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Innate lymphoid cells (ILCs) are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells. Inducible T-cell costimulator (ICOS) is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues. However, the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear. Here, we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s. ICOS costimulation enhanced the survival, proliferation, and capacity of ILC3s to produce cytokines (IL-22, IL-17A, IFN-γ, TNF, and GM-CSF). Via synergistic effects of ICOS and CD40 signaling, B cells promoted ILC3 functions, and ILC3-induced T-cell-independent B-cell IgA and IgM secretion primarily required CD40 signaling. Hence, ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.

Subcutaneous injection of insulin is the current standard medication for many diabetic patients. Convenient and painless noninvasive transdermal insulin delivery has long been pursued but yet succeeded due to no such technologies for large biomacromolecules. We find a tertiary amine oxide-based polyzwitterion, OPDMA, that can efficiently penetrate both the stratum corneum (SC) and viable epidermis into circulation. So its conjugate with insulin, OPDMA-I, applied on the skin can exhibit hypoglycemic effects as efficiently as subcutaneously injected insulin in type-1 diabetic mice and minipigs. The unique pH-dependent cationic-to-zwitterionic transition of OPDMA in the characteristic acidic-to-neutral pH gradient from the skin surface to deep SC enables fast transdermal delivery of OPDMA and its conjugate. On the skin, OPDMA binds to carboxylic acids in the acidic sebum layer, enriching OPDMA-I on the SC. As pH increases in deeper SC layers, binding between OPDMA-I and the skin weakens gradually, allowing for diffusion through inter-corneocyte gaps and penetration into viable epidermis and finally entering the systemic circulation via dermal lymphatic vessels. This process does not alter SC microstructures or cause any physiological changes in the skin. This study represents a groundbreaking example of noninvasive transdermal protein delivery.

New kinds of HIV-1 circulating recombinant forms (CRFs) and unique recombinant forms (URFs) earn a great prevalence in China nowadays. In this study, we identified 2 similar URFs (2016GXNNIDU037 and 2019QZLSIDU253) both isolated from intravenous drug users (IDUs) in Guangxi, China. Phylogenetic analysis of the near full-length genome (NFLG) revealed 2 URFs both clustered with CRF01_AE but setting up a monophyletic branch, supporting a high bootstrap value. Bootscan analysis and subregional recombinant analysis found that the NFLG of 2016GXNNIDU037 and 2019QZLSIDU253 were both composed of CRF01_AE and CRF07_BC, with 3 CRF07_BC mosaic segments inserted into CRF01_AE backbones. The CRF01_AE segments of the 2 URFs clustered with a previously reported cluster 2 lineage of CRF01_AE. The 5 recombinant breakpoints of the 2 URFs were quite similar. Distinct from CRF01_AE/CRF07_BC URFs reported before, 2016GXNNIDU037 and 2019QZLSIDU253 are new evidence of a high genetic variety of HIV-1 in Guangxi, which may pose new challenges to HIV-1 prevention and molecular epidemiological surveillance in China.

The biosynthetic gene cluster (BGC) for polyether antibiotic K-41A was identified from marine-derived Streptomyces sp. SCSIO 01680 and subjected to combinatorial biosynthetic study. Bioinformatics analyses, gene disruption, and metabolomics analyses afforded eight new derivatives and one known polyether, showcasing five region-specific methyltransferases Pak13, Pak15, Pak20, Pak31, and Pak38 and their respective modification loci. Moreover, bioassays revealed that two disaccharide-bearing polyethers, K-41B and K-41Bm, display enhanced anti-HIV and potent antibacterial activities.

Dynamic recombination is the driving force in the genetic diversity of human immunodeficiency virus type 1 (HIV-1). When multiple subtypes are circulating in the same area of a population, new HIV-1 strains are likely to be generated through recombination. In this study, we report a novel recombinant strain (2018GXQZLSHET001) of HIV-1, isolated from a HIV-1-positive heterosexual individual infected in Guangdong province, who recently lived in Guangxi province, China. Phylogenetic analysis of the near full-length genome suggested that 2018GXQZLSHET001 was a recombinant of strains CRF55_01B and subtype B. Similarity plotting and bootscaning showed that a subtype B segment was inserted into the CRF55_01B genome with one breakpoint in the nef and 3' long terminal repeat regions. Further subregion phylogenetic analysis demonstrated that the CRF55_01B segment originated from Guangdong. The subtype B segment was similar to a Thai B lineage. This indicated that the strain might be a novel recombinant, comprising sequences of both CRF55_01B and B. The emergence of this unique recombinant strain illustrated the complexity of the HIV-1 epidemic, and the need to strengthen molecular epidemiological surveillance and measures to reduce its spread.

Recently, an increasing number of circulating recombinant forms (CRFs) and unique recombinant forms of HIV-1 have been identified in China, contributing substantially to the genetic variability of this virus. This study reports a novel second-generation recombinant form of HIV-1 (GX2015QZLS204), composed of segments from the CRF07_BC and CRF01_AE strains, which was isolated from an HIV-positive male individual infected through heterosexual contact, while residing in the Guangxi province of southwest China. Analysis of the near full-length genome sequence showed that one segment of the CRF01_AE virus subtype was inserted into the CRF07_BC subtype backbone. Recombination analysis demonstrated that the genome of GX2015QZLS204 was separated into seven segments with six breakpoints. Subregion trees constructed by the neighbor-joining method confirmed that the CRF01_AE segment was from the previously identified CRF01_AE cluster 2, and the CRF07_BC segment correlated with the CRF07_BC strain originating from the Jiangxi and Xinjiang provinces of China. The emergence of GX2015QZLS204 highlights the frequent generation of novel recombinant forms and the increasing complications of the HIV-1 epidemic among heterosexual transmission (HET) groups in China. This highlights the importance of monitoring HIV-1 molecular epidemiological characteristics and the urgent need for reduction of the HIV-1 epidemic among HET groups in China.

6-Gingerol, an active herbal ingredient of ginger has various bioactivities such as anti-neurodegenerative disease, anti-inflammatory and so on. The aim of the present study was to enhance the oral...

This study aimed to prepare a self-microemulsifying drug delivery system loaded with myricitrin (M-SMEDDS) to improve the low oral bioavailability of myricitrin. Prepared M-SMEDDS consisted of an oil phase (ethyl oleate), a surfactant (Cremophor EL35) and a co-surfactant (dimethyl carbinol). M-SMEDDS was characterized using the particle size, zeta potential and encapsulation efficiency, while the pharmacokinetics studies were also investigated. The prepared M-SMEDDS exhibited stable physicochemical properties with a small average droplet size (21.68 ± 0.15 nm), negative zeta potential (−23.17 ± 1.03 mV) and high encapsulation efficiency (92.73%). The in vitro release study showed that myricitrin was significantly released from M-SMEDDS compared with the free myricitrin. The relative oral bioavailability of M-SMEDDS was 2.47-fold higher than that of the free drug. These results indicated that the preparation, in vitro and in vivo studies of M-SMEDDS could obviously improve the solubility and oral bioavailability of myricitrin. This study therefore provides preliminary evidence for further clinical research and application of M-SMEDDS.

Aims: The aim was to improve the absorption and bioavailability of [6]-shogaol with β-cyclodextrin (β-CD) prior to in vitro and in vivo evaluation.Methods: [6]-Shogaol/β-CDs inclusion complexes (6-...

Poor charge separation is the main factor that limits the photocatalytic hydrogen generation efficiency of organic conjugated polymers. In this work, a series of linear donor–acceptor (D–A) type oligomers are synthesized by a palladium-catalyzed Sonogashira–Hagihara coupling of electron-deficient diborane unit and different dihalide substitution sulfur functionalized monomers. Such diborane-based A unit exerts great impact on the resulting oligomers, including distinct semiconductor characters with isolated lowest unoccupied molecular orbital (LUMO) orbits locating in diborane-containing fragment, and elevated LUMO level higher than water reduction potential. Relative to A-A type counterpart, the enhanced dipole polarization effect in D–A oligomers facilitates separation of photogenerated charge carriers, as evidenced by notably prolonged electron lifetime. Owing to π–π stacking of rigid backbone, the oligomers can aggregate into an interesting 2D semicrystalline nanosheet (≈2.74 nm), which is rarely reported in linear polymeric photocatalysts prepared by similar carbon–carbon coupling reaction. Despite low surface area (30.3 m2 g−1), such ultrathin nanosheet D–A oligomer offers outstanding visible light (λ > 420 nm) hydrogen evolution rate of 833 µmol g−1 h−1, 14 times greater than its A-A analogue (61 µmol g−1 h−1). The study highlights the great potential of using boron element to construct D–A type oligomers for efficient photocatalytic hydrogen generation. © 2021 Wiley-VCH GmbH

Unmethylated CpG oligodeoxynucleotides (ODNs) activate plasmacytoid dendritic cells (pDCs) and B cells to induce humoral and cellular immunity, and are under development for the treatment of multiple cancers. However, the specific differences in antitumor effects among the three CpG ODN classes when administered as a monotherapy or in co-therapy with the anti-PD-1 antibody are unclear. We compared the immunostimulatory effects in vitro and antitumor effects in a CT26 subcutaneous mouse tumor model among the three CpG ODN classes. We found that CpG-A slightly suppressed tumor growth but possessed no synergistic antitumor effects with the anti-PD-1 antibody. CpG-B at low doses significantly inhibited tumor growth and possessed synergistic antitumor effects with the anti-PD-1 antibody. A high dose of CpG-C was required to achieve antitumor effects comparable to those of CpG-B, which was consistent with the immunostimulatory effects in B-cell proliferation and TLR9-NF-κB activation. Importantly, CpG-C in combination with anti-PD-1 antibody inhibited tumor growth more quickly and effectively than CpG-B because CpG-B significantly upregulated PD-L1 expression on multiple host immune cells to promote tumor immune escape. Moreover, co-therapy increased the infiltration of effector memory T cells. In summary, CpG-B and CpG-C with different optimal concentrations possessed strong antitumor effects, while CpG-C was more rapid and effective for co-therapy with the anti-PD-1 antibody.

Orally administrable anticancer nanomedicines are highly desirable due to their easy and repeatable administration, but are not yet feasible because the current nanomedicine cannot simultaneously overcome the strong mucus and villi barriers and thus have very low bioavailability (BA). Herein, this work presents the first polymeric micelle capable of fast mucus permeation and villi absorption and delivering paclitaxel (PTX) efficiently to tumors with therapeutic efficacy even better than intravenously administered polyethylene glycol based counterpart or free PTX. Poly[2-(N-oxide-N,N-diethylamino)ethyl methacrylate] (OPDEA), a water-soluble polyzwitterion, is highly nonfouling to proteins and other biomacromolecules such as mucin but can weakly bind to phospholipids. Therefore, the micelle of its block copolymer with poly(ε-caprolactone) (OPDEA-PCL) can efficiently permeate through the viscous mucus and bind to villi, which triggers transcytosis-mediated transepithelial transport into blood circulation for tumor accumulation. The orally administered micelles deliver PTX to tumors, efficiently inhibiting the growth of HepG2 and patient-derived hepatocellular carcinoma xenografts and triple-negative breast tumors. These results demonstrate that OPDEA-based micelles may serve as an efficient oral nanomedicine for delivering other small molecules or even large molecules.

The aim of this study was to develop liver targeting galangin-loaded liposomes (Galangin-Liposomes) and evaluate their oral bioavailability. Box Behnken design was applied to optimize the formulation of Galangin-Liposomes by assessing encapsulation efficiency. The optimized Galangin-Liposomes were characterized by zeta potential, encapsulation efficiency, morphology, stability and in vitro release. Meanwhile, in vivo pharmacokinetics and tissue distributions were studied. Morphology of the selected Galangin-Liposomes revealed spherical and uniformly distributed nanoparticles with size of 74.67 ± 7.09 nm and encapsulation efficiency of 92.36 ± 2.71%. The formulation also significantly increased the extent of galangin release in vitro as well as its oral bioavailability (470.12%) in vivo. Furthermore, the tissue distribution studies further showed that the Galangin-Liposomes were enriched in the liver and exhibited better hepatoprotective effects in CCl4-intoxicated mice compared with the free galangin (p

[6]-Gingerol, one of the components of the rhizome of Ginger, has a variety of biological activities such as anticoagulant, antioxidative, antitumor, anti-inflammatory, antihypertensive, and so forth. However, as one of the homologous phenolic ketones, [6]-gingerol is insoluble in water which limits its applications. Herein, we prepared [6]-gingerol proliposomes through modified thin-film dispersion method, which was spherical or oval, and physicochemically stable with narrow size distribution. Surprisingly, in vitro release of [6]-gingerol loaded proliposome compared with the free [6]-gingerol was significantly higher and its oral bioavailability increased 5-fold in vivo. Intriguingly, its antitumor effect was enhanced in the liposome formulation. Thus, our prepared [6]-gingerol proliposome proved to be a novel formulation for [6]-gingerol, which significantly improved its antitumor effect.

Janus nanoparticles with an anisotropic feature concentrated multiple properties on a single carrier, providing synergistic effects. In this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-DMMA) were constructed with a tumor-targeting ligand (hyaluronic acid, HA) modified on the one side and a charge reversal group (2,3-dimethylmaleic anhydride, DMMA) on the other side. The drug release of HA-JMSN/DOX-DMMA was positively correlated with the acidity of the environment. The cytotoxicity and cell uptake of HA-JMSN/DOX-DMMA were superior to the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-DMMA involved the clathrin-mediated endocytosis (HA) and the micropinocytosis (DMMA) at the same time, which indicated that they both participated in the interaction between nanoparticles and tumor cells. After being injected intravenously in mice, the distribution of HA-JMSN/DOX-DMMA in tumor was enhanced significantly. The antitumor therapy study in vivo showed that HA-JMSN/DOX-DMMA inhibited tumor growth and improved the survival rate of tumor-bearing mice effectively. In general, HA-JMSN/DOX-DMMA could take the synergistic effect of active targeting and charge reversal to deliver drug in tumor cells and kill them efficiently, which was a promising antitumor nanodrug.

The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35 nm), negative zeta potential (- 10.67 ± 0.86 mV), and high encapsulation efficiency (98.17 ± 0.24%). The in vitro release study indicated that the release rates of the formulation were obviously higher in different release media (HCl, pH 1.2; PBS, pH 6.8; double-distilled water, pH 7.0) compared with the ISL solution. The oral bioavailability of the ISL-SMEDDS was enhanced by 4.71 times in comparison with the free ISL solution. More importantly, ISL-SMEDDS significantly reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in the model rats. Collectively, the prepared ISL-SMEDDS proved to be potential carriers for enhancing the solubility and oral bioavailability of ISL, as well as ameliorating its anti-hyperuricemic effect.

This study was designed to investigate the bioavailability and targeting of myricetrin-loaded ternary micelles modified with and without TPGS. The particle diameters of myricetrin-loaded micelles and myricetrin-loaded-TPGS micelle were 30.93 ± 1.34 nm and 26.42 ± 0.89 nm, respectively, while their respective encapsulation efficiencies (m/m, %) were 83.3 ± 1.08 and 93.8 ± 1.18. The release rate of myricetrin in the micellar system clearly exceeded the free myricetrin in the three media (pH 6.8 phosphate buffer, pH 1.2 HCl solution and double distilled water).

The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger (

：6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol&rsquo, s solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG2k-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2&ndash, fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.

The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger (Zingiber officinale Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00 ± 0.26 nm and 0.18 ± 0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.

An efficient and mild method for the allylic oxidation of cyclic alkenes employing molecular oxygen and tert-butyl hydroperoxide as the oxidant, copper-manganese oxides as heterogeneous catalyst under ambient temperature is proposed. The catalyst, which was prepared by co-precipitation and characterized, was evaluated oxidation of isolongifolene as a typical mode substrate. The catalyst showed a good catalytic activity and remained nearly the same after four cycles. The scope of the reaction was investigated with a variety of cyclic alkenes compounds.

6-Gingerol, an active herbal ingredient of ginger has various bioactivities such as anti-neurodegenerative disease, anti-inflammatory and so on. The aim of the present study was to enhance the oral bioavailability and brain distribution of 6-Gingerol via polymeric micelles. A polymeric micelles drug delivery system of 6-Gingerol consisting of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and Poly (ethylene glycol)-poly (ε-caprolactone) (PEG-PCL) was prepared via solvent injection method. The developed 6-Gingerol-loaded TPGS/PEG-PCL micelles (6-GTPMs) were characterized based on particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), drug loading (DL) and

Isoliquiritigenin (ISL) has a great variety of pharmacological effects especially liver cancer therapy, but its poor solubility, bioavailability and liver targeting have limited its clinical use. In order to solve the aforementioned shortcomings, the TPGS-modified proliposomes loaded with ISL (ISL-TPGS-PLP) was prepared in this study. ISL-TPGS-PLP was fabricated via thin-film dispersion method and was characterized by the appearance, particle size, zeta potential and morphology. HPLC was used to evaluate entrapment efficiency (EE), in vitro release and stability of ISL-TPGS-PLP single or combined while appropriate physicochemical parameters were measured with DLS. Meanwhile, the pharmacokinetics and tissue distribution were also studied after oral administration. The results demonstrated that ISL-TPGS-PLP had a mean size of 23.8 ± 0.9 nm, high EE of 97.33 ± 0.40%. More importantly, nearly 90% ISL was released from ISL-TPGS-PLP within 24 h while only 50% was released from ISL suspension. In the pharmacokinetics study, the area under the curve (AUC0-24h) of ISL-TPGS-PLP was 1.53 times higher than that of ISL suspension. The Tissue distribution study showed that the ISL released from ISL-TPGS-PLP was higher in the liver than the free ISL suspension. Altogether, ISL-TPGS-PLP could ameliorate the ISL solubility, bioavailability and liver targeting ability, suggesting that ISL-TPGS-PLP could serve as a promising nanocarrier for liver cancer therapy.

This study investigated effects of UV-B radiation and CaCl

[6]-Shogaol, an alkylphenol compound purified from the root and stem of ginger (Zingiber officinale), has attracted considerable interest due to its potential anticancer, antioxidative and antirheumatic properties. However, the oral bioavailability of [6]-shogaol has been severely limited because of its poor solubility. In this study, a significant quantity of high-purity [6]-shogaol (yield: 3.6%; purity: 98.65%) was extracted and encapsulated in solid lipid nanoparticles (SLNs) via high-pressure homogenization (encapsulation efficiency: 87.67%) to improve its solubility and oral bioavailability. The resulting [6]-shogaol-loaded solid lipid nanoparticles (SSLNs) were stable, homogeneous and well-dispersed. Its mean particle size and zeta potential were 73.56 ± 5.62 nm and −15.2 ± 1.3 mV, respectively. Importantly, the in vitro release profile and in vivo oral bioavailability of SSLNs were significantly improved compared with the free drug. Furthermore, the SSLNs could remarkably lower the uric acid level via inhibiting the activity of xanthine oxidase and reduce the production of interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α) in the hyperuricemia/gouty arthritis rat model, when compared to the free [6]-shogaol. Collectively, SLNs could serve as a promising drug delivery system to improve the oral bioavailability of [6]-shogaol for effective treatment of gouty arthritis.

In this study, an optimized nanostructured lipid carriers (NLCs) were developed and investigated for improving the solubility and oral availability of 6-Gingerol (6G), an active and abundant component of ginger with limited applications due to its poor water solubility plus oral biological availability. The NLCs consisted of a solid lipid (glyceryl monostearate), another liquid lipid (decanoyl/octanoyl-glycerides) and mixed surfactants (Tween 80 and Poloxamer 188), and was prepared by high pressure homogenization method. The optimal 6G-NLC formulation was evaluated through physical properties such as appearance, mean particle size, zeta potential, encapsulation efficiency, and in vitro drug release, alongside techniques viz., transmission electron microscopy (TEM), differential scanning calorimetry (DSC), as well as powder X-ray diffraction (XRD). Pharmacokinetics were also evaluated in rats. The 6G-NLCs prepared with optimal formulation exhibited a homogenous spherical shape with mean particle size and zeta potential of 63.59 ± 5.54 nm and − 12.18 ± 1.06 mV. Encapsulation efficiency and drug loading were 76.71 ± 1.11 and 1.17 ± 0.35%, respectively. In vitro release profile of 6G from NLCs was sustained and fitted with Weibull equation. After oral administration of the 6G-NLCs, drug concentrations in serum, MRT, and AUC0-t were significantly higher as compared with the free 6G suspension. All these results indicated that the developed NLC formulation could be effective and promising drug carriers to improve the water solubility of 6G while sustaining the drug release as well as prolonging in vivo acting time of the drug coupled with oral bioavailability enhancement.

In this present study, we investigated the anti-hyperuricemic and anti-gouty arthritis effect of a puried water-soluble polysaccharide (LJP-1) obtained from Lonicera japonica. A series of characterization of the purified polysaccharide were carried out in this paper. Monosaccharide analysis showed that LJP-1 composed of glucuronic acid, glucose, galactose, arabinose, and xylose at the ratio of 2.43:1:2.09:1.95:1.96, respectively. The estimated molecular weight of LJP-1 was 17.5 kDa. LJP-1 belonged to pyranose and possessed α- and β -glycosidic configurations. Congo red test showed that LJP-1 had a spatial triple helix structure. In pharmacodynamic experiments, the anti-hyperuricemic activity of LJP-1 was studied using hyperuricemic SD rat model induced via potassium oxonate and hypoxanthine. The result showed that LJP-1 could obviously decrease the serum uric acid level and suppress xanthine oxidase (XOD) activity. Moreover, in the gouty arthritis model established by sodium urate crystals, the degree of swelling of the ankle joint, IL-1β, IL-6, TNF-α and COX-2-related inflammatory factors levels in murine serum all declined. Taken together, these results demonstrated that LJP-1 has anti-gouty arthritis effect. Therefore, LJP-1 could serve as a promising candidate for developing novel natural anti-gouty agent.

Myricitrin has many pharmacological effects, such as anti-inflammation, liver protection and anti-oxidation. However, its clinical application is limited by poor solubility and low oral bioavailability. The preparation of myricitrin-loaded proliposomes (MPs) was achieved via the combination of thin-film dispersion technique and freeze-drying method. The in vitro release of MPs compared with free myricitrin was measured in different dissolution media while the pharmacokinetic study was also conducted in rats. Moreover, the uric acid-lowering activity of MPs was investigated in the hyperuricemic rat model. The prepared myricitrin appeared to be spherical. Notably, compared with the free myricitrin, the cumulative release in vitro and in vivo oral bioavailability of MPs were markedly increased. Besides, the MPs could significantly lower the serum uric acid level as well as ameliorate liver and kidney damage in hyperuricemic rats compared with the model group. Therefore, the present work supports the fact that MPs improved the oral bioavailability of myricitrin for the prospect of clinical application.

In this paper, first we consider a stochastic SIR epidemic model with information variable and saturated incidence rate and show that this model has a unique positive solution. We investigate the asymptotic behavior of the solution. Second we study a stochastic SIR epidemic model under regime switching, we show that the model is stochastically stable under certain condition and the moment average in time of the model solution is bounded. Finally, we give some numerical simulations to illustrate our findings.

ObjectivesThis study aimed to identify factors that influence people’s willingness to volunteer and participation in emergency volunteering in northern China.Design/SettingThis study was conducted in Heilongjiang province in September and October 2014 using a mixed methods approach, which included a cross-sectional questionnaire survey on community residents and in–depth interviews with community residents and relevant organisational managers and officials in relation to emergency responses. A stratified cluster sampling strategy was employed to select questionnaire respondents.Participants2686 respondents completed the questionnaire survey; 19 key informants were interviewed.Primary and secondary outcome measuresWillingness to volunteer was the major concern of this study. Self-reported past experience of the participants in emergency volunteering served as a secondary outcome.Results65.7% of respondents were willing to volunteer in emergencies. 24.3% of respondents had participated in emergency actions. Higher levels of willingness to volunteer and participation in volunteering were found in those who resided in rural areas (OR=1.308 (1.064 to 1.608) for willingness; OR=1.518 (1.208 to 1.908) for participation), had stronger community attachment (OR=1.720 (1.429 to 2.069) for willingness; OR=1.547 (1.266 to 1.890) for participation), had higher recognition of responsibility (OR=1.981 (1.498 to 2.619) for willingness; OR=1.517 (1.177 to 1.955) for participation), demonstrated preparedness behaviour (OR=1.714 (1.424 to 2.064) for willingness; OR=1.391 (1.151 to 1.681) for participation) and were covered by injury insurance (OR=1.335 (1.102 to 1.619) for willingness; OR=1.822 (1.500 to 2.214) for participation). The in-depth interviews revealed that an inappropriate policy environment and poor volunteer organisational management were major barriers for converting willingness into actions.ConclusionA relatively high level of willingness to volunteer in emergencies in northern China is associated with a range of individual, community and institutional factors. Efforts should be made to translate willingness into effective contributions to the emergency response system. This can be done through improving policies, regulations, coordination mechanisms and volunteer training and support.