AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorec...AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision （TME）. METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the Amsterdam Cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records. RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）. CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.展开更多
Projections of future urban land change are essential for a range of sustainability assessments,including those related to biodiversity loss,carbon emissions,and agricultural land conversion.However,to what extent and...Projections of future urban land change are essential for a range of sustainability assessments,including those related to biodiversity loss,carbon emissions,and agricultural land conversion.However,to what extent and where current projections agree or disagree remains unknown.Here,we systematically compare existing global projections that are consistent with the Shared Socioeconomic Pathways.We find that the total global urban land area is expected to increase by 112%between 2020 and 2100(averaged across all projections),with a coefficient of variation of 0.81.This variation is mostly caused by the selection of the underlying drivers that are included in the different models.Regionally,the highest average growth rates are found in sub-Saharan Africa(+679%to+730%),while this region also has the highest variation across projections(coefficient of variation ranging from 2.02 to 2.18).When ranking scenarios within a study from the highest to the lowest projected increase in urban land,rankings are relatively similar for regions in the Global North,but not for regions in the Global South.The large disagreement across projections can lead to high uncertainties in assessments of future urban land change impacts,which can undermine the effectiveness of long-term planning,policymaking,and resource management decisions.展开更多
Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic ...Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.展开更多
Large-volume presses(LVPs)are widely utilized in diverse research fields—including high-pressure physics,chemistry,materials science,and Earth and planetary sciences—to investigate the physical and chemical properti...Large-volume presses(LVPs)are widely utilized in diverse research fields—including high-pressure physics,chemistry,materials science,and Earth and planetary sciences—to investigate the physical and chemical properties of materials under extreme high-pressure and hightemperature conditions.A prerequisite for achieving reproducible property measurements is the determination and control of pressure within experimental setups.However,the lack of precise pressure calibration in LVPs hinders the broader application of such devices in ultrahigh-pressure studies.This study employs a suite of standard phase transition-based pressure markers—comprising metallic conductors,semiconductors,and minerals—through both in situ and ex situ identification approaches,to establish pressure calibration curves ranging from 0.4 to>30 GPa for various types of LVP installed at the Center for High Pressure Science and Technology Advanced Research(HPSTAR),Beijing,including piston–cylinder,cubic,and multi-anvil presses.The results provide a unified and traceable pressure reference for highpressure experiments conducted at HPSTAR,while also offering technical guidance and calibration standards for other researchers utilizing similar LVP systems,thereby enabling more consistent comparison between different laboratories.This work facilitates the advancement of LVP research toward broader applications in higher-pressure regimes.展开更多
Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established a...Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.展开更多
Mycorrhizal symbioses are prevalent in terrestrial ecosystems and play essential roles in plant nutrition and health.However,the relative importance of plant evolutionary history,physiology,and eco-geographical factor...Mycorrhizal symbioses are prevalent in terrestrial ecosystems and play essential roles in plant nutrition and health.However,the relative importance of plant evolutionary history,physiology,and eco-geographical factors in shaping mycorrhizal fungal community assembly remains poorly understood.Here,we investigate how plant phylogeny,trophic mode,biogeographic distribution and environmental niche collectively influence the diversity and composition of mycorrhizal fungal communities across the Orchidaceae,spanning broad phylogenetic and ecological scales.By using family-wide orchid-fungal associations and global occurrence data,our analyses showed that the variation in fungal diversity and community structure can be partially explained by orchids’trophic mode,biogeographic distribution and environmental niche,but not by their overall phylogenetic relatedness.Among trophic modes,partially mycoheterotrophic orchids exhibited the highest level of fungal diversity(the lowest level of fungal specificity)in association with a broad range of phylogenetically dispersed fungal partners.Between biogeographical regions,a significantly higher level of fungal specificity was found for orchid species distributed in Australia than those in Eurasia and Africa.Furthermore,multivariate analyses showed that a small portion of the variation in fungal community structure was significantly related to broad climate,soil and vegetation variables,indicating the existence of large-scale habitat filtering on orchid mycorrhizal communities.Altogether,our findings indicate that mycorrhizal communities in the orchid family are likely shaped by multiple,intertwined factors related to orchid ecophysiology and biogeography on a global scale.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
本文评估了在过去20年间(2005-2024),管理学研究如何响应联合国可持续发展目标(Sustainable Development Goals,简称SDGs)。具体而言,本文比较了涵盖会计、金融、管理、市场营销与运营管理五大学科的18本国际顶尖商学与管理学期刊,以及...本文评估了在过去20年间(2005-2024),管理学研究如何响应联合国可持续发展目标(Sustainable Development Goals,简称SDGs)。具体而言,本文比较了涵盖会计、金融、管理、市场营销与运营管理五大学科的18本国际顶尖商学与管理学期刊,以及专注于中国管理研究的Management and Organization Review(MOR)在SDGs关注度上的差异。本文采用三种人工智能工具扫描论文摘要,并评估其与17项SDGs的契合度。结果显示,自2015年SDGs提出以来的10年间,其相关研究显著多于此前10年,增长最为显著的领域集中在SDG08(体面工作与经济增长)、SDG09(产业、创新与基础设施)以及SDG16(和平、正义与健全制度)。在所分析的期刊中,MOR在SDGs相关研究方面表现突出,凸显了其在负责任研究(Responsible Research)方面的学术引领重要作用。基于负责任研究的理念,本文进一步探讨了在学术研究中关注全体利益相关者(而非仅限股东)福祉的重要性。展开更多
Both fractional crystallization and fluid-melt-crystal interaction are involved in the formation of highly fractionated granites.This paper assessed those two processes using geochemistry of muscovite and tourmaline a...Both fractional crystallization and fluid-melt-crystal interaction are involved in the formation of highly fractionated granites.This paper assessed those two processes using geochemistry of muscovite and tourmaline and bulkrock chemistry of multi-phase Wangxianling granitoids,South China.Compositional variations suggest the coarse-grained muscovite granite is produced from fractional crystallization of the two-mica granite whereas the fine-grained muscovite granite represents a distinct magma pulse.Progressive fractionation of quartz,feldspar and biotite leads to elevated boron and aluminum content in melt which promoted muscovite and tourmaline to crystallize,which promotes two-mica granite evolving towards tourmaline-bearing muscovite granite.Fluid-melt-crystal interaction occurred at the magmatichydrothermal transitional stage and resulted in the textural and chemical zonings of tourmaline and muscovite in finegrained muscovite granite.The rims of both tourmaline and muscovite are characterized by the enrichment of fluid mobile elements such as Li,Mn,Cs and Zn and heavierδ^(11)B values of the tourmaline rims(-15.0‰to-13.6‰)compared to cores(-15.7‰to-14.3‰).Meanwhile,significant M-type REE tetrad effects(TE_(1,3)=1.07-1.18)and low K/Rb ratios(48-52)also correspond to fluid-melt-crystal interaction.This study shows zoned muscovite and tourmaline can be excellent tracers of fractional crystallization and late-stage fluid-melt-crystal interaction in highly evolved magmatic systems.展开更多
Addressing the existing gap in ethical research surrounding distinct technical characteristics of Robotic Process Automation enhanced with Artificial Intelligence (AI-RPA), this analysis examines the unique ethical di...Addressing the existing gap in ethical research surrounding distinct technical characteristics of Robotic Process Automation enhanced with Artificial Intelligence (AI-RPA), this analysis examines the unique ethical dimensions by positioning AI-RPA as a distinct technological subdivision. From an analytical perspective, this study highlights key characteristics such as minimal reliance on programming, rapid development cycles, and restricted algorithmic control, which differentiate AI-RPA from traditional AI systems. These characteristics underscore the need for tailored ethical considerations, to identify ethical perils within AI-RPA’s technological origins. By positioning AI-RPA as a distinct subdivision and examining its unique characteristics alongside their emerging ethical challenges, this paper enriches the evolving discourse on AI ethics, providing valuable insights for researchers, policymakers, and organizations implementing AI-RPA technologies.展开更多
The color cluster red,black and white occurs in the artistic,ritual and magical activities of virtually all cultures around the world,suggesting their preeminence in human symbolic thought.Among the various explanatio...The color cluster red,black and white occurs in the artistic,ritual and magical activities of virtually all cultures around the world,suggesting their preeminence in human symbolic thought.Among the various explanations that have been brought forth to account for the special status of these three colors are:1)evolutionary/ecological arguments,drawing support from vision science,perceptual philosophy and primate biology;2)cognitive arguments,which pay attention to how human beings categorize and create meaning out of perceptual experiences;3)linguistic arguments,as these are the earliest lexicalized color words in most languages;4)and diverse socio-cultural arguments.This paper will explore the manifestation of red,black and white–both in concrete terms,through the use and manipulation of materials,as well as abstract ideas–in Assyrian and Babylonian magical and ritual activities.It will highlight how meaning is created and communicated by relating colors to natural and supernatural phenomena and will further attempt to provide a methodological framework for the analysis of color symbolism.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highli...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.展开更多
Food allergies are abnormal immune responses triggered by specific foods,affecting the quality of life of millions of people worldwide.In recent years,the prevalence of food allergies has increased significantly,espec...Food allergies are abnormal immune responses triggered by specific foods,affecting the quality of life of millions of people worldwide.In recent years,the prevalence of food allergies has increased significantly,especially in Westernized countries,prompting the scientific community to explore the complex mechanisms behind them.Dietary patterns and specific dietary components are important factors related to the occurrence,development,and prevention of food allergies.Studies have shown that the Mediterranean diet,which is high in fiber,rich in antioxidants,and healthy fats,shows potential protective effects by promoting the balance of intestinal flora,maintaining the intestinal barrier,and regulating immunity.In contrast,a high-fat,high-sugar,low-fiber Western diet is associated with an increased risk of allergies.Key dietary components such as omega-3 fatty acids,dietary fiber,vitamins A,D,and E,and bioactive substances such as quercetin and curcumin can regulate immune tolerance through multiple pathways,including epigenetic regulation and affecting mitochondrial function.However,advanced glycation end products(AGEs),emulsifiers,artificial sweeteners produced by food processing,and pesticide residues(such as glyphosate)may damage the intestinal barrier,disrupt the flora,and increase the risk of allergies.This review explored the risk and protective factors for food allergies from a dietary perspective,thus benefiting the progress of intervention and therapy of food allergy.展开更多
文摘AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision （TME）. METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the Amsterdam Cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records. RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）. CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.
基金supported by the Netherlands Organization for Scientific Research NWO in the form of a VIDI grant(Grant No.VI.Vidi.198.008).
文摘Projections of future urban land change are essential for a range of sustainability assessments,including those related to biodiversity loss,carbon emissions,and agricultural land conversion.However,to what extent and where current projections agree or disagree remains unknown.Here,we systematically compare existing global projections that are consistent with the Shared Socioeconomic Pathways.We find that the total global urban land area is expected to increase by 112%between 2020 and 2100(averaged across all projections),with a coefficient of variation of 0.81.This variation is mostly caused by the selection of the underlying drivers that are included in the different models.Regionally,the highest average growth rates are found in sub-Saharan Africa(+679%to+730%),while this region also has the highest variation across projections(coefficient of variation ranging from 2.02 to 2.18).When ranking scenarios within a study from the highest to the lowest projected increase in urban land,rankings are relatively similar for regions in the Global North,but not for regions in the Global South.The large disagreement across projections can lead to high uncertainties in assessments of future urban land change impacts,which can undermine the effectiveness of long-term planning,policymaking,and resource management decisions.
文摘Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.
基金supported by the National Science Foundation of China(Grant Nos.U1530402 and U1930401).
文摘Large-volume presses(LVPs)are widely utilized in diverse research fields—including high-pressure physics,chemistry,materials science,and Earth and planetary sciences—to investigate the physical and chemical properties of materials under extreme high-pressure and hightemperature conditions.A prerequisite for achieving reproducible property measurements is the determination and control of pressure within experimental setups.However,the lack of precise pressure calibration in LVPs hinders the broader application of such devices in ultrahigh-pressure studies.This study employs a suite of standard phase transition-based pressure markers—comprising metallic conductors,semiconductors,and minerals—through both in situ and ex situ identification approaches,to establish pressure calibration curves ranging from 0.4 to>30 GPa for various types of LVP installed at the Center for High Pressure Science and Technology Advanced Research(HPSTAR),Beijing,including piston–cylinder,cubic,and multi-anvil presses.The results provide a unified and traceable pressure reference for highpressure experiments conducted at HPSTAR,while also offering technical guidance and calibration standards for other researchers utilizing similar LVP systems,thereby enabling more consistent comparison between different laboratories.This work facilitates the advancement of LVP research toward broader applications in higher-pressure regimes.
基金Outstanding Young Investigator Program of Capital Medical University,Grant/Award Number:A2308。
文摘Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.
基金the funding provided by the China Scholarship Council(Grant No.201804910634)the Ecology Fund of the Royal Netherlands Academy of Arts and Sciences(KNAWWF/807/19039)to Deyi Wang.
文摘Mycorrhizal symbioses are prevalent in terrestrial ecosystems and play essential roles in plant nutrition and health.However,the relative importance of plant evolutionary history,physiology,and eco-geographical factors in shaping mycorrhizal fungal community assembly remains poorly understood.Here,we investigate how plant phylogeny,trophic mode,biogeographic distribution and environmental niche collectively influence the diversity and composition of mycorrhizal fungal communities across the Orchidaceae,spanning broad phylogenetic and ecological scales.By using family-wide orchid-fungal associations and global occurrence data,our analyses showed that the variation in fungal diversity and community structure can be partially explained by orchids’trophic mode,biogeographic distribution and environmental niche,but not by their overall phylogenetic relatedness.Among trophic modes,partially mycoheterotrophic orchids exhibited the highest level of fungal diversity(the lowest level of fungal specificity)in association with a broad range of phylogenetically dispersed fungal partners.Between biogeographical regions,a significantly higher level of fungal specificity was found for orchid species distributed in Australia than those in Eurasia and Africa.Furthermore,multivariate analyses showed that a small portion of the variation in fungal community structure was significantly related to broad climate,soil and vegetation variables,indicating the existence of large-scale habitat filtering on orchid mycorrhizal communities.Altogether,our findings indicate that mycorrhizal communities in the orchid family are likely shaped by multiple,intertwined factors related to orchid ecophysiology and biogeography on a global scale.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
文摘本文评估了在过去20年间(2005-2024),管理学研究如何响应联合国可持续发展目标(Sustainable Development Goals,简称SDGs)。具体而言,本文比较了涵盖会计、金融、管理、市场营销与运营管理五大学科的18本国际顶尖商学与管理学期刊,以及专注于中国管理研究的Management and Organization Review(MOR)在SDGs关注度上的差异。本文采用三种人工智能工具扫描论文摘要,并评估其与17项SDGs的契合度。结果显示,自2015年SDGs提出以来的10年间,其相关研究显著多于此前10年,增长最为显著的领域集中在SDG08(体面工作与经济增长)、SDG09(产业、创新与基础设施)以及SDG16(和平、正义与健全制度)。在所分析的期刊中,MOR在SDGs相关研究方面表现突出,凸显了其在负责任研究(Responsible Research)方面的学术引领重要作用。基于负责任研究的理念,本文进一步探讨了在学术研究中关注全体利益相关者(而非仅限股东)福祉的重要性。
基金funded by the National Natural Science Foundation of China(Grant Nos.42072089 and 41530206)。
文摘Both fractional crystallization and fluid-melt-crystal interaction are involved in the formation of highly fractionated granites.This paper assessed those two processes using geochemistry of muscovite and tourmaline and bulkrock chemistry of multi-phase Wangxianling granitoids,South China.Compositional variations suggest the coarse-grained muscovite granite is produced from fractional crystallization of the two-mica granite whereas the fine-grained muscovite granite represents a distinct magma pulse.Progressive fractionation of quartz,feldspar and biotite leads to elevated boron and aluminum content in melt which promoted muscovite and tourmaline to crystallize,which promotes two-mica granite evolving towards tourmaline-bearing muscovite granite.Fluid-melt-crystal interaction occurred at the magmatichydrothermal transitional stage and resulted in the textural and chemical zonings of tourmaline and muscovite in finegrained muscovite granite.The rims of both tourmaline and muscovite are characterized by the enrichment of fluid mobile elements such as Li,Mn,Cs and Zn and heavierδ^(11)B values of the tourmaline rims(-15.0‰to-13.6‰)compared to cores(-15.7‰to-14.3‰).Meanwhile,significant M-type REE tetrad effects(TE_(1,3)=1.07-1.18)and low K/Rb ratios(48-52)also correspond to fluid-melt-crystal interaction.This study shows zoned muscovite and tourmaline can be excellent tracers of fractional crystallization and late-stage fluid-melt-crystal interaction in highly evolved magmatic systems.
文摘Addressing the existing gap in ethical research surrounding distinct technical characteristics of Robotic Process Automation enhanced with Artificial Intelligence (AI-RPA), this analysis examines the unique ethical dimensions by positioning AI-RPA as a distinct technological subdivision. From an analytical perspective, this study highlights key characteristics such as minimal reliance on programming, rapid development cycles, and restricted algorithmic control, which differentiate AI-RPA from traditional AI systems. These characteristics underscore the need for tailored ethical considerations, to identify ethical perils within AI-RPA’s technological origins. By positioning AI-RPA as a distinct subdivision and examining its unique characteristics alongside their emerging ethical challenges, this paper enriches the evolving discourse on AI ethics, providing valuable insights for researchers, policymakers, and organizations implementing AI-RPA technologies.
文摘The color cluster red,black and white occurs in the artistic,ritual and magical activities of virtually all cultures around the world,suggesting their preeminence in human symbolic thought.Among the various explanations that have been brought forth to account for the special status of these three colors are:1)evolutionary/ecological arguments,drawing support from vision science,perceptual philosophy and primate biology;2)cognitive arguments,which pay attention to how human beings categorize and create meaning out of perceptual experiences;3)linguistic arguments,as these are the earliest lexicalized color words in most languages;4)and diverse socio-cultural arguments.This paper will explore the manifestation of red,black and white–both in concrete terms,through the use and manipulation of materials,as well as abstract ideas–in Assyrian and Babylonian magical and ritual activities.It will highlight how meaning is created and communicated by relating colors to natural and supernatural phenomena and will further attempt to provide a methodological framework for the analysis of color symbolism.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.
基金the financial support received from the Open Project of National Center of Technology Innovation for Dairy(No.2024-KFKT-009)the Key R&D Program of Zhejiang Provincial Administration for Market Regulation(No.ZD2024001).
文摘Food allergies are abnormal immune responses triggered by specific foods,affecting the quality of life of millions of people worldwide.In recent years,the prevalence of food allergies has increased significantly,especially in Westernized countries,prompting the scientific community to explore the complex mechanisms behind them.Dietary patterns and specific dietary components are important factors related to the occurrence,development,and prevention of food allergies.Studies have shown that the Mediterranean diet,which is high in fiber,rich in antioxidants,and healthy fats,shows potential protective effects by promoting the balance of intestinal flora,maintaining the intestinal barrier,and regulating immunity.In contrast,a high-fat,high-sugar,low-fiber Western diet is associated with an increased risk of allergies.Key dietary components such as omega-3 fatty acids,dietary fiber,vitamins A,D,and E,and bioactive substances such as quercetin and curcumin can regulate immune tolerance through multiple pathways,including epigenetic regulation and affecting mitochondrial function.However,advanced glycation end products(AGEs),emulsifiers,artificial sweeteners produced by food processing,and pesticide residues(such as glyphosate)may damage the intestinal barrier,disrupt the flora,and increase the risk of allergies.This review explored the risk and protective factors for food allergies from a dietary perspective,thus benefiting the progress of intervention and therapy of food allergy.
