BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We ...BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.展开更多
Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial...Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial energy metabolism[1].Ginsenoside Rbi(Rbi),one of the most abundant natural ingredients in ginseng and Panax notoginseng,has been proven to protect the heart from MI/reperfusion injury(RI)[2].展开更多
For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language defi...For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.展开更多
Dear Editor,This letter proposes a deep synchronization control(DSC) method to synchronize grid-forming converters with power grids. The method involves constructing a novel controller for grid-forming converters base...Dear Editor,This letter proposes a deep synchronization control(DSC) method to synchronize grid-forming converters with power grids. The method involves constructing a novel controller for grid-forming converters based on the stable deep dynamics model. To enhance the performance of the controller, the dynamics model is optimized within the deep reinforcement learning(DRL) framework. Simulation results verify that the proposed method can reduce frequency deviation and improve active power responses.展开更多
Medium-entropy alloys(MEAs)that exhibit transformation-induced plasticity(TRIP)from face-centered cubic(FCC)to body-centered cubic(BCC)are considered promising for liquid hydrogen environments due to their remarkable ...Medium-entropy alloys(MEAs)that exhibit transformation-induced plasticity(TRIP)from face-centered cubic(FCC)to body-centered cubic(BCC)are considered promising for liquid hydrogen environments due to their remarkable cryogenic strength.Nonetheless,studies on hydrogen embrittlement(HE)in BCC-TRIP MEAs have not been conducted,although the TRIP effect and consequent BCC martensite usually deteriorate HE susceptibility.In these alloys,initial as-quenched martensite alters hydrogen diffusion and trap behavior,and deformation-induced martensitic transformation(DIMT)provides preferred crack propagation sites,which critically affects HE susceptibility.Therefore,this study aims to investigate the HE behav-ior of BCC-TRIP MEAs by designing four V10 Cr_(10)Co_(30)Fe_(50-x)Ni_(x)(x=0,1,2,and 3 at%)MEAs,adjusting both the initial phase constituent and phase metastability.A decreased Ni content leads to a reduced fraction and mechanical stability of FCC,which in turn increases HE susceptibility,as determined through electro-chemical hydrogen pre-charging and slow-strain rate tests The permeation test and thermal desorption analysis reveal that the hydrogen diffusivity and content are affected by initial BCC fraction,interconnectivity of BCC,and refined FCC.As these initial phase constituents differ between the alloys with FCC-and BCC-dominant initial phase,microstructural factors affecting HE are unveiled discretely among these alloy groups by correlation of hydrogen-induced crack behavior with hydrogen diffusion and trap behavior.In alloys with an FCC-dominant initial phase,the initial BCC fraction and DIMT initiation rate emerge as critical factors,rather than the extent of DIMT.For BCC-dominant alloys,the primary contributor is an increase in the initial BCC fraction,rather than the extent or rate of DIMT.The unraveled roles of microstructural factors provide insights into designing HE-resistant BCC-TRIP MEAs.展开更多
Fertility preservation and pregnancymanagement are critical considerations for patients undergoing organtransplantation.Innovations in assisted reproductive technologies,hormonalmodulation,and personalized medicine ha...Fertility preservation and pregnancymanagement are critical considerations for patients undergoing organtransplantation.Innovations in assisted reproductive technologies,hormonalmodulation,and personalized medicine have expanded options for these patients,who face unique challenges due to immunosuppressive therapy and organ functionconcerns.This mini-review explores advancements in cryopreservationtechniques,pre-conception counseling,and multidisciplinary strategies forsafe pregnancies post-transplantation.Emphasis is placed on balancing maternalhealth,graft function,and fetal outcomes.The integration of reproductive andtransplant medicine is paving the way for improved quality of life andreproductive autonomy for this patient population.展开更多
Pulpotomy,which belongs to vital pulp therapy,has become a strategy for managing pulpitis in recent decades.This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing l...Pulpotomy,which belongs to vital pulp therapy,has become a strategy for managing pulpitis in recent decades.This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes.Pulpotomy is categorized into partial pulpotomy(PP),the removal of a partial segment of the coronal pulp tissue,and full pulpotomy(FP),the removal of whole coronal pulp,which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth.Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality,the overall treatment plan,the patient’s general health status,and pulp inflammation reassessment during operation.This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics,Chinese Stomatological Association.It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment(RCT)on mature permanent teeth with pulpitis from a biological basis,the development of capping biomaterial,and the diagnostic considerations to evidence-based medicine.This expert statement intends to provide a clinical protocol of pulpotomy,which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.展开更多
Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,...Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,gastrointestinal dysfunction,and increased recurrence rates.When these concerns develop,traditional Chinese medicine(TCM)may have advantages.TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body.It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication.This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways,which reflects the flexibility of TCM in treating diseases and the advantages of multi-level,multipathway,and multi-target treatments for HPAG.展开更多
Herein,we present the electrocatalytic four-electron hydrogenation of oxalic acid into glycolic acid using black TiO_(2)as an electrocatalyst.Oxalic acid is an abundant compound found in several sources of organic was...Herein,we present the electrocatalytic four-electron hydrogenation of oxalic acid into glycolic acid using black TiO_(2)as an electrocatalyst.Oxalic acid is an abundant compound found in several sources of organic waste.The results showed a high selectivity of black TiO_(2)toward glycolic acid,with the formation of glyoxylic acid being the rate-limiting step (glyoxylic acid is the two-electron intermediate).The highest Faradaic efficiency (FE) of 69.6%±8.3% was achieved at 10.2 mA cm^(-2)in 4 h of electrolysis using an H-type cell operated at room temperature,with 50.2%±3.8% of oxalic acid conversion (degradation kinetic constant k=0.0042±0.0001 min-1),58.8%±7.0%of reaction yield and 1.2±0.18 g L-1of glycolic acid production.A theoretical model of black TiO_(2)coming from anatase TiO_(2)was implemented by introducing Ti3+defects,which gave black TiO_(2)the theoretical capability to easily transform oxalic acid into glycolic acid as experimentally observed.The reaction mechanism was supported and described in detail by density functional theory calculations,which revealed that surface Ti^(3+)states were the main catalytic sites.This is the first time that a detailed step-by-step mechanism at the atomic level has been proposed for this electrocatalytic reaction,which represents a valuable contribution to the understanding of this process of high energy/environmental interest.This is also the first time that black TiO_(2)has been used as an electrocatalyst for this sustainable process.展开更多
This research aims to explore the decoration of TiO_(2)substrates with silver nanoparticles as a means of enhancing the photocatalytic oxidation of organic compounds.The results show that decorated TiO_(2)substrates e...This research aims to explore the decoration of TiO_(2)substrates with silver nanoparticles as a means of enhancing the photocatalytic oxidation of organic compounds.The results show that decorated TiO_(2)substrates exhibit significantly higher photocatalytic activity in sunlight than undecorated substrates.Morphological analysis is performed,followed by optical and structural characterizations.Scanning electron microscopy analysis of the TiO_(2)reveals many nanotubular structures with particle sizes of∼134.4,148.8,and 132.7 nm at random locations.TiO_(2)is also found to have an absorbance range of 397.6 nm,from which it is known that the photocatalyst reacts in the presence of an ultraviolet source.From the Miller indices of the x-ray diffraction peaks,the preferred crystal orientation is found to be associated with a face-centered cubic structure with a crystallite size of 3.76 nm.Using these promising results,photocatalytic analysis is performed,revealing good degradation characteristics.This investigation reveals that TiO_(2)substrates coated with Ag nanoparticles possess significant potential for application in the photocatalytic oxidation of methylene blue dye,which is a crucial step toward establishing a cleaner environment.展开更多
The crossover between short-range and long-range(LR)universal behaviors remains a central theme in the physics of LR interacting systems.The competition between LR coupling and the Berezinskii-Kosterlitz-Thouless mech...The crossover between short-range and long-range(LR)universal behaviors remains a central theme in the physics of LR interacting systems.The competition between LR coupling and the Berezinskii-Kosterlitz-Thouless mechanism makes the problem more subtle and less understood in the two-dimensional(2D)XY model,a cornerstone for investigating low-dimensional phenomena and their implications in quantum computation.We study the 2D XY model with algebraically decaying interaction~1/r^(2+σ).Utilizing an advanced update strategy,we conduct LR Monte Carlo simulations of the model up to a linear size of L=8192.Our results demonstrate continuous phase transitions into a ferromagnetic phase forσ<2,which exhibit the simultaneous emergence of a long-ranged order and a power-law decaying correlation function due to the Goldstone mode.Furthermore,we fnd logarithmic scaling behaviors in the low-temperature phase atσ=2.The observed scaling behaviors in the low-temperature phase forσ≤2 agree with our theoretical analysis.Our fndings request further theoretical understanding and can be of practical application in cutting-edge experiments like Rydberg atom arrays.展开更多
The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke ...The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.展开更多
Reactive oxygen species(Ros)play a dual role in mammalian spermatozoa.At high levels,they are detrimental to sperm function since they can promote oxidative stress that produces oxidation of protein,lipids,and sperm D...Reactive oxygen species(Ros)play a dual role in mammalian spermatozoa.At high levels,they are detrimental to sperm function since they can promote oxidative stress that produces oxidation of protein,lipids,and sperm DNA.This oxidative damage is associated with male infertility.On the other hand,when RoS are produced at low levels,they participate in the redox signaling necessary for sperm capacitation.Capacitation-associated RoS are produced by the sperm oxidase,whose identity is still elusive,located in the plasma membrane of the spermatozoon.Ros,such as superoxide anion,hydrogen peroxide,nitric oxide,and peroxynitrite,activate protein kinases and inactivate protein phosphatases with the net increase of specific phosphorylation events.Peroxiredoxins(PRDXs),antioxidant enzymes that fight against oxidative stress,regulate redox signaling during capacitation.Among them,PRDX6,which possesses peroxidase and calcium-independent phospholipase A,(iPLA,)activities,is the primary regulator of redox signaling and the antioxidant response in human spermatozoa.The lysophosphatidic acid signaling is essential to maintain sperm viability by activating the phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)pathway,and it is regulated by PRDX6 iPLA2,protein kinase C(PKC),and receptor-type protein tyrosine kinase.The understanding of redox signaling is crucial to pave theway fornovel diagnostic tools and treatments of male infertility.展开更多
Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has become a growing health concern globally.Microvascular invasion and high tumor burden are key factors limiting the curative effect of selective internal radiation therapy(SI...BACKGROUND Hepatocellular carcinoma(HCC)has become a growing health concern globally.Microvascular invasion and high tumor burden are key factors limiting the curative effect of selective internal radiation therapy(SIRT).CASE SUMMARY This case study reports a 49-year-old woman who was diagnosed with China Liver Cancer Staging(CNLC)IIIa HCC and>15 cm tumor diameter.Initially,due to insufficient future liver remnant and vascular invasion,the tumor was unresectable;however,radical hepatectomy was performed after successful conversion therapy with SIRT using yttrium-90(90Y)resin microspheres followed by hepatic arterial infusion chemotherapy(HAIC)with tyrosine kinase inhibitor(TKI)and anti-programmed death-1(PD-1)antibody.SIRT using 90Y resin microspheres was given by the right hepatic artery and chemoembolization was simultaneously performed in the tumor’s feeding vessels from the right diaphragmatic artery.HAIC was followed every three weeks with lenvatinib and tislelizumab.At 4 months post-SIRT,the tumor was downstaged to CNLC Ib and the patient successfully underwent hepatectomy.The histopathological examination of the resected specimen showed extensive necrosis.CONCLUSION This case study provides evidence for an integrated treatment strategy combining SIRT and HAIC with TKI and anti-PD-1 antibodies for patients with large HCC and microvascular invasion.Further confirmatory trials are required in the future.展开更多
Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disord...Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disorders is extremely complex,with a wide spectrum of biological,psychological,and sociocultural factors being responsible for their appearance and development.In this sense,immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders,worsening mainly the central nervous system(neuroinflammation)and the periphery of the body(systemic inflammation).However,these alterations cannot be understood separately,but as part of a complex picture in which different factors and systems interact with each other.Psychoneuroimmunoendocrinology(PNIE)is the area responsible for studying the relationship between these elements and the impact of mind–body integration,placing the immune system as part of a whole.Thus,the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche,damage to the nervous system,alterations to the endocrine and metabolic systems,and disruption of the microbiota and intestinal ecosystem,as well as of other organs and,in turn,all these mechanisms are responsible for inducing and enhancing the immune dysfunction.Similarly,the clinical approach to these patients is usually multidisciplinary,and the therapeutic arsenal includes different pharmacological(for example,antidepressants,antipsychotics,and lithium)and non-pharmacological(i.e.,psychotherapy,lifestyle,and electroconvulsive therapy)treatments.These interventions also modulate the immune system and other elements of the PNIE in these patients,which may be interesting to understand the therapeutic success or failure of these approaches.In this sense,this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE.Likewise,an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients,in order to identify the mechanisms described and their possible uses as biomarkers.展开更多
Background For patients with locally advanced esophagogastric cancer,the standard of care in the UK is neoadjuvant chemotherapy(NAC)followed by surgery.Prehabilitation exercise training can improve physiological funct...Background For patients with locally advanced esophagogastric cancer,the standard of care in the UK is neoadjuvant chemotherapy(NAC)followed by surgery.Prehabilitation exercise training can improve physiological function and fitness.If such improvements translate to increased immune infiltration of tumors,exercise could be prescribed as an immune adjuvant during NAC and potentially improve clinical outcomes.As such,we aimed to determine whether prehabilitation increased tumor infiltrating lymphocytes(TILs).Methods We assessed 22 patients with locally advanced esophageal cancer on a randomized control trial comparing 16 weeks of low-to-moderate intensity twice weekly supervised and thrice weekly home-based exercise(Prehab:n=11)to no prehabilitation(Control:n=11).Our primary outcome was to compare tumor-immune responses between Controls and Prehab.We compared formalin-fixed paraffin-embedded tumors by high-resolution multispectral immunohistochemistry(mIHC)and NanoString spatial transcriptomics.Secondarily,we determined relationships between changes in fitness to the exercise training and tumor-immune measures.Specifically,we assessed percentage changes in peak cardiorespiratory fitness as assessed by peak oxygen uptake(VO_(2peak))before NAC(Baseline)and after 8 weeks of NAC(Post-NAC),and changes between Baseline and following 8 weeks of NAC recovery before surgery(Pre-surgery)and correlated changes in fitness with tumor-immune responses.Finally,as an exploratory aim,we assessed clinical outcomes between groups,including survival,therapy tolerance,and tumor regrading.Results We observed that Prehab had significantly more CD8+lymphocytes in their tumors(mean difference(diff.)=1.79,95%confidence interval(95%CI):0.76‒2.82,p<0.001)and their stroma(mean diff.=1.59,95%CI:0.66‒2.52,p<0.001)than the Controls.When normalized to total numbers of TILs,Prehab had higher levels of CD56+natural killer(NK)cells(median diff.=0.87,95%CI:0.25‒2.18),p=0.0274),consisting primarily of CD56^(dim)NK cells(median diff.=0.48,95%CI:0.03‒2.53),p=0.0464).Evaluation of the presence and localization of tumor-associated tertiary lymphoid structures(TLS)in the esophageal tumors revealed that most TLS were in the peritumoral regions.Prehab had a higher TLS cell density(cells/mm^(2);median diff.=18,959,95%CI:13,518‒22,635),p<0.001)and more clearly defined germinal centers indicative of mature TLS visually.We observed that Prehab maintained their VO_(2peak)during NAC while the Controls’VO_(2peak)reduced by 9.0%±10.2%(mean±SD)(Post-NAC:p=0.018).Pre-surgery,Prehab VO_(2peak)was a clinically meaningful 3.27±1.31 mL/kg/min higher than Controls(p=0.022).Between Baseline and Post-NAC,where the Prehab maintained VO_(2peak)better than Controls,there were significant positive associations with percentage changes in VO_(2peak)and the frequencies of CD8+TILs(r=0.531,p=0.016),programmed death-ligand 1+(PDL1+)cells(r=0.566,p=0.009),and granzyme B+(GrzB+)TILs(r=0.582,p=0.007).Similar relationships were observed for changes in VO_(2peak)from Baseline to Pre-Surgery only in the Prehab group.We observed no differences between groups regarding clinical outcomes such as survival,therapy tolerance,or tumor regrading.Conclusion We show that exercise training during NAC,which promotes higher levels of cardiorespiratory fitness than no exercise,is associated with increased frequencies of TILs and maturity of TLS.These data suggest that exercise during NAC enhances the immune system.Future studies are warranted to understand the clinical consequences of this.展开更多
Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
Interest in the use of cellulose nanomaterial’s continues to grow,both in research and industry,not only due to the abundance of raw materials,low toxicity and sustainability,but also due to the attractive physical a...Interest in the use of cellulose nanomaterial’s continues to grow,both in research and industry,not only due to the abundance of raw materials,low toxicity and sustainability,but also due to the attractive physical and chemical properties that make nanocelluloses useful for a wide range of end-use applications.Among the large number of potential uses,and nanocelluloses modification and processing strategies,the chosen topic of this review focuses exclusively on plant-derived cellulose microfibers/nanofibers(CNF)and cellulose nanocrystals(CNC)processed into 2D structures—nanopapers and nanofilms—fabricated as self-standing films or applied as coatings.The end uses considered are:combinationwith standard papers and cardboards for packaging,mendingmaterial for the conservation and protection of cellulosic heritage artifacts,and component-parts of complex designs of functional devices for energy harvesting and storage.In these contexts,nanocelluloses provide high mechanical and ecofriendly properties,transparency and tunable haze,as well as flexibility/bendability in the resulting films.All these characteristics make them extremely attractive to a market seeking for sustainable,light weight and low cost raw materials for the production of goods.General perspectives on the current advantages and disadvantages of using CNF and CNC in the selected areas are also reviewed.展开更多
Volcanic terrains exhibit a complex structure of pyroclastic deposits interspersed with sedimentary processes,resulting in irregular lithological sequences that lack lateral continuity and distinct stratigraphic patte...Volcanic terrains exhibit a complex structure of pyroclastic deposits interspersed with sedimentary processes,resulting in irregular lithological sequences that lack lateral continuity and distinct stratigraphic patterns.This complexity poses significant challenges for slope stability analysis,requiring the development of specialized techniques to address these issues.This research presents a numerical methodology that incorporates spatial variability,nonlinear material characterization,and probabilistic analysis using a Monte Carlo framework to address this issue.The heterogeneous structure is represented by randomly assigning different lithotypes across the slope,while maintaining predefined global proportions.This contrasts with the more common approach of applying probabilistic variability to mechanical parameters within a homogeneous slope model.The material behavior is defined using complex nonlinear failure criteria,such as the Hoek-Brown model and a parabolic model with collapse,both implemented through linearization techniques.The Discontinuity Layout Optimization(DLO)method,a novel numerical approach based on limit analysis,is employed to efficiently incorporate these advances and compute the factor of safety of the slope.Within this framework,the Monte Carlo procedure is used to assess slope stability by conducting a large number of simulations,each with a different lithotype distribution.Based on the results,a hybrid method is proposed that combines probabilistic modeling with deterministic design principles for the slope stability assessment.As a case study,the methodology is applied to a 20-m-high vertical slope composed of three lithotypes(altered scoria,welded scoria,and basalt)randomly distributed in proportions of 15%,60%,and 25%,respectively.The results show convergence of mean values after approximately 400 simulations and highlight the significant influence of spatial heterogeneity,with variations of the factor of safety between 5 and 12 in 85%of cases.They also reveal non-circular and mid-slope failure wedges not captured by traditional stability methods.Finally,an equivalent normal probability distribution is proposed as a reliable approximation of the factor of safety for use in risk analysis and engineering decision-making.展开更多
文摘BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.
文摘Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial energy metabolism[1].Ginsenoside Rbi(Rbi),one of the most abundant natural ingredients in ginseng and Panax notoginseng,has been proven to protect the heart from MI/reperfusion injury(RI)[2].
文摘For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.
基金supported in part by the National Natural Science Foundation of China(62033005,62273270)the Natural Science Foundation of Shaanxi Province(2023JC-XJ17)
文摘Dear Editor,This letter proposes a deep synchronization control(DSC) method to synchronize grid-forming converters with power grids. The method involves constructing a novel controller for grid-forming converters based on the stable deep dynamics model. To enhance the performance of the controller, the dynamics model is optimized within the deep reinforcement learning(DRL) framework. Simulation results verify that the proposed method can reduce frequency deviation and improve active power responses.
基金supported by the Korea Institute for Advance-ment of Technology(KIAT)grant funded by the Korea Government(MOTIE)(HRD Program for Industrial Innovation)(No.P0023676)the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(Nos.NRF-2022R1A5A1030054 and RS-2023-00281508).
文摘Medium-entropy alloys(MEAs)that exhibit transformation-induced plasticity(TRIP)from face-centered cubic(FCC)to body-centered cubic(BCC)are considered promising for liquid hydrogen environments due to their remarkable cryogenic strength.Nonetheless,studies on hydrogen embrittlement(HE)in BCC-TRIP MEAs have not been conducted,although the TRIP effect and consequent BCC martensite usually deteriorate HE susceptibility.In these alloys,initial as-quenched martensite alters hydrogen diffusion and trap behavior,and deformation-induced martensitic transformation(DIMT)provides preferred crack propagation sites,which critically affects HE susceptibility.Therefore,this study aims to investigate the HE behav-ior of BCC-TRIP MEAs by designing four V10 Cr_(10)Co_(30)Fe_(50-x)Ni_(x)(x=0,1,2,and 3 at%)MEAs,adjusting both the initial phase constituent and phase metastability.A decreased Ni content leads to a reduced fraction and mechanical stability of FCC,which in turn increases HE susceptibility,as determined through electro-chemical hydrogen pre-charging and slow-strain rate tests The permeation test and thermal desorption analysis reveal that the hydrogen diffusivity and content are affected by initial BCC fraction,interconnectivity of BCC,and refined FCC.As these initial phase constituents differ between the alloys with FCC-and BCC-dominant initial phase,microstructural factors affecting HE are unveiled discretely among these alloy groups by correlation of hydrogen-induced crack behavior with hydrogen diffusion and trap behavior.In alloys with an FCC-dominant initial phase,the initial BCC fraction and DIMT initiation rate emerge as critical factors,rather than the extent of DIMT.For BCC-dominant alloys,the primary contributor is an increase in the initial BCC fraction,rather than the extent or rate of DIMT.The unraveled roles of microstructural factors provide insights into designing HE-resistant BCC-TRIP MEAs.
基金Supported by European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘Fertility preservation and pregnancymanagement are critical considerations for patients undergoing organtransplantation.Innovations in assisted reproductive technologies,hormonalmodulation,and personalized medicine have expanded options for these patients,who face unique challenges due to immunosuppressive therapy and organ functionconcerns.This mini-review explores advancements in cryopreservationtechniques,pre-conception counseling,and multidisciplinary strategies forsafe pregnancies post-transplantation.Emphasis is placed on balancing maternalhealth,graft function,and fetal outcomes.The integration of reproductive andtransplant medicine is paving the way for improved quality of life andreproductive autonomy for this patient population.
基金supported by the National Natural Science Foundation of China(82170941 and 82370948 to Lu Zhang,82071110 and 82230029 to Zhi Chen)the National Key R&D Program of China(2018YFC1105100)。
文摘Pulpotomy,which belongs to vital pulp therapy,has become a strategy for managing pulpitis in recent decades.This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes.Pulpotomy is categorized into partial pulpotomy(PP),the removal of a partial segment of the coronal pulp tissue,and full pulpotomy(FP),the removal of whole coronal pulp,which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth.Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality,the overall treatment plan,the patient’s general health status,and pulp inflammation reassessment during operation.This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics,Chinese Stomatological Association.It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment(RCT)on mature permanent teeth with pulpitis from a biological basis,the development of capping biomaterial,and the diagnostic considerations to evidence-based medicine.This expert statement intends to provide a clinical protocol of pulpotomy,which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
基金Supported by National Natural Science Foundation of China,No.82374323and Hunan Graduate Research Innovation Project,No.2023CX15.
文摘Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,gastrointestinal dysfunction,and increased recurrence rates.When these concerns develop,traditional Chinese medicine(TCM)may have advantages.TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body.It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication.This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways,which reflects the flexibility of TCM in treating diseases and the advantages of multi-level,multipathway,and multi-target treatments for HPAG.
基金DGAPA (Dirección General de Asuntos del Personal Acadé-mico) under Projects No. IA103521, IA209223 and IN111722Supercomputing Department of the Universidad Nacional Autónoma de México for the computing resources under Projects No. LANCAD-UNAM-DGTIC-427 and LANCAD-UNAM-DGTIC-370CONAHCYT-México for their postdoctoral fellowships。
文摘Herein,we present the electrocatalytic four-electron hydrogenation of oxalic acid into glycolic acid using black TiO_(2)as an electrocatalyst.Oxalic acid is an abundant compound found in several sources of organic waste.The results showed a high selectivity of black TiO_(2)toward glycolic acid,with the formation of glyoxylic acid being the rate-limiting step (glyoxylic acid is the two-electron intermediate).The highest Faradaic efficiency (FE) of 69.6%±8.3% was achieved at 10.2 mA cm^(-2)in 4 h of electrolysis using an H-type cell operated at room temperature,with 50.2%±3.8% of oxalic acid conversion (degradation kinetic constant k=0.0042±0.0001 min-1),58.8%±7.0%of reaction yield and 1.2±0.18 g L-1of glycolic acid production.A theoretical model of black TiO_(2)coming from anatase TiO_(2)was implemented by introducing Ti3+defects,which gave black TiO_(2)the theoretical capability to easily transform oxalic acid into glycolic acid as experimentally observed.The reaction mechanism was supported and described in detail by density functional theory calculations,which revealed that surface Ti^(3+)states were the main catalytic sites.This is the first time that a detailed step-by-step mechanism at the atomic level has been proposed for this electrocatalytic reaction,which represents a valuable contribution to the understanding of this process of high energy/environmental interest.This is also the first time that black TiO_(2)has been used as an electrocatalyst for this sustainable process.
文摘This research aims to explore the decoration of TiO_(2)substrates with silver nanoparticles as a means of enhancing the photocatalytic oxidation of organic compounds.The results show that decorated TiO_(2)substrates exhibit significantly higher photocatalytic activity in sunlight than undecorated substrates.Morphological analysis is performed,followed by optical and structural characterizations.Scanning electron microscopy analysis of the TiO_(2)reveals many nanotubular structures with particle sizes of∼134.4,148.8,and 132.7 nm at random locations.TiO_(2)is also found to have an absorbance range of 397.6 nm,from which it is known that the photocatalyst reacts in the presence of an ultraviolet source.From the Miller indices of the x-ray diffraction peaks,the preferred crystal orientation is found to be associated with a face-centered cubic structure with a crystallite size of 3.76 nm.Using these promising results,photocatalytic analysis is performed,revealing good degradation characteristics.This investigation reveals that TiO_(2)substrates coated with Ag nanoparticles possess significant potential for application in the photocatalytic oxidation of methylene blue dye,which is a crucial step toward establishing a cleaner environment.
基金supported by the National Natural Science Foundation of China(Grant Nos.12204173 and 12275263)the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0301900)supported by the Natural Science Foundation of Fujian Province 802 of China(Grant No.2023J02032)。
文摘The crossover between short-range and long-range(LR)universal behaviors remains a central theme in the physics of LR interacting systems.The competition between LR coupling and the Berezinskii-Kosterlitz-Thouless mechanism makes the problem more subtle and less understood in the two-dimensional(2D)XY model,a cornerstone for investigating low-dimensional phenomena and their implications in quantum computation.We study the 2D XY model with algebraically decaying interaction~1/r^(2+σ).Utilizing an advanced update strategy,we conduct LR Monte Carlo simulations of the model up to a linear size of L=8192.Our results demonstrate continuous phase transitions into a ferromagnetic phase forσ<2,which exhibit the simultaneous emergence of a long-ranged order and a power-law decaying correlation function due to the Goldstone mode.Furthermore,we fnd logarithmic scaling behaviors in the low-temperature phase atσ=2.The observed scaling behaviors in the low-temperature phase forσ≤2 agree with our theoretical analysis.Our fndings request further theoretical understanding and can be of practical application in cutting-edge experiments like Rydberg atom arrays.
基金supported by MICIU(grant number PID2021-128133NB-100/AEI/FEDER10.13039/501100011033 to JMHG)by the National Institutes of Health(grant number R01 NS083858 to SAK)+1 种基金the Intramural Grants Program IGPP00057(to SAK)VIC enjoys a FPU contract from the Comunidad de Madrid(PIPF-2022/SAL-GL-25948)。
文摘The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.
基金supported by The Canadian Institutes of Health Research(PJT165962).
文摘Reactive oxygen species(Ros)play a dual role in mammalian spermatozoa.At high levels,they are detrimental to sperm function since they can promote oxidative stress that produces oxidation of protein,lipids,and sperm DNA.This oxidative damage is associated with male infertility.On the other hand,when RoS are produced at low levels,they participate in the redox signaling necessary for sperm capacitation.Capacitation-associated RoS are produced by the sperm oxidase,whose identity is still elusive,located in the plasma membrane of the spermatozoon.Ros,such as superoxide anion,hydrogen peroxide,nitric oxide,and peroxynitrite,activate protein kinases and inactivate protein phosphatases with the net increase of specific phosphorylation events.Peroxiredoxins(PRDXs),antioxidant enzymes that fight against oxidative stress,regulate redox signaling during capacitation.Among them,PRDX6,which possesses peroxidase and calcium-independent phospholipase A,(iPLA,)activities,is the primary regulator of redox signaling and the antioxidant response in human spermatozoa.The lysophosphatidic acid signaling is essential to maintain sperm viability by activating the phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)pathway,and it is regulated by PRDX6 iPLA2,protein kinase C(PKC),and receptor-type protein tyrosine kinase.The understanding of redox signaling is crucial to pave theway fornovel diagnostic tools and treatments of male infertility.
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
基金The Fujian Key Laboratory of Translational Cancer Medicine and The Yttrium Little Red Flower Health Fund Project of Henan Sunshine Medical and Health Development Foundation,No.HKP2024001.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has become a growing health concern globally.Microvascular invasion and high tumor burden are key factors limiting the curative effect of selective internal radiation therapy(SIRT).CASE SUMMARY This case study reports a 49-year-old woman who was diagnosed with China Liver Cancer Staging(CNLC)IIIa HCC and>15 cm tumor diameter.Initially,due to insufficient future liver remnant and vascular invasion,the tumor was unresectable;however,radical hepatectomy was performed after successful conversion therapy with SIRT using yttrium-90(90Y)resin microspheres followed by hepatic arterial infusion chemotherapy(HAIC)with tyrosine kinase inhibitor(TKI)and anti-programmed death-1(PD-1)antibody.SIRT using 90Y resin microspheres was given by the right hepatic artery and chemoembolization was simultaneously performed in the tumor’s feeding vessels from the right diaphragmatic artery.HAIC was followed every three weeks with lenvatinib and tislelizumab.At 4 months post-SIRT,the tumor was downstaged to CNLC Ib and the patient successfully underwent hepatectomy.The histopathological examination of the resected specimen showed extensive necrosis.CONCLUSION This case study provides evidence for an integrated treatment strategy combining SIRT and HAIC with TKI and anti-PD-1 antibodies for patients with large HCC and microvascular invasion.Further confirmatory trials are required in the future.
基金supported by the Instituto de Salud Carlos III(EstataldeI+D+I2020-2027)co-financed by the European Development Regional Fund“A way to achieve Europe”P2022/BMD-7321(Comunidad de Madrid)and ProACapital,Halekulani S.L.and MJR.
文摘Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disorders is extremely complex,with a wide spectrum of biological,psychological,and sociocultural factors being responsible for their appearance and development.In this sense,immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders,worsening mainly the central nervous system(neuroinflammation)and the periphery of the body(systemic inflammation).However,these alterations cannot be understood separately,but as part of a complex picture in which different factors and systems interact with each other.Psychoneuroimmunoendocrinology(PNIE)is the area responsible for studying the relationship between these elements and the impact of mind–body integration,placing the immune system as part of a whole.Thus,the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche,damage to the nervous system,alterations to the endocrine and metabolic systems,and disruption of the microbiota and intestinal ecosystem,as well as of other organs and,in turn,all these mechanisms are responsible for inducing and enhancing the immune dysfunction.Similarly,the clinical approach to these patients is usually multidisciplinary,and the therapeutic arsenal includes different pharmacological(for example,antidepressants,antipsychotics,and lithium)and non-pharmacological(i.e.,psychotherapy,lifestyle,and electroconvulsive therapy)treatments.These interventions also modulate the immune system and other elements of the PNIE in these patients,which may be interesting to understand the therapeutic success or failure of these approaches.In this sense,this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE.Likewise,an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients,in order to identify the mechanisms described and their possible uses as biomarkers.
文摘Background For patients with locally advanced esophagogastric cancer,the standard of care in the UK is neoadjuvant chemotherapy(NAC)followed by surgery.Prehabilitation exercise training can improve physiological function and fitness.If such improvements translate to increased immune infiltration of tumors,exercise could be prescribed as an immune adjuvant during NAC and potentially improve clinical outcomes.As such,we aimed to determine whether prehabilitation increased tumor infiltrating lymphocytes(TILs).Methods We assessed 22 patients with locally advanced esophageal cancer on a randomized control trial comparing 16 weeks of low-to-moderate intensity twice weekly supervised and thrice weekly home-based exercise(Prehab:n=11)to no prehabilitation(Control:n=11).Our primary outcome was to compare tumor-immune responses between Controls and Prehab.We compared formalin-fixed paraffin-embedded tumors by high-resolution multispectral immunohistochemistry(mIHC)and NanoString spatial transcriptomics.Secondarily,we determined relationships between changes in fitness to the exercise training and tumor-immune measures.Specifically,we assessed percentage changes in peak cardiorespiratory fitness as assessed by peak oxygen uptake(VO_(2peak))before NAC(Baseline)and after 8 weeks of NAC(Post-NAC),and changes between Baseline and following 8 weeks of NAC recovery before surgery(Pre-surgery)and correlated changes in fitness with tumor-immune responses.Finally,as an exploratory aim,we assessed clinical outcomes between groups,including survival,therapy tolerance,and tumor regrading.Results We observed that Prehab had significantly more CD8+lymphocytes in their tumors(mean difference(diff.)=1.79,95%confidence interval(95%CI):0.76‒2.82,p<0.001)and their stroma(mean diff.=1.59,95%CI:0.66‒2.52,p<0.001)than the Controls.When normalized to total numbers of TILs,Prehab had higher levels of CD56+natural killer(NK)cells(median diff.=0.87,95%CI:0.25‒2.18),p=0.0274),consisting primarily of CD56^(dim)NK cells(median diff.=0.48,95%CI:0.03‒2.53),p=0.0464).Evaluation of the presence and localization of tumor-associated tertiary lymphoid structures(TLS)in the esophageal tumors revealed that most TLS were in the peritumoral regions.Prehab had a higher TLS cell density(cells/mm^(2);median diff.=18,959,95%CI:13,518‒22,635),p<0.001)and more clearly defined germinal centers indicative of mature TLS visually.We observed that Prehab maintained their VO_(2peak)during NAC while the Controls’VO_(2peak)reduced by 9.0%±10.2%(mean±SD)(Post-NAC:p=0.018).Pre-surgery,Prehab VO_(2peak)was a clinically meaningful 3.27±1.31 mL/kg/min higher than Controls(p=0.022).Between Baseline and Post-NAC,where the Prehab maintained VO_(2peak)better than Controls,there were significant positive associations with percentage changes in VO_(2peak)and the frequencies of CD8+TILs(r=0.531,p=0.016),programmed death-ligand 1+(PDL1+)cells(r=0.566,p=0.009),and granzyme B+(GrzB+)TILs(r=0.582,p=0.007).Similar relationships were observed for changes in VO_(2peak)from Baseline to Pre-Surgery only in the Prehab group.We observed no differences between groups regarding clinical outcomes such as survival,therapy tolerance,or tumor regrading.Conclusion We show that exercise training during NAC,which promotes higher levels of cardiorespiratory fitness than no exercise,is associated with increased frequencies of TILs and maturity of TLS.These data suggest that exercise during NAC enhances the immune system.Future studies are warranted to understand the clinical consequences of this.
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
基金funded by Consejo Nacional de Investigaciones Cientificas y Tecnicas(CONICET,Argentina),grant number PIP 0991by Universidad Nacional de Mar del Plata(UNMdP,Argentina),grant number 15/G686-ING690/23.
文摘Interest in the use of cellulose nanomaterial’s continues to grow,both in research and industry,not only due to the abundance of raw materials,low toxicity and sustainability,but also due to the attractive physical and chemical properties that make nanocelluloses useful for a wide range of end-use applications.Among the large number of potential uses,and nanocelluloses modification and processing strategies,the chosen topic of this review focuses exclusively on plant-derived cellulose microfibers/nanofibers(CNF)and cellulose nanocrystals(CNC)processed into 2D structures—nanopapers and nanofilms—fabricated as self-standing films or applied as coatings.The end uses considered are:combinationwith standard papers and cardboards for packaging,mendingmaterial for the conservation and protection of cellulosic heritage artifacts,and component-parts of complex designs of functional devices for energy harvesting and storage.In these contexts,nanocelluloses provide high mechanical and ecofriendly properties,transparency and tunable haze,as well as flexibility/bendability in the resulting films.All these characteristics make them extremely attractive to a market seeking for sustainable,light weight and low cost raw materials for the production of goods.General perspectives on the current advantages and disadvantages of using CNF and CNC in the selected areas are also reviewed.
基金the project PID2022-139202OB-I00Neural Networks and Optimization Techniques for the Design and Safe Maintenance of Transportation Infrastructures:Volcanic Rock Geotechnics and Slope Stability(IA-Pyroslope),funded by the Spanish State Research Agency of the Ministry of Science,Innovation and Universities of Spain and the European Regional Development Fund,MCIN/AEI/10.13039/501100011033/FEDER,EU。
文摘Volcanic terrains exhibit a complex structure of pyroclastic deposits interspersed with sedimentary processes,resulting in irregular lithological sequences that lack lateral continuity and distinct stratigraphic patterns.This complexity poses significant challenges for slope stability analysis,requiring the development of specialized techniques to address these issues.This research presents a numerical methodology that incorporates spatial variability,nonlinear material characterization,and probabilistic analysis using a Monte Carlo framework to address this issue.The heterogeneous structure is represented by randomly assigning different lithotypes across the slope,while maintaining predefined global proportions.This contrasts with the more common approach of applying probabilistic variability to mechanical parameters within a homogeneous slope model.The material behavior is defined using complex nonlinear failure criteria,such as the Hoek-Brown model and a parabolic model with collapse,both implemented through linearization techniques.The Discontinuity Layout Optimization(DLO)method,a novel numerical approach based on limit analysis,is employed to efficiently incorporate these advances and compute the factor of safety of the slope.Within this framework,the Monte Carlo procedure is used to assess slope stability by conducting a large number of simulations,each with a different lithotype distribution.Based on the results,a hybrid method is proposed that combines probabilistic modeling with deterministic design principles for the slope stability assessment.As a case study,the methodology is applied to a 20-m-high vertical slope composed of three lithotypes(altered scoria,welded scoria,and basalt)randomly distributed in proportions of 15%,60%,and 25%,respectively.The results show convergence of mean values after approximately 400 simulations and highlight the significant influence of spatial heterogeneity,with variations of the factor of safety between 5 and 12 in 85%of cases.They also reveal non-circular and mid-slope failure wedges not captured by traditional stability methods.Finally,an equivalent normal probability distribution is proposed as a reliable approximation of the factor of safety for use in risk analysis and engineering decision-making.
