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Reconstructing historical forest fire risk in the non-satellite era using the improved forest fire danger index and long short-term memory deep learning-a case study in Sichuan Province,southwestern China

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Forest Ecosystems 2024年第1期11卷 87-99页

作者： Yuwen Peng Huiyi Su Min Sun mingshi Li Co-Innovation Center for Sustainable Forestry in Southern China Nanjing Forestry UniversityNanjing 210037China College of Forestry Nanjing Forestry UniversityNanjing 210037China

Historical forest fire risk databases are vital for evaluating the effectiveness of past forest management approaches,enhancing forest fire warnings and emergency response capabilities,and accurately budgeting potential carbon emissions resulting from fires.However,due to the unavailability of spatial information technology,such databases are extremely difficult to build reliably and completely in the non-satellite era.This study presented an improved forest fire risk reconstruction framework that integrates a deep learning-based time series prediction model and spatial interpolation to address the challenge in Sichuan Province,southwestern China.First,the forest fire danger index(FFDI)was improved by supplementing slope and aspect information.We compared the performances of three time series models,namely,the autoregressive integrated moving average(ARIMA),Prophet and long short-term memory(LSTM)in predicting the modified forest fire danger index(MFFDI).The bestperforming model was used to retrace the MFFDI of individual stations from 1941 to 1970.Following this,the Anusplin spatial interpolation method was used to map the distributions of the MFFDI at five-year intervals,which were then subjected to weighted overlay with the distance-to-river layer to generate forest fire risk maps for reconstructing the forest fire danger database.The results revealed LSTM as the most accurate in fitting and predicting the historical MFFDI,with a fitting determination coefficient(R^2)of 0.709,mean square error(MSE)of0.047,and validation R^2 and MSE of 0.508 and 0.11,respectively.Independent validation of the predicted forest fire risk maps indicated that 5 out of 7 historical forest fire events were located in forest fire-prone areas,which is higher than the results determined from the original FFDI(2 out of 7).This proves the effectiveness of the improved MFFDI and indicates a high level of reliability of the historical forest fire risk reconstruction method proposed in this study.

关键词： Forest fire risk reconstruction MFFDI Time series models LSTM ARIMA Prophet Anusplin

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Nanomaterial Assisted Exosome Analysis Using Mass Spectrometry

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Chemical Research in Chinese Universities 2024年第2期40卷 237-254页

作者： ZHANG Yi ZHOU Bokai LI Qiuning JIN mingshi BAI Yu Beijing National Laboratory for Molecular Sciences Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing100871P.R.China Department of Chemistry Yanbian UniversityYanji133002P.R.China

Exosomes,extracellular vesicles(EVs)that play crucial roles in biological processes,have emerged as attractive targets for noninvasive disease diagnosis and monitoring.Mass spectrometry(MS)offers high sensitivity,high throughput,and excellent qualification and quantification capacity,which is the ideal approach for exosome analysis.Nanomaterials’unique physiochemical properties,controllable morphology,and large surface area make them promising in biological sample pretreatment and detection.They contributed diverse functions to the exosome MS analysis,encompassing substrates for exosome isolation and cargos enrichment,matrices for laser desorption/ionization(LDI),read-out signals and supporters for signal amplification strategies,etc.In this review,recent progress in the applications of nanomaterial in the exosome MS analysis was summarized and a comprehensive discussion on the challenges and perspectives was proposed for the development of an advancing analysis approach of exosomes for the accurate diagnosis and monitoring of diseases.

关键词： Exosome Nanomaterial Enrichment Matrix Mass spectrometry

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Evaluating the pharmacokinetics of intrapulmonary administered ciprofloxacin solution for respiratory infections using in vivo and in silico PBPK rat model studies

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Chinese Chemical Letters 2023年第1期34卷 230-234页

作者： Changzhi Shi Jelisaveta Ignjatovic Junwei Wang Yi Guo Li Zhang Sandra Cvijic Dongmei Cun mingshi yang Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutical Technology and Cosmetology University of Belgrade-Faculty of PharmacyBelgrade 11221Serbia Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen DK-2100Denmark

Respiratory antibiotics have been proven clinically beneficial for the treatment of severe lung infections such as Pseudomonas aeruginosa.Maintaining a high local concentration of inhaled antibiotics for an extended time in the lung is crucial to ensure an adequate antimicrobial efficiency.In this study,we aim to investigate whether an extended exposure of ciprofloxacin(CIP),a model fluoroquinolone drug,in the lung epithelial lining fluid(ELF)could be achieved via a controlled-release formulation strategy.CIP solutions were intratracheally instilled to the rat lungs at 3 different rates,i.e.,T0h(fast),T2h(medium),and T4h(slow),to mimic different release profiles of inhaled CIP formulations in the lung.Subsequently,the concentration-time profiles of CIP in the plasma and the lung ELF were obtained,respectively,to determine topical exposure index(ELF-Plasma AUC Ratio,EPR).The in silico PBPK model,validated based on the in vivo data,was used to identify the key factors that influence the disposition of CIP in the plasma and lungs.The medium and slow rates groups exhibited much higher EPR than that fast instillation group.The ELF AUC of the medium and slow instillation groups were about 200 times higher than their plasma AUC.In contrast,the ELF AUC of the fast instillation group was only about 20 times higher than the plasma AUC.The generated whole-body PBPK rat model,validated by comparison with the in vivo data,revealed that drug pulmonary absorption rate was the key factor that determined pulmonary absorption of CIP.This study suggests that controlled CIP release from inhaled formulations may extend the exposure of CIP in the ELF post pulmonary administration.It also demonstrates that combining the proposed intratracheal installation model and in silico PBPK model is a useful approach to identify the key factors that influence the absorption and disposition of inhaled medicine.

关键词： Inhalation antibiotics Ciprofloxacin Controlled release PBPK modeling Lung infections

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The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1460-1472页

作者： Jingyi Li Yaqi Zhang Miaorong Yu Aohua Wang Yu Qiu Weiwei Fan Lars Hovgaard mingshi yang Yiming Li Rui Wang Xiuying Li Yong Gan School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Oral Formulation Development Novo Nordisk A/SMacilov 2760Denmark Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen 2100Denmark University of Texas at Dallas RichardsonTX 75080USA NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores.In this study,we demonstrate that the upregulated intestinal transporter(PCFT),which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats,mediates the uptake of the folic acid-grafted nanoparticles(FNP).Specifically,the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway,Golgi-targeting pathway and basolateral exocytosis,featuring a high oral insulin bioavailability of 14.4%in the diabetic rats.Conversely,in cells with relatively low PCFT expression,the positive surface charge contributes to the cellular uptake of FNP,and FNP are mainly degraded in the lysosomes.Overall,we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway.This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.

关键词： Ligand-modified nanoparticles Transporter Proton-coupled folate transporter Expression level Endocytosis Intracellular trafficking Diabetes Oral insulin delivery

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Influence of solvent mixtures on HPMCAS-celecoxib microparticles prepared by electrospraying

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Asian Journal of Pharmaceutical Sciences 2018年第6期13卷 584-591页

作者： Adam Bohr Yingya Wang Moritz Beck-Broichsitter mingshi yang Department of Pharmacy Faculty of Health and Medical SciencesUniversity of Copenhagen Department of Pharmaceutics and Biopharmacy Philipps-Universitat Chemical and Pharmaceutical Development Bayer AG Wuya College of Innovation Shenyang Pharmaceutical University

Hypromellose acetate succinate(HPMCAS) microparticles containing the poorly-water soluble drug celecoxib(CEL) were prepared by electrospraying intended for oral drug delivery. Various solvent mixtures with different solubility for CEL and HPMCAS were used to induce changes in the polymer structural conformation of the microparticles. The performance of the prepared microparticles was evaluated by studying the solid state from, particle size and morphology, radial drug distribution and drug release. CEL was amorphous in all electrosprayed HPMCAS microparticles. The particle size and morphology was dependent on the solubility of HPMCAS in the solvent mixture used with poorer solvents resulting in smaller microparticles with rougher appearance. The CEL distribution on the particles surface was relatively homogeneous and similar for all microparticles. Drug release from the microparticles was observed at a higher rate depending on the solubility of HPMCAS in the solvent used for electrospraying, and in all cases an at least 4-fold higher rate was observed compared with the crystalline drug. Drug precipitation from the supersaturated solution was inhibited by HPMCAS for all microparticles based on its parachute effect while crystalline CEL did not reach supersaturation. This study demonstrated that electrospraying can be used to produce microparticles with tailored properties for pharmaceutical application by adjusting solvent selection.

关键词： Celecoxib Electrospraying Hypromellose acetate succinate Oral drug delivery Polymeric microparticles Solvent mixture

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Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2565-2584页

作者： Yi Guo Hriday Bera Changzhi Shi Li Zhang Dongmei Cun mingshi yang Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen 2100Denmark

Pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma,chronic obstructive pulmonary diseases and respiratory infections,and systemic diseases such as diabetes.Most inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are transit.The inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration,but also enhance the clinical benefits to the patients with improved therapeutic outcomes.This article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled medicines.It starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure,which is followed by recent advances in various strategies to overcome these barriers.Finally,the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized.

关键词： Pulmonary drug delivery Pulmonary clearance pathways Pulmonary exposure Pharmaceutical strategies Inhaled sustained release formulations Local lung diseases Systemic diseases Pulmonary safety

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Special issue on “Formulation strategies and manufacturing technologies to enhance non-invasive drug delivery”

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Asian Journal of Pharmaceutical Sciences 2018年第6期13卷 505-506页

作者： Korbinian Lobmann Adam Bohr mingshi yang 不详

Oral dosage forms including tablets and capsules are themost commonly used drug products. For some poorly water-soluble and poorly permeable drugs injectable dosage formscan be used to circumvent the challenges of poo... 详细信息

关键词： non-invasive drug poor

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Sustained release donepezil loaded PLGA microspheres for injection:Preparation,in vitro and in vivo study

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Asian Journal of Pharmaceutical Sciences 2015年第5期10卷 405-414页

作者： Wenjia Guo Peng Quan Liang Fang Dongmei Cun mingshi yang Department of Pharmaceutics Shenyang Pharmaceutical University110016China Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenUniversitetsparken 22100 CopenhagenØDenmark

The purpose of this study was to develop a PLGA microspheres-based donepezil(DP)formulation which was expected to sustain release of DP for one week with high encapsulation efficiency(EE).DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method.The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size,morphology,drug loading and EE,physical state of DP in the matrix and in vitro and in vivo release behavior.DP microspheres were prepared successfully with average diameter of 30m,drug loading of 15.92±0.31%and EE up to 78.79±2.56%.Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface.Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres.The Tg of PLGA was increased with the addition of DP.The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model,which suggested the diffusion governing release mechanism.After single-dose administration of DP microspheres via subcutaneous injection in rats,the plasma concentration of DP reached peak concentration at 0.50 d,and then declined gradually,but was still detectable at 15 d.A good correlation between in vitro and in vivo data was obtained.The results suggest the potential use of DP microspheres for treatment of Alzheimer’s disease over long periods.

关键词： Donepezil PLGA Sustained release Microspheres In vitro and in vivo correlation

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Formulation and in vitro characterization of long-acting PLGA injectable microspheres encapsulating a peptide analog of LHRH

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Journal of Materials Science & Technology 2021年第4期63卷 133-144页

作者： Chengqian Zhang Lan Wu Anjin Tao Hriday Bera Xing Tang Dongmei Cun mingshi yang Wuya College of Innovation Shenyang Pharmaceutical UniversityWenhua Road 103110016 ShenyangChina Hybio Pharmaceutical Co. Ltd.Keji C.2nd Road 37518057 ShenzhenChina School of Pharmacy Shenyang Pharmaceutical UniversityWenhua Road 103110016 ShenyangChina Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenUniversitetsparken 22100 CopenhagenDenmark

The present study aimed to formulate triptorelin acetate(TA)into poly(D,L-lactic-co-glycolic)acid(PLGA)based injectable sustained-release microspheres(TA-PLGA-MS)by usingdouble emulsion solvent extraction/evaporation(DESE)technique and investigate the effects of various material attributes and process parameters on the quality attributes such as size,shape,surface morphology,encapsulation efficiency(EE)and in vitro release behavior of these microspheres.Variable compositions of the outer water phase,type of the organic solvents,volume ratios of inner water phase to oil phase,PLGA concentrations,and the powers for emulsification in the preparation of the microspheres showed an influence on their quality attributes.An optimal formulation(F-2)obtained from this univariate approach possess an excellent EE value of 63.5%±3.4%and an average volumetric particle size of 35.3±1.8μm.This formulation was further accomplished with different solidification rates assisted by variable incubation temperatures,which exhibited an impact on the shape/surface and inner morphology of the microspheres.The resultant microspheres also displayed different in vitro release patterns.The matrices processed with a high incubation temperature conferred the fastest and the most complete drug release profile over the period of 63 days.Thus,the solidification rate could be identified as one of the critical process parameters that affected the quality of the PLGA based injectable microspheres specifically designed for the prolonged delivery of TA.

关键词： sustained release PLGA

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Spray drying of fenofibrate loaded nanostructured lipid carriers

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Asian Journal of Pharmaceutical Sciences 2016年第4期11卷 507-515页

作者： Dengning Xia Neha Shrestha Jacco van de Streek Huiling Mu mingshi yang Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenUniversitetsparken2Copenhagen2100Denmark Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai201203China Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical UniversityShenyang110016China Key Laboratory of Smart Drug Delivery Ministry of EducationFudan UniversityShanghai201203China

The conversion of aqueous dispersion of nanostructured lipid carriers(NLCs) into dry powder by spray drying could be a useful approach to render NLCs with better physical chemical stability than the aqueous dispersion. In this study, aqueous NLC dispersion containing fenofibrate was converted into dry, easily reconstitutable powder using spray drying. A central composite face centered design(CCFD) was used to investigate the influence of the ratio of lipid to protectant(mannitol and trehalose) and crystallinity of spray-dried powder on the particle size, yield and residual moisture content of the dried powder. A linear relationship(R2= 0.9915) was established between the crystalline content of the spray-dried powders against the ratio of mannitol to trehalose from 3:7 to 10:0(w/w). Spray drying of NLC aqueous dispersion using a mannitol and trehalose mixture resulted in an increase in particle size of the NLCs after reconstitution in water as compared to that in the initial aqueous dispersion. The decrease in crystallinity of the dry powder by reducing the ratio of mannitol to trehalose could improve the reconstitution of the NLCs in water. However the yield and residual moisture content of dry powder decreased with an increase in the ratio of mannitol to trehalose. Lipid nanoparticles were able to retain the drug incorporation and the prolonged drug release profile after spray drying. The experimental model was robust, and suggested that spray drying is a viable technique for the conversion of NLCs into dry powder.

关键词： Fenofibrate Nanostructured lipid carriers Spray drying Design of experiments Central composite face-centered design

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