Currently approved therapeutical strategies for inflammatory bowel diseases(IBD)suffer from variable efficacy and association with risk of serious side effects.Therefore,efforts have been made in searching for alterna...Currently approved therapeutical strategies for inflammatory bowel diseases(IBD)suffer from variable efficacy and association with risk of serious side effects.Therefore,efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation.In this study,we show that the probiotic strain Ligilactobacillus salivarius Li01(Li01)and the phytochemical prebiotic resveratrol(RSV)have synergistic effect in ameliorating colitis in mice.Oral coadministration of Li01(109 CFU/d)and RSV(1.5 g/kg/d)promoted restoration of various inflammatory injuries and gut microbiota composition,exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice.The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1βand IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum.Moreover,the combination treatment was found to alter the composition and metabolism of the gut microbiota,especially influencing the production of short chain fatty acids and anti-inflammatory related molecules.The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor(AHR)and tryptophan metabolism pathway.Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites,including dihydroresveratrol(DHR),resveratrol-sulfate,and resveratrol-glucuronide.DHR was found to be the dominant metabolite of RSV in conventional and colitis mice.An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect.DHR is considered as a potential AHR ligand.The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1,SERT,and 5-HT7R leading to amelioration of colitis in mice.Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD;further investigation of this combination in clinical settings is warranted.展开更多
Developing functional ductal organoids(FDOs)is essential for liver regenerative medicine.We aimed to construct FDOs with biliary tree networks in rat decellularized liver scaffolds(DLSs)with primary cholangiocytes iso...Developing functional ductal organoids(FDOs)is essential for liver regenerative medicine.We aimed to construct FDOs with biliary tree networks in rat decellularized liver scaffolds(DLSs)with primary cholangiocytes isolated from mouse bile ducts.The developed FDOs were dynamically characterized by functional assays and metabolomics for bioprocess clarification.FDOs were reconstructed in DLSs retaining native structure and bioactive factors with mouse primary cholangiocytes expressing enriched biomarkers.Morphological assessment showed that biliary tree-like structures gradually formed from day 3 to day 14.The cholangiocytes in FDOs maintained high viability and expressed 11 specific biomarkers.Basal-apical polarity was observed at day 14 with immunostaining for E-cadherin and acetylatedα-tubulin.The rhodamine 123 transport assay and active collection of cholyl-lysyl-fluorescein exhibited the specific functions of bile secretion and transportation at day 14 compared to those in monolayer and hydrogel culture systems.The metabolomics analysis with 1075 peak pairs showed that serotonin,as a key molecule of the tryptophan metabolism pathway linked to biliary tree reconstruction,was specifically expressed in FDOs during the whole period of culture.Such FDOs with biliary tree networks and serotonin expression may be applied for disease modeling and drug screening,which paves the way for future clinical therapeutic applications.展开更多
Photoacoustic tomography(PAT) has the unique capability of visualizing optical absorption inside several centimeters-deep biological tissue with a high spatial resolution. However, single linear-array transducer-bas...Photoacoustic tomography(PAT) has the unique capability of visualizing optical absorption inside several centimeters-deep biological tissue with a high spatial resolution. However, single linear-array transducer-based PAT suffers from the limited-view challenge, and thus the synthetic aperture configuration is designed that still requires multichannel data acquisition hardware. Herein, a feasible synthetic aperture PAT based on compressed sensing reconstruction is proposed. Both the simulation and experimental results tested the theoretical model and validated that this approach can improve the image resolution and address the limited-view problem while preserving the target information with a fewer number of measurements.展开更多
The streak tube imaging light detection and ranging (LiDAR) is a new type of waveform sampling laser imaging radar whose echo signals are stripe images with a high frame rate. In this study, the morphological and st...The streak tube imaging light detection and ranging (LiDAR) is a new type of waveform sampling laser imaging radar whose echo signals are stripe images with a high frame rate. In this study, the morphological and statistical characteristics of stripe signals are analyzed in detail. Based on the concept of mathematical morphology denoising, connected domains are constructed in a noise- containing stripe image, and the noise is removed using the difference in connected domains area between signals and noises. It is shown that, for stripe signals, the proposed denoising method is significantly more efficient than Wiener filtering.展开更多
The work proposes a three-laser-beam streak tube imaging lidar system. Besides the main measuring laser beam,the second beam is used to decrease the error of time synchronization. The third beam has n+0.5 pixels' di...The work proposes a three-laser-beam streak tube imaging lidar system. Besides the main measuring laser beam,the second beam is used to decrease the error of time synchronization. The third beam has n+0.5 pixels' difference compared to the main measuring beam on a CCD, and it is used to correct the error caused by CCD discrete sampling. A three-dimensional(3D) imaging experiment using this scheme is carried out with time bin size of 0.066 ns(i.e., corresponding to a distance of 9.9 mm). An image of a 3D model is obtained with the depth resolution of 〈2 mm, which corresponds to ~0.2 pixel.展开更多
基金The animal experiments in this study were approved by the Tab of Animal Experimental Ethical Inspection of the First Affliated Hospital,College of Medicine,Zhejiang University(no.20211433).
文摘Currently approved therapeutical strategies for inflammatory bowel diseases(IBD)suffer from variable efficacy and association with risk of serious side effects.Therefore,efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation.In this study,we show that the probiotic strain Ligilactobacillus salivarius Li01(Li01)and the phytochemical prebiotic resveratrol(RSV)have synergistic effect in ameliorating colitis in mice.Oral coadministration of Li01(109 CFU/d)and RSV(1.5 g/kg/d)promoted restoration of various inflammatory injuries and gut microbiota composition,exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice.The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1βand IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum.Moreover,the combination treatment was found to alter the composition and metabolism of the gut microbiota,especially influencing the production of short chain fatty acids and anti-inflammatory related molecules.The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor(AHR)and tryptophan metabolism pathway.Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites,including dihydroresveratrol(DHR),resveratrol-sulfate,and resveratrol-glucuronide.DHR was found to be the dominant metabolite of RSV in conventional and colitis mice.An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect.DHR is considered as a potential AHR ligand.The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1,SERT,and 5-HT7R leading to amelioration of colitis in mice.Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD;further investigation of this combination in clinical settings is warranted.
基金supported by the National Key R&D Program of China(2022YFA1104102,2022YFA1104603,2022YFC2304801)the National Natural Science Foundation of China(81830073,82272426)+1 种基金the National Provincial special support program for high-level personnel recruitment(Ten-thousand Talents Program,2018RA4016)Zhejiang Public Welfare Project(LY21H030007,LGF21H200006).
文摘Developing functional ductal organoids(FDOs)is essential for liver regenerative medicine.We aimed to construct FDOs with biliary tree networks in rat decellularized liver scaffolds(DLSs)with primary cholangiocytes isolated from mouse bile ducts.The developed FDOs were dynamically characterized by functional assays and metabolomics for bioprocess clarification.FDOs were reconstructed in DLSs retaining native structure and bioactive factors with mouse primary cholangiocytes expressing enriched biomarkers.Morphological assessment showed that biliary tree-like structures gradually formed from day 3 to day 14.The cholangiocytes in FDOs maintained high viability and expressed 11 specific biomarkers.Basal-apical polarity was observed at day 14 with immunostaining for E-cadherin and acetylatedα-tubulin.The rhodamine 123 transport assay and active collection of cholyl-lysyl-fluorescein exhibited the specific functions of bile secretion and transportation at day 14 compared to those in monolayer and hydrogel culture systems.The metabolomics analysis with 1075 peak pairs showed that serotonin,as a key molecule of the tryptophan metabolism pathway linked to biliary tree reconstruction,was specifically expressed in FDOs during the whole period of culture.Such FDOs with biliary tree networks and serotonin expression may be applied for disease modeling and drug screening,which paves the way for future clinical therapeutic applications.
基金partially supported by the National Natural Science Foundation of China(Nos.61371045 and 11574064)the Shenzhen Science & Technology Program,China(No.JCYJ20160429115309834)the Science and Technology Development Plan Project of Shandong Province,China(Nos.2015GGX103016 and 2016GGX103032)
文摘Photoacoustic tomography(PAT) has the unique capability of visualizing optical absorption inside several centimeters-deep biological tissue with a high spatial resolution. However, single linear-array transducer-based PAT suffers from the limited-view challenge, and thus the synthetic aperture configuration is designed that still requires multichannel data acquisition hardware. Herein, a feasible synthetic aperture PAT based on compressed sensing reconstruction is proposed. Both the simulation and experimental results tested the theoretical model and validated that this approach can improve the image resolution and address the limited-view problem while preserving the target information with a fewer number of measurements.
文摘The streak tube imaging light detection and ranging (LiDAR) is a new type of waveform sampling laser imaging radar whose echo signals are stripe images with a high frame rate. In this study, the morphological and statistical characteristics of stripe signals are analyzed in detail. Based on the concept of mathematical morphology denoising, connected domains are constructed in a noise- containing stripe image, and the noise is removed using the difference in connected domains area between signals and noises. It is shown that, for stripe signals, the proposed denoising method is significantly more efficient than Wiener filtering.
基金supported by the National Key Scientific Instrument and Equipment Development Projects of China(No.2012YQ040164)
文摘The work proposes a three-laser-beam streak tube imaging lidar system. Besides the main measuring laser beam,the second beam is used to decrease the error of time synchronization. The third beam has n+0.5 pixels' difference compared to the main measuring beam on a CCD, and it is used to correct the error caused by CCD discrete sampling. A three-dimensional(3D) imaging experiment using this scheme is carried out with time bin size of 0.066 ns(i.e., corresponding to a distance of 9.9 mm). An image of a 3D model is obtained with the depth resolution of 〈2 mm, which corresponds to ~0.2 pixel.