Safety automation of complex mobile systems is a current topic issue in industry and research laboratories,especially in aeronautics.The dynamic models of these systems are nonlinear,Multi-Input Multi-Output(MIMO)and ...Safety automation of complex mobile systems is a current topic issue in industry and research laboratories,especially in aeronautics.The dynamic models of these systems are nonlinear,Multi-Input Multi-Output(MIMO)and tightly coupled.The nonlinearity resides in the dynamic equations and also in the aerodynamic coefficients’variability.This paper is devoted to developing the piloting law based on the combination of the robust differentiator with a dynamic adaptation of the gains and the robust controller via second order sliding mode,by using an aircraft in virtual simulated environments.To deal with the design of an autopilot controller,we propose an environment framework based on a Software In the Loop(SIL)methodology and we use Microsoft Flight Simulator(FS-2004)as the environment for plane simulation.The first order sliding mode control may be an appropriate solution to this piloting problem.However,its implementation generates a chattering phenomenon and a singularity problem.To overcome these problems,a new version of the adaptive differentiators for second order sliding modes is proposed and used for piloting.For the sliding mode algorithm,higher gains values may be used to improve accuracy;however this leads to an amplification of noise in the estimated signals.A good tradeoff between these two criteria(accuracy,robustness to noise ratio)is difficult to achieve.On the one hand,these values must increase the gains in order to derive a signal sweeping of some frequency ranges.On the other hand,low gains values have to be imposed to reduce noise amplification.So,our goal is to develop a differentiation algorithm in order to have a good compromise between error and robustness to noise ratio.To fit this requirement,a new version of differentiators with a higher order sliding modes and a dynamic adaptation of the gains,is proposed:the first order differentiator for the control of longitudinal speed and the second order differentiator for the control of the Euler angles.展开更多
We theoretically propose a multifunctional photonic differentiation （DIFF） scheme based on phase demodulation using two cascaded linear filters. The photonic D1FF has a diversity of output forms, such as the 1 st or...We theoretically propose a multifunctional photonic differentiation （DIFF） scheme based on phase demodulation using two cascaded linear filters. The photonic D1FF has a diversity of output forms, such as the 1 st order intensity DIFF, the 1 st order field DIFF and its inversion, and the 2nd-order field DIFF, depending on the relative shift between the optical carrier and the filter＇s resonant notches. As a proof, we also experimentally demonstrate the DIFF diversity using a phase modulator and two delay interferometers （Dis）. The calculated average deviation is less than 7% for all DIFF waveforms. Our schemes show the advantages of flexible DIFF functions and forms, which may have different optical applications. For example, high order field differentiators can be used to generate complex temporal waveforms, and intensity differentiators are useful for the ultra-wideband pulse generation.展开更多
This paper deals with Mckean-Vlasov backward stochastic differential equations with weak monotonicity coefficients.We first establish the existence and uniqueness of solutions to Mckean-Vlasov backward stochastic diff...This paper deals with Mckean-Vlasov backward stochastic differential equations with weak monotonicity coefficients.We first establish the existence and uniqueness of solutions to Mckean-Vlasov backward stochastic differential equations.Then we obtain a comparison theorem in one-dimensional situation.展开更多
The generation of synthetic trajectories has become essential in various fields for analyzing complex movement patterns.However,the use of real-world trajectory data poses significant privacy risks,such as location re...The generation of synthetic trajectories has become essential in various fields for analyzing complex movement patterns.However,the use of real-world trajectory data poses significant privacy risks,such as location reidentification and correlation attacks.To address these challenges,privacy-preserving trajectory generation methods are critical for applications relying on sensitive location data.This paper introduces DPIL-Traj,an advanced framework designed to generate synthetic trajectories while achieving a superior balance between data utility and privacy preservation.Firstly,the framework incorporates Differential Privacy Clustering,which anonymizes trajectory data by applying differential privacy techniques that add noise,ensuring the protection of sensitive user information.Secondly,Imitation Learning is used to replicate decision-making behaviors observed in real-world trajectories.By learning from expert trajectories,this component generates synthetic data that closely mimics real-world decision-making processes while optimizing the quality of the generated trajectories.Finally,Markov-based Trajectory Generation is employed to capture and maintain the inherent temporal dynamics of movement patterns.Extensive experiments conducted on the GeoLife trajectory dataset show that DPIL-Traj improves utility performance by an average of 19.85%,and in terms of privacy performance by an average of 12.51%,compared to state-of-the-art approaches.Ablation studies further reveal that DP clustering effectively safeguards privacy,imitation learning enhances utility under noise,and the Markov module strengthens temporal coherence.展开更多
BACKGROUND The treatment technology of liver cancer is progressing.In addition to traditional surgical resection,combined therapies of immunotherapy based on immune checkpoint inhibitors,chemotherapy,and transcatheter...BACKGROUND The treatment technology of liver cancer is progressing.In addition to traditional surgical resection,combined therapies of immunotherapy based on immune checkpoint inhibitors,chemotherapy,and transcatheter arterial chemoembolization for hepatocellular carcinoma are more and more widely used.Accurate preoperative diagnosis of liver cancer will provide important information for comprehensive treatment and prognosis evaluation of liver cancer.Sonazoidcontrast-enhanced ultrasound is not only helpful for the qualitative diagnosis of liver lesions,but also has great potential in the diagnosis of histological differentiation of liver cancer.AIM To assess the differentiation of hepatocellular carcinoma(HCC)by utilizing the parameters and imaging features of Sonazoid-contrast-enhanced ultrasound(CEUS).METHODS A retrospective analysis was conducted on the CEUS data of 239 lesions through case-control study.These patients received Sonazoid-CEUS within one week before surgery and were confirmed as HCC by postoperative pathology.Within the cases,patients were further categorized into well-differentiated and poorlydifferentiated group.Time-intensity curves of the region of interest in both arterial and Kupffer phases were generated,allowing for the acquisition of quantitative parameters to assess the diagnostic efficacy in distinguishing lesions between these two groups and determining an appropriate cut-off value.RESULTS Univariate analysis showed that the absolute value of enhancement intensity(EIAV),intensity ratio(IR)and intensity difference(ID)in Kupffer phase were statistically different between the groups with different degree(P=0.015,P=0.000,P=0.000).The sensitivity and specificity were 40.2%,82.4%,80.4% and 78.1%,86.9% and 74.5%,respectively,for differentiating HCC lesions with EIAV≥56.384 dB,IR≥1.215 and ID≥9.184 dB.The area under the receiver operating characteristic curve were 0.590,0.877,0.815.There was no significant difference in the parameters of arterial phase,including peak time,initial growth time,rise time and the absolute value of peak intensity of lesions between the two groups(P>0.05).Multivariate analysis showed that the level of alphafetoprotein(AFP)and IR were risk factors for poor differentiation(P=0.001).CONCLUSION Among the parameters of Sonazoid-CEUS,IR in Kupffer phase exhibits superior diagnostic efficacy with high sensitivity and specificity in the diagnose of pathological differentiation of HCC.Combined with preoperative AFP level,a more accurate diagnosis will be obtained.Compared with portal vein phase,Kupffer phase showed the ability to identify HCC lesions more sensitive.These findings hold significant guiding implications and reference value for clinical practice.展开更多
Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrins...Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrinsic mechanisms underlying the decision of a stem cell to proliferate,enter a dormant quiescent state or differentiate into a specific cell type remains incompletely understood.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention...BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention for its role in influencing their function,accessibility,and readiness for clinical use.AIM To identify the most suitable adipose source for MSC isolation and expansion for further applications.METHODS We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method.The MSCs were examined for their expansion using population doubling time,differentiation capacity using multilineage differentiation induction,surface markers using flow cytometry,and stability of chromosomes using the karyotyping method.Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.RESULTS MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2.All adipose-derived MSCs(AD-MSCs)exhibited the typical elongated,spindle-shaped morphology and comparable proliferation rate.They expressed positive surface markers(cluster of differentiation 73[CD73]:>97%,CD90:>98%,and CD105:>95%),and negative markers(<1%).All MSCs expressed similar levels of stemness genes(octamer-binding transcription factor 4,SRY-box 2,Krüppel-like factor,and MYC),colonyforming,and trilineage differentiation potential.Karyotyping analysis revealed normal chromosomal patterns in all samples,except one sample exhibiting a polymorphism(1qh+).Furthermore,the growth factors and cytokines of hepatocyte growth factor,vascular endothelial growth factor A,interleukin 6(IL-6),and IL-8 were detected in all AD-MSC conditioned media;but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs,respectively.CONCLUSION These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences,which are suitable for further expansion and various clinical applications.展开更多
AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induc...AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplanta...Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.展开更多
The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble dif...The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.展开更多
Optimizing the microchannel design of the next generation of chips requires an understanding of the in situ property evolution of the chip-based materials under fast cooling.This work overcomes the conventional relian...Optimizing the microchannel design of the next generation of chips requires an understanding of the in situ property evolution of the chip-based materials under fast cooling.This work overcomes the conventional reliance on reheating data of melt-quenched glasses by demonstrating direct observations of glass transition on cooling curves utilizing the most advanced fast differential scanning calorimetry.By leveraging an MEMS chip sensor that allows for rapid heat extraction from microgram-sized samples to a purged gas coolant,the device is able to reach ultra-fast cooling rates of up to 40,000 K·s^(−1).Four thermal regions are identified by examining the cooling behaviors of two metallic glasses.This is because the actual rate of the specimen can differ from the programmed rate,especially at high set rate when the actual rate decreases before the glass transition is completed.We define the operational window for reliable cooling curve analysis,build models with empirical and theoretical analyses to determine the maximum feasible cooling rate,and demonstrate how optimizing sample mass and environment temperature broaden this window.The method avoids deceptive structural relaxation effects verified by fictivetemperature analysis and permits the capture of full glass transition during cooling.展开更多
In order to better describe the phenomenon of biological invasion,this paper introduces a free boundary model of biological invasion.Firstly,the right free boundary is added to the equation with logistic terms.Secondl...In order to better describe the phenomenon of biological invasion,this paper introduces a free boundary model of biological invasion.Firstly,the right free boundary is added to the equation with logistic terms.Secondly,the existence and uniqueness of local solutions are proved by the Sobolev embedding theorem and the comparison principle.Finally,according to the relevant research data and contents of red fire ants,the diffusion area and nest number of red fire ants were simulated without external disturbance.This paper mainly simulates the early diffusion process of red fire ants.In the early diffusion stage,red fire ants grow slowly and then spread over a large area after reaching a certain number.展开更多
The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and contin...The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.展开更多
A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to ...A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.展开更多
Precisely estimating the state of health(SOH)of lithium-ion batteries is essential for battery management systems(BMS),as it plays a key role in ensuring the safe and reliable operation of battery systems.However,curr...Precisely estimating the state of health(SOH)of lithium-ion batteries is essential for battery management systems(BMS),as it plays a key role in ensuring the safe and reliable operation of battery systems.However,current SOH estimation methods often overlook the valuable temperature information that can effectively characterize battery aging during capacity degradation.Additionally,the Elman neural network,which is commonly employed for SOH estimation,exhibits several drawbacks,including slow training speed,a tendency to become trapped in local minima,and the initialization of weights and thresholds using pseudo-random numbers,leading to unstable model performance.To address these issues,this study addresses the challenge of precise and effective SOH detection by proposing a method for estimating the SOH of lithium-ion batteries based on differential thermal voltammetry(DTV)and an SSA-Elman neural network.Firstly,two health features(HFs)considering temperature factors and battery voltage are extracted fromthe differential thermal voltammetry curves and incremental capacity curves.Next,the Sparrow Search Algorithm(SSA)is employed to optimize the initial weights and thresholds of the Elman neural network,forming the SSA-Elman neural network model.To validate the performance,various neural networks,including the proposed SSA-Elman network,are tested using the Oxford battery aging dataset.The experimental results demonstrate that the method developed in this study achieves superior accuracy and robustness,with a mean absolute error(MAE)of less than 0.9%and a rootmean square error(RMSE)below 1.4%.展开更多
Metabolomics covers a wide range of applications in life sciences,biomedicine,and phytology.Data acquisition(to achieve high coverage and efficiency)and analysis(to pursue good classification)are two key segments invo...Metabolomics covers a wide range of applications in life sciences,biomedicine,and phytology.Data acquisition(to achieve high coverage and efficiency)and analysis(to pursue good classification)are two key segments involved in metabolomics workflows.Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups.However,insufficient feature extraction,inappropriate feature selection,overfitting,or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused.Using two ginseng varieties,namely Panax japonicus(PJ)and Panax japonicus var.major(PJvm),containing the similar ginsenosides,we integrated pseudo-targeted metabolomics and deep neural network(DNN)modeling to achieve accurate species differentiation.A pseudo-targeted metabolomics approach was optimized through data acquisition mode,ion pairs generation,comparison between multiple reaction monitoring(MRM)and scheduled MRM(sMRM),and chromatographic elution gradient.In total,1980 ion pairs were monitored within 23 min,allowing for the most comprehensive ginseng metabolome analysis.The established DNN model demonstrated excellent classification performance(in terms of accuracy,precision,recall,F1 score,area under the curve,and receiver operating characteristic(ROC))using the entire metabolome data and feature-selection dataset,exhibiting superior advantages over random forest(RF),support vector machine(SVM),extreme gradient boosting(XGBoost),and multilayer perceptron(MLP).Moreover,DNNs were advantageous for automated feature learning,nonlinear modeling,adaptability,and generalization.This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples.This established approach holds promise for plant metabolomics and is not limited to ginseng.展开更多
Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was dimini...Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.展开更多
文摘Safety automation of complex mobile systems is a current topic issue in industry and research laboratories,especially in aeronautics.The dynamic models of these systems are nonlinear,Multi-Input Multi-Output(MIMO)and tightly coupled.The nonlinearity resides in the dynamic equations and also in the aerodynamic coefficients’variability.This paper is devoted to developing the piloting law based on the combination of the robust differentiator with a dynamic adaptation of the gains and the robust controller via second order sliding mode,by using an aircraft in virtual simulated environments.To deal with the design of an autopilot controller,we propose an environment framework based on a Software In the Loop(SIL)methodology and we use Microsoft Flight Simulator(FS-2004)as the environment for plane simulation.The first order sliding mode control may be an appropriate solution to this piloting problem.However,its implementation generates a chattering phenomenon and a singularity problem.To overcome these problems,a new version of the adaptive differentiators for second order sliding modes is proposed and used for piloting.For the sliding mode algorithm,higher gains values may be used to improve accuracy;however this leads to an amplification of noise in the estimated signals.A good tradeoff between these two criteria(accuracy,robustness to noise ratio)is difficult to achieve.On the one hand,these values must increase the gains in order to derive a signal sweeping of some frequency ranges.On the other hand,low gains values have to be imposed to reduce noise amplification.So,our goal is to develop a differentiation algorithm in order to have a good compromise between error and robustness to noise ratio.To fit this requirement,a new version of differentiators with a higher order sliding modes and a dynamic adaptation of the gains,is proposed:the first order differentiator for the control of longitudinal speed and the second order differentiator for the control of the Euler angles.
基金Project supported by the National Basic Research Program of China(Grant No.2011CB301704)the Program for New Century Excellent Talents in Universities of China(Grant No.NCET-11-0168)+1 种基金the Foundation for the Author of National Excellent Doctoral Dissertation of China(Grant No.201139)the National Natural Science Foundation of China(Grant Nos.60901006 and 11174096)
文摘We theoretically propose a multifunctional photonic differentiation （DIFF） scheme based on phase demodulation using two cascaded linear filters. The photonic D1FF has a diversity of output forms, such as the 1 st order intensity DIFF, the 1 st order field DIFF and its inversion, and the 2nd-order field DIFF, depending on the relative shift between the optical carrier and the filter＇s resonant notches. As a proof, we also experimentally demonstrate the DIFF diversity using a phase modulator and two delay interferometers （Dis）. The calculated average deviation is less than 7% for all DIFF waveforms. Our schemes show the advantages of flexible DIFF functions and forms, which may have different optical applications. For example, high order field differentiators can be used to generate complex temporal waveforms, and intensity differentiators are useful for the ultra-wideband pulse generation.
基金Supported by the National Natural Science Foundation of China(12001074)the Research Innovation Program of Graduate Students in Hunan Province(CX20220258)+1 种基金the Research Innovation Program of Graduate Students of Central South University(1053320214147)the Key Scientific Research Project of Higher Education Institutions in Henan Province(25B110025)。
文摘This paper deals with Mckean-Vlasov backward stochastic differential equations with weak monotonicity coefficients.We first establish the existence and uniqueness of solutions to Mckean-Vlasov backward stochastic differential equations.Then we obtain a comparison theorem in one-dimensional situation.
基金supported by the Natural Science Foundation of Fujian Province of China(2025J01380)National Natural Science Foundation of China(No.62471139)+3 种基金the Major Health Research Project of Fujian Province(2021ZD01001)Fujian Provincial Units Special Funds for Education and Research(2022639)Fujian University of Technology Research Start-up Fund(GY-S24002)Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare(GY-H-24179).
文摘The generation of synthetic trajectories has become essential in various fields for analyzing complex movement patterns.However,the use of real-world trajectory data poses significant privacy risks,such as location reidentification and correlation attacks.To address these challenges,privacy-preserving trajectory generation methods are critical for applications relying on sensitive location data.This paper introduces DPIL-Traj,an advanced framework designed to generate synthetic trajectories while achieving a superior balance between data utility and privacy preservation.Firstly,the framework incorporates Differential Privacy Clustering,which anonymizes trajectory data by applying differential privacy techniques that add noise,ensuring the protection of sensitive user information.Secondly,Imitation Learning is used to replicate decision-making behaviors observed in real-world trajectories.By learning from expert trajectories,this component generates synthetic data that closely mimics real-world decision-making processes while optimizing the quality of the generated trajectories.Finally,Markov-based Trajectory Generation is employed to capture and maintain the inherent temporal dynamics of movement patterns.Extensive experiments conducted on the GeoLife trajectory dataset show that DPIL-Traj improves utility performance by an average of 19.85%,and in terms of privacy performance by an average of 12.51%,compared to state-of-the-art approaches.Ablation studies further reveal that DP clustering effectively safeguards privacy,imitation learning enhances utility under noise,and the Markov module strengthens temporal coherence.
文摘BACKGROUND The treatment technology of liver cancer is progressing.In addition to traditional surgical resection,combined therapies of immunotherapy based on immune checkpoint inhibitors,chemotherapy,and transcatheter arterial chemoembolization for hepatocellular carcinoma are more and more widely used.Accurate preoperative diagnosis of liver cancer will provide important information for comprehensive treatment and prognosis evaluation of liver cancer.Sonazoidcontrast-enhanced ultrasound is not only helpful for the qualitative diagnosis of liver lesions,but also has great potential in the diagnosis of histological differentiation of liver cancer.AIM To assess the differentiation of hepatocellular carcinoma(HCC)by utilizing the parameters and imaging features of Sonazoid-contrast-enhanced ultrasound(CEUS).METHODS A retrospective analysis was conducted on the CEUS data of 239 lesions through case-control study.These patients received Sonazoid-CEUS within one week before surgery and were confirmed as HCC by postoperative pathology.Within the cases,patients were further categorized into well-differentiated and poorlydifferentiated group.Time-intensity curves of the region of interest in both arterial and Kupffer phases were generated,allowing for the acquisition of quantitative parameters to assess the diagnostic efficacy in distinguishing lesions between these two groups and determining an appropriate cut-off value.RESULTS Univariate analysis showed that the absolute value of enhancement intensity(EIAV),intensity ratio(IR)and intensity difference(ID)in Kupffer phase were statistically different between the groups with different degree(P=0.015,P=0.000,P=0.000).The sensitivity and specificity were 40.2%,82.4%,80.4% and 78.1%,86.9% and 74.5%,respectively,for differentiating HCC lesions with EIAV≥56.384 dB,IR≥1.215 and ID≥9.184 dB.The area under the receiver operating characteristic curve were 0.590,0.877,0.815.There was no significant difference in the parameters of arterial phase,including peak time,initial growth time,rise time and the absolute value of peak intensity of lesions between the two groups(P>0.05).Multivariate analysis showed that the level of alphafetoprotein(AFP)and IR were risk factors for poor differentiation(P=0.001).CONCLUSION Among the parameters of Sonazoid-CEUS,IR in Kupffer phase exhibits superior diagnostic efficacy with high sensitivity and specificity in the diagnose of pathological differentiation of HCC.Combined with preoperative AFP level,a more accurate diagnosis will be obtained.Compared with portal vein phase,Kupffer phase showed the ability to identify HCC lesions more sensitive.These findings hold significant guiding implications and reference value for clinical practice.
基金supported by the Argentine Agency for the Promotion of Science and Technology ANPCyT(PICT2019-1472 to GP,PICT2019-4597 to FL,PICT2020-1524 to GP,and PICT2021-00627 to FL)supported by an Independent Career Position from CONICETsupported by a postdoctoral fellowship from ANPCyT。
文摘Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrinsic mechanisms underlying the decision of a stem cell to proliferate,enter a dormant quiescent state or differentiate into a specific cell type remains incompletely understood.
文摘BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention for its role in influencing their function,accessibility,and readiness for clinical use.AIM To identify the most suitable adipose source for MSC isolation and expansion for further applications.METHODS We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method.The MSCs were examined for their expansion using population doubling time,differentiation capacity using multilineage differentiation induction,surface markers using flow cytometry,and stability of chromosomes using the karyotyping method.Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.RESULTS MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2.All adipose-derived MSCs(AD-MSCs)exhibited the typical elongated,spindle-shaped morphology and comparable proliferation rate.They expressed positive surface markers(cluster of differentiation 73[CD73]:>97%,CD90:>98%,and CD105:>95%),and negative markers(<1%).All MSCs expressed similar levels of stemness genes(octamer-binding transcription factor 4,SRY-box 2,Krüppel-like factor,and MYC),colonyforming,and trilineage differentiation potential.Karyotyping analysis revealed normal chromosomal patterns in all samples,except one sample exhibiting a polymorphism(1qh+).Furthermore,the growth factors and cytokines of hepatocyte growth factor,vascular endothelial growth factor A,interleukin 6(IL-6),and IL-8 were detected in all AD-MSC conditioned media;but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs,respectively.CONCLUSION These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences,which are suitable for further expansion and various clinical applications.
基金Supported by the National Natural Science Fundation of China(No.82101107No.81471575).
文摘AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金supported by the National Natural Science Foundation of China,Nos.82271132(to YL),82101167(to BB)the Natural Science Foundation of Chongqing,Nos.CSTB2022NSCQ-MSX0020(to BB),cstc2019jcyj-msxmX0473(to FC).
文摘Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.
基金supported by FATALSDrug Project [Progetti di Ricerca@CNR SAC.AD002.173.058] from National Research Council,Italy (to CV)。
文摘The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.
基金supported by the National Natural Science Foundation of China (Grant Nos.92580120 and 52471188)。
文摘Optimizing the microchannel design of the next generation of chips requires an understanding of the in situ property evolution of the chip-based materials under fast cooling.This work overcomes the conventional reliance on reheating data of melt-quenched glasses by demonstrating direct observations of glass transition on cooling curves utilizing the most advanced fast differential scanning calorimetry.By leveraging an MEMS chip sensor that allows for rapid heat extraction from microgram-sized samples to a purged gas coolant,the device is able to reach ultra-fast cooling rates of up to 40,000 K·s^(−1).Four thermal regions are identified by examining the cooling behaviors of two metallic glasses.This is because the actual rate of the specimen can differ from the programmed rate,especially at high set rate when the actual rate decreases before the glass transition is completed.We define the operational window for reliable cooling curve analysis,build models with empirical and theoretical analyses to determine the maximum feasible cooling rate,and demonstrate how optimizing sample mass and environment temperature broaden this window.The method avoids deceptive structural relaxation effects verified by fictivetemperature analysis and permits the capture of full glass transition during cooling.
基金Supported by National Natural Science Foundation of China(12101482)Postdoctoral Science Foundation of China(2022M722604)+2 种基金General Project of Science and Technology of Shaanxi Province(2023-YBSF-372)The Natural Science Foundation of Shaan Xi Province(2023-JCQN-0016)Shannxi Mathmatical Basic Science Research Project(23JSQ042)。
文摘In order to better describe the phenomenon of biological invasion,this paper introduces a free boundary model of biological invasion.Firstly,the right free boundary is added to the equation with logistic terms.Secondly,the existence and uniqueness of local solutions are proved by the Sobolev embedding theorem and the comparison principle.Finally,according to the relevant research data and contents of red fire ants,the diffusion area and nest number of red fire ants were simulated without external disturbance.This paper mainly simulates the early diffusion process of red fire ants.In the early diffusion stage,red fire ants grow slowly and then spread over a large area after reaching a certain number.
基金supported by the National Natural Science Foundation of China,Nos.81901156(to ZZ),82271200(to ZZ),82171308(to XC)the Fundamental Research Funds for the Central Universities,No.xzy012022035(to ZZ)+1 种基金the Natural Science Foundation of Shaanxi Province,Nos.2021JM-261(to QK),2023-YBSF-303(to ZZ)Traditional Chinese Medicine Project of Shaanxi Province,No.2019-ZZ-JC047(to QK)。
文摘The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.
基金supported by the Army Laboratory Animal Foundation of China,No.SYDW[2020]22(to TC)the Shaanxi Provincial Key R&D Plan General Project of China,No.2022SF-236(to YM)the National Natural Science Foundation of China,No.82202070(to TC)。
文摘A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.
基金supported by the National Natural Science Foundation of China(NSFC)under Grant(No.51677058).
文摘Precisely estimating the state of health(SOH)of lithium-ion batteries is essential for battery management systems(BMS),as it plays a key role in ensuring the safe and reliable operation of battery systems.However,current SOH estimation methods often overlook the valuable temperature information that can effectively characterize battery aging during capacity degradation.Additionally,the Elman neural network,which is commonly employed for SOH estimation,exhibits several drawbacks,including slow training speed,a tendency to become trapped in local minima,and the initialization of weights and thresholds using pseudo-random numbers,leading to unstable model performance.To address these issues,this study addresses the challenge of precise and effective SOH detection by proposing a method for estimating the SOH of lithium-ion batteries based on differential thermal voltammetry(DTV)and an SSA-Elman neural network.Firstly,two health features(HFs)considering temperature factors and battery voltage are extracted fromthe differential thermal voltammetry curves and incremental capacity curves.Next,the Sparrow Search Algorithm(SSA)is employed to optimize the initial weights and thresholds of the Elman neural network,forming the SSA-Elman neural network model.To validate the performance,various neural networks,including the proposed SSA-Elman network,are tested using the Oxford battery aging dataset.The experimental results demonstrate that the method developed in this study achieves superior accuracy and robustness,with a mean absolute error(MAE)of less than 0.9%and a rootmean square error(RMSE)below 1.4%.
基金supported by the National Key R&D Program of China(Grant No.:2022YFC3501805)the National Natural Science Foundation of China(Grant No.:82374030)+2 种基金the Science and Technology Program of Tianjin in China(Grant No.:23ZYJDSS00030)the Tianjin Outstanding Youth Fund,China(Grant No.:23JCJQJC00030)the China Postdoctoral Science Foundation-Tianjin Joint Support Program(Grant No.:2023T030TJ).
文摘Metabolomics covers a wide range of applications in life sciences,biomedicine,and phytology.Data acquisition(to achieve high coverage and efficiency)and analysis(to pursue good classification)are two key segments involved in metabolomics workflows.Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups.However,insufficient feature extraction,inappropriate feature selection,overfitting,or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused.Using two ginseng varieties,namely Panax japonicus(PJ)and Panax japonicus var.major(PJvm),containing the similar ginsenosides,we integrated pseudo-targeted metabolomics and deep neural network(DNN)modeling to achieve accurate species differentiation.A pseudo-targeted metabolomics approach was optimized through data acquisition mode,ion pairs generation,comparison between multiple reaction monitoring(MRM)and scheduled MRM(sMRM),and chromatographic elution gradient.In total,1980 ion pairs were monitored within 23 min,allowing for the most comprehensive ginseng metabolome analysis.The established DNN model demonstrated excellent classification performance(in terms of accuracy,precision,recall,F1 score,area under the curve,and receiver operating characteristic(ROC))using the entire metabolome data and feature-selection dataset,exhibiting superior advantages over random forest(RF),support vector machine(SVM),extreme gradient boosting(XGBoost),and multilayer perceptron(MLP).Moreover,DNNs were advantageous for automated feature learning,nonlinear modeling,adaptability,and generalization.This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples.This established approach holds promise for plant metabolomics and is not limited to ginseng.
基金supported by grants from National Natural Science Foundation of China(82272444,81972031,81972033)China Postdoctoral Science Foundation(2022M722382)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-032A)。
文摘Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.
