A nomogram for predicting the risk of Clostridioides difficile infection in children with ulcerative colitis: development and validation

IntroductionThis study aimed to develop a dynamic nomogram model to predict the risk of Clostridioides difficile infection (CDI) in children with ulcerative colitis (UC).MethodsThis was a retrospective study that clinical data from pediatric diagnosis and treatment with UC at Zhengzhou University Children's Hospital between January 2018 and December 2024 were retrospectively reviewed. Patients were classified into CDI (n = 35) and non-CDI (n = 86) groups based on the presence or absence of CDI. Predictor variables were selected using least absolute shrinkage and selection operator (LASSO) regression and subsequently entered into a multivariate logistic regression model. Nomograms were then constructed based on the final logistic regression analysis. The model's performance and clinical utility were assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Internal validation was performed using 1,000 bootstrap resamples.ResultsA total of 121 children were included in the study. Based on LASSO and multivariate logistic regression analysis of 24 candidate variables, five independent risk factors for CDI in children with UC were identified: Pediatric Ulcerative Colitis Activity Index (PUCAI), erythrocyte sedimentation rate (ESR), vitamin D (Vit D), fecal calprotectin (FC), and antibiotic use exceeding seven days (all p < 0.05). The nomograms constructed with the above variables demonstrated excellent discriminative ability (C-index = 0.964, 95% CI: 0.932–0.997). The Hosmer-Lemeshow test (χ2 = 12.529, p = 0.129) and bootstrap validation revealed good concordance between the predicted probabilities and actual outcomes. Decision curve analysis (DCA) indicated significant net clinical benefit, and the model maintained robust consistency across relevant clinical subgroups.ConclusionsPUCAI, ESR, Vit D, FC, and use of antibiotic use exceeding seven days were the five independent risk factors for CDI in children with UC. The resulting nomogram may support clinicians in early diagnosis and timely adjustment of therapeutic strategies

IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming

Isocitrate dehydrogenase 1 (IDH1) is the key enzyme that can modulate cellular metabolism, epigenetic modification, and redox homeostasis. Gain-of-function mutations and decreased expression of IDH1 have been demonstrated to be associated with pathogenesis of various myeloid malignancies characterized by ineffective erythropoiesis, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the function and mechanism of IDH1 in human erythropoiesis still remains unclear. Here, utilizing the human erythropoiesis system, we present an evidence of IDH1-mediated chromatin state reprogramming besides its well-characterized metabolism effects. We found that knockdown IDH1 induced chromatin reorganization and subsequently led to abnormalities biological events in erythroid precursors, which could not be rescued by addition of reactive oxygen species (ROS) scavengers or supplementation of α-ketoglutarate (α-KG).We further revealed that knockdown IDH1 induces genome-wide changes in distribution and intensity of multiple histone marks, among which H3K79me3 was identified as a critical factor in chromatin state reprogramming. Integrated analysis of ChIP-seq, ATAC-seq, and RNA-seq recognized that SIRT1 was the key gene affected by IDH1 deficiency. Thus, our current work provided novel insights for further clarifying fundamental biological function of IDH1 which has substantial implications for an in-depth understanding of pathogenesis of diseases with IDH1 dysfunction and accordingly development of therapeutic strategies

Stage-specific dual function: EZH2 regulates human erythropoiesis by eliciting histone and non-histone methylation

Enhancer of zeste homolog 2 (EZH2) is the lysine methyltransferase of polycomb repressive complex 2 (PRC2) that catalyzes H3K27 tri-methylation. Aberrant expression and loss-of-function mutations of EZH2 have been demonstrated to be tightly associated with the pathogenesis of various myeloid malignancies characterized by ineffective erythropoiesis, such as myelodysplastic syndrome (MDS). However, the function and mechanism of EZH2 in human erythropoiesis still remains largely unknown. Here, we demonstrated that EZH2 regulates human erythropoiesis in a stage-specific, dual-function manner by catalyzing histone and non-histone methylation. During the early erythropoiesis, EZH2 deficiency caused cell cycle arrest in the G1 phase, which impaired cell growth and differentiation. Chromatin immunoprecipitation sequencing and RNA sequencing discovered that EZH2 knockdown caused a reduction of H3K27me3 and upregulation of cell cycle proteindependent kinase inhibitors. In contrast, EZH2 deficiency led to the generation of abnormal nuclear cells and impaired enucleation during the terminal erythropoiesis. Interestingly, EZH2 deficiency downregulated the methylation of HSP70 by directly interacting with HSP70. RNA-sequencing analysis revealed that the expression of AURKB was significantly downregulated in response to EZH2 deficiency. Furthermore, treatment with an AURKB inhibitor and small hairpin RNAmediated AURKB knockdown also led to nuclear malformation and decreased enucleation efficiency. These findings strongly suggest that EZH2 regulates terminal erythropoiesis through a HSP70 methylation-AURKB axis. Our findings have implications for improved understanding of ineffective erythropoiesis with EZH2 dysfunction

Hot Water Extraction of Antioxidants from Tea Leaves—Optimization of Brewing Conditions for Preparing Antioxidant-Rich Tea Drinks

There are billions of tea drinkers around the world. However, the optimized tea-brewing temperature and time conditions for achieving a higher concentration of antioxidants in tea drinks have not been thoroughly studied. Finding out the optimized brewing conditions can benefit tea drinkers significantly. In this work, we have studied ten antioxidants from seven different popular green, Oolong, black, and scented teas using hot water extraction followed by HPLC analysis. The antioxidant yield was evaluated at 25–100 °C with 5 to 720 min of brewing time. Our results show that the extraction efficiency was enhanced by increasing the water temperature and the highest yield of antioxidants was achieved at 100 °C. The antioxidant yield increased with prolonged brewing time. However, the degradation of antioxidants occurred when tea leaves were extracted for 120 to 720 min. Caffeine was found in all seven tea samples. At 100 °C, the caffein concentration in the tea extract ranged from 7.04 to 20.4 mg/g in Rizhao green tea. Longjing green tea contained the highest concentration of antioxidants (88 mg/g) in the 100 °C extract. Epigallocatechin and caffeine were the most abundant compounds found in all tea samples studied, ranging from 4.77 to 26.88 mg/g. The antioxidant yield was enhanced by increasing the extraction time to up to 60–120 min for all ten compounds studied.</jats:p

Hot Water Extraction of Antioxidants from Tea Leaves—Optimization of Brewing Conditions for Preparing Antioxidant-Rich Tea Drinks

There are billions of tea drinkers around the world. However, the optimized tea-brewing temperature and time conditions for achieving a higher concentration of antioxidants in tea drinks have not been thoroughly studied. Finding out the optimized brewing conditions can benefit tea drinkers significantly. In this work, we have studied ten antioxidants from seven different popular green, Oolong, black, and scented teas using hot water extraction followed by HPLC analysis. The antioxidant yield was evaluated at 25–100 °C with 5 to 720 min of brewing time. Our results show that the extraction efficiency was enhanced by increasing the water temperature and the highest yield of antioxidants was achieved at 100 °C. The antioxidant yield increased with prolonged brewing time. However, the degradation of antioxidants occurred when tea leaves were extracted for 120 to 720 min. Caffeine was found in all seven tea samples. At 100 °C, the caffein concentration in the tea extract ranged from 7.04 to 20.4 mg/g in Rizhao green tea. Longjing green tea contained the highest concentration of antioxidants (88 mg/g) in the 100 °C extract. Epigallocatechin and caffeine were the most abundant compounds found in all tea samples studied, ranging from 4.77 to 26.88 mg/g. The antioxidant yield was enhanced by increasing the extraction time to up to 60–120 min for all ten compounds studied

An improved LOS Guidance and Sail-Rudder Cooperative Controller for the Path Tracking of Unmanned Sailboats

Unmanned sailboats are driven only by wind, making them good platforms for the synchronous observation of air-sea interfaces over a large range. Compared with traditional unmanned ships, the unmanned sailboat involves simultaneous sail and rudder control for path tracking in unpredictable marine environments. The system is characterized by strong coupling and nonlinearity, creating challenges for the design of controllers. This paper combines line-of-sight (LOS) guidance with the introduction of a sideslip angle observer and model predictive control. A high-precision path tracking strategy suitable for cooperative sail and rudder control for unmanned sailboats is proposed. First, considering the lateral error easily caused by the large sideslip angle of sailboats, a full-path fixed-time guidance strategy with double fixed-time sideslip angle observers (DFSO) is proposed. Second, different from the previous strategy of decoupling the sail and rudder to control the speed and heading, the proposed cooperative control framework uses Lyapunov-based model predictive control (LMPC). The sailing speed and heading angle are both accounted for in the objective function, and the stability is verified by Lyapunov theory. Finally, the feasibility and superiority of this proposed method are confirmed by numerical simulation experiments involving the path tracking of a four degree of freedom sailboat model integrated with wind and waves in an ocean environment. IEE

Development and Characterization of an Asymmetric MZI Temperature Sensor Using Polymer Waveguides for Extended Temperature Measurement Scopes

To meet diverse industrial needs, temperature sensors with a wide measurement range have become a key element. In this paper, we propose an asymmetric Mach&ndash;Zehnder interferometer (MZI) temperature sensor based on polymer optical waveguides. Experimental results show that the output interference signal exhibits periodic changes with temperature variations. The device exhibits a temperature measurement range of 120 &deg;C and a sensitivity of 0.27 rad/&deg;C. This study provides an effective new approach for developing high-performance, low-cost temperature sensors suitable for an extended temperature measurement range