The development of pollution-free dyeing technology, including anhydrous dyeing and non-aqueous dyeing technologies, has always been an important way and research hot in energy conservation and emission reduction. Des...The development of pollution-free dyeing technology, including anhydrous dyeing and non-aqueous dyeing technologies, has always been an important way and research hot in energy conservation and emission reduction. Designing new structural dye molecules is the key to water-saving dyeing processes.Herein, three reactive dyes were designed and synthesized, which contained large planar multiconjugated systems and multi-reactive groups. The designed reactive dyes are expected to have high affinity and high fixations in non-aqueous or small bath dyeing processes. The reactive dyes were applied in the decamethylcyclopentasiloxane(DMCS) reverse micelle dyeing for cotton fabric. High exhaustion rate of 99.35%, 98.10% and 98.80%, and fixation rate of 95.15%, 96.34% and 94.40% for three dyes, R1,R2 and R3, could be respectively obtained. The dyes can be fully utilized and had excellent dyeing performance, fastness and levelling properties under the revere micelle dyeing. The cotton fabric is like an oil-water separator in the dyeing process, where the dye micelles rapidly absorb and permeate into the cotton fibers. DMCS circulates around the fabric to transfer mass and energy. After dyeing, the solvent can be separated quickly and reused. The new reactive dyes containing large planar and multi-conjugated systems have potential application in green and sustainable dyeing technology with less wastewater and higher utilization.展开更多
Psoriasis is a chronic inflammatory skin disease characterized by erythema,scaling,and skin thickening.Topical drug application is recommended as the first-line treatment.Many formulation strategies have been develope...Psoriasis is a chronic inflammatory skin disease characterized by erythema,scaling,and skin thickening.Topical drug application is recommended as the first-line treatment.Many formulation strategies have been developed and explored for enhanced topical psoriasis treatment.However,these preparations usually have low viscosity and limited retention on the skin surface,resulting in low drug delivery efficiency and poor patient satisfaction.In this study,we developed the first water-responsive gel(WRG),which has a distinct water-triggered liquid-to-gel phase transition property.Specifically,WRG was kept in a solution state in the absence of water,and the addition of water induced an immediate phase transition and resulted in a high viscosity gel.Curcumin was used as a model drug to investigate the potential of WRG in topical drug delivery against psoriasis.In vitro and in vivo data showed that WRG formulation could not only extend skin retention but also facilitate the drug permeating across the skin.In a mouse model of psoriasis,curcumin loaded WRG(CUR-WRG)effectively ameliorated the symptoms of psoriasis and exerted a potent anti-psoriasis effect by extending drug retention and facilitating drug penetration.Further mechanism study demonstrated that the anti-hyperplasia,anti-inflammation,anti-angiogenesis,anti-oxidation,and immunomodulation properties of curcumin were amplified by enhanced topical drug delivery efficiency.Notably,neglectable local or systemic toxicity was observed for CUR-WRG application.This study suggests that WRG is a promising formulation for topically psoriasis treatment.展开更多
The purpose of this study was to prepare glycyrrhizic acid nanoliposomes and evaluate the encapsulation efficiency and other properties of glycyrrhizic acid nanoliposomes, which would provide a reference for further r...The purpose of this study was to prepare glycyrrhizic acid nanoliposomes and evaluate the encapsulation efficiency and other properties of glycyrrhizic acid nanoliposomes, which would provide a reference for further research on Glycyrrhizic Acid in the treatment of liver diseases. Firstly, the preparation conditions of glycyrrhizic acid liposomes were optimized by the orthogonal design method. Then, glycyrrhizic acid liposomes were prepared by ultrasonic-film dispersion method and the encapsulation efficiency was determined by the HPLC method. Finally, the properties of glycyrrhizic acid nanoliposomes were also studied. The results showed that the optimal preparation conditions of liposomes were as follows: the ratio of drug to lipid was 1:30;Lecithin: cholesterol = 1:1;Hydration medium: pure water;Ultrasonic time: 120 s. The encapsulation efficiency of liposomes was about 90%. The final liposomes were round and uniform in distribution, with an average particle size of about 50 nm and absolute zeta potential of −28.9 mV. In this study, glycyrrhizic acid liposomes were prepared and the optimal preparation conditions were optimized. The encapsulation efficiency of the liposomes under the optimized conditions was determined. The evaluation of the morphology, size, particle size and stability of the liposomes was completed.展开更多
Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and ...Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.展开更多
Rho-associated kinase(ROCK) is a key regulatory protein involved in inflammatory secretion in microglia in the central nervous system.Our previous studies showed that ROCK inhibition enhances phagocytic activity in ...Rho-associated kinase(ROCK) is a key regulatory protein involved in inflammatory secretion in microglia in the central nervous system.Our previous studies showed that ROCK inhibition enhances phagocytic activity in microglia through the extracellular signal-regulated kinase(ERK) signaling pathway,but its effect on microglial migration was unknown.Therefore,in this study,we investigated the effects of the ROCK inhibitors Y27632 and fasudil on the migratory activity of primary cultured microglia isolated from the spinal cord,and we examined the underlying mechanisms.The microglia were treated with Y27632,fasudil and/or the ERK inhibitor U0126.Cellular morphology was observed by immunofluorescence.Transwell chambers were used to assess cell migration.ERK levels were measured by incell western blot assay.Y27632 and fasudil increased microglial migration,and the microglia were irregularly shaped and had many small processes.These inhibitors also upregulated the levels of phosphorylated ERK protein.The ERK inhibitor U0126 suppressed these effects of Y27632 and fasudil.These findings suggest that the ROCK inhibitors Y27632 and fasudil promote microglial migration in the spinal cord through the ERK signaling pathway.展开更多
Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholi...Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly'phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes.展开更多
The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At...The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At the same time,SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain;PSA modifi-cation can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood,thus achieving active targeting effect.These properties offer a variety of opportunities for applications in drug delivery systems.This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs,proteins and carriers in drug delivery systems.展开更多
The aim of the study was to prepare berberine hydrochloride long-circulating liposomes and optimize the formulation and process parameters,and investigate the influence of different factors on the encapsulation effici...The aim of the study was to prepare berberine hydrochloride long-circulating liposomes and optimize the formulation and process parameters,and investigate the influence of different factors on the encapsulation efficiency.Berberine hydrochloride liposomes were prepared in response to a transmembrane ion gradient that was established by ionophore A23187.Free and liposomal drug were separated by cation exchange resin,and then the amount of intraliposomal berberine hydrochloride was determined by UV spectrophotometry.The optimized encapsulation efficiency of berberine hydrochloride liposomes was 94.3%2.1%when the drug-to-lipid ratio was 1:20,and the mean diameter was 146.9 nm3.2 nm.As a result,the ionophore A23187-mediated ZnSO_(4)gradient method was suitable for the preparation of berberine hydrochloride liposomes that we could get the desired encapsulation efficiency and drug loading.展开更多
PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. Howev...PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. However, PEG-modified liposomes can induce accelerated blood clearance(ABC) upon repeated administration, and the extent of ABC phenomenon on the cytotoxic drugs-containing PEGylated liposomes is related to the dose of the cytotoxic drugs.In this study, EPI served as a model cytotoxic drug, a hydrophilic surfactant molecule,monosialylganglioside(GM1) was chosen and modified on the liposomes together with PEG.It was shown that upon mixed modification, when GM1 contents reached 10% or 15% mol,the ABC phenomenon of the PEGylated liposomal EPI significantly reduced. We also found that GM1 played an important role in abrogating the ABC phenomenon in both the induction phase and the effectuation phase. The results suggested that GM1 incorporation unfortunately did not avoid occurrence of ABC phenomenon completely, but GM1 modification on PEGylated liposomes may provide a significant improvement in clinical practice of PEGylated liposomes. Further study must be necessary.展开更多
BACKGROUND: Blood supply to the hippocampus is not provided by the middle cerebral artery. However, previous studies have shown that delayed neuronal death in the hippocampus may occur following focal cerebral ischem...BACKGROUND: Blood supply to the hippocampus is not provided by the middle cerebral artery. However, previous studies have shown that delayed neuronal death in the hippocampus may occur following focal cerebral ischemia induced by middle cerebral artery occlusion. OBJECTIVE: To observe the relationship between reactive changes in hippocampal astrocytes and delayed neuronal death in the hippocampal CA1 region following middle cerebral artery occlusion. DESIGN, TIME AND SETTING: The immunohistochemical, randomized, controlled animal study was performed at the Laboratory of Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from July to November 2007. MATERIALS: Rabbit anti-glial fibrillary acidic protein (GFAP) (Neomarkers, USA), goat anti-rabbit IgG (Sigma, USA) and ApoAlert apoptosis detection kit (Biosciences Clontech, USA) were used in this study. METHODS: A total of 42 healthy adult male Wistar rats, aged 3–5 months, were randomly divided into a sham operation group (n = 6) and a cerebral ischemia/reperfusion group (n = 36). In the cerebral ischemia/reperfusion group, cerebral ischemia/reperfusion models were created by middle cerebral artery occlusion. In the sham operation group, the thread was only inserted into the initial region of the internal carotid artery, and middle cerebral artery occlusion was not induced. Rats in the cerebral ischemia/reperfusion group were assigned to a delayed neuronal death (+) subgroup and a delayed neuronal death (–) subgroup, according to the occurrence of delayed neuronal death in the ischemic side of the hippocampal CA1 region following cerebral ischemia. MAIN OUTCOME MEASURES: Delayed neuronal death in the hippocampal CA1 region was measured by Nissl staining. GFAP expression and delayed neuronal death changes were measured in the rat hippocampal CA1 region at the ischemic hemisphere by double staining for GFAP and TUNEL. RESULTS: After 3 days of ischemia/reperfusion, astrocytes with abnormal morphology were detected in the rat hippocampal CA1 region in the delayed neuronal death (+) subgroup. No significant difference in GFAP expression was found in the rat hippocampal CA1 region at the ischemic hemisphere in the sham operation group, delayed neuronal death (+) subgroup and delayed neuronal death (–) subgroup (P 〉 0.05). After 7 days of ischemia/reperfusion, many GFAP-positive cells, which possessed a large cell body and an increased number of processes, were activated in the rat hippocampal CA1 region at the ischemic hemisphere. GFAP expression in the hippocampal CA1 region was greater in the delayed neuronal death (+) subgroup and delayed neuronal death (–) subgroup compared with the sham operation group (P 〈 0.01). Moreover, GFAP expression was significantly greater in the delayed neuronal death (–) subgroup than in the delayed neuronal death (+) subgroup (P 〈 0.01). After 30 days of ischemia/reperfusion, GFAP-positive cells were present in scar-like structures in the rat hippocampal CA1 region at the ischemic hemisphere. GFAP expression was significantly greater in the delayed neuronal death (+) subgroup and delayed neuronal death (–) subgroup compared with the sham operation group (P 〈 0.05). GFAP expression was significantly lower in the delayed neuronal death (–) subgroup than in the delayed neuronal death (+) subgroup (P 〈 0.05). The delayed neuronal death rates were 42% (5/12), 33% (4/12) and 33% (4/12) at 3, 7 and 30 days, respectively, followingischemia/reperfusion. No significant differences were detected at various time points (χ2 = 0.341, P 〉 0.05). CONCLUSION: The activation of astrocytes was poor in the hippocampal CA1 region during the early stages of ischemia, which is an important reason for delayed neuronal death. Glial scar formation aggravated delayed neuronal death during the advanced ischemic stage.展开更多
Binders are of vital importance in stabilizing the cathodes to enhance the cycling stability of lithiumsulfur(Li-S) batteries. However, conventional binders are typically confronted with the drawback of inability for ...Binders are of vital importance in stabilizing the cathodes to enhance the cycling stability of lithiumsulfur(Li-S) batteries. However, conventional binders are typically confronted with the drawback of inability for adsorbing lithium polysulfide(Li PS), thus resulting in severe active material losing and rapid capacity fading. Herein, a novel water-soluble hyperbranched poly(amidoamine)(HPAA) binder with controllable hyperbranched molecular structure and abundant amino end groups for Li-S battery is designed and fabricated, which can improve efficient adsorption for Li PS and stability of the sulfur cathodes. Besides, the strong intermolecular hydrogen bonds in HPAA binder can contribute to the structural stability of S cathode and integration of the conductive paths. Therefore, the Li-S battery with this functional binder exhibits excellent cycle performance with a capacity retention of 91% after 200 cycles at 0.1 C.Even at a high sulfur loading of 5.3 mg cm-2, a specific capacity of 601 mA h g-1 can also be achieved.Density functional theory(DFT) calculation further demonstrates that the enhanced electrochemical stability derives from the high binding energy between amino groups and LiP S and the wide electrochemical window(6.87 e V) of HPAA molecule. Based on the above all, this functional polymer will lighten a new species of binders for eco-friendly sulfur cathodes and significantly promote the practical applications of high-performance Li-S batteries.展开更多
Accelerated blood clearance(ABC) phenomenon is common in many PEGylated nanocarriers, whose mechanism has not been completely elucidated yet. In this study, the correlation between Kupffer cells(KCs) and ABC phenomeno...Accelerated blood clearance(ABC) phenomenon is common in many PEGylated nanocarriers, whose mechanism has not been completely elucidated yet. In this study, the correlation between Kupffer cells(KCs) and ABC phenomenon has been studied by KCs-targeted liposomes inducing ABC phenomenon and KCs depletion. In other words, the 4-aminophenyl-α-D-mannopyranoside(APM) lipid derivative DSPE-PEG 2000-APM(DPM), and 4-aminophenyl-β-L-fucopyranoside(APF) lipid derivative DSPE-PEG 2000-APF(DPF) were conjugated and modified on alendronate sodium(AD) liposomes to specifically target and deplete KCs. The dualligand modified PEGylated liposomes(MFPL) showed stronger ability to damage KCs in vitro and in vivo, which also could indirectly illustrate that dual-ligand modification could better target KCs. Besides, the hepatic biodistribution and pharmacokinetics could directly prove that MFPL had a stronger targeting ability to KCs. In addition, in depletion rats, plasma concentration and splenic biodistribution of MFPL and PEGylated liposomes(PL) were significantly elevated and hepatic biodistribution was significantly reduced, which demonstrated that KCs played an important role on elimination of nanoparticles. What’s more, ABC phenomenon of the secondary injection of PL was stronger in KCs depletion rats than that in normal rats, which indicated that depletion of KCs prolonged the circulation of PL in the first injection repeatedly stimulating B-cells in the marginal region of the spleen and causing it to secrete more IgM antibodies. This could also illustrate that anti-PEG IgM takes up a major station compared with KCs. Most important of all, KCs-targeted liposomes could induce a stronger ABC phenomenon than PL in normal rats, which declared that based on the same IgM concentration, the more the KCs were stimulated, the stronger ABC phenomenon was induced. However, in depletion rats, this difference of ABC phenomenon between PL and MFPL could no more exist, further demonstrating that KCs could participate and play a certain role in the ABC phenomenon.展开更多
This study examined an isothermal CO2 gasification of four chars prepared via two different methods,i.e.,conventional and microwave-assisted pyrolysis,by the approach of thermogravimetric analysis.Physical,chemical,an...This study examined an isothermal CO2 gasification of four chars prepared via two different methods,i.e.,conventional and microwave-assisted pyrolysis,by the approach of thermogravimetric analysis.Physical,chemical,and structural behaviours of chars were examined using ultimate analysis,X-ray diffraction,and scanning electronic microscopy.Kinetic parameters were calculated by applying the shrinking unreacted core(SCM)and random pore(RPM)models.Moreover,char-CO2 gasification was further simulated by using Aspen Plus to investigate thermodynamic performances in terms of syngas composition and cold gas efficiency(CGE).The microwave-induced char has the largest C/H mass ratio and most ordered carbon structure,but the smallest gasification reactivity.Kinetic analysis indicates that the RPM is better for describing both gasification conversion and reaction rates of the studied chars,and the activation energies and pre-exponential factors varied in the range of 78.45–194.72 kJ/mol and 3.15–102,231.99 s−1,respectively.In addition,a compensation effect was noted during gasification.Finally,the microwave-derived char exhibits better thermodynamic performances than the conventional chars,with the highest CGE and CO molar concentration of 1.30%and 86.18%,respectively.Increasing the pyrolysis temperature,gasification temperature,and CO2-to-carbon molar ratio improved the CGE.展开更多
This paper proposes the operation principle and a new flux estimation method for sensorless control strategy for the dual-fed flux modulated electric motor(DFFM).The DFFM is designed based on the flux modulation theor...This paper proposes the operation principle and a new flux estimation method for sensorless control strategy for the dual-fed flux modulated electric motor(DFFM).The DFFM is designed based on the flux modulation theory,it includes two stator windings and one rotor which simplify the mechanical structure.The rotor has only modulation iron and no permanent magnets on it,so there is no cogging torque problem in this motor.With adjustment of the outer and inner stator flux rotating frequency and amplitude,different rotation speed and torque of the sandwiched rotor can be gained for the DFFM.Furthermore,an improved flux estimation based sensorless control strategy is performed on the proposed machine to fit the two winding set control situation.The startup and performance of the proposed control strategy is verified by the simulation and experiments.展开更多
Energy crisis promotes the development of renewable energy, especially the solar energy. Sun tracking system proposed in this paper is such a device for efficiency improvement. This closed loop tracking system with tw...Energy crisis promotes the development of renewable energy, especially the solar energy. Sun tracking system proposed in this paper is such a device for efficiency improvement. This closed loop tracking system with two axis sun tracking method is controlled by a programmable logic controller (PLC) and is used for a large dish solar collector. A combination tracking mode combined active and passive tracking methods used in the design make the tracker efficient whatever the circumstances. Two stepper motors and two reduction boxes move the device towards the sun with chain transmission. Besides sun tracking, the system also has functions of overheat monitoring, wind speed monitoring and measurement of illumination.展开更多
As an integral part of the internal air system of aero-engines,the axial throughflow of the cooling air can interact with the cavity flow between the rotating compressor disks,forming a threedimensional,unsteady,and u...As an integral part of the internal air system of aero-engines,the axial throughflow of the cooling air can interact with the cavity flow between the rotating compressor disks,forming a threedimensional,unsteady,and unstable flow field.The flow characteristics in an engine-like rotating multi-stage cavity with throughflow were investigated using particle image velocimetry,flow visualization technology and three-dimensional unsteady Reynolds-Averaged Navier-Stokes (RANS)simulations.The focus of current research was to understand the distribution of the mean swirl ratio and its variation with a wide range of non-dimensional parameters in the co-rotating cavity with high inlet pre-swirl axial throughflow.The maximum axial Reynolds number and rotational Reynolds numbers could reach 4.41×10^(4)and 1.24×10^(6),respectively.The velocity measurement results indicate that the mean swirl ratio is greater than 1 and decreases with an increase in the radial position.The flow structure is dominated by the Rossby number,and two different flow patterns (flow penetration and flow stratification) are identified and confirmed by flow visualization images.In the absence of buoyancy,the flow penetration caused by the precession of the throughflow makes it easier for the throughflow to reach a high radius region.Satisfactory consistency of results between measurements and numerical calculations is obtained.This study provides a theoretical basis and data support for toroidal vortex breakdown,which is of practical significance for the design of high-pressure compressor cavities.展开更多
Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects th...Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.展开更多
基金supported by Natural Science Foundation of Shanghai (20ZR1400300)Textile Vision Applied Basic Research Project (J202005)National Key Research & Development Program of China (2017YFB0309600)。
文摘The development of pollution-free dyeing technology, including anhydrous dyeing and non-aqueous dyeing technologies, has always been an important way and research hot in energy conservation and emission reduction. Designing new structural dye molecules is the key to water-saving dyeing processes.Herein, three reactive dyes were designed and synthesized, which contained large planar multiconjugated systems and multi-reactive groups. The designed reactive dyes are expected to have high affinity and high fixations in non-aqueous or small bath dyeing processes. The reactive dyes were applied in the decamethylcyclopentasiloxane(DMCS) reverse micelle dyeing for cotton fabric. High exhaustion rate of 99.35%, 98.10% and 98.80%, and fixation rate of 95.15%, 96.34% and 94.40% for three dyes, R1,R2 and R3, could be respectively obtained. The dyes can be fully utilized and had excellent dyeing performance, fastness and levelling properties under the revere micelle dyeing. The cotton fabric is like an oil-water separator in the dyeing process, where the dye micelles rapidly absorb and permeate into the cotton fibers. DMCS circulates around the fabric to transfer mass and energy. After dyeing, the solvent can be separated quickly and reused. The new reactive dyes containing large planar and multi-conjugated systems have potential application in green and sustainable dyeing technology with less wastewater and higher utilization.
基金This research was supported by National Natural Science Foundation of China(Grant No.81903551)Natural Science Foundation of Zhejiang Province(Grant No.LYY22H300001)+3 种基金Wenzhou Municipal Science and Technology Bureau(Grant No.ZY2019007)Zhejiang postdoctoral scientific research project(Grant No.ZJ2021024)Wenzhou Municipal Key Laboratory of Pediatric Pharmacy(Grant No.WZEY02)Excellent Young Scientist Training Program fund from Wenzhou Medical University.
文摘Psoriasis is a chronic inflammatory skin disease characterized by erythema,scaling,and skin thickening.Topical drug application is recommended as the first-line treatment.Many formulation strategies have been developed and explored for enhanced topical psoriasis treatment.However,these preparations usually have low viscosity and limited retention on the skin surface,resulting in low drug delivery efficiency and poor patient satisfaction.In this study,we developed the first water-responsive gel(WRG),which has a distinct water-triggered liquid-to-gel phase transition property.Specifically,WRG was kept in a solution state in the absence of water,and the addition of water induced an immediate phase transition and resulted in a high viscosity gel.Curcumin was used as a model drug to investigate the potential of WRG in topical drug delivery against psoriasis.In vitro and in vivo data showed that WRG formulation could not only extend skin retention but also facilitate the drug permeating across the skin.In a mouse model of psoriasis,curcumin loaded WRG(CUR-WRG)effectively ameliorated the symptoms of psoriasis and exerted a potent anti-psoriasis effect by extending drug retention and facilitating drug penetration.Further mechanism study demonstrated that the anti-hyperplasia,anti-inflammation,anti-angiogenesis,anti-oxidation,and immunomodulation properties of curcumin were amplified by enhanced topical drug delivery efficiency.Notably,neglectable local or systemic toxicity was observed for CUR-WRG application.This study suggests that WRG is a promising formulation for topically psoriasis treatment.
文摘The purpose of this study was to prepare glycyrrhizic acid nanoliposomes and evaluate the encapsulation efficiency and other properties of glycyrrhizic acid nanoliposomes, which would provide a reference for further research on Glycyrrhizic Acid in the treatment of liver diseases. Firstly, the preparation conditions of glycyrrhizic acid liposomes were optimized by the orthogonal design method. Then, glycyrrhizic acid liposomes were prepared by ultrasonic-film dispersion method and the encapsulation efficiency was determined by the HPLC method. Finally, the properties of glycyrrhizic acid nanoliposomes were also studied. The results showed that the optimal preparation conditions of liposomes were as follows: the ratio of drug to lipid was 1:30;Lecithin: cholesterol = 1:1;Hydration medium: pure water;Ultrasonic time: 120 s. The encapsulation efficiency of liposomes was about 90%. The final liposomes were round and uniform in distribution, with an average particle size of about 50 nm and absolute zeta potential of −28.9 mV. In this study, glycyrrhizic acid liposomes were prepared and the optimal preparation conditions were optimized. The encapsulation efficiency of the liposomes under the optimized conditions was determined. The evaluation of the morphology, size, particle size and stability of the liposomes was completed.
文摘Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.
基金supported by the National Natural Science Foundation of China,No.81471200,81771341
文摘Rho-associated kinase(ROCK) is a key regulatory protein involved in inflammatory secretion in microglia in the central nervous system.Our previous studies showed that ROCK inhibition enhances phagocytic activity in microglia through the extracellular signal-regulated kinase(ERK) signaling pathway,but its effect on microglial migration was unknown.Therefore,in this study,we investigated the effects of the ROCK inhibitors Y27632 and fasudil on the migratory activity of primary cultured microglia isolated from the spinal cord,and we examined the underlying mechanisms.The microglia were treated with Y27632,fasudil and/or the ERK inhibitor U0126.Cellular morphology was observed by immunofluorescence.Transwell chambers were used to assess cell migration.ERK levels were measured by incell western blot assay.Y27632 and fasudil increased microglial migration,and the microglia were irregularly shaped and had many small processes.These inhibitors also upregulated the levels of phosphorylated ERK protein.The ERK inhibitor U0126 suppressed these effects of Y27632 and fasudil.These findings suggest that the ROCK inhibitors Y27632 and fasudil promote microglial migration in the spinal cord through the ERK signaling pathway.
文摘Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly'phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes.
基金the National Natural Science Foundation of China(Grant No.81373334).
文摘The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At the same time,SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain;PSA modifi-cation can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood,thus achieving active targeting effect.These properties offer a variety of opportunities for applications in drug delivery systems.This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs,proteins and carriers in drug delivery systems.
文摘The aim of the study was to prepare berberine hydrochloride long-circulating liposomes and optimize the formulation and process parameters,and investigate the influence of different factors on the encapsulation efficiency.Berberine hydrochloride liposomes were prepared in response to a transmembrane ion gradient that was established by ionophore A23187.Free and liposomal drug were separated by cation exchange resin,and then the amount of intraliposomal berberine hydrochloride was determined by UV spectrophotometry.The optimized encapsulation efficiency of berberine hydrochloride liposomes was 94.3%2.1%when the drug-to-lipid ratio was 1:20,and the mean diameter was 146.9 nm3.2 nm.As a result,the ionophore A23187-mediated ZnSO_(4)gradient method was suitable for the preparation of berberine hydrochloride liposomes that we could get the desired encapsulation efficiency and drug loading.
基金supported by the National Natural Science Foundation of China (Grant No.81373334)
文摘PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. However, PEG-modified liposomes can induce accelerated blood clearance(ABC) upon repeated administration, and the extent of ABC phenomenon on the cytotoxic drugs-containing PEGylated liposomes is related to the dose of the cytotoxic drugs.In this study, EPI served as a model cytotoxic drug, a hydrophilic surfactant molecule,monosialylganglioside(GM1) was chosen and modified on the liposomes together with PEG.It was shown that upon mixed modification, when GM1 contents reached 10% or 15% mol,the ABC phenomenon of the PEGylated liposomal EPI significantly reduced. We also found that GM1 played an important role in abrogating the ABC phenomenon in both the induction phase and the effectuation phase. The results suggested that GM1 incorporation unfortunately did not avoid occurrence of ABC phenomenon completely, but GM1 modification on PEGylated liposomes may provide a significant improvement in clinical practice of PEGylated liposomes. Further study must be necessary.
基金the National Outstanding Youth Foundation Program, No. 30725019 the Natural Science Foundation of Hubei Province, No. 2007ABA174
文摘BACKGROUND: Blood supply to the hippocampus is not provided by the middle cerebral artery. However, previous studies have shown that delayed neuronal death in the hippocampus may occur following focal cerebral ischemia induced by middle cerebral artery occlusion. OBJECTIVE: To observe the relationship between reactive changes in hippocampal astrocytes and delayed neuronal death in the hippocampal CA1 region following middle cerebral artery occlusion. DESIGN, TIME AND SETTING: The immunohistochemical, randomized, controlled animal study was performed at the Laboratory of Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from July to November 2007. MATERIALS: Rabbit anti-glial fibrillary acidic protein (GFAP) (Neomarkers, USA), goat anti-rabbit IgG (Sigma, USA) and ApoAlert apoptosis detection kit (Biosciences Clontech, USA) were used in this study. METHODS: A total of 42 healthy adult male Wistar rats, aged 3–5 months, were randomly divided into a sham operation group (n = 6) and a cerebral ischemia/reperfusion group (n = 36). In the cerebral ischemia/reperfusion group, cerebral ischemia/reperfusion models were created by middle cerebral artery occlusion. In the sham operation group, the thread was only inserted into the initial region of the internal carotid artery, and middle cerebral artery occlusion was not induced. Rats in the cerebral ischemia/reperfusion group were assigned to a delayed neuronal death (+) subgroup and a delayed neuronal death (–) subgroup, according to the occurrence of delayed neuronal death in the ischemic side of the hippocampal CA1 region following cerebral ischemia. MAIN OUTCOME MEASURES: Delayed neuronal death in the hippocampal CA1 region was measured by Nissl staining. GFAP expression and delayed neuronal death changes were measured in the rat hippocampal CA1 region at the ischemic hemisphere by double staining for GFAP and TUNEL. RESULTS: After 3 days of ischemia/reperfusion, astrocytes with abnormal morphology were detected in the rat hippocampal CA1 region in the delayed neuronal death (+) subgroup. No significant difference in GFAP expression was found in the rat hippocampal CA1 region at the ischemic hemisphere in the sham operation group, delayed neuronal death (+) subgroup and delayed neuronal death (–) subgroup (P 〉 0.05). After 7 days of ischemia/reperfusion, many GFAP-positive cells, which possessed a large cell body and an increased number of processes, were activated in the rat hippocampal CA1 region at the ischemic hemisphere. GFAP expression in the hippocampal CA1 region was greater in the delayed neuronal death (+) subgroup and delayed neuronal death (–) subgroup compared with the sham operation group (P 〈 0.01). Moreover, GFAP expression was significantly greater in the delayed neuronal death (–) subgroup than in the delayed neuronal death (+) subgroup (P 〈 0.01). After 30 days of ischemia/reperfusion, GFAP-positive cells were present in scar-like structures in the rat hippocampal CA1 region at the ischemic hemisphere. GFAP expression was significantly greater in the delayed neuronal death (+) subgroup and delayed neuronal death (–) subgroup compared with the sham operation group (P 〈 0.05). GFAP expression was significantly lower in the delayed neuronal death (–) subgroup than in the delayed neuronal death (+) subgroup (P 〈 0.05). The delayed neuronal death rates were 42% (5/12), 33% (4/12) and 33% (4/12) at 3, 7 and 30 days, respectively, followingischemia/reperfusion. No significant differences were detected at various time points (χ2 = 0.341, P 〉 0.05). CONCLUSION: The activation of astrocytes was poor in the hippocampal CA1 region during the early stages of ischemia, which is an important reason for delayed neuronal death. Glial scar formation aggravated delayed neuronal death during the advanced ischemic stage.
基金the Startup Research Fund of Dongguan University of Technology(KCYKYQD2017015)Leading Talents of Innovation and Entrepreneurship of the Dongguan City D2017(16)the Australian Research Council(ARC)through the ARC Discovery project(DP160104340)。
文摘Binders are of vital importance in stabilizing the cathodes to enhance the cycling stability of lithiumsulfur(Li-S) batteries. However, conventional binders are typically confronted with the drawback of inability for adsorbing lithium polysulfide(Li PS), thus resulting in severe active material losing and rapid capacity fading. Herein, a novel water-soluble hyperbranched poly(amidoamine)(HPAA) binder with controllable hyperbranched molecular structure and abundant amino end groups for Li-S battery is designed and fabricated, which can improve efficient adsorption for Li PS and stability of the sulfur cathodes. Besides, the strong intermolecular hydrogen bonds in HPAA binder can contribute to the structural stability of S cathode and integration of the conductive paths. Therefore, the Li-S battery with this functional binder exhibits excellent cycle performance with a capacity retention of 91% after 200 cycles at 0.1 C.Even at a high sulfur loading of 5.3 mg cm-2, a specific capacity of 601 mA h g-1 can also be achieved.Density functional theory(DFT) calculation further demonstrates that the enhanced electrochemical stability derives from the high binding energy between amino groups and LiP S and the wide electrochemical window(6.87 e V) of HPAA molecule. Based on the above all, this functional polymer will lighten a new species of binders for eco-friendly sulfur cathodes and significantly promote the practical applications of high-performance Li-S batteries.
基金supported by the National Natural Science Foundation of China (Nos. 81373334 and 81573375)
文摘Accelerated blood clearance(ABC) phenomenon is common in many PEGylated nanocarriers, whose mechanism has not been completely elucidated yet. In this study, the correlation between Kupffer cells(KCs) and ABC phenomenon has been studied by KCs-targeted liposomes inducing ABC phenomenon and KCs depletion. In other words, the 4-aminophenyl-α-D-mannopyranoside(APM) lipid derivative DSPE-PEG 2000-APM(DPM), and 4-aminophenyl-β-L-fucopyranoside(APF) lipid derivative DSPE-PEG 2000-APF(DPF) were conjugated and modified on alendronate sodium(AD) liposomes to specifically target and deplete KCs. The dualligand modified PEGylated liposomes(MFPL) showed stronger ability to damage KCs in vitro and in vivo, which also could indirectly illustrate that dual-ligand modification could better target KCs. Besides, the hepatic biodistribution and pharmacokinetics could directly prove that MFPL had a stronger targeting ability to KCs. In addition, in depletion rats, plasma concentration and splenic biodistribution of MFPL and PEGylated liposomes(PL) were significantly elevated and hepatic biodistribution was significantly reduced, which demonstrated that KCs played an important role on elimination of nanoparticles. What’s more, ABC phenomenon of the secondary injection of PL was stronger in KCs depletion rats than that in normal rats, which indicated that depletion of KCs prolonged the circulation of PL in the first injection repeatedly stimulating B-cells in the marginal region of the spleen and causing it to secrete more IgM antibodies. This could also illustrate that anti-PEG IgM takes up a major station compared with KCs. Most important of all, KCs-targeted liposomes could induce a stronger ABC phenomenon than PL in normal rats, which declared that based on the same IgM concentration, the more the KCs were stimulated, the stronger ABC phenomenon was induced. However, in depletion rats, this difference of ABC phenomenon between PL and MFPL could no more exist, further demonstrating that KCs could participate and play a certain role in the ABC phenomenon.
基金This work was financially supported by the National Key Research and Development Program of China(2017YFB0602601)the Key Research and Development Program of Ningxia Hui Autonomous Region(2019BCH01001).
文摘This study examined an isothermal CO2 gasification of four chars prepared via two different methods,i.e.,conventional and microwave-assisted pyrolysis,by the approach of thermogravimetric analysis.Physical,chemical,and structural behaviours of chars were examined using ultimate analysis,X-ray diffraction,and scanning electronic microscopy.Kinetic parameters were calculated by applying the shrinking unreacted core(SCM)and random pore(RPM)models.Moreover,char-CO2 gasification was further simulated by using Aspen Plus to investigate thermodynamic performances in terms of syngas composition and cold gas efficiency(CGE).The microwave-induced char has the largest C/H mass ratio and most ordered carbon structure,but the smallest gasification reactivity.Kinetic analysis indicates that the RPM is better for describing both gasification conversion and reaction rates of the studied chars,and the activation energies and pre-exponential factors varied in the range of 78.45–194.72 kJ/mol and 3.15–102,231.99 s−1,respectively.In addition,a compensation effect was noted during gasification.Finally,the microwave-derived char exhibits better thermodynamic performances than the conventional chars,with the highest CGE and CO molar concentration of 1.30%and 86.18%,respectively.Increasing the pyrolysis temperature,gasification temperature,and CO2-to-carbon molar ratio improved the CGE.
文摘This paper proposes the operation principle and a new flux estimation method for sensorless control strategy for the dual-fed flux modulated electric motor(DFFM).The DFFM is designed based on the flux modulation theory,it includes two stator windings and one rotor which simplify the mechanical structure.The rotor has only modulation iron and no permanent magnets on it,so there is no cogging torque problem in this motor.With adjustment of the outer and inner stator flux rotating frequency and amplitude,different rotation speed and torque of the sandwiched rotor can be gained for the DFFM.Furthermore,an improved flux estimation based sensorless control strategy is performed on the proposed machine to fit the two winding set control situation.The startup and performance of the proposed control strategy is verified by the simulation and experiments.
文摘Energy crisis promotes the development of renewable energy, especially the solar energy. Sun tracking system proposed in this paper is such a device for efficiency improvement. This closed loop tracking system with two axis sun tracking method is controlled by a programmable logic controller (PLC) and is used for a large dish solar collector. A combination tracking mode combined active and passive tracking methods used in the design make the tracker efficient whatever the circumstances. Two stepper motors and two reduction boxes move the device towards the sun with chain transmission. Besides sun tracking, the system also has functions of overheat monitoring, wind speed monitoring and measurement of illumination.
文摘As an integral part of the internal air system of aero-engines,the axial throughflow of the cooling air can interact with the cavity flow between the rotating compressor disks,forming a threedimensional,unsteady,and unstable flow field.The flow characteristics in an engine-like rotating multi-stage cavity with throughflow were investigated using particle image velocimetry,flow visualization technology and three-dimensional unsteady Reynolds-Averaged Navier-Stokes (RANS)simulations.The focus of current research was to understand the distribution of the mean swirl ratio and its variation with a wide range of non-dimensional parameters in the co-rotating cavity with high inlet pre-swirl axial throughflow.The maximum axial Reynolds number and rotational Reynolds numbers could reach 4.41×10^(4)and 1.24×10^(6),respectively.The velocity measurement results indicate that the mean swirl ratio is greater than 1 and decreases with an increase in the radial position.The flow structure is dominated by the Rossby number,and two different flow patterns (flow penetration and flow stratification) are identified and confirmed by flow visualization images.In the absence of buoyancy,the flow penetration caused by the precession of the throughflow makes it easier for the throughflow to reach a high radius region.Satisfactory consistency of results between measurements and numerical calculations is obtained.This study provides a theoretical basis and data support for toroidal vortex breakdown,which is of practical significance for the design of high-pressure compressor cavities.
基金funded and supported by the Department of Science and Technology of Guangdong Province(No.2022B1111020005)Key Laboratory of Guangdong Provincial Food and Drug Administration(No.2021ZDB03)+3 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(No.Guochao Liao,2019)Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515130005,2022A1515110270,202201011563)The Bureau of Science and Technology of Guangzhou City(No.HMJH_(2)019000)。
文摘Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.