BD diagnosis in uveitis. The diagnostic threshold of ICBD criteria could be considered adjustable according to medical specialty, disease prevalence and local practice characteristics.

Relationship between self-reported sleep duration during week-/work-days and metabolic syndrome from NHANES 2013 to 2016.

PURPOSE: This research aimed at determining the relationship between self-reported sleep duration during week-/work-days and metabolic syndrome (MetS) from NHANES 2013 to 2016. METHODS: This study analyzed data from 11,181 people aged 16 or older who took part in the NHANES (National Health and Nutrition Examination Surveys) from 2013 to 2016. A standard questionnaire was used to define self-reported sleep duration, and MetS was defined on the basis of the NCEP (National Cholesterol Education Program)/ATP III revised diagnostic criteria. Logistic regression and restricted cubic splines (RCS) models were used to assess the relationship between self-reported sleep duration and MetS. RESULTS: The overall prevalence of MetS in the study cohort was 26.1%, with 24.8% for males and 27.3% for females. After adjusting for potential confounding factors, MetS was significantly associated with self-reported short sleep duration (odds ratio = 1.16, 95% confidence interval = 1.03-1.31, P = 0.013) but not with long sleep duration (P = 0.117). RCS regression revealed that self-reported sleep duration was nonlinearly related to MetS (P for nonlinearity = 0.0026). The risk of MetS decreased with increased sleep duration for durations of less than 7 h/day, while there was no association for longer sleep durations. CONCLUSION: These results suggest that self-reported short sleep duration is a risk factor for MetS, while long sleep duration is not.

Surveillance of Liver Function in Uveitis with or without Chronic HBV Infection.

INTRODUCTION: Immunosuppressive therapy for uveitis may cause liver damage. METHODS: To investigate incidence of liver damage during uveitis treatment, we compared serological Hepatitis B core antibody (HBcAb) status with risk of liver dysfunction in all participants (n = 992), in anterior uveitis (AU) (n = 489), and combined of intermediate, posterior, or panuveitis (IPPU) patients (n = 503). The primary endpoint was incidence of elevated serum alanine aminotransferase level above 2-fold upper limits of normal within 6 months. RESULTS: The incidence rate of primary endpoint for HBcAb-negative and HBcAb-positive patients was 65 and 212 per 1,000 person years, respectively. The absolute rate difference was 147 (95% confidence interval [CI], 80-213) per 1,000 person years. HBcAb positivity was associated with a higher risk for primary endpoint in all participants (adjusted hazard ratio [aHR], 3.53; 95% CI, 1.79-6.99; p value = 2.8 × 10-4) and in IPPU (aHR, 3.80; 95% CI, 1.61-9.01; p value = 0.002). No significant association with primary endpoint was observed for HBcAb positivity in AU (aHR, 3.21; 95% CI, 0.94-10.95; p value = 0.063). AU was mainly treated with topical eye drops (74.0%), whereas IPPU cases received systemic therapy including prednisone (94.0%), cyclosporine (80.9%), or other additionally combined immunomodulatory agents (14.9%). CONCLUSION: Noninfectious uveitis cases with HBcAb positivity have an increased risk of liver damage. This association was predominantly driven by IPPU but was not significant in AU, suggesting that the association is mediated by systemic therapy.

Characterization of Stem Nodes Associated with Carbon Partitioning in Maize in Response to Nitrogen Availability.

Stem node has been found to be a hub for controlling mineral nutrient distribution in gramineous plants. However, the characteristics of stem nodes associated with whole-plant carbon partitioning in maize (Zea mays L.) and their responses to nitrogen (N) availability remains elusive. Maize plants were grown in greenhouse under low to high N supply. Plant growth, sugar accumulation, and sugar transporters in nodes and leaves, as well as the anatomical structure of nodes, were investigated at vegetative phase. When compared to N-sufficient plants, low-N availability stunted growth and resulted in 49-64% less sugars in leaves, which was attributed to low photosynthesis or the accelerated carbon export, as evidenced by more 13C detected further below leaf tips. Invariably higher sugar concentrations were found in the stem nodes, rather than in the leaves across N treatments, indicating a crucial role of nodes in facilitating whole-plant carbon partitioning. More and smaller vascular bundles and phloem were observed in stem nodes of N-deficient plants, while higher sugar levels were found in the bottom nodes than in the upper ones. Low-N availability upregulated the gene expressions of sugar transporters, which putatively function in nodes such as ZmSWEETs and ZmSUTs at the bottom stem, but suppressed them in the upper ones, showing a developmental impact on node function. Further, greater activity of sugar transporters in the bottom nodes was associated with less sugars in leaves. Overall, these results highlighted that stem nodes may play an important role in facilitating long-distance sugar transport in maize.

Nomogram for predicting cancer-specific survival in undifferentiated pleomorphic sarcoma: A Surveillance, Epidemiology, and End Results -based study.

INTRODUCTION: The purpose of this study was to construct and validate a nomogram for predicting cancer-specific survival (CSS) in undifferentiated pleomorphic sarcoma (UPS) patients at 3, 5, and 8 years after the diagnosis. METHODS: Data for UPS patients were extracted from the SEER (Surveillance, Epidemiology, and End Results) database. The patients were randomly divided into a training cohort (70%) and a validation cohort (30%). The backward stepwise Cox regression model was used to select independent prognostic factors. All of the factors were integrated into the nomogram to predict the CSS rates in UPS patients at 3, 5, and 8 years after the diagnosis. The nomogram' s performance was then validated using multiple indicators, including the area under the time-dependent receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, decision-curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification improvement (NRI). RESULTS: This study included 2,009 UPS patients. Ten prognostic factors were identified after analysis of the Cox regression model in the training cohort, which were year of diagnosis, age, race, primary site, histological grade, T, N, M stage, surgery status, and insurance status. The nomogram was then constructed and validated internally and externally. The relatively high C-indexes and AUC values indicated that the nomogram has good discrimination ability. The calibration curves revealed that the nomogram was well calibrated. NRI and IDI values were both improved, indicating that our nomogram was superior to the AJCC (American Joint Committee on Cancer) system. DCA curves demonstrated that the nomogram was clinically useful. CONCLUSIONS: The first nomogram for predicting the prognosis of UPS patients has been constructed and validated. Its usability and performance showed that the nomogram can be applied to clinical practice. However, further external validation is still needed.

Competitive Risk Analysis of Prognosis in Patients With Cecum Cancer: A Population-Based Study.

BACKGROUND: The presence of competing risks means that the results obtained using the classic Cox proportional-hazards model for the factors affecting the prognosis of patients diagnosed with cecum cancer (CC) may be biased. OBJECTIVE: The purpose of this study was to establish a competitive risk model for patients diagnosed with CC to evaluate the relevant factors affecting the prognosis of patients, and to compare the results with the classical COX proportional risk model. METHODS: We extracted data on patients diagnosed with CC registered between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The univariate analysis utilized the cumulative incidence function and Gray's test, while a multivariate analysis was performed using the Fine-Gray, cause-specific (CS), and Cox proportional-hazards models. RESULTS: The 54463 eligible patients diagnosed with CC included 24387 who died: 12087 from CC and 12300 from other causes. The multivariate Fine-Gray analysis indicated that significant factors affecting the prognosis of patients diagnosed with CC include: age, race, AJCC stage, differentiation grade, tumor size, surgery, radiotherapy, chemotherapy and regional lymph nodes metastasis. Due to the presence of competitive risk events, COX model results could not provide accurate estimates of effects and false-negative results occurred. In addition, COX model misestimated the direction of association between regional lymph node metastasis and cumulative risk of death in patients diagnosed with CC. Competitive risk models tend to be more advantageous when analyzing clinical survival data with multiple endpoints. CONCLUSIONS: The present study can help clinicians to make better clinical decisions and provide patients diagnosed with CC with better support.

Relationship Between Body Mass Index and Kidney Stones Based on Dose-Response Analyses Using Restricted Cubic Splines Applied to NHANES 2011-2016 Data.

OBJECTIVE: The objective of the study was to estimate the dose-response relationship between body mass index (BMI) and the self-reported prevalence of kidney stones based on a restricted cubic spline (RCS) method. METHODS: This cross-sectional study analyzed 13,223 adults aged ≥20 years who had participated in the National Health and Nutrition Examination Survey performed during 2011-2016. Kidney stones were identified using a standard questionnaire, and physical examinations were used to determine BMI. Logistic regression was used to assess the relationship between BMI and the prevalence of kidney stones, with the dose-response relationship explored using RCSs. RESULTS: The overall prevalence of kidney stones was 9.7%: 10.6% in males and 8.9% in females. After adjusting for potential confounders, compared with those with a BMI in quartile 1, the odds ratios of kidney stones among those with BMIs in quartiles 2, 3, and 4 were 1.45, 1.60, and 2.00, respectively (95% confidence interval = 1.21-1.75, 1.33-1.92, and 1.67-2.39; all P < .001). Multivariate RCS regression revealed that BMI was related to kidney stones in a nonlinear manner (P for nonlinearity <0.001). There was a significant positive relationship, with the curves being steeper when BMI was <28 kg/m2. CONCLUSION: This analysis of National Health and Nutrition Examination Survey data has demonstrated that BMI is significantly associated with the prevalence of kidney stones.

Association between physical activity and kidney stones based on dose-response analyses using restricted cubic splines.

BACKGROUND: This study aimed to determine whether there is a dose-response relationship between physical activity and the self-reported prevalence of kidney stone, based on a restricted cubic splines (RCS) method. METHODS: This study analyzed 8931 adults aged ≥20 years who had participated in the National Health and Nutrition Examination Survey (NHANES) during 2013-16. Kidney stones and physical activity were defined using a standard questionnaire, and metabolic equivalents (MET) were used to quantify the physical activity level. Logistic regression was used to assess the association between physical activity and the risk of kidney stones, and the dose-response relationship was explored using RCS. RESULTS: Kidney stones were present in 10.3% of the analyzed individuals: 11.5% of males and 9.2% of females. After adjusting for potential confounders, compared with the first quartile (Q1) of MET, the odds ratios (ORs) of kidney stones for those with Q2, Q3 and Q4 of MET were 0.72 [95% confidence interval (CI)=0.59-0.87], 0.77 (95% CI = 0.63-0.93) and 0.63 (95% CI = 0.51-0.78), respectively (all P < 0.01). The RCS regression showed that physical activity was related to kidney stones in a non-linear manner (P for non-linearity = 0.0100). The prevalence of kidney stones decreasing as physical activity increased, reaching a plateau for physical activity at approximately 2480 MET-min week-1 (OR = 0.75, 95% CI = 0.63-0.91). CONCLUSIONS: Physical activity is inversely associated with the prevalence of kidney stones, and the dose-response relationship has a plateau, after which the prevalence of kidney stones does not change with the increase of physical activity.

Inhibition of PI3K/Akt/mTOR signaling pathway alleviates ovarian cancer chemoresistance through reversing epithelial-mesenchymal transition and decreasing cancer stem cell marker expression.

BACKGROUND: Ovarian cancer is the most common malignant tumor of the female reproductive tract. Chemoresistance is a major challenge for current ovarian cancer therapy. However, the mechanism underlying epithelial ovarian cancer (EOC) chemoresistance is not completely uncovered. The phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is an important intracellular pathway in regulating cell cycle, quiescence, and proliferation. The aim of this study is to investigate the role of PI3K/Akt/mTOR signaling pathway and its association with epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) marker expression in EOC chemoresistance. METHODS: The expressions of EMT and CSC markers were detected by immunofluorescence, western blot, and quantitative real-time PCR. BEZ235, a dual PI3K/mTOR inhibitor, was employed to investigate the role of PI3K/Akt/ mTOR signaling in regulating EMT and CSC marker expression. Students' t test and one-way ANOVA with Tukey's post-hoc test were used to compare the data from different groups. RESULTS: We found that EMT and CSC marker expression were significantly enhanced in chemoresistant EOC cells, which was accompanied by the activation of PI3K/Akt/mTOR signaling. Compared with single cisplatin treatment, combined treatment with BEZ235 and cisplatin significantly disrupted the colony formation ability, induced higher ROS level and more apoptosis in chemoresistant EOC cells. Furthermore, the combination approach effectively inhibited PI3K/Akt/mTOR signaling pathway, reversed EMT, and decreased CSC marker expression in chemoresistant EOC cells compared with cisplatin mono-treatment. CONCLUSIONS: Our results first demonstrate that EMT and enhanced CSC marker expression triggered by activated PI3K/Akt/mTOR signaling are involved in the chemoresistance of EOC, and BEZ235 in combination with cisplatin might be a promising treatment option to reverse EOC chemoresistance.

Enhanced Capacitance of TiO2 Nanotubes with a Double-Layer Structure Fabricated in NH4F/H3PO4 Mixed Electrolyte.

TiO2 is an attractive electrode material in fast charging/discharging supercapacitors because of its high specific surface area. However, the low capacitance of TiO2 nanotubes as-anodized in the classical electrolyte restricts their further application in supercapacitors. Here, we study the performances of larger-diameter nanotubes with a double-layer structure fabricated in an NH4F/phosphoric acid (H3PO4) mixed electrolyte. Results show that the double-layer structure increased the specific surface area of nanotubes owing to the cavities between the double layers and the porous structure on walls. After soaking in H3PO4 aqueous solution for 40 min, the nanotubes anodized in the mixed electrolyte containing 6 wt % H3PO4 show a specific capacitance of 13.89 mF cm-2, ∼3.11 times that of the pristine nanotubes in the classical electrolyte. The specific surface area of the soaked nanotubes is up to 113.2 m2 g-1, which is ∼2.94 times that of the pristine nanotubes. The values of specific surface area of the anodized nanotubes and the soaked nanotubes fabricated in the mixed electrolyte containing 6 wt % H3PO4 are roughly equal. It demonstrated that the specific surface area increased mainly due to the double-layer structure. The double-layer structure reveals a new strategy to enhance the specific capacitance of TiO2 nanotubes.

Nomograms for predicting the survival rate for cervical cancer patients who undergo radiation therapy: a SEER analysis.

Aim: To integrate multiple independent risk factors to establish prognostic nomograms for better predicting overall survival and disease-specific survival in patients with cervical cancer receiving radiation therapy. Materials & methods: Cox analysis used to construct nomograms. The C-index, time-dependent receiver operating characteristic and calibration plots were used to evaluate the performance. The discrimination abilities were compared using the decision curve analysis, net reclassification improvement and integrated discrimination improvement. Results: After randomization, 2869 and 1230 cervical cancer patients were included in the training and validation sets, respectively. Nomograms that incorporated all of the significant independent factors for predicting the 3- and 5-year overall survival and disease-specific survival in the training cohort were established. Conclusion: Compared with the International Federation of Gynecology and Obstetrics staging system, the proposed nomograms exhibit superior prognostic discrimination and survival prediction.

Development and validation of a nomogram containing the prognostic determinants of chondrosarcoma based on the Surveillance, Epidemiology, and End Results database.

BACKGROUND: We aimed to develop and validate a reliable nomogram for predicting the disease-specific survival (DSS) of chondrosarcoma patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2004 to 2015 to identify cases of histologically confirmed chondrosarcoma. Multivariate Cox regression analysis was performed to identify independent prognostic factors and construct a nomogram for predicting the 3- and 5-year DSS rates. Predictive values were compared between the new model and the American Joint Committee on Cancer (AJCC) staging system using concordance indexes (C-indexes), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). RESULTS: Multivariate Cox regression identified 1180 patients, who were used to establish a nomogram based on a new model containing the predictive variables of age, socioeconomic status, tumor size, surgery status, chemotherapy status, and AJCC staging. In the nomogram, age at diagnosis is the factor with the highest risk, followed by AJCC stage IV and tumor size > 100 mm. Both the C-index and the calibration plots demonstrated the good performance of the nomogram. Moreover, both NRI and IDI were improved compared to the AJCC staging system, and also DCA demonstrated that the nomogram is clinically useful. CONCLUSION: We have developed a reliable nomogram for determining the prognosis and treatment outcomes of chondrosarcoma patients that is superior to the traditional AJCC staging system.