Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epid...Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.展开更多
The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern.Microcystin-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely di...The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern.Microcystin-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely distributed in eutrophic waters.MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals.However,the underlying mechanisms of MCLR-induced liver toxicity are unclear.Herein,we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice.We established the first single-cell atlas ofmouse livers in response to MC-LR.Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treatedwith MC-LR are highly heterogeneous.Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3,which potentially contributed to hepatocyte apoptosis in response to MC-LR.Moreover,MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes.Furthermore,the MC-LR increased several subtypes of CD8+T cells with highly expressed multiple cytokines and chemokines.Overall,apart from directly inducing hepatocytes apoptosis,MC-LR activated proinflammatory Kupffer cell and CD8+T cells,and their interaction may constitute a hostile microenvironment that contributes to liver injury.Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.展开更多
Chronic alcohol consumption causes liver steatosis,cell death,and inflammation.Melatonin(MLT)is reported to alleviate alcoholic liver disease(ALD)-induced injury.However,its direct regulating targets in hepatocytes ar...Chronic alcohol consumption causes liver steatosis,cell death,and inflammation.Melatonin(MLT)is reported to alleviate alcoholic liver disease(ALD)-induced injury.However,its direct regulating targets in hepatocytes are not fully understood.In the current study,a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT.MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models(optimal doses of 10μmol/L and 5 mg/kg,respectively),including lowered liver steatosis,cell death,and inflammation.RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase(TERT)was a key downstream effector of MLT.Biophysical assay found that epidermal growth factor receptor(EGFR)on the hepatocyte surface was a direct binding and regulating target of MLT.Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection,partly through the regulation of nuclear brahma-related gene-1(BRG1).Long-term administration(90 days)of MLT in healthy mice did not cause evident adverse effect.In conclusion,MLT is an efficacious and safe agent for ALD alleviation.Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis.MLT might be used as a complimentary agent for alcoholics.展开更多
Objective:Due to limited imaging conditions,the quality of fundus images is often unsatisfactory,especially for images photographed by handheld fundus cameras.Here,we have developed an automated method based on combin...Objective:Due to limited imaging conditions,the quality of fundus images is often unsatisfactory,especially for images photographed by handheld fundus cameras.Here,we have developed an automated method based on combining two mirror-symmetric generative adversarial networks(GANs)for image enhancement.Methods:A total of 1047 retinal images were included.The raw images were enhanced by a GAN-based deep enhancer and another methods based on luminosity and contrast adjustment.All raw images and enhanced images were anonymously assessed and classified into 6 levels of quality classification by three experienced ophthalmologists.The quality classification and quality change of images were compared.In addition,imagedetailed reading results for the number of dubiously pathological fundi were also compared.Results:After GAN enhancement,42.9% of images increased their quality,37.5%remained stable,and 19.6%decreased.After excluding the images at the highest level(level 0)before enhancement,a large number(75.6%)of images showed an increase in quality classification,and only a minority(9.3%)showed a decrease.The GANenhanced method was superior for quality improvement over a luminosity and contrast adjustment method(P<0.001).In terms of image reading results,the consistency rate fluctuated from 86.6%to 95.6%,and for the specific disease subtypes,both discrepancy number and discrepancy rate were less than 15 and 15%,for two ophthalmologists.Conclusions:Learning the style of high-quality retinal images based on the proposed deep enhancer may be an effective way to improve the quality of retinal images photographed by handheld fundus cameras.展开更多
基金supported by the National Natural Science Foundation of China,No.82122009 (to JX)Science Research Foundation ofAier Eye Hospital Group,No.AM2001D1 (to JX)the Natural Science Foundation of Hunan Province,No.2020JJ5002 (to SJ)。
文摘Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.
基金supported by the National Key Research and Development Program of China(Nos.2020YFA0908000 and 2022YFC2303600)the Guangdong-Dongguan Joint Fund Regional Cultivation Project(No.2021B1515140033)+7 种基金the Dongguan Science and Technology of Social Development Program(No.20221800905732)the National Natural Science Foundation of China(Nos.82074098,82374063,82274182,81841001,and 82173914)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases),Shenzhen Science and Technology Innovation Commission(Nos.JCYJ20220818102613029,JCYJ20210324114014039,and JCYJ20210324115800001)Guangdong Basic and Applied Basic Research Foundation(No.2020A1515110549)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202002)Shenzhen Governmental Sustainable Development Fund(No.KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases(No.ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(No.SZGSP001).
文摘The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern.Microcystin-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely distributed in eutrophic waters.MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals.However,the underlying mechanisms of MCLR-induced liver toxicity are unclear.Herein,we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice.We established the first single-cell atlas ofmouse livers in response to MC-LR.Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treatedwith MC-LR are highly heterogeneous.Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3,which potentially contributed to hepatocyte apoptosis in response to MC-LR.Moreover,MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes.Furthermore,the MC-LR increased several subtypes of CD8+T cells with highly expressed multiple cytokines and chemokines.Overall,apart from directly inducing hepatocytes apoptosis,MC-LR activated proinflammatory Kupffer cell and CD8+T cells,and their interaction may constitute a hostile microenvironment that contributes to liver injury.Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.
基金supported by grants from National Natural Science Foundation of China(82122009,82170605,81873573 and 81970515)Guangdong Natural Science Funds for Distinguished Young Scholar(2019B151502013,China)。
文摘Chronic alcohol consumption causes liver steatosis,cell death,and inflammation.Melatonin(MLT)is reported to alleviate alcoholic liver disease(ALD)-induced injury.However,its direct regulating targets in hepatocytes are not fully understood.In the current study,a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT.MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models(optimal doses of 10μmol/L and 5 mg/kg,respectively),including lowered liver steatosis,cell death,and inflammation.RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase(TERT)was a key downstream effector of MLT.Biophysical assay found that epidermal growth factor receptor(EGFR)on the hepatocyte surface was a direct binding and regulating target of MLT.Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection,partly through the regulation of nuclear brahma-related gene-1(BRG1).Long-term administration(90 days)of MLT in healthy mice did not cause evident adverse effect.In conclusion,MLT is an efficacious and safe agent for ALD alleviation.Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis.MLT might be used as a complimentary agent for alcoholics.
文摘Objective:Due to limited imaging conditions,the quality of fundus images is often unsatisfactory,especially for images photographed by handheld fundus cameras.Here,we have developed an automated method based on combining two mirror-symmetric generative adversarial networks(GANs)for image enhancement.Methods:A total of 1047 retinal images were included.The raw images were enhanced by a GAN-based deep enhancer and another methods based on luminosity and contrast adjustment.All raw images and enhanced images were anonymously assessed and classified into 6 levels of quality classification by three experienced ophthalmologists.The quality classification and quality change of images were compared.In addition,imagedetailed reading results for the number of dubiously pathological fundi were also compared.Results:After GAN enhancement,42.9% of images increased their quality,37.5%remained stable,and 19.6%decreased.After excluding the images at the highest level(level 0)before enhancement,a large number(75.6%)of images showed an increase in quality classification,and only a minority(9.3%)showed a decrease.The GANenhanced method was superior for quality improvement over a luminosity and contrast adjustment method(P<0.001).In terms of image reading results,the consistency rate fluctuated from 86.6%to 95.6%,and for the specific disease subtypes,both discrepancy number and discrepancy rate were less than 15 and 15%,for two ophthalmologists.Conclusions:Learning the style of high-quality retinal images based on the proposed deep enhancer may be an effective way to improve the quality of retinal images photographed by handheld fundus cameras.
