The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in ...The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in the pathogenesis of the disease, based on the work of the authors(Takasugi et al., 2011;Komai et al., 2024).展开更多
Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include...Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.展开更多
Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of...Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of user preferences.To address this,we propose a Conditional Generative Adversarial Network(CGAN)that generates diverse and highly relevant itineraries.Our approach begins by constructing a conditional vector that encapsulates a user’s profile.This vector uniquely fuses embeddings from a Heterogeneous Information Network(HIN)to model complex user-place-route relationships,a Recurrent Neural Network(RNN)to capture sequential path dynamics,and Neural Collaborative Filtering(NCF)to incorporate collaborative signals from the wider user base.This comprehensive condition,further enhanced with features representing user interaction confidence and uncertainty,steers a CGAN stabilized by spectral normalization to generate high-fidelity latent route representations,effectively mitigating the data sparsity problem.Recommendations are then formulated using an Anchor-and-Expand algorithm,which selects relevant starting Points of Interest(POI)based on user history,then expands routes through latent similarity matching and geographic coherence optimization,culminating in Traveling Salesman Problem(TSP)-based route optimization for practical travel distances.Experiments on a real-world check-in dataset validate our model’s unique generative capability,achieving F1 scores ranging from 0.163 to 0.305,and near-zero pairs−F1 scores between 0.002 and 0.022.These results confirm the model’s success in generating novel travel routes by recommending new locations and sequences rather than replicating users’past itineraries.This work provides a robust solution for personalized travel planning,capable of generating novel and compelling routes for both new and existing users by learning from collective travel intelligence.展开更多
Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual pat...Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.展开更多
BACKGROUND Chronic inflammatory pain is associated with increased expression of interleukin(IL)-1,an inflammatory cytokine,and activity on its receptor(IL-1R).In response,the body produces IL-1R antagonist(IL-1Ra)to r...BACKGROUND Chronic inflammatory pain is associated with increased expression of interleukin(IL)-1,an inflammatory cytokine,and activity on its receptor(IL-1R).In response,the body produces IL-1R antagonist(IL-1Ra)to reduce this signaling.Autologous conditioned serum(ACS)is the only biologic therapy for spinal pathologies that enhances the action of endogenous IL-1Ra reserves to improve symptoms.This systematic review investigates the effectiveness of ACS in treating pain and dis-ability caused by spinal pathologies.AIM To evaluate the use of ACS as a conservative management option for spinal path-ology.METHODS A systematic review of PubMed/Medline was performed to identify studies inve-stigating administration of ACS for treatment of any spinal pathology.RESULTS Six articles were included,comprising 684 patients treated with epidural(n=133)or transforaminal(n=551)ACS injections.Patients had an average age of 54.0 years with slight female predominance(53.2%).The lumbar spine was most com-monly treated,with 567 patients(82.9%)receiving injections for lumbar radicu-lopathy(n=67),degenerative disc disease(DDD)(n=372),or spinal stenosis(n=128);cervical injections were performed in 109 patients(15.9%).Mean(SD)follow-up was 21.7(4.8)weeks from first ACS injection.All studies investigating mecha-nical lumbar and lumbar or cervical radicular pain reported significant pain re-duction at final follow-up compared to baseline.ACS achieved comparable or su-perior results to lumbar epidural steroid injections.Adverse events were reported in 21 patients(3.1%),with no serious adverse events.CONCLUSION ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies,including cervical and lumbar radiculopathies.展开更多
AIMS To study the quantitative ultrastucture of neu- roendocrine cells of gastric mucosa on normal anc pathological conditions including the duodenal ulcer (DU) and Zollinger-Ellison syndrome (ZES). METHODS The neuroe...AIMS To study the quantitative ultrastucture of neu- roendocrine cells of gastric mucosa on normal anc pathological conditions including the duodenal ulcer (DU) and Zollinger-Ellison syndrome (ZES). METHODS The neuroendocrine cells of the gastric mucosa of eight normal subjects,six patients with DU and five patients with ZES were quantitatively investi- gated with electro microscope and ultrastructure image analyzer. RESULTS The volume density of neuroendocrine cells in DU was 1.3% and 0.8% (vs 1.6% and 0.9%,P>0.05) in gastric antrum and corpus respectively. In antrum,G cells was of 65% (P< 0.05),D cells decreased in cell density (3% vs 9.5%) and in number of cell per unit area (P<0.01). In corpus,the cell density of ECL cells increased (49% vs 30%,P<0.05);D cells and EC cells decreasec (2% P<0.01 and 4% P<0.05,respectively),and the number of D cell per unit area markedly decreased. In ZES,D cells in corpus decreased in cell density (4% vs 22%,P<0.01) and P cells also decreased (11% vs 24%,P<0.05). The density of ECL cells increased (65% vs 30%,P<0.01). CONCLUSIONS In DU and ZES,both the number and type of NE cells present some changes. Incresed gastrin in DU and ZES patients may be caused by the decrease of D cells and somatostatin secretion.展开更多
Ti(C,N)-Mo_(2)C-Ni cermet as alternative materials was explored for use in alkaline conditions,replacing the WC-Co cemented carbides,since Co is classified as a potentially carcinogenic substance and there is potentia...Ti(C,N)-Mo_(2)C-Ni cermet as alternative materials was explored for use in alkaline conditions,replacing the WC-Co cemented carbides,since Co is classified as a potentially carcinogenic substance and there is potential hazard of“hard metal disease”under the exposure to cobalt dust.The changes in microstructure,corrosion rate and volumetric loss rate of the two materials were compared under electrochemical corrosion and erosion-corrosion in alkaline environment.The results demonstrates that Ti(C,N)-Mo_(2)C-Ni cermet undergoes passivation when exposed to electrochemical corrosion of NaOH solution,resulting in a significant increase in oxygen content on the corroded surface.The corrosion rate of cermet is approximately one order of magnitude lower than that of the cemented carbide.Under the erosion-corrosion of an alkaline sand-water mixture,both the cermet and cemented carbide experience a gradual increase in volumetric loss rate with prolonging the erosion time.During erosion,the rim phase in cermet is fragile,so cracks easily penetrate it while the core phase remains intact.The medium-grained cemented carbide commonly demonstrates transgranular fracture mode,while in the fine-grained cemented carbide,cracks tend to propagate along phase boundaries.The erosive wear and damage caused by sand particles play a predominant role in the erosion-corrosion process of alkaline sand-water mixtures.This process represents an accelerated destructive phenomenon influenced and intensified by the combined effects of corrosion and erosion.It is confirmed that using cermet as an alternative anti-wear material to cemented carbides is feasible under alkaline conditions,and even better.展开更多
Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may...Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.展开更多
Actuator faults can be critical in turbofan engines as they can lead to stall,surge,loss of thrust and failure of speed control.Thus,fault diagnosis of gas turbine actuators has attracted considerable attention,from b...Actuator faults can be critical in turbofan engines as they can lead to stall,surge,loss of thrust and failure of speed control.Thus,fault diagnosis of gas turbine actuators has attracted considerable attention,from both academia and industry.However,the extensive literature that exists on this topic does not address identifying the severity of actuator faults and focuses mainly on actuator fault detection and isolation.In addition,previous studies of actuator fault identification have not dealt with multiple concurrent faults in real time,especially when these are accompanied by sudden failures under dynamic conditions.This study develops component-level models for fault identification in four typical actuators used in high-bypass ratio turbofan engines under both dynamic and steady-state conditions and these are then integrated with the engine performance model developed by the authors.The research results reported here present a novel method of quantifying actuator faults using dynamic effect compensation.The maximum error for each actuator is less than0.06%and 0.07%,with average computational time of less than 0.0058 s and 0.0086 s for steady-state and transient cases,respectively.These results confirm that the proposed method can accurately and efficiently identify concurrent actuator fault for an engine operating under either transient or steady-state conditions,even in the case of a sudden malfunction.The research results emonstrate the potential benefit to emergency response capabilities by introducing this method of monitoring the health of aero engines.展开更多
Human leukocyte antigen-G(HLA-G) is a non-classical HLA class Ⅰ molecule that differs from classical HLA class Ⅰ molecules by low polymorphism and tissue distribution. HLA-G is a tolerogenic molecule with an immune-...Human leukocyte antigen-G(HLA-G) is a non-classical HLA class Ⅰ molecule that differs from classical HLA class Ⅰ molecules by low polymorphism and tissue distribution. HLA-G is a tolerogenic molecule with an immune-modulatory and anti-inflammatory function on both innate and adaptative immunity. This peculiar characteristic of HLA-G has led to investigations of its role in pathological conditions in order to define possible uses in diagnosis, prevention and treatment. In recent years, HLA-G has been shown to have an important implication in different inflammatory and autoimmune diseases, pregnancy complications, tumor development and aggressiveness, and susceptibility to viral infections. In fact, HLA-G molecules have been reported to alternate at both genetic and protein level in different disease situations, supporting its crucial role in pathological conditions. Specific pathologies show altered levels of soluble(s)HLA-G and different HLA-G gene polymorphisms seem to correlate with disease. This review aims to update scientific knowledge on the contribution of HLA-G in managing pathological conditions.展开更多
Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy ...Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.展开更多
In cold regions,rock structures will be weakened by freeze-thaw cycles under various water immersion conditions.Determining how water immersion conditions impact rock deterioration under freeze-thaw cycles is critical...In cold regions,rock structures will be weakened by freeze-thaw cycles under various water immersion conditions.Determining how water immersion conditions impact rock deterioration under freeze-thaw cycles is critical to assess accurately the frost resistance of engineered rock.In this paper,freeze-thaw cycles(temperature range of-20℃-20℃)were performed on the sandstones in different water immersion conditions(fully,partially and non-immersed in water).Then,computed tomography(CT)tests were conducted on the sandstones when the freeze-thaw number reached 0,5,10,15,20 and 30.Next,the effects of water immersion conditions on the microstructure deterioration of sandstone under freezethaw cycles were evaluated using CT spatial imaging,porosity and damage factor.Finally,focusing on the partially immersed condition,the immersion volume rate was defined to understand the effects of immersion degree on the freeze-thaw damage of sandstone and to propose a damage model considering the freeze-thaw number and immersion degree.The results show that with increasing freeze-thaw number,the porosities and damage factors under fully and partially immersed conditions increase continuously,while those under non-immersed condition first increase and then remain approximately constant.The most severe freeze-thaw damage occurs in fully immersed condition,followed by partially immersed condition and finally non-immersed condition.Interestingly,the freeze-thaw number and the immersion volume rate both impact the microstructure deterioration of the partially immersed sandstone.For the same freeze-thaw number,the damage factor increases approximately linearly with increasing immersion volume rate,and the increasing immersion degree exacerbates the microstructure deterioration of sandstone.Moreover,the proposed model can effectively estimate the freeze-thaw damage of partially immersed sandstone with different immersion volume rates.展开更多
The potential of 2-amino-1-propanol(AP)as a novel depressant in selectively floating ilmenite from titanaugite under weakly acidic conditions was investigated.Micro-flotation results show that AP significantly reduces...The potential of 2-amino-1-propanol(AP)as a novel depressant in selectively floating ilmenite from titanaugite under weakly acidic conditions was investigated.Micro-flotation results show that AP significantly reduces the recovery of titanaugite while having no evident impact on ilmenite flotation.Subsequent bench-scale flotation tests further confirm a remarkable improvement in separation efficiency upon the introduction of AP.Contact angle and adsorption tests reveal a stronger affinity of AP towards the titanaugite surface in comparison to ilmenite.Zeta potential measurements and X-ray photoelectron spectroscopy(XPS)analyses exhibit favorable adsorption characteristics of AP on titanaugite,resulting from a synergy of electrostatic attraction and chemical interaction.In contrast,electrostatic repulsion hinders any significant interaction between AP and the ilmenite surface.These findings highlight the potential of AP as a highly efficient depressant for ilmenite flotation,paving the way for reduced reliance on sulfuric acid in the industry.展开更多
Aging is a major risk factor for many human diseases,including cognitive impairment,which affects a large population of the elderly.In the past few decades,our understanding of the molecular and cellular mechanisms un...Aging is a major risk factor for many human diseases,including cognitive impairment,which affects a large population of the elderly.In the past few decades,our understanding of the molecular and cellular mechanisms underlying the changes associated with aging and age-related diseases has expanded greatly,shedding light on the potential role of these changes in cognitive impairment.In this article,we review recent advances in understanding of the mechanisms underlying brain aging under normal and pathological conditions,compare their similarities and differences,discuss the causative and adaptive mechanisms of brain aging,and finally attempt to find some rules to guide us on how to promote healthy aging and prevent age-related diseases.展开更多
Although time-dependent deformation of geomaterials underpins slope-failure prediction models,the influence of strain rate on shearing strength and deformation behavior of loess remains unclear.The consolidated undrai...Although time-dependent deformation of geomaterials underpins slope-failure prediction models,the influence of strain rate on shearing strength and deformation behavior of loess remains unclear.The consolidated undrained(CU)and drained(CD)triaxial testing elucidated the impact of strain rate(0.005–0.3 mm/min)on strength envelopes,deformation moduli,pore pressures,and dilatancy characteristics of unsaturated and quasi-saturated loess.Under drained conditions with a controlled matric suction of 50 kPa,increasing strain rates from 0.005 mm/min to 0.011 mm/min induced decreases in failure deviatoric stress(qf),initial deformation modulus(Ei),and cohesion(c),while friction angles remained unaffected.Specimens displayed initial contractive volumetric strains transitioning to dilation across varying confining pressures.Higher rates diminished contractive volumetric strains and drainage volumes,indicating reduced densification and strength in the shear zone.Under undrained conditions,both unsaturated and quasi-saturated(pore pressure coefficient B=0.75)loess exhibited deteriorating mechanical properties with increasing rates from 0.03 mm/min to 0.3 mm/min.For unsaturated loess,reduced contractive volumetric strains at higher rates manifested relatively looser structures in the pre-peak stress phase.The strength decrement in quasi-saturated loess arose from elevated excess porewater pressures diminishing effective stresses.Negative porewater pressures emerged in quasi-saturated loess at lower confining pressures and strain rates.Compared to previous studies,the qf and Ei exhibited rate sensitivity below threshold values before attaining minima with marginal subsequent influence.The underlying mechanism mirrors the transition from creep to accelerated deformation phase of landslides.展开更多
The northwestern margin of Junggar Basin is the region with the richest oil sand resources in China.For better understanding the enrichment rules and deployment of exploration and development of regional oil sand,it i...The northwestern margin of Junggar Basin is the region with the richest oil sand resources in China.For better understanding the enrichment rules and deployment of exploration and development of regional oil sand,it is of great scientific significance to study the accumulation conditions of oil sand in different strata and mining areas of the Junggar Basin.Through a large number of field investigations,drilling verification and sampling tests,it is found that the oil sand in the region covers an area of 2000 km^(2),with shallow and thick reservoir,and predicted resource of 180 million tons.The oil sand resources are mainly distributed in four geological strata,namely the Middle Triassic Karamay Formation,Early Jurassic Badaowan Formation,Late Jurassic Qigu Formation,and Early Cretaceous Qingshuihe Formation.The reservoir is mainly composed of sandstone with high porosity and permeability,and the reservoir space is mainly intergranular pores with a medium average oil content.The oil sand deposit in the region is a typical destructive oil reservoir.The crude oil in the oil sand layer is degraded and thickened from the deep to the shallow,the content of saturated hydrocarbon decreased,and the content of aromatic hydrocarbon,non-hydrocarbon and asphaltene increased.The oil source comes from the deep Permian hydrocarbon-generating depression.Unconformities,faults and marginal fan delta-braided river depositional systems constitute effective migration and storage systems.Caprocks of the Upper Triassic Baijiantan Formation,Lower Jurassic Sangonghe Formation and Lower Cretaceous Hutubihe Formation were formed by three large scale lake transgressions.The Indosinian,Yanshan and Late Yanshan movements are the main driving forces for the migration of deep oil and gas to the shallow edge to form oil sand deposits.It is considered that the oil sand in the northwestern margin of Junggar Basin is of a slope complex migration type.展开更多
Rechargeable zinc(Zn)-ion batteries(RZIBs) with hydrogel electrolytes(HEs) have gained significant attention in the last decade owing to their high safety, low cost, sufficient material abundance, and superb environme...Rechargeable zinc(Zn)-ion batteries(RZIBs) with hydrogel electrolytes(HEs) have gained significant attention in the last decade owing to their high safety, low cost, sufficient material abundance, and superb environmental friendliness, which is extremely important for wearable energy storage applications. Given that HEs play a critical role in building flexible RZIBs, it is urgent to summarize the recent advances in this field and elucidate the design principles of HEs for practical applications. This review systematically presents the development history, recent advances in the material fundamentals, functional designs, challenges, and prospects of the HEs-based RZIBs. Firstly, the fundamentals, species, and flexible mechanisms of HEs are discussed, along with their compatibility with Zn anodes and various cathodes. Then, the functional designs of hydrogel electrolytes in harsh conditions are comprehensively discussed, including high/low/wide-temperature windows, mechanical deformations(e.g., bending, twisting, and straining), and damages(e.g., cutting, burning, and soaking). Finally, the remaining challenges and future perspectives for advancing HEs-based RZIBs are outlined.展开更多
Landslide susceptibility prediction(LSP)is significantly affected by the uncertainty issue of landslide related conditioning factor selection.However,most of literature only performs comparative studies on a certain c...Landslide susceptibility prediction(LSP)is significantly affected by the uncertainty issue of landslide related conditioning factor selection.However,most of literature only performs comparative studies on a certain conditioning factor selection method rather than systematically study this uncertainty issue.Targeted,this study aims to systematically explore the influence rules of various commonly used conditioning factor selection methods on LSP,and on this basis to innovatively propose a principle with universal application for optimal selection of conditioning factors.An'yuan County in southern China is taken as example considering 431 landslides and 29 types of conditioning factors.Five commonly used factor selection methods,namely,the correlation analysis(CA),linear regression(LR),principal component analysis(PCA),rough set(RS)and artificial neural network(ANN),are applied to select the optimal factor combinations from the original 29 conditioning factors.The factor selection results are then used as inputs of four types of common machine learning models to construct 20 types of combined models,such as CA-multilayer perceptron,CA-random forest.Additionally,multifactor-based multilayer perceptron random forest models that selecting conditioning factors based on the proposed principle of“accurate data,rich types,clear significance,feasible operation and avoiding duplication”are constructed for comparisons.Finally,the LSP uncertainties are evaluated by the accuracy,susceptibility index distribution,etc.Results show that:(1)multifactor-based models have generally higher LSP performance and lower uncertainties than those of factors selection-based models;(2)Influence degree of different machine learning on LSP accuracy is greater than that of different factor selection methods.Conclusively,the above commonly used conditioning factor selection methods are not ideal for improving LSP performance and may complicate the LSP processes.In contrast,a satisfied combination of conditioning factors can be constructed according to the proposed principle.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
Let d(n;r_(1),q_(1),r_(2),q_(2))be the number of factorization n=n_(1)n_(2)satisfying n_i≡r_i(mod q_i)(i=1,2)andΔ(x;r_(1),q_(1),r_(2),q_(2))be the error term of the summatory function of d(n;r_(1),q_(1),r_(2),q_(2))...Let d(n;r_(1),q_(1),r_(2),q_(2))be the number of factorization n=n_(1)n_(2)satisfying n_i≡r_i(mod q_i)(i=1,2)andΔ(x;r_(1),q_(1),r_(2),q_(2))be the error term of the summatory function of d(n;r_(1),q_(1),r_(2),q_(2)).Suppose x≥(q_(1)q_(2))^(1+ε),1≤r_i≤q_i,and(r_i,q_i)=1(i=1,2).This paper studies the power moments and sign changes ofΔ(x;r_(1),q_(1),r_(2),q_(2)).We prove that for sufficiently large constant C,Δ(q_(1)q_(2)x:r_(1),q_(1),r_(2),q_(2))changes sign in the interval[T,T+C√T]for any large T.Meanwhile,we show that for small constants c and c,there exist infinitely many subintervals of length c√log^(-7)T in[T,2T]where±Δ(q_(1)q_(2)x:r_(1),q_(1),r_(2),q_(2))>cx^(1/4)always holds.展开更多
基金supported by a grant from the Japan Foundation for applied enzymology (to NT)the Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (26430059, 17K08272, and 20K07014 to NT)+1 种基金the establishment of university fellowships toward the creation of science technology innovation (JPMJFS2128)a Grant-in-Aid for JSPS Fellows (23KJ1603)(to MK)。
文摘The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in the pathogenesis of the disease, based on the work of the authors(Takasugi et al., 2011;Komai et al., 2024).
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN)。
文摘Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.
基金supported by the Chung-Ang University Research Grants in 2023.Alsothe work is supported by the ELLIIT Excellence Center at Linköping–Lund in Information Technology in Sweden.
文摘Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of user preferences.To address this,we propose a Conditional Generative Adversarial Network(CGAN)that generates diverse and highly relevant itineraries.Our approach begins by constructing a conditional vector that encapsulates a user’s profile.This vector uniquely fuses embeddings from a Heterogeneous Information Network(HIN)to model complex user-place-route relationships,a Recurrent Neural Network(RNN)to capture sequential path dynamics,and Neural Collaborative Filtering(NCF)to incorporate collaborative signals from the wider user base.This comprehensive condition,further enhanced with features representing user interaction confidence and uncertainty,steers a CGAN stabilized by spectral normalization to generate high-fidelity latent route representations,effectively mitigating the data sparsity problem.Recommendations are then formulated using an Anchor-and-Expand algorithm,which selects relevant starting Points of Interest(POI)based on user history,then expands routes through latent similarity matching and geographic coherence optimization,culminating in Traveling Salesman Problem(TSP)-based route optimization for practical travel distances.Experiments on a real-world check-in dataset validate our model’s unique generative capability,achieving F1 scores ranging from 0.163 to 0.305,and near-zero pairs−F1 scores between 0.002 and 0.022.These results confirm the model’s success in generating novel travel routes by recommending new locations and sequences rather than replicating users’past itineraries.This work provides a robust solution for personalized travel planning,capable of generating novel and compelling routes for both new and existing users by learning from collective travel intelligence.
基金supported by the Natural Science Foundation of Guangdong Province(No.2021B1515120053)Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515140166).
文摘Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.
文摘BACKGROUND Chronic inflammatory pain is associated with increased expression of interleukin(IL)-1,an inflammatory cytokine,and activity on its receptor(IL-1R).In response,the body produces IL-1R antagonist(IL-1Ra)to reduce this signaling.Autologous conditioned serum(ACS)is the only biologic therapy for spinal pathologies that enhances the action of endogenous IL-1Ra reserves to improve symptoms.This systematic review investigates the effectiveness of ACS in treating pain and dis-ability caused by spinal pathologies.AIM To evaluate the use of ACS as a conservative management option for spinal path-ology.METHODS A systematic review of PubMed/Medline was performed to identify studies inve-stigating administration of ACS for treatment of any spinal pathology.RESULTS Six articles were included,comprising 684 patients treated with epidural(n=133)or transforaminal(n=551)ACS injections.Patients had an average age of 54.0 years with slight female predominance(53.2%).The lumbar spine was most com-monly treated,with 567 patients(82.9%)receiving injections for lumbar radicu-lopathy(n=67),degenerative disc disease(DDD)(n=372),or spinal stenosis(n=128);cervical injections were performed in 109 patients(15.9%).Mean(SD)follow-up was 21.7(4.8)weeks from first ACS injection.All studies investigating mecha-nical lumbar and lumbar or cervical radicular pain reported significant pain re-duction at final follow-up compared to baseline.ACS achieved comparable or su-perior results to lumbar epidural steroid injections.Adverse events were reported in 21 patients(3.1%),with no serious adverse events.CONCLUSION ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies,including cervical and lumbar radiculopathies.
文摘AIMS To study the quantitative ultrastucture of neu- roendocrine cells of gastric mucosa on normal anc pathological conditions including the duodenal ulcer (DU) and Zollinger-Ellison syndrome (ZES). METHODS The neuroendocrine cells of the gastric mucosa of eight normal subjects,six patients with DU and five patients with ZES were quantitatively investi- gated with electro microscope and ultrastructure image analyzer. RESULTS The volume density of neuroendocrine cells in DU was 1.3% and 0.8% (vs 1.6% and 0.9%,P>0.05) in gastric antrum and corpus respectively. In antrum,G cells was of 65% (P< 0.05),D cells decreased in cell density (3% vs 9.5%) and in number of cell per unit area (P<0.01). In corpus,the cell density of ECL cells increased (49% vs 30%,P<0.05);D cells and EC cells decreasec (2% P<0.01 and 4% P<0.05,respectively),and the number of D cell per unit area markedly decreased. In ZES,D cells in corpus decreased in cell density (4% vs 22%,P<0.01) and P cells also decreased (11% vs 24%,P<0.05). The density of ECL cells increased (65% vs 30%,P<0.01). CONCLUSIONS In DU and ZES,both the number and type of NE cells present some changes. Incresed gastrin in DU and ZES patients may be caused by the decrease of D cells and somatostatin secretion.
基金Chongqing Light Alloy Materials and Processing Engineering Technology Research Center Open Fund Project(GCZX201903)Yunnan Province Major Science and Technology Special Project Plan(202302AA310038)Sichuan University-Suining Municipal-University Cooperation Project(2023CDSN-12)。
文摘Ti(C,N)-Mo_(2)C-Ni cermet as alternative materials was explored for use in alkaline conditions,replacing the WC-Co cemented carbides,since Co is classified as a potentially carcinogenic substance and there is potential hazard of“hard metal disease”under the exposure to cobalt dust.The changes in microstructure,corrosion rate and volumetric loss rate of the two materials were compared under electrochemical corrosion and erosion-corrosion in alkaline environment.The results demonstrates that Ti(C,N)-Mo_(2)C-Ni cermet undergoes passivation when exposed to electrochemical corrosion of NaOH solution,resulting in a significant increase in oxygen content on the corroded surface.The corrosion rate of cermet is approximately one order of magnitude lower than that of the cemented carbide.Under the erosion-corrosion of an alkaline sand-water mixture,both the cermet and cemented carbide experience a gradual increase in volumetric loss rate with prolonging the erosion time.During erosion,the rim phase in cermet is fragile,so cracks easily penetrate it while the core phase remains intact.The medium-grained cemented carbide commonly demonstrates transgranular fracture mode,while in the fine-grained cemented carbide,cracks tend to propagate along phase boundaries.The erosive wear and damage caused by sand particles play a predominant role in the erosion-corrosion process of alkaline sand-water mixtures.This process represents an accelerated destructive phenomenon influenced and intensified by the combined effects of corrosion and erosion.It is confirmed that using cermet as an alternative anti-wear material to cemented carbides is feasible under alkaline conditions,and even better.
基金supported partly by the National Natural Science Foundation of China,No.82071332the Chongqing Natural Science Foundation Joint Fund for Innovation and Development,No.CSTB2023NSCQ-LZX0041 (both to ZG)。
文摘Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
基金support by the National Natural Science Foundation of China(Grant No.52402520)。
文摘Actuator faults can be critical in turbofan engines as they can lead to stall,surge,loss of thrust and failure of speed control.Thus,fault diagnosis of gas turbine actuators has attracted considerable attention,from both academia and industry.However,the extensive literature that exists on this topic does not address identifying the severity of actuator faults and focuses mainly on actuator fault detection and isolation.In addition,previous studies of actuator fault identification have not dealt with multiple concurrent faults in real time,especially when these are accompanied by sudden failures under dynamic conditions.This study develops component-level models for fault identification in four typical actuators used in high-bypass ratio turbofan engines under both dynamic and steady-state conditions and these are then integrated with the engine performance model developed by the authors.The research results reported here present a novel method of quantifying actuator faults using dynamic effect compensation.The maximum error for each actuator is less than0.06%and 0.07%,with average computational time of less than 0.0058 s and 0.0086 s for steady-state and transient cases,respectively.These results confirm that the proposed method can accurately and efficiently identify concurrent actuator fault for an engine operating under either transient or steady-state conditions,even in the case of a sudden malfunction.The research results emonstrate the potential benefit to emergency response capabilities by introducing this method of monitoring the health of aero engines.
文摘Human leukocyte antigen-G(HLA-G) is a non-classical HLA class Ⅰ molecule that differs from classical HLA class Ⅰ molecules by low polymorphism and tissue distribution. HLA-G is a tolerogenic molecule with an immune-modulatory and anti-inflammatory function on both innate and adaptative immunity. This peculiar characteristic of HLA-G has led to investigations of its role in pathological conditions in order to define possible uses in diagnosis, prevention and treatment. In recent years, HLA-G has been shown to have an important implication in different inflammatory and autoimmune diseases, pregnancy complications, tumor development and aggressiveness, and susceptibility to viral infections. In fact, HLA-G molecules have been reported to alternate at both genetic and protein level in different disease situations, supporting its crucial role in pathological conditions. Specific pathologies show altered levels of soluble(s)HLA-G and different HLA-G gene polymorphisms seem to correlate with disease. This review aims to update scientific knowledge on the contribution of HLA-G in managing pathological conditions.
文摘Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.
基金funding support from the National Natural Science Foundation of China(Grant No.12172019).
文摘In cold regions,rock structures will be weakened by freeze-thaw cycles under various water immersion conditions.Determining how water immersion conditions impact rock deterioration under freeze-thaw cycles is critical to assess accurately the frost resistance of engineered rock.In this paper,freeze-thaw cycles(temperature range of-20℃-20℃)were performed on the sandstones in different water immersion conditions(fully,partially and non-immersed in water).Then,computed tomography(CT)tests were conducted on the sandstones when the freeze-thaw number reached 0,5,10,15,20 and 30.Next,the effects of water immersion conditions on the microstructure deterioration of sandstone under freezethaw cycles were evaluated using CT spatial imaging,porosity and damage factor.Finally,focusing on the partially immersed condition,the immersion volume rate was defined to understand the effects of immersion degree on the freeze-thaw damage of sandstone and to propose a damage model considering the freeze-thaw number and immersion degree.The results show that with increasing freeze-thaw number,the porosities and damage factors under fully and partially immersed conditions increase continuously,while those under non-immersed condition first increase and then remain approximately constant.The most severe freeze-thaw damage occurs in fully immersed condition,followed by partially immersed condition and finally non-immersed condition.Interestingly,the freeze-thaw number and the immersion volume rate both impact the microstructure deterioration of the partially immersed sandstone.For the same freeze-thaw number,the damage factor increases approximately linearly with increasing immersion volume rate,and the increasing immersion degree exacerbates the microstructure deterioration of sandstone.Moreover,the proposed model can effectively estimate the freeze-thaw damage of partially immersed sandstone with different immersion volume rates.
基金supported by the National Key Research and Development Program of China(No.2019YFC1803501)the National Natural Science Foundation of China(No.52074357)+2 种基金the Natural Science Foundation of Hunan Province,China(No.2022JJ30713)the Vanadium Titanium Union Foundationthe Project of Technology Innovation Center for Comprehensive Utilization of Strategic Mineral Resources,Ministry of Natural Resources,China。
文摘The potential of 2-amino-1-propanol(AP)as a novel depressant in selectively floating ilmenite from titanaugite under weakly acidic conditions was investigated.Micro-flotation results show that AP significantly reduces the recovery of titanaugite while having no evident impact on ilmenite flotation.Subsequent bench-scale flotation tests further confirm a remarkable improvement in separation efficiency upon the introduction of AP.Contact angle and adsorption tests reveal a stronger affinity of AP towards the titanaugite surface in comparison to ilmenite.Zeta potential measurements and X-ray photoelectron spectroscopy(XPS)analyses exhibit favorable adsorption characteristics of AP on titanaugite,resulting from a synergy of electrostatic attraction and chemical interaction.In contrast,electrostatic repulsion hinders any significant interaction between AP and the ilmenite surface.These findings highlight the potential of AP as a highly efficient depressant for ilmenite flotation,paving the way for reduced reliance on sulfuric acid in the industry.
文摘Aging is a major risk factor for many human diseases,including cognitive impairment,which affects a large population of the elderly.In the past few decades,our understanding of the molecular and cellular mechanisms underlying the changes associated with aging and age-related diseases has expanded greatly,shedding light on the potential role of these changes in cognitive impairment.In this article,we review recent advances in understanding of the mechanisms underlying brain aging under normal and pathological conditions,compare their similarities and differences,discuss the causative and adaptive mechanisms of brain aging,and finally attempt to find some rules to guide us on how to promote healthy aging and prevent age-related diseases.
文摘Although time-dependent deformation of geomaterials underpins slope-failure prediction models,the influence of strain rate on shearing strength and deformation behavior of loess remains unclear.The consolidated undrained(CU)and drained(CD)triaxial testing elucidated the impact of strain rate(0.005–0.3 mm/min)on strength envelopes,deformation moduli,pore pressures,and dilatancy characteristics of unsaturated and quasi-saturated loess.Under drained conditions with a controlled matric suction of 50 kPa,increasing strain rates from 0.005 mm/min to 0.011 mm/min induced decreases in failure deviatoric stress(qf),initial deformation modulus(Ei),and cohesion(c),while friction angles remained unaffected.Specimens displayed initial contractive volumetric strains transitioning to dilation across varying confining pressures.Higher rates diminished contractive volumetric strains and drainage volumes,indicating reduced densification and strength in the shear zone.Under undrained conditions,both unsaturated and quasi-saturated(pore pressure coefficient B=0.75)loess exhibited deteriorating mechanical properties with increasing rates from 0.03 mm/min to 0.3 mm/min.For unsaturated loess,reduced contractive volumetric strains at higher rates manifested relatively looser structures in the pre-peak stress phase.The strength decrement in quasi-saturated loess arose from elevated excess porewater pressures diminishing effective stresses.Negative porewater pressures emerged in quasi-saturated loess at lower confining pressures and strain rates.Compared to previous studies,the qf and Ei exhibited rate sensitivity below threshold values before attaining minima with marginal subsequent influence.The underlying mechanism mirrors the transition from creep to accelerated deformation phase of landslides.
基金granted by the Xinjiang Geological Exploration Fund。
文摘The northwestern margin of Junggar Basin is the region with the richest oil sand resources in China.For better understanding the enrichment rules and deployment of exploration and development of regional oil sand,it is of great scientific significance to study the accumulation conditions of oil sand in different strata and mining areas of the Junggar Basin.Through a large number of field investigations,drilling verification and sampling tests,it is found that the oil sand in the region covers an area of 2000 km^(2),with shallow and thick reservoir,and predicted resource of 180 million tons.The oil sand resources are mainly distributed in four geological strata,namely the Middle Triassic Karamay Formation,Early Jurassic Badaowan Formation,Late Jurassic Qigu Formation,and Early Cretaceous Qingshuihe Formation.The reservoir is mainly composed of sandstone with high porosity and permeability,and the reservoir space is mainly intergranular pores with a medium average oil content.The oil sand deposit in the region is a typical destructive oil reservoir.The crude oil in the oil sand layer is degraded and thickened from the deep to the shallow,the content of saturated hydrocarbon decreased,and the content of aromatic hydrocarbon,non-hydrocarbon and asphaltene increased.The oil source comes from the deep Permian hydrocarbon-generating depression.Unconformities,faults and marginal fan delta-braided river depositional systems constitute effective migration and storage systems.Caprocks of the Upper Triassic Baijiantan Formation,Lower Jurassic Sangonghe Formation and Lower Cretaceous Hutubihe Formation were formed by three large scale lake transgressions.The Indosinian,Yanshan and Late Yanshan movements are the main driving forces for the migration of deep oil and gas to the shallow edge to form oil sand deposits.It is considered that the oil sand in the northwestern margin of Junggar Basin is of a slope complex migration type.
基金supported by the National Natural Science Foundation of China (22379038)Science Research Project of Hebei Education Department (JZX2024015)+4 种基金Shijiazhuang Science and Technology Plan Project (241791357A)Central Guidance for Local Science and Technology Development Funds Project (246Z4408G)Excellent Youth Research Innovation Team of Hebei University (QNTD202410)High-level Talents Research Start-Up Project of Hebei University (521100224223)Hebei Province Innovation Capability Enhancement Plan Project (22567620H)。
文摘Rechargeable zinc(Zn)-ion batteries(RZIBs) with hydrogel electrolytes(HEs) have gained significant attention in the last decade owing to their high safety, low cost, sufficient material abundance, and superb environmental friendliness, which is extremely important for wearable energy storage applications. Given that HEs play a critical role in building flexible RZIBs, it is urgent to summarize the recent advances in this field and elucidate the design principles of HEs for practical applications. This review systematically presents the development history, recent advances in the material fundamentals, functional designs, challenges, and prospects of the HEs-based RZIBs. Firstly, the fundamentals, species, and flexible mechanisms of HEs are discussed, along with their compatibility with Zn anodes and various cathodes. Then, the functional designs of hydrogel electrolytes in harsh conditions are comprehensively discussed, including high/low/wide-temperature windows, mechanical deformations(e.g., bending, twisting, and straining), and damages(e.g., cutting, burning, and soaking). Finally, the remaining challenges and future perspectives for advancing HEs-based RZIBs are outlined.
基金funded by the Natural Science Foundation of China(Grant Nos.42377164 and 41972280)the Badong National Observation and Research Station of Geohazards(Grant No.BNORSG-202305).
文摘Landslide susceptibility prediction(LSP)is significantly affected by the uncertainty issue of landslide related conditioning factor selection.However,most of literature only performs comparative studies on a certain conditioning factor selection method rather than systematically study this uncertainty issue.Targeted,this study aims to systematically explore the influence rules of various commonly used conditioning factor selection methods on LSP,and on this basis to innovatively propose a principle with universal application for optimal selection of conditioning factors.An'yuan County in southern China is taken as example considering 431 landslides and 29 types of conditioning factors.Five commonly used factor selection methods,namely,the correlation analysis(CA),linear regression(LR),principal component analysis(PCA),rough set(RS)and artificial neural network(ANN),are applied to select the optimal factor combinations from the original 29 conditioning factors.The factor selection results are then used as inputs of four types of common machine learning models to construct 20 types of combined models,such as CA-multilayer perceptron,CA-random forest.Additionally,multifactor-based multilayer perceptron random forest models that selecting conditioning factors based on the proposed principle of“accurate data,rich types,clear significance,feasible operation and avoiding duplication”are constructed for comparisons.Finally,the LSP uncertainties are evaluated by the accuracy,susceptibility index distribution,etc.Results show that:(1)multifactor-based models have generally higher LSP performance and lower uncertainties than those of factors selection-based models;(2)Influence degree of different machine learning on LSP accuracy is greater than that of different factor selection methods.Conclusively,the above commonly used conditioning factor selection methods are not ideal for improving LSP performance and may complicate the LSP processes.In contrast,a satisfied combination of conditioning factors can be constructed according to the proposed principle.
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supported by the Talent Fund of Beijing Jiaotong University(No.2020RC012)NSFC(No.11871295),supported by NSFC(No.11971476),supported by NSFC(No.12071421)。
文摘Let d(n;r_(1),q_(1),r_(2),q_(2))be the number of factorization n=n_(1)n_(2)satisfying n_i≡r_i(mod q_i)(i=1,2)andΔ(x;r_(1),q_(1),r_(2),q_(2))be the error term of the summatory function of d(n;r_(1),q_(1),r_(2),q_(2)).Suppose x≥(q_(1)q_(2))^(1+ε),1≤r_i≤q_i,and(r_i,q_i)=1(i=1,2).This paper studies the power moments and sign changes ofΔ(x;r_(1),q_(1),r_(2),q_(2)).We prove that for sufficiently large constant C,Δ(q_(1)q_(2)x:r_(1),q_(1),r_(2),q_(2))changes sign in the interval[T,T+C√T]for any large T.Meanwhile,we show that for small constants c and c,there exist infinitely many subintervals of length c√log^(-7)T in[T,2T]where±Δ(q_(1)q_(2)x:r_(1),q_(1),r_(2),q_(2))>cx^(1/4)always holds.
