Butyrate ameliorated ferroptosis in ulcerative colitis through modulating Nrf2/GPX4 signal pathway and improving intestinal barrier.

Oxidative stress and intestinal inflammation are main pathological features of ulcerative colitis (UC). Ferroptosis, characterized by iron accumulation and lipid peroxidation, is closely related to the pathologic process of UC. 16S rRNA sequencing for intestinal microbiota analysis and gas chromatography-mass spectrometry (GC-MS) for short-chain fatty acid (SCFA) contents clearly demonstrated lower amounts of butyrate-producing bacteria and butyrate in colitis mice. However, the precise mechanisms of sodium butyrate (NaB) in treating UC remain largely unclear. We found that ferroptosis occurred in colitis models, as evidenced by the inflammatory response, intracellular iron level, mitochondria ultrastructural observations and associated protein expression. NaB inhibited ferroptosis in colitis, significantly rescued weight loss and colon shortening in mice and reduced inflammatory lesions and mitochondrial damage. Furthermore, NaB improved intestinal barrier integrity and markedly suppressed the expression of pro-ferroptosis proteins. Conversely, the protein expression of anti-ferroptosis markers including nuclear factor erythroid-related Factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4), was significantly upregulated with NaB treatment. Moreover, the knockdown of Nrf2 reversed the anti-colitis effect of NaB. Taken together, NaB exhibited a protective effect by ameliorating ferroptosis in experimental colitis through Nrf2/GPX4 signaling and improving intestinal barrier integrity, which provides a novel mechanism for NaB prevention of UC.

Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Machine-Learning-Enabled Ligand Screening for Cs/Sr Crystallizing Separation.

The reprocessing of spent nuclear fuel is critical for the sustainability of the nuclear energy industry. However, several key separation processes present challenges in this regard, calling for continuous research into next-generation separation materials. Herein, we propose a high-throughput screening framework to improve efficiency in identifying potential ligands that selectively coordinate metal cations of interest in liquid wastes that considers multiple key chemical characteristics, including aqueous solubility, pKa, and coordination bond length. Machine-learning models were designed for the fast and accurate prediction of these characteristics by using graph convolution and transfer-learning techniques. Suitable ligands for Cs/Sr crystallizing separation were identified through the "computational funnel", and several top-ranking, nontoxic, low-cost ligands were selected for experimental verification.

Machine-Learning-Guided Identification of Coordination Polymer Ligands for Crystallizing Separation of Cs/Sr.

Separation of Cs/Sr is one of many coordination-chemistry-centered processes in the grand scheme of spent nuclear fuel reprocessing, a critical link for a sustainable nuclear energy industry. To deploy a crystallizing Cs/Sr separation technology, we planned to systematically screen and identify candidate ligands that can efficiently and selectively bind to Sr2+ and form coordination polymers. Therefore, we mined the Cambridge Structural Database for characteristic structural information and developed a machine-learning-guided methodology for ligand evaluation. The optimized machine-learning model, correlating the molecular structures of the ligands with the predicted coordinative properties, generated a ranking list of potential compounds for Cs/Sr selective crystallization. The Sr2+ sequestration capability and selectivity over Cs+ of the promising ligands identified (squaric acid and chloranilic acid) were subsequently confirmed experimentally, with commendable performances, corroborating the artificial-intelligence-guided strategy.

Early Fault Diagnosis Method for Batch Process Based on Local Time Window Standardization and Trend Analysis.

The products of a batch process have high economic value. Meanwhile, a batch process involves complex chemicals and equipment. The variability of its operation leads to a high failure rate. Therefore, early fault diagnosis of batch processes is of great significance. Usually, the available information of the sensor data in batch processing is obscured by its noise. The multistage variation of data results in poor diagnostic performance. This paper constructed a standardized method to enlarge fault information as well as a batch fault diagnosis method based on trend analysis. First, an adaptive standardization based on the time window was created; second, utilizing quadratic fitting, we extracted a data trend under the window; third, a new trend recognition method based on the Euclidean distance calculation principle was composed. The method was verified in penicillin fermentation. We constructed two test datasets: one based on an existing batch, and one based on an unknown batch. The average diagnostic rate of each group was 100% and 87.5%; the mean diagnosis time was the same; 0.2083 h. Compared with traditional fault diagnosis methods, this algorithm has better fault diagnosis ability and feature extraction ability.

Improved Random Forest Algorithm Based on Decision Paths for Fault Diagnosis of Chemical Process with Incomplete Data.

Fault detection and diagnosis (FDD) has received considerable attention with the advent of big data. Many data-driven FDD procedures have been proposed, but most of them may not be accurate when data missing occurs. Therefore, this paper proposes an improved random forest (RF) based on decision paths, named DPRF, utilizing correction coefficients to compensate for the influence of incomplete data. In this DPRF model, intact training samples are firstly used to grow all the decision trees in the RF. Then, for each test sample that possibly contains missing values, the decision paths and the corresponding nodes importance scores are obtained, so that for each tree in the RF, the reliability score for the sample can be inferred. Thus, the prediction results of each decision tree for the sample will be assigned to certain reliability scores. The final prediction result is obtained according to the majority voting law, combining both the predicting results and the corresponding reliability scores. To prove the feasibility and effectiveness of the proposed method, the Tennessee Eastman (TE) process is tested. Compared with other FDD methods, the proposed DPRF model shows better performance on incomplete data.

Comprehensive Machine Learning-Based Model for Predicting Compressive Strength of Ready-Mix Concrete.

Considering that compressive strength (CS) is an important mechanical property parameter in many design codes, in order to ensure structural safety, concrete CS needs to be tested before application. However, conducting CS tests with multiple influencing variables is costly and time-consuming. To address this issue, a machine learning-based modeling framework is put forward in this work to evaluate the concrete CS under complex conditions. The influential factors of this process are systematically categorized into five aspects: man, machine, material, method and environment (4M1E). A genetic algorithm (GA) was applied to identify the most important influential factors for CS modeling, after which, random forest (RF) was adopted as the modeling algorithm to predict the CS from the selected influential factors. The effectiveness of the proposed model was tested on a case study, and the high Pearson correlation coefficient (0.9821) and the low mean absolute percentage error and delta (0.0394 and 0.395, respectively) indicate that the proposed model can deliver accurate and reliable results.

Integrated Diagnostic Framework for Process and Sensor Faults in Chemical Industry.

This study considers the problem of distinguishing between process and sensor faults in nonlinear chemical processes. An integrated fault diagnosis framework is proposed to distinguish chemical process sensor faults from process faults. The key idea of the framework is to embed the cycle temporal algorithm into the dynamic kernel principal component analysis to improve the fault detection speed and accuracy. It is combined with the fault diagnosis method based on the reconstruction-based contribution graph to diagnose the fault variables and then distinguish the two fault types according to their characteristics. Finally, the integrated fault diagnosis framework is applied to the Tennessee Eastman process and acid gas absorption process, and its effectiveness is proved.

DLX6-AS1 is a potential biomarker and therapeutic target in cancer initiation and progression.

Long noncoding RNAs (lncRNAs) are involved in multiple functions such as the regulation of cellular homeostasis. They play prominent roles in the pathogenesis of human cancer, and contribute to every hallmark of cancer. The novel cancer-related lncRNA DLX6 antisense RNA 1 (DLX6-AS1) plays an essential regulatory role in enhancing and initiating carcinogenesis and tumor progression. This progression is due to the aberrant regulation of downstream factors in vitro as well as in vivo. DLX6-AS1 is significantly dysregulated in various cancers. DLX6-AS1 functions in tumor initiation and progression are regulated at the epigenetic, transcription, and posttranscriptional regulation levels. DLX6-AS1 functions as an oncogene, binding to miRNA targeting sites competing endogenous RNAs and causing the upregulation of downstream tumor-related genes and carcinogenesis. The regulation and detailed molecular mechanisms of DLX6-AS1 and its potential role in malignancies are comprehensively described in this paper. DLX6-AS1 has the potential to become a novel biomarker and therapeutic target for cancer.

Correction: Combined mechanistic and genetic programming approach to modeling pilot NBR production: influence of feed compositions on rubber Mooney viscosity.

[This corrects the article DOI: 10.1039/D0RA07257E.].

Fucoidan-based micelles as P-selectin targeted carriers for synergistic treatment of acute kidney injury.

Acute kidney injury (AKI) is a life-threatening disease without effective treatment. The utilization of curcumin (Cur) for the treatment of AKI is still facing challenges due to its poor water-solubility and low bioavailability. Herein, kidney-targeted octenyl succinic anhydride-grafted fucoidan loaded with Cur (OSA-Fucoidan/Cur) was fabricated for synergistic treatment of AKI. It was found that OSA-Fucoidan/Cur micelles had a sustained drug release behavior and excellent physicochemical stability. Cellular uptake studies demonstrated that the specific binding between fucoidan and P-selectin overexpressed on H2O2-stimulated HUVECs contributed to the higher internalization of OSA-Fucoidan/Cur micelles by the cells. In addition, OSA-Fucoidan micelles exhibited an ideal kidney-targeted characteristic in lipopolysaccharide (LPS)-induced AKI mice. In vivo studies showed that the combination of Cur and OSA-Fucoidan endowed the OSA-Fucoidan/Cur micelles with synergistically anti-inflammatory and antioxidant abilities, thereby largely enhancing the therapeutic efficacy of AKI. Therefore, OSA-Fucoidan/Cur micelles may represent a potential kidney-targeted nanomedicine for effective treatment of AKI.

Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe3+ as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer.

Hepatic cancer is a serious disease with high morbidity and mortality. Theranostic agents with effective diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer. Herein, we aimed to develop a novel mesoporous polydopamine (MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging (MRI)-guided cancer chemo-photothermal therapy. Superparamagnetic iron oxide (SPIO)-loaded MPDA NPs (MPDA@SPIO) was firstly prepared, followed by modifying with a targeted molecule of sialic acid (SA) and chelating with Fe3+ (SA-MPDA@SPIO/Fe3+ NPs). After that, doxorubicin (DOX)-loaded SA-MPDA@SPIO/Fe3+ NPs (SA-MPDA@SPIO/DOX/Fe3+) was prepared for tumor theranostics. The prepared SAPEG-MPDA@SPIO/Fe3+ NPs were water-dispersible and biocompatible as evidenced by MTT assay. In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability, with relaxivity of being r1 = 4.29 mM-1s-1 and r2 = 105.53 mM-1s-1, respectively. SAPEG-MPDA@SPIO/Fe3+ NPs could effectively encapsulate the DOX, showing dual pH- and thermal-triggered drug release behavior. In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe3+ NPs could effectively target to the hepatic tumor tissue, which was possibly due to the specific interaction between SA and the overexpressed E-selectin. This behavior also endowed SA-MPDA@SPIO/DOX/Fe3+ NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification. In addition, SAPEG-MPDA@SPIO/DOX/Fe3+ NPs displayed a superior therapeutic effect, which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy. These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe3+ NPs is an effective targeted nanoplatform for tumor theranostics, having potential value in the effective treatment of hepatic cancer.

Combined mechanistic and genetic programming approach to modeling pilot NBR production: influence of feed compositions on rubber Mooney viscosity.

Mooney viscosity is an essential parameter in quality control during the production of nitrile-butadiene rubber (NBR) by emulsion polymerization. A process model that could help understand the influence of feed compositions on the Mooney viscosity of NBR products is of vital importance for its intelligent manufacture. In this work, a process model comprised of a mechanistic model based on emulsion polymerization kinetics and a data-driven model derived from genetic programming (GP) for Mooney viscosity is developed to correlate the feed compositions (including impurities) and process conditions to Mooney viscosity of NBR products. The feed compositions are inputs of the mechanistic model to generate the number-, weight-averaged molecular weights (M n, M w) and branching degree (BRD) of NBR polymers. With these generated data, the GP model is used to output the optimal correlation for the Mooney viscosity of NBR. In a pilot NBR production, Mooney viscosity data of NBR predicted by the process model agree quite well with experimental values. Furthermore, the process model enables the analyses of the univariate and multivariate influence of feed compositions on NBR Mooney viscosity, and the variables include the contents of vinyl acetylene and dimer in 1,3-butadiene, as well as the mass flow rate of the chain transfer agent (CTA) in the process. Based on the results, it is recommended to control the content of vinyl acetylene in the 1,3-butadiene feed below 14 ppm and the content of dimer below 1100 ppm. This developed process model would help stabilize NBR viscosity for a better control of the product quality.

Surgically treated rare intestinal bleeding due to submucosal hematoma in a patient on oral anticoagulant therapy: A case report.

RATIONALE: Bleeding in the gastrointestinal tract is a common complication of oral anticoagulant therapy (AT), and it usually appears as mucosal erosion or ulcer; however, intestinal submucosal hematoma (ISH) is an uncommon cause of hemorrhage. PATIENT CONCERNS: This report presents the case of a 70-year-old woman with acute hematochezia induced by AT. She underwent computed tomography and endoscopy. DIAGNOSES: Colon submucosal hematoma. INTERVENTIONS: Conservative treatment had no effect, and the patient underwent emergency surgery. OUTCOMES: Surgical resection showed hemorrhage and necrosis in the left colon, and the patient recovered 24 hours after surgery and continued AT. LESSONS: The present case indicates that the ISH should be kept in mind as a complication of AT. It can be managed conservatively in some stable patients, but emergency surgery may be needed in some serious situations.

Genome-Wide Analysis of Barrett's Adenocarcinoma. A First Step Towards Identifying Patients at Risk and Developing Therapeutic Paths.

BACKGROUND: Barrett's esophagus metaplasia is the key precursor lesion of esophageal adenocarcinoma. The aim of this study was to find a subset of markers that may allow the identification of patients at risk for esophageal adenocarcinoma, and to determine genes differentially expressed in esophageal squamous cell carcinoma. METHODS: Laser capture microdissection technique was applied to procure cells from defined regions. Genome-wide RNA profiling was performed on esophageal adenocarcinoma (n = 21), Barrett's esophagus (n = 20), esophageal squamous carcinoma (n = 9) and healthy esophageal biopsies (n = 18) using the Affymetrix Human Genome U133plus 2.0 array. Microarray results were validated by quantitative real-time polymerase chain reaction in a second and independent cohort and by immunohistochemistry of two putative markers in a third independent cohort. RESULTS: Through unsupervised hierarchical clustering and principal component analysis, samples were separated into four distinct groups that match perfectly with histology. Many genes down-regulated in esophageal cancers belong to the epidermal differentiation complex or the related GO-group "cornified envelope" of terminally differentiated keratinocytes. Similarly, retinol metabolism was strongly down-regulated. Genes showing strong overexpression in esophageal carcinomas belong to the GO groups extracellular region /matrix such as MMP1, CTHRC1, and INHBA. According to an analysis of genes strongly up-regulated in both esophageal adenocarcinoma and Barrett's esophagus, REG4 might be of particular interest as an early marker for esophageal adenocarcinoma. CONCLUSIONS: Our study provides high quality data, which could serve for identification of potential biomarkers of Barrett's esophagus at risk of esophageal adenocarcinoma progression.

[Expression and significance of trefoil factor 1 protein and serum pepsinogen in benign and malignant gastric ulcers].

OBJECTIVE: To explore the clinical significance of trefoil factor 1 (TFF1) protein expression and serum pepsinogen (PG) concentration in benign and malignant gastric ulcers. METHODS: The TFF1 protein expression was evaluated by immunohistochemistry in biopsies of gastric mucosa from 18 normal controls, 25 patients with gastric ulcer and 13 patients with ulcerative gastric cancer at our hospital during January to June 2011. The serum concentrations of PGI and PGII were detected by enzyme-linked immunosorbent assay (ELISA) and PG/PGII (PGR) was subsequently calculated. RESULTS: The expression of TFF1 protein increased significantly in ulcerative and peripheral gastric mucosa and peripheral mucosa of gastric cancers versus that in normal controls and the ulcerocancer group (3.04% ± 0.20%, 3.00% ± 0.20%, 3.23% ± 0.26% vs 1.67% ± 0.18%, 0.46% ± 0.18%, all P < 0.01). The elevated expression of TFF1 increased the risk of gastric ulcer (OR: 1.365, 95%CI: 1.065 - 1.749, P = 0.014) while the down-regulation of TFF1 significantly increased the risk of ulcerocancer (OR: 3.067, 95%CI: 1.391 - 6.757, P = 0.005). The serum levels of PGI and PGII in gastric ulcer group were significantly higher than that in normal control and ulcerocancer group ((150 ± 27), (28 ± 9) vs (121 ± 22), (17 ± 7), (79 ± 12), (20 ± 5) µg/L,all P < 0.01). The PGI level and PGR decreased significantly in the ulcerocancer group versus normal control (both P < 0.01). But there was no statistical difference in PGII (P > 0.05). Receiver operating characteristic curve analysis revealed that PGI and PGR were valuable for the diagnosis of malignant gastric cancer with an area under curve of 0.975 and 0.914 respectively. CONCLUSIONS: The expression of TFF1 protein increases in gastric ulcer but decreases in gastric ulcerocancer. The elevated serum levels of PGI and PGII indicate benign ulcer while a marked decline of serum PG I and PGR serves as a risk signal of malignant gastric ulcer. The evaluation of expression profiles of TFF1 protein and PGs is helpful for the differentiation of benign gastric ulcer from malignant ulcerocancer.

In vivo tumor imaging using a novel RNAi-based detection mechanism.

A new concept of tumor imaging is introduced using a siRNA-based probe that is capable of amplifying a specific endogenous fluorescence emission in cancerous tissue. In previous studies, we demonstrated a significant downregulation of Ferrochelatase (FECH) mRNA-expression in colorectal carcinomas leading to the accumulation of protoporphyrin IX (PpIX), a fluorescent metabolite of the heme synthesis. In this article, we report on first in vivo experiments in xenografted nude mice using folate-coupled liposomes or dendritic polyglycerolamine nanoparticles carrying ferrochelatase-siRNA to enhance PpIX-derived fluorescence in the tumor tissue. Tiny tumor foci could be monitored by the emission of PpIX fluorescence in vivo. Due to the omnipresence of the heme synthesis pathway, targeted application of ferrochelatase-siRNA may provide a general means for molecular imaging. FROM THE CLINICAL EDITOR: A new concept of tumor imaging is presented in this paper using a siRNA-based probe detecting protoporphyrin IX (PpIX), a fluorescent metabolite of the heme synthesis previously demonstrated to accumulate in cancer tissue.

Esophageal stents for leaks and perforations.

Stenting of esophageal leaks, ie, anastomotic leaks or perforations, might be a minimally invasive alternative to surgery in most clinical situations. However, it must be emphasized that surgery should be considered if stent treatment in combination with drainage and antibiotics does not improve the clinical condition of the patient. Stent insertion should be performed as soon as possible after diagnosis of the leak.

BCL9-2 promotes early stages of intestinal tumor progression.

BACKGROUND & AIMS: The roles of the 2 BCL9 and 2 Pygopus genes in Wnt to ß-catenin signaling are not clear in vertebrates. We examined their expression and function in normal and tumor intestinal epithelia in mice and humans. METHODS: Specific antibodies were generated to characterize the BCL9 and Pygopus proteins in normal intestine and in colon tumors. Targets of BCL9 and Pygopus in colon cancer cells were analyzed using small interfering RNA analysis. Transgenic mice were created that overexpressed BCL9-2 in intestine; these were crossed with APCMin/+ mice to create BCL9-2;APCMin/+ mice. RESULTS: BCL9 and Pygopus2 were expressed in all normal intestinal and colon cancer cells. BCL9-2 was detectable only in the villi, not in the crypts of normal intestine. BCL9-2 was up-regulated in adenomas and in almost all colon tumors, with a concomitant increase of Pygopus2, whereas levels of BCL9 were similar between normal and cancer cells. Transgenic overexpression of BCL9-2 in the intestine of BCL9-2; APCMin/+ mice increased formation of adenomas that progressed to invasive tumors, resulting in reduced survival time. Using small interfering RNA analysis, we found that BCL9s and Pygopus are not targets of Wnt in colon cancer cells, but Wnt signaling correlated with levels of BCL9-2. BCL9-2 regulated expression of ß-catenin-dependent and -independent target genes that have been associated with early stages of intestinal tumorigenesis. CONCLUSIONS: BCL9-2 promotes early phases of intestinal tumor progression in humans and in transgenic mice. BCL9-2 increases the expression of a subset of canonical Wnt target genes but also regulates genes that are required for early stages of tumor progression.

Management of esophageal anastomotic leaks, perforations, and fistulae with self-expanding plastic stents.

OBJECTIVE: Esophageal anastomotic leaks, perforations, and fistulae are associated with considerable morbidity and mortality. The aim of the present study was to assess the efficacy of self-expanding plastic stents in the treatment of esophageal leaks. METHODS: From 2001 to 2009, 41 patients with postoperative anastomotic leaks (n = 30), esophageal perforations (n = 6), or fistulae (n = 5) were treated by endoscopic insertion of self-expanding plastic stents. The clinical outcome of the patients was analyzed, including leak healing, morbidity, and mortality. RESULTS: Self-expanding plastic stents were successfully inserted in all 41 patients without procedure-related complications. Non-ventilated patients received oral feeding an average of 3.9 days after stent placement. Complete leak healing was obtained in 27 of 30 patients (90%) with anastomotic leaks and 5 patients (83%) with perforation. Sealing of fistulae by the stents was achieved in all 5 patients, and closure of the fistula was observed in 2 patients (40%). The mean healing time was 30 days for anastomotic leaks, 15 days for esophageal perforations, and 16 days for fistulae. Stent migration occurred in 14 cases, but endoscopic reintervention and new stent placement were successful in all cases. In-hospital mortality after treatment of esophageal leaks with stents was 10%. CONCLUSIONS: In combination with effective interventional or surgical drainage, stenting is a viable option for the treatment of esophageal anastomotic leaks and perforations, but the success in tracheoesophageal fistula is limited.