Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recogni...Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.展开更多
Research data infrastructures form the cornerstone in both cyber and physical spaces,driving the progression of the data-intensive scientific research paradigm.This opinion paper presents an overview of global researc...Research data infrastructures form the cornerstone in both cyber and physical spaces,driving the progression of the data-intensive scientific research paradigm.This opinion paper presents an overview of global research data infrastructure,drawing insights from national roadmaps and strategic documents related to research data infrastructure.It emphasizes the pivotal role of research data infrastructures by delineating four new missions aimed at positioning them at the core of the current scientific research and communication ecosystem.The four new missions of research data infrastructures are:(1)as a pioneer,to transcend the disciplinary border and address complex,cutting-edge scientific and social challenges with problem-and data-oriented insights;(2)as an architect,to establish a digital,intelligent,flexible research and knowledge services environment;(3)as a platform,to foster the high-end academic communication;(4)as a coordinator,to balance scientific openness with ethics needs.展开更多
Tree plantation and forest restoration are the major strategies for enhancing terrestrial carbon sequestration and mitigating climate change.The Grain for Green Project in China has positively impacted global carbon s...Tree plantation and forest restoration are the major strategies for enhancing terrestrial carbon sequestration and mitigating climate change.The Grain for Green Project in China has positively impacted global carbon sequestration and the trend towards fragmentation of plantation forests.Limited studies have been conducted on changes in plantation biomass and stand structure caused by fragmentation,and the effect of fragmentation on the carbon storage of plantation forests remains unclear.This study evaluated the differences between carbon storage and stand structure in black locust forests in fragmented and continuous landscape in the Ansai District,China and discussed the effects of ecological significance of four landscape indices on carbon storage and tree density.We used structural equation modelling to explore the direct and indirect effects of fragmentation,edge,abiotic factors,and stand structure on above-ground carbon storage.Diameter at breast height(DBH)in fragmented forests was 53.3%thicker,tree density was 40.9%lower,and carbon storage was 49.8%higher than those in continuous forests;for all given DBH>10 cm,the trees in fragmented forests were shorter than those in continuous forests.The patch area had a negative impact on carbon storage,i.e.,the higher the degree of fragmentation,the lower the density of the tree;and fragmentation and distance to edge(DTE)directly increased canopy coverage.However,canopy coverage directly decreased carbon storage,and fragmentation directly increased carbon storage and tree density.In non-commercial forests,fragmentation reduces the carbon storage potential of plantation,and the influence of patch area,edge,and patchy connection on plantation should be considered when follow-up trees are planted and for the plantation management.Thus,expanding the area of plantation patches,repairing the edges of complex-shaped patches,enhancing the connectivity of similar patches,and applying nutrients to plantation forests at regular intervals are recommended in fragmented areas of the Loess Plateau.展开更多
The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As t...The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain function.In the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.展开更多
The place and placeness are believed to be a crucial perspective for comprehending the transformative dynamics of tourist destinations in the context of globalization and the rapid development of the tourism industry....The place and placeness are believed to be a crucial perspective for comprehending the transformative dynamics of tourist destinations in the context of globalization and the rapid development of the tourism industry.As the material carrier of language,linguistic landscape is an intermediary for people to endow emotions and personalities into the place,becoming an effective path for exploring the place-making in a certain area.Mogan Mountain is a famous national tourist resort,which is located in Mogan Mountain Town,Deqing County,Huzhou City,China.This is a good case area for studying the relationship between linguistic landscape and placemaking in tourist destinations.There are two theories that form the theoretical foundation of the study,namely the place and the geosemiotics.Firstly,the results showed the overall style of the linguistic landscape.Multilingual labelling(52.7%),official signs(55.3%),and standardized Chinese characters predominantly shaped the linguistic landscape,with English and other languages being complementary.Secondly,from the perspective of three dimensions of the geosemiotics framework,such as inscription,language preference,and placement position,we conduct a comprehensive semiotic analysis of the linguistic landscape,which encompasses diverse facets such as fonts,materials,shifts in state,text vectors,and symmetrical arrangements.Finally,we explore the influence of linguistic landscapes on the place-making of Mogan Mountain through the dimensions of location,locale,and sense of place.The information on linguistic landscapes indicates the geographical location.These linguistic landscapes play an important role in constructing the language order,nostalgic atmosphere,exotic atmosphere,and elegant and tasteful lifestyle of the public space in Mogan Mountain.Readers of linguistic landscapes,including tourists and residents,generate and identify with the unique sense of place in Mogan Mountain.These linguistic landscapes construct the destination placeness of Mogan Mountain that combines both foreign and nostalgic styles,and the integration of Chinese and Western cultures.It will help promote the image positioning of tourism destinations and have practical guiding significance for the tourism planning,landscape-making,language management,and other aspects of tourism destinations.展开更多
Translation regulation is an important layer of gene expression:Generation of genome-wide expression datasets at multi-omics levels in spatial,temporal,and cell-type resolution is essential for deciphering brain compl...Translation regulation is an important layer of gene expression:Generation of genome-wide expression datasets at multi-omics levels in spatial,temporal,and cell-type resolution is essential for deciphering brain complexity.Regulation of gene expression is a highly dynamic process aiming at the production of precise levels of gene products to guarantee optimal cellular function,in response to physiological cues.Speedy advances in next-generation sequencing enabled the understanding of epigenomic and transcriptomic dynamic landscapes of different brain regions along development,aging,and disease progression.However,the correlation of the“transcriptome”with protein levels is poor because numerous mRNAs are subjected to manipulation of their translation efficiency,to warrant a favorable result under certain conditions.Hence,it is widely accepted that regulation at the translation level is a vital layer of gene expression.Quantification of actively translated mRNA populations(i.e.,“translatome”)is a more reliable predictor of the“proteome”(Wang et al.,2020).展开更多
Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment,but challenges related to resistance and toxicity still remain.Due to the advancement of immuno-oncology,an incr...Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment,but challenges related to resistance and toxicity still remain.Due to the advancement of immuno-oncology,an increasing number of novel immunoregulatory targets and mechanisms are being revealed,with relevant therapies promising to improve clinical immunotherapy in the foreseeable future.Therefore,comprehending the larger picture is important.In this review,we analyze and summarize the current landscape of preclinical and translational mechanistic research,drug development,and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint inhibitors.Along with further clarification of cancer immunobiology and advances in antibody engineering,agents targeting additional inhibitory immune checkpoints,including LAG-3,TIM-3,TIGIT,CD47,and B7 family members are becoming an important part of cancer immunotherapy research and discovery,as are structurally and functionally optimized novel anti-PD-(L)1 and anti-CTLA-4 agents and agonists of co-stimulatory molecules of T cells.Exemplified by bispecific T cell engagers,newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical benefits.Next-generation agents also include immune epigenetic drugs and cytokine-based therapeutics.Cell therapies,cancer vaccines,and oncolytic viruses are not covered in this review.This comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.展开更多
Computational Intelligent(CI)systems represent a pivotal intersection of cutting-edge technologies and complex engineering challenges aimed at solving real-world problems.This comprehensive body of work delves into th...Computational Intelligent(CI)systems represent a pivotal intersection of cutting-edge technologies and complex engineering challenges aimed at solving real-world problems.This comprehensive body of work delves into the realm of CI,which is designed to tackle intricate and multifaceted engineering problems through advanced computational techniques.The history of CI systems is a fascinating journey that spans several decades and has its roots in the development of artificial intelligence and machine learning techniques.Through a wide array of practical examples and case studies,this special issue bridges the gap between theoretical concepts and practical implementation,shedding light on how CI systems can optimize processes,design solutions,and inform decisions in complex engineering landscapes.This compilation stands as an essential resource for both novice learners and seasoned practitioners,offering a holistic perspective on the potential of CI in reshaping the future of engineering problem-solving.展开更多
The Annual Report on Cardiovascular Health and Diseases in China(2022) intricate landscape of cardiovascular health in China. This section dissects cardiovascular risk factors in China which including hypertension, dy...The Annual Report on Cardiovascular Health and Diseases in China(2022) intricate landscape of cardiovascular health in China. This section dissects cardiovascular risk factors in China which including hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease, metabolic syndrome and air pollution. Hypertension prevalence has steadily increased in China,with efforts to control it facing challenges in achieving optimal rates, especially in rural areas. Interventions like salt substitutes and intensive blood pressure control show promise but need improvement. Abnormal lipid levels, indicative of dyslipidemia,have risen significantly, posing a risk for cardiovascular diseases. Despite efforts, many patients struggle to achieve target lipid levels, necessitating improved treatment strategies. Both type 1 and type 2 diabetes mellitus affect millions of adults in China,with long-term complications adding to the disease burden. Early intervention and effective management are crucial to mitigate its impact. Prevalent among older adults, chronic kidney disease is associated with diabetes mellitus, hypertension, and cardiovascular diseases, necessitating comprehensive management approaches. The prevalence of metabolic syndrome, characterized by a cluster of risk factors, has increased in both adults and adolescents, calling for lifestyle modifications and public health interventions. Ambient and household air pollution remain significant environmental risk factors, despite some improvements in air quality. Continued efforts to reduce emissions are essential for mitigating associated health risks. Addressing these risk factors requires a multifaceted approach, including public health initiatives, policy interventions, and individual-level strategies to promote healthy lifestyles and reduce environmental exposures. Surveillance and research efforts are crucial for monitoring trends and developing effective strategies to lessen the burden of cardiovascular diseases in China.展开更多
The Annual Report on Cardiovascular Health and Diseases in China(2022) intricate landscape of cardiovascular health in China. This is the fourth section of the report with a specific focus on epidemiology and current ...The Annual Report on Cardiovascular Health and Diseases in China(2022) intricate landscape of cardiovascular health in China. This is the fourth section of the report with a specific focus on epidemiology and current management of cardiovascular disease(CVD) in China. This section of the report highlights the epidemiological trends of CVD in China. It reveal a concerning rise in prevalence, with approximately 330 million affected individuals, including significant numbers with stroke, coronary artery disease(CAD), heart failure, and other conditions. CVD stands as the primary cause of mortality among both urban and rural populations, accounting for nearly half of all deaths in 2020. Mortality rates are notably higher in rural areas compared to urban centers since 2009. While age-standardized mortality rates have decreased, the absolute number of CVD deaths has increased, primarily due to population aging. Ischemic heart disease, hemorrhagic and ischemic strokes are the leading causes of CVD-related deaths. Notably, the burden of atherosclerotic cardiovascular disease has risen substantially, with atherosclerotic cardiovascular disease-related deaths increasing from 1990 to 2016. The incidence of ischemic stroke and ischemic heart disease has shown similar increasing trends over the past three decades. CAD mortality, particularly acute myocardial infarction, has been on the rise, with higher mortality rates observed in rural areas since 2016. The prevalence of CAD has increased significantly, with over 11 million patients identified in 2013. Studies assessing hospital performance in managing acute coronary syndrome reveal gaps in adherence to guideline-recommended strategies, with disparities in care quality across hospitals. However, initiatives like the China Patient-centered Evaluative Assessment of Cardiac Events(PEACE)-Retrospective AMI Study and the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome(CCC-ACS) project aim to improve patient outcomes through enhanced care protocols. Moreover, advancements in medical technology, such as quantitative flow ratio-guided lesion selection during percutaneous coronary intervention, show promise in improving clinical outcomes for patients undergoing intervention.展开更多
Human disturbances are considered to break reproduction barriers among species.Significant increases in hybridization events have been reported among a large number of taxonomic groups in anthropogenic environments,pr...Human disturbances are considered to break reproduction barriers among species.Significant increases in hybridization events have been reported among a large number of taxonomic groups in anthropogenic environments,providing novel insights into species evolution mechanisms and conservation management in the Anthropocene.The Eastern Golden Frog(Pelophylax plancyi)and BlackSpotted Frog(P.nigromaculatus)are two sympatric anuran species with a long history of mitochondrial genome introgression in highly urbanized continental East Asia.However,there is only limited understanding of the pattern of their contemporary hybridization and factors influencing their interspecific relationship under anthropogenic disturbances.Here,interspecific hybridization between P.plancyi and P.nigromaculatus at the population level was investigated in Shanghai.All except two haplotypes obtained from both species in Shanghai were mixed together,and located in the introgression clade,implying multiple ancient mitochondrial introgression events occurred in the populations of our study area.Asymmetric genetic introgression was detected by microsatellite markers,with 0.7%of P.plancyi and 14.6%of P.nigromaculatus identified as contemporary admixed individuals.Consistent with the trend of population density,higher genetic diversity of neutral microsatellite loci was found in the more abundant P.plancyi;however,variation in mitochondrial(Cyt-b)and nuclear(POMC)genes was higher in relatively rare P.nigromaculatus.The population density of P.plancyi and number of water patches within local habitats were significantly positively correlated with both occurrences and proportions of admixed individuals in the populations of P.plancyi and P.nigromaculatus.Considering the prevalent transformation of habitats in urbanized areas,these results imply that a high population density in isolated artificially altered habitats is likely to increase interspecific hybridization.Thus,population monitoring and improvement of landscape connectivity between habitats would be needed to control the intensity of interspecific hybridization between P.plancyi and P.nigromaculatus in anthropogenic-disturbed environments.展开更多
The House Martin(Delichon urbicum)is a common farmland bird species in the European landscape,yet its population numbers are currently in decline.However,it is not yet sufficiently explained why this long-term decline...The House Martin(Delichon urbicum)is a common farmland bird species in the European landscape,yet its population numbers are currently in decline.However,it is not yet sufficiently explained why this long-term decline occurs.To fill this gap in our knowledge,we investigated how land cover composition affects the abundance of House Martins on the landscape scale by using nationwide citizen science data.Utilizing a generalised linear mixed-effect model(GLMM),we evaluated 12,094 records from the Czech Republic spanning 2009-2017.Our analysis underscores the significance of land cover type in shaping House Martin abundance.More specifically,our results indicate that within agricultural land covers“naturally managed arable lands”exhibited significant positive effect,while forests,orchards,and vineyards were deemed less favourable for House Martin populations.Within urban land covers,we found a clear distinction in the impact on House Martin populations,with a positive effect observed in urban infrastructure,development areas,and post-industrial sites(i.e.,UrbanAreas),while an indifferent impact was noted within urban green spaces and landscaped areas(i.e.,GreenUrban).Notably,our findings suggest that the simple spatial,age,and species structure typical of forests in Europe,and similarly,the uniform structure of parks and gardens,may be responsible for the decline in the abundance of the House Martin.We advocate for the preservation or enhancement of urban greenery,expansion of natural vegetation in rural areas and adoption of ecological management practices in orchards and vineyards to mitigate further declines in House Martin populations.展开更多
Mountainous regions have disadvantages in economic development because of harsh physical and climatic conditions.However,winter tourism activities are one of the key components for supporting economic development in t...Mountainous regions have disadvantages in economic development because of harsh physical and climatic conditions.However,winter tourism activities are one of the key components for supporting economic development in the highlands.Establishing a ski resort area supports direct and indirect employment in a region,and it stops immigration from mountainous regions to other places.This research aimed to assess the potential ski areas using a multi criteria evaluation technique in the Van region which is located in the eastern part of Türkiye.In this context,snow cover duration,sun effect,slope,slope length,elevation,population density,distance from main roads and lake visibility were used as input factors in the decision making process.Each factor was standardized using a fuzzy technique based on existing well-known ski centers in Türkiye.The weight of inputs was defined by applying a survey to the professional skiers.The most important factors were detected as transportation opportunities and snow covers whereas,the least important factors were elevation and population density.Additionally,lake visibility was very important to make a difference from other existing facilities in the region.Therefore,it was included as constraints and lake visible areas were extracted at the final stage of the research.Potential ski areas were mapped in three levels as professional,intermediate and beginner skiers.One of the suitable areas was selected as a sample projection and for the 3D simulation of the ski investment area.Potential costs and benefits were discussed.It was found that a ski tourism area investment can be amortized in 3 years in the region.展开更多
Dominant technology formation is the key for the hightech industry to“cross the chasm”and gain an established foothold in the market(and hence disrupt the regime).Therefore,a stimulus-response model is proposed to i...Dominant technology formation is the key for the hightech industry to“cross the chasm”and gain an established foothold in the market(and hence disrupt the regime).Therefore,a stimulus-response model is proposed to investigate the dominant technology by exploring its formation process and mechanism.Specifically,based on complex adaptive system theory and the basic stimulus-response model,we use a combination of agent-based modeling and system dynamics modeling to capture the interactions between dominant technology and the socio-technical landscape.The results indicate the following:(i)The dynamic interaction is“stimulus-reaction-selection”,which promotes the dominant technology’s formation.(ii)The dominant technology’s formation can be described as a dynamic process in which the adaptation intensity of technology standards increases continuously until it becomes the leading technology under the dual action of internal and external mechanisms.(iii)The dominant technology’s formation in the high-tech industry is influenced by learning ability,the number of adopting users and adaptability.Therein,a“critical scale”of learning ability exists to promote the formation of leading technology:a large number of adopting users can promote the dominant technology’s formation by influencing the adaptive response of technology standards to the socio-technical landscape and the choice of technology standards by the socio-technical landscape.There is a minimum threshold and a maximum threshold for the role of adaptability in the dominant technology’s formation.(iv)The socio-technical landscape can promote the leading technology’s shaping in the high-tech industry,and different elements have different effects.This study promotes research on the formation mechanism of dominant technology in the high-tech industry,presents new perspectives and methods for researchers,and provides essential enlightenment for managers to formulate technology strategies.展开更多
The cold regions are located in high latitudes and cold climates.The local excellent ornamental plant resources are relatively scarce.The plant species that are suitable for both ornamental and productive benefits of ...The cold regions are located in high latitudes and cold climates.The local excellent ornamental plant resources are relatively scarce.The plant species that are suitable for both ornamental and productive benefits of landscape of flower sea construction are also even fewer.Therefore,it is imperative to introduce and screen the plant resources suitable for cold regions to create the landscape of flower sea.The rape,an oilseed crop,was used as a research object in order to create a productive flower landscape with both ornamental and economic values in cold regions.Four rape flower varieties,Qingza No.5,7,9,and 11,were introduced from Qinghai Hufeng Agricultural Science and Technology Group Co.,Ltd.They were planted in the experimental practice base of Northeast Agricultural University in three batches.Development characteristics and seed yield of rape flowers on different sowing dates were studied.The fuzzy probability method was used to comprehensively evaluate the varieties.The results showed that the rape flowers grew well in Harbin City during the experimental sowing period,which could form a good landscape of flower sea and had a considerable rapeseed yield.It could be widely used in cold urban and rural areas,such as Harbin City.In view of the experimental results,the strategies of creating a productive landscape of rape flower sea were proposed and the economic benefits were analyzed.It could change the status quo of a uniform landscape of flower sea in cold regions,help the development of rural tourism,and promote local economic income.展开更多
The role of Landscape Character Assessment(LCA)at the level of territorial landscape governance spans both natural and social sciences.By analyzing the development history,research distribution,methods and application...The role of Landscape Character Assessment(LCA)at the level of territorial landscape governance spans both natural and social sciences.By analyzing the development history,research distribution,methods and applications of cutting-edge cases of LCA in China,the following conclusions are drawn:①the LCA research in China originated earlier than that in Europe,but has not yet been systematically applied to the implementation of urban and rural planning at all levels;②the fundamental theory of LCA in China has been well constructed,with three main research directions:technologyled,assessment-led,and assessment combined with other theories;③the development of LCA in rural areas is more mature than in urban areas,but the progress of research is uneven across regions;④the current research presents significant“bottom-up”academic characteristics,and there is an urgent need for government decision-making authorities and academia to jointly promote a“top-down”standardized governance mechanism to comprehensively promote the modernization of territorial landscape governance.展开更多
With the rapid development of urbanization,landscape architecture has become an indispensable component of daily life.In order to achieve better landscape effects and protect the ecological environment,landscape ecolo...With the rapid development of urbanization,landscape architecture has become an indispensable component of daily life.In order to achieve better landscape effects and protect the ecological environment,landscape ecology theory can be integrated into landscape planning to carry out disciplinary crossing and integration research between landscape ecology and landscape architecture.In this study,based on the basic theories of landscape ecology,the waterfront landscape of Dapo Town was designed,with the aim to achieve ecological balance in planning,showcase biodiversity,and create a harmonious landscape ecological environment which can benefit both nature and people.This design combined artificial and natural elements while improving the natural environment,which promoted a harmonious relationship between humans and nature,thus enriching the spatial organization of the city,and playing a role in regulating the urban environment and climate.展开更多
Garden landscape is a beautiful complex formed by space and time complementing each other and acting together.Garden plants are the core landscaping elements in garden landscape construction.It is necessary to flexibl...Garden landscape is a beautiful complex formed by space and time complementing each other and acting together.Garden plants are the core landscaping elements in garden landscape construction.It is necessary to flexibly use a variety of plant landscaping methods to create a richer and more vivid natural landscape,and promote the improvement of the quality of the living environment and the harmonious coexistence between man and nature.展开更多
Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,s...Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.展开更多
基金supported by the National Natural Science Foundation of China(No.82172408)Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)+1 种基金The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100).
文摘Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.
基金the National Social Science Fund of China(Grant No.22CTQ031)Special Project on Library Capacity Building of the Chinese Academy of Sciences(Grant No.E2290431).
文摘Research data infrastructures form the cornerstone in both cyber and physical spaces,driving the progression of the data-intensive scientific research paradigm.This opinion paper presents an overview of global research data infrastructure,drawing insights from national roadmaps and strategic documents related to research data infrastructure.It emphasizes the pivotal role of research data infrastructures by delineating four new missions aimed at positioning them at the core of the current scientific research and communication ecosystem.The four new missions of research data infrastructures are:(1)as a pioneer,to transcend the disciplinary border and address complex,cutting-edge scientific and social challenges with problem-and data-oriented insights;(2)as an architect,to establish a digital,intelligent,flexible research and knowledge services environment;(3)as a platform,to foster the high-end academic communication;(4)as a coordinator,to balance scientific openness with ethics needs.
基金supported by the National Natural Science Foundation of China(32201429)the College of Landscape Architecture and Art,Northwest A&F University,China.
文摘Tree plantation and forest restoration are the major strategies for enhancing terrestrial carbon sequestration and mitigating climate change.The Grain for Green Project in China has positively impacted global carbon sequestration and the trend towards fragmentation of plantation forests.Limited studies have been conducted on changes in plantation biomass and stand structure caused by fragmentation,and the effect of fragmentation on the carbon storage of plantation forests remains unclear.This study evaluated the differences between carbon storage and stand structure in black locust forests in fragmented and continuous landscape in the Ansai District,China and discussed the effects of ecological significance of four landscape indices on carbon storage and tree density.We used structural equation modelling to explore the direct and indirect effects of fragmentation,edge,abiotic factors,and stand structure on above-ground carbon storage.Diameter at breast height(DBH)in fragmented forests was 53.3%thicker,tree density was 40.9%lower,and carbon storage was 49.8%higher than those in continuous forests;for all given DBH>10 cm,the trees in fragmented forests were shorter than those in continuous forests.The patch area had a negative impact on carbon storage,i.e.,the higher the degree of fragmentation,the lower the density of the tree;and fragmentation and distance to edge(DTE)directly increased canopy coverage.However,canopy coverage directly decreased carbon storage,and fragmentation directly increased carbon storage and tree density.In non-commercial forests,fragmentation reduces the carbon storage potential of plantation,and the influence of patch area,edge,and patchy connection on plantation should be considered when follow-up trees are planted and for the plantation management.Thus,expanding the area of plantation patches,repairing the edges of complex-shaped patches,enhancing the connectivity of similar patches,and applying nutrients to plantation forests at regular intervals are recommended in fragmented areas of the Loess Plateau.
文摘The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain function.In the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.
基金the National Natural Science Foundation of China (Grant No. 41971171)The National Social Science Foundation of China (Grant No. 21BYY098) for funding support
文摘The place and placeness are believed to be a crucial perspective for comprehending the transformative dynamics of tourist destinations in the context of globalization and the rapid development of the tourism industry.As the material carrier of language,linguistic landscape is an intermediary for people to endow emotions and personalities into the place,becoming an effective path for exploring the place-making in a certain area.Mogan Mountain is a famous national tourist resort,which is located in Mogan Mountain Town,Deqing County,Huzhou City,China.This is a good case area for studying the relationship between linguistic landscape and placemaking in tourist destinations.There are two theories that form the theoretical foundation of the study,namely the place and the geosemiotics.Firstly,the results showed the overall style of the linguistic landscape.Multilingual labelling(52.7%),official signs(55.3%),and standardized Chinese characters predominantly shaped the linguistic landscape,with English and other languages being complementary.Secondly,from the perspective of three dimensions of the geosemiotics framework,such as inscription,language preference,and placement position,we conduct a comprehensive semiotic analysis of the linguistic landscape,which encompasses diverse facets such as fonts,materials,shifts in state,text vectors,and symmetrical arrangements.Finally,we explore the influence of linguistic landscapes on the place-making of Mogan Mountain through the dimensions of location,locale,and sense of place.The information on linguistic landscapes indicates the geographical location.These linguistic landscapes play an important role in constructing the language order,nostalgic atmosphere,exotic atmosphere,and elegant and tasteful lifestyle of the public space in Mogan Mountain.Readers of linguistic landscapes,including tourists and residents,generate and identify with the unique sense of place in Mogan Mountain.These linguistic landscapes construct the destination placeness of Mogan Mountain that combines both foreign and nostalgic styles,and the integration of Chinese and Western cultures.It will help promote the image positioning of tourism destinations and have practical guiding significance for the tourism planning,landscape-making,language management,and other aspects of tourism destinations.
基金funded by the Israel Science Foundation(grants No.1036/12 and 1228/20)(to OES).
文摘Translation regulation is an important layer of gene expression:Generation of genome-wide expression datasets at multi-omics levels in spatial,temporal,and cell-type resolution is essential for deciphering brain complexity.Regulation of gene expression is a highly dynamic process aiming at the production of precise levels of gene products to guarantee optimal cellular function,in response to physiological cues.Speedy advances in next-generation sequencing enabled the understanding of epigenomic and transcriptomic dynamic landscapes of different brain regions along development,aging,and disease progression.However,the correlation of the“transcriptome”with protein levels is poor because numerous mRNAs are subjected to manipulation of their translation efficiency,to warrant a favorable result under certain conditions.Hence,it is widely accepted that regulation at the translation level is a vital layer of gene expression.Quantification of actively translated mRNA populations(i.e.,“translatome”)is a more reliable predictor of the“proteome”(Wang et al.,2020).
基金supported by grants from 1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC21003)the National Natural Science Foundation of China(Grant Nos.82373021)+2 种基金the National Clinical Research Center for Geriatrics(Z2021JC001)Sichuan Provincial Research Foundation(24NSFSC6862)Outstanding Youth Talent Foundation for Science and Technology of Sichuan Province(2022JDJQ0056).
文摘Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment,but challenges related to resistance and toxicity still remain.Due to the advancement of immuno-oncology,an increasing number of novel immunoregulatory targets and mechanisms are being revealed,with relevant therapies promising to improve clinical immunotherapy in the foreseeable future.Therefore,comprehending the larger picture is important.In this review,we analyze and summarize the current landscape of preclinical and translational mechanistic research,drug development,and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint inhibitors.Along with further clarification of cancer immunobiology and advances in antibody engineering,agents targeting additional inhibitory immune checkpoints,including LAG-3,TIM-3,TIGIT,CD47,and B7 family members are becoming an important part of cancer immunotherapy research and discovery,as are structurally and functionally optimized novel anti-PD-(L)1 and anti-CTLA-4 agents and agonists of co-stimulatory molecules of T cells.Exemplified by bispecific T cell engagers,newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical benefits.Next-generation agents also include immune epigenetic drugs and cytokine-based therapeutics.Cell therapies,cancer vaccines,and oncolytic viruses are not covered in this review.This comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.
文摘Computational Intelligent(CI)systems represent a pivotal intersection of cutting-edge technologies and complex engineering challenges aimed at solving real-world problems.This comprehensive body of work delves into the realm of CI,which is designed to tackle intricate and multifaceted engineering problems through advanced computational techniques.The history of CI systems is a fascinating journey that spans several decades and has its roots in the development of artificial intelligence and machine learning techniques.Through a wide array of practical examples and case studies,this special issue bridges the gap between theoretical concepts and practical implementation,shedding light on how CI systems can optimize processes,design solutions,and inform decisions in complex engineering landscapes.This compilation stands as an essential resource for both novice learners and seasoned practitioners,offering a holistic perspective on the potential of CI in reshaping the future of engineering problem-solving.
文摘The Annual Report on Cardiovascular Health and Diseases in China(2022) intricate landscape of cardiovascular health in China. This section dissects cardiovascular risk factors in China which including hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease, metabolic syndrome and air pollution. Hypertension prevalence has steadily increased in China,with efforts to control it facing challenges in achieving optimal rates, especially in rural areas. Interventions like salt substitutes and intensive blood pressure control show promise but need improvement. Abnormal lipid levels, indicative of dyslipidemia,have risen significantly, posing a risk for cardiovascular diseases. Despite efforts, many patients struggle to achieve target lipid levels, necessitating improved treatment strategies. Both type 1 and type 2 diabetes mellitus affect millions of adults in China,with long-term complications adding to the disease burden. Early intervention and effective management are crucial to mitigate its impact. Prevalent among older adults, chronic kidney disease is associated with diabetes mellitus, hypertension, and cardiovascular diseases, necessitating comprehensive management approaches. The prevalence of metabolic syndrome, characterized by a cluster of risk factors, has increased in both adults and adolescents, calling for lifestyle modifications and public health interventions. Ambient and household air pollution remain significant environmental risk factors, despite some improvements in air quality. Continued efforts to reduce emissions are essential for mitigating associated health risks. Addressing these risk factors requires a multifaceted approach, including public health initiatives, policy interventions, and individual-level strategies to promote healthy lifestyles and reduce environmental exposures. Surveillance and research efforts are crucial for monitoring trends and developing effective strategies to lessen the burden of cardiovascular diseases in China.
文摘The Annual Report on Cardiovascular Health and Diseases in China(2022) intricate landscape of cardiovascular health in China. This is the fourth section of the report with a specific focus on epidemiology and current management of cardiovascular disease(CVD) in China. This section of the report highlights the epidemiological trends of CVD in China. It reveal a concerning rise in prevalence, with approximately 330 million affected individuals, including significant numbers with stroke, coronary artery disease(CAD), heart failure, and other conditions. CVD stands as the primary cause of mortality among both urban and rural populations, accounting for nearly half of all deaths in 2020. Mortality rates are notably higher in rural areas compared to urban centers since 2009. While age-standardized mortality rates have decreased, the absolute number of CVD deaths has increased, primarily due to population aging. Ischemic heart disease, hemorrhagic and ischemic strokes are the leading causes of CVD-related deaths. Notably, the burden of atherosclerotic cardiovascular disease has risen substantially, with atherosclerotic cardiovascular disease-related deaths increasing from 1990 to 2016. The incidence of ischemic stroke and ischemic heart disease has shown similar increasing trends over the past three decades. CAD mortality, particularly acute myocardial infarction, has been on the rise, with higher mortality rates observed in rural areas since 2016. The prevalence of CAD has increased significantly, with over 11 million patients identified in 2013. Studies assessing hospital performance in managing acute coronary syndrome reveal gaps in adherence to guideline-recommended strategies, with disparities in care quality across hospitals. However, initiatives like the China Patient-centered Evaluative Assessment of Cardiac Events(PEACE)-Retrospective AMI Study and the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome(CCC-ACS) project aim to improve patient outcomes through enhanced care protocols. Moreover, advancements in medical technology, such as quantitative flow ratio-guided lesion selection during percutaneous coronary intervention, show promise in improving clinical outcomes for patients undergoing intervention.
基金supported by the National Natural Science Foundation of China(32071529)the Yangtze Delta Estuarine Wetland Ecosystem Observation and Research Station(Z202204)+1 种基金Shanghai Key Lab for Urban Ecological Processes and EcoRestoration(SHUES2020B06,SHUES2021C04)the Fundamental Research Funds for the Central Universities.
文摘Human disturbances are considered to break reproduction barriers among species.Significant increases in hybridization events have been reported among a large number of taxonomic groups in anthropogenic environments,providing novel insights into species evolution mechanisms and conservation management in the Anthropocene.The Eastern Golden Frog(Pelophylax plancyi)and BlackSpotted Frog(P.nigromaculatus)are two sympatric anuran species with a long history of mitochondrial genome introgression in highly urbanized continental East Asia.However,there is only limited understanding of the pattern of their contemporary hybridization and factors influencing their interspecific relationship under anthropogenic disturbances.Here,interspecific hybridization between P.plancyi and P.nigromaculatus at the population level was investigated in Shanghai.All except two haplotypes obtained from both species in Shanghai were mixed together,and located in the introgression clade,implying multiple ancient mitochondrial introgression events occurred in the populations of our study area.Asymmetric genetic introgression was detected by microsatellite markers,with 0.7%of P.plancyi and 14.6%of P.nigromaculatus identified as contemporary admixed individuals.Consistent with the trend of population density,higher genetic diversity of neutral microsatellite loci was found in the more abundant P.plancyi;however,variation in mitochondrial(Cyt-b)and nuclear(POMC)genes was higher in relatively rare P.nigromaculatus.The population density of P.plancyi and number of water patches within local habitats were significantly positively correlated with both occurrences and proportions of admixed individuals in the populations of P.plancyi and P.nigromaculatus.Considering the prevalent transformation of habitats in urbanized areas,these results imply that a high population density in isolated artificially altered habitats is likely to increase interspecific hybridization.Thus,population monitoring and improvement of landscape connectivity between habitats would be needed to control the intensity of interspecific hybridization between P.plancyi and P.nigromaculatus in anthropogenic-disturbed environments.
基金supported by an internal grant agency from the Faculty of AgriSciences of Mendel University in Brno(AF-IGA2022-IP-034).
文摘The House Martin(Delichon urbicum)is a common farmland bird species in the European landscape,yet its population numbers are currently in decline.However,it is not yet sufficiently explained why this long-term decline occurs.To fill this gap in our knowledge,we investigated how land cover composition affects the abundance of House Martins on the landscape scale by using nationwide citizen science data.Utilizing a generalised linear mixed-effect model(GLMM),we evaluated 12,094 records from the Czech Republic spanning 2009-2017.Our analysis underscores the significance of land cover type in shaping House Martin abundance.More specifically,our results indicate that within agricultural land covers“naturally managed arable lands”exhibited significant positive effect,while forests,orchards,and vineyards were deemed less favourable for House Martin populations.Within urban land covers,we found a clear distinction in the impact on House Martin populations,with a positive effect observed in urban infrastructure,development areas,and post-industrial sites(i.e.,UrbanAreas),while an indifferent impact was noted within urban green spaces and landscaped areas(i.e.,GreenUrban).Notably,our findings suggest that the simple spatial,age,and species structure typical of forests in Europe,and similarly,the uniform structure of parks and gardens,may be responsible for the decline in the abundance of the House Martin.We advocate for the preservation or enhancement of urban greenery,expansion of natural vegetation in rural areas and adoption of ecological management practices in orchards and vineyards to mitigate further declines in House Martin populations.
文摘Mountainous regions have disadvantages in economic development because of harsh physical and climatic conditions.However,winter tourism activities are one of the key components for supporting economic development in the highlands.Establishing a ski resort area supports direct and indirect employment in a region,and it stops immigration from mountainous regions to other places.This research aimed to assess the potential ski areas using a multi criteria evaluation technique in the Van region which is located in the eastern part of Türkiye.In this context,snow cover duration,sun effect,slope,slope length,elevation,population density,distance from main roads and lake visibility were used as input factors in the decision making process.Each factor was standardized using a fuzzy technique based on existing well-known ski centers in Türkiye.The weight of inputs was defined by applying a survey to the professional skiers.The most important factors were detected as transportation opportunities and snow covers whereas,the least important factors were elevation and population density.Additionally,lake visibility was very important to make a difference from other existing facilities in the region.Therefore,it was included as constraints and lake visible areas were extracted at the final stage of the research.Potential ski areas were mapped in three levels as professional,intermediate and beginner skiers.One of the suitable areas was selected as a sample projection and for the 3D simulation of the ski investment area.Potential costs and benefits were discussed.It was found that a ski tourism area investment can be amortized in 3 years in the region.
基金supported by the Shanghai Philosophy and Social Science Foundation(2022ECK004)Shanghai Soft Science Research Project(23692123400)。
文摘Dominant technology formation is the key for the hightech industry to“cross the chasm”and gain an established foothold in the market(and hence disrupt the regime).Therefore,a stimulus-response model is proposed to investigate the dominant technology by exploring its formation process and mechanism.Specifically,based on complex adaptive system theory and the basic stimulus-response model,we use a combination of agent-based modeling and system dynamics modeling to capture the interactions between dominant technology and the socio-technical landscape.The results indicate the following:(i)The dynamic interaction is“stimulus-reaction-selection”,which promotes the dominant technology’s formation.(ii)The dominant technology’s formation can be described as a dynamic process in which the adaptation intensity of technology standards increases continuously until it becomes the leading technology under the dual action of internal and external mechanisms.(iii)The dominant technology’s formation in the high-tech industry is influenced by learning ability,the number of adopting users and adaptability.Therein,a“critical scale”of learning ability exists to promote the formation of leading technology:a large number of adopting users can promote the dominant technology’s formation by influencing the adaptive response of technology standards to the socio-technical landscape and the choice of technology standards by the socio-technical landscape.There is a minimum threshold and a maximum threshold for the role of adaptability in the dominant technology’s formation.(iv)The socio-technical landscape can promote the leading technology’s shaping in the high-tech industry,and different elements have different effects.This study promotes research on the formation mechanism of dominant technology in the high-tech industry,presents new perspectives and methods for researchers,and provides essential enlightenment for managers to formulate technology strategies.
基金the National Nature Science Foundation of China(31770437)。
文摘The cold regions are located in high latitudes and cold climates.The local excellent ornamental plant resources are relatively scarce.The plant species that are suitable for both ornamental and productive benefits of landscape of flower sea construction are also even fewer.Therefore,it is imperative to introduce and screen the plant resources suitable for cold regions to create the landscape of flower sea.The rape,an oilseed crop,was used as a research object in order to create a productive flower landscape with both ornamental and economic values in cold regions.Four rape flower varieties,Qingza No.5,7,9,and 11,were introduced from Qinghai Hufeng Agricultural Science and Technology Group Co.,Ltd.They were planted in the experimental practice base of Northeast Agricultural University in three batches.Development characteristics and seed yield of rape flowers on different sowing dates were studied.The fuzzy probability method was used to comprehensively evaluate the varieties.The results showed that the rape flowers grew well in Harbin City during the experimental sowing period,which could form a good landscape of flower sea and had a considerable rapeseed yield.It could be widely used in cold urban and rural areas,such as Harbin City.In view of the experimental results,the strategies of creating a productive landscape of rape flower sea were proposed and the economic benefits were analyzed.It could change the status quo of a uniform landscape of flower sea in cold regions,help the development of rural tourism,and promote local economic income.
基金Sponsored by General Project of Natural Science Foundation of Beijing City(8202017)Postgraduate Research&Practice Innovation Program of Jiangsu Province(SJCX23_1257).
文摘The role of Landscape Character Assessment(LCA)at the level of territorial landscape governance spans both natural and social sciences.By analyzing the development history,research distribution,methods and applications of cutting-edge cases of LCA in China,the following conclusions are drawn:①the LCA research in China originated earlier than that in Europe,but has not yet been systematically applied to the implementation of urban and rural planning at all levels;②the fundamental theory of LCA in China has been well constructed,with three main research directions:technologyled,assessment-led,and assessment combined with other theories;③the development of LCA in rural areas is more mature than in urban areas,but the progress of research is uneven across regions;④the current research presents significant“bottom-up”academic characteristics,and there is an urgent need for government decision-making authorities and academia to jointly promote a“top-down”standardized governance mechanism to comprehensively promote the modernization of territorial landscape governance.
文摘With the rapid development of urbanization,landscape architecture has become an indispensable component of daily life.In order to achieve better landscape effects and protect the ecological environment,landscape ecology theory can be integrated into landscape planning to carry out disciplinary crossing and integration research between landscape ecology and landscape architecture.In this study,based on the basic theories of landscape ecology,the waterfront landscape of Dapo Town was designed,with the aim to achieve ecological balance in planning,showcase biodiversity,and create a harmonious landscape ecological environment which can benefit both nature and people.This design combined artificial and natural elements while improving the natural environment,which promoted a harmonious relationship between humans and nature,thus enriching the spatial organization of the city,and playing a role in regulating the urban environment and climate.
文摘Garden landscape is a beautiful complex formed by space and time complementing each other and acting together.Garden plants are the core landscaping elements in garden landscape construction.It is necessary to flexibly use a variety of plant landscaping methods to create a richer and more vivid natural landscape,and promote the improvement of the quality of the living environment and the harmonious coexistence between man and nature.
文摘Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.