The present study was performed to investigate the preventative effect of Lactobacillus plantarum on diarrhea in relation to intestinal barrier function in young piglets challenged with ...enterotoxigenic Escherichia coli (ETEC) K88. Seventy-two male piglets (4 d old) were assigned to 2 diets (antibiotic-free basal diet with or without L. plantarum, 5 × 10(10) cfu/kg diet) and subsequently challenged or not with ETEC K88 (1 × 10(8) cfu per pig) on d 15 in a 2 × 2 factorial arrangement of treatments. Feed intake and BW were measured on d 15 and 18 (3 d after challenge) for determination of growth performance. On d 18, 1 piglet from each pen was slaughtered to evaluate small intestinal morphology and expression of tight junction proteins at the mRNA and protein levels while another piglet was used for the intestinal permeability test. Before and after ETEC K88 challenge, piglets fed L. plantarum had greater BW, ADG, and ADFI (P < 0.05) and marginally greater G:F (P < 0.10) compared to piglets fed the unsupplemented diet. After ETEC K88 challenge, the challenged piglets did not show an impaired growth performance but had greater incidence of diarrhea compared to the nonchallenged piglets. There was an interaction between dietary L. plantarum and ETEC K88 challenge (P < 0.05) as L. plantarum prevented the ETEC K88-induced diarrhea. Piglets challenged with ETEC K88 also had greater urinary lactulose:mannitol and plasma concentration of endotoxin, shorter villi, deeper crypt depth, and reduced villous height:crypt depth in the duodenum and jejunum and decreased zonula occludens-1 mRNA and occludin mRNA and protein expression in the jejunum (P < 0.05). These deleterious effects caused by ETEC K88 were inhibited by feeding L. plantarum (P < 0.05). There were no effects of either treatment on the morphology and expression of tight junction proteins in ileum. In conclusion, L. plantarum, given to piglets in early life, improved performance and effectively prevented the diarrhea in young piglets induced by ETEC K88 challenge by improving function of the intestinal barrier by protecting intestinal morphology and intestinal permeability and the expression of genes for tight junction proteins (zonula occludens-1 and occludin).
We demonstrate a long-term stable, all-fiber, erbium-doped femtosecond laser mode-locked by a black phosphorus saturable absorber. The saturable absorber, fabricated by scalable and highly ...controllable inkjet printing technology, exhibits strong nonlinear optical response and is stable for long-term operation against intense irradiation, overcoming a key drawback of this material. The oscillator delivers self-starting, 102 fs stable pulses centered at 1555 nm with 40 nm spectral bandwidth. This represents the shortest pulse duration achieved from black phosphorus in a fiber laser to date. Our results demonstrate the great potential for black phosphorus as an excellent candidate for long-term stable ultrashort pulse generation.
We demonstrate a ytterbium (Yb) and an erbium (Er)-doped fiber laser Q-switched by a solution processed, optically uniform, few-layer tungsten disulfide saturable absorber (WS2-SA). Nonlinear optical ...absorption of the WS2-SA in the sub-bandgap region, attributed to the edge-induced states, is characterized by 3.1% and 4.9% modulation depths with 1.38 and 3.83 MW/cm(2) saturation intensities at 1030 and 1558 nm, respectively. By integrating the optically uniform WS2-SA in the Yb- and Er-doped laser cavities, we obtain self-starting Q-switched pulses with microsecond duration and kilohertz repetition rates at 1030 and 1558 nm. Our work demonstrates broadband sub-bandgap saturable absorption of a single, solution processed WS2-SA, providing new potential efficacy for WS2 in ultrafast photonic applications.
Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis ...with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.
Predicting drug-protein interactions from heterogeneous biological data sources is a key step for in silico drug discovery. The difficulty of this prediction task lies in the rarity of known ...drug-protein interactions and myriad unknown interactions to be predicted. To meet this challenge, a manifold regularization semi-supervised learning method is presented to tackle this issue by using labeled and unlabeled information which often generates better results than using the labeled data alone. Furthermore, our semi-supervised learning method integrates known drug-protein interaction network information as well as chemical structure and genomic sequence data.
Using the proposed method, we predicted certain drug-protein interactions on the enzyme, ion channel, GPCRs, and nuclear receptor data sets. Some of them are confirmed by the latest publicly available drug targets databases such as KEGG.
We report encouraging results of using our method for drug-protein interaction network reconstruction which may shed light on the molecular interaction inference and new uses of marketed drugs.
Summary
Background
Tong‐Xie‐Yao‐Fang (TXYF) is a Chinese herbal formula for treating chronic diarrhoea accompanied by abdominal pain. The results were inconsistent in previous trials examining its ...effect.
Aim
To study the efficacy of TXYF granules for treating diarrhoea‐predominant irritable bowel syndrome (IBS‐D).
Methods
We performed a double‐blind, placebo‐controlled randomised trial and enrolled 160 participants with IBS‐D. The participants had VAS scores ≥3 cm in IBS‐D global symptoms and ≥2 days in a week with abdominal pain and loose stools (Bristol score 5, 6 or 7). They were randomly assigned to received TXYF or placebo during a treatment period of 4 weeks, and they were followed up for 8 weeks after treatment. The primary outcome was adequate relief of IBS‐D global symptoms for at least 2 of 4 weeks during weeks 1‐4. Secondary outcomes included mean weekly VAS scores of IBS‐D major symptoms, mean weekly stool frequency, mean weekly Bristol score, and adverse events.
Results
155 of 160 patients completed the trial. We found a significantly higher rate of adequate relief of global symptoms in TXFY group during weeks 1 to 4 (57.5% vs 37.5%, χ2 = 5.6391, P = 0.017); logistic regression analysis showed a similar result (OR 2.2, 95% CI 1.2‐4.4, P = 0.016). Most of the secondary outcomes showed superiority of TXYF over placebo in weekly assessment from week 3 to week 7. The adverse event rate was low in both groups (3.8% vs 3.8%, P = 1.000).
Conclusion
During a 4 week trial, TXFY granules were superior to placebo in controlling symptoms of IBS‐D.
Linked ContentThis article is linked to Vitta and Sayuk and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14902 and https://doi.org/10.1111/apt.14906.
Background
Glycolysis is a critical pathway in cellular glucose metabolism that provides energy and participates in immune responses. However, whether glycolysis is involved in NOD‐like receptor ...family protein 3 (NLRP3) inflammasome activation and phagocytosis of macrophages in response to Treponema pallidum infection remains unclear.
Objectives
To investigate the role of glycolysis in activating the NLRP3 inflammasome for regulating phagocytosis in macrophages in response to T. pallidum protein Tp47 and its associated mechanisms.
Methods
Interactions between activation of the NLRP3 inflammasome and phagocytosis and the role of glycolysis in Tp47‐treated macrophages were investigated through experiments on peritoneal macrophages and human monocytic cell line‐derived macrophages.
Results
Activation of phagocytosis and NLRP3 inflammasome were observed in Tp47‐treated macrophages. Treatment with NLRP3 inhibitor MCC950 or si‐NLRP3 attenuated Tp47‐induced phagocytosis. Glycolysis and glycolytic capacity were enhanced by Tp47 stimulation in macrophages, and a change in the levels of glycolytic metabolites (phosphoenolpyruvate, citrate and lactate) was induced by Tp47 in macrophages. Inhibition of glycolysis with 2‐deoxy‐D‐glucose, a glycolysis inhibitor, decreased the activation of NLRP3. Expression of M2 isoform of pyruvate kinase (PKM2), an enzyme catalysing a rate‐limiting reaction in the glycolytic pathway, was upregulated in Tp47‐stimulated macrophages. Inhibition of PKM2 with shikonin or si‐PKM2 decreased glycolysis and NLRP3 activation.
Conclusion
Tp47 promotes phagocytosis in macrophages by activating the NLRP3 inflammasome, which is induced by the enhancement of PKM2‐dependent glycolysis.
A midfrequency (2-6 kHz) geoacoustic parameter inversion approach is proposed using a moving source and single receiver. The source motion creates a synthetic horizontal line array (SHLA), and the ...received signals, by source-receiver reciprocity, can be used to estimate the sediment/bottom parameters using matched field inversion (MFI). Using a wideband signal, the arrival times of multipaths are estimated using compressive sensing, from which one can estimate the source-receiver range, water depth, sediment thickness, and sound speed. This information is difficult to get at low frequencies due to the limited bandwidth. MFI is carried out using the frequency-coherent cost function and does not require the data to be precisely synchronized. Sensitivities of inversion of geoacoustic parameters are also studied. Performance using the SHLA is shown to be comparable to that using the conventional horizontal and vertical line array, and is shown to be sensitive to sediment attenuation-one of the difficult parameters to estimate. The proposed scheme uses short range (50-150 m) data, and requires a low-level source that can be carried by an autonomous underwater vehicle (AUV). With the AUV traveling between nodes in a distributed sensors network, the inversion can be conducted over a large area.
This paper investigates electrospinning of a natural biopolymer, gelatin, and the mass concentration-mechanical property relationship of the resulting nanofiber membranes. It has been recognized that ...although gelatin can be easily dissolved in water the gelatin/water solution was unable to electrospin into ultra fine fibers. A different organic solvent, 2,2,2-trifluoroethanol, is proven suitable for gelatin, and the resulting solution with a mass concentration in between 5 and 12.5% can be successfully electrospun into nanofibers of a diameter in a range from 100 to 340 nm. Further lower or higher mass concentration was inapplicable in electrospinning at ambient conditions. We have found in this study that the highest mechanical behavior did not occur to the nanofibrous membrane electrospun from the lowest or the highest mass concentration solution. Instead, the nanofiber mat that had the finest fiber structure and no beads on surface obtained from the 7.5% mass concentration exhibited the largest tensile modulus and ultimate tensile strength, which are respectively 40 and 60% greater than those produced from the remaining mass concentration, i.e. 5, 10, and 12.5%, solutions.
Adipose-resident T cells (ARTs) regulate metabolic and inflammatory responses in obesity, but ART activation signals are poorly understood. Here, we describe class II major histocompatibility complex ...(MHCII) as an important component of high-fat-diet (HFD)-induced obesity. Microarray analysis of primary adipocytes revealed that multiple genes involved in MHCII antigen processing and presentation increased in obese women. In mice, adipocyte MHCII increased within 2 weeks on HFD, paralleling increases in proinflammatory ART markers and decreases in anti-inflammatory ART markers, and preceding adipose tissue macrophage (ATM) accumulation and proinflammatory M1 polarization. Mouse 3T3-L1 and primary adipocytes activated T cells in an antigen-specific, contact-dependent manner, indicating that adipocyte MHCII is functional. HFD-fed MHCII−/− mice developed less adipose inflammation and insulin resistance than did wild-type mice, despite developing similar adiposity. These investigations uncover a mechanism whereby a HFD-induced adipocyte/ART dialog involving MHCII instigates adipose inflammation and, together with ATM MHCII, escalates its progression.
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► Obesity enhances MHCII expression in primary human and mouse adipocytes ► Adipocytes activate CD4+ ARTs via MHCII and leptin to induce adipose inflammation ► Macrophage changes in adipose follow adipocyte and T cell interactions during HFD ► Adaptive immune mechanisms are essential to obesity-induced adipose inflammation
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