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Obesity is an established risk factor for many diseases including intestinal cancer. One of the responsible mechanisms is the chronic inflammation driven by obesity. However, it remains to be defined whether diet-induced obesity exacerbates the intestinal inflammatory status by cytokines produced in adipose tissue or the high fat diet first alters the gut microbiota and then drives intestinal inflammation. To address this question, we fed C57BL/6 mice with a high fat diet (HF, 60%) and sacrificed them sequentially after 8, 12, and 16 weeks, and then compositions of gut microbiota and expressions of antimicrobial peptides were determined. The compositions of gut microbiota were altered at 8 wk HF feeding, followed with reduced Paneth antimicrobial peptides lysozyme and Reg IIIγ after 12 and 16 wk HF feeding (p < 0.05), whereas elevations of circulating inflammatory cytokines IFNγ and TNF-α were observed until feeding a HF diet for 16 weeks (p < 0.05). These results indicated that high fat diet may stimulate intestinal inflammation via altering gut microbiota, and it occurs prior to the potential influence by circulating inflammatory cytokines. These findings emphasized the importance of microbiota, in addition to adipose tissue per se, in driving intestinal inflammation, which may thereafter promote intestinal tumorigenesis.

As a crucial component in task-oriented dialog systems, the Natural Language Generation (NLG) module converts a dialog act represented in a semantic form into a response in natural language. The success of traditional template-based or statistical models typically relies on heavily annotated data, which is infeasible for new domains. Therefore, it is pivotal for an NLG system to generalize well with limited labelled data in real applications.To this end, we present FEWSHOTWOZ, the first NLG benchmark to simulate the few-shot learning setting in task-oriented dialog systems. Further, we develop the SC-GPT 1 model. It is pre-trained on a large set of annotated NLG corpus to acquire the controllable generation ability, and fine-tuned with only a few domain-specific labels to adapt to new domains. Experiments on FEWSHOTWOZ and the large Multi-Domain-WOZ datasets show that the proposed SC-GPT significantly outperforms existing methods, measured by various automatic metrics and human evaluations.

We present ConvLab, an open-source multidomain end-to-end dialog system platform, that enables researchers to quickly set up experiments with reusable components and compare a large set of different approaches, ranging from conventional pipeline systems to endto-end neural models, in common environments. ConvLab offers a set of fully annotated datasets and associated pre-trained reference models. As a showcase, we extend the MultiWOZ dataset with user dialog act annotations to train all component models and demonstrate how ConvLab makes it easy and effortless to conduct complicated experiments in multi-domain end-to-end dialog settings.

Autophagy is a major intracellular degradative process by which cytoplasmic materials are sequestered in double-membraned vesicles and degraded upon fusion with lysosomes. Under normal circumstances, basal autophagy is necessary to maintain cellular homeostasis by scavenging dysfunctional or damaged organelles or proteins. In addition to its vital homeostatic role, this degradation pathway has been implicated in many different cellular processes such as cell apoptosis, inflammation, pathogen clearance, and antigen presentation and thereby has been linked to a variety of human disorders, including metabolic conditions, neurodegenerative diseases, cancers, and infectious diseases. The skin, the largest organ of the body, serves as the first line of defense against many different environmental insults; however, only a few studies have examined the effect of autophagy on the pathogenesis of skin diseases. This review provides an overview of the mechanisms of autophagy and highlights recent findings relevant to the role of autophagy in skin diseases and strategies for therapeutic modulation.

AimsGenistein, an isoflavone derivative found in soy, is known as a promising treatment for rheumatoid arthritis (RA). However, the detailed molecular mechanism of genistein in suppression of proinflammatory cytokine production remains ambiguous. The aim of this work was to evaluate the signal pathway by which genistein modulates inflammatory cytokine expression.Materials and methodsMH7A cells were stimulated with tumor necrosis factor (TNF)-α and incubated with genistein, and interleukin (IL)-1β, IL-6, and IL-8 production was measured by enzyme-linked immunosorbent assay. Nuclear translocation of nuclear factor (NF)-κB was measured by a confocal fluorescence microscopy. The intracellular accumulation of reactive oxygen species (ROS) was monitored using the fluorescent probe 5-6-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate. Signal-transduction protein expression was measured by Western blot.ResultsGenistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-α-induced NF-κB translocation as well as phosphorylation of IκB kinase-α/β and IκBα, and also suppressed TNF-α-induced AMPK inhibition. The production of IL-1β, IL-6, and IL-8 induced by TNF-α was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might inhibit IL-1β, IL-6, and IL-8 production induced by TNF-α. In addition, we also found that pretreatment with the adenosine monophosphate-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside obviously inhibited TNF-α-induced proinflammatory cytokine production. These observations suggest that the inhibitory effect of genistein on TNF-α-induced proinflammatory cytokine production is dependent on AMPK activation.ConclusionThese findings indicate that genistein suppressed TNF-α-induced inflammation by inhibiting the ROS/Akt/NF-κB pathway and promoting AMPK activation in MH7A cells.

At present, rheumatoid arthritis (RA) is considered a type of autoimmune disease. Its pathology is not certain, and effective drugs with less toxicity have not been established. The establishment and application of animal models are effective methods for RA research, especially using animal models similar to humans. Arthritis is more heterogeneous, and this is an important starting point when discussing animal models for arthritis. Animal models are instrumental in understanding the etiology and pathogenetic mechanisms of RA. Appropriate animal models should be selected according to experiments because they have different traits. Various methods have been applied to induce arthritis in animal experimental models, which have provided important insights into the etiopathogenetic mechanisms of human RA. This review was written to give a broad introduction of the current stage of RA model and hope to offer beneficial help for RA-related research.

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