Variations in coastline geometry caused by coastal engineering affect tides, storm surges, and storm tides. Three cluster land reclamation projects have been planned for construction in the Jiaojiang Estuary during th...Variations in coastline geometry caused by coastal engineering affect tides, storm surges, and storm tides. Three cluster land reclamation projects have been planned for construction in the Jiaojiang Estuary during the period from 2011 to 2023. They will cause significant changes in coastline geometry. In this study, a surge-tide coupled model was established based on a three-dimensional finite-volume coastal ocean model(FVCOM). A series of numerical experiments were carried out to investigate the effects of variations in coastline geometry on tides, storm surges, and storm tides. This model was calibrated using data observed at the Haimen and Ruian gauge stations and then used to reproduce the tides, storm surges, and storm tides in the Jiaojiang Estuary caused by Typhoon Winnie in 1997. Results show that the high tide level, peak storm surge, and high storm tide level at the Haimen Gauge Station increased along with the completion of reclamation projects, and the maximum increments caused by the third project were 0.13 m, 0.50 m, and 0.43 m, respectively. The envelopes with maximum storm tide levels of 7.0 m and 8.0 m inside the river mouth appeared to move seaward, with the latter shifting 1.8 km, 3.3 km, and 4.4 km due to the first project, second project, and third project, respectively. The results achieved in this study contribute to reducing the effects of, and preventing storm disasters after the land reclamation in the Jiaojiang Estuary.展开更多
Guanidinylated bioresponsive poly(amido amine)s polymers, CAR-CBA and CHL-CBA, weresynthesized by Michael-type addition reaction between guanidine hydrochloride(CAR) orchlorhexidine(CHL) and N,N-cystaminebisacrylamide...Guanidinylated bioresponsive poly(amido amine)s polymers, CAR-CBA and CHL-CBA, weresynthesized by Michael-type addition reaction between guanidine hydrochloride(CAR) orchlorhexidine(CHL) and N,N-cystaminebisacrylamide(CBA). Previous studies have shownthat both polymers had high transfection efficiencies as gene delivery carriers. In this study,we investigated the nucleolus localization abilities and cellular internalization pathways ofthese two polymers in gene delivery. Each polymer condensed plasmid DNA(p DNA) andformed nanoparticle complexes, and then their transfection studies were performed inMCF-7 cells. Both complexes were found enriched in nucleolus after cellular transfection,and their transfection efficiencies were significantly improved when transfection was per-formed on MCF-7 cells arrested at M phase. The transfection efficiency of CAR-CBA-pDNAwas inhibited by chlorpromazine, and cell endosomes were disrupted after being exposedto CAR-CBA-pDNA. In regards to CHL-CBA-pDNA, its transfection efficiency was not affected by three types of endocytosis inhibitors used in the study, and CHL-CBA-pDNA showed no effect on endosomes. Cellular lactate dehydrogenase release and membrane morphology were changed after cells were transfected by the two complexes. The results indicated that both CAR-CBA and CHL-CBA polymers demonstrated good nucleolus localization abilities. It was beneficial for transfection when cells were arrested at M phase. CAR-CBA-pDNA cellular internalization was involved with clathrin-mediated endocytosis pathway, and escaping from endosomal entrapment, while the cellular uptake of CHL-CBA-pDNA occurs via clathrin-and caveolae-independent mechanism.展开更多
RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, p...RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs,the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles. Currently, viruses, synthetic polymers, and lipid-based carriers are among the most widely studied vehicles for small RNA delivery. However, many drawbacks are reported to be associated with these delivery vehicles. There is a pressing need to replace them with more efficient and better-tolerated approaches. Exosomes secreted from the endocytic compartment of live cells, are a subtype of endogenous extracellular vesicles that transfer genetic and biochemical information among different cells, thus playing an important role in cellcell communication. Recently, accumulating attention has been focused on harnessing exosomes as nanaocarriers for small RNAs delivery. Due to their natural role in shuttling endogenous nucleic acid in our body, exosomes may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing foreign RNA carriers. Importantly,exosomes own intrinsic homing capacity that can guide small RNAs across natural membranous barriers. Moreover, such a capacity can be further improved by adding appropriate targeting moieties. In this manuscript, we briefly review the progress and challenges of RNAi therapy, and discuss the potential of exosomes' applications in small RNA delivery with focus on the most recent advances in exosome-based small RNA delivery for disease therapy.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
Bioequivalence(BE) assessment of topical dermatological products is a long standing challenge. The development of generic topical dermatological products has often been hampered due to the limited number of acceptable...Bioequivalence(BE) assessment of topical dermatological products is a long standing challenge. The development of generic topical dermatological products has often been hampered due to the limited number of acceptable approaches, which are capable of determining the BE between generic products and reference list products. The aim of this manuscript is to review different BE assessment approaches of topical dermatological products. Besides, the advances in BE evaluation and biowaivers are also provided. Currently, except in the case of dermatological corticosteroids, the golden rule to establish the BE of most topical dermatological products still heavily relied on clinical endpoint trials,which are often unreliable, time-consuming and expensive. The regulatory agencies and pharmaceutical industries are forging ahead to the development of new surrogate BE assessment approaches for other topical dermatological products. These promising approaches include dermatopharmacokinetic study(DPK), dermal microdialysis(DMD), in vitro studies, pharmacokinetic study(PK), near-infrared spectrometry(NIR), and confocal Raman spectroscopy(CRS). In addition, the expansion of biowaivers for topical dermatological products has been explored by pharmaceutical scientists. In conclusion, to accelerate the development and approval of topical dermatological products, emphasis should be put on the following areas, i.e., optimizing and standardizing the existing BE assessment methods, exploring novel alternatives of BE assessment approaches, and expanding biowaivers for topical dermatological products.展开更多
A cationic gene delivery vector, guanidinylated disulfide-containing poly(amido amine)(CARCBA), was synthesized by Michael addition reaction between N,N′-cystaminebisacrylamide(CBA) and guanidine hydrochloride(CAR). ...A cationic gene delivery vector, guanidinylated disulfide-containing poly(amido amine)(CARCBA), was synthesized by Michael addition reaction between N,N′-cystaminebisacrylamide(CBA) and guanidine hydrochloride(CAR). Gel permeation chromatography(GPC) was used to evaluate the molecular weight of synthesized CAR-CBA. Polyethyleneimine(PEI) with molecular weight of 25 kDa was adopted as a reference, and polyethylene glycols(PEG) with different molecular weights were used to establish a standard curve for determining the molecular weight of CAR-CBA. The effects of two critical factors, namely columns and eluents,on the molecular weight measurement of CAR-CBA were investigated to optimize the GPC quantitative method. The results showed that Ultrahydrogel columns(120, 250) and HAc–NaAc(0.5 M, pH 4.5) buffer solution were the optimal column and GPC eluent, respectively.The molecular weight of the synthesized CAR-CBA was analyzed by the optimized GPC method and determined to be 24.66 kDa.展开更多
基金supported by the National Nature Science Foundation of China(Grant No.40776007)Projects Founded by the Science and Technology Department of Zhejiang Province(Grant No.2009C03008-1)
文摘Variations in coastline geometry caused by coastal engineering affect tides, storm surges, and storm tides. Three cluster land reclamation projects have been planned for construction in the Jiaojiang Estuary during the period from 2011 to 2023. They will cause significant changes in coastline geometry. In this study, a surge-tide coupled model was established based on a three-dimensional finite-volume coastal ocean model(FVCOM). A series of numerical experiments were carried out to investigate the effects of variations in coastline geometry on tides, storm surges, and storm tides. This model was calibrated using data observed at the Haimen and Ruian gauge stations and then used to reproduce the tides, storm surges, and storm tides in the Jiaojiang Estuary caused by Typhoon Winnie in 1997. Results show that the high tide level, peak storm surge, and high storm tide level at the Haimen Gauge Station increased along with the completion of reclamation projects, and the maximum increments caused by the third project were 0.13 m, 0.50 m, and 0.43 m, respectively. The envelopes with maximum storm tide levels of 7.0 m and 8.0 m inside the river mouth appeared to move seaward, with the latter shifting 1.8 km, 3.3 km, and 4.4 km due to the first project, second project, and third project, respectively. The results achieved in this study contribute to reducing the effects of, and preventing storm disasters after the land reclamation in the Jiaojiang Estuary.
基金supported by National Natural Science Foundation of China (Grant no. 81373335)
文摘Guanidinylated bioresponsive poly(amido amine)s polymers, CAR-CBA and CHL-CBA, weresynthesized by Michael-type addition reaction between guanidine hydrochloride(CAR) orchlorhexidine(CHL) and N,N-cystaminebisacrylamide(CBA). Previous studies have shownthat both polymers had high transfection efficiencies as gene delivery carriers. In this study,we investigated the nucleolus localization abilities and cellular internalization pathways ofthese two polymers in gene delivery. Each polymer condensed plasmid DNA(p DNA) andformed nanoparticle complexes, and then their transfection studies were performed inMCF-7 cells. Both complexes were found enriched in nucleolus after cellular transfection,and their transfection efficiencies were significantly improved when transfection was per-formed on MCF-7 cells arrested at M phase. The transfection efficiency of CAR-CBA-pDNAwas inhibited by chlorpromazine, and cell endosomes were disrupted after being exposedto CAR-CBA-pDNA. In regards to CHL-CBA-pDNA, its transfection efficiency was not affected by three types of endocytosis inhibitors used in the study, and CHL-CBA-pDNA showed no effect on endosomes. Cellular lactate dehydrogenase release and membrane morphology were changed after cells were transfected by the two complexes. The results indicated that both CAR-CBA and CHL-CBA polymers demonstrated good nucleolus localization abilities. It was beneficial for transfection when cells were arrested at M phase. CAR-CBA-pDNA cellular internalization was involved with clathrin-mediated endocytosis pathway, and escaping from endosomal entrapment, while the cellular uptake of CHL-CBA-pDNA occurs via clathrin-and caveolae-independent mechanism.
基金the financial support from the National Natural Science Foundation of China (Grant No.81373335)Liaoning Province Natural Science Foundation (Grant No.20170541025)
文摘RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs,the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles. Currently, viruses, synthetic polymers, and lipid-based carriers are among the most widely studied vehicles for small RNA delivery. However, many drawbacks are reported to be associated with these delivery vehicles. There is a pressing need to replace them with more efficient and better-tolerated approaches. Exosomes secreted from the endocytic compartment of live cells, are a subtype of endogenous extracellular vesicles that transfer genetic and biochemical information among different cells, thus playing an important role in cellcell communication. Recently, accumulating attention has been focused on harnessing exosomes as nanaocarriers for small RNAs delivery. Due to their natural role in shuttling endogenous nucleic acid in our body, exosomes may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing foreign RNA carriers. Importantly,exosomes own intrinsic homing capacity that can guide small RNAs across natural membranous barriers. Moreover, such a capacity can be further improved by adding appropriate targeting moieties. In this manuscript, we briefly review the progress and challenges of RNAi therapy, and discuss the potential of exosomes' applications in small RNA delivery with focus on the most recent advances in exosome-based small RNA delivery for disease therapy.
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.
文摘Bioequivalence(BE) assessment of topical dermatological products is a long standing challenge. The development of generic topical dermatological products has often been hampered due to the limited number of acceptable approaches, which are capable of determining the BE between generic products and reference list products. The aim of this manuscript is to review different BE assessment approaches of topical dermatological products. Besides, the advances in BE evaluation and biowaivers are also provided. Currently, except in the case of dermatological corticosteroids, the golden rule to establish the BE of most topical dermatological products still heavily relied on clinical endpoint trials,which are often unreliable, time-consuming and expensive. The regulatory agencies and pharmaceutical industries are forging ahead to the development of new surrogate BE assessment approaches for other topical dermatological products. These promising approaches include dermatopharmacokinetic study(DPK), dermal microdialysis(DMD), in vitro studies, pharmacokinetic study(PK), near-infrared spectrometry(NIR), and confocal Raman spectroscopy(CRS). In addition, the expansion of biowaivers for topical dermatological products has been explored by pharmaceutical scientists. In conclusion, to accelerate the development and approval of topical dermatological products, emphasis should be put on the following areas, i.e., optimizing and standardizing the existing BE assessment methods, exploring novel alternatives of BE assessment approaches, and expanding biowaivers for topical dermatological products.
基金the National Natural Science Foundation of China for financial support(No.81373335)
文摘A cationic gene delivery vector, guanidinylated disulfide-containing poly(amido amine)(CARCBA), was synthesized by Michael addition reaction between N,N′-cystaminebisacrylamide(CBA) and guanidine hydrochloride(CAR). Gel permeation chromatography(GPC) was used to evaluate the molecular weight of synthesized CAR-CBA. Polyethyleneimine(PEI) with molecular weight of 25 kDa was adopted as a reference, and polyethylene glycols(PEG) with different molecular weights were used to establish a standard curve for determining the molecular weight of CAR-CBA. The effects of two critical factors, namely columns and eluents,on the molecular weight measurement of CAR-CBA were investigated to optimize the GPC quantitative method. The results showed that Ultrahydrogel columns(120, 250) and HAc–NaAc(0.5 M, pH 4.5) buffer solution were the optimal column and GPC eluent, respectively.The molecular weight of the synthesized CAR-CBA was analyzed by the optimized GPC method and determined to be 24.66 kDa.
