Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol chan...Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.展开更多
Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patien...Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
Although momentum strategies result in abnormal profitability,thereby challenging the efficient market hypothesis(EMH),concerns persist regarding their reliability due to their significant volatility and susceptibilit...Although momentum strategies result in abnormal profitability,thereby challenging the efficient market hypothesis(EMH),concerns persist regarding their reliability due to their significant volatility and susceptibility to substantial losses.In this study,we investigate the limitations of these strategies and propose a solution.Our literature review reveals that the volatile profits are due to statistical analyses that assume the persistence of past patterns,leading to unreliable results in out-of-sample scenarios when underlying mechanisms evolve.Statistical analysis,the predominant method in financial economics,often proves inadequate in explaining market fluctuations and predicting crashes.To overcome these limitations,a paradigm shift towards dynamic approaches is essential.Drawing inspiration from three groundbreaking economists,we introduce the extended Samuelson model(ESM),a dynamic model that connects price changes to market participant actions.This paradigm transition uncovers several significant findings.First,timely signals indicate momentum initiations,cessations,and reversals,validated using S&P 500 data from 1999 to 2023.Second,ESM predicts the 1987 Black Monday crash weeks in advance,offering a new perspective on its underlying cause.Third,we classify sequential stock price data into eight distinct market states,including their thresholds for transitions,laying the groundwork for market trend predictions and risk assessments.Fourth,the ESM is shown to be a compelling alternative to EMH,offering potent explanatory and predictive power based on a single,realistic assumption.Our findings suggest that ESM has the potential to provide policymakers with proactive tools,enabling financial institutions to enhance their risk assessment and management strategies.展开更多
Substantial evidence points to the early onset of peripheral inflammation in the development of Parkinson's disease(PD),supporting the“body-first”hypothesis.However,there remains a notable absence of PD-specific...Substantial evidence points to the early onset of peripheral inflammation in the development of Parkinson's disease(PD),supporting the“body-first”hypothesis.However,there remains a notable absence of PD-specific animal models induced by inflammatory cytokines.This study introduces a novel mouse model of PD driven by the proinflammatory cytokine CXCL1,identified in our previous research.The involvement of CXCL1 in PD pathogenesis was validated using subacute and chronic MPTP-induced mouse models.Based on these findings,2-month-old C57BL/6J mice were intravenously administered CXCL1(20 ng/kg/day)for 2 weeks(5 days per week),successfully replicating motor deficits and pathological alterations in the substantia nigra observed in the chronic MPTP model.These results demonstrate the potential of CXCL1-induced inflammation as a mechanism for PD modeling.The model revealed activation of the PPAR signaling pathway in CXCL1-mediated neuronal damage by CXCL1.Linoleic acid,a PPAR-γactivator,significantly mitigated MPTPand CXCL1-induced toxicity and reduced serum CXCL1levels.In addition,the CXCL1-injected mouse model shortened the timeline for developing chronic PD mouse model to 2 weeks,offering an efficient platform for studying inflammation-driven processes in PD.The findings provide critical insights into the inflammatory mechanisms underlying PD and identify promising therapeutic targets for intervention.展开更多
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
Based on the hindcasts from five subseasonal-to-seasonal(S2S)models participating in the S2S Prediction Project,this study evaluates the performance of the multimodel ensemble(MME)approach in predicting the subseasona...Based on the hindcasts from five subseasonal-to-seasonal(S2S)models participating in the S2S Prediction Project,this study evaluates the performance of the multimodel ensemble(MME)approach in predicting the subseasonal precipitation anomalies during summer in China and reveals the contributions of possible driving factors.The results suggest that while single-model ensembles(SMEs)exhibit constrained predictive skills within a limited forecast lead time of three pentads,the MME illustrates an enhanced predictive skill at a lead time of up to four pentads,and even six pentads,in southern China.Based on both deterministic and probabilistic verification metrics,the MME consistently outperforms SMEs,with a more evident advantage observed in probabilistic forecasting.The superior performance of the MME is primarily attributable to the increase in ensemble size,and the enhanced model diversity is also a contributing factor.The reliability of probabilistic skill is largely improved due to the increase in ensemble members,while the resolution term does not exhibit consistent improvement.Furthermore,the Madden–Julian Oscillation(MJO)is revealed as the primary driving factor for the successful prediction of summer precipitation in China using the MME.The improvement by the MME is not solely attributable to the enhancement in the inherent predictive capacity of the MJO itself,but derives from its capability in capturing the more realistic relationship between the MJO and subseasonal precipitation anomalies in China.This study establishes a scientific foundation for acknowledging the advantageous predictive capability of the MME approach in subseasonal predictions of summer precipitation in China,and sheds light on further improving S2S predictions.展开更多
BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whethe...BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whether endoscopic activity will improve in CD patients.METHODS This is a single-center retrospective study that included patients diagnosed with CD from January 2014 to December 2022.The patients were randomly divided into a modeling group(70%)and an internal validation group(30%),with an external validation group from January 2023 to March 2024.Univariate and binary logistic regression analyses were conducted to identify independent risk factors,which were used to construct a nomogram model.The model's performance was evaluated using receiver operating characteristic curves,calibration curves,and decision curve analysis(DCA).Additionally,further sensitivity analyses were performed.RESULTS One hundred seventy patients were included in the training group,while 64 were included in the external validation group.A binary logistic stepwise regression analysis revealed that the changes in the amplitudes of albumin(ALB)and fibrinogen(FIB)were independent risk factors for endoscopic improvement.A nomogram model was developed based on these risk factors.The area under the curve of the model for the training group,internal validation group,and external validation group were 0.802,0.788,and 0.787,respectively.The average absolute errors of the calibration curves were 0.011,0.016,and 0.018,respectively.DCA indicated that the model performs well in clinical practice.Additionally,sensitivity analysis demonstrated that the model has strong robustness and applicability.CONCLUSION Our study shows that changes in the amplitudes of ALB and FIB are effective predictors of endoscopic improvement in patients with CD during follow-up visits compared to their previous ones.展开更多
To promote the global dissemination of Chinese culture,the translation of Chinese classic literature has garnered widespread attention in the translation field.Literary translation criticism plays an essential role in...To promote the global dissemination of Chinese culture,the translation of Chinese classic literature has garnered widespread attention in the translation field.Literary translation criticism plays an essential role in the development of translation endeavors.This paper will analyze three versions of English translations of Shen Congwen’s novella Border Town using Reiss’s translation criticism model and summarize their performance in terms of formal equivalence and aesthetic effect,linguistic components,and extra-linguistic components.展开更多
BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relation...BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.展开更多
Based on BERTopic Model,the paper combines qualitative and quantitative methods to explore the reception of Can Xue’s translated works by analyzing readers’book reviews posted on Goodreads and Lovereading.We first c...Based on BERTopic Model,the paper combines qualitative and quantitative methods to explore the reception of Can Xue’s translated works by analyzing readers’book reviews posted on Goodreads and Lovereading.We first collected book reviews from these two well-known websites by Python.Through topic analysis of these reviews,we identified recurring topics,including details of her translated works and appreciation of their translation quality.Then,employing sentiment and content analysis methods,the paper explored the emotional attitudes and the specific thoughts of readers toward Can Xue and her translated works.The fingdings revealed that,among the 408 reviews,though the reception of Can Xue’s translated works was relatively positive,the current level of attention and recognition remains insufficient.However,based on the research results,the paper can derive valuable insights into the translation and dissemination processes such as adjusting translation and dissemination strategies,so that the global reach of Chinese literature and culture can be better facilitated.展开更多
Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induct...Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD:transforming growth factor-β1(TGF-β1),fibrin,sodium tetradecyl sulfate(STS)combined with TGF-β1,and polidocanol(POL)combined with TGF-β1.The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature.The STS+TGF-β1 combination resulted in both histological and morphological alterations,but with a high incidence of localized necrosis that led to animal death.The POL+TGF-β1 combination produced pathological changes and curvature comparable to STS+TGF-β1 and led to fewer complications.In conclusion,fibrin,STS+TGF-β1,and POL+TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats.The POL+TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.展开更多
This paper,grounded in the theory of business model innovation,examines the Chinese People’s Health Press(人民卫生出版社)as a case study to explore strategies for innovating business models within the context of prof...This paper,grounded in the theory of business model innovation,examines the Chinese People’s Health Press(人民卫生出版社)as a case study to explore strategies for innovating business models within the context of professional publishing convergence development.The research posits that effective business model innovation in this domain necessitates a comprehensive reform of its constituent elements.It advocates for a systematic approach to reconstructing value propositions,enhancing value creation and delivery processes,and optimizing value capture mechanisms to achieve desired outcomes.展开更多
The corrosion problems of high-voltage power transmission conductors typically occur in environments with electric fields.However,current research mainly focuses on atmospheric corrosion of metals with limited attenti...The corrosion problems of high-voltage power transmission conductors typically occur in environments with electric fields.However,current research mainly focuses on atmospheric corrosion of metals with limited attention to the combined effects of electric fields and atmospheric conditions on metal corrosion.This study established a corrosion prediction model that considers the effects of electric fields and dynamic boundaries.Because of the influence of dynamic boundaries,this model can calculate parameters such as corrosion rate,corrosion depth,corrosion product accumulation and ion concentration for metal samples with and without an external electric field.The model is validated through indoor accelerated corrosion tests under low applied electric fields and by using aluminium alloy conductor samples from high electric field regions of actual±500 kV power transmission lines.The results indicate that the corrosion rate of aluminium alloys initially increases and then decreases over time.Additionally,the corrosion rate of aluminium alloys under an applied electric field is higher than that without an electric field during the same period.The mechanism of increased corrosion rate is analysed to be that the presence of the electric field accelerates the cathode reaction rate of the electrode.The corrosion rate of the sample increased by about 78%under a lower electric field(0-20 kV/m)and by about 2.75 times under a higher electric field around 2000 kV/m.展开更多
High-fidelity tactile rendering offers significant potential for improving the richness and immersion of touchscreen interactions.This study focuses on a quantitative description of tactile rendering fidelity using a ...High-fidelity tactile rendering offers significant potential for improving the richness and immersion of touchscreen interactions.This study focuses on a quantitative description of tactile rendering fidelity using a custom-designed hybrid electrovibration and mechanical vibration(HEM)device.An electrovibration and mechanical vibration(EMV)algorithm that renders 3D gratings with different physical heights was proposed and shown to achieve 81%accuracy in shape recognition.Models of tactile rendering fidelity were established based on the evaluation of the height discrimination threshold,and the psychophysical-physical relationships between the discrimination and reference heights were well described by a modification of Weber’s law,with correlation coefficients higher than 0.9.The physiological-physical relationship between the pulse firing rate and the physical stimulation voltage was modeled using the Izhikevich spiking model with a logarithmic relationship.展开更多
The numerical simulation of the fluid flow and the flexible rod(s)interaction is more complicated and has lower efficiency due to the high computational cost.In this paper,a semi-resolved model coupling the computatio...The numerical simulation of the fluid flow and the flexible rod(s)interaction is more complicated and has lower efficiency due to the high computational cost.In this paper,a semi-resolved model coupling the computational fluid dynamics and the flexible rod dynamics is proposed using a two-way domain expansion method.The gov-erning equations of the flexible rod dynamics are discretized and solved by the finite element method,and the fluid flow is simulated by the finite volume method.The interaction between fluids and solid rods is modeled by introducing body force terms into the momentum equations.Referred to the traditional semi-resolved numerical model,an anisotropic Gaussian kernel function method is proposed to specify the interactive forces between flu-ids and solid bodies for non-circle rod cross-sections.A benchmark of the flow passing around a single flexible plate with a rectangular cross-section is used to validate the algorithm.Focused on the engineering applications,a test case of a finite patch of cylinders is implemented to validate the accuracy and efficiency of the coupled model.展开更多
Quantification of river flood risks is a prerequisite for floodplain management and development.The lower Yellow River(LYR)is characterized by a complex channel–floodplain system,which is prone to flooding but inhabi...Quantification of river flood risks is a prerequisite for floodplain management and development.The lower Yellow River(LYR)is characterized by a complex channel–floodplain system,which is prone to flooding but inhabits a large population on the floodplains.Many floodplain management modes have been presented,but implementation effects of these management modes have not been evaluated correctly.An integrated model was first proposed to evaluate the flood risks to people’s life and property,covering an improved module of two-dimensional(2D)morphodynamic processes and a module of flood risk evaluation for people,buildings and crops on the floodplains.Two simulation cases were then conducted to validate the model accuracy,including the hyperconcentrated flood event and dike-breach induced flood event occurring in the LYR.Finally,the integrated model was applied to key floodplains in the LYR,and the effects of different floodplain management modes were quantified on the risks to people’s life and property under an extreme flood event.Results indicate that:①Satisfactory accuracy was achieved in the simulation of these two flood events.The maximum sediment concentration was just underestimated by 9%,and the simulated inundation depth agreed well with the field record;②severe inundation was predicted to occur in most domains under the current topography(SchemeⅠ),which would be alleviated after implementing different floodplain management modes,with the area in slight inundation degree accounting for a large proportion under the mode of“construction of protection embankment”(SchemeⅡ)and the area in medium inundation degree occupying a high ratio under the mode of“floodplain partition harnessing”(SchemeⅢ);and③compared with SchemeⅠ,the high-risk area for people’s life and property would reduce by 21%–49%under SchemeⅡ,and by 35%–93%under SchemeⅢ.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82200784,32271311Qizhen Foundation,No.226‐2023‐00008(all to LH).
文摘Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.
基金supported by the Canadian Institutes of Health Research(DFD-181599)the National Institutes of Health(T32AG058527)to RJB and R0190106435 to VM.
文摘Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
文摘Although momentum strategies result in abnormal profitability,thereby challenging the efficient market hypothesis(EMH),concerns persist regarding their reliability due to their significant volatility and susceptibility to substantial losses.In this study,we investigate the limitations of these strategies and propose a solution.Our literature review reveals that the volatile profits are due to statistical analyses that assume the persistence of past patterns,leading to unreliable results in out-of-sample scenarios when underlying mechanisms evolve.Statistical analysis,the predominant method in financial economics,often proves inadequate in explaining market fluctuations and predicting crashes.To overcome these limitations,a paradigm shift towards dynamic approaches is essential.Drawing inspiration from three groundbreaking economists,we introduce the extended Samuelson model(ESM),a dynamic model that connects price changes to market participant actions.This paradigm transition uncovers several significant findings.First,timely signals indicate momentum initiations,cessations,and reversals,validated using S&P 500 data from 1999 to 2023.Second,ESM predicts the 1987 Black Monday crash weeks in advance,offering a new perspective on its underlying cause.Third,we classify sequential stock price data into eight distinct market states,including their thresholds for transitions,laying the groundwork for market trend predictions and risk assessments.Fourth,the ESM is shown to be a compelling alternative to EMH,offering potent explanatory and predictive power based on a single,realistic assumption.Our findings suggest that ESM has the potential to provide policymakers with proactive tools,enabling financial institutions to enhance their risk assessment and management strategies.
基金supported by the National Natural Science Foundation of China (32471049,32170984,32471188,32200802)Natural Science Foundation of Shandong Province (ZR2023QH110)。
文摘Substantial evidence points to the early onset of peripheral inflammation in the development of Parkinson's disease(PD),supporting the“body-first”hypothesis.However,there remains a notable absence of PD-specific animal models induced by inflammatory cytokines.This study introduces a novel mouse model of PD driven by the proinflammatory cytokine CXCL1,identified in our previous research.The involvement of CXCL1 in PD pathogenesis was validated using subacute and chronic MPTP-induced mouse models.Based on these findings,2-month-old C57BL/6J mice were intravenously administered CXCL1(20 ng/kg/day)for 2 weeks(5 days per week),successfully replicating motor deficits and pathological alterations in the substantia nigra observed in the chronic MPTP model.These results demonstrate the potential of CXCL1-induced inflammation as a mechanism for PD modeling.The model revealed activation of the PPAR signaling pathway in CXCL1-mediated neuronal damage by CXCL1.Linoleic acid,a PPAR-γactivator,significantly mitigated MPTPand CXCL1-induced toxicity and reduced serum CXCL1levels.In addition,the CXCL1-injected mouse model shortened the timeline for developing chronic PD mouse model to 2 weeks,offering an efficient platform for studying inflammation-driven processes in PD.The findings provide critical insights into the inflammatory mechanisms underlying PD and identify promising therapeutic targets for intervention.
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
基金sponsored by the National Natural Science Foundation of China(Grant Nos.42175052 and U2442206)the Joint Research Project for Meteorological Capacity Improvement(Grant No.23NLTSQ007,23NLTSZ003)+2 种基金the Innovative Development Special Project of the China Meteorological Administration(Grant No.CXFZ2023J002)the National Key R&D Program of China(Grant No.2023YFC3007700,2024YFC3013100)the China Meteorological Administration Youth Innovation Team(Grant No.CMA2024QN06)。
文摘Based on the hindcasts from five subseasonal-to-seasonal(S2S)models participating in the S2S Prediction Project,this study evaluates the performance of the multimodel ensemble(MME)approach in predicting the subseasonal precipitation anomalies during summer in China and reveals the contributions of possible driving factors.The results suggest that while single-model ensembles(SMEs)exhibit constrained predictive skills within a limited forecast lead time of three pentads,the MME illustrates an enhanced predictive skill at a lead time of up to four pentads,and even six pentads,in southern China.Based on both deterministic and probabilistic verification metrics,the MME consistently outperforms SMEs,with a more evident advantage observed in probabilistic forecasting.The superior performance of the MME is primarily attributable to the increase in ensemble size,and the enhanced model diversity is also a contributing factor.The reliability of probabilistic skill is largely improved due to the increase in ensemble members,while the resolution term does not exhibit consistent improvement.Furthermore,the Madden–Julian Oscillation(MJO)is revealed as the primary driving factor for the successful prediction of summer precipitation in China using the MME.The improvement by the MME is not solely attributable to the enhancement in the inherent predictive capacity of the MJO itself,but derives from its capability in capturing the more realistic relationship between the MJO and subseasonal precipitation anomalies in China.This study establishes a scientific foundation for acknowledging the advantageous predictive capability of the MME approach in subseasonal predictions of summer precipitation in China,and sheds light on further improving S2S predictions.
文摘BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whether endoscopic activity will improve in CD patients.METHODS This is a single-center retrospective study that included patients diagnosed with CD from January 2014 to December 2022.The patients were randomly divided into a modeling group(70%)and an internal validation group(30%),with an external validation group from January 2023 to March 2024.Univariate and binary logistic regression analyses were conducted to identify independent risk factors,which were used to construct a nomogram model.The model's performance was evaluated using receiver operating characteristic curves,calibration curves,and decision curve analysis(DCA).Additionally,further sensitivity analyses were performed.RESULTS One hundred seventy patients were included in the training group,while 64 were included in the external validation group.A binary logistic stepwise regression analysis revealed that the changes in the amplitudes of albumin(ALB)and fibrinogen(FIB)were independent risk factors for endoscopic improvement.A nomogram model was developed based on these risk factors.The area under the curve of the model for the training group,internal validation group,and external validation group were 0.802,0.788,and 0.787,respectively.The average absolute errors of the calibration curves were 0.011,0.016,and 0.018,respectively.DCA indicated that the model performs well in clinical practice.Additionally,sensitivity analysis demonstrated that the model has strong robustness and applicability.CONCLUSION Our study shows that changes in the amplitudes of ALB and FIB are effective predictors of endoscopic improvement in patients with CD during follow-up visits compared to their previous ones.
文摘To promote the global dissemination of Chinese culture,the translation of Chinese classic literature has garnered widespread attention in the translation field.Literary translation criticism plays an essential role in the development of translation endeavors.This paper will analyze three versions of English translations of Shen Congwen’s novella Border Town using Reiss’s translation criticism model and summarize their performance in terms of formal equivalence and aesthetic effect,linguistic components,and extra-linguistic components.
文摘BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.
基金supported by the 2023 Youth Fund for Humanities and Social Sciences Research by the Ministry of Education of the People’s Republic of China(Grant No.23YJC740004).
文摘Based on BERTopic Model,the paper combines qualitative and quantitative methods to explore the reception of Can Xue’s translated works by analyzing readers’book reviews posted on Goodreads and Lovereading.We first collected book reviews from these two well-known websites by Python.Through topic analysis of these reviews,we identified recurring topics,including details of her translated works and appreciation of their translation quality.Then,employing sentiment and content analysis methods,the paper explored the emotional attitudes and the specific thoughts of readers toward Can Xue and her translated works.The fingdings revealed that,among the 408 reviews,though the reception of Can Xue’s translated works was relatively positive,the current level of attention and recognition remains insufficient.However,based on the research results,the paper can derive valuable insights into the translation and dissemination processes such as adjusting translation and dissemination strategies,so that the global reach of Chinese literature and culture can be better facilitated.
基金supported by the National Natural Science Foundation of China(grant No.81971380 and No.82301822).
文摘Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD:transforming growth factor-β1(TGF-β1),fibrin,sodium tetradecyl sulfate(STS)combined with TGF-β1,and polidocanol(POL)combined with TGF-β1.The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature.The STS+TGF-β1 combination resulted in both histological and morphological alterations,but with a high incidence of localized necrosis that led to animal death.The POL+TGF-β1 combination produced pathological changes and curvature comparable to STS+TGF-β1 and led to fewer complications.In conclusion,fibrin,STS+TGF-β1,and POL+TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats.The POL+TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
文摘This paper,grounded in the theory of business model innovation,examines the Chinese People’s Health Press(人民卫生出版社)as a case study to explore strategies for innovating business models within the context of professional publishing convergence development.The research posits that effective business model innovation in this domain necessitates a comprehensive reform of its constituent elements.It advocates for a systematic approach to reconstructing value propositions,enhancing value creation and delivery processes,and optimizing value capture mechanisms to achieve desired outcomes.
基金supported by National Key Research and Development Program of China,Grant/Award Number:2024YFB4206900.
文摘The corrosion problems of high-voltage power transmission conductors typically occur in environments with electric fields.However,current research mainly focuses on atmospheric corrosion of metals with limited attention to the combined effects of electric fields and atmospheric conditions on metal corrosion.This study established a corrosion prediction model that considers the effects of electric fields and dynamic boundaries.Because of the influence of dynamic boundaries,this model can calculate parameters such as corrosion rate,corrosion depth,corrosion product accumulation and ion concentration for metal samples with and without an external electric field.The model is validated through indoor accelerated corrosion tests under low applied electric fields and by using aluminium alloy conductor samples from high electric field regions of actual±500 kV power transmission lines.The results indicate that the corrosion rate of aluminium alloys initially increases and then decreases over time.Additionally,the corrosion rate of aluminium alloys under an applied electric field is higher than that without an electric field during the same period.The mechanism of increased corrosion rate is analysed to be that the presence of the electric field accelerates the cathode reaction rate of the electrode.The corrosion rate of the sample increased by about 78%under a lower electric field(0-20 kV/m)and by about 2.75 times under a higher electric field around 2000 kV/m.
基金Supported by the National Natural Science Foundation of China under Grants 61631010 and 61806085.
文摘High-fidelity tactile rendering offers significant potential for improving the richness and immersion of touchscreen interactions.This study focuses on a quantitative description of tactile rendering fidelity using a custom-designed hybrid electrovibration and mechanical vibration(HEM)device.An electrovibration and mechanical vibration(EMV)algorithm that renders 3D gratings with different physical heights was proposed and shown to achieve 81%accuracy in shape recognition.Models of tactile rendering fidelity were established based on the evaluation of the height discrimination threshold,and the psychophysical-physical relationships between the discrimination and reference heights were well described by a modification of Weber’s law,with correlation coefficients higher than 0.9.The physiological-physical relationship between the pulse firing rate and the physical stimulation voltage was modeled using the Izhikevich spiking model with a logarithmic relationship.
基金supported by Shanghai 2021“Science and Technology Innovation Action Plan”:Social Development Science and Technology Research Project(Grant No.21DZ1202703).
文摘The numerical simulation of the fluid flow and the flexible rod(s)interaction is more complicated and has lower efficiency due to the high computational cost.In this paper,a semi-resolved model coupling the computational fluid dynamics and the flexible rod dynamics is proposed using a two-way domain expansion method.The gov-erning equations of the flexible rod dynamics are discretized and solved by the finite element method,and the fluid flow is simulated by the finite volume method.The interaction between fluids and solid rods is modeled by introducing body force terms into the momentum equations.Referred to the traditional semi-resolved numerical model,an anisotropic Gaussian kernel function method is proposed to specify the interactive forces between flu-ids and solid bodies for non-circle rod cross-sections.A benchmark of the flow passing around a single flexible plate with a rectangular cross-section is used to validate the algorithm.Focused on the engineering applications,a test case of a finite patch of cylinders is implemented to validate the accuracy and efficiency of the coupled model.
基金supported by the National Natural Science Foundation of China(U2243238)the Program of the National Key Research and Development Plan(2023YFC3209304).
文摘Quantification of river flood risks is a prerequisite for floodplain management and development.The lower Yellow River(LYR)is characterized by a complex channel–floodplain system,which is prone to flooding but inhabits a large population on the floodplains.Many floodplain management modes have been presented,but implementation effects of these management modes have not been evaluated correctly.An integrated model was first proposed to evaluate the flood risks to people’s life and property,covering an improved module of two-dimensional(2D)morphodynamic processes and a module of flood risk evaluation for people,buildings and crops on the floodplains.Two simulation cases were then conducted to validate the model accuracy,including the hyperconcentrated flood event and dike-breach induced flood event occurring in the LYR.Finally,the integrated model was applied to key floodplains in the LYR,and the effects of different floodplain management modes were quantified on the risks to people’s life and property under an extreme flood event.Results indicate that:①Satisfactory accuracy was achieved in the simulation of these two flood events.The maximum sediment concentration was just underestimated by 9%,and the simulated inundation depth agreed well with the field record;②severe inundation was predicted to occur in most domains under the current topography(SchemeⅠ),which would be alleviated after implementing different floodplain management modes,with the area in slight inundation degree accounting for a large proportion under the mode of“construction of protection embankment”(SchemeⅡ)and the area in medium inundation degree occupying a high ratio under the mode of“floodplain partition harnessing”(SchemeⅢ);and③compared with SchemeⅠ,the high-risk area for people’s life and property would reduce by 21%–49%under SchemeⅡ,and by 35%–93%under SchemeⅢ.
