Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In t...Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue(cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.展开更多
BACKGROUND As the main component of oral contraceptives(OCs),ethinylestradiol(EE)has been widely applied as a model drug to induce murine intrahepatic cholestasis.The clinical counterpart of EE-induced cholestasis inc...BACKGROUND As the main component of oral contraceptives(OCs),ethinylestradiol(EE)has been widely applied as a model drug to induce murine intrahepatic cholestasis.The clinical counterpart of EE-induced cholestasis includes women who are taking OCs,sex hormone replacement therapy,and susceptible pregnant women.Taking intrahepatic cholestasis of pregnancy(ICP)as an example,ICP consumes the medical system due to its high-risk fetal burden and the impotency of ursodeoxycholic acid in reducing adverse perinatal outcomes.AIM To explore the mechanisms and therapeutic strategies of EE-induced cholestasis based on the liver immune microenvironment.METHODS Male C57BL/6J mice or invariant natural killer T(iNKT)cell deficiency(Jα18-/-mice)were administered with EE(10 mg/kg,subcutaneous)for 14 d.RESULTS Both Th1 and Th2 cytokines produced by NKT cells increased in the liver skewing toward a Th1 bias.The expression of the chemokine/chemokine receptor Cxcr6/Cxcl16,toll-like receptors,Ras/Rad,and PI3K/Bad signaling was upregulated after EE administration.EE also influenced bile acid synthase Cyp7a1,Cyp8b1,and tight junctions ZO-1 and Occludin,which might be associated with EEinduced cholestasis.iNKT cell deficiency(Jα18-/-mice)robustly alleviated cholestatic liver damage and lowered the expression of the abovementioned signaling pathways.CONCLUSION Hepatic NKT cells play a pathogenic role in EE-induced intrahepatic cholestasis.Our research improves the understanding of intrahepatic cholestasis by revealing the hepatic immune microenvironment and also provides a potential clinical treatment by regulating iNKT cells.展开更多
BACKGROUND： Tobacco smoke exposure is recognized as a health risk for pregnant women and it is increasingly evident that tobacco smoke affects the development of brain. Recently, associations between maternal smoking...BACKGROUND： Tobacco smoke exposure is recognized as a health risk for pregnant women and it is increasingly evident that tobacco smoke affects the development of brain. Recently, associations between maternal smoking during pregnancy and subsequent mental health problems in offspring have been reported. OBJECTIVE： To observe the effect of passive smoking on the morphology of nerve tissues and the ultrastructure of neuroepithelial cells during embryogenesis in golden hamster at different pregnant period. DESIGN： A randomized control study. SETTING： Department of Histology and embryology, Qingdao University. MATERIALS： Adult golden hamsters, including 40 males and 40 females that had not delivered, weighing （105±5） g, were provided by Shenyang Changsheng Biotechnology, Co.,Ltd. At 20 ： 00 - 21 ： 00, one male and one female were matched in each cage, and their mating was observed. The vaginal swabs were examined the next day and the day of positive sperm was taken as embryonic day 1 （E1）. METHODS： The experiment was completed in the Department of Histology and Embryology of Qingdao University from September 2001 to September 2003. （1） Abnormality caused by smoking, grouping and model establishment： A total of 40 healthy pregnant golden hamsters were randomly divided into control group （n =20） and experimental group （n =20）. The hamsters in the experimental group were exposed to tobacco smoke from embryonic day 4 to 7, 3 times per day, continuously 1 hour per time, 1 cigarette per golden hamster, for 4 consecutive days in the self-made chamber. The animals in the control group were given the same conditions as those in the experimental group except exposure to smoke. （2） Observation with transmission electron microscope： According to different gestational ages, the experimental group and the control group were all divided 4 subgroups （Groups A, B, C and D） respectively, and 5 hamsters in each subgroup. The pregnant golden hamsters were anaesthetized with 1 g/L pentobarbital sodium at 12 ： 00 and 18 ： 00 at E8, 8 ： 00 at E9 and 8 ： 00 at E10, and all the pregnant uteruses were divulsed under the stereomicroscope. The development of the neural plate, neural groove and neural tube were observed. Meanwhile, the amount of normal embryos and abnormal embryos including the neural tube defect ratios were recorded. （3） Electron microscopic specimen preparation and observation： Three embryos of each group ad libtium were fixed. The alternations of neuroepithelial ultrastrnctures were observed with transmission and scanning electron microscopes. MAIN OUTCOME MEASURES： （1） The incidences of abnormality of nervous system development were observed under stereomicroscope and scanning electron microscope in smoking group and the control group; （2） Alternations of neuroepithelial ultrastructures were observed with transmission electron microscope. RESULTS： All the 40 pregnant golden hamsters were involved in the final analysis. （1） Manifestations and incidence of nervous system dysplasia： Passive smoking could induce dymorphogenesis during neurnlation, which mainly presented as growth retardation, spina bifida and failure of formation of neural tubes; The incidences of the nervous system dysplasia in the experimental groups [20%（10/49）, 27%（14/51）, 32% （19/59）, 27% （17/63）] were higher than those in the corresponding control groups [0. 2% （1/57）, 4% （2/53）, 4% （2/52）, P 〈 0.01]. （2） Histomorphological changes at different time points after spermatiation observed with transmission and scanning electron microscopes： In the control group, the embryos formed C-shape columned embryos, anterior and posterior neuropores were all closure at 10 ： 00 on E10; In the experimental group, unfused anterior and posterior neuropores still could be found, and some embryos presented spina bifida at 10 ： 00 on E10. In the control group, neuroepithelial cell arranged tidily and closely, the boundary of the cells was clear, the flee surface of neuroepithelial had a mass of long and regular microvillus, and the surface of mesenchymal cell around the neuroepithelium had many processes which mutually related at 12 ： 00 on E8. In the experimental group, the neuroepithelial cells arranged irregularly and the intercellular spaces became wide at 12 ： 00 on E8. The apical portion of many neuroepithelial cells bulged into the lumen and many microvilli were shorted and swollen. The quantity of the microvillus reduced gradually, evenly disappeared with the increasing of gestational age at 18：00 on E8. Under transmission electron microscope, the neuroepithelial cells in experimental embryos arranged irregularly. There were many visible materials in the intercellular space which increased the breadth and anomaly. It was apparent that passive smoking evoked major alterations in neuroepithelial cytoarchitecture. Junctional complex reduced. Many microvilli were shorted and swollen, even the apical portion of many neuroepithelial cells bulged, and abscised into the lumen. A lot of vacuolation appeared in the cytoplasm of neuroepithelia and mesenchymal cell around the neuroepithelium. The cristae of mitochondria reduced even disappeared, and some mitochondria became elongate. Irregular nuclear, increased heterochromatin and karyopycnosis/karyorrhexis were observed easily. Perinuclear cisternae partially swelled and embraced tangible material （maybe the material from nuclear）. Some death cells separated into a lot of apoptotic bodies. Some apoptotic bodies were found in the cytoplasm of other healthy-looking or healthy cells. CONCLUSION： Passive smoking may induce degeneration, apoptosis, and cells loss in the neural epithelium, thereby result in failure of formation and differentiation of neural tube. It is an important way by which passive smoking caused neural tube defects.展开更多
Keriya River,one of the ancient Four Green Corridors in the Tarim Basin,recording the changes of climate-environment and the ancient Silk Road of the region.According to the archaeological data,historical materials an...Keriya River,one of the ancient Four Green Corridors in the Tarim Basin,recording the changes of climate-environment and the ancient Silk Road of the region.According to the archaeological data,historical materials and paleoclimates information,its eeo-environment and climate have taken great changes since the 1.09 Ma B.P,especially during the recent 2,000 years,many famous ancient cities having been abandoned and the south route of the Silk Road has been moved southward.This study illustrates the capability of the remote sensing data(radar data,topographic data and optical images)and historical materials,in mapping the ancient drainage networks.A major paleodrainage system of Keriya River has linked the Kunlun Mountains to the Tienshan Mountains,possibly as far back as the early Pleistocene.The Keriya River will have important implications for not only the understanding of the paleoenvironments and paleoclimates of Tarim Basin from the early Pleistocene to the Holocene,but also the changes of the Silk Road.展开更多
Polysaccharides of Momordica charantia have been reported to be the primary bioactive components that confer its antioxidant activity. To some degree, antioxidants may provide beneficial effects on neuronal damage ind...Polysaccharides of Momordica charantia have been reported to be the primary bioactive components that confer its antioxidant activity. To some degree, antioxidants may provide beneficial effects on neuronal damage induced by seizures. However, the protective effects of Momordica charantia polysaccharides (MCPs) on seizures remain unclear. In this study, our purpose was to investigate the effects of MCPs on oxidative stress and neurodegeneration in an experimental Kainic acid (KA)-induced rat seizure model. MCPs treatments decreased the level of malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus of the KA-induced animal model. Moreover, MCPs significantly attenuated KA-induced neuronal loss in the CA1 and CA3 hippocampal regions. Based on these results, MCPs exert neuroprotective effects by attenuating KA-induced neuronal damage in the brain through their free radical scavenging activities.展开更多
The interest in covalent drugs has resurged in recent decades,spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening.Herein,we present CarsiDock...The interest in covalent drugs has resurged in recent decades,spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening.Herein,we present CarsiDock-Cov,a new paradigm distinguishing itself as the first deep learning(DL)-guided approach for covalent docking.CarsiDock-Cov retains the core components of its non-covalent predecessor,leveraging a DL model pretrained on millions of docking complexes to predict protein—ligand distance matrices,along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses.Additionally,it incorporates several key enhance-ments specifically tailored to optimize the protocol for covalent docking applications.Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands,and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor,but also exhibits competitive performance against various state-of-the-art covalent docking tools.Collectively,our approach represents a significant advance in co-valent docking methodology,offering an automated and efficient solution that shows considerable prom-ise for accelerating covalent drug discovery and design.展开更多
Dear Editor,Chemerin functions as both an adipocytokine and a chemotactic factor and plays key roles in adipogenesis and inflammation(Bozaoglu et al.,2007;Bondue et al.,2011).The chemerin receptors chemokine-like rece...Dear Editor,Chemerin functions as both an adipocytokine and a chemotactic factor and plays key roles in adipogenesis and inflammation(Bozaoglu et al.,2007;Bondue et al.,2011).The chemerin receptors chemokine-like receptor 1(CMKLR1)and G protein-coupled receptor 1(GPR1),play crucial roles in regulating obesity,inflammation,and cancer,highlighting their potential as therapeutic targets(Bozaoglu et al.,2007;Ernst and Sinal,2010;Su et al.,2021).Although both receptors recognize the same ligand,chemerin,and share high sequence identity,they exhibit distinct signaling properties and biological functions(Bozaoglu et al.,2007;De Henau et al.,2016;Fischer et al.,2021).CMKLR1 is the canonical chemerin receptor that mediates both G protein and arrestin signaling,while GPR1 exhibits weak G protein signaling but strong arrestin-dependent and-independent internalization(De Henau et al.,2016;Fig.1A and 1B).The chemerin-CMKLR1 axis regulates lipid and glucose metabolism(Kennedy and Davenport,2018),and is associated with chronic inflammation,obesity,and obesity-related disorders such as insulin resistance and metabolic syndrome,with several compounds and antibodies under preclinical or early clinical investigation(Goralski et al.,2007;Kennedy et al.,2016;Trilleaud et al.,2021).In contrast,the mechanisms of atypical signaling and biological function of GPR1 remain unclear.展开更多
Socialmedia such as Twitter is increasingly beingused as an effective platform to observe human behaviors in disastrous events.However,uneven social media use among different groups of population in different regions ...Socialmedia such as Twitter is increasingly beingused as an effective platform to observe human behaviors in disastrous events.However,uneven social media use among different groups of population in different regions could lead to biased consequences and affect disaster resilience.This paper studies the Twitter use during 2017 Hurricane Harvey in 76 counties in Texas and Louisiana.We seek to answer a fundamental question:did socialgeographical disparities of Twitter use exist during the three phases of emergency management(preparedness,response,recovery)?We employed a Twitter data mining framework to process the data and calculate two indexes:Ratio and Sentiment.Regression analyses between the Ratio indexes and the social-geographical characteristics of the counties at the three phrases reveal significant social and geographical disparities in Twitter use during Hurricane Harvey.Communities with higher disasterrelated Twitter use in Harvey generally were communities having better social and geographical conditions.These results of Twitter use patterns can be used to compare with future similar studies to see whether the Twitter use disparities have increased or decreased.Future research is also needed to examine the effects of Twitter use disparities on disaster resilience and to test whether Twitter use can predict community resilience.展开更多
Craters, one of the most significant features of the lunar surface, have been widely researched because they offer us the relative age of the surface unit as well as crucial geological information. Research on crater ...Craters, one of the most significant features of the lunar surface, have been widely researched because they offer us the relative age of the surface unit as well as crucial geological information. Research on crater detec- tion algorithms （CDAs） of the Moon and other planetary bodies has concentrated on detecting them from imagery data, but the computational cost of detecting large craters using images makes these CDAs impractical. This paper presents a new approach to crater detection that utilizes a digital elevation model instead of images; this enables fully automatic global detection of large craters. Craters were delineated by terrain attributes, and then thresholding maps of terrain attributes were used to transform topographic data into a binary image, finally craters were detected by using the Hough Transform from the binary image. By using the proposed algorithm, we produced a catalog of all craters ≥ 10 km in diameter on the lunar surface and analyzed their distribution and population characteristics.展开更多
This paper develops a social media-disaster resilience analysis framework by categorizing types of social media use and their challenges to better understand and assess its role in disaster resilience research and man...This paper develops a social media-disaster resilience analysis framework by categorizing types of social media use and their challenges to better understand and assess its role in disaster resilience research and management.The framework is derived primarily from several case studies of Twitter use in three hurricane events in the United States-Hurricanes Isaac,Sandy,and Harvey.The paper first outlines four major contributions of social media data for disaster resilience research and management,which include serving as an effective communication platform,providing ground truth information for emergency response and rescue operations,providing information on people's sentiments,and allowing predictive modeling.However,there are four_key challenges to its uses,which include,easy spreading of false information,social and geographical disparities of Twitter use,technical issues on processing and analyzing big and noisy data,especially on improving the locational accuracy of the tweets,and algorithm bias in Al and other types of modeling.Then,the paper proposes twenty strategies that the four sectors of the social media community-organizations,individuals,social media companies,and researchers-could take to improve social media use to increase disaster resilience.展开更多
The Covid-19 has presented an unprecedented challenge to public health worldwide.However,residents in different countries showed diverse levels of Covid-19 awareness during the outbreak and suffered from uneven health...The Covid-19 has presented an unprecedented challenge to public health worldwide.However,residents in different countries showed diverse levels of Covid-19 awareness during the outbreak and suffered from uneven health impacts.This study analyzed the global Twitter data from January 1st to June 30th,2020,to answer two research questions.What are the linguistic and geographical disparities of public awareness in the Covid-19 outbreak period reflected on social media?Does significant association exist between the changing Covid-19 awareness and the pandemic outbreak?We established a Twitter data mining framework calculating the Ratio index to quantify and track awareness.The lag correlations between awareness and health impacts were examined at global and country levels.Results show that users presenting the highest Covid-19 awareness were mainly those tweeting in the official languages of India and Bangladesh.Asian countries showed more disparities in awareness than European countries,and awareness in Eastern Europe was higher than in central Europe.Finally,the Ratio index had high correlations with global mortality rate,global case fatality ratio,and country-level mortality rate,with 21-31,35-42,and 13–18 leading days,respectively.This study yields timely insights into social media use in understanding human behaviors for public health research.展开更多
Quantitative assessment of community resilience can provide support for hazard mitigation,disaster risk reduction,disaster relief,and long-term sustainable development.Traditional resilience assessment tools are mostl...Quantitative assessment of community resilience can provide support for hazard mitigation,disaster risk reduction,disaster relief,and long-term sustainable development.Traditional resilience assessment tools are mostly theory-driven and lack empirical validation,which impedes scientific understanding of community resilience and practical decision-making of resilience improvement.In the advent of the Big Data Era,the increasing data availability and advances in computing and modeling techniques offer new opportunities to understand,measure,and promote community resilience.This article provides a comprehensive review of the definitions of community resilience,along with the traditional and emerging data and methods of quantitative resilience measurement.The theoretical bases,modeling principles,advantages,and disadvantages of the methods are discussed.Finally,we point out research avenues to overcome the existing challenges and develop robust methods to measure and promote community resilience.This article establishes guidance for scientists to further advance disaster research and for planners and policymakers to design actionable tools to develop sustainable and resilient communities.展开更多
Catalyst innovation lies at the heart of transition-metal-catalyzed reaction development.In this article,we have explored the C(sp2)–H alkenylation activity with novel spirocyclic N-heterocyclic carbene(NHC)-based cy...Catalyst innovation lies at the heart of transition-metal-catalyzed reaction development.In this article,we have explored the C(sp2)–H alkenylation activity with novel spirocyclic N-heterocyclic carbene(NHC)-based cyclometalated ruthenium pincer catalyst system,SNRu-X.After screening catalyst and condition,a high valent Ru(Ⅳ)dioxide(X=O_(2))species has demonstrated superior reactivity in the catalytic alkenylation of aromatic and olefinic C–H bonds with unactivated alkenyl bromides and triflates.This reaction has achieved the easy construction of a wide range of(hetero)aromatic alkenes and dienes,in good to excellent yields with exclusive selectivity.Preliminary mechanistic studies indicate that this reaction may proceed through a single electron transfer(SET)triggered oxidative addition,by doing so,providing valuable complementary to classical alkenylation reactions that are dependent on activated alkenyl precursors.展开更多
With the increased frequency of natural hazards and disasters and consequent losses,it is imperative to develop efficient and timely strategies for emergency response and relief operations.In this paper,we propose a c...With the increased frequency of natural hazards and disasters and consequent losses,it is imperative to develop efficient and timely strategies for emergency response and relief operations.In this paper,we propose a cyberGIS-enabled multi-criteria spatial decision support system for supporting rapid decision making during emergency management.It combines a high-performance computing environment(cyberGIS-Jupyter)and multi-criteria decision analysis models(Weighted Sum Model(WSM)and Technique for Order Preference by Similarity to Ideal Solution Model(TOPSIS))with various types of social vulnerability indicators to solve decision problems that contain conflicting evaluation criteria in a flood emergency situation.Social media data(e.g.Twitter data)was used as an additional tool to support the decision-making process.Our case study involves two decision goals generated based on a past flood event in the city of Austin,Texas,U.S.A.As our result shows,WSM produces more diverse values and higher output category estimations than the TOPSIS model.Finally,the model was validated using an innovative questionnaire.This cyberGIS-enabled spatial decision support system allows collaborative problem solving and efficient knowledge transformation between decision makers,where different emergency responders can formulate their decision objectives,select relevant evaluation criteria,and perform interactive weighting and sensitivity analyses.展开更多
The intensity of extreme weather events has been increasing,posing a unique threat to society and highlighting the importance of our electrical power system,a key component in our infrastructure.In severe weather even...The intensity of extreme weather events has been increasing,posing a unique threat to society and highlighting the importance of our electrical power system,a key component in our infrastructure.In severe weather events,quickly identifying power outage impact zones and affected communities is crucial for informed disaster response.However,a lack of household-level power outage data impedes timely and precise assessments.To address these challenges,we introduced an analytical workflow using NASA’s Black Marble daily nighttime light(NTL)images to detect power outages from the 2021 Winter Storm Uri.This workflow includes adjustments to mitigate viewing angle and snow reflection effects.Power outage is detected by comparing storm-time and baseline(normal condition)NTL images using an empirical adjusted equation.The outcomes of the workflow are 500-meter resolution power outage maps,which have the optimal correlation with real outage tracking data when NTL intensity is reduced by 26%.With the resultant power outage maps,we analyzed the relations between power outages and disadvantaged populations in 126 Texas counties and 4182 census tracts to evaluate environmental justice in the storm.The results show that Latino/Hispanic communities tend to suffer more from power outages at both the county and census tract levels.展开更多
基金supported by the National Natural Science Foundation of China,No. 81671164 (to SHQ)the Natural Science Foundation of Jiangsu Province of China,No. BK20211348 (to SHQ)Xuzhou Basic Research Program,No. KC21030 (to LYH)。
文摘Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue(cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.
基金Supported by the National Natural Science Foundation of China,No.82073948 and 81703626National Innovation and Entrepreneurship Training Program for Undergraduate,No.202210316040Z。
文摘BACKGROUND As the main component of oral contraceptives(OCs),ethinylestradiol(EE)has been widely applied as a model drug to induce murine intrahepatic cholestasis.The clinical counterpart of EE-induced cholestasis includes women who are taking OCs,sex hormone replacement therapy,and susceptible pregnant women.Taking intrahepatic cholestasis of pregnancy(ICP)as an example,ICP consumes the medical system due to its high-risk fetal burden and the impotency of ursodeoxycholic acid in reducing adverse perinatal outcomes.AIM To explore the mechanisms and therapeutic strategies of EE-induced cholestasis based on the liver immune microenvironment.METHODS Male C57BL/6J mice or invariant natural killer T(iNKT)cell deficiency(Jα18-/-mice)were administered with EE(10 mg/kg,subcutaneous)for 14 d.RESULTS Both Th1 and Th2 cytokines produced by NKT cells increased in the liver skewing toward a Th1 bias.The expression of the chemokine/chemokine receptor Cxcr6/Cxcl16,toll-like receptors,Ras/Rad,and PI3K/Bad signaling was upregulated after EE administration.EE also influenced bile acid synthase Cyp7a1,Cyp8b1,and tight junctions ZO-1 and Occludin,which might be associated with EEinduced cholestasis.iNKT cell deficiency(Jα18-/-mice)robustly alleviated cholestatic liver damage and lowered the expression of the abovementioned signaling pathways.CONCLUSION Hepatic NKT cells play a pathogenic role in EE-induced intrahepatic cholestasis.Our research improves the understanding of intrahepatic cholestasis by revealing the hepatic immune microenvironment and also provides a potential clinical treatment by regulating iNKT cells.
基金the Natural Science Foundation of Shandong Province, No. Y98C13042
文摘BACKGROUND： Tobacco smoke exposure is recognized as a health risk for pregnant women and it is increasingly evident that tobacco smoke affects the development of brain. Recently, associations between maternal smoking during pregnancy and subsequent mental health problems in offspring have been reported. OBJECTIVE： To observe the effect of passive smoking on the morphology of nerve tissues and the ultrastructure of neuroepithelial cells during embryogenesis in golden hamster at different pregnant period. DESIGN： A randomized control study. SETTING： Department of Histology and embryology, Qingdao University. MATERIALS： Adult golden hamsters, including 40 males and 40 females that had not delivered, weighing （105±5） g, were provided by Shenyang Changsheng Biotechnology, Co.,Ltd. At 20 ： 00 - 21 ： 00, one male and one female were matched in each cage, and their mating was observed. The vaginal swabs were examined the next day and the day of positive sperm was taken as embryonic day 1 （E1）. METHODS： The experiment was completed in the Department of Histology and Embryology of Qingdao University from September 2001 to September 2003. （1） Abnormality caused by smoking, grouping and model establishment： A total of 40 healthy pregnant golden hamsters were randomly divided into control group （n =20） and experimental group （n =20）. The hamsters in the experimental group were exposed to tobacco smoke from embryonic day 4 to 7, 3 times per day, continuously 1 hour per time, 1 cigarette per golden hamster, for 4 consecutive days in the self-made chamber. The animals in the control group were given the same conditions as those in the experimental group except exposure to smoke. （2） Observation with transmission electron microscope： According to different gestational ages, the experimental group and the control group were all divided 4 subgroups （Groups A, B, C and D） respectively, and 5 hamsters in each subgroup. The pregnant golden hamsters were anaesthetized with 1 g/L pentobarbital sodium at 12 ： 00 and 18 ： 00 at E8, 8 ： 00 at E9 and 8 ： 00 at E10, and all the pregnant uteruses were divulsed under the stereomicroscope. The development of the neural plate, neural groove and neural tube were observed. Meanwhile, the amount of normal embryos and abnormal embryos including the neural tube defect ratios were recorded. （3） Electron microscopic specimen preparation and observation： Three embryos of each group ad libtium were fixed. The alternations of neuroepithelial ultrastrnctures were observed with transmission and scanning electron microscopes. MAIN OUTCOME MEASURES： （1） The incidences of abnormality of nervous system development were observed under stereomicroscope and scanning electron microscope in smoking group and the control group; （2） Alternations of neuroepithelial ultrastructures were observed with transmission electron microscope. RESULTS： All the 40 pregnant golden hamsters were involved in the final analysis. （1） Manifestations and incidence of nervous system dysplasia： Passive smoking could induce dymorphogenesis during neurnlation, which mainly presented as growth retardation, spina bifida and failure of formation of neural tubes; The incidences of the nervous system dysplasia in the experimental groups [20%（10/49）, 27%（14/51）, 32% （19/59）, 27% （17/63）] were higher than those in the corresponding control groups [0. 2% （1/57）, 4% （2/53）, 4% （2/52）, P 〈 0.01]. （2） Histomorphological changes at different time points after spermatiation observed with transmission and scanning electron microscopes： In the control group, the embryos formed C-shape columned embryos, anterior and posterior neuropores were all closure at 10 ： 00 on E10; In the experimental group, unfused anterior and posterior neuropores still could be found, and some embryos presented spina bifida at 10 ： 00 on E10. In the control group, neuroepithelial cell arranged tidily and closely, the boundary of the cells was clear, the flee surface of neuroepithelial had a mass of long and regular microvillus, and the surface of mesenchymal cell around the neuroepithelium had many processes which mutually related at 12 ： 00 on E8. In the experimental group, the neuroepithelial cells arranged irregularly and the intercellular spaces became wide at 12 ： 00 on E8. The apical portion of many neuroepithelial cells bulged into the lumen and many microvilli were shorted and swollen. The quantity of the microvillus reduced gradually, evenly disappeared with the increasing of gestational age at 18：00 on E8. Under transmission electron microscope, the neuroepithelial cells in experimental embryos arranged irregularly. There were many visible materials in the intercellular space which increased the breadth and anomaly. It was apparent that passive smoking evoked major alterations in neuroepithelial cytoarchitecture. Junctional complex reduced. Many microvilli were shorted and swollen, even the apical portion of many neuroepithelial cells bulged, and abscised into the lumen. A lot of vacuolation appeared in the cytoplasm of neuroepithelia and mesenchymal cell around the neuroepithelium. The cristae of mitochondria reduced even disappeared, and some mitochondria became elongate. Irregular nuclear, increased heterochromatin and karyopycnosis/karyorrhexis were observed easily. Perinuclear cisternae partially swelled and embraced tangible material （maybe the material from nuclear）. Some death cells separated into a lot of apoptotic bodies. Some apoptotic bodies were found in the cytoplasm of other healthy-looking or healthy cells. CONCLUSION： Passive smoking may induce degeneration, apoptosis, and cells loss in the neural epithelium, thereby result in failure of formation and differentiation of neural tube. It is an important way by which passive smoking caused neural tube defects.
基金Acknowledgments This work was supported by the National Natural Science Foundation of China(Grant No.41271427)and the National Key Technology R&D Program(Grant No.2012BAH27B05).
文摘Keriya River,one of the ancient Four Green Corridors in the Tarim Basin,recording the changes of climate-environment and the ancient Silk Road of the region.According to the archaeological data,historical materials and paleoclimates information,its eeo-environment and climate have taken great changes since the 1.09 Ma B.P,especially during the recent 2,000 years,many famous ancient cities having been abandoned and the south route of the Silk Road has been moved southward.This study illustrates the capability of the remote sensing data(radar data,topographic data and optical images)and historical materials,in mapping the ancient drainage networks.A major paleodrainage system of Keriya River has linked the Kunlun Mountains to the Tienshan Mountains,possibly as far back as the early Pleistocene.The Keriya River will have important implications for not only the understanding of the paleoenvironments and paleoclimates of Tarim Basin from the early Pleistocene to the Holocene,but also the changes of the Silk Road.
文摘Polysaccharides of Momordica charantia have been reported to be the primary bioactive components that confer its antioxidant activity. To some degree, antioxidants may provide beneficial effects on neuronal damage induced by seizures. However, the protective effects of Momordica charantia polysaccharides (MCPs) on seizures remain unclear. In this study, our purpose was to investigate the effects of MCPs on oxidative stress and neurodegeneration in an experimental Kainic acid (KA)-induced rat seizure model. MCPs treatments decreased the level of malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus of the KA-induced animal model. Moreover, MCPs significantly attenuated KA-induced neuronal loss in the CA1 and CA3 hippocampal regions. Based on these results, MCPs exert neuroprotective effects by attenuating KA-induced neuronal damage in the brain through their free radical scavenging activities.
基金supported by National Natural Science Foundation of China(22220102001,22303081)China Postdoctoral Science Foundation(2024M762886)Zhejiang Provincial Natural Science Foundation of China(LMS25B030003).
文摘The interest in covalent drugs has resurged in recent decades,spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening.Herein,we present CarsiDock-Cov,a new paradigm distinguishing itself as the first deep learning(DL)-guided approach for covalent docking.CarsiDock-Cov retains the core components of its non-covalent predecessor,leveraging a DL model pretrained on millions of docking complexes to predict protein—ligand distance matrices,along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses.Additionally,it incorporates several key enhance-ments specifically tailored to optimize the protocol for covalent docking applications.Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands,and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor,but also exhibits competitive performance against various state-of-the-art covalent docking tools.Collectively,our approach represents a significant advance in co-valent docking methodology,offering an automated and efficient solution that shows considerable prom-ise for accelerating covalent drug discovery and design.
基金supported by the National Key R&D Program of China 2022YFA1302900(B.W.and S.H.)National Natural Science Foundation of China grants 82121005(B.W.)and 32401012(M.H.)+4 种基金CAS Strategic Priority Research Program XDB37030100(B.W.and Q.Z.)Shanghai Pilot Program for Basic Research-Chinese Academy of Sciences,Shanghai Branch JCYJSHFY-2021-008(B.W.)Shanghai Science and Technology Development Foundation grant 22QA1412000(Y.Z.)Zhejiang Provincial Natural Science Foundation of China LQ24C050004(M.H.)Research Funds from Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences 2024HIAS-Y011(M.H.).
文摘Dear Editor,Chemerin functions as both an adipocytokine and a chemotactic factor and plays key roles in adipogenesis and inflammation(Bozaoglu et al.,2007;Bondue et al.,2011).The chemerin receptors chemokine-like receptor 1(CMKLR1)and G protein-coupled receptor 1(GPR1),play crucial roles in regulating obesity,inflammation,and cancer,highlighting their potential as therapeutic targets(Bozaoglu et al.,2007;Ernst and Sinal,2010;Su et al.,2021).Although both receptors recognize the same ligand,chemerin,and share high sequence identity,they exhibit distinct signaling properties and biological functions(Bozaoglu et al.,2007;De Henau et al.,2016;Fischer et al.,2021).CMKLR1 is the canonical chemerin receptor that mediates both G protein and arrestin signaling,while GPR1 exhibits weak G protein signaling but strong arrestin-dependent and-independent internalization(De Henau et al.,2016;Fig.1A and 1B).The chemerin-CMKLR1 axis regulates lipid and glucose metabolism(Kennedy and Davenport,2018),and is associated with chronic inflammation,obesity,and obesity-related disorders such as insulin resistance and metabolic syndrome,with several compounds and antibodies under preclinical or early clinical investigation(Goralski et al.,2007;Kennedy et al.,2016;Trilleaud et al.,2021).In contrast,the mechanisms of atypical signaling and biological function of GPR1 remain unclear.
基金the SBE Office of Multidisciplinary Activities(SMA)organization in Interdisciplinary Behavioral and Social Science Research(IBSS)Program(Award No.1620451)the NSF Social and Economic Sciences Division(SES)Hurricane Harvey 2017 Program(Award No.1762600)。
文摘Socialmedia such as Twitter is increasingly beingused as an effective platform to observe human behaviors in disastrous events.However,uneven social media use among different groups of population in different regions could lead to biased consequences and affect disaster resilience.This paper studies the Twitter use during 2017 Hurricane Harvey in 76 counties in Texas and Louisiana.We seek to answer a fundamental question:did socialgeographical disparities of Twitter use exist during the three phases of emergency management(preparedness,response,recovery)?We employed a Twitter data mining framework to process the data and calculate two indexes:Ratio and Sentiment.Regression analyses between the Ratio indexes and the social-geographical characteristics of the counties at the three phrases reveal significant social and geographical disparities in Twitter use during Hurricane Harvey.Communities with higher disasterrelated Twitter use in Harvey generally were communities having better social and geographical conditions.These results of Twitter use patterns can be used to compare with future similar studies to see whether the Twitter use disparities have increased or decreased.Future research is also needed to examine the effects of Twitter use disparities on disaster resilience and to test whether Twitter use can predict community resilience.
文摘Craters, one of the most significant features of the lunar surface, have been widely researched because they offer us the relative age of the surface unit as well as crucial geological information. Research on crater detec- tion algorithms （CDAs） of the Moon and other planetary bodies has concentrated on detecting them from imagery data, but the computational cost of detecting large craters using images makes these CDAs impractical. This paper presents a new approach to crater detection that utilizes a digital elevation model instead of images; this enables fully automatic global detection of large craters. Craters were delineated by terrain attributes, and then thresholding maps of terrain attributes were used to transform topographic data into a binary image, finally craters were detected by using the Hough Transform from the binary image. By using the proposed algorithm, we produced a catalog of all craters ≥ 10 km in diameter on the lunar surface and analyzed their distribution and population characteristics.
基金supported by U.S.National Science Foundation:[Grant Number Award#:1762600 and 1620451].
文摘This paper develops a social media-disaster resilience analysis framework by categorizing types of social media use and their challenges to better understand and assess its role in disaster resilience research and management.The framework is derived primarily from several case studies of Twitter use in three hurricane events in the United States-Hurricanes Isaac,Sandy,and Harvey.The paper first outlines four major contributions of social media data for disaster resilience research and management,which include serving as an effective communication platform,providing ground truth information for emergency response and rescue operations,providing information on people's sentiments,and allowing predictive modeling.However,there are four_key challenges to its uses,which include,easy spreading of false information,social and geographical disparities of Twitter use,technical issues on processing and analyzing big and noisy data,especially on improving the locational accuracy of the tweets,and algorithm bias in Al and other types of modeling.Then,the paper proposes twenty strategies that the four sectors of the social media community-organizations,individuals,social media companies,and researchers-could take to improve social media use to increase disaster resilience.
基金supported by Texas A&M Institute of Data Science(TAMIDS)under the Data Resource Development Program.
文摘The Covid-19 has presented an unprecedented challenge to public health worldwide.However,residents in different countries showed diverse levels of Covid-19 awareness during the outbreak and suffered from uneven health impacts.This study analyzed the global Twitter data from January 1st to June 30th,2020,to answer two research questions.What are the linguistic and geographical disparities of public awareness in the Covid-19 outbreak period reflected on social media?Does significant association exist between the changing Covid-19 awareness and the pandemic outbreak?We established a Twitter data mining framework calculating the Ratio index to quantify and track awareness.The lag correlations between awareness and health impacts were examined at global and country levels.Results show that users presenting the highest Covid-19 awareness were mainly those tweeting in the official languages of India and Bangladesh.Asian countries showed more disparities in awareness than European countries,and awareness in Eastern Europe was higher than in central Europe.Finally,the Ratio index had high correlations with global mortality rate,global case fatality ratio,and country-level mortality rate,with 21-31,35-42,and 13–18 leading days,respectively.This study yields timely insights into social media use in understanding human behaviors for public health research.
基金supported by the U.S.National Science Foundation under the Methodology,Measurement&Statistics(MMS)Program(Award#:2102019)the Human Networks&Data Science Infrastructure Program(Award#:2318204&2318206)+1 种基金the Smart and Connected Communities(Award#:2325631)Texas A&M University Innovation[X]Program.
文摘Quantitative assessment of community resilience can provide support for hazard mitigation,disaster risk reduction,disaster relief,and long-term sustainable development.Traditional resilience assessment tools are mostly theory-driven and lack empirical validation,which impedes scientific understanding of community resilience and practical decision-making of resilience improvement.In the advent of the Big Data Era,the increasing data availability and advances in computing and modeling techniques offer new opportunities to understand,measure,and promote community resilience.This article provides a comprehensive review of the definitions of community resilience,along with the traditional and emerging data and methods of quantitative resilience measurement.The theoretical bases,modeling principles,advantages,and disadvantages of the methods are discussed.Finally,we point out research avenues to overcome the existing challenges and develop robust methods to measure and promote community resilience.This article establishes guidance for scientists to further advance disaster research and for planners and policymakers to design actionable tools to develop sustainable and resilient communities.
基金suported by the National Natural Science Foundation of China(2187,1117,91956203)the“111”Program of Minister of Education,Beijing National Laboratory for Molecular Sciences(BNLMS202109)the Science and Technology Commission of Shanghai Municipality(19JC1430100)。
文摘Catalyst innovation lies at the heart of transition-metal-catalyzed reaction development.In this article,we have explored the C(sp2)–H alkenylation activity with novel spirocyclic N-heterocyclic carbene(NHC)-based cyclometalated ruthenium pincer catalyst system,SNRu-X.After screening catalyst and condition,a high valent Ru(Ⅳ)dioxide(X=O_(2))species has demonstrated superior reactivity in the catalytic alkenylation of aromatic and olefinic C–H bonds with unactivated alkenyl bromides and triflates.This reaction has achieved the easy construction of a wide range of(hetero)aromatic alkenes and dienes,in good to excellent yields with exclusive selectivity.Preliminary mechanistic studies indicate that this reaction may proceed through a single electron transfer(SET)triggered oxidative addition,by doing so,providing valuable complementary to classical alkenylation reactions that are dependent on activated alkenyl precursors.
基金supported by the U.S.National Science Foundation under[grant numbers:1047916,1429699,1443080,1551492,and 1664119].
文摘With the increased frequency of natural hazards and disasters and consequent losses,it is imperative to develop efficient and timely strategies for emergency response and relief operations.In this paper,we propose a cyberGIS-enabled multi-criteria spatial decision support system for supporting rapid decision making during emergency management.It combines a high-performance computing environment(cyberGIS-Jupyter)and multi-criteria decision analysis models(Weighted Sum Model(WSM)and Technique for Order Preference by Similarity to Ideal Solution Model(TOPSIS))with various types of social vulnerability indicators to solve decision problems that contain conflicting evaluation criteria in a flood emergency situation.Social media data(e.g.Twitter data)was used as an additional tool to support the decision-making process.Our case study involves two decision goals generated based on a past flood event in the city of Austin,Texas,U.S.A.As our result shows,WSM produces more diverse values and higher output category estimations than the TOPSIS model.Finally,the model was validated using an innovative questionnaire.This cyberGIS-enabled spatial decision support system allows collaborative problem solving and efficient knowledge transformation between decision makers,where different emergency responders can formulate their decision objectives,select relevant evaluation criteria,and perform interactive weighting and sensitivity analyses.
基金supported by a research grant ftom the National Science Foundation under the Meth-odology,Measurement&Statistics(MMS)Program(Award No.2102019).
文摘The intensity of extreme weather events has been increasing,posing a unique threat to society and highlighting the importance of our electrical power system,a key component in our infrastructure.In severe weather events,quickly identifying power outage impact zones and affected communities is crucial for informed disaster response.However,a lack of household-level power outage data impedes timely and precise assessments.To address these challenges,we introduced an analytical workflow using NASA’s Black Marble daily nighttime light(NTL)images to detect power outages from the 2021 Winter Storm Uri.This workflow includes adjustments to mitigate viewing angle and snow reflection effects.Power outage is detected by comparing storm-time and baseline(normal condition)NTL images using an empirical adjusted equation.The outcomes of the workflow are 500-meter resolution power outage maps,which have the optimal correlation with real outage tracking data when NTL intensity is reduced by 26%.With the resultant power outage maps,we analyzed the relations between power outages and disadvantaged populations in 126 Texas counties and 4182 census tracts to evaluate environmental justice in the storm.The results show that Latino/Hispanic communities tend to suffer more from power outages at both the county and census tract levels.
