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| 1 | Manganese salts function as potent adjuvants显示文摘Aluminum-containing adjuvants have been used for nearly 100 years to enhance immune responses in billions of doses of vaccines.To date,only a few adjuvants have been approved for use in humans,among which aluminum-containing adjuvants are the only ones widely used.However,the medical need for potent and safe adjuvants is currently continuously increasing,especially those triggering cellular immune responses for cytotoxic T lymphocyte activation,which are urgently needed for the development of efficient virus and cancer vaccines.Manganese is an essential micronutrient required for diverse biological activities,but its functions in immunity remain undefined.We previously reported that Mn^(2+) is important in the host defense against cytosolic dsDNA by facilitating cGAS-STING activation and that Mn^(2+)alone directly activates cGAS independent of dsDNA,leading to an unconventional catalytic synthesis of 2′3′-cGAMP.Herein,we found that Mn^(2+) strongly promoted immune responses by facilitating antigen uptake,presentation,and germinal center formation via both cGAS-STING and NLRP3 activation.Accordingly,a colloidal manganese salt(Mn jelly,MnJ)was formulated to act not only as an immune potentiator but also as a delivery system to stimulate humoral and cellular immune responses,inducing antibody production and CD4^(+)/CD8^(+)T-cell proliferation and activation by either intramuscular or intranasal immunization.When administered intranasally,MnJ also worked as a mucosal adjuvant,inducing high levels of secretory IgA.MnJ showed good adjuvant effects for all tested antigens,including T cell-dependent and T cell-independent antigens,such as bacterial capsular polysaccharides,thus indicating that it is a promising adjuvant candidate. | Rui Zhang Chenguang Wang Yukun Guan Xiaoming Wei Mengyin Sha Mengran Yi Miao Jing Mengze Lv Wen Guo Jing Xu Yi Wan Xin-Ming Jia Zhengfan Jiang | 2021 | Cellular & Molecular Immunology2021，18，5： | 7 |
| 2 | Application of hot melt extrusion to enhance the dissolution and oral bioavailability of oleanolic acid显示文摘The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test.The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64(OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture(PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC(P < 0.05) and Cmax(P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA. | Nannan Gao Mengran Guo Qiang Fu Zhonggui He | 2017 | Asian Journal of Pharmaceutical Sciences2017，12，1： | 5 |
| 3 | Comparison of solid dispersion and nanosuspension for improvement of drug absorption显示文摘Currently, drug discovery technology is heavily dependent oncombinatorial chemistry and high throughput screening, resultingin more and more poorly water-soluble drugs, eitherclass II (low solubility and high permeability) or IV (low solubilityand low permeability) in the standard biopharmaceuticalclassification system. Owing to the importance of solubility/dissolution for oral absorption, formulation scientists face agreat challenge.Thus, strategies have been proposed to improvethe solubility and dissolution rate. Among these approaches,solid dispersion [1] and nanosuspension [2] are the most usuallyused. However, which one is better for improving the in vitrodissolution and in vivo bioavailability? | Qiang Fu Mengran Guo Zhonggui He | 2016 | Asian Journal of Pharmaceutical Sciences2016，11，1： | 1 |
| 4 | A lipid-based LMP2-mRNA vaccine to treat nasopharyngeal carcinoma显示文摘Nasopharyngeal carcinoma(NPC)is a serious and highly invasive epithelial malignancy that is closely associated with Epstein‒Barr virus(EBV).Due to the lack of therapeutic vaccines for NPC,we selected EBV latent membrane protein 2(LMP2)as a preferable targeting antigen to develop a lipid-based LMP2-mRNA(mLMP2)vaccine.Full-length mLMP2 expressing LMP2 was first synthesized using an in vitro transcription method and then encapsulated into(2,3-dioleacyl propyl)trimethylammonium chloride(DOTAP)-based cationic liposomes to obtain the mRNA vaccine(LPX-mLMP2).The cell assays showed that the antigenpresenting cells were capable of highly efficient uptake of LPX-mLMP2 and expression of LMP2.LMP2 could subsequently be presented to form the peptide-major histocompatibility complex(pMHC).Furthermore,LPX-mLMP2 could accumulate in the spleen,express antigens,promote the maturation of dendritic cells and stimulate antigen-specific T-cell responses in vivo.It dramatically inhibited the tumor growth of the LMP2-expressing tumor model after three doses of vaccination.Additionally,the proliferation of antigen-specific T cells in the tumor site made a good sign for the promise of mRNA vaccines in virus-induced cancer.Overall,we provided a newly developed antigen-encoding mRNA vaccine with advantages against NPC.We also demonstrated that mRNA vaccines are attractive candidates for cancer immunotherapy. | Mengran Guo Xing Duan Xingchen Peng Zhaohui Jin Hai Huang Wen Xiao Qian Zheng Yongqi Deng Na Fan Kepan Chen Xiangrong Song | 2023 | Nano Research2023，16，4： | 1 |
| 5 | Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine显示文摘The extraordinary advantages associated with mRNA vaccines,including their high efficiency,relatively low severity of side effects,and ease of manufacture,have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers.Nevertheless,most mRNA delivery carriers have many disadvantages,such as high toxicity,poor biocompatibility,and low efficiency in vivo,which have hindered the widespread use of mRNA vaccines.To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier,a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate(SA).Intriguingly,the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA,which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA.In addition,we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting.Finally,we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E.G7-OVA tumor-bearing mice,dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect.Therefore,we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects. | Xing Duan Yi Zhang Mengran Guo Na Fan Kepan Chen Shugang Qin Wen Xiao Qian Zheng Hai Huang Xiawei Wei Yuquan Wei Xiangrong Song | 2023 | Acta Pharmaceutica Sinica B2023，13，3： | 1 |
| 6 | Oral nanoparticles containing naringenin suppress atherosclerotic progression by targeting delivery to plaque macrophages显示文摘Atherosclerosis is the main cause of ischemic stroke and myocardial infarction diseases.Nanoparticles have shown unique benefits for atherosclerosis treatment by targeting the lesional macrophages of plaques.However,most of the nanocarriers are administered intravenously,which is inconvenient and may cause complications.Herein,we developed an oral lipid-polymer based nanoparticles(FA-LNPs)decorated with folic acid,which can not only effectively overcome intestinal mucosal-epithelial barrier by increasing the transmembrane transport through intestinal epithelial and the accumulation in Peyer’s patches but also actively target to the aortic plaque sites and accumulate in lesional macrophages.Subsequently,naringenin(Nrg),one of the antiinflammation drugs,was designed to be the oral nanomedicine(FA-LNPs/Nrg)for the first time via the encapsulation of FALNPs.FA-LNPs/Nrg presented highly anti-atherosclerotic efficacy.After the atherosclerotic ApoE−/−mice were treated by FALNPs/Nrg via oral administration for three months,the aortic lesion area,plaque area,and necrotic core area of the aortic root were significantly decreased.Meanwhile,the lipid-related blood parameters recovered to normal levels.Our study provides a promising approach to atherosclerosis treatment based on the novel oral targeting delivery system. | Mengran Guo Zhongshan He Zhaohui Jin Lingjing Huang Jingmei Yuan Shugang Qin Xinchun Wang Lili Cao Xiangrong Song | 2023 | Nano Research2023，16，1： | 0 |
| 7 | In operando-formed interface between silver and perovskite oxide for efficient electroreduction of carbon dioxide to carbon monoxide显示文摘Electrochemical carbon dioxide(CO_(2))reduction(ECR)is a promising technology to produce valuable fuels and feedstocks from CO_(2).Despite large efforts to develop ECR catalysts,the investigation of the catalytic performance and electrochemical behavior of complex metal oxides,especially perovskite oxides,is rarely reported.Here,the inorganic perovskite oxide Ag-doped(La_(0.8)Sr_(0.2))_(0.95)Ag_(0.05)MnO_(3-δ)(LSA0.05M)is reported as an efficient electrocatalyst for ECR to CO for the first time,which exhibits a Faradaic efficiency(FE)of 84.3%,a remarkable mass activity of 75Ag^(-1)(normalized to the mass of Ag),and stability of 130 h at a moderate overpotential of 0.79 V.The LSA0.05M catalyst experiences structure reconstruction during ECR,creating the in operando-formed interface between the perovskite and the evolved Ag phase.The evolved Ag is uniformly distributed with a small particle size on the perovskite surface.Theoretical calculations indicate the reconstruction of LSA0.05M during ECR and reveal that the perovskite-Ag interface provides adsorption sites for CO_(2) and accelerates the desorption of the*CO intermediate to enhance ECR.This study presents a novel high-performance perovskite catalyst for ECR andmay inspire the future design of electrocatalysts via the in operando formation of metal-metal oxide interfaces. | Xinhao Wu Yanan Guo Yuxing Gu Fenghua Xie Mengran Li Zhiwei Hu Hong-Ji Lin Chih-Wen Pao Yu-Cheng Huang Chung-Li Dong Vanessa KPeterson Ran Ran Wei Zhou Zongping Shao | 2023 | Carbon Energy2023，5，4： | 0 |
| 8 | Transient Simulation and Optimization of Regional Integrated Energy System显示文摘A modeling method of regional integrated energy system based on bus method and transient simulation is proposed,and the system optimization is based on the dynamic balance of supply and demand in the whole year energy supply cycle.A CCHP systemof gas turbine coupled with ground source heat pump and electric refrigeration unit is constructed.The energy relationship of the systemis described by bus structure,and the transient calculationmodel is built on TRNSYS platform.The weighted sum of annual total cost saving rate,primary energy saving rate and environmental pollutant shadow cost saving rate is taken as the optimized objective function,and on the basis of annual dynamic balance,the Hooke-Jeeves algorithm is used for optimization of the system configuration.A complex commercial area in Beijing is taken as an example,and different weighting coefficients are set for optimization of the system configuration.The results show that,from the perspective of economy,environmental benefit and primary energy consumption,performance of the system increases and then decreases with rise of gas turbine power;under the simulated cooling/heating load,the maximum number of optimum configuration is seen in the combination of 35 kW gas turbine+723 kW GSHP and 1178 kW electric chiller;in comparison with traditional distributed system,the annual cost saving rate,primary energy saving rate and environmental pollutant shadow cost saving rate of the system are 29.4%,49.6%and 58.2%,respectively. | Xueqin Tian Mengran Cui Tong Xu Jinfei Sun Xinlei Wang Jiangxiang Guo De-Gejirifu Na Wang | 2022 | Energy Engineering2022，119，3： | 0 |
| 9 | Simple Analysis on Change Features of Total Solar Radiation in Sanjiang Plain显示文摘The yearly,quarterly,monthly and daily change tendencies of total solar radiation at Jiamusi station of Sanjiang Plain were analyzed by statistical approach such as linear tendency estimate with its hourly ground meteorological observation data during 1986 to 2015.The research results indicated that the yearly tendency rate of total solar radiation was increasing obviously,with the velocity of 114.30 MJ/(m2·10 a),while the yearly total solar radiation was 3 667.28-4 935.88 MJ/m^2,and that of March to September was higher than the average.The summer total solar radiation was the most,followed by spring,and that of all the seasons increased except autumn which decreased.The daily total solar radiation increased rapidly from the last ten days of January and reached the peak at the end of June,while it plummeted from the beginning of September to the middle ten days of November,then tended to be gentle.The amount of 5-year total solar radiation was less after 1980s while it was more before1990s,and the total solar radiation was decreasing from 1996 to 2005 but on the contrary it kept increasing in recent ten years.Over the years the earliest record of solar radiation appeared at 05:00 and the latest at 20:00,and the daily variation of the hourly solar radiation got a normal distribution centered on 12:00 to 13:00. | Na Hongyan Hou Fang Lv Hongyu Guo Bing Zhao Mengran | 2017 | Meteorological and Environmental Research2017，8，1： | 0 |
| 10 | Dynamic Simulation and Performance Analysis on Multi-Energy Coupled CCHP System显示文摘Although the Combined Cooing,Heating and Power System(hereinafter referred to as“CCHP”)improves the capacity utilization rate and energy utilization efficiency,single use of CCHP system cannot realize dynamic matching between supply and demand loads due to the unbalance features of the user’s cooling and heating loads.On the basis of user convenience and wide applicability of clean air energy,this paper tries to put forward a coupled CCHP system with combustion gas turbine and ASHP ordered power by heat,analyze trends of such parameters as gas consumption and power consumption of heat pump in line with adjustment of heating load proportion of combustion gas turbine,and optimize the system ratio in the method of annual costs and energy environmental benefit assessment.Based on the analysis of the hourly simulation and matching characteristics of the cold and hot load of the 100 thousand square meter building,it is found that the annual cost of the air source heat pump is low,but the energy and environmental benefits are poor.It will lead to 6.35%shortage of cooling load in summer.Combined with the evaluation method of primary energy consumption and zero carbon dioxide emission,the coupling system of CHHP and air source heat pump with 41%gas turbine load ratio is the best configuration.This system structure and optimization method can provide some reference for the development of CCHP coupling system. | Xueqin Tian Jinfei Sun Tong Xu Mengran Cui Xinlei Wang Jianxiang Guo De-gejirifu Na Wang | 2022 | Energy Engineering2022，119，2： | 0 |
| 11 | Preparation and in vitro Evaluation of Salidroside Nanoparticle显示文摘[Objectives]To use poly(lactic-co-glycolic acid)(PLGA)nanoparticles to improve the bioavailability and brain entrance capability of Salidroside(Sal).[Methods]An emulsion solvent evaporation approach was used to create PLGA nanoparticles(Sal-NP).The preparation parameters were optimized using a single factor experiment.The particle size and zeta potential were determined using the laser particle analyzer,and the morphology of the nanoparticles was observed using transmission electron microscopy.The encapsulation efficiency and drug loading were determined using HPLC.Subsequently,the in vitro drug release was determined using a dynamic dialysis method,and the cellular uptake and cytotoxicity were determined using the bEnd3 cell model.[Results]The ultrasonic time and power for preparing Sal-NP were 6 min and 100 W,respectively.The size of the nanoparticles was 162.0±74.86 nm,and the morphology of Sal-NP was spherical like.After 48 h,the cumulative release of Sal-NP was 62%,indicating that Sal showed a controlled release property in Sal-NP.Cellular uptake study showed that the PLGA nanoparticles remarkably increased the internalization than control group(P<0.001).In addition,Sal-NPs were non-toxic to cells at concentrations ranging from 12.5 to 100μM.[Conclusions]PLGA nanoparticles is promising to be exploited in Alzheimer's disease research due to the increasing absorption and controlled release advantages for Sal. | Yue FENG Wei ZOU Mengran GUO Xing LAN Lili HE | 2022 | Medicinal Plant2022，13，2： | 0 |
| 12 | Preparation, optimization and in vitro–in vivo investigation for capsules of the choline salt of febuxostat显示文摘The objective of the present study was to exhibit the enhanced water-solubility and in vivo oral absorption when febuxostat(FXT) became the salt formation of choline. The formation of the choline salt of febuxostat was confirmed by X-ray powder diffraction, infrared spectroscopy analysis and differential scanning calorimetry. The direct filling method was used to develop a capsule formulation. Cellactose 80 was used as the filler due to its good fluidity, while cross-linked polyvinylpyrrolidone(PVPP) and magnesium stearate(MS) were used as the disintegrant and lubricant, respectively. Then the in vitro release of the formulation was carried out in five different dissolution media including HCl solution(pH 1.2),acetate buffer(pH 4.5), phosphate buffer(pH 6.8 and pH 7.2) and water. Evident improvement of release for choline febuxostat(CXT) was presented in water while the dissolution degree was decreased for CXT in the medium of phosphate buffer(pH 6.8) in comparison with FXT. Furthermore, the pharmacokinetics of CXT was studied in rats using UPLC-MS/MS compared with FXT. The data acquired illustrated that AUC0-24 h of CXT and FXT were22,245.96 ± 7342.92 μg·h/l and 12,249.70 ± 2024.04 μg·h/l, respectively. The relative bioavailability of CXT to FXT was about 181.6% and the P value of AUC0-24 h was less than 0.05. It showed significant difference between the two drugs after oral administration. In conclusion, the water-solubility and oral bioavailability were both improved remarkably for the choline salt of febuxostat and choline salinization was proved an effective way to increase the in vivo absorption for FXT. | Xuemei Han Wanpeng Qi Wenxiang Dong Mengran Guo Panqin Ma Jing Wang | 2016 | Asian Journal of Pharmaceutical Sciences2016，11，6： | 0 |
| 13 | A novel oral prodrug-targeting transporter MCT 1: 5-fluorouracil-dicarboxylate monoester conjugates显示文摘Monocarboxylate transporter 1(MCT1)is responsible for oral absorption of short-chain monocarboxylic acids from small intestine,hence,it’s likely to serve as an ideal design target for the development of oral prodrugs.However,potential application of MCT1 to facilitate the oral delivery is still unclear.Irregular oral absorption,poor permeability and bioavailability greatly limit the oral delivery efficiency of 5-fluorouracil(5-FU).Herein,we design three 5-FU-fatty acid conjugates targeting intestinal MCT1 with different lipophilic linkages.Interestingly,due to high MCT1 affinity and good gastrointestinal stability,5-FUoctanedioic acid monoester prodrug exhibited significant improvement in membrane permeability(13.1-fold)and oral bioavailability(4.1-fold)compared to 5-FU.More surprisingly,stability experiment in intestinal homogenates showed that 5-FU prodrugs could be properly activated to release 5-FU within intestinal cells,which provides an ideal foundation for the improvement of oral bioavailability.In summary,good gastrointestinal stability,high membrane permeability and appropriate intestinal cell bioactivation are the important factors for high-efficiency 5-FU oral prodrugs,and such work provides a good platform for the development of novel oral prodrugs targeting intestinal transporters. | Yixin Sun Dongyang Zhao Gang Wang Qikun Jiang Mengran Guo Qiming Kan Zhonggui He Jin Sun | 2019 | Asian Journal of Pharmaceutical Sciences2019，14，6： | 0 |
| 14 | Core-shell lipid-polymeric nanoparticles for enhanced oral bioavailability and antihypertensive efficacy of KY5 peptide显示文摘Hypertension is the leading risk factor for death and disability, and hypertensive patients always need long-term oral antihypertensive drugs. Some bioactive peptides that extracted from animals or plants have shown excellent advantages on antihypertension. However, the oral delivery of these peptides is always failure on account of instability and poor absorption in the gastrointestinal tract. Herein, we developed a core-shell lipid-polymeric nanoparticle for oral delivery of a highly efficient antihypertensive peptide KY5(KY5-CSs). KY5-CSs had a particle size of 216.7 ± 2.5 nm, with a narrow PDI of 0.07 ± 0.01.The zeta potential was-4.1 ± 0.1 m V. It exhibited good stability in 4 ℃ and possessed a controlled release behavior in gastrointestinal tract. The cellular uptake study proved that the lipid shell imparted unique capability of permeation across the mucus layer and internalization by Caco-2/HT-29 cells. In addition, KY5-CSs enhanced in situ intestinal absorption in SD rats. The pharmacokinetic studies and antihypertensive efficacy showed a superior oral absorption and antihypertensive effect of KY5-CSs than KY5-NPs. In conclusion, the core-shell lipid-polymeric nanoparticles will provide attractive potential for oral delivery of antihypertensive peptides. | Jingmei Yuan Mengran Guo Shengnan Zhao Jinhua Li Xinchun Wang Jian Yang Zhaohui Jin Xiangrong Song | 2023 | Chinese Chemical Letters2023，34，4： | 0 |
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