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Fascinating properties are displayed by high-performance ionogel-based flexible strain sensors, thereby gaining increasing attention in various applications ranging from human motion monitoring to soft robotics. However, the integration of excellent properties such as optical and mechanical properties and satisfactory sensing performance for one ionogel sensor is still a challenge. In particular, fatigue-resistant and self-healing properties are essential to continuous sensing. Herein, we design a flexible ion-conductive sensor based on a multifunctional ionogel with a double network using polyacrylamide, amino-modified agarose, 1,3,5-benzenetricarboxaldehyde and 1-ethyl-3-methylimidazolium chloride. The ionogel exhibits comprehensive properties including high transparency (95%), nonflammability, strong adhesion and good temperature tolerance (about -96 to 260 °C), especially adaptive for extreme conditions. The dynamic imine bonds and abundant hydrogen bonds endow the ionogel with excellent self-healing capability, to realize rapid self-repair within minutes, as well as good mechanical properties and ductility to dissipate input energy and realize high resilience. Notably, unexpected fluorescence has been observed for the ionogel because of the gelation-induced emission phenomenon. Flexible strain sensors prepared directly from ionogels can sensitively monitor and differentiate various human motions, exhibiting a fast response time (38 ms), high sensitivity (gauge factor = 3.13 at 800% strain), good durability (1000 cycles) and excellent stability over a wide temperature range (-30 to 80 °C). Therefore, the prepared ionogel as a high-performance flexible strain sensor in this study shows tremendous potential in wearable devices and soft ionotronics.

α-Glucosidase is the key enzyme on carbohydrate metabolism, and its bioactive inhibitors are supposed to be an effective therapeutic for type 2 diabetes mellitus. During our continuing study for discovering α-glucosidase inhibitors, a fungus GDZZ-G2 which is derived from a medicinal plant Callicarpa kwangtungensis Chun, exhibited significant inhibition on α-glucosidase. The strain was identified as Fusarium incarnatum by morphological and molecular methods. Further bioassay-guided fractionation result in six known secondary metabolites (1-6). All the compounds except 4 were isolated from F. incarnatum for the first time. Among them, an anthraquinonoid (S)-1,3,6-trihydroxy-7-(1-hydroxyethyl)anthracene-9,10-dione (compound 1) exhibited strong inhibitory effect against α-glucosidase (IC

Sucralose is one of the most widely used artificial sweeteners, free of nutrients and calories. Its approval and uses correlate with many of the worldwide epidemiological changes in inflammatory bowel disease (IBD). Multiple animal studies by us and others showed that sucralose exacerbated ileitis in SAMP1/YitFc mice and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. In this study, we further investigated the effect of sucralose on dextran sulfate sodium (DSS)-induced colitis in mice and the associated mechanisms. Male C57BL/6 mice received 1.5 mg ml-1 sucralose in drinking water for 6 weeks. Then, 2.5% DSS was added to drinking water for 7 days to induce ulcerative colitis (UC). The results showed that, compared with the DSS group, administration of sucralose exacerbated the severity of colitis as indicated by the further decrease in body weight, increase in disease activity index (DAI) and the expression of pro-inflammatory cytokines, as well as the activation of the TLR5-MyD88-NF-κB signaling pathway, and the disturbances of intestinal barrier function, along with changes in the intestinal microbiota. Our findings indicate that sucralose may increase the susceptibility to DSS-induced colitis through causing dysbiosis of intestinal microbiota and damage to the intestinal barrier.

Background: This study aimed to compare the Hospital Anxiety and Depression Scale (HADS) and the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in evaluating anxiety and depression in psoriatic arthritis (PsA) patients. Methods: A total of 70 PsA patients were enrolled. Demographic and clinical characteristics were collected after enrollment. HADS-A and SAS were used to evaluate the anxiety of PsA patients, while HADS-D and SDS were used to evaluate the depression of PsA patients. Results: Similar results were observed in detecting the rate of anxiety by HADS-A and SAS (27.1 vs. 21.4%, p = 0.424), and there was no difference in classifying the severity of anxiety by HADS-A and SAS (p = 0.347). The Spearman test also disclosed that HADS-A score was positively associated with SAS score (p <0.001). The rates of depression were similar by HADS-D and SDS (27.1 vs. 40.0%; p = 0.108). However, different results were observed in grading the severity of anxiety by HADS-D and SDS (p = 0.009), and no correlation was observed between HADS-D and SDS scores (p = 0.138). The consumption of time for HADS assessment was shorter than that for SAS/SDS assessment (p < 0.001). In addition, a positive correlation of HADS-A score with patients’ global assessment (PGA) (p = 0.022) and fatigue scores (p = 0.028) was discovered, and HADS-D score was positively associated with PGA score (p = 0.019). SAS or SDS score presented less correlation with clinical features of PsA patients, which illuminated that only SAS score was positively associated with duration of psoriasis (p = 0.030). Conclusion: HADS seems to be a better option for anxiety and depression assessment than SAS/SDS in PsA patients.

Unconjugated bilirubin (UCB) is generally considered toxic but has gained recent prominence for its anti-inflammatory properties. However, the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved.To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis.Acute colitis was induced by 3% (Mice treated with UCB had significantly relieved severity of colitis, including lower DAI, longer colon length, and lower spleen weight (colon length: 4.92 ± 0.09 cmUCB can protect intestinal barrier function, regulate normal intestinal homeostasis, and suppress inflammation

Xanthine oxidase (XO) catalyzes the oxidation of hypoxanthine to xanthine, which is further converted to uric acid. The excessive production or reduced excretion of the purine terminal metabolite may lead to hyperuricemia. In our ongoing search for new xanthine oxidase inhibitors, 14 endophytic fungi were isolated for the first time from a medicinal plant Callicarpa kwangtungensis Chun, and the ethyl acetate extracts of their culture filtrates were screened for XO inhibitory activity. The extract from an endophytic fungus, characterized as Alternaria alternata GDZZ-J6, exhibited the most potent inhibition of XO. Further fractionation of its secondary metabolites led to the isolation of six compounds. Among them, mycotoxin alternariol (AOH), a dibenzo-α-pyrone derivative, had strong inhibitory activity on XO, and the IC

α-Glucosidase plays an important role in catalyzing the hydrolytic cleavage of disaccharides into monosaccharides. In this study, a phytochemical investigation of the potential α-glucosidase inhibitory fraction from the aerial parts of Euonymus fortunei led to the isolation and identification of two new tetracyclic triterpenoids, fortunenones A and B (1–2), together with 11 known triterpenoids (3–13). Fortunenones A and B are rare C32 triterpenoids possessing a 24,24-dimethyl group. The partial isolated compounds were evaluated their effects on α-glucosidase, of which echinochlorin D (5), lupenone (7), wilforlide B (12), and wilforlide A (13) exhibited remarkable inhibitory effects with the half inhibitory concentration ranged from 207.2 × 10−6 M to 388.3 × 10−6 M compared with the positive control, acarbose. An enzyme kinetics analysis by Lineweaver-Burk plots revealed that the inhibition types of the four active compounds were all mixed inhibition. Molecular docking further revealed that hydrophobic interactions and hydrogen bonds play an important role in the inhibition of α-glucosidase activity. Our results demonstrate the potential of E. fortunei extract and its constituents to inhibit α-glucosidase.

This paper presents the optimized back propagation neural network (BPNN) method for fault diagnosis of the variable refrigerant flow air conditioning (VRF) system in the heating mode. A feature variable set optimization approach of diagnosis models is proposed based on data mining method. First, the correlation analysis method is used to eliminate redundant variables. Then, the association rule mining method is used to optimize the feature set (FS) selection. Five FSs (FS1-FS5) are obtained by optimized feature variable selection. FS1 is the original set. FS2 is the set obtained by correlation analysis and FS3-FS5 are the sets obtained by the association rule mining. The fault diagnosis models with different FSs are evaluated using four fault experiments which include outdoor unit heat exchanger air-side fouling, four-way reversing valve fault, refrigerant undercharge and refrigerant overcharge faults. The results show that the correlation analysis method can effectively eliminate redundant variables and the association rule mining method is feasible to optimize the FSs for fault diagnosis. The BPNN-FS5 model shows the best fault diagnosis performance of the VRF system in the heating mode, whose fault diagnosis correct rate has increased from 88.71% to 96.40% and hit rates of four faults are higher than 90%.

A novel heavy metal chelating agent, dithiocarboxylate-functionalized polyaminoamide dendrimer (PAMAM-0G-DTC), was evaluated for the stabilization of heavy metals from municipal solids waste incineration (MSWI) fly ash. PAMAM-0G-DTC achieved overall stabilization performance at a lower dosage (3% w/w) and a wider pH range (2–13) compared to conventional chelating agents such as sodium dimethyl dithiocarbamate (SDD) and dithiocarboxylate-functionalized tetraethylenepentamine (TEPA-DTC). The leaching toxicity of Pb and Cd in the MSWI fly ash by PAMAM-0G-DTC stabilization met the landfill requirements but could not be achieved by SDD and TEPA-DTC even at a 10 wt% concentration. Sequential chemical extraction of fly ash before and after stabilization shows that PAMAM-0G-DTC can be combined with active heavy metals in water-soluble, interchangeable, and carbonate states to form more stable heavy metals in organic and residual states. Mechanistic studies show that multiple PAMAM-0G-DTC molecules can combine with multiple heavy metals to form three-dimensional network-like super-molecular compounds with an infinite extension of space size. This makes the heavy metals more stable and embedded in the network-like super-molecular structure, thus minimizing the potential risk of leaching. Overall, by forming more geochemically stable phases, the treatment of fly ash with PAMAM-0G-DTC has a strong ability to reduce the toxic leaching of heavy metals at a lower dosage and suppress the risk of secondary pollution in a landfill at a wide range of pH values (2–13).

Background The aim of the current study was to investigate the long non-coding RNA (lncRNA) expression profiles in psoriatic arthritis (PSA) patients by RNA sequencing, and to further explore potential biomarkers that were able to predict PSA risk and activity. Methods LncRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMC) of 4 PSA patients and 4 normal controls (NCs) were detected by RNA sequencing, followed by comprehensive bioinformatic analyses. Subsequently, 3 top upregulated and 2 top downregulated lncRNAs were chosen for further validation in 93 PSA patients and 93 NCs by quantitative polymerase chain reaction (qPCR) assay. Results Totally 76 upregulated and 54 downregulated lncRNAs, as well as 231 upregulated and 102 downregulated mRNAs were discovered in PSA patients compared with NCs. Enrichment analyses revealed that they were mostly associated with nucleosome, extracellular exosome and extracellular matrix, and the top enriched pathways were systemic lupus erythematosus (SLE), alcoholism and viral carcinogenesis. qPCR assay showed that lnc-RP11-701H24.7 and lnc-RNU12 were upregulated in PSA patients compared with NCs, and they could predict PSA risk with high area under curves. Besides, lnc-RP11-701H24.7 was positively associated with ESR, SJC, TJC and pain VAS score while lnc-RNU12 was positively correlated with PASI score, CRP and PGA score, implying that both of them were positively correlated with disease activity. Conclusion Our study facilitates comprehensive understanding of lncRNA expression profiles in PSA pathogenesis, and discovers that lnc-RP11-701H24.7 and lnc-RNU12 might be served as novel biomarkers for PSA risk and activity. Electronic supplementary material The online version of this article (10.1186/s12865-019-0297-9) contains supplementary material, which is available to authorized users.

Porcine epidemic diarrhea caused by porcine epidemic diarrhea virus (PEDV) is a highly contagious disease in newborn piglets. The spike (S) protein is the surface glycoprotein of PEDV, which can induce specific neutralization antibodies and is a candidate antigen for vaccination attempts. In our study, the S1 region of PEDV strain CH/JLDH/2016 spike gene was inserted into the Lactococcus lactis expression vector, pNZ8149, resulting in recombinant plasmid pNZ8149-S1, and the immunogenicity of recombinant L. lactis pNZ8149-S1/NZ3900 was evaluated in mice. After immunization, significantly higher levels of anti-PEDV serum IgG antibodies and mucosal sIgA antibodies were detected in mice orally administered with pNZ8149-S1/NZ3900, compared with control groups pNZ8149/NZ3900, NZ3900, and phosphate buffered saline (p 0.01). Lymphocyte proliferation assay results showed that the recombinant L. lactis pNZ8149-S1/NZ3900 significantly stimulated the proliferation of splenic lymphocytes (p 0.01). In addition, the recombinant L. lactis vaccine could induce high levels of IL-4 and IFN-γ in immunized mice (p 0.01). The results of our study suggest that the recombinant L. lactis pNZ8149-S1/NZ3900 can provide a promising vaccine strategy against PEDV infection.

Objective Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are devastating diseases of the gut. At present, all the treatments are mainly targeting symptoms like inflammation. The disease remains regarded as incurable, largely due to lacking of knowledge on its etiology. Our previous studies suggested that impaired inactivation of digestive proteases by deconjugated bilirubin in experimental colitis, thus bacterial β-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD. Methods We first analyzed β-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of β-glucuronidase on experimental colitis was investigated in detail by administration of β-glucuronidase (from E. coli) and fecal material transplantation to mice with 3% DSS in drinking water for 7 days. Results Mice with colitis showed unchanged activity of β-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial β-glucuronidase at 100 U or above alleviated DSS-induced colitis as demonstrated by the less body weight loss, less disease activity score, increased expression of tight junction proteins and decreased gut permeability, decreases in MPO, TNF-α, IL-1β, TLR-4 and MyD88, and increase in IL-10 and IκBα in gut, restored fecal β-glucuronidase and gut microbiota along with decreases in fecal digestive proteases. Transplantation of fecal material from control to colitis mice showed similar effects as treatment with β-glucuronidase. Conclusions Bacterial β-glucuronidase showed strong inhibition on colitis along with the reduction in fecal digestive proteases, which may be a crucial diagnostic and therapeutic target for IBD.

Table S1. Primers used in qPCR validation. (DOCX 15 kb)

Pulse diagnosis is an important part of the theoretical system of Traditional Chinese Medicine. In this paper we propose a new and an efficient framework to recognize pulse signal in nonlinear angle. Firstly the EEMD (ensemble empirical mode decomposition) method is used to filter out baseline drifting noise, and the result is proved to be effective. Then the MFDFA(multi-fractal detrended fluctuation analysis) method is used to get Hurst index, Renyi index and multi-fractal spectrum. Hurst index is related with the long-range correlations, Renyi index is related with the multi-fractal characteristics, and multi-fractal spectrum contains Δa and Δƒ characteristics. Finally, four kinds of pulse signals are recognized by PSO-SVM after extract multi-fractal spectrum feature. Experiment results demonstrate the effectiveness of our proposed method.

Background The aim of this study was to investigate the regulative activity of (5R)-5-hydroxytriptolide (LLDT-8) on receptor activator of nuclear factor κ-B ligand (RANKL)/receptor activator of nuclear factor κ-B (RANK)/Osteoprotegerin (OPG) system in rheumatoid arthritis (RA) and its anti-osteoclastogenesis mechanism. Methods The expression of OPG, RANK and RANKL in CD3+ T leukomonocytes in both peripheral blood and synovial fluid of RA patients was evaluated by flow cytometry. The levels of interleukin (IL) 1β, IL-6, IL-10, IL-21 and IL-23 in the supernatants of peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were assayed by ELISA. Tartaric acid phosphatase (TRAP) staining was used to identify the osteoclast-like cells derived from RAW264.7. Western blotting analysis was used to check the downstream molecules of RANKL. Results LLDT-8 increased the rate of OPG expression in CD3+ T leukomonocytes in peripheral blood as well as the ratio of OPG/RANKL in both peripheral blood and synovial fluid. LLDT-8 inhibited IL-1β, IL-6, IL-21 and IL-23 secretion, but promoted the secretion of IL-10 in the supernatants of PBMCs and SFMCs. In addition, LLDT-8 decreased the number of TRAP-positive cells derived from RAW264.7 in the presence of RANKL and M-CSF. Furthermore, LLDT-8 also inhibited the expression of p-IκB, a key regulator of RANKL signaling pathway. Conclusions LLDT-8 exerts its anti-osteoclastogenesis effect in RA probably through regulating RANKL/RANK/OPG system and its downstream signaling pathway as well as cytokine productions.