All engineering projects consist of several steps, and one of the main tasks is to identify and characterize the most important features of rock types that will be excavated, crushed, or mined for any particular usage...All engineering projects consist of several steps, and one of the main tasks is to identify and characterize the most important features of rock types that will be excavated, crushed, or mined for any particular usage purpose, from a single residential building to major works of infrastructure. Laboratory investigation on engineering geology is thus conducted in order to determine the most relevant rock properties when designing structures such as mining shafts, tunnels, buildings, or reservoir dams to be built in sites associated with rocks. A wide range of laboratory tests is available, making the correct choice of test methods greatly relevant to determine the key property for the planned use of the rock. This paper is an illustrative case of laboratory testing of basaltic rocks to be used as riprap in a reservoir dam. It shows the important role of the petrographic study carried out to analyze the distribution pattern of smectite clay minerals. Test results are explained for the assessment of rock alterability, an essential aspect for the selection of the most suitable basalt variety for the envisaged conditions of use.展开更多
This review summarizes studies of hydrothermal alteration minerals at the Qiucun gold deposit in southeastern China and focuses on characterization and mapping of the deposit using hyperspectral remote sensing.The dep...This review summarizes studies of hydrothermal alteration minerals at the Qiucun gold deposit in southeastern China and focuses on characterization and mapping of the deposit using hyperspectral remote sensing.The deposit exhibits multistage fluid-rock interaction,as evidenced by systematic alteration assemblages,including silicification,sericitization by white micas,the development of argillaceous clays,variable chloritization,and locally significant carbonate alteration.We describe the genetic importance of such mineral groups and emphasize their diagnostic Visible and Near-Infrared to Short-Wave Infrared(VNIR-SWIR)spectral signatures,especially Al-OH,Mg-OH/Fe-OH,and CO3 absorption bands,which make it possible to distinguish between minerals,not to mention the fact that,in some instances,compositional trends may be predicted.This review’s methodological advances are discussed beginning with data collection at satellite,airborne,and ground levels,proceeding to processing procedures,such as atmospheric and topographic correction,and culminating in spectral analysis,including continuum removal,spectral matching,and unmixing/classification techniques.An integrated study of hyperspectral findings reveals that alteration minerals develop spatially coherent zones that are strongly controlled by fault/fracture structures and host-rock reactivity,producing proximal silicification/sericitization cores and larger silicified/larcenies of argillaceous rocks owing to diverse apex coverings of carbonate.This should be combined with petrography and geochemistry to address overprinting,mixed pixels,and surface weathering,and to couple mineral maps with ore-forming processes.The review finds that hyperspectral remote sensing offers a solid modeling platform for the deposit-scale alteration at Qiucun and other hydrothermal gold systems,and outlines the directions for future research to integrate quantitatively and more threedimensional alteration characterization.展开更多
The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifact...The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.展开更多
Endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy remains a challenging field in therapeutic endoscopy due to the complex anatomical reconstructions that limit access to t...Endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy remains a challenging field in therapeutic endoscopy due to the complex anatomical reconstructions that limit access to the biliary tree.Over the past two decades,device-assisted enteroscopy(DAE),including singleballoon,double-balloon,and motorized spiral enteroscopy,has expanded the feasibility of ERCP in this population,with overall technical success rates generally reported between 70%and 90%.Nevertheless,these techniques are technically demanding,time-consuming,and frequently affected by limited reach and unstable positioning.More recently,interventional endoscopic ultrasound(EUS)-guided procedures have emerged as highly effective alternatives,significantly improving clinical outcomes in selected patients,particularly in those with long-limb Roux-en-Y reconstructions where conventional methods are less effective.Percutaneous transhepatic biliary drainage continues to represent a valuable salvage option when endoscopic approaches fail,though it is associated with a greater burden of reinterventions and adverse events.This minireview provides a comprehensive overview of the main endoscopic strategies for biliary drainage in altered anatomy,focusing on technical considerations,efficacy,and safety profiles of DAE-assisted ERCP,EUS-guided interventions,and motorized systems.The evolving landscape of biliary drainage in this setting highlights the need for tailored treatment strategies,multidisciplinary collaboration,referral to high-volume centers,and further prospective studies to refine patient selection and optimize clinical outcomes.展开更多
Non-native plants are increasingly recognized as ecosystem engineers across a wide range of ecosystems.While their impacts on understory composition have been widely documented,consequences for community assembly rema...Non-native plants are increasingly recognized as ecosystem engineers across a wide range of ecosystems.While their impacts on understory composition have been widely documented,consequences for community assembly remain largely unexplored.We investigated the engineering impacts of Sorbaria sorbifolia,a naturalized Rosaceae shrub,on abiotic conditions and understory community assembly in Central European forests.Across 60 plots spanning coniferous and deciduous stands,we quantified light availability,organic layer C/N ratio and thickness,and understory functional diversity along an invasion gradient.Using ordination and linear regression,we found that increasing S.sorbifolia cover reduced light availability,thickened the organic layer,and altered C/N ratio in contrasting,forest-type-specific ways.In coniferous stands,invasion increased C/N and strongly suppressed understory light,whereas in deciduous stands it reduced C/N with weaker shading effects.These changes translate into consistent declines in functional richness and dispersion,particularly in coniferous forests where invasion led to homogenization of the understory.Trait shifts indicated stronger habitat filtering under invasion,with declines in specific leaf area(SLA)and increases in leaf dry matter content and seed mass,reflecting exclusion of light-demanding species and persistence of stress-tolerant taxa and woody seedlings.Remarkably,once S.sorbifolia exceeded~50%cover,positive relationships between habitat properties and understory functional diversity collapsed,replaced by uniform light limitation.This threshold effect highlights S.sorbifolia as an ecosystem engineer,capable of transforming forest structure and regeneration trajectories.Early detection and management are therefore crucial to prevent long-term homogenization and the formation of novel,invasion-driven forest states.展开更多
Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend ...Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend against illness,and maintain homeostasis)syndrome is considered a critical syndrome in traditional Chinese medicine(TCM)and is associated with poor prognosis in heart failure(HF).This study investigates the clinical,metabolic,and transcriptomic differences between heart failure patients with and without Qi deficiency syndrome.Methods:56 heart failure patients were evaluated using a Qi deficiency syndrome scale and divided into Qi deficiency syndrome(QD)and non-Qi deficiency(non-QD)groups based on the median score.Clinical characteristics,including baseline N-terminal pro-B-type natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),total diuretic use during hospitalization,and 90-day rehospitalization rates,were compared between the groups.Differentially expressed genes(DEGs)and differential metabolites were identified,followed by enrichment analyses and validation using qPCR and Western blot in AC16 cardiomyocytes.Results:QD patients exhibited significantly higher NT-proBNP levels,lower LVEF,and increased 90-day rehospitalization rates.Metabolomic profiling revealed lipid metabolism disruptions,notably in linoleic acid and phospholipid pathways.Transcriptomic analysis highlighted 17 DEGs,including CISD2,a critical mitochondrial regulator,which was downregulated in QD patients.Correlation analysis identified significant associations between DEGs(e.g.,CISD2,BPGM)and lipid metabolites such as PC(16:0/P-16:0).Functional knockdown of CISD2 in AC16 cells led to upregulation of lipid oxidation enzymes ALOX15 and CYP1A2,linking CISD2 dysfunction to lipid metabolic dysregulation.Conclusion:Qi deficiency is associated with more severe heart failure symptoms,worse prognosis,and distinct metabolic and transcriptomic profiles,particularly in lipid metabolism.CISD2 emerges as a potential therapeutic target,offering new avenues for integrating molecular insights with TCM approaches to optimize HF management.展开更多
Epithermal deposits are characterized by complex low-temperature hydrothermal alterations, but the links between mineralization and superimposed alteration are obscure and require further elucidation. This study emplo...Epithermal deposits are characterized by complex low-temperature hydrothermal alterations, but the links between mineralization and superimposed alteration are obscure and require further elucidation. This study employs shortwave infrared(SWIR) spectral scalars for alteration mineral mapping and three-dimensional modeling of the Ulan Uzhur Ag polymetallic deposit, a newly discovered epithermal deposit in the Qimantagh. Alteration zoning transitions from illitemuscovite-carbonate-pyrite in the core(Zone Ⅰ), through muscovite ± illite-kaolinite-chlorite-carbonate(Zone Ⅱ), to muscovite-chlorite-biotite(Zone Ⅲ) at the periphery. The Zone Ⅰ with mineralization features long-wavelength white mica(wAlOH > 2207 nm) with a high Illite Crystallinity(IC)(mean > 2.0), suggesting a relatively high-temperature environment conducive to mineralization. Petrographic analyses with fluid inclusion and IC curve characteristics suggests that fluid boiling may be a pivotal mechanism for mineral precipitation. Furthermore, surface mapping and deep threedimensional modeling of spectral characteristics reveal a correlation between long-wavelength white mica, high IC and mineralization zones. These findings indicate that SWIR spectroscopy reveal the evolution of fluids and provide valuable guidance for future exploration efforts.展开更多
This paper systematically analyzes the reservoir-forming characteristics and cretaceous shale oil types in four major hydrocarbon-generating sags(Qingxi,Ying'er,Huahai,and Shida)of the Jiuquan Basin,based on the d...This paper systematically analyzes the reservoir-forming characteristics and cretaceous shale oil types in four major hydrocarbon-generating sags(Qingxi,Ying'er,Huahai,and Shida)of the Jiuquan Basin,based on the data of experiments for microscopic and geochemical analysis of reservoirs.The hydrothermal alteration-induced reservoir-forming model and its reservoir-controlling effect in the Qingxi Sag are discussed,and the exploration potential of shale oil in these four sags are evaluated.(1)The Qingxi Sag is widely developed with mud shale,dolomitic shale,and laminated argillaceous dolomite in the Cretaceous,which can be defined as mixed shale as a whole.The source rocks in this area are of good quality and high maturity,formed in a saline water sedimentary environment,and rich in dolomite,with a strong hydrocarbon generation capacity and excellent oil generation conditions.The reservoir space has been significantly modified by hydrothermal process,with well-developed dissolution pores and microfractures,recording favorable reservoir conditions for shale oil enrichment.Overall,this sag has large reservoir thickness and large resource volume,making it the most realistic shale oil exploration target in the Jiuquan Basin.However,it faces challenges such as great burial depth(deeper than 4500 m)and strong tectonic stress.(2)The Ying'er,Huahai,and Shida sags all feature sand-mud interbeds consisting of fan delta front thin sandbodies and lacustrine mud shale in the Cretaceous,having good source rock quality and favorable conditions for interbedded-type shale oil accumulation.The source rocks are insufficient in thermal evolution degree and unevenly distributed,and favorable shale oil resources are mainly endowed near the center of the sags.Reservoirs are primarily composed of siltstone to fine sandstone,suggesting relatively good reservoir conditions,generally with small burial depth(3000-4000 m)and the possibility of local sweet spots.It is noted that the Ying'er Sag has already produced low-mature to mature oil,qualifying it as a near-term realistic shale oil exploration area.展开更多
Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulat...Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.展开更多
Load frequency control(LFC)is a critical function to balance the power consumption and generation.Thegrid frequency is a crucial indicator for maintaining balance.However,the widely used information and communication ...Load frequency control(LFC)is a critical function to balance the power consumption and generation.Thegrid frequency is a crucial indicator for maintaining balance.However,the widely used information and communication infrastructure for LFC increases the risk of being attacked by malicious actors.The dynamic load altering attack(DLAA)is a typical attack that can destabilize the power system,causing the grid frequency to deviate fromits nominal value.Therefore,in this paper,we mathematically analyze the impact of DLAA on the stability of the grid frequency and propose the network parameter regulation(NPR)to mitigate the impact.To begin with,the dynamic LFC model is constructed by highlighting the importance of the network parameter.Then,we model the DLAA and analyze its impact on LFC using the theory of second-order dynamic systems.Finally,we model the NPR and prove its effect in mitigating the DLAA.Besides,we construct a least-effort NPR considering its infrastructure cost and aim to reduce the operation cost.Finally,we carry out extensive simulations to demonstrate the impact of the DLAA and evaluate the mitigation performance of NPR.The proposed cost-benefit NPR approach can not only mitigate the impact of DLAA with 100%and also save 41.18$/MWh in terms of the operation cost.展开更多
When teaching neurology students about epilepsy,selecting appropriate antiseizure medications(ASMs)based on seizure type is a fundamental objective.Carbamazepine(CBZ),a widely used first-line ASM,is effective against ...When teaching neurology students about epilepsy,selecting appropriate antiseizure medications(ASMs)based on seizure type is a fundamental objective.Carbamazepine(CBZ),a widely used first-line ASM,is effective against focal seizures,generalized tonic-clonic seizures,and mixed seizure patterns[1].However,CBZ paradoxically aggravates absence seizures,as demonstrated by increased 36 Hz spike-and-wave discharges(SWDs)in both patients and animal models[2,3].While prior studies implicated altered GABAA receptor function in the thalamic ventrobasal complex[4],the precise mechanisms remained unclear.Recently,an inspiring study published on PNAS by Jang et al.from Stanford University has highlighted the thalamic reticular nucleus(RT)as the key brain region responsible for CBZ's aggravating effect on absence seizures[5].The combination of transgenic mouse models,optogenetics,and detailed electrophysiology in the original study provided exceptional precision in probing mechanistic insights,which greatly strengthens the conclusions.展开更多
Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,...Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.展开更多
Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential a...Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential as a therapeutic strategy to reverse age-related skeletal senescence and promote bone regeneration.Meanwhile,other age-related mechanisms,involving altered cellular functions,impaired intercellular crosstalk,disturbed tissue microenvironment,and decreased regenerative capacity,synergistically contribute to the pathogenesis.In this review,we outline the cellular senescence and other age-related mechanisms in developing skeletal diseases,including osteoporosis,intervertebral disc degeneration,osteoarthritis,rheumatoid arthritis,bone tumors and ankylosing spondylitis,with the aim of comprehensively understanding their detrimental effects on the aged skeleton and screening the potential targets for anti-aging therapy within the skeletal system.展开更多
Biomarker and stable carbon isotope analyses are presented for the Garau Formation of the Cretaceous Age,an important source rock in western Iran,to reveal its potential as an oilprone source rock.The C_(28)/C_(29)ste...Biomarker and stable carbon isotope analyses are presented for the Garau Formation of the Cretaceous Age,an important source rock in western Iran,to reveal its potential as an oilprone source rock.The C_(28)/C_(29)sterane ratio value range(0.72 to 0.83)of bitumen samples from the formation suggests that they were likely formed during phytoplankton blooms.Sterane,hopane,and isoprenoid/n-alkane ratios indicate that the formation's organic matter predominantly consists of algae,and bacteria,accompanied by some reworked material derived from higher plants.Due to the predominance of anoxic conditions and the actions of sulfate-reducing bacteria,the bitumen present is enriched with sulfur compounds.The percentages of saturates,aromatics,and nitrogen-sulfuroxygen(NSO)fractions in the bitumen samples classify them as naphthenic oils.Isotope analysis reveals that biodegradation and water-washing have reduced the concentrations of some volatile saturates and low molecular weight aromatics in the bitumen samples.These actions have resulted in distinctiveδ^(13)C values for the formation's kerogen and bitumen fractions.The formation's organic matter has been subjected to high-temperature thermal regimes and has entered the oil-generation window at the sampled localities,with vitrinite reflectance(%R_(C))varying between 0.7%and 0.75%.展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental...Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.展开更多
Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histo...Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.展开更多
Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterat...Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.展开更多
Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopeni...Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopenia is common in patients with MASLD,with a prevalence ranging from 20%to 40%depending on the population and diagnostic criteria used.In advanced stages,such as metabolic dysfunction-associated steatohepatitis and fibrosis,its prevalence is even higher.Sarcopenia exacerbates insulin resistance,systemic inflammation,and oxidative stress,all of which worsen MASLD.It is an independent risk factor for fibrosis progression and poor outcomes including mortality.Myosteatosis refers to the abnormal accumulation of fat within muscle tissue,leading to decreased muscle quality.Myosteatosis is prevalent(>30%)in patients with MASLD,especially those with obesity or type 2 diabetes,although this can vary with the imaging techniques used.It reduces muscle strength and metabolic efficiency,further contributing to insulin resistance and is usually associated with advanced liver disease,cardiovascular complications,and lower levels of physical activity.Altered muscle metabolism,which includes mitochondrial dysfunction and impaired amino acid metabolism,has been reported in metabolic syndromes,including MASLD,although its actual prevalence is unknown.Altered muscle metabolism limits glucose uptake and oxidation,worsening hyperglycemia and lipotoxicity.Reduced muscle perfusion and oxygenation due to endothelial dysfunction and systemic metabolic alterations are common in MASLD associated with comorbidities,such as obesity,hypertension,and atherosclerosis.It decrea-ses the muscle capacity for aerobic metabolism,leading to fatigue and reduced physical activity in patients with MASLD,aggravating metabolic dysfunction.Various SMA in MASLD worsen insulin resistance and hepatic fat accumulation,may accelerate progression to fibrosis and cirrhosis,and increase the risk of cardiovascular disease and mortality.Management strategies for SMA include resistance training,aerobic exercise,and nutritional support(e.g.,high-protein diets,vitamin D,and omega-3 fatty acids),which are essential for mitigating skeletal muscle loss and improving outcomes.However,pharmacological agents that target the muscle and liver(such as glucagon-like peptide-1 receptor agonists)show promise but have not yet been approved for the treatment of MASLD.展开更多
文摘All engineering projects consist of several steps, and one of the main tasks is to identify and characterize the most important features of rock types that will be excavated, crushed, or mined for any particular usage purpose, from a single residential building to major works of infrastructure. Laboratory investigation on engineering geology is thus conducted in order to determine the most relevant rock properties when designing structures such as mining shafts, tunnels, buildings, or reservoir dams to be built in sites associated with rocks. A wide range of laboratory tests is available, making the correct choice of test methods greatly relevant to determine the key property for the planned use of the rock. This paper is an illustrative case of laboratory testing of basaltic rocks to be used as riprap in a reservoir dam. It shows the important role of the petrographic study carried out to analyze the distribution pattern of smectite clay minerals. Test results are explained for the assessment of rock alterability, an essential aspect for the selection of the most suitable basalt variety for the envisaged conditions of use.
基金supported by the Jiangsu Province Frontier Leading Technology Basic Research Special Project-Research on the New Optoelectronic Imaging and Information Processing Basic Theory and Method(No:BK20192003).
文摘This review summarizes studies of hydrothermal alteration minerals at the Qiucun gold deposit in southeastern China and focuses on characterization and mapping of the deposit using hyperspectral remote sensing.The deposit exhibits multistage fluid-rock interaction,as evidenced by systematic alteration assemblages,including silicification,sericitization by white micas,the development of argillaceous clays,variable chloritization,and locally significant carbonate alteration.We describe the genetic importance of such mineral groups and emphasize their diagnostic Visible and Near-Infrared to Short-Wave Infrared(VNIR-SWIR)spectral signatures,especially Al-OH,Mg-OH/Fe-OH,and CO3 absorption bands,which make it possible to distinguish between minerals,not to mention the fact that,in some instances,compositional trends may be predicted.This review’s methodological advances are discussed beginning with data collection at satellite,airborne,and ground levels,proceeding to processing procedures,such as atmospheric and topographic correction,and culminating in spectral analysis,including continuum removal,spectral matching,and unmixing/classification techniques.An integrated study of hyperspectral findings reveals that alteration minerals develop spatially coherent zones that are strongly controlled by fault/fracture structures and host-rock reactivity,producing proximal silicification/sericitization cores and larger silicified/larcenies of argillaceous rocks owing to diverse apex coverings of carbonate.This should be combined with petrography and geochemistry to address overprinting,mixed pixels,and surface weathering,and to couple mineral maps with ore-forming processes.The review finds that hyperspectral remote sensing offers a solid modeling platform for the deposit-scale alteration at Qiucun and other hydrothermal gold systems,and outlines the directions for future research to integrate quantitatively and more threedimensional alteration characterization.
文摘The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.
文摘Endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy remains a challenging field in therapeutic endoscopy due to the complex anatomical reconstructions that limit access to the biliary tree.Over the past two decades,device-assisted enteroscopy(DAE),including singleballoon,double-balloon,and motorized spiral enteroscopy,has expanded the feasibility of ERCP in this population,with overall technical success rates generally reported between 70%and 90%.Nevertheless,these techniques are technically demanding,time-consuming,and frequently affected by limited reach and unstable positioning.More recently,interventional endoscopic ultrasound(EUS)-guided procedures have emerged as highly effective alternatives,significantly improving clinical outcomes in selected patients,particularly in those with long-limb Roux-en-Y reconstructions where conventional methods are less effective.Percutaneous transhepatic biliary drainage continues to represent a valuable salvage option when endoscopic approaches fail,though it is associated with a greater burden of reinterventions and adverse events.This minireview provides a comprehensive overview of the main endoscopic strategies for biliary drainage in altered anatomy,focusing on technical considerations,efficacy,and safety profiles of DAE-assisted ERCP,EUS-guided interventions,and motorized systems.The evolving landscape of biliary drainage in this setting highlights the need for tailored treatment strategies,multidisciplinary collaboration,referral to high-volume centers,and further prospective studies to refine patient selection and optimize clinical outcomes.
文摘Non-native plants are increasingly recognized as ecosystem engineers across a wide range of ecosystems.While their impacts on understory composition have been widely documented,consequences for community assembly remain largely unexplored.We investigated the engineering impacts of Sorbaria sorbifolia,a naturalized Rosaceae shrub,on abiotic conditions and understory community assembly in Central European forests.Across 60 plots spanning coniferous and deciduous stands,we quantified light availability,organic layer C/N ratio and thickness,and understory functional diversity along an invasion gradient.Using ordination and linear regression,we found that increasing S.sorbifolia cover reduced light availability,thickened the organic layer,and altered C/N ratio in contrasting,forest-type-specific ways.In coniferous stands,invasion increased C/N and strongly suppressed understory light,whereas in deciduous stands it reduced C/N with weaker shading effects.These changes translate into consistent declines in functional richness and dispersion,particularly in coniferous forests where invasion led to homogenization of the understory.Trait shifts indicated stronger habitat filtering under invasion,with declines in specific leaf area(SLA)and increases in leaf dry matter content and seed mass,reflecting exclusion of light-demanding species and persistence of stress-tolerant taxa and woody seedlings.Remarkably,once S.sorbifolia exceeded~50%cover,positive relationships between habitat properties and understory functional diversity collapsed,replaced by uniform light limitation.This threshold effect highlights S.sorbifolia as an ecosystem engineer,capable of transforming forest structure and regeneration trajectories.Early detection and management are therefore crucial to prevent long-term homogenization and the formation of novel,invasion-driven forest states.
基金supported by the Sanming Project of Medicine in Shenzhen[SZZYSM202206001]National Natural Science Foundation of China[82004320 and 82374383]+3 种基金Natural Science Foundation of Guangdong Province of China[2022A1515011710 and 2022A1515010679]Shenzhen Science and Technology Innovation Committee[JCYJ20220530141407017 and JCYJ20240813153619026]2024 High-quality Development Research Project of Shenzhen Bao’an Public Hospital[YNXM2024078]and Shenzhen Bao’an Chinese Medicine Hospital Research Program[BAZYY20220702].
文摘Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend against illness,and maintain homeostasis)syndrome is considered a critical syndrome in traditional Chinese medicine(TCM)and is associated with poor prognosis in heart failure(HF).This study investigates the clinical,metabolic,and transcriptomic differences between heart failure patients with and without Qi deficiency syndrome.Methods:56 heart failure patients were evaluated using a Qi deficiency syndrome scale and divided into Qi deficiency syndrome(QD)and non-Qi deficiency(non-QD)groups based on the median score.Clinical characteristics,including baseline N-terminal pro-B-type natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),total diuretic use during hospitalization,and 90-day rehospitalization rates,were compared between the groups.Differentially expressed genes(DEGs)and differential metabolites were identified,followed by enrichment analyses and validation using qPCR and Western blot in AC16 cardiomyocytes.Results:QD patients exhibited significantly higher NT-proBNP levels,lower LVEF,and increased 90-day rehospitalization rates.Metabolomic profiling revealed lipid metabolism disruptions,notably in linoleic acid and phospholipid pathways.Transcriptomic analysis highlighted 17 DEGs,including CISD2,a critical mitochondrial regulator,which was downregulated in QD patients.Correlation analysis identified significant associations between DEGs(e.g.,CISD2,BPGM)and lipid metabolites such as PC(16:0/P-16:0).Functional knockdown of CISD2 in AC16 cells led to upregulation of lipid oxidation enzymes ALOX15 and CYP1A2,linking CISD2 dysfunction to lipid metabolic dysregulation.Conclusion:Qi deficiency is associated with more severe heart failure symptoms,worse prognosis,and distinct metabolic and transcriptomic profiles,particularly in lipid metabolism.CISD2 emerges as a potential therapeutic target,offering new avenues for integrating molecular insights with TCM approaches to optimize HF management.
基金supported by the Natural Science Foundation of China(Grant No.42372346,41802080,42030809,41873043).
文摘Epithermal deposits are characterized by complex low-temperature hydrothermal alterations, but the links between mineralization and superimposed alteration are obscure and require further elucidation. This study employs shortwave infrared(SWIR) spectral scalars for alteration mineral mapping and three-dimensional modeling of the Ulan Uzhur Ag polymetallic deposit, a newly discovered epithermal deposit in the Qimantagh. Alteration zoning transitions from illitemuscovite-carbonate-pyrite in the core(Zone Ⅰ), through muscovite ± illite-kaolinite-chlorite-carbonate(Zone Ⅱ), to muscovite-chlorite-biotite(Zone Ⅲ) at the periphery. The Zone Ⅰ with mineralization features long-wavelength white mica(wAlOH > 2207 nm) with a high Illite Crystallinity(IC)(mean > 2.0), suggesting a relatively high-temperature environment conducive to mineralization. Petrographic analyses with fluid inclusion and IC curve characteristics suggests that fluid boiling may be a pivotal mechanism for mineral precipitation. Furthermore, surface mapping and deep threedimensional modeling of spectral characteristics reveal a correlation between long-wavelength white mica, high IC and mineralization zones. These findings indicate that SWIR spectroscopy reveal the evolution of fluids and provide valuable guidance for future exploration efforts.
基金Supported by the CNPC Science and Technology Project(2023YQX10110)。
文摘This paper systematically analyzes the reservoir-forming characteristics and cretaceous shale oil types in four major hydrocarbon-generating sags(Qingxi,Ying'er,Huahai,and Shida)of the Jiuquan Basin,based on the data of experiments for microscopic and geochemical analysis of reservoirs.The hydrothermal alteration-induced reservoir-forming model and its reservoir-controlling effect in the Qingxi Sag are discussed,and the exploration potential of shale oil in these four sags are evaluated.(1)The Qingxi Sag is widely developed with mud shale,dolomitic shale,and laminated argillaceous dolomite in the Cretaceous,which can be defined as mixed shale as a whole.The source rocks in this area are of good quality and high maturity,formed in a saline water sedimentary environment,and rich in dolomite,with a strong hydrocarbon generation capacity and excellent oil generation conditions.The reservoir space has been significantly modified by hydrothermal process,with well-developed dissolution pores and microfractures,recording favorable reservoir conditions for shale oil enrichment.Overall,this sag has large reservoir thickness and large resource volume,making it the most realistic shale oil exploration target in the Jiuquan Basin.However,it faces challenges such as great burial depth(deeper than 4500 m)and strong tectonic stress.(2)The Ying'er,Huahai,and Shida sags all feature sand-mud interbeds consisting of fan delta front thin sandbodies and lacustrine mud shale in the Cretaceous,having good source rock quality and favorable conditions for interbedded-type shale oil accumulation.The source rocks are insufficient in thermal evolution degree and unevenly distributed,and favorable shale oil resources are mainly endowed near the center of the sags.Reservoirs are primarily composed of siltstone to fine sandstone,suggesting relatively good reservoir conditions,generally with small burial depth(3000-4000 m)and the possibility of local sweet spots.It is noted that the Ying'er Sag has already produced low-mature to mature oil,qualifying it as a near-term realistic shale oil exploration area.
文摘Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.
基金supported by the project Major Scientific and Technological Special Project of Guizhou Province([2024]014).
文摘Load frequency control(LFC)is a critical function to balance the power consumption and generation.Thegrid frequency is a crucial indicator for maintaining balance.However,the widely used information and communication infrastructure for LFC increases the risk of being attacked by malicious actors.The dynamic load altering attack(DLAA)is a typical attack that can destabilize the power system,causing the grid frequency to deviate fromits nominal value.Therefore,in this paper,we mathematically analyze the impact of DLAA on the stability of the grid frequency and propose the network parameter regulation(NPR)to mitigate the impact.To begin with,the dynamic LFC model is constructed by highlighting the importance of the network parameter.Then,we model the DLAA and analyze its impact on LFC using the theory of second-order dynamic systems.Finally,we model the NPR and prove its effect in mitigating the DLAA.Besides,we construct a least-effort NPR considering its infrastructure cost and aim to reduce the operation cost.Finally,we carry out extensive simulations to demonstrate the impact of the DLAA and evaluate the mitigation performance of NPR.The proposed cost-benefit NPR approach can not only mitigate the impact of DLAA with 100%and also save 41.18$/MWh in terms of the operation cost.
基金supported by the National Natural Science Foundation of China(82173796)the Research Project of Zhejiang Chinese Medical University(2023JKZDZC04).
文摘When teaching neurology students about epilepsy,selecting appropriate antiseizure medications(ASMs)based on seizure type is a fundamental objective.Carbamazepine(CBZ),a widely used first-line ASM,is effective against focal seizures,generalized tonic-clonic seizures,and mixed seizure patterns[1].However,CBZ paradoxically aggravates absence seizures,as demonstrated by increased 36 Hz spike-and-wave discharges(SWDs)in both patients and animal models[2,3].While prior studies implicated altered GABAA receptor function in the thalamic ventrobasal complex[4],the precise mechanisms remained unclear.Recently,an inspiring study published on PNAS by Jang et al.from Stanford University has highlighted the thalamic reticular nucleus(RT)as the key brain region responsible for CBZ's aggravating effect on absence seizures[5].The combination of transgenic mouse models,optogenetics,and detailed electrophysiology in the original study provided exceptional precision in probing mechanistic insights,which greatly strengthens the conclusions.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,and Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022).
文摘Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
基金supported by the National Natural Science Foundation of China(82172468,82372436)Outstanding Youth Fund of Jiangsu Province(BK2024047)+1 种基金China Postdoctoral Science Foundation(2023T160553)Postgraduate Research&Practice Innovation Program of Jiangsu Province(SJCX22-1819).
文摘Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential as a therapeutic strategy to reverse age-related skeletal senescence and promote bone regeneration.Meanwhile,other age-related mechanisms,involving altered cellular functions,impaired intercellular crosstalk,disturbed tissue microenvironment,and decreased regenerative capacity,synergistically contribute to the pathogenesis.In this review,we outline the cellular senescence and other age-related mechanisms in developing skeletal diseases,including osteoporosis,intervertebral disc degeneration,osteoarthritis,rheumatoid arthritis,bone tumors and ankylosing spondylitis,with the aim of comprehensively understanding their detrimental effects on the aged skeleton and screening the potential targets for anti-aging therapy within the skeletal system.
文摘Biomarker and stable carbon isotope analyses are presented for the Garau Formation of the Cretaceous Age,an important source rock in western Iran,to reveal its potential as an oilprone source rock.The C_(28)/C_(29)sterane ratio value range(0.72 to 0.83)of bitumen samples from the formation suggests that they were likely formed during phytoplankton blooms.Sterane,hopane,and isoprenoid/n-alkane ratios indicate that the formation's organic matter predominantly consists of algae,and bacteria,accompanied by some reworked material derived from higher plants.Due to the predominance of anoxic conditions and the actions of sulfate-reducing bacteria,the bitumen present is enriched with sulfur compounds.The percentages of saturates,aromatics,and nitrogen-sulfuroxygen(NSO)fractions in the bitumen samples classify them as naphthenic oils.Isotope analysis reveals that biodegradation and water-washing have reduced the concentrations of some volatile saturates and low molecular weight aromatics in the bitumen samples.These actions have resulted in distinctiveδ^(13)C values for the formation's kerogen and bitumen fractions.The formation's organic matter has been subjected to high-temperature thermal regimes and has entered the oil-generation window at the sampled localities,with vitrinite reflectance(%R_(C))varying between 0.7%and 0.75%.
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
基金supported by funds from the Italian Ministry of Health,Ricerca Finalizzata,(Grant N.GR-2013-02355882 and GR-2021-12373946 to AL)5x1000 Project of the Istituto Superiore di Sanità(Project code:ISS5x1000_21-949432e8c9be to AL)the European Union–NextGeneration EU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 Project PE_00000019“HEAL ITALIA”to EA(CUP I83C22001830006)。
文摘Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.
基金supported by an under-40 grant from the Italian Association for Alzheimer’s Research [AIRALZH AGYR2021]the Strategic University Projects–Young Researcher Independence grant [YRG2021] from the Università Campus Bio-Medico di Roma (Rome, Italy)(to LLB)+1 种基金Italian Ministry of Health [Research Grant:GR-2019-12370446]the American Alzheimer’s Association [AARG-22-922961](to PK)。
文摘Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.
基金funded by national funds,through the Foundation for Science and Technology(FCT)-project UIDB/50026/2020,UIDP/50026/2020(to NAS),EXPL/MEDPAT/0931/2021(to SM)Financial support was provided by Prémios Santa Casa Neurociências-Prize Melo e Castro for Spinal Cord Injury Research(MC-18-2021)+2 种基金Wings For Life Spinal Cord Research Foundation(WFL-PT-14/23)"la Caixa"Foundation(HR23-00484)(to NAS)the FCT for the Scientific Employment Stimulus to NAS and SM(CEECIND/04794/2017 and CEECIND/01902/2017)。
文摘Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.
基金Supported by Russian Science Foundation,No.19-76-30014.
文摘Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopenia is common in patients with MASLD,with a prevalence ranging from 20%to 40%depending on the population and diagnostic criteria used.In advanced stages,such as metabolic dysfunction-associated steatohepatitis and fibrosis,its prevalence is even higher.Sarcopenia exacerbates insulin resistance,systemic inflammation,and oxidative stress,all of which worsen MASLD.It is an independent risk factor for fibrosis progression and poor outcomes including mortality.Myosteatosis refers to the abnormal accumulation of fat within muscle tissue,leading to decreased muscle quality.Myosteatosis is prevalent(>30%)in patients with MASLD,especially those with obesity or type 2 diabetes,although this can vary with the imaging techniques used.It reduces muscle strength and metabolic efficiency,further contributing to insulin resistance and is usually associated with advanced liver disease,cardiovascular complications,and lower levels of physical activity.Altered muscle metabolism,which includes mitochondrial dysfunction and impaired amino acid metabolism,has been reported in metabolic syndromes,including MASLD,although its actual prevalence is unknown.Altered muscle metabolism limits glucose uptake and oxidation,worsening hyperglycemia and lipotoxicity.Reduced muscle perfusion and oxygenation due to endothelial dysfunction and systemic metabolic alterations are common in MASLD associated with comorbidities,such as obesity,hypertension,and atherosclerosis.It decrea-ses the muscle capacity for aerobic metabolism,leading to fatigue and reduced physical activity in patients with MASLD,aggravating metabolic dysfunction.Various SMA in MASLD worsen insulin resistance and hepatic fat accumulation,may accelerate progression to fibrosis and cirrhosis,and increase the risk of cardiovascular disease and mortality.Management strategies for SMA include resistance training,aerobic exercise,and nutritional support(e.g.,high-protein diets,vitamin D,and omega-3 fatty acids),which are essential for mitigating skeletal muscle loss and improving outcomes.However,pharmacological agents that target the muscle and liver(such as glucagon-like peptide-1 receptor agonists)show promise but have not yet been approved for the treatment of MASLD.
