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Flexible electrodes have attracted the interest of a wide range of people because they can monitor human health signals like ECG, EMG and EEG as wearable devices. However, PDMS-based membrane electrodes have the problem of difficulty in depositing metal layers, while fabric electrodes have high contact impedance. Furthermore, the widely used Ag/AgCl electrodes have the shortcomings of skin inflammation or skin irritation. Therefore, we fabricate a skin-like electrical conductive electrode via electroless silver plating on the surface of regenerated cellulose membrane, in which the cellulose membrane is obtained by the dissolution of cotton fiber with green solvent ionic liquid [Bmim]Cl. The as-prepared biocompatible electrode with low skin-electrode contact impedance can be used as a dry electrode for a long-term period of use. The impedance at 700 Hz is only 8 kΩ/cm2, and the conductivity can reach 252 s/cm. After 5 hours of wear, the skin contact impedance of the electrode was only 10 kΩ/cm2 under 700 Hz(when AgNO3 was used at a concentration of 0.20 mol/L). Importantly, the electrodes not only provide a stable and clear ECG signal, but also offer a high level of comfort and low impedance, when used for long-term health monitoring.

Background During the manufacturing and storage, nutrients in infant formulae are sensitive to oxidative degradation and are prone to form unpleasant smells followed by a reduction in bioaccessibility. Therefore, it is possible to prepare microcapsules by embedding functional ingredients in a homogeneous or heterogeneous matrix. Currently, microcapsules used as carriers in dairy are a relatively promising technology. Scope and approach The differences of nutrients in infant formulae and breast milk, and challenges in the fortification of functional ingredients in infant formulae are reviewed. Then we summarize delivery systems that have been used or could potentially be applied to encapsulate the functional ingredients for infant formulae, such as casein, ethyl cellulose, maltodextrin, whey protein, and Maillard reaction products. Besides, the application of liposomes in the food field and the feasibility of liposomes to deliver nutrients in infant formulae are discussed. Key findings and conclusions Nowadays, microcapsules have shown broad application prospects in food science and nutrition. In particular, liposomes, as biocompatible and biodegradable delivery systems, encapsulate essential nutrients for infants, such as lactoferrin, vitamins, and functional lipids. Despite the relative improvements toward the extension of liposome application, additional efforts for its application in infant formulae must be attempted. For the practical application of liposomes in infant formulae, higher quality wall materials with reasonable price should be developed, and their biological assessment including safety and bioaccessibility, should be performed in the future.

Type 2 diabetes mellitus (T2DM) is known as a complex genetic disease characterized by genetic and environmental factors. The imbalanced intestinal flora and intestinal mucosal barrier are considered to be related to T2DM. Curcumin has been proved to affect the progression of T2DM. T2DM animal was established by low-dose streptozotocin intraperitoneal injection combined with high-fat diet (HFD) feeding. Hematoxylin and eosin (HE) staining and transfer electron microscopy (TEM) were used to observe morphological changes of intestinal tissues of T2DM rats. Insulin and glucose tolerance tests were performed to investigate the influence of curcumin on blood glucose. Curcumin significantly improved the intestinal integrity, hyperglycemia and insulin resistance in diabetic rats. The metabolic endotoxemia induced by HFD in diabetic rats was inhibited remarkably. Curcumin reversed gut microbiota dysbiosis in diabetic rats caused by HFD. We demonstrated that curcumin could protect intestinal mucosal barrier, improve insulin resistance and reduce blood glucose in diabetic rats. This study might provide experimental evidence for the prevention and treatment in T2DM.

Our previous studies have shown that the nutritional properties of peanut meal after fermentation are markedly improved. In this study, in order to facilitate the further utilisation of peanut meal, we investigated the effects of its fermentation extract by Bacillus natto (FE) on cognitive ability, antioxidant activity of brain and protein expression of hippocampus of ageing rats induced by d-galactose. Seventy-two female sd rats aged 4–5 months were randomly divided into six groups: normal control group, ageing model group, FE low-dose group, FE medium-dose group, FE high-dose group and vitamin E positive control group. Morris water maze (MWM) test was performed to evaluate their effects on learning and memory ability in ageing rats. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of brain, HE staining and the expression of γ-aminobutyric acid receptor 1 (GABABR1) and N-methyl-d-aspartic acid 2B receptor in the hippocampus of rats were measured. The results show that FE supplementation can effectively alleviate the decrease of thymus index induced by ageing, decrease the escape latency of MWM by 66·06 %, brain MDA by 28·04 %, hippocampus GABABR1 expression by 7·98 % and increase brain SOD by 63·54 % in ageing model rats. This study provides evidence for its anti-ageing effects and is a research basis for potential nutritional benefits of underutilised food by-products.

Background Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility. Experimental We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA257-264) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine. Results In vitro experiments revealed that the antigen uptake of BMDCs after nanovaccine incubation was two times higher than pure OVA or OVA@Al at 12 h. The BMDCs were well activated by p38 MAPK signaling pathway. Furthermore, the nano-vaccine induced antigen escape from lysosome into cytoplasm with 10 times increased cross-presentation activity than those of OVA or OVA@Al. Regarding the transport of antigen into draining lymph nodes (LNs), the nano-vaccine could rapidly transfer antigen to LNs by passive lymphatic drainage and active DC transport. The antigen+ cells in inguinal/popliteal LNs for the nano-vaccine were increased over two folds comparing to OVA@Al and OVA at 12 h. Moreover, the antigen of nano-vaccine stayed in LNs for over 7 days, germinal center formation over two folds higher than those of OVA@Al and OVA. After immunization, the nano-vaccine induced a much higher ratio of IgG2c/IgG1 than OVA@Al. It also effectively activated CD4+ T, CD8+ T and B cells for immune memory with a strong cellular response. Conclusion These results indicated that DDAB/PLGA NP was a potent platform to improve vaccine immunogenicity by p38 signaling pathway in BMDCs, enhancing transport of antigens to LNs, and higher immunity response. Graphical Abstract

We recently showed that inhibition of hypoxia-induced factor-1α (HIF-1α) decreased acute ischemic stroke-induced blood-brain barrier (BBB) damage. However, factors that induce the upregulation of HIF-1α expression remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase played a critical role in reperfusion-induced BBB damage after stroke. However, the role of NADPH oxidase in BBB injury during the acute ischemia stage remains unclear. This study is aimed at investigating the role of NADPH oxidase in BBB injury and the expression of HIF-1α after acute ischemic stroke. A sutured middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke in rats. Our results show that the inhibition of NADPH oxidase by apocynin can significantly reduce the BBB damage caused by 2 h ischemic stroke accompanied by reducing the degradation of tight junction protein occludin. In addition, treatment with apocynin significantly decreased the upregulation of HIF-1α induced by 2 h MCAO. More importantly, apocynin could also inhibit the MMP-2 upregulation. Of note, HIF-1α was not colocalized with a bigger blood vessel. Taken together, our results showed that inhibition of NADPH oxidase-mediated HIF-1α upregulation reduced BBB damage accompanied by downregulating MMP-2 expression and occludin degradation after 2 h ischemia stroke. These results explored the mechanism of BBB damage after acute ischemic stroke and may help reduce the associated cerebral hemorrhage transformation after thrombolysis and endovascular treatment after ischemic stroke.

Ultra-light electromagnetic (EM) wave absorbers with strong absorption bandwidth are highly desired in reducing EM pollution. Herein, a series of nanocomposites with ZnO nanoparticles decorated nanoscale reduced graphene oxide (NRGO) were synthesized via a simple and efficient hydrothermal process. The characterizations reveal that NRGO with layered structure possesses intensive folds and the ZnO nanoparticles are well attached on the surface of NRGO. The EM parameters demonstrate that the EM wave absorption properties of ZnO/NRGO nanocomposite are closely related to the amount of NRGO. The minimum reflection loss (RL) values of ZnO/NRGO-10, ZnO/NRGO-15 and ZnO/NRGO-20 are − 44.4 dB with a thickness of 4.5 mm, − 39.6 dB with a thickness of 2.5 mm and − 18.8 dB with a thickness of 2.0 mm, respectively. The largest effective absorption bandwidths of ZnO/NRGO-10, ZnO/NRGO-15 and ZnO/NRGO-20 are 5.5 GHz at 2.5 mm, 5.2 GHz at 2.5 mm and 5.5 GHz at 2.0 mm, respectively. These outstanding EM wave absorption properties resulting from the multiple reflection, various polarization relaxation processes and synergistic effects between ZnO and NRGO. It is believed that as-synthesized ZnO/NRGO nanocomposite could be used as promising EM wave absorber.

The present work reports the construction of polypyrrole (PPy) hydrogels directly with the as-synthesized PPy nanotubes (PPy-NTs) through infiltration of poly vinyl alcohol (PVA) and poly(acrylic acid) (PAA) solutions. This method avoids the time-consuming purification of the in-situ formed conducting hydrogels and provides a facile way to incorporate nanostructured conducting polymers evenly into the hydrogel matrix. PPy-NTs/PVA/PAA hydrogels with dual cross-linking networks were prepared through multiple freeze-thawing cycles followed by coordination with iron (III) ions. The tensile and compression strength of the hydrogels are ca. 54 kPa and 160 kPa, respectively. The PPy-NTs/PVA/PAA hydrogel was mainly electronic conducting dominated, and it showed the highest conductivity of ca. 0.04 S/cm after swollen in 0.2 M HCl (with 2wt% of PPy-NTs). Benefited from the high aspect ratio and high conductivity of PPy nanotubes, it is probable to mediate the PPy content and the integrity of the electronic conducting pathways to develop high-performance hydrogel materials used as strain sensors.

Melatonin has been characterized as a growth regulator in plants. Melatonin shares tryptophan as the precursor with the auxin indole-3-acetic acid (IAA), but the interplay between melatonin and IAA remains controversial. In this study, we aimed to dissect the relationship between melatonin and IAA in regulating Arabidopsis primary root growth. We observed that melatonin concentrations ranging from 10–9 to 10–6 M functioned as IAA mimics to promote primary root growth in Arabidopsis wild type, as well as in pin-formed (pin) single and double mutants. Transcriptome analysis showed that changes in gene expression after melatonin and IAA treatment were moderately correlated. Most of the IAA-regulated genes were co-regulated by melatonin, indicating that melatonin and IAA regulated a similar subset of genes. Melatonin partially rescued primary root growth defects in pin single and double mutant plants. However, melatonin treatment had little effect on primary root growth in the presence of high concentrations of auxin biosynthesis inhibitors, or polar transport inhibitor, and could not rescue the root length defect of the IAA biosynthesis quintuple mutant yucQ. Therefore, we propose that melatonin promotes primary root growth in an IAA-dependent manner.

Oligosaccharides are one of the major bioactive components in Codonopsis pilosula. The present study was to investigate the protective effect of C. pilosula oligosaccharides (CPO) on d-galactose (D...

Electrocardiography is one of the most significant technologies for detecting cardiovascular diseases. Nowadays, the problems of various electrodes still meet a great challenge. Herein, we design a low cost, environmentally friendly and flexible conductive electrode using cellulose and polyvinyl alcohol as a substrate assembled with conductive polymer polythiophene by in situ oxidative polymerization, and the green solvent 1-butyl-3-methylimidazolium chloride as a crosslinking agent. The polyvinyl alcohol/cellulose/PEDOT:PSS(PCPP) composite electrode has excellent features of flexibility, low skin contact impedance and comfortable contact with skin. When the load of EDOT reaches 15 wt%, the electrode is stable and can clearly monitor the characteristic wave of ECG signals. Therefore, based on cellulosic biopolymer and conductive polymer PEDOT:PSS, an environmentally friendly, flexible and stable PCPP composite electrode is obtained and can be a promising candidate applied in the fields of energy storage and ECG sensing.

Herein, binary CuS/BTO and ternary CuS/Ag/BTO composite photocatalysts have been fabricated by anchoring CuS and Ag nanoparticles onto BaTiO3 (BTO) polyhedra. The as-prepared composite photocatalysts were characterized by means of the techniques of transmission/scanning electron microscopy, x-ray powder diffraction, ultraviolet–visible diffuse reflectance spectroscopy, x-ray photoelectron spectroscopy and photoluminescence spectroscopy. Transient photocurrent and electrochemical impedance spectroscopy measurements suggest that the ternary 5%CuS/(1%Ag/BTO) composite possesses the highest separation efficiency of electron/hole pairs. The photodegradation experiments were conducted by using simulated sunlight as the light source to decompose Rhodamine B in water solution. The 5%CuS/(1%Ag/BTO) and 5%CuS/BTO composites are demonstrated to have the highest and second highest photodegradation activity, respectively. As compared with that of bare BaTiO3 and CuS, the photoactivity of 5%CuS/(1%Ag/BTO) is increased to 3.3 and 2.0 times, respectively. The electron/hole separation mechanism and the role of localized surface plasmon resonance of Ag nanoparticles in the dye photodegradaton were systematically investigated.

Upcycle of waste fabrics has been a promising project since it can reduce textile pollution and provide a prospect to waste management. In this work, a multiple recyclable transparent functional film was fabricated through ionic liquid (IL) assisted regeneration process with a higher yield of 90.40 %, compared with other polymer regeneration process using IL. Fourier Transfer Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), UV–vis Spectrophotometer, as well as tensile strength test were carried out to explore the performance of the regenerated jute film. This transparent renewable jute film can be made into many functional materials, like packaging materials, electrically conductive films or information storage devices. Furthermore, it can be dissolved in IL and regenerate new films for multiple cycles, which can still maintain a relatively high transparency and a considerable mechanical property. Compared to other fabric recycle process, the solvent and production both can be effectively recycled, which can be considered as a green and sustainable tool to manage waste fabrics.

Electrochemical water splitting into hydrogen is a promising strategy for hydrogen production powered by solar energy. However, the cell voltage of an electrolyzer is still too high for practical application, which is mainly limited by the sluggish oxygen evolution reaction process. To this end, hybrid water electrolyzers have drawn tremendous attention. Herein, coaxial Ni/Ni3S2@N-doped nanofibers are directly grown on nickel foam (NF), which is highly active for hydrogen evolution reaction. Meanwhile, the Ni3S2@N-doped nanofibers on NF prepared in an Ar atmosphere display superior urea oxidation reaction performance to previously reported catalysts. The cell voltage is about 1.50 V in urea electrolysis to deliver a current density of 20 mA cm-2, lower than that of a traditional water electrolyzer (1.82 V). The current density is around 77% relative to its initial value of 20 mA cm-2 after 20 h, superior to Pt/C|Ir/C-based urea electrolysis (14%). It is found that the synergistic effect between metallic Ni and Ni3S2, as well as the interfacial effect between metal centers and N-doped carbon, favors the initial dissociation of H2O and the adsorption/desorption of H* with thermal neutral Gibbs free energy. Meanwhile, the in-situ generated NiOOH on the outer surface of Ni3S2 possessed lower electrochemical activation energy for urea decomposition. Meanwhile, the abundant oxygen vacancies in electrodes could expose more active sites for the adsorption of intermediates, including H* and OOH*. It is also found that the hierarchical nanostructure of densely packed nanowires provides ideal electronic and ionic transport paths for fast electrocatalytic kinetics. The present work indicated that the modulation of compositions and hierarchical nanostructure is effective to prepare efficient catalysts for H2 production via urea electrolysis.

BACKGROUND AND PURPOSE Psoriasis is a chronic immune-mediated inflammatory skin disease that easily recurs and is difficult to cure. DGT is a novel synthetic heterocyclic diterpenoid, whose structure has not been previously reported. We have investigated the action of DGT against psoriasis, specifically the hyperproliferation of epidermal keratinocytes, angiogenesis and pathogenic inflammatory responses. EXPERIMENTAL APPROACH We investigated its pharmacokinetics in skin after topical administration. We characterized its pharmacological actions in vitro and in vivo using cell proliferation assay, cell apoptosis assay, diethylstilbestrol-induced mouse vaginal epithelial cell mitosis model, tube formation assay, cell migration assay, chick embryonic chorioallantoic membrane (CAM) assay, histological, flow cytometric analysis and imiquimod (IMQ)-induced psoriasis-like model. KEY RESULTS DGT was found to be mainly distributed in the epidermis and dermis, which indicated that DGT was suitable as a topical treatment. DGT inhibited cell proliferation and induced apoptotic cell death of keratinocytes in vitro and in vivo. Moreover, DGT inhibited endothelial cell proliferation, tube formation and migration of in vitro angiogenesis, as well as in vivo CAM angiogenesis. In an IMQ-induced psoriasis-like skin inflammation murine model, topical application of DGT ameliorated keratinocyte proliferation and inflammatory response, especially in IL-17-related psoriasiform dermatitis. Furthermore, our results demonstrated that DGT prevented these pathological processes of psoriasis through suppression of STAT3 phosphorylation. CONCLUSION AND IMPLICATIONS DGT has great potential as a novel therapeutic agent for the treatment of psoriatic skin disease.

Electrochemical degradation of sulfamethoxazole (SMX) and its metabolite acetyl-sulfamethoxazole (Ac-SMX) by Ti/SnO2-Sb/Er-PbO2 were investigated. Results indicated that the electrochemical degradation of SMX and Ac-SMX followed pseudo-first-order kinetics. The rate constants of SMX and Ac-SMX were 0.268 and 0.072 min-1 at optimal current density of 10 and 14 mA/cm2, respectively. Transformation products of SMX and Ac-SMX were identified and the possible degradation pathways, including the cleavage of S-N bond, opening ring of isoxazole and nitration of amino group, were proposed. Total organic carbon removal of SMX was nearly 63.2% after 3 h electrochemical degradation. 22.4% nitrogen of SMX was transformed to NO3-, and 98.8% sulfur of SMX was released as SO42-. According to quantitative structure-activity relationship model, toxicities of SMX and Ac-SMX to aquatic organisms significantly decreased after electrochemical degradation. Electric energy consumption for 90% SMX and Ac-SMX degradation was determined to be 0.58-8.97 and 6.88-44.19 Wh/L at different experimental conditions, respectively. Compared with parent compound SMX, the metabolite Ac-SMX is more refractory and toxic, which emphasizes the importance of taking its metabolites into account when investigating the disposal of pharmaceuticals from wastewater.

Background The application of liposomal system in food area allowing carried and controlled bioactive-molecules release has been considered one of the main strategies used to improve nutrients stability, to increase individualized absorptivity, and to enhance quality-of-food. Scope and approach The preparation methods including traditional and novel technologies and formation mechanism of liposomes are reviewed. Then we discuss how liposomes are designed and applied to alter properties for food quality improvement and nutrient-modification in dairy, beverages, meat and other products. Besides, the changes in liposomal structure and molecules bioavailability within the gastrointestinal tract, along with the cell uptake pathways of liposomes, generally employed adhesion, fusion, endocytosis, lipid exchange, and its relevant factors are emphasized. Key findings and conclusions So far, a rapidly increased achievement of liposomes in food science and nutraceuticals has already gained, and the digestion behavior and the followed absorption mechanism have been explored. For further successful development and wide use of liposomes, promising preparation approaches and safe formula in future study on food must be exploited, albeit with designing the efficacious and targeted deliver in human body.

In this study, a series of liquid crystal copolyurethanes based on mesogenic biphenyl diol and two aromatic biphenyl diisocyanate were synthesized via polyaddition method. Chemical structure of the...

In this study, wholly aromatic phosphorus-containing thermotropic liquid crystal polymers (TLCP) derived from 6-hydroxy-2-naphthenic acid (HNA), terephthalic acid (TA) and 10-(2,5-Dihydroxypheny)-1...

Gastric emptying refers to a process in which the stomach discharges its contents into the small intestine to further digest and absorb nutrients. Understanding the mechanisms of gastric emptying and relationships between food and individuals is of paramount importance for the design and manufacture of novel and healthy foods. For ethical and cost reasons, in vivo tests are not always possible. In vitro digestion models therefore play a key role in current exploration of gastric emptying. This review outlines the mechanisms and physiology of gastric emptying, including calories, viscosity, composition of the food, age and gender of the individual. In addition, recent progress on in vitro static and dynamic gastric digestion models and future research trends are included in this review.

In this study, three novel main-chain liquid-crystal polyurethanes based on mesogenic diol 4,4ʹ-bis(6-hydroxyhexoxy)biphenyl (BP6), azo diol 4,4ʹ-bis(6-hydroxyhexyloxy)-azobenzene (BHHAB) and 4,4ʹ-...

The electron transport properties in bis[2-(2-hydroxyphenyl)-pyridine] beryllium (Bepp2) doped 8-hydroxyquinolinolatolithium (Liq) are investigated by impedance spectroscopy (IS). The Nyquist curve...

To enhance the solubility of polyanilines (PANI), polymeric ionic liquid (PIL) was introduced into the polymerization synthesis of PANI with various proportions. The structure and properties of the modified PANIs were characterized by 1H NMR, Fourier transform infrared spectroscopy, thermogravimetric analysis, ultraviolet-visible spectrum, etc. It was found that the obtained PANIs doped with PILs were soluble in various organic solvents such as N,N-dimethyl formamide and acetonitrile. Compared with the pure PANI, the PANIs doped by PILs showed remarkable solubility and their chemical structure and conductivity kept integrated.

AIM To screen a lactic acid bacteria (LAB) strain for good adaption in alfalfa ensiling and to evaluate its effects on alfalfa ensiling. METHODS AND RESULTS Lactobacillus plantarum (LP) strain ZZU203 was selected due to its superior ability to acidify structural carbohydrate metabolite and alfalfa powder. Alfalfa was ensiled with LP FG1 (from a commercial inoculant), LP ZZU203, or a no-additive control (CK) for 60 d. The two silages with LP additives significantly (P

Tamoxifen is a successful endocrine therapy drug for estrogen receptor–positive (ER+) breast cancer. However, resistance to tamoxifen compromises the efficacy of endocrine treatment. In the present study, we identified potential tamoxifen resistance–related gene markers and investigated their mechanistic details. First, we established two ER + breast cancer cell lines resistant to tamoxifen, named MCF-7/TMR and BT474/TMR. Gene expression profiling showed that CXXC finger protein 4 (CXXC4) expression is lower in MCF-7/TMR cells than in MCF-7 cells. Furthermore, CXXC4 mRNA and protein expression are lower in the resistant cell lines than in the corresponding parental cell lines. We also investigated the correlation between CXXC4 and endocrine resistance in ER + breast cancer cells. CXXC4 knockdown accelerates cell proliferation in vitro and in vivo and renders breast cancer cells insensitive to tamoxifen, whereas CXXC4 overexpression inhibits cancer cell growth and increases tamoxifen sensitivity of resistant cells. In addition, we demonstrated that CXXC4 inhibits Wnt/β-catenin signaling in cancer cells by modulating the phosphorylation of GSK-3β, influencing the integrity of the β-catenin degradation complex. Silencing the CXXC4 gene upregulates expression of cyclinD1 and c-myc (the downstream targets of Wnt signaling) and promotes cell cycle progression. Conversely, ectopic expression of CXXC4 downregulates the expression of these proteins and arrests the cell cycle in the G0/G1 phase. Finally, the small-molecule inhibitor XAV939 suppresses Wnt signaling and sensitizes resistant cells to tamoxifen. These results indicate that components of Wnt pathway that are early in response to tamoxifen could be involved as an intrinsic factor of the transition to endocrine resistance, and inhibition of Wnt signaling may be an effective therapeutic strategy to overcome tamoxifen resistance. Keywords: CXXC finger protein 4, CXXC4, Estrogen receptor–positive breast cancer, Tamoxifen resistance, Cell cycle, Wnt/β-catenin

The synthesis and modification of high performance thermotropic liquid crystal polyesters (TLCP) are still being investigated due to their excellent properties. In this study modification o...

As an important edible traditional Chinese medicine, Codonopsis pilosula has good immunomodulation effects. This study focuses on C. pilosula oligosaccharides (CPO), which are the sweetness components of C. pilosula. CPO were obtained through systematic separation and purification (the yield is 14.3%), and the effect of CPO on the immunological activities of immunocompromised mice induced by cyclophosphamide (CTX) was evaluated. The results showed that CPO could increase immune organ indices, phagocytic index and immunoglobulin contents, stimulate the proliferation of splenic lymphocytes (coordinating with ConA and LPS), enhance the earlap swelling of the DTH reaction, promote the production of NO and cytokines (IL-2 and IFN-γ) and upregulate the expression of the corresponding mRNA. In addition, CPO upregulated the protein expression of phosphorylated p38, phosphorylated ERK1/2 and phosphorylated JNK, which indicated that CPO might exert immunomodulatory effects through the MAPK signaling pathway. These findings indicated that CPO are important immunomodulatory components in C. pilosula and could be developed as immunomodulators in medicine or functional food areas.

Background: Glial-derived neurotrophic factor (GDNF) has been demonstrated to promote the therapeutic effect of mesenchymal stem cells on ameliorating renal injury. The mechanism may involve the transfer of endogenous molecules, but these factors remain unknown. Methods: GDNF was transfected into human adipose mesenchymal stem cells via a lentiviral transfection system and exosomes were isolated (GDNF-AMSC-exos). Using unilateral ureteral obstruction (UUO) mouse models and human umbilical vein endothelial cells (HUVECs) against hypoxia/serum deprivation (H/SD) injury models we investigated whether GDNF-AMSC-exos ameliorate peritubular capillary (PTC) loss in tubulointerstitial fibrosis, and whether this effect is meditated by SIRT1 signaling pathway. Additionally, by using SIRT1 activators or siRNA, the roles of the candidate mRNA and its downstream gene in GDNF-AMSC-exo-induced regulation of endothelial cell function were assessed. Findings: GDNF-AMSC-exos resulted in significantly decreased PTC rarefaction and renal fibrosis scores in mice with UUO. In vitro studies revealed that GDNF-AMSC-exos exert cytoprotective effects on HUVECs against H/SD injury by stimulating migration, angiogenesis and conferring apoptosis resistance. Mechanistically, GDNF-AMSC-exos enhanced SIRT1 signaling, which accompanied by increased protein levels of phosphorylated eNOS (p-eNOS). In addition, we have confirmed the SIRT1-eNOS interaction in HUVECs by immunoprecipitation. Interpretation: Our study unveils a mechanism by which exosomes ameliorate renal fibrosis: GDNF-AMSC-exos may activate an angiogenesis program in surviving PTCs after injury by activating the SIRT1/eNOS signaling pathway. This finding suggests that inhibition of chronic kidney disease (CKD) progression requires long-term suppression of fibrosis via renal microvascular repair and angiogenesis and that GDNF-AMSC-exos therapy is a promising strategy for achieving this goal. Funding Statement: This work were supported by projects of the National Natural Science Foundation of China (81270769 and 81803473); a project of the Jiangsu Provincial Natural Science Foundation (BK20161172); a project of the Jiangsu Provincial Commission of Health and Family Planning (H201628); projects of the Jiangsu Provincial Post Graduate Innovation Plan (KYCX18-2178, KYCX17-1708, SJCX17-0560, SJCX18-0715); the Municipal Key Research and Development Project of Xuzhou (KC18212); the “Liu ge yi Gong Cheng” project of Jiangsu High-Level Personnel (LGY2016043); a school class project of Xuzhou Medical University (2017KJ13); and the Xuzhou Science and Technology Bureau Applied Basic Research Program( KC18041 and KC 19069). Declaration of Interests: All the authors declared no competing interests. Ethics Approval Statement: Approval of all research involving human participants was obtained from the Institutional Review Board of the Affiliated Hospital of Xuzhou Medical University (permit number: xyfylw2013032). All experiments involving animals followed the animal use protocol enacted by the Institutional Animal Care and Use Committee of Xuzhou Medical University.