JOURNAL OF PHARMACEUTICAL SCIENCES
·
2023
·
IF 3.8
Ya Xu,Huiyang Li,Nan Sun,Bingmei Yao,Wenjin Dai,Jian Wang,Sujia Si,Shuo Liu,Liqun Jiang
Background High Altitude Pulmonary Edema (HAPE) seriously threatens the health of people at high altitudes. There are drug treatments for HAPE, and dry powder formulations (DPFs) represent a rapid and accessible delivery vehicle for these drugs. However, there are presently no reports on the inhalability of DPFs in low-pressure environments. Given the reduced atmospheric pressure typical at high altitudes, conventional DPFs might not be suitable for inhalation. Therefore, it is necessary to elucidate the deposition behaviors of dry powder in the respiratory tract at low pressure, as well as to improve their pulmonary deposition efficiency via adjustments to their formulation and design. Methods The effect of air pressure, inspiratory velocity, and particle properties (such as size, density, and aerodynamic diameter) on pulmonary deposition of DPFs was calculated by a computational fluid dynamics (CFD)-coupled discrete phase model. DPFs of various aerodynamic diameters were prepared by spray drying, and the inhalability of these DPFs in a low-pressure environment was evaluated in mice. Finally, a mouse model of HAPE was established, and the treatment of HAPE by nifedipine-loaded DPFs with small aerodynamic diameter was validated. Results CFD results showed that low pressure decreased the deposition of DPFs in the lungs. At 0.5 standard atmosphere, DPFs with aerodynamic diameter of ∼2.0 μm could not enter the lower respiratory tract; however, a decrease in the physical diameter, density, and, consequently, the aerodynamic diameter of the DPFs was able to enhance pulmonary deposition of these powders. To validate the CFD results, three kinds of dry powder with aerodynamic diameters of 0.66, 0.98, and 2.00 μm were prepared by spray drying. Powders with smaller aerodynamic diameter could be inhaled into the lungs of mice more effectively, and, consequently could ameliorate the progression of HAPE more effectively than conventional powders. These results were consistent with the CFD results. Conclusions Low atmospheric pressure can prevent the pulmonary deposition of DPFs at high altitudes. Compared with conventional DPFs, powders with smaller aerodynamic diameter can be effectively inhaled at these pressures and thus might be more suitable for the treatment the HAPE.
研究领域:
药剂学
·
呼吸病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FUEL
·
2024
·
IF 6.7
Hao Sun,Wugao Zhang,Yixuan Wang
CeO 2 nanoparticles are effective fuel additives that enhance fuel spray, atomization, and combustion characteristics due to their high catalytic activity and excellent thermal properties. When added to fuel, CeO 2 nanoparticles significantly improve in-cylinder combustion, and engine performance, and reduce pollutant emissions under normal engine operating conditions. Diesel engines encounter persistent challenges during cold starts at low temperatures and high altitudes. However, there is limited research on the effects of CeO 2 nanoparticles on ignition and combustion at low temperatures and cold start performance. This study aims to evaluate the impact of CeO 2 nanoparticles doping in diesel fuel on the cold start performance of diesel engines in high-altitude and low-temperature environments. Diesel fuel doped with CeO 2 nanoparticles at various concentrations was prepared using magnetic stirring and ultrasonication. The cold start performance of the test engine was assessed in an environmental chamber. This work investigated and evaluated the improvements of CeO 2 nanoparticles on cold start performance from three perspectives: general low-temperature conditions, high-altitude environments, and extreme low-temperature scenarios with diethyl ether premixing. Experimental results indicate that incorporating CeO 2 nanoparticles expanded the critical temperature required for a successful cold start from 0 °C to −5 °C. At high altitudes, the addition of CeO 2 nanoparticles effectively increased the proportion of efficient combustion, evidenced by single peak and parent peak patterns during cold starts. CeO 2 nanoparticles facilitated the transition from low-temperature to high-temperature reactions, promoting fuel ignition during the first injection cycle and reducing speed fluctuations during cold starts with diethyl ether premixing at −40 °C. Furthermore, adding CeO 2 nanoparticles prevented detonation and rapid pressure surges during cold starts. Overall, doping diesel fuel with CeO 2 nanoparticles proves to be an effective method for enhancing cold start performance in diesel engines. This study offers a novel approach for improving diesel engine cold start performance in high-altitude and low-temperature conditions.
研究领域:
能源工程
·
环境科学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 3
·341
·
IF 5.5
Qingqing Huang,Xingyue Han,Jin Li,Xilin Li,Xin Chen,Jianwen Hou,Sixun Yu,Shaobing Zhou,Gu Gong,Haifeng Shu
Background/Objectives:Orally or intravenously administered acetaminophen experiences considerable liver first-pass elimination and may cause liver/kidney damage. This work examined the pharmacological effects of acetaminophen-loaded poly(lactic-co-glycolic acid) nanoparticles (AAP PLGA NPs) intranasally administered to mice rapidly entering high altitudes.Methods:AAP PLGA NPs were prepared using ultrasonication-assisted emulsification and solvent evaporation and characterized in terms of drug encapsulation efficiency and loading, in vitro and in vivo release behaviors, and toxicity to hippocampal neurons. In vivo fluorescence imaging was used to monitor the concentrations of AAP PLGA NPs (labeled with indocyanine green) in the brain and blood of the mice after intranasal administration. The effects of these NPs on the pain threshold in mice rapidly entering high altitudes were evaluated through hot plate and tail flick experiments.Results:The AAP PLGA NPs were found to be noncytotoxic, highly biocompatible and stable, with a drug encapsulation efficiency and loading capacity of 42.53% and 3.87%, respectively. The in vitro release of acetaminophen lasted for up to 72 h, and the release rate was ~82%. After intranasal administration in vivo, the drug release occurred slowly, and the drug was mainly concentrated in the brain. Compared with nonencapsulated acetaminophen, the intranasal administration of AAP PLGA NPs resulted in higher brain levels of the drug and delayed its elimination, thus increasing the pain threshold in mice rapidly entering high altitudes.Conclusions:The proposed strategy addresses the common problems of intranasal drug administration (low retention time and bioavailability) and paves the way for effective pain management in high-altitude environments.
研究领域:
药理学
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纳米医学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Fungi
·
2024
·Vol. 10
·期 11
·736
·
IF 4.2
Guo-Jun Zhou,Wei-Jia Xiong,Wei Xu,Zheng-Rong Dou,Bo-Chao Liu,Xue-Li Li,Hao Du,Hai-Feng Li,Yong-Zeng Zhang,Bei Jiang,Kai-Ling Wang
Astragalus, a group of legume plants, has a pronounced rhizosphere effect. Many species ofAstragaluswith limited resource reserves are distributed in the high-altitude area of northern Yunnan, China. Although some of these plants have high medicinal value, the recognition of them is still at a low level. The aim of this research is to explore the species diversity of cultivable rhizofungi derived fromAstragalus acaulis,A. forrestiiandA. ernestiigrowing in a special high–cold environment of northwest Yunnan and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fermented substrate of the rhizofungusAspergillus calidoustusAA12 derived from the plantA. acaulisshowed broad-spectrum antibacterial activity and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the speciesA. calidoustus, including sesterterpine 6-epi-ophiobolin G; three sesquiterpenes, penicisochroman A, pergillin and 7-methyl-2-(1-methylethylethlidene)-furo [3,2-H]isoquinoline-3-one; and three polyketides, trypacidin, 1,2-seco-trypacidin and questin. Among them, the compound 6-epi-ophiobolin G exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL and a prominent inhibitory effect on the biofilm ofStreptococcus agalactiaeat an MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity againstPlasmodium falciparumstrains 3D7 and chloroquine-resistant Dd2 at the half-maximal inhibitory concentration (IC50) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizofungi from characteristicAstragalusplants in special high–cold environments and further increased the library of fungi available for natural anti-infectious product screening.
研究领域:
微生物学
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药理学
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植物科学
·
天然产物化学
✓ 已验证
DOI
高影响因子
BRAIN RESEARCH
·
2019
·
IF 2.929
Linjie Wei,Jianbo Zhang,Bo Zhang,Junjun Geng,Qiang Tan,Ling Wang,Zhi Chen,Hua Feng,Gang Zhu
Background Traumatic brain injury (TBI) leads to severe mortality and disability, in which secondary injury induced by complement activation plays an important role. TBI tends to be associated with more severe cerebral edema and worse neurological functional recovery if it occurs in high-altitude areas than in low-altitude areas. However, the underlying mechanism of this difference is unknown. Thus, we used cobra venom factor (CVF) to deplete complement C3 in simulated high-altitude areas to explore whether the differences in outcome at different altitudes are related to secondary injury caused by complement C3. Methods The weight-drop model was adopted to induce TBI in rats. Rats were randomly divided into the following groups: sham + saline (sham), high altitude + TBI + saline (HAT), high altitude + TBI + CVF (H-CVF), low altitude + TBI + saline (LAT), and low altitude + TBI + CVF (L-CVF). Brain contusion and edema volumes, brain water content, myelin basic protein (MBP) expression, tumor necrosis factor alpha (TNF-a) expression, interleukin 1 beta (IL1B) expression, mortality rate, neurological function, and complement component 3 (C3) mRNA expression were measured by techniques such as Evans blue fluorescence, Perls staining, TUNEL staining, ELISA, immunohistochemistry and Western blotting to evaluate correlations between complement activation and secondary injury. Results The activation of complement after TBI was significantly higher at high altitude than at low altitude. High-altitude TBI resulted in a leakier blood-brain barrier, more severe cerebral edema and higher mortality than low-altitude TBI did. In addition, high-altitude TBI tended to be associated with more MBP degradation, ferric iron deposition, neuronal apoptosis, and inflammatory factor deposition than low-altitude TBI. All of these effects of TBI were partially reversed by inhibiting complement activation using CVF. Conclusion Our study provided evidence that TBI at high altitude leads to severe edema and high mortality and disability rates. Complement C3 activation is one of the important factors contributing to secondary brain injury.
研究领域:
神经科学
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免疫学
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病理生理学
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实验医学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2024
·
IF 2.6
Chunqing Wang,Xin Huang,Ziyan Tang,Yizhi Zhang,Meng Wei,Shumin Du,Xingshuang Song,Yanping Wu,Qiang Chi,Xiaomei Zhuang,Du Lina,Yiguan Jin
Sleep disorders are one of the most common acute reactions on the plateau, which can cause serious complications. However, there is no effective and safe treatment currently available. Nimodipine (NMD) is a dihydropyridine calcium channel blocker with neuroprotective and vasodilating activity, mainly used for the treatment of ischemic brain injury. Commercial oral or injectable NMD formulations are not a good option for central neuron diseases due to their poor brain delivery. In this study, nimodipine dissolving microneedles (NDMNs) were prepared for the prevention of sleep disorders caused by hypoxia. NDMNs were composed of NMD and polyvinyl pyrrolidone (PVP) K90 with a conical morphology and high rigidity. After administration of NDMNs on the back neck of mice, the concentration of NMD in the brain was significantly higher than that of oral medication as was confirmed by the fluorescent imaging on mouse models. NDMNs enhanced cognitive function, alleviated oxidative stress, and improved the sleep quality of mice with high-altitude sleep disorders. The blockage of calcium ion overloading may be an important modulation mechanism. NDMNs are a promising and user-friendly formulation for the prevention of high-altitude sleep disorders.
研究领域:
药理学
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神经科学
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睡眠医学
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高原医学
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Yong-Ze Lu,Jing Han,Wei-Jia Zhang,Ji Sun,Xin Li,Zhong-lian Yang,Jun-Ling Yang,Shu-Ping Li,Guang-Can Zhu
At high altitude, wastewater aeration efficiency is low, which is detrimental to nitrification in conventional biological nitrogen removal. The combined partial nitritation and anaerobic ammonium oxidation (CPNA) process requires little oxygen and can be appropriate in low-pressure conditions. As such, in this study, we investigated the effect of air pressure on CPNA using a laboratory-scale reactor. We found that low air pressure promoted the removal of total inorganic nitrogen (TIN), achieving a TIN removal rate of 43,000 mg·N/(kg·VSS·d). The secretion of extracellular polymeric substances under low air pressure was not significantly different from that under ordinary air pressure, indicating no adverse effects on microbial aggregation ability, stability, or settleability. The abundance of aerobic ammonia-oxidizing bacteria (AeAOB) increased from 0.2% to 5.6%, and the activity of anaerobic ammonia-oxidizing bacteria (AnAOB) enhanced, giving AeAOB and AnAOB a competitive advantage over nitrite-oxidizing bacteria, thus forming a microbial community structure favorable to the CPNA process. Our further analysis of the results of batch tests in serum bottles confirmed the positive effect of low air pressure on the anaerobic ammonium oxidation (anammox) process, with a 28.5% ± 1.9% improvement in the specific anammox rate at 70 kPa compared with 100 kPa. AnAOB activity increased, which was reflected in the intracellular heme content increasing from 0.56 ± 0.18 μmol/(g·VSS) at 100 kPa to 2.56 ± 0.20 μmol/(g·VSS) at 70 kPa. We clarified the CPNA-process-promoting effect of low air pressure, which shows potential for nitrogen removal in high-altitude regions.
研究领域:
环境工程
·
微生物学
·
污水处理
✓ 已验证
DOI
PubMed
高影响因子
Communications Biology
·
2023
·Vol. 6
·期 1
·1-15
·
IF 5.9
Feng Tao,Pucker Boas,Kuang Tianhui,Song Bo,Yang Ya,Lin Nan,Zhang Huajie,Moore Michael J.,Brockington Samuel F.,Wang Qingfeng,Deng Tao,Wang Hengchang,Sun Hang
Glasshouse plants are species that trap warmth via specialized morphology and physiology, mimicking a human glasshouse. In the Himalayan alpine region, the highly specialized glasshouse morphology has independently evolved in distinct lineages to adapt to intensive UV radiation and low temperature. Here we demonstrate that the glasshouse structure – specialized cauline leaves – is highly effective in absorbing UV light but transmitting visible and infrared light, creating an optimal microclimate for the development of reproductive organs. We reveal that this glasshouse syndrome has evolved at least three times independently in the rhubarb genus Rheum . We report the genome sequence of the flagship glasshouse plant Rheum nobile and identify key genetic network modules in association with the morphological transition to specialized glasshouse leaves, including active secondary cell wall biogenesis, upregulated cuticular cutin biosynthesis, and suppression of photosynthesis and terpenoid biosynthesis. The distinct cell wall organization and cuticle development might be important for the specialized optical property of glasshouse leaves. We also find that the expansion of LTRs has likely played an important role in noble rhubarb adaptation to high elevation environments. Our study will enable additional comparative analyses to identify the genetic basis underlying the convergent occurrence of glasshouse syndrome.
研究领域:
植物学
·
遗传学
·
植物生态学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Horticulturae
·
2022
·Vol. 8
·期 11
·1029
·
IF 2.923
Qing-Fang Xu,Liang Fan,Kai-Xiang Lu,Dong-Mei Zhao,Ming-Xia Zhang,Jian Cai
Both free and glycosidically bound forms of volatile compounds in Vidal grapes from the Shangri-La high-altitude region during the on-vine non-destructive dehydration process were investigated by headspace solid-phase micro-extraction (HS-SPME) combined with gas chromatography–mass spectrometry (GC-MS), following which the data were processed by multivariate statistical analysis. Fatty-acid-derived volatiles (FADs), amino-acid-derived volatiles (AADs), and isoprene-derived volatiles (IPDs), which occurred mainly in bound forms, were the three major volatiles in dehydrated Vidal grapes. Water-loss concentration, biosynthesis, and biodegradation all occurred during dehydration, eventually modifying some volatiles significantly, especially some powerful odorants such as hexanal,trans-2-hexenal, 2-phenethyl acetate, β-myrcene, linalool, geraniol,cis-rose oxide, and β-damascenone. 1-Octen-3-ol was relatively stable during the non-destructive on-vine dehydration process and its content in grape juice was mainly determined by the concentration effect. 2,4-Di-tert-butylphenol, 2-phenethyl acetate, 2-methyl-1-propanol, and hexanol were screened as some of the most important metabolic markers to discriminate grapes at different dehydration degrees. Our study also highlights the fundamental importance of the expression of volatile content in the metabolomic study of grape berries.Keywords:late harvest;over-ripening;dessert wine;metabolomics;clustered heatmap;OPLS-DA
研究领域:
农学
·
食品科学
·
分析化学
·
植物生理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）