Objective: The objective of this work is to search for a novel method to explore the disrupted pathways associated with periodontitis(PD) based on the network level.Methods: Firstly, the differential expression genes(...Objective: The objective of this work is to search for a novel method to explore the disrupted pathways associated with periodontitis(PD) based on the network level.Methods: Firstly, the differential expression genes(DEGs) between PD patients and cognitively normal subjects were inferred based on LIMMA package. Then, the proteinprotein interactions(PPI) in each pathway were explored by Empirical Bayesian(EB) coexpression program. Specifically, we determined the 100 th weight value as the threshold value of the disrupted pathways of PPI by constructing the randomly model and confirmed the weight value of each pathway. Meanwhile, we dissected the disrupted pathways under the weight value > the threshold value. Pathways enrichment analyses of DEGs were carried out based on Expression Analysis Systematic Explored(EASE) test. Finally, the better method was selected based on the more rich and significant obtained pathways by comparing the two methods. Results: After the calculation of LIMMA package, we estimated 524 DEGs in all. Then we determined 0.115222 as the threshold value of the disrupted pathways of PPI. When the weight value>0.115222, there were 258 disrupted pathways of PPI enriched in. Additionally, we observed those 524 DEGs that were enriched in 4 pathways under EASE=0.1.Conclusion: We proposed a novel network method inferring the disrupted pathway for PD. The disrupted pathways might be underlying biomarkers for treatment associated with PD.展开更多
The Durkan Complex is a key tectonic element of the Makran accretionary prism(SE Iran)and it has been interpreted as representing a continental margin succession.We present here a multidisciplinary study of the wester...The Durkan Complex is a key tectonic element of the Makran accretionary prism(SE Iran)and it has been interpreted as representing a continental margin succession.We present here a multidisciplinary study of the western Durkan Complex,which is based on new geological,stratigraphic,biostratigraphic data,as well as geochemical data of the volcanic and meta-volcanic rocks forming this complex.Our data show that this complex consists of distinct tectonic slices showing both non-metamorphic and very low-grade metamorphic deformed successions.Stratigraphic and biostratigraphic data allow us to recognize three types of successions.Type-Ⅰis composed by a Coniacian-early Campanian pelagic succession with intercalation of pillow lavas and minor volcaniclastic rocks.Type-Ⅱsuccession includes a volcanic sequence passing to a volcano-sedimentary sequence with Cenomanian pelagic limestones,followed by a hemipelagic sequence.This succession is characterized by abundant mass-transport deposits.Type-Ⅲsuccession includes volcanic and volcano-sedimentary sequences,which are stratigraphically covered by a Cenomanian platform succession.The latter is locally followed by a hemipelagic sequence.The volcanic rocks in the different successions show alkaline geochemical affinity,suggesting an origin from an oceanic within-plate setting.Our new results indicate that the western Durkan Complex represents fragments of seamounts tectonically incorporated in the Makran accretionary wedge during the latest Late Cretaceous-Paleocene.We propose that incorporation of seamounts in the frontal prism caused a shortening of the whole convergent margin and possibly contributed to controlling the deformation style in the Makran Accretionary Wedge during Late Cretaceous-Paleocene times.展开更多
To provide a much more resilient transport scheme for tractor and trailer transportation systems,this paper explores the generation method of tractor and trailer transport schemes considering the influence of disrupte...To provide a much more resilient transport scheme for tractor and trailer transportation systems,this paper explores the generation method of tractor and trailer transport schemes considering the influence of disrupted events.Three states of tractors including towing loaded trailers,towing empty trailers,and idle driving are taken into account.Based on the disruption management theory,a scheduling model is constructed to minimize the total deviation cost including transportation time,transportation path,and number of used vehicles under the three states of tractors.A heuristics based on the contract net and simulated annealing algorithm is designed to solve the proposed model.Through comparative analysis of examples with different numbers of newly added transportation tasks and different types of road networks,the performance of the contract net algorithm in terms of deviations in idle driving paths,empty trailer paths,loaded trailer paths,time,number of used vehicles,and total deviation cost are analyzed.The results demonstrate the effectiveness of the model and algorithm,highlighting the superiority of the disruption management model and the contract net annealing algorithm.The study provides a reference for handling unexpected events in the tractor and trailer transportation industry.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Background:The bacterial biofilm poses a significant challenge to traditional antibiotic therapy.There is a great need to develop novel antibiofilm agents combined with biofilm disrupting and bacteria-killing without ...Background:The bacterial biofilm poses a significant challenge to traditional antibiotic therapy.There is a great need to develop novel antibiofilm agents combined with biofilm disrupting and bacteria-killing without the dependence of antibiotic.Methods:Herein,we prepared ultrasound/magnetic field-responsive ferroferric oxide nanoparticles(Fe_(3)O_(4))/glucose oxidase microbubbles(FGMB)to form a cascade catalytic system for effective removing methicillin-resistant Staphylococcus aureus biofilms.FGMB were prepared through interfacial self-assembly of Fe_(3)O_(4) nanoparticles(NPs)and glucose oxidase(GOx)at the gas-liquid interface stabilized by surfactants.Under ultrasound/magnetic field stimulation,FGMB disrupted biofilm architecture through microbubble collapse-induced microjets and magnetically driven displacement.Simultaneously,ultrasound-triggered rupture of FGMB released GOx and Fe_(3)O_(4) NPs.Glucose can be oxidized by GOx to generate gluconic acid and hydrogen peroxide which was subsequently catalyzed into hydroxyl radicals by Fe_(3)O_(4) NPs,enabling chemical eradication of biofilm-embedded bacteria.Results:Optical microscopy images demonstrated that FGMB have spherical structure with average size of approximately 17μm.FGMB showed a 65.4%decrease in methicillin-resistant Staphylococcus aureus biofilm biomass and 1.1 log bacterial inactivation efficiency(91.2%),suggesting effective biofilm elimination.In vitro experimental results also indicate that FGMB have good biocompatibility.Conclusion:This antibiofilm strategy integrated dual modes of physical biofilm disruption with chemical bacteria-killing shows great potential as a versatile,non-resistant strategy for bacterial biofilm elimination.展开更多
Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across m...Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across multiple conditions and its underlying mechanisms is the subject of ongoing investigation.This review synthesized current evidence to explore the association between NRH and psychiatric disorders from epidemiological,genetic,and neurobiological perspectives.We systematically identified and appraised relevant literature investigating NRH prevalence in psychiatric populations and potential explanatory mechanisms.Epidemiological evidence indicates an elevated prevalence of NRH,particularly within neurodevelopmental disorders.Potential contributing mechanisms identified include early developmental disruptions,shared genetic predispositions,and atypical patterns of brain lateralization.While the association between NRH and psychiatric conditions,especially neurodevelopmental disorders,is evident,the causal pathways and relative contributions of identified mechanisms are complex and debated.This review highlighted key areas requiring further research to elucidate these relationships.展开更多
Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,...Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,this may lead to permanent impairements resulting in a loss of quality of life and a high socioeconomic burden.展开更多
With the support by the National Natural Science Foundation of China,a collaboration led by Prof.Wang Jianmin(王建民)from the Institute of High Energy Physics,Chinese Academy of Sciences proposes a new mechanism for t...With the support by the National Natural Science Foundation of China,a collaboration led by Prof.Wang Jianmin(王建民)from the Institute of High Energy Physics,Chinese Academy of Sciences proposes a new mechanism for the origin of the broad-line region in Active Galactic Nuclei,which was published展开更多
In this paper I will consider the intersection between family tragedy,trauma,and affective uses of narration in two Australian novels:Surrender(Hartnett,2005)and The Danger Game(Ashton,2009).In both of these novels,na...In this paper I will consider the intersection between family tragedy,trauma,and affective uses of narration in two Australian novels:Surrender(Hartnett,2005)and The Danger Game(Ashton,2009).In both of these novels,narratological techniques are utilised to represent a grief beyond words—the tragic loss of a close family member,specifically,a sibling.Both novels use disruptions in narrative forms—particularly in the inherent expectations readers bring to the forms of first,second and third person narration.These narrative disruptions mirror the disruptions of identity experienced by the characters in these texts.Moreover,as we engage with the traumatic content through a fractured subjectivity presented by these texts,our identities as readers,too,become fractured and disrupted.These disruptions of identity echo that which is experienced by the characters themselves through their loss.By analysing the link between these disruptions and the content of these novels,we get a better understanding of the ways in which f ictive worlds can represent psychological issues.The narration of these novels and their engagement with childhood sibling loss enable us to begin to create and understand a broader aesthetic of representational trauma.展开更多
In large cities with heavily congested metro lines, unexpected disturbances often occur, which may cause severe delay of multiple trains, blockage of partial lines, and reduction of passenger service. Metro dispatcher...In large cities with heavily congested metro lines, unexpected disturbances often occur, which may cause severe delay of multiple trains, blockage of partial lines, and reduction of passenger service. Metro dispatchers have taken a practical strategy of rescheduling the timetable and adding several backup trains in storage tracks to alleviate waiting passengers from crowding the platforms and recover from such disruptions. In this study,we first develop a mixed integer programming model to determine the optimal train rescheduling plan with considerations of in-service and backup trains. The aim of train rescheduling is to frequently dispatch trains to evacuate delayed passengers after the disruption. Given the nonlinearity of the model, several linearization techniques are adapted to reformulate the model into an equivalent linear model that can be easily handled by the optimization software. Numerical experiments are implemented to verify the effectiveness of the proposed train rescheduling approach.展开更多
Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture....Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture.In this study,we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM.Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.Mechanistically,SIRT3 suppression results in hyperacetylation of FOXO3,hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria.Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3,thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM.Collectively,our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control,crucial for maintaining bone homeostasis in T2DM.These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.展开更多
Fusobacterium is a genus of obligate anaerobic gram-negative bacilli that usually colonize the oropharynx,gastrointestinal tract,upper respiratory tract,and vaginal mucosa of humans as a part of the normal flora.[1,2]...Fusobacterium is a genus of obligate anaerobic gram-negative bacilli that usually colonize the oropharynx,gastrointestinal tract,upper respiratory tract,and vaginal mucosa of humans as a part of the normal flora.[1,2]Infections may occur once host defense mechanisms are altered and mucosal barriers are disrupted.[3]The clinical spectrum is wide and includes pharyngitis,sinusitis,abscess formation,puerperal infections,bacteremia,and septic shock.Within this genus,two species are most commonly isolated:Fusobacterium nucleatum and Fusobacterium necrophorum(F.necrophorum).F.necrophorum is usually associated with Lemierre’s syndrome,[4,5]a type of septic thrombophlebitis of the internal jugular vein.展开更多
The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting...The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.展开更多
EHL-2 is a compact,high-field spherical tokamak designed to explore the potential of an advanced p-11B nuclear fusion reactor.Due to its high plasma current and thermal energy,it is crucial to mitigate the impact asso...EHL-2 is a compact,high-field spherical tokamak designed to explore the potential of an advanced p-11B nuclear fusion reactor.Due to its high plasma current and thermal energy,it is crucial to mitigate the impact associated with disruptions to ensure the safe operation of EHL-2.This paper evaluates the performance requirements of the disruption prediction system on EHL-2,with a particular focus on applying generalizable knowledge transfer from existing devices to future ones.Furthermore,the key characteristics of disruption mitigation strategies are analyzed,and their overall mitigation performance on EHL-2 is assessed.This insight provides valuable guidance for optimizing the engineering design of EHL-2 and identifying its optimal operational regime.展开更多
Vascular disrupting agents(VDAs)can destroy tumor vasculature and lead to tumor ischemia and hypoxia,resulting in tumor necrosis.However,VDAs are easy to induce the upregulation of genes that are associated with cance...Vascular disrupting agents(VDAs)can destroy tumor vasculature and lead to tumor ischemia and hypoxia,resulting in tumor necrosis.However,VDAs are easy to induce the upregulation of genes that are associated with cancer cell drug resistance and angiogenesis in tumor cells.Hypoxia-activated chemotherapy will be an ideal supplement to VDAs therapy since it can help to fully utilize the ischemia and hypoxia induced by VDAs to realize a synergistic antitumor therapeutic outcome.Here,we design a liposome whose surface is modified with a tumor-homing peptide Cys-Arg-Glu-Lys-Ala(CREKA,which can specifically target tumor vessels and stroma)and whose aqueous cavity and lipid bilayer are loaded by a hypoxia-activatable drug banoxantrone dihydrochloride(AQ4N)and a VDA combretastatin A4(CA4),respectively.CA4 can selectively target vascular endothelial cells and destroy the tumor blood vessels,which will cause the rapid inhibition of blood flow in tumor and enhance the hypoxia in the tumor region.As a consequence,AQ4N can exert its boosted cytotoxicity under the enhanced hypoxic environment.The as-prepared liposome with a uniform particle size exhibits good stability and high cancer cell killing efficacy in vitro.In addition,in vivo experiments confirm the excellent tumortargeting/accumulation,tumor vasculature-damaging,and tumor inhibition effects of the liposome.This work develops a liposomal which can achieve safe and effective tumor suppression without external stimulus excitation by only single injection,and is expected to benefit the future development of effective antitumor liposomal drugs.展开更多
The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions.Human development occurs under the influence of gravity,shie...The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions.Human development occurs under the influence of gravity,shielded from space radiation by Earth’s magnetic field,and within an environment characterized by 24-hour day-night cycles resulting from Earth’s rotation,thus deviating from these conditions necessitates adaptive responses for survival.With upcoming manned lunar and Martian missions approaching rapidly,it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health.This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth,to analyze how microgravity,space radiation,and disrupted circadian affect cardiovascular well-being.Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction,which may be exacerbated by space radiation.Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations,cytoskeletal damage,and myofibril changes.Disruptions in circadian rhythms caused by factors such as microgravity,light exposure,and irregular work schedules,could further exacerbate cardiovascular issues.However,current research tends to predominantly focus on disruptions in the core clock gene,overlooking the multifactorial nature of circadian rhythm disturbances in space.Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks,to preserve astronaut health and ensure mission success.展开更多
Background:Long-term exposure to toxic substances increases the risk of their accumulation and triggering endocrine disruption.The ill-planned irrigation systems in Uzbekistan led to severe environmental disasters,res...Background:Long-term exposure to toxic substances increases the risk of their accumulation and triggering endocrine disruption.The ill-planned irrigation systems in Uzbekistan led to severe environmental disasters,resulting in aridization and the spread of organochlorine pesticides and toxic metals across the region.Objective:We investigate the influence of negative environmental factors on hormonal activities such as sex steroids,gonadotropic hormones,and growth factors,in addition to potential disruptions in growth rate and anthropometric indicators in prepubertal adolescents living in this region.Methods:This study included 405 prepubertal boys aged 11 to 13 years,residing in the cities of Muynak(unfavorable region)and Nukus(favorable region)of Uzbekistan.We measured 20 anthropometric parameters and assessed somatotype by the Heath-Carter method,peak height velocity(PHV),and maturity offset based on Mirwald's equation.In addition,the endocrine profile of 8 hormonal parameters was assessed,which includes growth factors,gonadotropins,sex steroids,and thyroid status.Results:We observed a positive dependence of physique,rate of maturation,and level of androgens,stimulated by gonadotropin hormones.Children living in unfavorable environmental regions show a decrease in folliclestimulating hormone,luteinizing hormone,total testosterone(the best predictor),and anthropometric signs of androgen deficiency.These resulted in an increase in maturity offset and PHV,combined with lower skeletal density and ectomorphic somatotype compared to their peers living in favorable environmental regions.Conclusion:Regional differences in stature,body weight,and anthropometric parameters of adipose tissue,growth factor axis,and thyroid hormones are the influencing indices in the regulation of growth in prepubertal children.We hypothesize that the inhibition of the gonadotropin-testosterone axis may result from endocrine disruption due to higher levels of toxic metals and pesticide exposure.展开更多
Purpose:This study examines why papers with high CD indices(measuring research disruptiveness)increasingly show reduced citation impact and investigates whether this represents genuine impact reduction or methodologic...Purpose:This study examines why papers with high CD indices(measuring research disruptiveness)increasingly show reduced citation impact and investigates whether this represents genuine impact reduction or methodological artifacts.Design/methodology/approach:We analyzed 29 million papers(1950-2016)using Poisson regression to examine relationships between the CD index and citation count,with controls for fields,team size,and reference count.Findings:Papers with high CD indices showed reduced citation impact over time.However,when controlling for increasing reference counts in papers,this relationship reversed,revealing a positive association.Papers with more references exhibit lower CD indices owing to the index’s sensitivity to the reference count,while achieving higher citation counts.Alternative innovation metrics consistently show positive correlations with citation impact.Research limitations:The approach may not adequately capture the reduced citation impact of highly disruptive papers with fewer references.The analysis is limited to journal articles and shows correlation rather than causality.Practical implications:The apparent undervaluation of disruptive research stems from methodological artifacts in the CD index calculation driven by evolving reference patterns.Researchers should control for the reference count when using this metric.Originality/value:This study reveals that bias against disruptive research is specific to the CD index’s calculation methodology,identifying reference behavior as the key factor affecting the relationship between disruption metrics and citation impact.展开更多
This study investigates the influence of runaway current in runaway plasmas on the dynamics of sawtooth oscillations and resultant loss of runaway electrons(RE)using the 3D magnetohydrodynamic(MHD)code M3D-C^(1)(Jardi...This study investigates the influence of runaway current in runaway plasmas on the dynamics of sawtooth oscillations and resultant loss of runaway electrons(RE)using the 3D magnetohydrodynamic(MHD)code M3D-C^(1)(Jardin et al 2012 J.Comput.Sci.Discovery 6014002).Using an HL-2A-like equilibrium,we confirm that in the linear phase,the impact of REs on resistive internal kink instabilities is consistent with previous research.In the nonlinear phase,as the runaway current fully replaces the plasmas current,we observe a significant suppression of sawtooth oscillations,with the first sawtooth cycle occurring earlier compared to the case without runaway current.Following the first sawtooth collapse,plasma current density,runaway current density,and safety factor(q)flatten within the q=1 surface,albeit displaying fine structures.Subsequently,the growing high torodial(n)and poloidal(m)mode number modes disrupt the magnetic surfaces,leading to the loss of REs outside the q=1 surface,while minimally affecting the majority of REs well-confined within it.Thus,in the current model,the physical processes associated with the presence of sawtooth oscillations do not effectively dissipate runaway current,as REs are assumed to be collisionless.In addition,the final profile of runaway current density exhibits increased steepening near the q=1 surface in contrast to the initial profile,displaying a distinctive corrugated inhomogeneity influenced by the growing fluctuation of the n=0 component.Finally,detailed convergence tests are conducted to validate the numerical simulations.展开更多
文摘Objective: The objective of this work is to search for a novel method to explore the disrupted pathways associated with periodontitis(PD) based on the network level.Methods: Firstly, the differential expression genes(DEGs) between PD patients and cognitively normal subjects were inferred based on LIMMA package. Then, the proteinprotein interactions(PPI) in each pathway were explored by Empirical Bayesian(EB) coexpression program. Specifically, we determined the 100 th weight value as the threshold value of the disrupted pathways of PPI by constructing the randomly model and confirmed the weight value of each pathway. Meanwhile, we dissected the disrupted pathways under the weight value > the threshold value. Pathways enrichment analyses of DEGs were carried out based on Expression Analysis Systematic Explored(EASE) test. Finally, the better method was selected based on the more rich and significant obtained pathways by comparing the two methods. Results: After the calculation of LIMMA package, we estimated 524 DEGs in all. Then we determined 0.115222 as the threshold value of the disrupted pathways of PPI. When the weight value>0.115222, there were 258 disrupted pathways of PPI enriched in. Additionally, we observed those 524 DEGs that were enriched in 4 pathways under EASE=0.1.Conclusion: We proposed a novel network method inferring the disrupted pathway for PD. The disrupted pathways might be underlying biomarkers for treatment associated with PD.
基金funded by Darius Project(Head M.Marroni)by the PRA project of the Pisa University(Head S.Rocchi),grants from IGG-CNRFAR-2018 Project of the Ferrara University(Head E.S.and V.L.)。
文摘The Durkan Complex is a key tectonic element of the Makran accretionary prism(SE Iran)and it has been interpreted as representing a continental margin succession.We present here a multidisciplinary study of the western Durkan Complex,which is based on new geological,stratigraphic,biostratigraphic data,as well as geochemical data of the volcanic and meta-volcanic rocks forming this complex.Our data show that this complex consists of distinct tectonic slices showing both non-metamorphic and very low-grade metamorphic deformed successions.Stratigraphic and biostratigraphic data allow us to recognize three types of successions.Type-Ⅰis composed by a Coniacian-early Campanian pelagic succession with intercalation of pillow lavas and minor volcaniclastic rocks.Type-Ⅱsuccession includes a volcanic sequence passing to a volcano-sedimentary sequence with Cenomanian pelagic limestones,followed by a hemipelagic sequence.This succession is characterized by abundant mass-transport deposits.Type-Ⅲsuccession includes volcanic and volcano-sedimentary sequences,which are stratigraphically covered by a Cenomanian platform succession.The latter is locally followed by a hemipelagic sequence.The volcanic rocks in the different successions show alkaline geochemical affinity,suggesting an origin from an oceanic within-plate setting.Our new results indicate that the western Durkan Complex represents fragments of seamounts tectonically incorporated in the Makran accretionary wedge during the latest Late Cretaceous-Paleocene.We propose that incorporation of seamounts in the frontal prism caused a shortening of the whole convergent margin and possibly contributed to controlling the deformation style in the Makran Accretionary Wedge during Late Cretaceous-Paleocene times.
基金support provided by the National Natural Science Foundation of China(Grant No.52362055)the Science and Technology Plan Project of Guangxi Zhuang Autonomous Region(Grant No.2021AC19334)Guangxi Science and Technology Major Program(Grant No.AA23062053).
文摘To provide a much more resilient transport scheme for tractor and trailer transportation systems,this paper explores the generation method of tractor and trailer transport schemes considering the influence of disrupted events.Three states of tractors including towing loaded trailers,towing empty trailers,and idle driving are taken into account.Based on the disruption management theory,a scheduling model is constructed to minimize the total deviation cost including transportation time,transportation path,and number of used vehicles under the three states of tractors.A heuristics based on the contract net and simulated annealing algorithm is designed to solve the proposed model.Through comparative analysis of examples with different numbers of newly added transportation tasks and different types of road networks,the performance of the contract net algorithm in terms of deviations in idle driving paths,empty trailer paths,loaded trailer paths,time,number of used vehicles,and total deviation cost are analyzed.The results demonstrate the effectiveness of the model and algorithm,highlighting the superiority of the disruption management model and the contract net annealing algorithm.The study provides a reference for handling unexpected events in the tractor and trailer transportation industry.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金supported by the National Natural Science Foundation of China(22375101)the Natural Science of Colleges and Universities in Jiangsu Province(24KJB430027).
文摘Background:The bacterial biofilm poses a significant challenge to traditional antibiotic therapy.There is a great need to develop novel antibiofilm agents combined with biofilm disrupting and bacteria-killing without the dependence of antibiotic.Methods:Herein,we prepared ultrasound/magnetic field-responsive ferroferric oxide nanoparticles(Fe_(3)O_(4))/glucose oxidase microbubbles(FGMB)to form a cascade catalytic system for effective removing methicillin-resistant Staphylococcus aureus biofilms.FGMB were prepared through interfacial self-assembly of Fe_(3)O_(4) nanoparticles(NPs)and glucose oxidase(GOx)at the gas-liquid interface stabilized by surfactants.Under ultrasound/magnetic field stimulation,FGMB disrupted biofilm architecture through microbubble collapse-induced microjets and magnetically driven displacement.Simultaneously,ultrasound-triggered rupture of FGMB released GOx and Fe_(3)O_(4) NPs.Glucose can be oxidized by GOx to generate gluconic acid and hydrogen peroxide which was subsequently catalyzed into hydroxyl radicals by Fe_(3)O_(4) NPs,enabling chemical eradication of biofilm-embedded bacteria.Results:Optical microscopy images demonstrated that FGMB have spherical structure with average size of approximately 17μm.FGMB showed a 65.4%decrease in methicillin-resistant Staphylococcus aureus biofilm biomass and 1.1 log bacterial inactivation efficiency(91.2%),suggesting effective biofilm elimination.In vitro experimental results also indicate that FGMB have good biocompatibility.Conclusion:This antibiofilm strategy integrated dual modes of physical biofilm disruption with chemical bacteria-killing shows great potential as a versatile,non-resistant strategy for bacterial biofilm elimination.
文摘Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across multiple conditions and its underlying mechanisms is the subject of ongoing investigation.This review synthesized current evidence to explore the association between NRH and psychiatric disorders from epidemiological,genetic,and neurobiological perspectives.We systematically identified and appraised relevant literature investigating NRH prevalence in psychiatric populations and potential explanatory mechanisms.Epidemiological evidence indicates an elevated prevalence of NRH,particularly within neurodevelopmental disorders.Potential contributing mechanisms identified include early developmental disruptions,shared genetic predispositions,and atypical patterns of brain lateralization.While the association between NRH and psychiatric conditions,especially neurodevelopmental disorders,is evident,the causal pathways and relative contributions of identified mechanisms are complex and debated.This review highlighted key areas requiring further research to elucidate these relationships.
文摘Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,this may lead to permanent impairements resulting in a loss of quality of life and a high socioeconomic burden.
文摘With the support by the National Natural Science Foundation of China,a collaboration led by Prof.Wang Jianmin(王建民)from the Institute of High Energy Physics,Chinese Academy of Sciences proposes a new mechanism for the origin of the broad-line region in Active Galactic Nuclei,which was published
文摘In this paper I will consider the intersection between family tragedy,trauma,and affective uses of narration in two Australian novels:Surrender(Hartnett,2005)and The Danger Game(Ashton,2009).In both of these novels,narratological techniques are utilised to represent a grief beyond words—the tragic loss of a close family member,specifically,a sibling.Both novels use disruptions in narrative forms—particularly in the inherent expectations readers bring to the forms of first,second and third person narration.These narrative disruptions mirror the disruptions of identity experienced by the characters in these texts.Moreover,as we engage with the traumatic content through a fractured subjectivity presented by these texts,our identities as readers,too,become fractured and disrupted.These disruptions of identity echo that which is experienced by the characters themselves through their loss.By analysing the link between these disruptions and the content of these novels,we get a better understanding of the ways in which f ictive worlds can represent psychological issues.The narration of these novels and their engagement with childhood sibling loss enable us to begin to create and understand a broader aesthetic of representational trauma.
基金supported by the National Natural Science Foundation of China (Nos. 61503020, 61403020 and U1434209)the Beijing Laboratory of Urban Rail Transit, the Beijing Key Laboratory of Urban Rail Transit Automation and Controlthe Major Program of Beijing Municipal Science & Technology Commission under Grant Z161100001016006
文摘In large cities with heavily congested metro lines, unexpected disturbances often occur, which may cause severe delay of multiple trains, blockage of partial lines, and reduction of passenger service. Metro dispatchers have taken a practical strategy of rescheduling the timetable and adding several backup trains in storage tracks to alleviate waiting passengers from crowding the platforms and recover from such disruptions. In this study,we first develop a mixed integer programming model to determine the optimal train rescheduling plan with considerations of in-service and backup trains. The aim of train rescheduling is to frequently dispatch trains to evacuate delayed passengers after the disruption. Given the nonlinearity of the model, several linearization techniques are adapted to reformulate the model into an equivalent linear model that can be easily handled by the optimization software. Numerical experiments are implemented to verify the effectiveness of the proposed train rescheduling approach.
基金supported by the National Key Research and Development Project (2021YFA1201404)National Natural Science Foundation of China Major Project (81991514)+6 种基金General Project (82272530, 82372459)Jiangsu Province Medical Innovation Center of Orthopedic Surgery (CXZX202214)Jiangsu Provincial Key Medical Center FoundationJiangsu Provincial Medical Outstanding Talent FoundationJiangsu Provincial Medical Youth Talent FoundationJiangsu Provincial Key Medical Talent Foundationthe Fundamental Research Funds for the Central Universities (14380493, 14380494)
文摘Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture.In this study,we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM.Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.Mechanistically,SIRT3 suppression results in hyperacetylation of FOXO3,hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria.Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3,thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM.Collectively,our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control,crucial for maintaining bone homeostasis in T2DM.These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.
文摘Fusobacterium is a genus of obligate anaerobic gram-negative bacilli that usually colonize the oropharynx,gastrointestinal tract,upper respiratory tract,and vaginal mucosa of humans as a part of the normal flora.[1,2]Infections may occur once host defense mechanisms are altered and mucosal barriers are disrupted.[3]The clinical spectrum is wide and includes pharyngitis,sinusitis,abscess formation,puerperal infections,bacteremia,and septic shock.Within this genus,two species are most commonly isolated:Fusobacterium nucleatum and Fusobacterium necrophorum(F.necrophorum).F.necrophorum is usually associated with Lemierre’s syndrome,[4,5]a type of septic thrombophlebitis of the internal jugular vein.
基金supported by the grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85602-R)the Spanish Ministry of Science and Innovation(PID2020-119638RB-I00 to EGR)FPU-program(FPU17/02616 to JCG)。
文摘The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.
基金supported by the ENN Group,the ENN Energy Research Institute and National Natural Science Foundation of China(No.12205122).
文摘EHL-2 is a compact,high-field spherical tokamak designed to explore the potential of an advanced p-11B nuclear fusion reactor.Due to its high plasma current and thermal energy,it is crucial to mitigate the impact associated with disruptions to ensure the safe operation of EHL-2.This paper evaluates the performance requirements of the disruption prediction system on EHL-2,with a particular focus on applying generalizable knowledge transfer from existing devices to future ones.Furthermore,the key characteristics of disruption mitigation strategies are analyzed,and their overall mitigation performance on EHL-2 is assessed.This insight provides valuable guidance for optimizing the engineering design of EHL-2 and identifying its optimal operational regime.
基金supported by the Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University),Ministry of Education(No.GKE-KF202305)the Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor,and the Natural Science Foundation of Jiangsu Province(No.BK20211510)。
文摘Vascular disrupting agents(VDAs)can destroy tumor vasculature and lead to tumor ischemia and hypoxia,resulting in tumor necrosis.However,VDAs are easy to induce the upregulation of genes that are associated with cancer cell drug resistance and angiogenesis in tumor cells.Hypoxia-activated chemotherapy will be an ideal supplement to VDAs therapy since it can help to fully utilize the ischemia and hypoxia induced by VDAs to realize a synergistic antitumor therapeutic outcome.Here,we design a liposome whose surface is modified with a tumor-homing peptide Cys-Arg-Glu-Lys-Ala(CREKA,which can specifically target tumor vessels and stroma)and whose aqueous cavity and lipid bilayer are loaded by a hypoxia-activatable drug banoxantrone dihydrochloride(AQ4N)and a VDA combretastatin A4(CA4),respectively.CA4 can selectively target vascular endothelial cells and destroy the tumor blood vessels,which will cause the rapid inhibition of blood flow in tumor and enhance the hypoxia in the tumor region.As a consequence,AQ4N can exert its boosted cytotoxicity under the enhanced hypoxic environment.The as-prepared liposome with a uniform particle size exhibits good stability and high cancer cell killing efficacy in vitro.In addition,in vivo experiments confirm the excellent tumortargeting/accumulation,tumor vasculature-damaging,and tumor inhibition effects of the liposome.This work develops a liposomal which can achieve safe and effective tumor suppression without external stimulus excitation by only single injection,and is expected to benefit the future development of effective antitumor liposomal drugs.
基金supported by the National Natural Science Fund for Distinguished Young Scholars of China(82125004).
文摘The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions.Human development occurs under the influence of gravity,shielded from space radiation by Earth’s magnetic field,and within an environment characterized by 24-hour day-night cycles resulting from Earth’s rotation,thus deviating from these conditions necessitates adaptive responses for survival.With upcoming manned lunar and Martian missions approaching rapidly,it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health.This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth,to analyze how microgravity,space radiation,and disrupted circadian affect cardiovascular well-being.Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction,which may be exacerbated by space radiation.Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations,cytoskeletal damage,and myofibril changes.Disruptions in circadian rhythms caused by factors such as microgravity,light exposure,and irregular work schedules,could further exacerbate cardiovascular issues.However,current research tends to predominantly focus on disruptions in the core clock gene,overlooking the multifactorial nature of circadian rhythm disturbances in space.Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks,to preserve astronaut health and ensure mission success.
文摘Background:Long-term exposure to toxic substances increases the risk of their accumulation and triggering endocrine disruption.The ill-planned irrigation systems in Uzbekistan led to severe environmental disasters,resulting in aridization and the spread of organochlorine pesticides and toxic metals across the region.Objective:We investigate the influence of negative environmental factors on hormonal activities such as sex steroids,gonadotropic hormones,and growth factors,in addition to potential disruptions in growth rate and anthropometric indicators in prepubertal adolescents living in this region.Methods:This study included 405 prepubertal boys aged 11 to 13 years,residing in the cities of Muynak(unfavorable region)and Nukus(favorable region)of Uzbekistan.We measured 20 anthropometric parameters and assessed somatotype by the Heath-Carter method,peak height velocity(PHV),and maturity offset based on Mirwald's equation.In addition,the endocrine profile of 8 hormonal parameters was assessed,which includes growth factors,gonadotropins,sex steroids,and thyroid status.Results:We observed a positive dependence of physique,rate of maturation,and level of androgens,stimulated by gonadotropin hormones.Children living in unfavorable environmental regions show a decrease in folliclestimulating hormone,luteinizing hormone,total testosterone(the best predictor),and anthropometric signs of androgen deficiency.These resulted in an increase in maturity offset and PHV,combined with lower skeletal density and ectomorphic somatotype compared to their peers living in favorable environmental regions.Conclusion:Regional differences in stature,body weight,and anthropometric parameters of adipose tissue,growth factor axis,and thyroid hormones are the influencing indices in the regulation of growth in prepubertal children.We hypothesize that the inhibition of the gonadotropin-testosterone axis may result from endocrine disruption due to higher levels of toxic metals and pesticide exposure.
基金supported by the Basic Research Program for Young Students(Doctoral Students)of the National Natural Science Foundation of China(#724B2015)。
文摘Purpose:This study examines why papers with high CD indices(measuring research disruptiveness)increasingly show reduced citation impact and investigates whether this represents genuine impact reduction or methodological artifacts.Design/methodology/approach:We analyzed 29 million papers(1950-2016)using Poisson regression to examine relationships between the CD index and citation count,with controls for fields,team size,and reference count.Findings:Papers with high CD indices showed reduced citation impact over time.However,when controlling for increasing reference counts in papers,this relationship reversed,revealing a positive association.Papers with more references exhibit lower CD indices owing to the index’s sensitivity to the reference count,while achieving higher citation counts.Alternative innovation metrics consistently show positive correlations with citation impact.Research limitations:The approach may not adequately capture the reduced citation impact of highly disruptive papers with fewer references.The analysis is limited to journal articles and shows correlation rather than causality.Practical implications:The apparent undervaluation of disruptive research stems from methodological artifacts in the CD index calculation driven by evolving reference patterns.Researchers should control for the reference count when using this metric.Originality/value:This study reveals that bias against disruptive research is specific to the CD index’s calculation methodology,identifying reference behavior as the key factor affecting the relationship between disruption metrics and citation impact.
基金supported in part by the National Key R&D Program of China (No.2022YFE03040002)the Natural Science Foundation of Sichuan (No.2022NSFSC1814)+3 种基金National Natural Science Foundation of China (Nos.12305246,12175053 and 12261131622)the Italian Ministry of Foreign Affairs (No.CN23GR02)the Fundamental Research Funds for the Central Universitiessupported by US Department of Energy (No.DE-AC0209CH11466)。
文摘This study investigates the influence of runaway current in runaway plasmas on the dynamics of sawtooth oscillations and resultant loss of runaway electrons(RE)using the 3D magnetohydrodynamic(MHD)code M3D-C^(1)(Jardin et al 2012 J.Comput.Sci.Discovery 6014002).Using an HL-2A-like equilibrium,we confirm that in the linear phase,the impact of REs on resistive internal kink instabilities is consistent with previous research.In the nonlinear phase,as the runaway current fully replaces the plasmas current,we observe a significant suppression of sawtooth oscillations,with the first sawtooth cycle occurring earlier compared to the case without runaway current.Following the first sawtooth collapse,plasma current density,runaway current density,and safety factor(q)flatten within the q=1 surface,albeit displaying fine structures.Subsequently,the growing high torodial(n)and poloidal(m)mode number modes disrupt the magnetic surfaces,leading to the loss of REs outside the q=1 surface,while minimally affecting the majority of REs well-confined within it.Thus,in the current model,the physical processes associated with the presence of sawtooth oscillations do not effectively dissipate runaway current,as REs are assumed to be collisionless.In addition,the final profile of runaway current density exhibits increased steepening near the q=1 surface in contrast to the initial profile,displaying a distinctive corrugated inhomogeneity influenced by the growing fluctuation of the n=0 component.Finally,detailed convergence tests are conducted to validate the numerical simulations.
