Current evidence for oligodendrocyte precursor cell involvement in Parkinson’s disease:Oligodendroglial cells comprise a large cell population in the substantia nigra(SN).We recently reported a stable portion of olig...Current evidence for oligodendrocyte precursor cell involvement in Parkinson’s disease:Oligodendroglial cells comprise a large cell population in the substantia nigra(SN).We recently reported a stable portion of oligodendrocyte precursor cells(OPCs)in the SN pars compacta(SNpc)in a 1:1 ratio with dopaminergic neurons:15%of cells in neonate and young mice,rising to 20%in aged mice.Moreover,this portion represents only 45%of all oligodendroglial cells in the SNpc and 54%of all oligodendroglial cells in the SN pars reticulata(SNpr)(Fitzgerald et al.,2025).The SN is a deeply located area of the midbrain and the site of dopaminergic degeneration in Parkinson’s disease(PD).Recent advancement of single-cell transcriptomics revealed the involvement of non-neuronal cells in PD,with PD risk variants being strongly associated with oligodendroglia(reviewed by Salazar Campos et al.,2025).展开更多
Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape ...Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape neural circuits(Fang and Bai,2023),by releasing neuromodulators,pruning synapses,maintaining the homeostasis of extracellular potassium concentration,and interacting with endothelial cells.展开更多
This study systematically investigates the cyclization reaction mechanisms between n-C_(4)H_(3)(1-buten-3-yn-1-yl)and i-C_(4)H_(3)(2-buten-3-yn-1-yl)radicals with acetylene(C_(2)H_(2))using density functional theory(D...This study systematically investigates the cyclization reaction mechanisms between n-C_(4)H_(3)(1-buten-3-yn-1-yl)and i-C_(4)H_(3)(2-buten-3-yn-1-yl)radicals with acetylene(C_(2)H_(2))using density functional theory(DFT)and transition state theory(TST).The results reveal that the reaction of n-C_(4)H_(3)with acetylene proceeds via a radical chain mechanism through an additioncyclization pathway,yielding phenyl(sixmembered ring),fulvenyl(five-membered ring),and four-membered ring intermediates.The product formation rates follow the order:fulvenyl(five-membered ring)>phenyl(six-membered ring)>four-membered ring.For i-C_(4)H_(3),the intermediate structures depend on the carbon position of i-C_(4)H_(3)where acetylene addition occurs:addition at the C2 position predominantly generates fulvenyl(five-membered ring)as the primary product,whereas addition at the C4 position may lead to phenyl(six-membered ring),fulvenyl(five-membered ring),or four-membered ring intermediates,with the four-membered ring forming most rapidly and the six-membered ring the slowest.Theoretical analyses demonstrate that the selectivity of reaction pathways is primarily governed by structural differences between the isomers.This work provides atomic-scale insights into the cyclization processes between acetylene and C_(4)H_(3)species,establishing a foundation for refining models of soot precursor formation.展开更多
Investigating the damage evolution of surrounding rock under thermal shock cycles is crucial for ensuring the stability of engineering rock masses.This study performed Brazilian splitting tests on granite specimens un...Investigating the damage evolution of surrounding rock under thermal shock cycles is crucial for ensuring the stability of engineering rock masses.This study performed Brazilian splitting tests on granite specimens under varying temperature and cycle conditions,employing acoustic emission monitoring,digital image correlation,and three-dimensional scanning technology.A systematic analysis was conducted on the patterns of damage evolution,failure precursor,and response mechanisms under combined thermal and cyclic loading.Experimental results show that both P-wave velocity and tensile strength degrade significantly with increasing temperature and cycle count,with temperature having a more pronounced effect than cycle count.Notably,damage evolution exhibits a dual-threshold behavior in which degradation accelerates markedly above 400℃ and stabilizes after 5 thermal cycles.Fracture surfaces evolve from initially planar to rugged morphologies,with peak-valley height differences at 600℃ being approximately three times greater than those at 200℃.Furthermore,based on acoustic emission energy entropy analysis,we introduce a novel failure precursor indicator where the sustained increase and critical surge in average entropy serve as reliable early-warning signals for impending rock failure.These findings establish a solid theoretical basis and practical methodology for damage assessment and instability early-warning systems in high-temperature rock engineering.展开更多
The recycling of waste activated carbon is of great significance in environmental protection.Porous mullite ceramics were prepared by impregnating the mullite precursor with activated carbon,adding a pore-forming agen...The recycling of waste activated carbon is of great significance in environmental protection.Porous mullite ceramics were prepared by impregnating the mullite precursor with activated carbon,adding a pore-forming agent,and adopting aluminum sulfate octahydrate,ammonia and silica micropowder as raw materials,waste activated carbon after heat treatment as the pore-forming agent,and sodium polyacrylate(PAAS)as the dispersant.The effects of the activated carbon additions(1.5%,3.0%,5.2%,and 7.8%,by mass)and PAAS additions(1%,2%,and 3%,extra adding,by mass)on the physical properties,phase composition and microstructure of the porous ceramics were studied.The results show that:(1)as a pore-forming agent,activated carbon promotes the formation of pores inside the samples,while the apparent porosity of the samples increases significantly with the increasing activated carbon addition;when the activated carbon addition is 7.8%,the apparent porosity of the sample is 65.7%,the cold compressive strength is 4.62 MPa,the peak pore size is around 3.5μm,and the pore size distribution is uniform;(2)appropriate PAAS helps to improve the dispersion of activated carbon in the samples and the comprehensive performance of the porous mullite ceramics;when the PAAS addition is 2%,the apparent porosity of the sample is 71.8%,the cold compressive strength is 5.53 MPa,the peak pore size is around 3μm,and the pore size distribution is optimized;however,excessive PAAS increases the liquid phase in the system,resulting in over sintering of mullite and a decrease in the porosity.展开更多
Ceramic 4D printing,which integrates dynamic deformation with additive manufacturing,demonstrates significant potential in intelligent manufacturing,on-demand shaping of complex structures,and multifunctional device d...Ceramic 4D printing,which integrates dynamic deformation with additive manufacturing,demonstrates significant potential in intelligent manufacturing,on-demand shaping of complex structures,and multifunctional device development.Its core advantage lies in endowing materials with environmentally responsive dynamic deformation capabilities.However,current technologies still face limitations in responsiveness,reversibility,and mechanical performance.To address these challenges,this study proposes a programmable ceramic precursor system based on synergistic reinforcement of phase-separating hydrogels and shape memory polymers,combined with a nano-ceramic particle enhancement strategy.Using stereolithography 3D printing,high-precision fabrication of complex structures was achieved.By adjusting precursor composition,programming time,and structural thickness,the phase-separation kinetics-driven delayed recovery mechanism was elucidated,enabling precise control over recovery onset time.Furthermore,the thermal response mechanism of the precursor materials is explored,along with their potential for multi-shape transformation in biomedical applications,which is further extended to shape memory polymer systems.By employing a layered printing strategy,the autonomous reversible deformation of ceramic precursors is realized,providing new possibilities for specific applications.展开更多
0 INTRODUCTION Due to the sudden and highly destructive nature of slope rock collapse,developing effective early warning systems has become an urgent challenge in geotechnical engineering(Cai and Detournay,2024;Loew e...0 INTRODUCTION Due to the sudden and highly destructive nature of slope rock collapse,developing effective early warning systems has become an urgent challenge in geotechnical engineering(Cai and Detournay,2024;Loew et al.,2017).Traditional monitoring methods primarily target the acceleration stage preceding disasters(such as displacement monitoring for landslides and debris flows),which is effective for early warning of plastic collapse disasters but often inadequate for brittle failure modes(Walter et al.,2019;Chao et al.,2018;Crosta et al.,2017).展开更多
Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
INTRODUCTION.On May 1st,2024,around 2:10 a.m.,a catastrophic collapse occurred along the Meilong Expressway near Meizhou City,Guangdong Province,China,at coordinates 24°29′24″N and 116°40′25″E.This colla...INTRODUCTION.On May 1st,2024,around 2:10 a.m.,a catastrophic collapse occurred along the Meilong Expressway near Meizhou City,Guangdong Province,China,at coordinates 24°29′24″N and 116°40′25″E.This collapse resulted in a pavement failure of approximately 17.9 m in length and covering an area of about 184.3 m^(2)(Chinanews,2024).展开更多
Rockburst precursors are critical for disaster warning,yet the complexity of rockburst has hindered the identification of a unified precursor.Furthermore,the influence of loading rates(LRs)on acoustic emission(AE)prec...Rockburst precursors are critical for disaster warning,yet the complexity of rockburst has hindered the identification of a unified precursor.Furthermore,the influence of loading rates(LRs)on acoustic emission(AE)precursors in different rock types remains poorly understood.This study investigates the AE characteristics and early warning times of rockburst in slate and mica-schist under four LRs(0.05,0.15,0.25,and 0.5 MPa/s)using true triaxial unloading tests.The micro-crack state of the samples was evaluated using entropy,while critical slowing down(CSD)theory was applied to interpret AE precursors.The results reveal that as the LR increases,the rockburst stress of both rocks initially rises and then declines,with mica-schist exhibiting more severe damage and a higher dominance of tensile cracks.Notably,identifying rockburst precursors in mica-schist proved more challenging compared to slate.Among the methods tested,AE amplitude variance outperformed entropy in precursor identification.Additionally,the rockburst early warning time was found to be negatively correlated with the LR,with mica-schist consistently showing shorter warning times than slate.The CSD-derived precursor,due to its enhanced sensitivity,is recommended for early warning systems.These findings provide new insights into the role of LRs in rockburst dynamics and offer practical guidance for improving precursor identification and disaster mitigation strategies.展开更多
C/C-ZrC composites were prepared by precursor infiltration and pyrolysis using the organic zirconium as precursor.The conversion mechanisms of the precursors such as the thermal behavior,structural evolution,phase com...C/C-ZrC composites were prepared by precursor infiltration and pyrolysis using the organic zirconium as precursor.The conversion mechanisms of the precursors such as the thermal behavior,structural evolution,phase composition,microstructure,composition of the precursors and products were analyzed by thermal gravimetric analyzer,Fourier transform infrared spectrometer,X-ray diffraction and scanning electron microscope.The results indicate that the ZrC precursor transforms to inorganic ZrO2 from room temperature to 1200 ℃,then reduces to ZrC at 1600 ℃ through the carbothermal reduction reaction.The microstructure of the C/C-ZrC composites was also investigated.The composites exhibit an interesting structure,a coating composed of ZrC ceramic covers the exterior of the composite,and the ZrC ceramic is embedded in the pores of the matrix inside the composite.展开更多
Polyacrylonitrile (PAN) precursor is a core precursor for the preparation of high-performance carbon fibers. Its unique chemical structure and physical properties directly contributes to the microstructure and mechani...Polyacrylonitrile (PAN) precursor is a core precursor for the preparation of high-performance carbon fibers. Its unique chemical structure and physical properties directly contributes to the microstructure and mechanical properties of carbon fibers, and therefore affect the overall performance of pultruded composites. This study systematically investigated the influence of PAN precursor properties on the degree of graphitization, surface morphology and mechanical properties of carbon fibers by regulating the molecular weight distribution, stretching ratio and impurity content of PAN precursor, and analyzed the mechanism of action of carbon fiber properties on the interfacial bonding strength and tensile/ bending properties of composites in combination with the pultrusion process. The results showed that when the filament stretchability was increased to 4.5 times, the axial orientation of carbon fibers increased by 18% and the tensile strength reached 520 MPa;Filaments with impurity content below 0.3% increase carbon fiber yield by 5.2% and interlaminar shear strength of composites by 23%. This study provides a theoretical basis for raw material screening and process optimization of high-performance carbon fibers and their composites.展开更多
The increasing sophistication of cyberattacks,coupled with the limitations of rule-based detection systems,underscores the urgent need for proactive and intelligent cybersecurity solutions.Traditional intrusion detect...The increasing sophistication of cyberattacks,coupled with the limitations of rule-based detection systems,underscores the urgent need for proactive and intelligent cybersecurity solutions.Traditional intrusion detection systems often struggle with detecting early-stage threats,particularly in dynamic environments such as IoT,SDNs,and cloud infrastructures.These systems are hindered by high false positive rates,poor adaptability to evolving threats,and reliance on large labeled datasets.To address these challenges,this paper introduces CyberGuard-X,an AI-driven framework designed to identify attack precursors—subtle indicators of malicious intent—before full-scale intrusions occur.CyberGuard-X integrates anomaly detection,time-series analysis,and multi-stage classification within a scalable architecture.The model leverages deep learning techniques such as autoencoders,LSTM networks,and Transformer layers,supported by semi-supervised learning to enhance detection of zero-day and rare threats.Extensive experiments on benchmark datasets(CICIDS2017,CSE-CIC-IDS2018,and UNSW-NB15)demonstrate strong results,including 96.1%accuracy,94.7%precision,and 95.3%recall,while achieving a zero-day detection rate of 84.5%.With an inference time of 12.8 ms and 34.5%latency reduction,the model supports real-time deployment in resource-constrained environments.CyberGuard-X not only surpasses baseline models like LSTM and Random Forest but also enhances proactive threat mitigation across diverse network settings.展开更多
The growing environmental awareness,the search for alternatives to fossil resources,and the goal of achieving a circular economy have all contributed to the increasing valorization of biowaste to produce bio-based pol...The growing environmental awareness,the search for alternatives to fossil resources,and the goal of achieving a circular economy have all contributed to the increasing valorization of biowaste to produce bio-based polymers and other high-value products.Among the various biowaste materials,lignin has gained significant attention due to its high aromatic carbon content,low cost,and abundance.Lignin is predominantly sourced as a byproduct from the paper industry,available in large quantities from hardwood and softwood,with variations in chemical structure and susceptibility to hydrolysis.This study focuses on softwood lignin obtained through the LignoForce^(TM) technology,comparing the thermal and chemical characteristics,and stability,of a recently produced batch with that of a batch that has been stored for four years.Additionally,the development of lignin-based thermoplastic polymer mixtures using Polyethylene Terephthalate Glycol(PET-G)and a blend of Polycarbonate and Acrylonitrile-Butadiene-Styrene(PC/ABS)with high lignin content(50–60 wt%)is explored,as well as the production of filaments for carbon fiber production.For this purpose,following melt mixing,the lignin-based mixtures were spun into filaments,which were subsequently subjected to thermal stabilization in an oxidative atmosphere.The lignin phase was well distributed in the PET-Gmatrix and the twomaterials presented a good interface,which further improved after thermal treatment under an oxidative atmosphere.After thermal treatment an increase in tensile modulus,tensile strength,and elongation at break of approximately 160%,200%,and 100%,respectively,was observed,confirming the good interface established,and consistent with structural changes such as cross-linking.Conversely,the PC/ABS blend did not form a good interface with the lignin domains after melt mixing.Although the interactions improved after thermal treatment,the tensile strength and elongation at break decreased by approximately 30%,while themodulus increased by approximately 20%.Overall,the good processability of the lignin/polymer mixtures into filaments,and their physical,chemical,and mechanical characterization before and after thermal oxidation are good indicators of the potential as precursors for carbon fiber production.展开更多
This study investigates the instability characteristics of dynamic disasters resulting from disruption caused by extracting resources underground. Utilizing the split Hopkinson pressure bar (SHPB) system, the dynamic ...This study investigates the instability characteristics of dynamic disasters resulting from disruption caused by extracting resources underground. Utilizing the split Hopkinson pressure bar (SHPB) system, the dynamic response mechanism of coal energy evolution is examined, and the energy instability criterion is established. The validity of the instability criterion is explored from the standpoint of damage progression. The results demonstrate that the energy conversion mechanism undergoes a fundamental alternation under impact disturbance. Moreover, the energy release rate as well as the energy dissipation rate undergo comparable changes across distinct levels of impact disturbance. The distinction between the energy release rate and the energy dissipation rate (DRD) increases as coal mass deformation grows. Prior to coal facing instability and failure, the DRD experienced an inflection point followed by a sharp decrease. In conjunction with the discussion on the damage evolution, the physical and mechanical significance of DRD remains clear, which can essentially describe the whole impact loading process. The phenomenon that the inflection point appears and DRD subsequently suddenly decreases can be employed as the energy criterion prior to the failure of instability. Furthermore, this paper provides significant reference for the prediction of dynamic instability of coal under dynamic disturbance.展开更多
Metal composites produced through the liquid metal dealloying(LMD)process feature an advanced matrix-matrix composite structure,where two metallic materials form a continuous,three-dimensional interconnected network.T...Metal composites produced through the liquid metal dealloying(LMD)process feature an advanced matrix-matrix composite structure,where two metallic materials form a continuous,three-dimensional interconnected network.This study investigates the effects of Ti Cu precursor compositions on dealloying behavior and microstructural evolution in liquid Mg,using Ti_(50)Cu_(50)and Ti_(30)Cu_(70)precursors.The initial microstructure of the precursor significantly influences dealloying kinetics and phase transitions.The single-phase Ti_(50)Cu_(50)precursor exhibits a faster initial dealloying rate due to its homogeneous structure,yet complete dealloying requires 90 min.In contrast,the dualphase Ti_(30)Cu_(70)precursor achieves complete dealloying in 30 min,demonstrating the impact of a higher Cu concentration on accelerating the process kinetics.Additionally,the study explores the coarsening behavior and hardness variations during the LMD process,along with the microstructural characteristics of Mg-Ti composites fabricated from these two precursors.The findings highlight the critical role of precursor composition in tailoring the microstructure and properties of Mg-Ti composites produced through the LMD process,demonstrating its potential for advanced composite material manufacturing.展开更多
The current generation of ultrahigh temperature ceramic precursors typically encounters obstacles in achieving high ceramic yields(<40 wt.%)due to the challenges in integrating significant amounts of boron,which ha...The current generation of ultrahigh temperature ceramic precursors typically encounters obstacles in achieving high ceramic yields(<40 wt.%)due to the challenges in integrating significant amounts of boron,which hampers their conversion into boride-based ultrahigh temperature ceramics.To tackle these challenges,a serious of pioneering liquid multi-component hafnium-containing ceramic SiHfCB precursors(with different Hf/Si ratios)have been developed.These novel precursors are featured with stable molec-ular structure and high ceramic yield which were successfully created through a novel one-pot polymer-ization process.They present in liquid form and their structure is characterized by C-C bonds forming its main chain with branched chains of O-Si-O,Si-O-Hf,Si-O-B,and B-O-Hf which have untapped advantages including uniform component dispersion,and excellent fluidity.The ceramic yield of SiHfCB precursor with Hf/Si of 0.2 is remarkably up to 68.6 wt.%at 1500℃,and their Hf content exceeded 50 wt.%.Of particular interest,the pyrolyzed product HfB_(2)-SiC nanopowders derived from the SiHfCB precursor with Hf/Si of 0.2,consist of nanopowders in the 40-60 nm range with a density of 5.23 g cm^(−3).Remarkably,this material demonstrates exceptional performance in ultrahigh temperature oxygen-containing environ-ments at 2500℃,showing near-zero ablation with a linear ablation rate of just 2.5×10^(−4) mm s^(−1).Post-ablation analysis of the microstructure reveals that the formation of a lava-like HfO_(2) and HfO_(2)-SiO_(2) oxide layer effectively blocks oxygen penetration and provides excellent oxidation resistance.The inno-vative SiHfCB hafnium-containing ceramic precursor offers a groundbreaking solution for the preparation of lightweight ultrahigh-temperature ceramics.This development is poised to provide robust technical support for the use of ultrahigh temperature ceramics in non-ablative thermal protective systems,partic-ularly in the construction of hypersonic vehicles,where ultrahigh temperature resilience is crucial.展开更多
BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal ...BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal biopsies is challenging due to histomorphological overlaps,variability in pathological diagnosis consistency,and limited reproducibility.AIM To evaluate the diagnostic utility of P53,Ki67,P504S,and IMP3 in gastric cancer and its precancerous lesions,focusing on their effectiveness in distinguishing AH,LGD,HGD,and AC.METHODS From January 2018 to September 2020,a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors(2019).The specimens were categorized into four groups:AH,LGD,HGD,and AC.Immunohistochemistry was employed to assess the expression status of P53,Ki67,P504S,and IMP3.Intergroup comparisons were performed using theχ^(2)test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.RESULTS The expression rate of P504S was highest in the LGD group(53.3%,16/30),while IMP3 expression was highest in the AC group(41.9%,26/62),followed by the HGD group(33.3%).Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups(P<0.001).Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD,HGD,and AC groups(P<0.001),as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups,and between the LGD group and the HGD and AC groups(P<0.001).Additionally,significant correlations were found between P504S and the polarity expression pattern of Ki67,and between IMP3 and the mutation expression pattern of P53(P<0.001).The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67“polarity”expression pattern.IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern.The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.The rational use of P504S,Ki67,IMP3,and p53 can help distinguish gastric cancer and precancerous lesions,improving the early cancer diagnosis rate.展开更多
Objective To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A(SV2A)influences the distribution of amyloid precursor protein(APP)in the trans-Golgi network(TGN),endolysosomal system...Objective To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A(SV2A)influences the distribution of amyloid precursor protein(APP)in the trans-Golgi network(TGN),endolysosomal system,and cell membranes and to reveal the effects of SV2A on APP amyloid degradation.Methods Colocalization analysis of APP with specific tagged proteins in the TGN,ensolysosomal system,and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP.APP,β-site amyloid precursor protein cleaving enzyme 1(BACE1)expressions,and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing.Results APP localization was reduced in the TGN,early endosomes,late endosomes,and lysosomes,whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons.Moreover,Arl5b(ADP-ribosylation factor 5b),a protein responsible for transporting APP from the TGN to early endosomes,was upregulated by SV2A.SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis.In addition,products of APP amyloid degradation,including sAPPβ,Aβ1-42,and Aβ1-40,were decreased in SV2A-overexpressed cells.Conclusion These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway,which slows APP amyloid degradation.展开更多
Chronic cerebral hypoperfusion leads to white matter injury(WMI),which plays a significant role in contributing to vascular cognitive impairment.While 13-docosenamide is a type of fatty acid amide,it remains unclear w...Chronic cerebral hypoperfusion leads to white matter injury(WMI),which plays a significant role in contributing to vascular cognitive impairment.While 13-docosenamide is a type of fatty acid amide,it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion.In this study,we conducted bilateral common carotid artery stenosis(BCAS)surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment.Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice.Mechanistically,13-docosenamide specifically binds to cannabinoid receptor 1(CNR1)in oligodendrocyte precursor cells(OPCs).This interaction results in an upregulation of ubiquitin-specific peptidase 33(USP33)-mediated CNR1 deubiquitination,subsequently increasing CNR1 protein expression,activating the phosphorylation of the AKT/mTOR pathway,and promoting the differentiation of OPCs.In conclusion,our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.展开更多
文摘Current evidence for oligodendrocyte precursor cell involvement in Parkinson’s disease:Oligodendroglial cells comprise a large cell population in the substantia nigra(SN).We recently reported a stable portion of oligodendrocyte precursor cells(OPCs)in the SN pars compacta(SNpc)in a 1:1 ratio with dopaminergic neurons:15%of cells in neonate and young mice,rising to 20%in aged mice.Moreover,this portion represents only 45%of all oligodendroglial cells in the SNpc and 54%of all oligodendroglial cells in the SN pars reticulata(SNpr)(Fitzgerald et al.,2025).The SN is a deeply located area of the midbrain and the site of dopaminergic degeneration in Parkinson’s disease(PD).Recent advancement of single-cell transcriptomics revealed the involvement of non-neuronal cells in PD,with PD risk variants being strongly associated with oligodendroglia(reviewed by Salazar Campos et al.,2025).
基金supported by DeutscheForschungsgemeinschaft(BA 8014/1-1 to XB)University of Saarland(NanoBioMed Young Investigatorgrant 2021 to XB,Anschubsfinanzierung2024to XB,HOMFORExzellenz2025 andAnschubsfinanzierung2025 to LPF)the ChinaPharmaceutical University(UndergraduateInternship Program to YZ).
文摘Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape neural circuits(Fang and Bai,2023),by releasing neuromodulators,pruning synapses,maintaining the homeostasis of extracellular potassium concentration,and interacting with endothelial cells.
基金Supported by the National Key Research and Development Program of China(2022YFB4301400)the Basic Science(Natural Science)Research Project for Higher Education Institutions in Jiangsu Province(24KJD580001)。
文摘This study systematically investigates the cyclization reaction mechanisms between n-C_(4)H_(3)(1-buten-3-yn-1-yl)and i-C_(4)H_(3)(2-buten-3-yn-1-yl)radicals with acetylene(C_(2)H_(2))using density functional theory(DFT)and transition state theory(TST).The results reveal that the reaction of n-C_(4)H_(3)with acetylene proceeds via a radical chain mechanism through an additioncyclization pathway,yielding phenyl(sixmembered ring),fulvenyl(five-membered ring),and four-membered ring intermediates.The product formation rates follow the order:fulvenyl(five-membered ring)>phenyl(six-membered ring)>four-membered ring.For i-C_(4)H_(3),the intermediate structures depend on the carbon position of i-C_(4)H_(3)where acetylene addition occurs:addition at the C2 position predominantly generates fulvenyl(five-membered ring)as the primary product,whereas addition at the C4 position may lead to phenyl(six-membered ring),fulvenyl(five-membered ring),or four-membered ring intermediates,with the four-membered ring forming most rapidly and the six-membered ring the slowest.Theoretical analyses demonstrate that the selectivity of reaction pathways is primarily governed by structural differences between the isomers.This work provides atomic-scale insights into the cyclization processes between acetylene and C_(4)H_(3)species,establishing a foundation for refining models of soot precursor formation.
基金supported by National Natural Science Foundation of China (Nos.52264006,52364004,and 52464005)the Guizhou Provincial Science and Technology Foundation (No.GCC[2022]005-1)。
文摘Investigating the damage evolution of surrounding rock under thermal shock cycles is crucial for ensuring the stability of engineering rock masses.This study performed Brazilian splitting tests on granite specimens under varying temperature and cycle conditions,employing acoustic emission monitoring,digital image correlation,and three-dimensional scanning technology.A systematic analysis was conducted on the patterns of damage evolution,failure precursor,and response mechanisms under combined thermal and cyclic loading.Experimental results show that both P-wave velocity and tensile strength degrade significantly with increasing temperature and cycle count,with temperature having a more pronounced effect than cycle count.Notably,damage evolution exhibits a dual-threshold behavior in which degradation accelerates markedly above 400℃ and stabilizes after 5 thermal cycles.Fracture surfaces evolve from initially planar to rugged morphologies,with peak-valley height differences at 600℃ being approximately three times greater than those at 200℃.Furthermore,based on acoustic emission energy entropy analysis,we introduce a novel failure precursor indicator where the sustained increase and critical surge in average entropy serve as reliable early-warning signals for impending rock failure.These findings establish a solid theoretical basis and practical methodology for damage assessment and instability early-warning systems in high-temperature rock engineering.
文摘The recycling of waste activated carbon is of great significance in environmental protection.Porous mullite ceramics were prepared by impregnating the mullite precursor with activated carbon,adding a pore-forming agent,and adopting aluminum sulfate octahydrate,ammonia and silica micropowder as raw materials,waste activated carbon after heat treatment as the pore-forming agent,and sodium polyacrylate(PAAS)as the dispersant.The effects of the activated carbon additions(1.5%,3.0%,5.2%,and 7.8%,by mass)and PAAS additions(1%,2%,and 3%,extra adding,by mass)on the physical properties,phase composition and microstructure of the porous ceramics were studied.The results show that:(1)as a pore-forming agent,activated carbon promotes the formation of pores inside the samples,while the apparent porosity of the samples increases significantly with the increasing activated carbon addition;when the activated carbon addition is 7.8%,the apparent porosity of the sample is 65.7%,the cold compressive strength is 4.62 MPa,the peak pore size is around 3.5μm,and the pore size distribution is uniform;(2)appropriate PAAS helps to improve the dispersion of activated carbon in the samples and the comprehensive performance of the porous mullite ceramics;when the PAAS addition is 2%,the apparent porosity of the sample is 71.8%,the cold compressive strength is 5.53 MPa,the peak pore size is around 3μm,and the pore size distribution is optimized;however,excessive PAAS increases the liquid phase in the system,resulting in over sintering of mullite and a decrease in the porosity.
基金supported by the National Natural Science Foundation of China(Grant Nos.52025053 and 52235006)the Jilin Provincial Scientific and Technological Development Program(20220204119YY)the Natural Science Foundation of Shandong Province(ZR2023ME154)。
文摘Ceramic 4D printing,which integrates dynamic deformation with additive manufacturing,demonstrates significant potential in intelligent manufacturing,on-demand shaping of complex structures,and multifunctional device development.Its core advantage lies in endowing materials with environmentally responsive dynamic deformation capabilities.However,current technologies still face limitations in responsiveness,reversibility,and mechanical performance.To address these challenges,this study proposes a programmable ceramic precursor system based on synergistic reinforcement of phase-separating hydrogels and shape memory polymers,combined with a nano-ceramic particle enhancement strategy.Using stereolithography 3D printing,high-precision fabrication of complex structures was achieved.By adjusting precursor composition,programming time,and structural thickness,the phase-separation kinetics-driven delayed recovery mechanism was elucidated,enabling precise control over recovery onset time.Furthermore,the thermal response mechanism of the precursor materials is explored,along with their potential for multi-shape transformation in biomedical applications,which is further extended to shape memory polymer systems.By employing a layered printing strategy,the autonomous reversible deformation of ceramic precursors is realized,providing new possibilities for specific applications.
基金supported by the National Key R&D Program of China(No.2023YFC3081400)the National Natural Science Foundation of China(No.41702371)+3 种基金the Open Fund Project of State Key Laboratory of Mining Response and Disaster Prevention in Deep Coal Mines(No.SKLMRDPC22KF13)the Supported by State key Laboratory of Mining Disaster Prevention and Control(Shandong University of Science and Technology),Ministry of Education(No.DPEPM202502)the Open Fund Research Project Supported by State Key Laboratory of Strata Intelligent Control and Green Mining Co-founded by Shandong Province and the Ministry of Science and Technology(No.SICGM202503)the Fund of Chongqing Key Laboratory of Facility Damage Mechanism and Protection in Highland Mountain Environment(No.LQ24KFJJ09)。
文摘0 INTRODUCTION Due to the sudden and highly destructive nature of slope rock collapse,developing effective early warning systems has become an urgent challenge in geotechnical engineering(Cai and Detournay,2024;Loew et al.,2017).Traditional monitoring methods primarily target the acceleration stage preceding disasters(such as displacement monitoring for landslides and debris flows),which is effective for early warning of plastic collapse disasters but often inadequate for brittle failure modes(Walter et al.,2019;Chao et al.,2018;Crosta et al.,2017).
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
基金supported by the National Natural Science Foundation of China(Nos.42371094,41907253)partially supported by the Interdisciplinary Cultivation Program of Xidian University(No.21103240005)the Postdoctoral Fellowship Program of CPSF(No.GZB20240589)。
文摘INTRODUCTION.On May 1st,2024,around 2:10 a.m.,a catastrophic collapse occurred along the Meilong Expressway near Meizhou City,Guangdong Province,China,at coordinates 24°29′24″N and 116°40′25″E.This collapse resulted in a pavement failure of approximately 17.9 m in length and covering an area of about 184.3 m^(2)(Chinanews,2024).
基金supported by the National Natural Science Foundation of China(Nos.52374119,42477142 and 42277154)Natural Science Foundation of Jiangsu Province(No.BK20242059)+1 种基金the open fund of State Key Laboratory of Hydraulics and Mountain River Engineering(No.SKHL2306)the High-level Talent Introduction Project of Changzhou University(No.ZMF24020037)。
文摘Rockburst precursors are critical for disaster warning,yet the complexity of rockburst has hindered the identification of a unified precursor.Furthermore,the influence of loading rates(LRs)on acoustic emission(AE)precursors in different rock types remains poorly understood.This study investigates the AE characteristics and early warning times of rockburst in slate and mica-schist under four LRs(0.05,0.15,0.25,and 0.5 MPa/s)using true triaxial unloading tests.The micro-crack state of the samples was evaluated using entropy,while critical slowing down(CSD)theory was applied to interpret AE precursors.The results reveal that as the LR increases,the rockburst stress of both rocks initially rises and then declines,with mica-schist exhibiting more severe damage and a higher dominance of tensile cracks.Notably,identifying rockburst precursors in mica-schist proved more challenging compared to slate.Among the methods tested,AE amplitude variance outperformed entropy in precursor identification.Additionally,the rockburst early warning time was found to be negatively correlated with the LR,with mica-schist consistently showing shorter warning times than slate.The CSD-derived precursor,due to its enhanced sensitivity,is recommended for early warning systems.These findings provide new insights into the role of LRs in rockburst dynamics and offer practical guidance for improving precursor identification and disaster mitigation strategies.
基金Project (2011CB605801) supported by the National Basic Research Program of ChinaProject (CX2012B042) supported by the Graduated Students' Scientific Research Innovation Project in Hunan Province of China
文摘C/C-ZrC composites were prepared by precursor infiltration and pyrolysis using the organic zirconium as precursor.The conversion mechanisms of the precursors such as the thermal behavior,structural evolution,phase composition,microstructure,composition of the precursors and products were analyzed by thermal gravimetric analyzer,Fourier transform infrared spectrometer,X-ray diffraction and scanning electron microscope.The results indicate that the ZrC precursor transforms to inorganic ZrO2 from room temperature to 1200 ℃,then reduces to ZrC at 1600 ℃ through the carbothermal reduction reaction.The microstructure of the C/C-ZrC composites was also investigated.The composites exhibit an interesting structure,a coating composed of ZrC ceramic covers the exterior of the composite,and the ZrC ceramic is embedded in the pores of the matrix inside the composite.
文摘Polyacrylonitrile (PAN) precursor is a core precursor for the preparation of high-performance carbon fibers. Its unique chemical structure and physical properties directly contributes to the microstructure and mechanical properties of carbon fibers, and therefore affect the overall performance of pultruded composites. This study systematically investigated the influence of PAN precursor properties on the degree of graphitization, surface morphology and mechanical properties of carbon fibers by regulating the molecular weight distribution, stretching ratio and impurity content of PAN precursor, and analyzed the mechanism of action of carbon fiber properties on the interfacial bonding strength and tensile/ bending properties of composites in combination with the pultrusion process. The results showed that when the filament stretchability was increased to 4.5 times, the axial orientation of carbon fibers increased by 18% and the tensile strength reached 520 MPa;Filaments with impurity content below 0.3% increase carbon fiber yield by 5.2% and interlaminar shear strength of composites by 23%. This study provides a theoretical basis for raw material screening and process optimization of high-performance carbon fibers and their composites.
文摘The increasing sophistication of cyberattacks,coupled with the limitations of rule-based detection systems,underscores the urgent need for proactive and intelligent cybersecurity solutions.Traditional intrusion detection systems often struggle with detecting early-stage threats,particularly in dynamic environments such as IoT,SDNs,and cloud infrastructures.These systems are hindered by high false positive rates,poor adaptability to evolving threats,and reliance on large labeled datasets.To address these challenges,this paper introduces CyberGuard-X,an AI-driven framework designed to identify attack precursors—subtle indicators of malicious intent—before full-scale intrusions occur.CyberGuard-X integrates anomaly detection,time-series analysis,and multi-stage classification within a scalable architecture.The model leverages deep learning techniques such as autoencoders,LSTM networks,and Transformer layers,supported by semi-supervised learning to enhance detection of zero-day and rare threats.Extensive experiments on benchmark datasets(CICIDS2017,CSE-CIC-IDS2018,and UNSW-NB15)demonstrate strong results,including 96.1%accuracy,94.7%precision,and 95.3%recall,while achieving a zero-day detection rate of 84.5%.With an inference time of 12.8 ms and 34.5%latency reduction,the model supports real-time deployment in resource-constrained environments.CyberGuard-X not only surpasses baseline models like LSTM and Random Forest but also enhances proactive threat mitigation across diverse network settings.
基金funded by Project Better Plastics—Plastics in a Circular Economy—PPS4(Circularity by Alternative Feedstocks)Grant agreement ID:POCI-01-0247-FEDER-046091RR was funded by FCT through the PhD grant with reference UI/BD/154446/2022.
文摘The growing environmental awareness,the search for alternatives to fossil resources,and the goal of achieving a circular economy have all contributed to the increasing valorization of biowaste to produce bio-based polymers and other high-value products.Among the various biowaste materials,lignin has gained significant attention due to its high aromatic carbon content,low cost,and abundance.Lignin is predominantly sourced as a byproduct from the paper industry,available in large quantities from hardwood and softwood,with variations in chemical structure and susceptibility to hydrolysis.This study focuses on softwood lignin obtained through the LignoForce^(TM) technology,comparing the thermal and chemical characteristics,and stability,of a recently produced batch with that of a batch that has been stored for four years.Additionally,the development of lignin-based thermoplastic polymer mixtures using Polyethylene Terephthalate Glycol(PET-G)and a blend of Polycarbonate and Acrylonitrile-Butadiene-Styrene(PC/ABS)with high lignin content(50–60 wt%)is explored,as well as the production of filaments for carbon fiber production.For this purpose,following melt mixing,the lignin-based mixtures were spun into filaments,which were subsequently subjected to thermal stabilization in an oxidative atmosphere.The lignin phase was well distributed in the PET-Gmatrix and the twomaterials presented a good interface,which further improved after thermal treatment under an oxidative atmosphere.After thermal treatment an increase in tensile modulus,tensile strength,and elongation at break of approximately 160%,200%,and 100%,respectively,was observed,confirming the good interface established,and consistent with structural changes such as cross-linking.Conversely,the PC/ABS blend did not form a good interface with the lignin domains after melt mixing.Although the interactions improved after thermal treatment,the tensile strength and elongation at break decreased by approximately 30%,while themodulus increased by approximately 20%.Overall,the good processability of the lignin/polymer mixtures into filaments,and their physical,chemical,and mechanical characterization before and after thermal oxidation are good indicators of the potential as precursors for carbon fiber production.
基金Projects(51934007,12072363,52004268) supported by the National Natural Science Foundation of ChinaProject(22KJD440002) supported by the Natural Science Fund for Colleges and Universities in Jiangsu Province,China。
文摘This study investigates the instability characteristics of dynamic disasters resulting from disruption caused by extracting resources underground. Utilizing the split Hopkinson pressure bar (SHPB) system, the dynamic response mechanism of coal energy evolution is examined, and the energy instability criterion is established. The validity of the instability criterion is explored from the standpoint of damage progression. The results demonstrate that the energy conversion mechanism undergoes a fundamental alternation under impact disturbance. Moreover, the energy release rate as well as the energy dissipation rate undergo comparable changes across distinct levels of impact disturbance. The distinction between the energy release rate and the energy dissipation rate (DRD) increases as coal mass deformation grows. Prior to coal facing instability and failure, the DRD experienced an inflection point followed by a sharp decrease. In conjunction with the discussion on the damage evolution, the physical and mechanical significance of DRD remains clear, which can essentially describe the whole impact loading process. The phenomenon that the inflection point appears and DRD subsequently suddenly decreases can be employed as the energy criterion prior to the failure of instability. Furthermore, this paper provides significant reference for the prediction of dynamic instability of coal under dynamic disturbance.
基金supported by the National Research Foundation of Korea(NRF)grants funded by the Korea government(MSIT)(Nos.RS-2024–00351052 and RS-2024–00450561)。
文摘Metal composites produced through the liquid metal dealloying(LMD)process feature an advanced matrix-matrix composite structure,where two metallic materials form a continuous,three-dimensional interconnected network.This study investigates the effects of Ti Cu precursor compositions on dealloying behavior and microstructural evolution in liquid Mg,using Ti_(50)Cu_(50)and Ti_(30)Cu_(70)precursors.The initial microstructure of the precursor significantly influences dealloying kinetics and phase transitions.The single-phase Ti_(50)Cu_(50)precursor exhibits a faster initial dealloying rate due to its homogeneous structure,yet complete dealloying requires 90 min.In contrast,the dualphase Ti_(30)Cu_(70)precursor achieves complete dealloying in 30 min,demonstrating the impact of a higher Cu concentration on accelerating the process kinetics.Additionally,the study explores the coarsening behavior and hardness variations during the LMD process,along with the microstructural characteristics of Mg-Ti composites fabricated from these two precursors.The findings highlight the critical role of precursor composition in tailoring the microstructure and properties of Mg-Ti composites produced through the LMD process,demonstrating its potential for advanced composite material manufacturing.
基金supported by the Key Program of the National Natural Science Foundation of China(No.52032003)the Major Program of the National Natural Science Foundation of China(No.52293372)+2 种基金the National Natural Science Foundation of China(No.51972082)the National Natural Science Foundation of China(No.52102093)the National Natural Science Foundation of China(No.52172041)and the science foundation of national key laboratory of science and technology on advanced composites in special environments.
文摘The current generation of ultrahigh temperature ceramic precursors typically encounters obstacles in achieving high ceramic yields(<40 wt.%)due to the challenges in integrating significant amounts of boron,which hampers their conversion into boride-based ultrahigh temperature ceramics.To tackle these challenges,a serious of pioneering liquid multi-component hafnium-containing ceramic SiHfCB precursors(with different Hf/Si ratios)have been developed.These novel precursors are featured with stable molec-ular structure and high ceramic yield which were successfully created through a novel one-pot polymer-ization process.They present in liquid form and their structure is characterized by C-C bonds forming its main chain with branched chains of O-Si-O,Si-O-Hf,Si-O-B,and B-O-Hf which have untapped advantages including uniform component dispersion,and excellent fluidity.The ceramic yield of SiHfCB precursor with Hf/Si of 0.2 is remarkably up to 68.6 wt.%at 1500℃,and their Hf content exceeded 50 wt.%.Of particular interest,the pyrolyzed product HfB_(2)-SiC nanopowders derived from the SiHfCB precursor with Hf/Si of 0.2,consist of nanopowders in the 40-60 nm range with a density of 5.23 g cm^(−3).Remarkably,this material demonstrates exceptional performance in ultrahigh temperature oxygen-containing environ-ments at 2500℃,showing near-zero ablation with a linear ablation rate of just 2.5×10^(−4) mm s^(−1).Post-ablation analysis of the microstructure reveals that the formation of a lava-like HfO_(2) and HfO_(2)-SiO_(2) oxide layer effectively blocks oxygen penetration and provides excellent oxidation resistance.The inno-vative SiHfCB hafnium-containing ceramic precursor offers a groundbreaking solution for the preparation of lightweight ultrahigh-temperature ceramics.This development is poised to provide robust technical support for the use of ultrahigh temperature ceramics in non-ablative thermal protective systems,partic-ularly in the construction of hypersonic vehicles,where ultrahigh temperature resilience is crucial.
基金Supported by The Science and Technology Research Project of Anyang,No.2022C01SF074。
文摘BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal biopsies is challenging due to histomorphological overlaps,variability in pathological diagnosis consistency,and limited reproducibility.AIM To evaluate the diagnostic utility of P53,Ki67,P504S,and IMP3 in gastric cancer and its precancerous lesions,focusing on their effectiveness in distinguishing AH,LGD,HGD,and AC.METHODS From January 2018 to September 2020,a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors(2019).The specimens were categorized into four groups:AH,LGD,HGD,and AC.Immunohistochemistry was employed to assess the expression status of P53,Ki67,P504S,and IMP3.Intergroup comparisons were performed using theχ^(2)test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.RESULTS The expression rate of P504S was highest in the LGD group(53.3%,16/30),while IMP3 expression was highest in the AC group(41.9%,26/62),followed by the HGD group(33.3%).Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups(P<0.001).Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD,HGD,and AC groups(P<0.001),as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups,and between the LGD group and the HGD and AC groups(P<0.001).Additionally,significant correlations were found between P504S and the polarity expression pattern of Ki67,and between IMP3 and the mutation expression pattern of P53(P<0.001).The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67“polarity”expression pattern.IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern.The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.The rational use of P504S,Ki67,IMP3,and p53 can help distinguish gastric cancer and precancerous lesions,improving the early cancer diagnosis rate.
基金supported by grants from the State Key Program of the National Natural Science Foundation of China(grant number 82030064)Beijing Hospital Authority Youth Program(grant number QML20230812)+2 种基金Research and Development Foundation of Capital Medical University(grant number PYZ23052)National Natural Science Youth Cultivation Project of Xuanwu Hospital,Capital Medical University(grant number QNPY202317)Capital Medical University Research and Cultivation Fund(grant number PYZ23049).
文摘Objective To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A(SV2A)influences the distribution of amyloid precursor protein(APP)in the trans-Golgi network(TGN),endolysosomal system,and cell membranes and to reveal the effects of SV2A on APP amyloid degradation.Methods Colocalization analysis of APP with specific tagged proteins in the TGN,ensolysosomal system,and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP.APP,β-site amyloid precursor protein cleaving enzyme 1(BACE1)expressions,and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing.Results APP localization was reduced in the TGN,early endosomes,late endosomes,and lysosomes,whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons.Moreover,Arl5b(ADP-ribosylation factor 5b),a protein responsible for transporting APP from the TGN to early endosomes,was upregulated by SV2A.SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis.In addition,products of APP amyloid degradation,including sAPPβ,Aβ1-42,and Aβ1-40,were decreased in SV2A-overexpressed cells.Conclusion These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway,which slows APP amyloid degradation.
基金supported by the National Natural Science Foundation of China(82130036)the STI2030-Major Projects(2022ZD0211800)Jiangsu Province Key Medical Discipline(ZDXK202216).
文摘Chronic cerebral hypoperfusion leads to white matter injury(WMI),which plays a significant role in contributing to vascular cognitive impairment.While 13-docosenamide is a type of fatty acid amide,it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion.In this study,we conducted bilateral common carotid artery stenosis(BCAS)surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment.Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice.Mechanistically,13-docosenamide specifically binds to cannabinoid receptor 1(CNR1)in oligodendrocyte precursor cells(OPCs).This interaction results in an upregulation of ubiquitin-specific peptidase 33(USP33)-mediated CNR1 deubiquitination,subsequently increasing CNR1 protein expression,activating the phosphorylation of the AKT/mTOR pathway,and promoting the differentiation of OPCs.In conclusion,our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
