In this paper we present a strategy for tuning the crystal morphology of pharmaceutical compounds by the appropriate choice of solvent via an optimization model. A three-stage approach involving a pre-design stage, a ...In this paper we present a strategy for tuning the crystal morphology of pharmaceutical compounds by the appropriate choice of solvent via an optimization model. A three-stage approach involving a pre-design stage, a product design stage and a post-design experimental verification stage is presented. The pre-design stage addresses the tormulation of the property constraint tor crystal morphology. This involves crystallization experiments aria development of property models and constraints for morphology. In the design stage various property requirements for the solvent along with crystal morphology are considered and the product design problem is formulated as a mixed integer nonlinear programming model.The design stage provides an optimal solvent/list of candidate solvents. Similar to the pre-design stage, in the post design experimental verification stage, the morphology of the crystals （precipitated from the designed solvent） is verified through crystallization experiments followed by product characterization via scanni＇ng electron microscopy, powder X-ray diffraction imaging and Fourier transform spectra analysis.展开更多
Coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCo V-2), has become a global pandemic. Clinical evidence suggests that the intestine is another high-risk organ for SAR...Coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCo V-2), has become a global pandemic. Clinical evidence suggests that the intestine is another high-risk organ for SARS-Co V-2 infection besides the lungs. However, a model that can accurately reflect the response of the human intestine to the virus is still lacking. Here, we created an intestinal infection model on a chip that allows the recapitulation of human relevant intestinal pathophysiology induced by SARSCo V-2 at organ level. This microengineered gut-on-chip reconstitutes the key features of the intestinal epithelium-vascular endothelium barrier through the three-dimensional(3 D) co-culture of human intestinal epithelial, mucin-secreting, and vascular endothelial cells under physiological fluid flow. The intestinal epithelium showed permissiveness for viral infection and obvious morphological changes with injury of intestinal villi, dispersed distribution of mucus-secreting cells, and reduced expression of tight junction(E-cadherin), indicating the destruction of the intestinal barrier integrity caused by virus.Moreover, the vascular endothelium exhibited abnormal cell morphology, with disrupted adherent junctions. Transcriptional analysis revealed abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection(e.g., upregulated cytokine genes), which may contribute to the injury of the intestinal barrier associated with gastrointestinal symptoms. This human organ system can partially mirror intestinal barrier injury and the human response to viral infection, which is not possible in existing in vitro culture models. It provides a unique and rapid platform to accelerate COVID-19 research and develop novel therapies.展开更多
A custom built 1310 nm center wavelength swept source optical coherence tomography instrument was used to measure morphological changes in treated and newly diagnosed untreated glaucomatous human Schlemm’s canal(SC)....A custom built 1310 nm center wavelength swept source optical coherence tomography instrument was used to measure morphological changes in treated and newly diagnosed untreated glaucomatous human Schlemm’s canal(SC).Thirty-seven primary open-angle glaucoma patients were divided into two groups depending on the patients having been treated or not.The statistical results showed that there were significant differences between the treated and untreated groups’SC areas(treated,7935.6875±680.003μm2;untreated,3890.71875±871.49844μm2;P<0.001),the circumferences(treated,580.37891±44.96529μm;untreated,381.9026±41.22123μm;P<0.001),and the long diameters(treated,272.87806±25.7254μm;untreated,185.24047±19.72786μm;P<0.001).We hypothesize that,after drug treatment,the SC will expand and the morphometric values especially the areas will become larger,thus helping to reduce intraocular pressure.展开更多
文摘In this paper we present a strategy for tuning the crystal morphology of pharmaceutical compounds by the appropriate choice of solvent via an optimization model. A three-stage approach involving a pre-design stage, a product design stage and a post-design experimental verification stage is presented. The pre-design stage addresses the tormulation of the property constraint tor crystal morphology. This involves crystallization experiments aria development of property models and constraints for morphology. In the design stage various property requirements for the solvent along with crystal morphology are considered and the product design problem is formulated as a mixed integer nonlinear programming model.The design stage provides an optimal solvent/list of candidate solvents. Similar to the pre-design stage, in the post design experimental verification stage, the morphology of the crystals （precipitated from the designed solvent） is verified through crystallization experiments followed by product characterization via scanni＇ng electron microscopy, powder X-ray diffraction imaging and Fourier transform spectra analysis.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29050301,XDB32030200,and XDA16020900)the National Key R&D Program of China(2017YFB0405404)+6 种基金the National Science and Technology Major Project(2018ZX09201017-001-001)Yunnan Key Research and Development Program(202003AD150009)the National Natural Science Foundation of China(31671038,31971373,8170347081803492)China Postdoctoral Science Foundation(2019M660065)Innovation Program of Science and Research from the Dalian Institute of Chemical PhysicsChinese Academy of Sciences(DICP I201934)。
文摘Coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCo V-2), has become a global pandemic. Clinical evidence suggests that the intestine is another high-risk organ for SARS-Co V-2 infection besides the lungs. However, a model that can accurately reflect the response of the human intestine to the virus is still lacking. Here, we created an intestinal infection model on a chip that allows the recapitulation of human relevant intestinal pathophysiology induced by SARSCo V-2 at organ level. This microengineered gut-on-chip reconstitutes the key features of the intestinal epithelium-vascular endothelium barrier through the three-dimensional(3 D) co-culture of human intestinal epithelial, mucin-secreting, and vascular endothelial cells under physiological fluid flow. The intestinal epithelium showed permissiveness for viral infection and obvious morphological changes with injury of intestinal villi, dispersed distribution of mucus-secreting cells, and reduced expression of tight junction(E-cadherin), indicating the destruction of the intestinal barrier integrity caused by virus.Moreover, the vascular endothelium exhibited abnormal cell morphology, with disrupted adherent junctions. Transcriptional analysis revealed abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection(e.g., upregulated cytokine genes), which may contribute to the injury of the intestinal barrier associated with gastrointestinal symptoms. This human organ system can partially mirror intestinal barrier injury and the human response to viral infection, which is not possible in existing in vitro culture models. It provides a unique and rapid platform to accelerate COVID-19 research and develop novel therapies.
基金supported by the Sichuan Youth Science&Technology Foundation(2013JQ0028)the National Natural Science Foundation of China(61108082)+1 种基金the West Light Foundation of the Chinese Academy of Sciencesthe National Major Scientific Equipment Program(2012YQ120080)
文摘A custom built 1310 nm center wavelength swept source optical coherence tomography instrument was used to measure morphological changes in treated and newly diagnosed untreated glaucomatous human Schlemm’s canal(SC).Thirty-seven primary open-angle glaucoma patients were divided into two groups depending on the patients having been treated or not.The statistical results showed that there were significant differences between the treated and untreated groups’SC areas(treated,7935.6875±680.003μm2;untreated,3890.71875±871.49844μm2;P<0.001),the circumferences(treated,580.37891±44.96529μm;untreated,381.9026±41.22123μm;P<0.001),and the long diameters(treated,272.87806±25.7254μm;untreated,185.24047±19.72786μm;P<0.001).We hypothesize that,after drug treatment,the SC will expand and the morphometric values especially the areas will become larger,thus helping to reduce intraocular pressure.
