Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate diarrhea-predominant IBS patients (D-IBS) that display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose / mannitol method. All subjects ingested 5 g laclulose and 2 g mannitol in 100 ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue (MVAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients have increased intestinal membrane permeability as measured by the lactulose / mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8±5.4) compared to IBS patients with normal membrane permeability and sensitivity (51.6±12.7) and controls (6.1 ± 5.6) (p<0.001). A subset of D-IBS patients have increased intestinal membrane permeability that is associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.
How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here we report that extracellular vesicles (EVs) with TGF-β1-dependent immunosuppressive activity are produced by intestinal epithelial cells (IECs) under physiological conditions. Transfer of these EVs into inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium salt decreases IBD severity by inducing regulatory T cells and immunosuppressive dendritic cells. In contrast, decreased endogenous EV production promotes IBD development. IECs produce EVs with increased levels of TGF-β1 upon IBD development in an ERK-dependent manner. Furthermore, these EVs tend to localize in the intestinal tract associated with epithelial cell adhesion molecule (EpCAM). Knockdown of EpCAM in vivo increases the severity of murine IBD, and the protective effect of EVs from IECs with decreased EpCAM on murine IBD is blunted. Therefore, our study indicates that EVs from IECs participate in maintaining the intestinal tract immune balance.
Colorectal cancer (CRC) is one of the most frequent malignant neoplasms worldwide. Up to now, no biomarker has been used to predict the prognosis and surveillance of patients with CRC. Recently, the association between osteopontin (OPN) overexpression and the prognosis of CRC was investigated widely, but the results were inconsistent. Therefore, the aim of present meta-analysis was to assess the prognostic effect of osteopontin in patients with CRC. PubMed, EMBASE, Web of Science, Scopus and Chinese Medical Database were systematically searched. A total of 15 studies containing 1698 patients were included in our meta-analysis. The pooled data of studies showed that high OPN expression was significantly associated with high tumor grades (OR = 2.24, 95% CI 1.55–3.23), lymph node metastasis (OR = 2.36, 95% CI 1.71–3.26) and tumor distant metastasis (OR = 2.38, 95% CI 1.01–5.60). Moreover, high OPN expression was significantly associated with the 2-year (HR 1.97, 95% CI 1.30–3.00), 3-year (HR 1.82, 95% CI 1.24–2.68), 5 year (HR 1.53, 95% CI 1.28–1.82) survival rates and overall survival (OS, HR 1.70, 95% CI 1.12–2.60), respectively. These results indicated that OPN could serve as a prognostic biomarker and as a potential therapeutic target for CRC.
Background: Well over 700,000 United States military personnel participated in the Persian Gulf War in which they developed chronic health disorders of undetermined etiology. Up to 25% of Veterans had persistent and chronic gastrointestinal (GI) symptoms, which they suspected were related to their military service in the Gulf. Aim: The overall aim of the current study was to evaluate intestinal permeability in previously deployed Gulf War Veterans who developed chronic GI symptoms during their tour in the Persian Gulf. Methods: To accomplish this, we evaluated intestinal permeability (IP) using the urinary lactulose/mannitol test. Measurements of intestinal permeability were then correlated with mean ratings of daily abdominal pain, frequency of bowel movements, and consistency of bowel movements on the Bristol Stool Scale in all Veterans. Results: A total of 73 veterans had documented chronic GI symptoms (diarrhea, abdominal pain) and were included in the study. A total of 29/73 (39%) of veterans has increased IP and had a higher average daily stool frequency (P<0.05); increased liquid stools as indicated by a higher Bristol Stool Scale (P<0.01); and a higher mean M-VAS abdominal pain rating (P<0.01). Pearson correlation coefficients revealed that there was a positive correlation between increased IP and stool frequency, Bristol Stool Scale, and M-VAS abdominal pain rating. Conclusions: Our study demonstrates that deployed Gulf War Veterans with persistent GI symptoms commonly have increased intestinal permeability that potentiates the severity of abdominal pain, diarrhea, and stool consistency. These new findings in our study are important as they may lead to novel diagnostic biomarkers for returning Gulf War Veterans who suffer from chronic functional gastrointestinal disorders. These advances are also important for an increasing number of veterans who are now serving in the Persian Gulf and are at a high risk of developing these chronic pain disorders.
The mass adoption of electric vehicles is hindered by the inadequate extreme fast charging (XFC) performance (i.e., less than 15 min charging time to reach 80% state of charge) of commercial high-specific-energy (i.e., >200 Wh/kg) lithium-ion batteries (LIBs). Here, to enable the XFC of commercial LIBs, we propose the regulation of the battery’s self-generated heat via active thermal switching. We demonstrate that retaining the heat during XFC with the switch OFF boosts the cell’s kinetics while dissipating the heat after XFC with the switch ON reduces detrimental reactions in the battery. Without modifying cell materials or structures, the proposed XFC approach enables reliable battery operation by applying <15 min of charge and 1 h of discharge. These results are almost identical regarding operativity for the same battery type tested applying a 1 h of charge and 1 h of discharge, thus, meeting the XFC targets set by the United States Department of Energy. Finally, we also demonstrate the feasibility of integrating the XFC approach in a commercial battery thermal management system.
Dispersion drying is an essential step in an enormous number of research and industry fields, including self-assembly, membrane fabrication, printing, battery electrode fabrication, painting, and large-scale solar cell fabrication. The drying process of a dispersion directly influences the structure and properties of the resulting dried film. Thus, it is important to investigate the underlying physics of dispersion drying and the effects of different drying parameters. This article reviews modeling studies of coating drying processes, along with corresponding experimental observations. We have divided drying processes into two conceptual stages. In the first drying stage, liquid evaporation, particle sedimentation and Brownian motion compete and affect the particle distribution during drying and thus in the final film structure. We have included a comprehensive discussion of the influences of drying parameters, such as evaporation rate, particle sizes and temperature, on the above competition and the resulting film structure. A drying regime map describing where different drying phenomena dominate was formulated based on the literature. We also extended our discussion to the practical applications of battery slurry drying an essential step in conventional battery electrode manufacturing. In the second drying stage, the physics of porous drying and crack formation are reviewed. This review aims to provide a comprehensive understanding of dispersion drying mechanisms and to provide guidance in the design of film products with favorable structures and properties for targeted practical applications.
Our findings show that there is widespread somatic hypersensitivity in veterans with GWI/GI symptoms that is positively correlated with abdominal pain ratings. In addition, veterans with somatic hypersensitivity that overlap have the greatest number of extraintestinal symptoms. These findings may have a translational benefit: strategies for developing more effective therapeutic agents that can reduce and/or prevent somatic and GI symptoms in veterans deployed to future military conflicts.
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