To ensure the reliability of learned information,most insects require multiple intervals of experience before storing the information as long-term memory(LTM),and this requirement has been validated in insects from th...To ensure the reliability of learned information,most insects require multiple intervals of experience before storing the information as long-term memory(LTM),and this requirement has been validated in insects from the behavioral to the molecular level.Recent studies have shown that some insects can form LTM after one-trial experience,although the mechanisms underlying one-trial LTM formation are not well understood.Therefore,understanding the mechanisms underlying rapid learning and subsequent preference formation in insects is crucial.Here we show that the agricultural pest Bactrocera dorsalis can rapidly form LTM,which is dependent on protein synthesis,and that the formation of LTM requires high energy support at the cost of reduced survival.Furthermore,based on a liquid chromatography-mass spectrometry(LC-MS)metabolomics approach,we found that LTM-related processes are sequentially coupled to two processes for energy generation,the TCA cycle and oxidative phosphorylation.This was further confirmed by blocking these energy generation processes.Our results provide a theoretical basis for the development of behavioral modulators in oriental fruit flies that target energy generation metabolites,as well as a new perspective on the rapid formation of LTM in insects.展开更多
Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:...Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:To investigate mitochondrial damage and the effects of resveratrol on inflammation,cognitive function,and mitochondrial quality control in APP/PS1 mice.Methods:Comparative analysis of mitochondrial DNA(mtDNA)damage was conducted between 10-month-old APP/PS1 mice and age-matched C57BL/6 mice.Assessments included measurement of amyloid-βlevels,inflammatory markers,swimming distance in the Morris water maze,and gut microbiome composition.Resveratrol’s effects on cytokine expression,mtDNA levels in plasma,and activation of Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)and phosphoinositide 3-kinase/protein kinase B(also known as Akt)/mechanistic target of rapamycin complex 1(PI3K/Akt/mTORC1)signaling pathways were also evaluated.Results:APP/PS1 mice exhibited significantly increased mtDNA damage in the prefrontal cortex,midbrain,and cerebellum,alongside higher amyloid-βlevels and inflammatory markers.Resveratrol treatment led to reduced expression of pro-inflammatory cytokines,a decrease in Proteobacteria levels,and lower cell-free mtDNA in plasma.Partial improvement in long-term spatial memory was observed in APP/PS1 mice following resveratrol treatment,likely due to its anti-inflammatory properties.Activation of the Nrf2/ARE signaling pathway and markers of PI3K/Akt/mTORC1 axis activation were noted,with the latter regulating long-term potentiation.Conclusion:Resveratrol demonstrates potential in mitigating inflammation and improving mitochondrial quality control in APP/PS1 mice,but it does not reduce amyloid-βlevels,highlighting the complexity of AD pathology and the need for further research.展开更多
Objective To evaluate whether the thermotaxis tracking model is suitable for assessing long-term memory （LTM） in the nematode Caenorhabditis elegans. Methods Animals were trained at 20℃ overnight in presence of foo...Objective To evaluate whether the thermotaxis tracking model is suitable for assessing long-term memory （LTM） in the nematode Caenorhabditis elegans. Methods Animals were trained at 20℃ overnight in presence of food. The percentage of animals performing isothermal tracking （IT） behavior was measured at different time intervals after the training. Results The percentage of animals performing IT behavior, the numbers of body bends inside and outside the training temperature, and the expression patterns of AFD and AIY neurons were similar to those in control animals at 36 and 48 h after training; whereas when extending to 60, 72, and 84 h, locomotory behavior defects were observed in the assayed animals, suggesting that this thermal tracking model is feasible for analyzing LTM at 36 and 48 h after training. Moreover, the percent-age of animals performing IT behavior was reduced at 18, 36, and 48 h after training in neuronal calcium sensor-1 gene （nsc-1） mutant animals compared with that in wild-type N2 animals. In addition, exposure to plumbum （Pb） significantly repressed the LTM at 18, 36, and 48 h after training in both wild-type N2 and ncs-1 mutant animals. Conclusion The thermotaxis tracking model is suitable for evaluating the LTM regulated by NCS-1, and can be employed for elucidating regulatory functions of specific genes or effects of stimuli on memory in C. elegans.展开更多
Long-term memory(LTM)in the climate system has been well recognized and applied in different research fields,but the origins of this property are still not clear.In this work,the authors contribute to this issue by st...Long-term memory(LTM)in the climate system has been well recognized and applied in different research fields,but the origins of this property are still not clear.In this work,the authors contribute to this issue by studying model simulations under different scenarios.The global mean temperatures from pre-industrial control runs(pi Control),historical(all forcings)simulations,natural forcing only simulations(Historical Nat),greenhouse gas forcing only simulations(Historical GHG),etc.,are analyzed using the detrended fluctuation analysis.The authors find that the LTM already exists in the pi Control simulations,indicating the important roles of internal natural variability in producing the LTM.By comparing the results among different scenarios,the LTM from the piControl runs is further found to be strengthened by adding natural forcings such as the volcanic forcing and the solar forcing.Accordingly,the observed LTM in the climate system is suggested to be mainly controlled by both the‘internal’natural variability and the‘external’natural forcings.The anthropogenic forcings,however,may weaken the LTM.In the projections from RCP2.6 to RCP8.5,a weakening trend of the LTM strength is found.In view of the close relations between the climate memory and the climate predictability,a reduced predictability may be expected in a warming climate.展开更多
Objective: To observe the effects on spatial long-term memory in the rats with vascular dementia(VD)treated with moxibustion for resolving stasis and promoting meridian circulation.Methods: The modified 2-vascular occ...Objective: To observe the effects on spatial long-term memory in the rats with vascular dementia(VD)treated with moxibustion for resolving stasis and promoting meridian circulation.Methods: The modified 2-vascular occlusion(2-VO) method was used to prepare VD animal model. The rats were randomized into a sham-operation group, a model group, a moxibustion group and a western medication group, 15 rats in each one. In the moxibustion group, mild warm moxibustion was applied to"Bǎihuì(百会 GV 20)" "DàZhuī(大椎 GV 14)" and "Shéntíng(神庭 GV 24)". 20 min at each point, once a day, for 3 weeks consecutively. In the western medicaion group, mouse nerve growth factor(NGF) was injected intraperitoneally, 0.18 mL/kg, once a day, for 3 weeks consecutively. Morris water maze test was used, the time of the first passing platform, the frequency of passing-platform and swimming speed in120 s were determined of the rats in each group. Western blot were used to test the protein expressions of hippocampal Nestin and DCX.Results: At the end of three courses of treatment, compared with sham-operation group, the difference was not significant statistically in swimming speed in the model group, the moxibustion group and the western medication group separately(all P>0.05). Three days after modeling, the mean of escape latency was prolonged obviously in the modeled rats compared with the rats in the shamoperation group(88.84 ± 19.94 vs 18.15 ±9.41, P< 0.01). At the end of three courses of treatment, compared with the sham-operation group(22.01 ± 10.07), the mean of escape latency was different statistically in the model group(89.18± 19.70), the moxibustion group(37.21 ±13.31) and the western medication group separately(51.50± 16.15), all P<0.01. Compared with the model group, the mean of escape latency was shortened in the moxibustion group and western medication group respectively(37.21 ± 13.31 vs89.18 ± 19.70, 51.50 ± 16.15 vs 89.18 ± 19.70, both P< 0.01). Compared with the western medication group,there was no statistical significant difference in the mean of escape latency in the moxibustion group(37.21 ± 13.31 vs 51.50 ±16.15, P> 0.05). Compared with the sham-operation group, the frequency of passing-platform was decreased in the model group(0.73 ±0.96 vs 2.60 ±1.45, P<0.01); compared with model group, the frequency of passing-platform was increased in the moxibustion group and the western medicine group and the statistically significant difference presented in the moxibustion group(2.06 ± 1.33 vs 0.73 ±0.96, P<0.01). Compared with the sham-operation group, the time of first passing-platform was prolonged in the model group(87.86 ± 33.25 vs 36.13 +29.76, P< 0.01). Compared with the model group,the time of first passing-platform was shortened in the moxibustion group and the western medicine group respectively(49.53 ±29.48 vs 87.86 ± 33.25.P< 0.01; 58.98 ± 36.22 vs 87.86 ±33.25, P< 0.05). After three courses of treatment, compared with the sham-operation group, Nestin expression was reduced in the model group,(0.33 ±0.12 vs 0.51 ±0.02, P<0.05) and was increased in the moxibustion group and the western medication group respectively(1.33 ± 0.17 vs 0.51 ± 0.02. 1.39 ± 0.10 vs 0.51 ±0.02, both P< 0.01).Compared with the model group, Nestin expression was increased in the moxibustion group and the western medication group, respectively(1.33 ± 0.17 vs 0.33±0.12. 1.39±0.10 vs 0.33 ±0.12, both P< 0.01).Compared with the western medication group, the difference was not significant statistically in the moxibustion group(1.33±0.17 vs 1.39±0.10, P>0.05). After three courses of treatment, compared with the sham-operation group, DCX expression was decreased in the model group, but without significant difference(0.44±0.20 vs 0.51 ±0.26, P> 0.05), the expression was increased in the moxibustion group and the western medication group respectively(0.98±0.25 vs 0.51±0.26. P< 0.05; 1.11±0.43 vs 0.51 ±0.26,P<0.01). Compared with the model group, DCX expression was obviously increased in the moxibustion group and the western medication group(0.98 ± 0.25 vs 0.44 ± 0.20. 1.11 ± 0.43 vs 0.44 ± 0.20, both P<0.01). The difference in DCX expression was not statistically significant between the western medication group and the moxibustion group(0.98 ± 0.25 vs 1.11 ± 0.43. P> 0.05).Conclusion: Moxibustion apparently improves the long-term memory in VD rats.展开更多
To investigate effects and possible mechanism of Ro 20-1724, a PDE4 inhibitor, on long-time learning and memory ability following repeated ketamine exposure in immature rats. Methods: Sixty 21-day-old SD rats were ran...To investigate effects and possible mechanism of Ro 20-1724, a PDE4 inhibitor, on long-time learning and memory ability following repeated ketamine exposure in immature rats. Methods: Sixty 21-day-old SD rats were randomly divided into five groups (n = 12): C: Normal control group, S: Saline control group, K: Ketamine, K + Ro:?Ketamine + Ro 20-1724, K + E: Ketamine + ethanol vehicle. Ro 20-1724 (0.5 mg·kg-1) or its vehicle (ethanol) was administered intraperitoneally 30 minutes after ketamine anesthesia (70 mg·kg-1), daily for seven days. Nine weeks after birth, the Morris water maze was used to test the ability of learning and spatial localization memory on the rats. Following behavioral testing, animals’ hippocampi were removed for Western blot and electron microscopic examination. Results: In the Morris water maze test, compared with controls, the escape latency in groups exposed to ketamine or ketamine plus the ethanol vehicle were significantly prolonged (P P < 0.05), and the expression of p-CREB in the hippocampus was also decreased (P 0.05), while there was no significant difference between control groups and animals treated with Ro 20-1724 following ketamine exposure (P > 0.05). Electron microscopy demonstrated degenerative changes in hippocampal neurons of animals repetitively exposed to 70 mg·kg-1 Ketamine, which was ameliorated by Ro 20-1724 (0.5 mg·kg-1). Conclusion: The PDE-4 inhibitor Ro 20-1724 (0.5 mg·kg-1<span展开更多
Photonic platforms are gradually emerging as a promising option to encounter the ever-growing demand for artificial intelligence,among which photonic time-delay reservoir computing(TDRC)is widely anticipated.While suc...Photonic platforms are gradually emerging as a promising option to encounter the ever-growing demand for artificial intelligence,among which photonic time-delay reservoir computing(TDRC)is widely anticipated.While such a computing paradigm can only employ a single photonic device as the nonlinear node for data processing,the performance highly relies on the fading memory provided by the delay feedback loop(FL),which sets a restriction on the extensibility of physical implementation,especially for highly integrated chips.Here,we present a simplified photonic scheme for more flexible parameter configurations leveraging the designed quasi-convolution coding(QC),which completely gets rid of the dependence on FL.Unlike delay-based TDRC,encoded data in QC-based RC(QRC)enables temporal feature extraction,facilitating augmented memory capabilities.Thus,our proposed QRC is enabled to deal with time-related tasks or sequential data without the implementation of FL.Furthermore,we can implement this hardware with a low-power,easily integrable vertical-cavity surface-emitting laser for high-performance parallel processing.We illustrate the concept validation through simulation and experimental comparison of QRC and TDRC,wherein the simpler-structured QRC outperforms across various benchmark tasks.Our results may underscore an auspicious solution for the hardware implementation of deep neural networks.展开更多
Polyurethane-fluorinated polysiloxane(PU-^(F)PDMS)with high-strength,high-bonding and low surface en-ergy is synthesized as the matrix,and the PU-^(F)PDMS/MCs/Ag marine anti-fouling coating on the sur-face of imitatio...Polyurethane-fluorinated polysiloxane(PU-^(F)PDMS)with high-strength,high-bonding and low surface en-ergy is synthesized as the matrix,and the PU-^(F)PDMS/MCs/Ag marine anti-fouling coating on the sur-face of imitation crab shells is constructed by assembling butenolide@1,1-stilbene-modified hydrolyzed polyglycidyl methacrylate/graphene oxide microcapsules(Bu@PGMAm/GO MCs)with compact multi-shell structure and Ag nanoparticles(AgNPs)step by step on the PU-^(F)PDMS matrix.The PU-^(F)PDMS/MCs/Ag bionic anti-fouling coatings achieve long-term and stable anti-fouling effect under the combination of robust low-surface-energy PU-^(F)PDMS matrix,steady-state sustained release of butenolide encapsulated by the compact multi-shell,bionic surface formed by the microcapsules and AgNPs,and the release of Ag^(+).The shear strength,tensile strength,and elongation at break of the PU-^(F)PDMS/MCs/Ag are 3.53 MPa,6.7 MPa,and 192.83%,respectively.Its static contact angle and sliding angle are 161.8°and 3.6°,respectively.The antibacterial rate of PU-^(F)PDMS/MCs/Ag against Escherichia coli,Staphylococcus aureus,and Candida albicans can reach 100%.Compared with glass blank,PU,PU-^(F)PDMS,PU-^(F)PDMS/Ag,and PU-^(F)PDMS/MCs,both the adhesion number and coverage percentage of chlorella adhere to PU-^(F)PDMS/MCs/Ag are the minimum values,which are 600 cell mm^(-2) and 1.53%,respectively.After 6 months of marine field test,the primer blank,PU,PU-^(F)PDMS all show different degrees of attachment by shellfish,spirorbis,al-gae and other biofouling,while the PU-^(F)PDMS/MCs/Ag coating is still not covered with biofouling,while the PU-^(F)PDMS/MCs/Ag coatings still exhibit little attachment of marine fouling.The PU-^(F)PDMS/MCs/Ag bionic anti-fouling coatings are expected to be widely used in the fields of anti-fouling,anti-icing,anti-fogging,drag reduction,self-cleaning,and antibacterial.展开更多
Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering va...Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.展开更多
BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge...BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge.Fear conditioning and extinction in animal models offer insights into its mechanisms.Our previous research indi-cates that DNA methyltransferases play a role in fear memory renewal.AIM To investigate the role of DNA methylation in the extinction of fear memory,with the goal of identifying potential strategies to enhance the efficacy of exposure therapy for fear-related disorders.METHODS This study investigated the role of DNA methylation in fear memory extinction in mice.DNA methylation was manipulated using N-phthalyl-L-tryptophan(RG108)to reduce methylation and L-methionine injections to enhance it.Neuronal activity,and dendritic spine density was measured following extinction training.RESULTS RG108 suppressed extinction,reduced spine density,and inhibited neuronal activity.Methionine injections facilitated extinction.CONCLUSION DNA methylation is crucial for fear memory extinction.Enhancing methylation may improve the efficacy of exposure therapy,offering a potential strategy to treat fear-related disorders.展开更多
Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and society.Previous studies have shown correlations between obesity,T2D...Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and society.Previous studies have shown correlations between obesity,T2D,and neurodegenera-tive diseases,including dementia.It is imperative to further understand the relation-ship between obesity,T2D,and cognitive deficits.Methods:This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet(HFD)and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross(CC)mice.The CC mice are a genetically diverse panel derived from eight inbred strains.Results:Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line,C57BL/6J.CC037 line exhibited a substantial increase in body weight on HFD,whereas line CC005 ex-hibited differing responses based on sex.Glucose tolerance tests revealed significant variations,with some lines like CC005 showing a marked increase in area under the curve(AUC)values on HFD.Organ weights,including brain,spleen,liver,and kidney,varied significantly among the lines and sexes in response to HFD.Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background.Conclusions:Our study establishes a foundation for future quantitative trait loci map-ping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease(AD),caused by obesity and T2D.The genetic components may offer new tools for early prediction and prevention.展开更多
Kawasaki disease(KD)is a significant pediatric vasculitis known for its potential to cause severe coronary artery complications.Despite the effectiveness of initial treatments,such as intravenous immunoglobulin,KD pat...Kawasaki disease(KD)is a significant pediatric vasculitis known for its potential to cause severe coronary artery complications.Despite the effectiveness of initial treatments,such as intravenous immunoglobulin,KD patients can experience long-term cardiovascular issues,as evidenced by a recent case report of an adult who suffered a ST-segment elevation myocardial infarction due to previous KD in the World Journal of Clinical Cases.This editorial emphasizes the critical need for long-term management and regular surveillance to prevent such complications.By drawing on recent research and case studies,we advocate for a structured approach to follow-up care that includes routine cardiac evaluations and preventive measures.展开更多
This study investigates the application of Learnable Memory Vision Transformers(LMViT)for detecting metal surface flaws,comparing their performance with traditional CNNs,specifically ResNet18 and ResNet50,as well as o...This study investigates the application of Learnable Memory Vision Transformers(LMViT)for detecting metal surface flaws,comparing their performance with traditional CNNs,specifically ResNet18 and ResNet50,as well as other transformer-based models including Token to Token ViT,ViT withoutmemory,and Parallel ViT.Leveraging awidely-used steel surface defect dataset,the research applies data augmentation and t-distributed stochastic neighbor embedding(t-SNE)to enhance feature extraction and understanding.These techniques mitigated overfitting,stabilized training,and improved generalization capabilities.The LMViT model achieved a test accuracy of 97.22%,significantly outperforming ResNet18(88.89%)and ResNet50(88.90%),aswell as the Token to TokenViT(88.46%),ViT without memory(87.18),and Parallel ViT(91.03%).Furthermore,LMViT exhibited superior training and validation performance,attaining a validation accuracy of 98.2%compared to 91.0%for ResNet 18,96.0%for ResNet50,and 89.12%,87.51%,and 91.21%for Token to Token ViT,ViT without memory,and Parallel ViT,respectively.The findings highlight the LMViT’s ability to capture long-range dependencies in images,an areawhere CNNs struggle due to their reliance on local receptive fields and hierarchical feature extraction.The additional transformer-based models also demonstrate improved performance in capturing complex features over CNNs,with LMViT excelling particularly at detecting subtle and complex defects,which is critical for maintaining product quality and operational efficiency in industrial applications.For instance,the LMViT model successfully identified fine scratches and minor surface irregularities that CNNs often misclassify.This study not only demonstrates LMViT’s potential for real-world defect detection but also underscores the promise of other transformer-based architectures like Token to Token ViT,ViT without memory,and Parallel ViT in industrial scenarios where complex spatial relationships are key.Future research may focus on enhancing LMViT’s computational efficiency for deployment in real-time quality control systems.展开更多
N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis a...N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.展开更多
The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because o...The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because of its straightforward,single-solution evolution framework.However,a potential draw-back of IGA is the lack of utilization of historical information,which could lead to an imbalance between exploration and exploitation,especially in large-scale DPFSPs.As a consequence,this paper develops an IGA with memory and learning mechanisms(MLIGA)to efficiently solve the DPFSP targeted at the mini-malmakespan.InMLIGA,we incorporate a memory mechanism to make a more informed selection of the initial solution at each stage of the search,by extending,reconstructing,and reinforcing the information from previous solutions.In addition,we design a twolayer cooperative reinforcement learning approach to intelligently determine the key parameters of IGA and the operations of the memory mechanism.Meanwhile,to ensure that the experience generated by each perturbation operator is fully learned and to reduce the prior parameters of MLIGA,a probability curve-based acceptance criterion is proposed by combining a cube root function with custom rules.At last,a discrete adaptive learning rate is employed to enhance the stability of the memory and learningmechanisms.Complete ablation experiments are utilized to verify the effectiveness of the memory mechanism,and the results show that this mechanism is capable of improving the performance of IGA to a large extent.Furthermore,through comparative experiments involving MLIGA and five state-of-the-art algorithms on 720 benchmarks,we have discovered that MLI-GA demonstrates significant potential for solving large-scale DPFSPs.This indicates that MLIGA is well-suited for real-world distributed flow shop scheduling.展开更多
Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitatio...Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.展开更多
(TiZrHf)_(50)Ni_(30)Cu_(20-x)Co_(x)(x=2,4,6,at%)high-entropy high-temperature shape memory alloys were fabricated by watercooled copper crucible in a magnetic levitation vacuum melting furnace,and the effects of Co co...(TiZrHf)_(50)Ni_(30)Cu_(20-x)Co_(x)(x=2,4,6,at%)high-entropy high-temperature shape memory alloys were fabricated by watercooled copper crucible in a magnetic levitation vacuum melting furnace,and the effects of Co content on microstructure and mechanical properties were investigated.The results indicate that the grain size of the alloy decreases with increasing the Co content.In the as-cast state,the alloy consists primarily of the B19′phase,with a trace of B2 phase.The fracture morphology is predominantly composed of the B19′phase,whereas the B2 phase is nearly absent.Increasing the Co content or reducing the sample dimensions(d)markedly enhance the compressive strength and ductility of the alloy.When d=2 mm,the(TiZrHf)_(50)Ni_(30)Cu_(14)Co_(6) alloy demonstrates the optimal mechanical properties,achieving a compressive strength of 2142.39±1.8 MPa and a plasticity of 17.31±0.3%.The compressive cyclic test shows that with increasing the compressive strain,the residual strain of the(TiZrHf)_(50)Ni_(30)Cu_(14)Co_(6) alloy increases while the recovery ability declines.The superelastic recovery capability of the alloy is continuously enhanced.The superelastic recovery rate increases from 1.36%to 2.12%,the residual strain rate rises from 1.79%to 5.52%,the elastic recovery rate ascends from 3.86%to 7.36%,while the total recovery rate declines from 74.48%to 63.20%.展开更多
The memory behavior in liquid crystals(LCs)that is characterized by low cost,large area,high speed,and high-density memory has evolved from a mere scientific curiosity to a technology that is being applied in a variet...The memory behavior in liquid crystals(LCs)that is characterized by low cost,large area,high speed,and high-density memory has evolved from a mere scientific curiosity to a technology that is being applied in a variety of commodities.In this study,we utilized molybdenum disulfide(MoS_(2))nanoflakes as the vip in a homotropic LCs host to modulate the overall memory effect of the hybrid.It was found that the MoS₂nanoflakes within the LCs host formed agglomerates,which in turn resulted in an accelerated response of the hybrids to the external electric field.However,this process also resulted in a slight decrease in the threshold voltage.Additionally,it was observed that MoS₂nanoflakes in a LCs host tend to align homeotropically under an external electric field,thereby accelerating the refreshment of the memory behavior.The incorporation of a mass fraction of 0.1%2μm MoS₂nanoflakes into the LCs host was found to significantly reduce the refreshing memory behavior in the hybrid to 94.0 s under an external voltage of 5 V.These findings illustrate the efficacy of regulating the rate of memory behavior for a variety of potential applications.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
基金funded by the National Natural Science Foundation of China(32072486 and 31971424)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20240511)。
文摘To ensure the reliability of learned information,most insects require multiple intervals of experience before storing the information as long-term memory(LTM),and this requirement has been validated in insects from the behavioral to the molecular level.Recent studies have shown that some insects can form LTM after one-trial experience,although the mechanisms underlying one-trial LTM formation are not well understood.Therefore,understanding the mechanisms underlying rapid learning and subsequent preference formation in insects is crucial.Here we show that the agricultural pest Bactrocera dorsalis can rapidly form LTM,which is dependent on protein synthesis,and that the formation of LTM requires high energy support at the cost of reduced survival.Furthermore,based on a liquid chromatography-mass spectrometry(LC-MS)metabolomics approach,we found that LTM-related processes are sequentially coupled to two processes for energy generation,the TCA cycle and oxidative phosphorylation.This was further confirmed by blocking these energy generation processes.Our results provide a theoretical basis for the development of behavioral modulators in oriental fruit flies that target energy generation metabolites,as well as a new perspective on the rapid formation of LTM in insects.
基金supported by the Russian science foundation(grant#22-74-00115 to A.P.G.).
文摘Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:To investigate mitochondrial damage and the effects of resveratrol on inflammation,cognitive function,and mitochondrial quality control in APP/PS1 mice.Methods:Comparative analysis of mitochondrial DNA(mtDNA)damage was conducted between 10-month-old APP/PS1 mice and age-matched C57BL/6 mice.Assessments included measurement of amyloid-βlevels,inflammatory markers,swimming distance in the Morris water maze,and gut microbiome composition.Resveratrol’s effects on cytokine expression,mtDNA levels in plasma,and activation of Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)and phosphoinositide 3-kinase/protein kinase B(also known as Akt)/mechanistic target of rapamycin complex 1(PI3K/Akt/mTORC1)signaling pathways were also evaluated.Results:APP/PS1 mice exhibited significantly increased mtDNA damage in the prefrontal cortex,midbrain,and cerebellum,alongside higher amyloid-βlevels and inflammatory markers.Resveratrol treatment led to reduced expression of pro-inflammatory cytokines,a decrease in Proteobacteria levels,and lower cell-free mtDNA in plasma.Partial improvement in long-term spatial memory was observed in APP/PS1 mice following resveratrol treatment,likely due to its anti-inflammatory properties.Activation of the Nrf2/ARE signaling pathway and markers of PI3K/Akt/mTORC1 axis activation were noted,with the latter regulating long-term potentiation.Conclusion:Resveratrol demonstrates potential in mitigating inflammation and improving mitochondrial quality control in APP/PS1 mice,but it does not reduce amyloid-βlevels,highlighting the complexity of AD pathology and the need for further research.
文摘Objective To evaluate whether the thermotaxis tracking model is suitable for assessing long-term memory （LTM） in the nematode Caenorhabditis elegans. Methods Animals were trained at 20℃ overnight in presence of food. The percentage of animals performing isothermal tracking （IT） behavior was measured at different time intervals after the training. Results The percentage of animals performing IT behavior, the numbers of body bends inside and outside the training temperature, and the expression patterns of AFD and AIY neurons were similar to those in control animals at 36 and 48 h after training; whereas when extending to 60, 72, and 84 h, locomotory behavior defects were observed in the assayed animals, suggesting that this thermal tracking model is feasible for analyzing LTM at 36 and 48 h after training. Moreover, the percent-age of animals performing IT behavior was reduced at 18, 36, and 48 h after training in neuronal calcium sensor-1 gene （nsc-1） mutant animals compared with that in wild-type N2 animals. In addition, exposure to plumbum （Pb） significantly repressed the LTM at 18, 36, and 48 h after training in both wild-type N2 and ncs-1 mutant animals. Conclusion The thermotaxis tracking model is suitable for evaluating the LTM regulated by NCS-1, and can be employed for elucidating regulatory functions of specific genes or effects of stimuli on memory in C. elegans.
基金supported by the National Natural Science Foundation of China grant number 41675088the CAS Pioneer Hundred Talents Program。
文摘Long-term memory(LTM)in the climate system has been well recognized and applied in different research fields,but the origins of this property are still not clear.In this work,the authors contribute to this issue by studying model simulations under different scenarios.The global mean temperatures from pre-industrial control runs(pi Control),historical(all forcings)simulations,natural forcing only simulations(Historical Nat),greenhouse gas forcing only simulations(Historical GHG),etc.,are analyzed using the detrended fluctuation analysis.The authors find that the LTM already exists in the pi Control simulations,indicating the important roles of internal natural variability in producing the LTM.By comparing the results among different scenarios,the LTM from the piControl runs is further found to be strengthened by adding natural forcings such as the volcanic forcing and the solar forcing.Accordingly,the observed LTM in the climate system is suggested to be mainly controlled by both the‘internal’natural variability and the‘external’natural forcings.The anthropogenic forcings,however,may weaken the LTM.In the projections from RCP2.6 to RCP8.5,a weakening trend of the LTM strength is found.In view of the close relations between the climate memory and the climate predictability,a reduced predictability may be expected in a warming climate.
基金Supported by National Natural Science Foundation of China:81473785Project of National Veteran TCM Expert Inheritance Studio
文摘Objective: To observe the effects on spatial long-term memory in the rats with vascular dementia(VD)treated with moxibustion for resolving stasis and promoting meridian circulation.Methods: The modified 2-vascular occlusion(2-VO) method was used to prepare VD animal model. The rats were randomized into a sham-operation group, a model group, a moxibustion group and a western medication group, 15 rats in each one. In the moxibustion group, mild warm moxibustion was applied to"Bǎihuì(百会 GV 20)" "DàZhuī(大椎 GV 14)" and "Shéntíng(神庭 GV 24)". 20 min at each point, once a day, for 3 weeks consecutively. In the western medicaion group, mouse nerve growth factor(NGF) was injected intraperitoneally, 0.18 mL/kg, once a day, for 3 weeks consecutively. Morris water maze test was used, the time of the first passing platform, the frequency of passing-platform and swimming speed in120 s were determined of the rats in each group. Western blot were used to test the protein expressions of hippocampal Nestin and DCX.Results: At the end of three courses of treatment, compared with sham-operation group, the difference was not significant statistically in swimming speed in the model group, the moxibustion group and the western medication group separately(all P>0.05). Three days after modeling, the mean of escape latency was prolonged obviously in the modeled rats compared with the rats in the shamoperation group(88.84 ± 19.94 vs 18.15 ±9.41, P< 0.01). At the end of three courses of treatment, compared with the sham-operation group(22.01 ± 10.07), the mean of escape latency was different statistically in the model group(89.18± 19.70), the moxibustion group(37.21 ±13.31) and the western medication group separately(51.50± 16.15), all P<0.01. Compared with the model group, the mean of escape latency was shortened in the moxibustion group and western medication group respectively(37.21 ± 13.31 vs89.18 ± 19.70, 51.50 ± 16.15 vs 89.18 ± 19.70, both P< 0.01). Compared with the western medication group,there was no statistical significant difference in the mean of escape latency in the moxibustion group(37.21 ± 13.31 vs 51.50 ±16.15, P> 0.05). Compared with the sham-operation group, the frequency of passing-platform was decreased in the model group(0.73 ±0.96 vs 2.60 ±1.45, P<0.01); compared with model group, the frequency of passing-platform was increased in the moxibustion group and the western medicine group and the statistically significant difference presented in the moxibustion group(2.06 ± 1.33 vs 0.73 ±0.96, P<0.01). Compared with the sham-operation group, the time of first passing-platform was prolonged in the model group(87.86 ± 33.25 vs 36.13 +29.76, P< 0.01). Compared with the model group,the time of first passing-platform was shortened in the moxibustion group and the western medicine group respectively(49.53 ±29.48 vs 87.86 ± 33.25.P< 0.01; 58.98 ± 36.22 vs 87.86 ±33.25, P< 0.05). After three courses of treatment, compared with the sham-operation group, Nestin expression was reduced in the model group,(0.33 ±0.12 vs 0.51 ±0.02, P<0.05) and was increased in the moxibustion group and the western medication group respectively(1.33 ± 0.17 vs 0.51 ± 0.02. 1.39 ± 0.10 vs 0.51 ±0.02, both P< 0.01).Compared with the model group, Nestin expression was increased in the moxibustion group and the western medication group, respectively(1.33 ± 0.17 vs 0.33±0.12. 1.39±0.10 vs 0.33 ±0.12, both P< 0.01).Compared with the western medication group, the difference was not significant statistically in the moxibustion group(1.33±0.17 vs 1.39±0.10, P>0.05). After three courses of treatment, compared with the sham-operation group, DCX expression was decreased in the model group, but without significant difference(0.44±0.20 vs 0.51 ±0.26, P> 0.05), the expression was increased in the moxibustion group and the western medication group respectively(0.98±0.25 vs 0.51±0.26. P< 0.05; 1.11±0.43 vs 0.51 ±0.26,P<0.01). Compared with the model group, DCX expression was obviously increased in the moxibustion group and the western medication group(0.98 ± 0.25 vs 0.44 ± 0.20. 1.11 ± 0.43 vs 0.44 ± 0.20, both P<0.01). The difference in DCX expression was not statistically significant between the western medication group and the moxibustion group(0.98 ± 0.25 vs 1.11 ± 0.43. P> 0.05).Conclusion: Moxibustion apparently improves the long-term memory in VD rats.
文摘To investigate effects and possible mechanism of Ro 20-1724, a PDE4 inhibitor, on long-time learning and memory ability following repeated ketamine exposure in immature rats. Methods: Sixty 21-day-old SD rats were randomly divided into five groups (n = 12): C: Normal control group, S: Saline control group, K: Ketamine, K + Ro:?Ketamine + Ro 20-1724, K + E: Ketamine + ethanol vehicle. Ro 20-1724 (0.5 mg·kg-1) or its vehicle (ethanol) was administered intraperitoneally 30 minutes after ketamine anesthesia (70 mg·kg-1), daily for seven days. Nine weeks after birth, the Morris water maze was used to test the ability of learning and spatial localization memory on the rats. Following behavioral testing, animals’ hippocampi were removed for Western blot and electron microscopic examination. Results: In the Morris water maze test, compared with controls, the escape latency in groups exposed to ketamine or ketamine plus the ethanol vehicle were significantly prolonged (P P < 0.05), and the expression of p-CREB in the hippocampus was also decreased (P 0.05), while there was no significant difference between control groups and animals treated with Ro 20-1724 following ketamine exposure (P > 0.05). Electron microscopy demonstrated degenerative changes in hippocampal neurons of animals repetitively exposed to 70 mg·kg-1 Ketamine, which was ameliorated by Ro 20-1724 (0.5 mg·kg-1). Conclusion: The PDE-4 inhibitor Ro 20-1724 (0.5 mg·kg-1<span
基金National Natural Science Foundation of China(62171305,62405206,62004135,62001317,62111530301)Natural Science Foundation of Jiangsu Province(BK20240778,BK20241917)+3 种基金State Key Laboratory of Advanced Optical Communication Systems and Networks,China(2023GZKF08)China Postdoctoral Science Foundation(2024M752314)Postdoctoral Fellowship Program of CPSF(GZC20231883)Innovative and Entrepreneurial Talent Program of Jiangsu Province(JSSCRC2021527).
文摘Photonic platforms are gradually emerging as a promising option to encounter the ever-growing demand for artificial intelligence,among which photonic time-delay reservoir computing(TDRC)is widely anticipated.While such a computing paradigm can only employ a single photonic device as the nonlinear node for data processing,the performance highly relies on the fading memory provided by the delay feedback loop(FL),which sets a restriction on the extensibility of physical implementation,especially for highly integrated chips.Here,we present a simplified photonic scheme for more flexible parameter configurations leveraging the designed quasi-convolution coding(QC),which completely gets rid of the dependence on FL.Unlike delay-based TDRC,encoded data in QC-based RC(QRC)enables temporal feature extraction,facilitating augmented memory capabilities.Thus,our proposed QRC is enabled to deal with time-related tasks or sequential data without the implementation of FL.Furthermore,we can implement this hardware with a low-power,easily integrable vertical-cavity surface-emitting laser for high-performance parallel processing.We illustrate the concept validation through simulation and experimental comparison of QRC and TDRC,wherein the simpler-structured QRC outperforms across various benchmark tasks.Our results may underscore an auspicious solution for the hardware implementation of deep neural networks.
基金supported by the National Natural Science Foundation of China(Nos.52003148 and 52261045)the State Key Laboratory of Marine Resource Utilization in South China Sea,Hainan University(No.MRUKF2021023)+3 种基金the Key Research and Development Project of Shaanxi Province(No.2023-YBGY-475)the Key Scientific Research Project of Education Department of Shaanxi Province(No.22JS003)the Industrialization Project of the State Key Laboratory of Biological Resources and Ecological Environment(Cultivation)of Qinba Region(No.SXC-2310)the key cultivation project funds of Shaanxi University of Technology(No.SLGKYXM2201).
文摘Polyurethane-fluorinated polysiloxane(PU-^(F)PDMS)with high-strength,high-bonding and low surface en-ergy is synthesized as the matrix,and the PU-^(F)PDMS/MCs/Ag marine anti-fouling coating on the sur-face of imitation crab shells is constructed by assembling butenolide@1,1-stilbene-modified hydrolyzed polyglycidyl methacrylate/graphene oxide microcapsules(Bu@PGMAm/GO MCs)with compact multi-shell structure and Ag nanoparticles(AgNPs)step by step on the PU-^(F)PDMS matrix.The PU-^(F)PDMS/MCs/Ag bionic anti-fouling coatings achieve long-term and stable anti-fouling effect under the combination of robust low-surface-energy PU-^(F)PDMS matrix,steady-state sustained release of butenolide encapsulated by the compact multi-shell,bionic surface formed by the microcapsules and AgNPs,and the release of Ag^(+).The shear strength,tensile strength,and elongation at break of the PU-^(F)PDMS/MCs/Ag are 3.53 MPa,6.7 MPa,and 192.83%,respectively.Its static contact angle and sliding angle are 161.8°and 3.6°,respectively.The antibacterial rate of PU-^(F)PDMS/MCs/Ag against Escherichia coli,Staphylococcus aureus,and Candida albicans can reach 100%.Compared with glass blank,PU,PU-^(F)PDMS,PU-^(F)PDMS/Ag,and PU-^(F)PDMS/MCs,both the adhesion number and coverage percentage of chlorella adhere to PU-^(F)PDMS/MCs/Ag are the minimum values,which are 600 cell mm^(-2) and 1.53%,respectively.After 6 months of marine field test,the primer blank,PU,PU-^(F)PDMS all show different degrees of attachment by shellfish,spirorbis,al-gae and other biofouling,while the PU-^(F)PDMS/MCs/Ag coating is still not covered with biofouling,while the PU-^(F)PDMS/MCs/Ag coatings still exhibit little attachment of marine fouling.The PU-^(F)PDMS/MCs/Ag bionic anti-fouling coatings are expected to be widely used in the fields of anti-fouling,anti-icing,anti-fogging,drag reduction,self-cleaning,and antibacterial.
基金supported by grants from the Medical Engineering Jiont Fund of the Fudan University(No.IDH2310117)。
文摘Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.
基金Supported by National Natural Science Foundation of China,No.82360231Yunnan Basic Research Program General Project,No.202401AT070075+1 种基金Dali Basic Research Program Key Project,No.202301A020021Youth Special Project for Basic Research of Local Universities in Yunnan Province,No.202301BA070001-127.
文摘BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge.Fear conditioning and extinction in animal models offer insights into its mechanisms.Our previous research indi-cates that DNA methyltransferases play a role in fear memory renewal.AIM To investigate the role of DNA methylation in the extinction of fear memory,with the goal of identifying potential strategies to enhance the efficacy of exposure therapy for fear-related disorders.METHODS This study investigated the role of DNA methylation in fear memory extinction in mice.DNA methylation was manipulated using N-phthalyl-L-tryptophan(RG108)to reduce methylation and L-methionine injections to enhance it.Neuronal activity,and dendritic spine density was measured following extinction training.RESULTS RG108 suppressed extinction,reduced spine density,and inhibited neuronal activity.Methionine injections facilitated extinction.CONCLUSION DNA methylation is crucial for fear memory extinction.Enhancing methylation may improve the efficacy of exposure therapy,offering a potential strategy to treat fear-related disorders.
文摘Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and society.Previous studies have shown correlations between obesity,T2D,and neurodegenera-tive diseases,including dementia.It is imperative to further understand the relation-ship between obesity,T2D,and cognitive deficits.Methods:This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet(HFD)and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross(CC)mice.The CC mice are a genetically diverse panel derived from eight inbred strains.Results:Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line,C57BL/6J.CC037 line exhibited a substantial increase in body weight on HFD,whereas line CC005 ex-hibited differing responses based on sex.Glucose tolerance tests revealed significant variations,with some lines like CC005 showing a marked increase in area under the curve(AUC)values on HFD.Organ weights,including brain,spleen,liver,and kidney,varied significantly among the lines and sexes in response to HFD.Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background.Conclusions:Our study establishes a foundation for future quantitative trait loci map-ping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease(AD),caused by obesity and T2D.The genetic components may offer new tools for early prediction and prevention.
文摘Kawasaki disease(KD)is a significant pediatric vasculitis known for its potential to cause severe coronary artery complications.Despite the effectiveness of initial treatments,such as intravenous immunoglobulin,KD patients can experience long-term cardiovascular issues,as evidenced by a recent case report of an adult who suffered a ST-segment elevation myocardial infarction due to previous KD in the World Journal of Clinical Cases.This editorial emphasizes the critical need for long-term management and regular surveillance to prevent such complications.By drawing on recent research and case studies,we advocate for a structured approach to follow-up care that includes routine cardiac evaluations and preventive measures.
基金funded by Woosong University Academic Research 2024.
文摘This study investigates the application of Learnable Memory Vision Transformers(LMViT)for detecting metal surface flaws,comparing their performance with traditional CNNs,specifically ResNet18 and ResNet50,as well as other transformer-based models including Token to Token ViT,ViT withoutmemory,and Parallel ViT.Leveraging awidely-used steel surface defect dataset,the research applies data augmentation and t-distributed stochastic neighbor embedding(t-SNE)to enhance feature extraction and understanding.These techniques mitigated overfitting,stabilized training,and improved generalization capabilities.The LMViT model achieved a test accuracy of 97.22%,significantly outperforming ResNet18(88.89%)and ResNet50(88.90%),aswell as the Token to TokenViT(88.46%),ViT without memory(87.18),and Parallel ViT(91.03%).Furthermore,LMViT exhibited superior training and validation performance,attaining a validation accuracy of 98.2%compared to 91.0%for ResNet 18,96.0%for ResNet50,and 89.12%,87.51%,and 91.21%for Token to Token ViT,ViT without memory,and Parallel ViT,respectively.The findings highlight the LMViT’s ability to capture long-range dependencies in images,an areawhere CNNs struggle due to their reliance on local receptive fields and hierarchical feature extraction.The additional transformer-based models also demonstrate improved performance in capturing complex features over CNNs,with LMViT excelling particularly at detecting subtle and complex defects,which is critical for maintaining product quality and operational efficiency in industrial applications.For instance,the LMViT model successfully identified fine scratches and minor surface irregularities that CNNs often misclassify.This study not only demonstrates LMViT’s potential for real-world defect detection but also underscores the promise of other transformer-based architectures like Token to Token ViT,ViT without memory,and Parallel ViT in industrial scenarios where complex spatial relationships are key.Future research may focus on enhancing LMViT’s computational efficiency for deployment in real-time quality control systems.
基金supported by the Natural Science Foundation of Heilongjiang Province of China,Outstanding Youth Foundation,No.YQ2022H003 (to DW)。
文摘N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.
基金supported in part by the National Key Research and Development Program of China under Grant No.2021YFF0901300in part by the National Natural Science Foundation of China under Grant Nos.62173076 and 72271048.
文摘The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because of its straightforward,single-solution evolution framework.However,a potential draw-back of IGA is the lack of utilization of historical information,which could lead to an imbalance between exploration and exploitation,especially in large-scale DPFSPs.As a consequence,this paper develops an IGA with memory and learning mechanisms(MLIGA)to efficiently solve the DPFSP targeted at the mini-malmakespan.InMLIGA,we incorporate a memory mechanism to make a more informed selection of the initial solution at each stage of the search,by extending,reconstructing,and reinforcing the information from previous solutions.In addition,we design a twolayer cooperative reinforcement learning approach to intelligently determine the key parameters of IGA and the operations of the memory mechanism.Meanwhile,to ensure that the experience generated by each perturbation operator is fully learned and to reduce the prior parameters of MLIGA,a probability curve-based acceptance criterion is proposed by combining a cube root function with custom rules.At last,a discrete adaptive learning rate is employed to enhance the stability of the memory and learningmechanisms.Complete ablation experiments are utilized to verify the effectiveness of the memory mechanism,and the results show that this mechanism is capable of improving the performance of IGA to a large extent.Furthermore,through comparative experiments involving MLIGA and five state-of-the-art algorithms on 720 benchmarks,we have discovered that MLI-GA demonstrates significant potential for solving large-scale DPFSPs.This indicates that MLIGA is well-suited for real-world distributed flow shop scheduling.
基金supported by STI2030-Major Projects,No.2022ZD0207600(to LZ)the National Natural Science Foundation of China,Nos.32070955(to LZ),U22A20301(to KFS)+3 种基金the Natural Science Foundation of Guangdong Province,No.2021A1515012197(to HO)Guangzhou Core Medical Disciplines Project,No.2021-2023(to HO)Key Research and Development Plan of Ningxia Hui Automomous Region,No.2022BEG01004(to KFS)Science and Technology Program of Guangzhou,China,No.202007030012(to KFS and LZ)。
文摘Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.
基金National Natural Science Foundation of China(12404230,52061027)Science and Technology Program Project of Gansu Province(22YF7GA155)+1 种基金Lanzhou Youth Science and Technology Talent Innovation Project(2023-QN-91)Zhejiang Provincial Natural Science Foundation of China(LY23E010002)。
文摘(TiZrHf)_(50)Ni_(30)Cu_(20-x)Co_(x)(x=2,4,6,at%)high-entropy high-temperature shape memory alloys were fabricated by watercooled copper crucible in a magnetic levitation vacuum melting furnace,and the effects of Co content on microstructure and mechanical properties were investigated.The results indicate that the grain size of the alloy decreases with increasing the Co content.In the as-cast state,the alloy consists primarily of the B19′phase,with a trace of B2 phase.The fracture morphology is predominantly composed of the B19′phase,whereas the B2 phase is nearly absent.Increasing the Co content or reducing the sample dimensions(d)markedly enhance the compressive strength and ductility of the alloy.When d=2 mm,the(TiZrHf)_(50)Ni_(30)Cu_(14)Co_(6) alloy demonstrates the optimal mechanical properties,achieving a compressive strength of 2142.39±1.8 MPa and a plasticity of 17.31±0.3%.The compressive cyclic test shows that with increasing the compressive strain,the residual strain of the(TiZrHf)_(50)Ni_(30)Cu_(14)Co_(6) alloy increases while the recovery ability declines.The superelastic recovery capability of the alloy is continuously enhanced.The superelastic recovery rate increases from 1.36%to 2.12%,the residual strain rate rises from 1.79%to 5.52%,the elastic recovery rate ascends from 3.86%to 7.36%,while the total recovery rate declines from 74.48%to 63.20%.
文摘The memory behavior in liquid crystals(LCs)that is characterized by low cost,large area,high speed,and high-density memory has evolved from a mere scientific curiosity to a technology that is being applied in a variety of commodities.In this study,we utilized molybdenum disulfide(MoS_(2))nanoflakes as the vip in a homotropic LCs host to modulate the overall memory effect of the hybrid.It was found that the MoS₂nanoflakes within the LCs host formed agglomerates,which in turn resulted in an accelerated response of the hybrids to the external electric field.However,this process also resulted in a slight decrease in the threshold voltage.Additionally,it was observed that MoS₂nanoflakes in a LCs host tend to align homeotropically under an external electric field,thereby accelerating the refreshment of the memory behavior.The incorporation of a mass fraction of 0.1%2μm MoS₂nanoflakes into the LCs host was found to significantly reduce the refreshing memory behavior in the hybrid to 94.0 s under an external voltage of 5 V.These findings illustrate the efficacy of regulating the rate of memory behavior for a variety of potential applications.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
