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
The thermal deformation behavior of FV520B stainless steel is investigated.Isothermal compression tests were conducted at temperatures ranging from 600 to 900℃ and strain rates from 0.001 to 10 s^(−1).The true stress...The thermal deformation behavior of FV520B stainless steel is investigated.Isothermal compression tests were conducted at temperatures ranging from 600 to 900℃ and strain rates from 0.001 to 10 s^(−1).The true stress–strain curves were corrected for friction and temperature due to the drum shape and adiabatic heating.The comparison shows that there is a large difference between the stress before and after the correction,which proves that the correction is necessary.Five constitutive models were developed:the original Arrhenius model,the strain correction Arrhenius model,a new modified Arrhenius model,the back propagation neural network model(BPNN)and the dandelion optimization BPNN model(DO-BPNN).The DO-BPNN model showed the highest prediction accuracy though it was more computationally intensive than the other models.The new modified Arrhenius model performed a better predictive capacity than the strain correction version,while it showed a negligible increase in the number of parameters and computational time.Although artificial neural network-based models exhibit superior accuracy compared to the Arrhenius models,their application in finite element simulations still faces notable challenges.展开更多
Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly ...Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).展开更多
BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized th...BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized that clinical indicators predict hepatitis B surface antigen(HBsAg)clearance during retreatment.AIM To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.METHODS In this retrospective cohort study,we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital(2017-2025).Predictors were identified through univariate Cox,least absolute shrinkage and selection operator,and multivariate Cox regression.Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index,with risk stratification by X-tile optimization.RESULTS HBsAg clearance rate was 20.74%(28/135).Independent predictors included:Combination nucleos(t)ide analogue(NA)therapy during initial treatment[hazard ratio(HR)=0.276,95%confidence interval(CI):0.092-0.833],baseline HBsAg at retreatment(HR=0.571,95%CI:0.410-0.795),HBsAg decline after initial treatment(HR=2.050,95%CI:1.108-3.793),and treatment interval(HR=1.013/week,95%CI:1.008-1.018).The retreatment HBsAg clearance prediction score(RHCP-S)demonstrated area under the curve of 0.920(95%CI:0.863-0.946),sensitivity of 92.3%,specificity of 79.3%.Clearance rates differed significantly:RHCP-S challenge group(≤74 points):3.45%,RHCP-S probable group(74-110 points):29.63%,RHCP-S dominant group(≥110 points):80.95%(P<0.001).CONCLUSION The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74%(28/135).The RHCP-S model identifies optimal retreatment candidates(≥110 points)with 80.95%clearance probability,associated with the absence of combination NA therapy during initial treatment,greater initial HBsAg decline,longer intervals,and lower retreatment HBsAg.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
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
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
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
Against the backdrop of globalization and regional economic integration,border tourism,as a unique form of tourism,is increasingly emerging as a significant driving force for promoting economic development in border r...Against the backdrop of globalization and regional economic integration,border tourism,as a unique form of tourism,is increasingly emerging as a significant driving force for promoting economic development in border regions,fostering cultural exchange,and strengthening international cooperation.The northwestern Yunnan region,located in China’s Southwestern frontier,is a key area bordering Southeast and South Asian countries,endowed with abundant border tourism resources.This article delves into the border tourism models and pathways for border development and prosperity in ethnic regions,using a case study of the Northwest Yunnan region to analyze the mechanisms and influencing factors of border tourism in promoting local economic development,social progress,and cultural heritage.This provides empirical evidence for further understanding the development patterns of border tourism and also contributes to strengthening ethnic unity and maintaining harmony and stability in border regions.This study addresses the current research gap in exploring the development models and pathways of border tourism in specific regions,offering valuable references and insights for future related research.展开更多
Using the“Civil Aviation Oral English”course as a case study,we operationalize the ideological and political education(IPE)integrated evaluation system for oral English courses in higher vocational education,which i...Using the“Civil Aviation Oral English”course as a case study,we operationalize the ideological and political education(IPE)integrated evaluation system for oral English courses in higher vocational education,which is based on Kirkpatrick’s Model,into a tripartite teaching evaluation system.The system encompasses three components such as learning objective attainment,individual developmental progress,and value-added competency assessment.The proposed system facilitates three-dimensional,multi-level,and scientifically validated teaching evaluation.This approach aligns with the holistic development of students’knowledge structures,professional competencies,moral qualities,and emotional intelligence.The study provides novel methodological perspectives for IPE evaluation in vocational oral English instruction,particularly in:curriculum-based ideological mapping,competency growth metrics,and value internalization assessment.展开更多
Driven by the dual carbon goals and the national strategy for the high-quality development of the advanced manufacturing industry,along with the trend of economic transformation,China’s new energy vehicle market has ...Driven by the dual carbon goals and the national strategy for the high-quality development of the advanced manufacturing industry,along with the trend of economic transformation,China’s new energy vehicle market has experienced explosive growth,which has spurred a surge in the construction of domestic charging infrastructure.Charging infrastructure not only supports achieving dual carbon goals and the development of the new energy vehicle industry but also undertakes the new historical mission of infrastructure in China’s new development stage,becoming a crucial infrastructure connecting energy decarbonization and transportation electrification[1].In recent years,central and local governments have placed great emphasis on this field.They have introduced policies from various angles,including comprehensive macro-level measures,government planning,financial subsidies,charging rates,industry management,and scientific and technological innovation,to promote the moderately advanced development of charging facilities.展开更多
The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is la...The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.展开更多
A“water”accelerated metal-free catalytic system has been discovered for the Mukaiyama-aldol reaction.The system involves the use of B(C_(6)F_(5))_(3) as a catalyst,which is water-tolerant and able to activate the ca...A“water”accelerated metal-free catalytic system has been discovered for the Mukaiyama-aldol reaction.The system involves the use of B(C_(6)F_(5))_(3) as a catalyst,which is water-tolerant and able to activate the carbonyl group through a hydrogen bonding network generated by the catalyst.This activation method allows the reactions to be performed with very low catalyst loading,as low as 0.5 mol%.The scope of substrates is broad and a wide variety of functional groups are well tolerated.Diverse aliphatic aldehydes,aromatic aldehydes,unsaturated aldehydes and aromatic ketones coupled with silyl enol ethers/silyl ketone acetals to generate their correspondingβ-hydroxy carbonyl compounds in moderate to good yields.This discovery represents a significant advancement in the field of organic synthesis,as it provides a new,practical and sustainable solution for carbon-carbon bond formation in water.展开更多
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.
基金supported by the National Natural Science Foundation of China(Grant No.52275373)the National Natural Science Foundation of China(Grant No.52105397)the Open Foundation of National Key Laboratory of Metal Forming Technology and Heavy Equipment(Grant No.S2308100.W08).
文摘The thermal deformation behavior of FV520B stainless steel is investigated.Isothermal compression tests were conducted at temperatures ranging from 600 to 900℃ and strain rates from 0.001 to 10 s^(−1).The true stress–strain curves were corrected for friction and temperature due to the drum shape and adiabatic heating.The comparison shows that there is a large difference between the stress before and after the correction,which proves that the correction is necessary.Five constitutive models were developed:the original Arrhenius model,the strain correction Arrhenius model,a new modified Arrhenius model,the back propagation neural network model(BPNN)and the dandelion optimization BPNN model(DO-BPNN).The DO-BPNN model showed the highest prediction accuracy though it was more computationally intensive than the other models.The new modified Arrhenius model performed a better predictive capacity than the strain correction version,while it showed a negligible increase in the number of parameters and computational time.Although artificial neural network-based models exhibit superior accuracy compared to the Arrhenius models,their application in finite element simulations still faces notable challenges.
基金National Key R&D Program of China,Grant/Award Number:2023YFC3402000National Institutes for Food and Drug Control,State Key Laboratory of Drug Regulatory Science,Grant/Award Number:2023SKLDRS0124。
文摘Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).
基金Supported by the Tianjin Health Research Project(Key Project),No.TJWJ2024ZD004Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034A.
文摘BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized that clinical indicators predict hepatitis B surface antigen(HBsAg)clearance during retreatment.AIM To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.METHODS In this retrospective cohort study,we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital(2017-2025).Predictors were identified through univariate Cox,least absolute shrinkage and selection operator,and multivariate Cox regression.Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index,with risk stratification by X-tile optimization.RESULTS HBsAg clearance rate was 20.74%(28/135).Independent predictors included:Combination nucleos(t)ide analogue(NA)therapy during initial treatment[hazard ratio(HR)=0.276,95%confidence interval(CI):0.092-0.833],baseline HBsAg at retreatment(HR=0.571,95%CI:0.410-0.795),HBsAg decline after initial treatment(HR=2.050,95%CI:1.108-3.793),and treatment interval(HR=1.013/week,95%CI:1.008-1.018).The retreatment HBsAg clearance prediction score(RHCP-S)demonstrated area under the curve of 0.920(95%CI:0.863-0.946),sensitivity of 92.3%,specificity of 79.3%.Clearance rates differed significantly:RHCP-S challenge group(≤74 points):3.45%,RHCP-S probable group(74-110 points):29.63%,RHCP-S dominant group(≥110 points):80.95%(P<0.001).CONCLUSION The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74%(28/135).The RHCP-S model identifies optimal retreatment candidates(≥110 points)with 80.95%clearance probability,associated with the absence of combination NA therapy during initial treatment,greater initial HBsAg decline,longer intervals,and lower retreatment HBsAg.
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.
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.
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 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.
文摘Against the backdrop of globalization and regional economic integration,border tourism,as a unique form of tourism,is increasingly emerging as a significant driving force for promoting economic development in border regions,fostering cultural exchange,and strengthening international cooperation.The northwestern Yunnan region,located in China’s Southwestern frontier,is a key area bordering Southeast and South Asian countries,endowed with abundant border tourism resources.This article delves into the border tourism models and pathways for border development and prosperity in ethnic regions,using a case study of the Northwest Yunnan region to analyze the mechanisms and influencing factors of border tourism in promoting local economic development,social progress,and cultural heritage.This provides empirical evidence for further understanding the development patterns of border tourism and also contributes to strengthening ethnic unity and maintaining harmony and stability in border regions.This study addresses the current research gap in exploring the development models and pathways of border tourism in specific regions,offering valuable references and insights for future related research.
基金supported by grants from“2023 Research on Vocational English Curriculum Reform:‘Implementation Path of Ideological and Political Education in Vocational English Courses for Higher Vocational Education Under the New Curriculum Standards’(Grant No.WYJZW-2023GD0029)”“The Special Project of 2024 on‘Reading and Teacher Development’Under the 14th Five-Year Plan of the China Tao Xingzhi Research Association(Grant No.CTXZRA202411937GD)”.
文摘Using the“Civil Aviation Oral English”course as a case study,we operationalize the ideological and political education(IPE)integrated evaluation system for oral English courses in higher vocational education,which is based on Kirkpatrick’s Model,into a tripartite teaching evaluation system.The system encompasses three components such as learning objective attainment,individual developmental progress,and value-added competency assessment.The proposed system facilitates three-dimensional,multi-level,and scientifically validated teaching evaluation.This approach aligns with the holistic development of students’knowledge structures,professional competencies,moral qualities,and emotional intelligence.The study provides novel methodological perspectives for IPE evaluation in vocational oral English instruction,particularly in:curriculum-based ideological mapping,competency growth metrics,and value internalization assessment.
文摘Driven by the dual carbon goals and the national strategy for the high-quality development of the advanced manufacturing industry,along with the trend of economic transformation,China’s new energy vehicle market has experienced explosive growth,which has spurred a surge in the construction of domestic charging infrastructure.Charging infrastructure not only supports achieving dual carbon goals and the development of the new energy vehicle industry but also undertakes the new historical mission of infrastructure in China’s new development stage,becoming a crucial infrastructure connecting energy decarbonization and transportation electrification[1].In recent years,central and local governments have placed great emphasis on this field.They have introduced policies from various angles,including comprehensive macro-level measures,government planning,financial subsidies,charging rates,industry management,and scientific and technological innovation,to promote the moderately advanced development of charging facilities.
文摘The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.
基金financial support from the Start-up Grant of Nanjing Tech University(Nos.38274017103,38037037)financial support from Distinguished University Professor grant(Nanyang Technological University)+1 种基金the Agency for Science,Technology and Research(A∗STAR)under its MTC Individual Research Grants(No.M21K2c0114)RIE2025 MTC Programmatic Fund(No.M22K9b0049).
文摘A“water”accelerated metal-free catalytic system has been discovered for the Mukaiyama-aldol reaction.The system involves the use of B(C_(6)F_(5))_(3) as a catalyst,which is water-tolerant and able to activate the carbonyl group through a hydrogen bonding network generated by the catalyst.This activation method allows the reactions to be performed with very low catalyst loading,as low as 0.5 mol%.The scope of substrates is broad and a wide variety of functional groups are well tolerated.Diverse aliphatic aldehydes,aromatic aldehydes,unsaturated aldehydes and aromatic ketones coupled with silyl enol ethers/silyl ketone acetals to generate their correspondingβ-hydroxy carbonyl compounds in moderate to good yields.This discovery represents a significant advancement in the field of organic synthesis,as it provides a new,practical and sustainable solution for carbon-carbon bond formation in water.
