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
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
The story of Goethe’s invention of'world literature'while reading a Chinese novel is an interesting one,for it prefigures the presence of alterity in the very formation of the concept.Whether we consider worl...The story of Goethe’s invention of'world literature'while reading a Chinese novel is an interesting one,for it prefigures the presence of alterity in the very formation of the concept.Whether we consider world literature as a theoretical recognition of writing to be literature or as a body of actual texts,we often frame our discussion in a language of duality:self/other,culture/cosmopolitanism,nation/world,etc.While the force of world literature has always been its alluring ideal of'one-world-ness',it is time for us to better account for its embedded alterity,which is what energizes world literature as a discipline of study in the 21stcentury.The place to start,this essay will argue,is translation/reading.Translation as reading is not only the material condition for world literature,where texts of different language congregate to form a'republic of letters',but also creates the site of an'afterlife'in which the textuality of world literature becomes visible and realized.Like writing itself,however,translation is not a transparent text for meaning.It is an exchange of alterity,but not its equivalent.The varying strategies in translation deal with alterity,thus invigorate the discourse of sameness and difference in the concept of world literature.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
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
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
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
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
Altered rock,often encountered in major engineering projects,can seriously affect the stability of rocks and slopes surrounding deeply buried tunnels.This study addressed the alteration mechanism,alteration degree cla...Altered rock,often encountered in major engineering projects,can seriously affect the stability of rocks and slopes surrounding deeply buried tunnels.This study addressed the alteration mechanism,alteration degree classification,and mechanical parameters of altered rock in engineering project areas using field testing,thin slice identification,X-ray diffraction,and major element testing.Results showed that the altered rock types in the areas of the Pingjiang Pumped Storage Power Station,Hunan Province,and a diversion tunnel in northern Xinjiang Uygur Autonomous Region include biotite granodiorite,biotite monzogranite,and cataclastic granite,and that the main alteration mechanisms are chloritization of biotite and clayization of feldspar minerals.The altered rocks were classified as slightly,moderately,or strongly altered according to their apparent characteristics,rebound value,longitudinal wave velocity,metamorphic mineral content,and porosity.The bulk density,elastic modulus,cohesion,and internal friction angle(Poisson’s ratio)of the altered rocks decreased(increased)with increase in the degree of alteration.Numerical simulations showed that in altered rock slope areas,the zone of strong rock alteration and the moderate-strong alteration contact zone exhibit locally large deformations that represent a certain hazard to engineering projects.These results provide valuable guidance and support for major projects in altered rock areas.展开更多
The patterns of metal distribution and alteration zonation in magmatic-hydrothermal systems primarily focus on porphyry deposit and other closely associated types,such as skarn,epithermal and distal vein deposits(e.g....The patterns of metal distribution and alteration zonation in magmatic-hydrothermal systems primarily focus on porphyry deposit and other closely associated types,such as skarn,epithermal and distal vein deposits(e.g.,Zheng,2022;Hutchison et al.,2020;Cooke et al.,2011;Hedenquist et al.,1998).展开更多
Climate change is altering river regimes in mountainous regions,affecting water availability and the functioning of aquatic ecosystems.In the Andes Mountains,characterizing the natural flow regime is essential for est...Climate change is altering river regimes in mountainous regions,affecting water availability and the functioning of aquatic ecosystems.In the Andes Mountains,characterizing the natural flow regime is essential for establishing operational conditions that balance multiple water uses(irrigation,supply,hydropower)with the conservation of high-elevation ecosystems in the context of increasing hydroclimatic variability.This study analyzes extreme hydrological conditions in nivoglacial rivers of the upper Mendoza River Basin(Argentina),using indicators of magnitude,frequency,duration,and timing of high(HP)and low(LP)pulses.Daily flow records from the Cuevas,Vacas,Tupungato,and Mendoza Rivers were used to define eight ecologically relevant extreme hydrological parameters over the period 1956–2023.The results reveal a reduction in the magnitude of extreme flows since 2010(−30%to–55%)and significant delays in their timing,with maximum and minimum flow shifting by 15–20 days later in recent decades.The duration of LP events increased by 120%–240%in the Cuevas,Tupungato,and Mendoza Rivers,while in the Tupungato River,HP events tended to occur less frequently but with longer durations.These changes are associated with a 0.1℃decade^(−1)rise in mean temperature and a∼25%decrease in precipitation since 2009.Such trends have major implications for water resource management and the resilience of high-Andean ecosystems under climate warming.展开更多
Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for ...Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for patients with advanced NSCLC bearing sensitive EGFR mutations,significantly prolongs the progression-free survival(PFS)to 25.5 months1.Despite great breakthroughs in survival data,patients inevitably experience disease progression.A large meta-analysis has indicated that,compared with chemother-apy,immuno-based therapies achieve longer PFS in patients with EGFR mutation who progressed on third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)2.Therefore,immunotherapies are often used after EGFR-TKI resistance is observed.展开更多
As one of the typical deposits in the Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province,the Daliangzi Pb-Zn deposit has a close genetic relationship with the structural system of the black/fracture zone formed under ...As one of the typical deposits in the Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province,the Daliangzi Pb-Zn deposit has a close genetic relationship with the structural system of the black/fracture zone formed under the action of the NWW-approximately EW strike-slip structures in the metallogenic province.The R1 black/fracture zone has a close relationship with ore forming;however,the mechanism of the rock-and ore-controlling action of the structural system remains unclear.Based on a detailed analysis of the tectonite-mineralized alteration lithofacies of the R1 black/fracture zone,the tectonite-mineralized alteration lithofacies zones can be divided into four types in succession outward from the Pb-Zn mineralization center(F_(5),F_(100),and other faults),i.e.,(1)the brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone;(2)the stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone;(3)the veined pyrite-sulfide-dolomitic cataclasite facies zone;(4)the fine-veined calcite-black carbonized dolomite facies zone.With the evolution of the ore-forming fluid,the homogenization temperature decreases from Zone 1 to Zone 4;the salinity increases from Zone 1 to Zone 2 and then it decreases from Zones 3 and 4.The fluid density shows little change overall.The contents of Zn,Pb,Cu,Ga,Ge,Cd,Ag,and other metallogenic elements,Zn/Pb ratio,and CaO/MgO mole ratio decrease gradually from Zone 1 to Zone 4,and the REE fractionation,calcilization,silicification,and pyritization enhance gradually from Zone 1 to Zone 4.This series of changes is the product of diapirism(cryptoexplosion)of strike-slip structures and the black/fracture zone,among which the second-order structures derived from NWW-approximately EW-striking dextral shear-tension faults F_(1)and F_(15)control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones.Therefore,this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of the black/fracture zone and proposes that Zones 1 and 2 provide important prospecting criteria.展开更多
Background:The pentose-phosphate pathway(PPP)plays a vital role in cell growth and metabolic reprogramming.However,its role in human cancer remains unclear.Methods:We conducted a systematic analysis to investigate the...Background:The pentose-phosphate pathway(PPP)plays a vital role in cell growth and metabolic reprogramming.However,its role in human cancer remains unclear.Methods:We conducted a systematic analysis to investigate the complex and crucial roles of the PPP using multi-omics data frommore than 10,000 samples across 33 cancer types sourced frommultiple databases,including the Molecular Signature Databases,The Cancer Genome Atlas,and Cancer Single-cell State Atlas.Independent cohorts such as IMvigor210 and Liver Cancer-RIKEN,Japan Project from International Cancer Genome Consortium(ICGC-LIRI-JP).Results:PPP-related genes were upregulated in most cancers,a phenomenon possibly driven by copy number variation and DNA methylation.Single-cell analysis revealed significant tumor-promoting features of PPP.We developed a PPP activity score to quantify the overall expression of PPP-related genes.PPP activity scores were significantly correlated with multiple hallmark pathways,the tumor microenvironment,cancer stemness,and immune-related signatures.Drug analysis revealed that high PPP activity scores contributed to resistance to drug-targeting pathways,including PI3K/mTOR,RTK,and TP53 signaling.In addition,PPP activity scores are potential predictors of immunotherapy outcomes.Prognostic analysis revealed that whereas individual PPP-related genes had varying effects on survival,high PPP activity scores were generally associated with poor prognosis,particularly in liver cancer.Conclusions:This study underscores the critical molecular and clinical roles of the PPP in human cancers and highlights its potential as a promising target for cancer treatment.展开更多
The offshore Tanzanian Basin contains numerous igneous intrusions emplaced at various stratigraphic levels.Previous studies indicate these intrusions have impacted petroleum systems,affecting key elements such as sour...The offshore Tanzanian Basin contains numerous igneous intrusions emplaced at various stratigraphic levels.Previous studies indicate these intrusions have impacted petroleum systems,affecting key elements such as source rocks,reservoirs,seals,migration pathways,and trapping mechanisms.However,due to the limited number of wells drilled in the region,there have been few studies reporting the associated thermal effects on source rock maturation and their role in hydrocarbon generation.To gain a comprehensive understanding of the intricate relationship between intrusions and the petroleum system,particularly source rock,an integrated geochemical and resistivity log analysis was carried out.The geochemical results show that the Cretaceous-Cenozoic sediments of the study area have low total organic carbon contents(TOC<1 wt%),kerogen yield(<1 Mg HC/g),and Hydrogen Index(<100 Mg HC/g),primarily composed of TypeⅢ(gas-prone)to TypeⅣ(inert)kerogens.These sediments have undergone varying levels of thermal maturity,ranging from post-mature(within Cretaceous),matured(in Paleocene)to immature(in Eocene)thermal states.The Cretaceous strata located proximal to the intrusions exhibit significant thermal alteration,resulting in a reduction of both organic matter(OM)content and source potential compared to the Eocene and Paleocene samples.This observation is consistent with the estimated paleotemperature(T)and resistivity log(ILD)along the depth profile,which have mapped local thermal alteration increasing from base Paleocene to Cretaceous.These findings have implications for source rock potential and thermal evolution history in the offshore Tanzanian Basin.This study highlights the necessity for thorough subsurface mapping in the area to identify both younger and older intrusive rocks.These intrusions pose a potential risk in petroleum exploration,especially when they intrude into matured source rock intervals.展开更多
The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate,and the neonatal ovarian immune microenvironment,particularly its modulation by estrogen,has not been comprehensively char...The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate,and the neonatal ovarian immune microenvironment,particularly its modulation by estrogen,has not been comprehensively characterized.In this study,the effects of 17β-estradiol(E_(2)),a key regulator of immune function,were investigated using single-cell transcriptomic profiling of C57BL/6J neonatal mouse ovaries after E_(2)treatment.Results revealed dynamic alterations in the proportion of immune cell types after E_(2)treatment,accompanied by changes in cytokine and chemokine expression.Detailed analyses of gene expression,cell states,and developmental trajectories across distinct cell types indicated that E_(2)treatment influenced cell differentiation and development.Notably,E_(2)treatment reduced the abundance of macrophages and promoted a phenotypic transition from M1 to M2 macrophages.These findings demonstrate that the neonatal mouse ovarian immune microenvironment is sensitive to estrogenic modulation,which governs both the distribution and functional specialization of resident immune cells,offering novel mechanistic insights into the immunomodulatory roles of estrogen across various immune cell types.展开更多
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.
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.
文摘The story of Goethe’s invention of'world literature'while reading a Chinese novel is an interesting one,for it prefigures the presence of alterity in the very formation of the concept.Whether we consider world literature as a theoretical recognition of writing to be literature or as a body of actual texts,we often frame our discussion in a language of duality:self/other,culture/cosmopolitanism,nation/world,etc.While the force of world literature has always been its alluring ideal of'one-world-ness',it is time for us to better account for its embedded alterity,which is what energizes world literature as a discipline of study in the 21stcentury.The place to start,this essay will argue,is translation/reading.Translation as reading is not only the material condition for world literature,where texts of different language congregate to form a'republic of letters',but also creates the site of an'afterlife'in which the textuality of world literature becomes visible and realized.Like writing itself,however,translation is not a transparent text for meaning.It is an exchange of alterity,but not its equivalent.The varying strategies in translation deal with alterity,thus invigorate the discourse of sameness and difference in the concept of world literature.
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.
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 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.
基金the National Key Research and Development Project of China(No.2019YFC1509704)the National Natural Science Foundation of China(Nos.U1704243,41741019,41977249 and 42090052)+2 种基金the Henan Province Science and Technology Research Project(Nos.192102310006,232102320035)the Innovation Fund for Doctoral Students of North China University of Water Resources and Electric Power(No.NCWUBC202313)the Key Research Project Plan for Higher Education Institutions in Henan Province(No.24A410003).
文摘Altered rock,often encountered in major engineering projects,can seriously affect the stability of rocks and slopes surrounding deeply buried tunnels.This study addressed the alteration mechanism,alteration degree classification,and mechanical parameters of altered rock in engineering project areas using field testing,thin slice identification,X-ray diffraction,and major element testing.Results showed that the altered rock types in the areas of the Pingjiang Pumped Storage Power Station,Hunan Province,and a diversion tunnel in northern Xinjiang Uygur Autonomous Region include biotite granodiorite,biotite monzogranite,and cataclastic granite,and that the main alteration mechanisms are chloritization of biotite and clayization of feldspar minerals.The altered rocks were classified as slightly,moderately,or strongly altered according to their apparent characteristics,rebound value,longitudinal wave velocity,metamorphic mineral content,and porosity.The bulk density,elastic modulus,cohesion,and internal friction angle(Poisson’s ratio)of the altered rocks decreased(increased)with increase in the degree of alteration.Numerical simulations showed that in altered rock slope areas,the zone of strong rock alteration and the moderate-strong alteration contact zone exhibit locally large deformations that represent a certain hazard to engineering projects.These results provide valuable guidance and support for major projects in altered rock areas.
基金supported by the National Natural Science Foundation of China(Nos.42122012,U2444208)the Inner Mongolia Academician Project(No.2022-TZH03)the Fundamental Research Funds for the Central Universities(No.2652023001)。
文摘The patterns of metal distribution and alteration zonation in magmatic-hydrothermal systems primarily focus on porphyry deposit and other closely associated types,such as skarn,epithermal and distal vein deposits(e.g.,Zheng,2022;Hutchison et al.,2020;Cooke et al.,2011;Hedenquist et al.,1998).
基金National Scientific and Technical Research Council of Argentina(CONICET),Grant/Award Number:PIBAA2022-202328720210100485CO。
文摘Climate change is altering river regimes in mountainous regions,affecting water availability and the functioning of aquatic ecosystems.In the Andes Mountains,characterizing the natural flow regime is essential for establishing operational conditions that balance multiple water uses(irrigation,supply,hydropower)with the conservation of high-elevation ecosystems in the context of increasing hydroclimatic variability.This study analyzes extreme hydrological conditions in nivoglacial rivers of the upper Mendoza River Basin(Argentina),using indicators of magnitude,frequency,duration,and timing of high(HP)and low(LP)pulses.Daily flow records from the Cuevas,Vacas,Tupungato,and Mendoza Rivers were used to define eight ecologically relevant extreme hydrological parameters over the period 1956–2023.The results reveal a reduction in the magnitude of extreme flows since 2010(−30%to–55%)and significant delays in their timing,with maximum and minimum flow shifting by 15–20 days later in recent decades.The duration of LP events increased by 120%–240%in the Cuevas,Tupungato,and Mendoza Rivers,while in the Tupungato River,HP events tended to occur less frequently but with longer durations.These changes are associated with a 0.1℃decade^(−1)rise in mean temperature and a∼25%decrease in precipitation since 2009.Such trends have major implications for water resource management and the resilience of high-Andean ecosystems under climate warming.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82273162)Jiangsu Cancer Hospital Science and Technology Development Fund Project(Grant No.YSZD202409).
文摘Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for patients with advanced NSCLC bearing sensitive EGFR mutations,significantly prolongs the progression-free survival(PFS)to 25.5 months1.Despite great breakthroughs in survival data,patients inevitably experience disease progression.A large meta-analysis has indicated that,compared with chemother-apy,immuno-based therapies achieve longer PFS in patients with EGFR mutation who progressed on third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)2.Therefore,immunotherapies are often used after EGFR-TKI resistance is observed.
基金funded by the programs of the National Natural Science Foundation(Nos.42172086,41572060,U1133602)the Program of‘Yunling Scholar’of Yunnan province(2014)+1 种基金the Projects of the Yunnan Engineering Laboratory of Mineral Resources Prediction and Evaluation(YM Lab)(2010)the Innovation Team of Yunnan Province and KMUST(2008,2012).
文摘As one of the typical deposits in the Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province,the Daliangzi Pb-Zn deposit has a close genetic relationship with the structural system of the black/fracture zone formed under the action of the NWW-approximately EW strike-slip structures in the metallogenic province.The R1 black/fracture zone has a close relationship with ore forming;however,the mechanism of the rock-and ore-controlling action of the structural system remains unclear.Based on a detailed analysis of the tectonite-mineralized alteration lithofacies of the R1 black/fracture zone,the tectonite-mineralized alteration lithofacies zones can be divided into four types in succession outward from the Pb-Zn mineralization center(F_(5),F_(100),and other faults),i.e.,(1)the brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone;(2)the stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone;(3)the veined pyrite-sulfide-dolomitic cataclasite facies zone;(4)the fine-veined calcite-black carbonized dolomite facies zone.With the evolution of the ore-forming fluid,the homogenization temperature decreases from Zone 1 to Zone 4;the salinity increases from Zone 1 to Zone 2 and then it decreases from Zones 3 and 4.The fluid density shows little change overall.The contents of Zn,Pb,Cu,Ga,Ge,Cd,Ag,and other metallogenic elements,Zn/Pb ratio,and CaO/MgO mole ratio decrease gradually from Zone 1 to Zone 4,and the REE fractionation,calcilization,silicification,and pyritization enhance gradually from Zone 1 to Zone 4.This series of changes is the product of diapirism(cryptoexplosion)of strike-slip structures and the black/fracture zone,among which the second-order structures derived from NWW-approximately EW-striking dextral shear-tension faults F_(1)and F_(15)control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones.Therefore,this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of the black/fracture zone and proposes that Zones 1 and 2 provide important prospecting criteria.
文摘Background:The pentose-phosphate pathway(PPP)plays a vital role in cell growth and metabolic reprogramming.However,its role in human cancer remains unclear.Methods:We conducted a systematic analysis to investigate the complex and crucial roles of the PPP using multi-omics data frommore than 10,000 samples across 33 cancer types sourced frommultiple databases,including the Molecular Signature Databases,The Cancer Genome Atlas,and Cancer Single-cell State Atlas.Independent cohorts such as IMvigor210 and Liver Cancer-RIKEN,Japan Project from International Cancer Genome Consortium(ICGC-LIRI-JP).Results:PPP-related genes were upregulated in most cancers,a phenomenon possibly driven by copy number variation and DNA methylation.Single-cell analysis revealed significant tumor-promoting features of PPP.We developed a PPP activity score to quantify the overall expression of PPP-related genes.PPP activity scores were significantly correlated with multiple hallmark pathways,the tumor microenvironment,cancer stemness,and immune-related signatures.Drug analysis revealed that high PPP activity scores contributed to resistance to drug-targeting pathways,including PI3K/mTOR,RTK,and TP53 signaling.In addition,PPP activity scores are potential predictors of immunotherapy outcomes.Prognostic analysis revealed that whereas individual PPP-related genes had varying effects on survival,high PPP activity scores were generally associated with poor prognosis,particularly in liver cancer.Conclusions:This study underscores the critical molecular and clinical roles of the PPP in human cancers and highlights its potential as a promising target for cancer treatment.
文摘The offshore Tanzanian Basin contains numerous igneous intrusions emplaced at various stratigraphic levels.Previous studies indicate these intrusions have impacted petroleum systems,affecting key elements such as source rocks,reservoirs,seals,migration pathways,and trapping mechanisms.However,due to the limited number of wells drilled in the region,there have been few studies reporting the associated thermal effects on source rock maturation and their role in hydrocarbon generation.To gain a comprehensive understanding of the intricate relationship between intrusions and the petroleum system,particularly source rock,an integrated geochemical and resistivity log analysis was carried out.The geochemical results show that the Cretaceous-Cenozoic sediments of the study area have low total organic carbon contents(TOC<1 wt%),kerogen yield(<1 Mg HC/g),and Hydrogen Index(<100 Mg HC/g),primarily composed of TypeⅢ(gas-prone)to TypeⅣ(inert)kerogens.These sediments have undergone varying levels of thermal maturity,ranging from post-mature(within Cretaceous),matured(in Paleocene)to immature(in Eocene)thermal states.The Cretaceous strata located proximal to the intrusions exhibit significant thermal alteration,resulting in a reduction of both organic matter(OM)content and source potential compared to the Eocene and Paleocene samples.This observation is consistent with the estimated paleotemperature(T)and resistivity log(ILD)along the depth profile,which have mapped local thermal alteration increasing from base Paleocene to Cretaceous.These findings have implications for source rock potential and thermal evolution history in the offshore Tanzanian Basin.This study highlights the necessity for thorough subsurface mapping in the area to identify both younger and older intrusive rocks.These intrusions pose a potential risk in petroleum exploration,especially when they intrude into matured source rock intervals.
基金supported by the National Natural Science Foundation of China(32072941)。
文摘The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate,and the neonatal ovarian immune microenvironment,particularly its modulation by estrogen,has not been comprehensively characterized.In this study,the effects of 17β-estradiol(E_(2)),a key regulator of immune function,were investigated using single-cell transcriptomic profiling of C57BL/6J neonatal mouse ovaries after E_(2)treatment.Results revealed dynamic alterations in the proportion of immune cell types after E_(2)treatment,accompanied by changes in cytokine and chemokine expression.Detailed analyses of gene expression,cell states,and developmental trajectories across distinct cell types indicated that E_(2)treatment influenced cell differentiation and development.Notably,E_(2)treatment reduced the abundance of macrophages and promoted a phenotypic transition from M1 to M2 macrophages.These findings demonstrate that the neonatal mouse ovarian immune microenvironment is sensitive to estrogenic modulation,which governs both the distribution and functional specialization of resident immune cells,offering novel mechanistic insights into the immunomodulatory roles of estrogen across various immune cell types.
