<div style="text-align:justify;"> With the high speed development of information technology, contemporary data from a variety of fields becomes extremely large. The number of features in many datasets ...<div style="text-align:justify;"> With the high speed development of information technology, contemporary data from a variety of fields becomes extremely large. The number of features in many datasets is well above the sample size and is called high dimensional data. In statistics, variable selection approaches are required to extract the efficacious information from high dimensional data. The most popular approach is to add a penalty function coupled with a tuning parameter to the log likelihood function, which is called penalized likelihood method. However, almost all of penalized likelihood approaches only consider noise accumulation and supurious correlation whereas ignoring the endogeneity which also appeared frequently in high dimensional space. In this paper, we explore the cause of endogeneity and its influence on penalized likelihood approaches. Simulations based on five classical pe-nalized approaches are provided to vindicate their inconsistency under endogeneity. The results show that the positive selection rate of all five approaches increased gradually but the false selection rate does not consistently decrease when endogenous variables exist, that is, they do not satisfy the selection consistency. </div>展开更多
This paper investigates the effectiveness of online reviews on addressing price endogeneity issue in an application to consumer demand for smartphone.We consider review variables as the substitutes of unobserved produ...This paper investigates the effectiveness of online reviews on addressing price endogeneity issue in an application to consumer demand for smartphone.We consider review variables as the substitutes of unobserved product quality in terms of a scalar variable as seen in previous methods.An aspect-based sentiment classification technique is designed to construct feature-related review variables from millions of review contents.We discuss the performance of review variables both in a hedonic pricing model and a conditional logit discrete choice model.Our results demonstrate that review variables show a good performance either as instruments for price or as explicit control variables in demand models.In detail,the pricing prediction accuracy increases 3.4%,which is considered as a significant improvement in the practice of forecasting.In the discrete choice model,the estimated price coefficient is biased in the positive direction without endogeneity correction.It is adjusted in the expected way after including review variables.The findings indicate that online reviews provide alternative sources of information in dealing with endogeneity in discrete choice models.We also analyze the differences in the preferences and needs of individual consumers to provide some practical implications of marketing.展开更多
This paper studies the endogeneity of WTO dummy variable in the gravity model about the trade in the region of China and ASEAN. We first present a two-stage test approach for the endogeneity of WTO dummy, then transfo...This paper studies the endogeneity of WTO dummy variable in the gravity model about the trade in the region of China and ASEAN. We first present a two-stage test approach for the endogeneity of WTO dummy, then transform the endogeneity problem to a simultaneous system about WTO and trade, and construct an MLE estimation approach to the simultaneous model. The estimate of the coefficient of WTO dummy is positive, as opposed to the negative sign in the exogeneity case. From the estimation of the endogenous model, WTO has creation fold effect and strong trade diversion effect on export model in the region.展开更多
The traffic flow pertinent modelling is essential for distinct strategy formulations.However,the present literature illustrated some needed improvements for such models,especially those related to lane-specific flow.G...The traffic flow pertinent modelling is essential for distinct strategy formulations.However,the present literature illustrated some needed improvements for such models,especially those related to lane-specific flow.Given such context,this study aims to bridge the research gap by generating regression models to investigate influential factors for traffic flow based on the data collected from one multilane freeway.With the Full Bayesian specification,the hierarchical models were built by accounting for three types of random effects:the structured and unstructured spatial effects,and the one addressing the multivariate heterogeneity across multiple lanes.The endogenous relationship of traffic flow of adjacent lanes was also explored by utilizing the capability of multivariate correlation structure for simultaneous estimation of lane flow.The model estimates revealed the presence of endogeneity with statistical significance for the flow of neighbouring lanes for both directions of travel.The impact of flow was not only limited to the adjacent lanes but also to non-adjacent lanes.The multivariate specification also confirmed interdependency for lane flows.Compared to conventional approaches,the more accurate model estimation in the study indicates the advantage of incorporating the various correlation structures in the models.展开更多
The enormous advantages of active transportation lead the transportation research focus towards enhancing the walking and biking trips.The present study explored the influential factors to the walking and biking trave...The enormous advantages of active transportation lead the transportation research focus towards enhancing the walking and biking trips.The present study explored the influential factors to the walking and biking travel frequency based on data obtained from the National Household Travel Survey California add-on survey.The study features some highlights.First,bivariate models were used to account for the common unobserved heterogeneity shared at both household and personal levels.Second,endogeneity was explicitly considered.Third,both variable importance ranking and correlation analysis are employed to determine the different features to be fed into each of the joint models.The results illustrated that the models developed with endogeneity performed better than the models without endogeneity.Four influential variables which includes mode to work by bicycle,public transit usage,count of household members,and multiple race responses,tend to have statistically significant impacts on walking and biking trips.展开更多
This paper studies variable selection problem in structural equation of a two-stage least squares （2SLS） model in presence of endogeneity which is commonly encountered in empirical economic studies. Model uncertaint...This paper studies variable selection problem in structural equation of a two-stage least squares （2SLS） model in presence of endogeneity which is commonly encountered in empirical economic studies. Model uncertainty and variable selection in the structural equation is an important issue as described in Andrews and Lu （2001） and Caner （2009）. The authors propose an adaptive Lasso 2SLS estimator for linear structural equation with endogeneity and show that it enjoys the oracle properties, i.e., the consistency in both estimation and model selection. In Monte Carlo simulations, the authors demonstrate that the proposed estimator has smaller bias and MSE compared with the bridge-type GMM estimator （Caner, 2009）. In a case study, the authors revisit the classic returns to education problem （Angrist and Krueger, 1991） using the China Population census data. The authors find that the education level not only has strong effects on income but also shows heterogeneity in different age cohorts.展开更多
In this paper,we propose a state-varying endogenous regime switching model(the SERS model),which includes the endogenous regime switching model by Chang et al.,the CCP model,as a special case.To estimate the unknown p...In this paper,we propose a state-varying endogenous regime switching model(the SERS model),which includes the endogenous regime switching model by Chang et al.,the CCP model,as a special case.To estimate the unknown parameters in the SERS model,we propose a maximum likelihood estimation method.Monte Carlo simulation results show that in the absence of state-varying endogeneity,the SERS model and the CCP model perform similarly,while in the presence of state-varying endogeneity,the SERS model performs much better than the CCP model.Finally,we use the SERS model to analyze Chinese stock market returns,and our empirical results show that there exists strongly state-varying endogeneity in volatility switching for the Shanghai Composite Index returns.Moreover,the SERS model can indeed produce a much more realistic assessment for the regime switching process than the one obtained by the CCP model.展开更多
Bottom-up and top-down endogenous automobile clusters exhibit distinct evolutionary traits and driving mechanisms,yet their comparative analysis remains understudied.Therefore,using Taizhou automobile industry cluster...Bottom-up and top-down endogenous automobile clusters exhibit distinct evolutionary traits and driving mechanisms,yet their comparative analysis remains understudied.Therefore,using Taizhou automobile industry cluster(TAIC)and Wuhu automobile industry cluster(WAIC)as cases,using historical statistical data and field interview data from the 1980s to 2023,combined with qualitative research methods of thematic and diachronic analysis,and quantitative research methods of social network analysis,we compare both endogenous automobile clusters’evolutionary traits and driving mechanisms.The results confirm both clusters undergo multi-scale spatial reconfiguration,organizational complexification,and intelligent networking technological transformation,yet diverge fundamentally:TAIC evolves through market-driven progressive expansion,transitioning from single to dual-core structures via private enterprise networking,with innovation following market-integrated logic and institutional thickness built on demand-driven evolution.Conversely,WAIC follows planned expansion,maintaining state-led hierarchical single-core stability through policy-driven breakthrough innovation and supply-dominated institutional construction-though both ultimately require formal-informal system synergy.Their coevolution is driven by dynamic interactions of path dependence(weakening influence),learning-innovation(strengthening influence),and relationship selection(inverted U-shaped trajectory),with divergent development paths rooted in TAIC’s grassroots self-organization genes versus WAIC’s top-level design genes,amplified by core enterprises’strategic disparities.The research findings can not only provide decision-making support for China’s industrial upgrading,but also contribute China’s insights to global economic governance.展开更多
Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as ...Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.展开更多
Fault-tolerant systems are crucial for ensuring the reliability and availability of missioncritical applications in modern computing environments.The dynamic heterogeneous redundancy(DHR)architecture is a key componen...Fault-tolerant systems are crucial for ensuring the reliability and availability of missioncritical applications in modern computing environments.The dynamic heterogeneous redundancy(DHR)architecture is a key component in constructing fault-tolerant systems,particularly in areas such as national security,power networks,and banking private networks.DHR is transforming the cyberspace security industry chain by accommodating a broader range of applications and increasingly capturing the market.However,the development of applications for DHR architecture encounters challenges due to the complexities of handling heterogeneity,managing dynamism,and maintaining usability.To address these issues,we introduce MimicStudio,a comprehensive development framework with a standardized workflow.To our knowledge,MimicStudio is the first effective solution for DHR software development.We present a detailed implementation of MimicStudio with a heterogeneous microcontroller unit project,encompassing three CPUs with different instruction set architectures.The paper evaluates MimicStudio’s support for essential features,including zero-copy synchronization,parallelized build,multi-core collaborative debugging,and dynamic adjustment of the software system’s structure.Our results show that MimicStudio provides a flexible and efficient solution for supporting the dynamic,heterogeneous,and redundant features of fault-tolerant systems.展开更多
Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within t...Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.展开更多
Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesio...Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vi...AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vision in eyes with endogenous endophthalmitis due to Klebsiella pneumoniae(K.pneumoniae)liver abscess.METHODS:In this single-center,retrospective case series of 18 patients with endogenous endophthalmitis due to K.pneumoniae liver abscess were analyzed.Ophthalmologic features of endophthalmitis at early,intermediate and advanced stages were obtained from eyes with endophthalmitis of different severities.Prompt vitrectomy was considered primarily for all eyes except for very early endophthalmitis.Intravitreal injections of antibiotics were performed in eyes with endophthalmitis in the very early stages and in eyes where vitrectomy was not available,and additional control of infection was needed after vitrectomy.Evisceration was performed in eyes with corneoscleral perforation,advanced endophthalmitis,perforation with preseptal or orbital cellulitis,uncontrolled infection,or severe pain with no vision.RESULTS:Mean(±standard deviation)age of the 18 patients with endophthalmitis was 64.5±12.2(range:32-84)y,and 14 patients(77.8%)were males.Endophthalmitis tended to involve the retinal parenchyma first and then progressed into the vitreous cavity and anterior segments.However,it presented a tendency to cause massive subretinal abscesses even after vitrectomy with silicone oil tamponade.Very high intraocular pressure with new vessels on the iris(41.7%)were also commonly observed.Although all but three patients had systemic disease such as diabetes or hypertension,visual prognosis after treatment did not appear to depend significantly on underlying comorbidities.A final best-corrected visual acuity better than 20/60 was achieved only when lesions were detected very early,with relatively good initial visual acuity,likely reflecting lower bacterial inoculation in the eye.CONCLUSION:Detection of early endophthalmitis lesions appears to be the only way to preserve good vision in patients with K.pneumoniae liver abscesses.Therefore,proper guidelines for ophthalmologic screening remain to be established for subjects at a high risk of endophthalmitis.展开更多
The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical ...The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical output still remains a significant challenge.Here,a strategy of inducing constrained phase separation on single nanofibers via shear force was proposed.Employing electrospinning technology,a polyacrylonitrile/polyvinylidene difluoride(PAN/PVDF)nanofibrous membrane was fabricated in one step,which enabled simultaneous piezoelectric and triboelectric conversion within a single-layer membrane.Each nanofiber contained independent components of PAN and PVDF and exhibited a rough surface.The abundant frictional contact points formed between these heterogeneous components contributed to an enhanced endogenous triboelectric output,showcasing an excellent synergistic effect of piezoelectric and triboelectric response in the nanofibrous membrane.Additionally,the component mass ratio influenced the microstructure,piezoelectric conformation and piezoelectric performance of the PAN/PVDF nanofibrous membranes.Through comprehensive performance comparison,the optimal mass ratio of PAN to PVDF was determined to be 9∶1.The piezoelectric devices made of the optimal PAN/PVDF nanofibrous membranes with rough nanofiber surfaces generated an output voltage of 20 V,which was about 1.8 times that of the smooth one at the same component mass ratio.The strategy of constrained phase separation on the surface of individual nanofibers provides a new approach to enhance the output performance of single-layer piezoelectric nanofibrous materials.展开更多
Ship outfitting is a key process in shipbuilding.Efficient and high-quality ship outfitting is a top priority for modern shipyards.These activities are conducted at different stations of shipyards.The outfitting plan ...Ship outfitting is a key process in shipbuilding.Efficient and high-quality ship outfitting is a top priority for modern shipyards.These activities are conducted at different stations of shipyards.The outfitting plan is one of the crucial issues in shipbuilding.In this paper,production scheduling and material ordering with endogenous uncertainty of the outfitting process are investigated.The uncertain factors in outfitting equipment production are usually decision-related,which leads to difficulties in addressing uncertainties in the outfitting production workshops before production is conducted according to plan.This uncertainty is regarded as endogenous uncertainty and can be treated as non-anticipativity constraints in the model.To address this problem,a stochastic two-stage programming model with endogenous uncertainty is established to optimize the outfitting job scheduling and raw material ordering process.A practical case of the shipyard of China Merchants Heavy Industry Co.,Ltd.is used to evaluate the performance of the proposed method.Satisfactory results are achieved at the lowest expected total cost as the complete kit rate of outfitting equipment is improved and emergency replenishment is reduced.展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine func...We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation o...Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.展开更多
文摘<div style="text-align:justify;"> With the high speed development of information technology, contemporary data from a variety of fields becomes extremely large. The number of features in many datasets is well above the sample size and is called high dimensional data. In statistics, variable selection approaches are required to extract the efficacious information from high dimensional data. The most popular approach is to add a penalty function coupled with a tuning parameter to the log likelihood function, which is called penalized likelihood method. However, almost all of penalized likelihood approaches only consider noise accumulation and supurious correlation whereas ignoring the endogeneity which also appeared frequently in high dimensional space. In this paper, we explore the cause of endogeneity and its influence on penalized likelihood approaches. Simulations based on five classical pe-nalized approaches are provided to vindicate their inconsistency under endogeneity. The results show that the positive selection rate of all five approaches increased gradually but the false selection rate does not consistently decrease when endogenous variables exist, that is, they do not satisfy the selection consistency. </div>
文摘This paper investigates the effectiveness of online reviews on addressing price endogeneity issue in an application to consumer demand for smartphone.We consider review variables as the substitutes of unobserved product quality in terms of a scalar variable as seen in previous methods.An aspect-based sentiment classification technique is designed to construct feature-related review variables from millions of review contents.We discuss the performance of review variables both in a hedonic pricing model and a conditional logit discrete choice model.Our results demonstrate that review variables show a good performance either as instruments for price or as explicit control variables in demand models.In detail,the pricing prediction accuracy increases 3.4%,which is considered as a significant improvement in the practice of forecasting.In the discrete choice model,the estimated price coefficient is biased in the positive direction without endogeneity correction.It is adjusted in the expected way after including review variables.The findings indicate that online reviews provide alternative sources of information in dealing with endogeneity in discrete choice models.We also analyze the differences in the preferences and needs of individual consumers to provide some practical implications of marketing.
文摘This paper studies the endogeneity of WTO dummy variable in the gravity model about the trade in the region of China and ASEAN. We first present a two-stage test approach for the endogeneity of WTO dummy, then transform the endogeneity problem to a simultaneous system about WTO and trade, and construct an MLE estimation approach to the simultaneous model. The estimate of the coefficient of WTO dummy is positive, as opposed to the negative sign in the exogeneity case. From the estimation of the endogenous model, WTO has creation fold effect and strong trade diversion effect on export model in the region.
基金Support for this study was provided by California Department of Transportation(Caltrans,No.65A0705)。
文摘The traffic flow pertinent modelling is essential for distinct strategy formulations.However,the present literature illustrated some needed improvements for such models,especially those related to lane-specific flow.Given such context,this study aims to bridge the research gap by generating regression models to investigate influential factors for traffic flow based on the data collected from one multilane freeway.With the Full Bayesian specification,the hierarchical models were built by accounting for three types of random effects:the structured and unstructured spatial effects,and the one addressing the multivariate heterogeneity across multiple lanes.The endogenous relationship of traffic flow of adjacent lanes was also explored by utilizing the capability of multivariate correlation structure for simultaneous estimation of lane flow.The model estimates revealed the presence of endogeneity with statistical significance for the flow of neighbouring lanes for both directions of travel.The impact of flow was not only limited to the adjacent lanes but also to non-adjacent lanes.The multivariate specification also confirmed interdependency for lane flows.Compared to conventional approaches,the more accurate model estimation in the study indicates the advantage of incorporating the various correlation structures in the models.
文摘The enormous advantages of active transportation lead the transportation research focus towards enhancing the walking and biking trips.The present study explored the influential factors to the walking and biking travel frequency based on data obtained from the National Household Travel Survey California add-on survey.The study features some highlights.First,bivariate models were used to account for the common unobserved heterogeneity shared at both household and personal levels.Second,endogeneity was explicitly considered.Third,both variable importance ranking and correlation analysis are employed to determine the different features to be fed into each of the joint models.The results illustrated that the models developed with endogeneity performed better than the models without endogeneity.Four influential variables which includes mode to work by bicycle,public transit usage,count of household members,and multiple race responses,tend to have statistically significant impacts on walking and biking trips.
基金Fan’s research was supported by the National Natural Science Foundation of China under Grant No.71671149the Fundamental Research Funds for the Central Universities under Grant No.20720171042+1 种基金the Natural Science Foundation of Fujian Province of China under Grant No.2016J01340Zhong’s research was supported by the National Natural Science Foundation of China under Grant Nos.11671334,11301435,and 11401497
文摘This paper studies variable selection problem in structural equation of a two-stage least squares （2SLS） model in presence of endogeneity which is commonly encountered in empirical economic studies. Model uncertainty and variable selection in the structural equation is an important issue as described in Andrews and Lu （2001） and Caner （2009）. The authors propose an adaptive Lasso 2SLS estimator for linear structural equation with endogeneity and show that it enjoys the oracle properties, i.e., the consistency in both estimation and model selection. In Monte Carlo simulations, the authors demonstrate that the proposed estimator has smaller bias and MSE compared with the bridge-type GMM estimator （Caner, 2009）. In a case study, the authors revisit the classic returns to education problem （Angrist and Krueger, 1991） using the China Population census data. The authors find that the education level not only has strong effects on income but also shows heterogeneity in different age cohorts.
基金The authors extend their sincere thanks to the editor and two referees for their insightful comments that helped improve the article substantially.This research is supported by the National Natural Science Foundation of China(Project 71803091)by the MOE(Ministry of Education in China)Project of Humanities and Social Sciences(Project 18YJC790015).
文摘In this paper,we propose a state-varying endogenous regime switching model(the SERS model),which includes the endogenous regime switching model by Chang et al.,the CCP model,as a special case.To estimate the unknown parameters in the SERS model,we propose a maximum likelihood estimation method.Monte Carlo simulation results show that in the absence of state-varying endogeneity,the SERS model and the CCP model perform similarly,while in the presence of state-varying endogeneity,the SERS model performs much better than the CCP model.Finally,we use the SERS model to analyze Chinese stock market returns,and our empirical results show that there exists strongly state-varying endogeneity in volatility switching for the Shanghai Composite Index returns.Moreover,the SERS model can indeed produce a much more realistic assessment for the regime switching process than the one obtained by the CCP model.
基金Under the auspices of National Natural Science Foundation of China(No.42571219)Key Project of Zhejiang Province Soft Science Research Plan(No.2023C25014)。
文摘Bottom-up and top-down endogenous automobile clusters exhibit distinct evolutionary traits and driving mechanisms,yet their comparative analysis remains understudied.Therefore,using Taizhou automobile industry cluster(TAIC)and Wuhu automobile industry cluster(WAIC)as cases,using historical statistical data and field interview data from the 1980s to 2023,combined with qualitative research methods of thematic and diachronic analysis,and quantitative research methods of social network analysis,we compare both endogenous automobile clusters’evolutionary traits and driving mechanisms.The results confirm both clusters undergo multi-scale spatial reconfiguration,organizational complexification,and intelligent networking technological transformation,yet diverge fundamentally:TAIC evolves through market-driven progressive expansion,transitioning from single to dual-core structures via private enterprise networking,with innovation following market-integrated logic and institutional thickness built on demand-driven evolution.Conversely,WAIC follows planned expansion,maintaining state-led hierarchical single-core stability through policy-driven breakthrough innovation and supply-dominated institutional construction-though both ultimately require formal-informal system synergy.Their coevolution is driven by dynamic interactions of path dependence(weakening influence),learning-innovation(strengthening influence),and relationship selection(inverted U-shaped trajectory),with divergent development paths rooted in TAIC’s grassroots self-organization genes versus WAIC’s top-level design genes,amplified by core enterprises’strategic disparities.The research findings can not only provide decision-making support for China’s industrial upgrading,but also contribute China’s insights to global economic governance.
基金supported by the National Natural Science Foundation of China,Nos.82372277(to ZW),82272361(to XS),82271395(to GL)Guangdong Province Basic and Applied Basic Research Fund Project,No.2024A1515010615(to XS)+1 种基金Guangdong Province Natural Youth Promotion Project,No.2314070000241(to GL)Guangzhou Science and Technology Project,No.2025A04J4740(to GL).
文摘Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.
基金supported by National Key Research and Development Program of China(No.2023YFB 4404200).
文摘Fault-tolerant systems are crucial for ensuring the reliability and availability of missioncritical applications in modern computing environments.The dynamic heterogeneous redundancy(DHR)architecture is a key component in constructing fault-tolerant systems,particularly in areas such as national security,power networks,and banking private networks.DHR is transforming the cyberspace security industry chain by accommodating a broader range of applications and increasingly capturing the market.However,the development of applications for DHR architecture encounters challenges due to the complexities of handling heterogeneity,managing dynamism,and maintaining usability.To address these issues,we introduce MimicStudio,a comprehensive development framework with a standardized workflow.To our knowledge,MimicStudio is the first effective solution for DHR software development.We present a detailed implementation of MimicStudio with a heterogeneous microcontroller unit project,encompassing three CPUs with different instruction set architectures.The paper evaluates MimicStudio’s support for essential features,including zero-copy synchronization,parallelized build,multi-core collaborative debugging,and dynamic adjustment of the software system’s structure.Our results show that MimicStudio provides a flexible and efficient solution for supporting the dynamic,heterogeneous,and redundant features of fault-tolerant systems.
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB)。
文摘Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
基金supported by the Qingdao Medical Health Research Project,No.2023-WJZD212(to XX)。
文摘Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
文摘AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vision in eyes with endogenous endophthalmitis due to Klebsiella pneumoniae(K.pneumoniae)liver abscess.METHODS:In this single-center,retrospective case series of 18 patients with endogenous endophthalmitis due to K.pneumoniae liver abscess were analyzed.Ophthalmologic features of endophthalmitis at early,intermediate and advanced stages were obtained from eyes with endophthalmitis of different severities.Prompt vitrectomy was considered primarily for all eyes except for very early endophthalmitis.Intravitreal injections of antibiotics were performed in eyes with endophthalmitis in the very early stages and in eyes where vitrectomy was not available,and additional control of infection was needed after vitrectomy.Evisceration was performed in eyes with corneoscleral perforation,advanced endophthalmitis,perforation with preseptal or orbital cellulitis,uncontrolled infection,or severe pain with no vision.RESULTS:Mean(±standard deviation)age of the 18 patients with endophthalmitis was 64.5±12.2(range:32-84)y,and 14 patients(77.8%)were males.Endophthalmitis tended to involve the retinal parenchyma first and then progressed into the vitreous cavity and anterior segments.However,it presented a tendency to cause massive subretinal abscesses even after vitrectomy with silicone oil tamponade.Very high intraocular pressure with new vessels on the iris(41.7%)were also commonly observed.Although all but three patients had systemic disease such as diabetes or hypertension,visual prognosis after treatment did not appear to depend significantly on underlying comorbidities.A final best-corrected visual acuity better than 20/60 was achieved only when lesions were detected very early,with relatively good initial visual acuity,likely reflecting lower bacterial inoculation in the eye.CONCLUSION:Detection of early endophthalmitis lesions appears to be the only way to preserve good vision in patients with K.pneumoniae liver abscesses.Therefore,proper guidelines for ophthalmologic screening remain to be established for subjects at a high risk of endophthalmitis.
基金National Natural Science Foundation of China(No.52373281)National Energy-Saving and Low-Carbon Materials Production and Application Demonstration Platform Program,China(No.TC220H06N)。
文摘The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical output still remains a significant challenge.Here,a strategy of inducing constrained phase separation on single nanofibers via shear force was proposed.Employing electrospinning technology,a polyacrylonitrile/polyvinylidene difluoride(PAN/PVDF)nanofibrous membrane was fabricated in one step,which enabled simultaneous piezoelectric and triboelectric conversion within a single-layer membrane.Each nanofiber contained independent components of PAN and PVDF and exhibited a rough surface.The abundant frictional contact points formed between these heterogeneous components contributed to an enhanced endogenous triboelectric output,showcasing an excellent synergistic effect of piezoelectric and triboelectric response in the nanofibrous membrane.Additionally,the component mass ratio influenced the microstructure,piezoelectric conformation and piezoelectric performance of the PAN/PVDF nanofibrous membranes.Through comprehensive performance comparison,the optimal mass ratio of PAN to PVDF was determined to be 9∶1.The piezoelectric devices made of the optimal PAN/PVDF nanofibrous membranes with rough nanofiber surfaces generated an output voltage of 20 V,which was about 1.8 times that of the smooth one at the same component mass ratio.The strategy of constrained phase separation on the surface of individual nanofibers provides a new approach to enhance the output performance of single-layer piezoelectric nanofibrous materials.
基金supported in part by the High-tech ship scientific research project of the Ministry of Industry and Information Technology of the People’s Republic of China,and the National Nature Science Foundation of China(Grant No.71671113)the Science and Technology Department of Shaanxi Province(No.2020GY-219)the Ministry of Education Collaborative Project of Production,Learning and Research(No.201901024016).
文摘Ship outfitting is a key process in shipbuilding.Efficient and high-quality ship outfitting is a top priority for modern shipyards.These activities are conducted at different stations of shipyards.The outfitting plan is one of the crucial issues in shipbuilding.In this paper,production scheduling and material ordering with endogenous uncertainty of the outfitting process are investigated.The uncertain factors in outfitting equipment production are usually decision-related,which leads to difficulties in addressing uncertainties in the outfitting production workshops before production is conducted according to plan.This uncertainty is regarded as endogenous uncertainty and can be treated as non-anticipativity constraints in the model.To address this problem,a stochastic two-stage programming model with endogenous uncertainty is established to optimize the outfitting job scheduling and raw material ordering process.A practical case of the shipyard of China Merchants Heavy Industry Co.,Ltd.is used to evaluate the performance of the proposed method.Satisfactory results are achieved at the lowest expected total cost as the complete kit rate of outfitting equipment is improved and emergency replenishment is reduced.
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
基金supported by the National Natural Science Foundation of China,No.81801907(to NC)Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research,No.ZDSYS20230626091402006(to NC)+2 种基金Sanming Project of Medicine in Shenzhen,No.SZSM201911002(to SL)Foundation of Shenzhen Committee for Science and Technology Innovation,Nos.JCYJ20230807110310021(to NC),JCYJ20230807110259002(to JL)Science and Technology Program of Guangzhou,No.2024A04J4716(to TL)。
文摘We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
基金made possible by the National Natural Science Foundation of China (32060422)。
文摘Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.
