Chronic low-level lead (Pb) exposure in children is known to cause a deficit in learning and memory. In vitro studies have demonstrated that Pb altered protein kinase C (PKC) activityt Especially, hippocampal PKC has ...Chronic low-level lead (Pb) exposure in children is known to cause a deficit in learning and memory. In vitro studies have demonstrated that Pb altered protein kinase C (PKC) activityt Especially, hippocampal PKC has been correlated with performance in several learning tasks. The effects of Pb exposure on hippocampal PKC were investigated during development at various postnatal ages: postnatal day (PN) 7, 14, 28, and 56. Two-tenth % Pb acetate was administered to pregnant and lactating dams and then administered to weanling rats in drinking water. PKC activity was measured in both membrane and cytosolic fractions from the hippocampi of the controls and Pb-exposed animals. Pb-induced increase in PKC activity in the cytosolic fraction was obsereved in the PN56 rats. In contrast, PKC activity was decreased by Pb at PN7 in the membrane fraction. Furthermore, a significant decrease in the ratio of membrane to cytosolic PKC activity which is representative of PKC distribution was observed in the PN28 and PN56 Pb-exposed rats relative to the same-age controls. This study indicates that chronic Pb exposure during development influences hippocampal PKC activity and distribution. These changes may be involved in the subclinical neurotoxicity of chronic Pb exposure in young children.展开更多
Chronic intermittent hypobaric hypoxia (CIHH) is a treatment of moderate hypoxia that simulates high altitude interrupted by normoxia. Growing evidence shows that CIHH has multiple beneficial effects on
To study biomarker of acrylamide （ACR） induced neuropathy, Wistar rats received 20 or 40 mg/kg of ACR by ip injection and the levels of light neurofilament （NF-L）, middle NF （NF-M）, heavy NF （NF-H）, β-actin, ...To study biomarker of acrylamide （ACR） induced neuropathy, Wistar rats received 20 or 40 mg/kg of ACR by ip injection and the levels of light neurofilament （NF-L）, middle NF （NF-M）, heavy NF （NF-H）, β-actin, α-tubulin, and β-tubulin proteins in serum were evaluated using both SDS-PAGE and Western blotting. Compared to controls, NF-L and NF-M decreased,展开更多
Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution...Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution’in our environment[1]and subject living organisms to various sources of electromagnetic emissions.These emissions include;microwaves.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
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
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
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
The primary clinical manifestation of osteoarthritis (OA) is pain, yet considerable variability exists in the pain experience among OA patients. This narrative review aims to explore the mechanisms driving OA pain het...The primary clinical manifestation of osteoarthritis (OA) is pain, yet considerable variability exists in the pain experience among OA patients. This narrative review aims to explore the mechanisms driving OA pain heterogeneity to inform the development of targeted interventions that improve treatment efficacy and patient outcomes. A comprehensive literature search was conducted across multiple databases (PubMed, Scopus, and Google Scholar) for papers published between January 1, 2020, and December 31, 2024. Inclusion criteria focused on studies addressing pain mechanisms and therapeutic interventions in OA. This review identifies key mechanisms of OA pain, including joint alterations, angiogenesis, nervous system involvement, peripheral and central sensitization, and psychosocial factors. It highlights the underlying distinct mechanisms in OA pain, which contribute to the variability in individuals’ responses to treatment. It was suggested that interactions between neuroimmune and neurovascular systems are key contributors to chronic pain in OA. This narrative review emphasizes the complexity of OA pain, highlighting the importance of thoroughly understanding the underlying mechanisms for developing personalized and effective pain management strategies. Additional research is required to refine treatment approaches and explore long-term effects.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
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
AIM:To investigate the effect of pharmacological pupil alterations on intraocular lens(IOL)power calculations.METHODS:A systematic review and Meta-analysis of studies published before December 2023 in the PubMed,Embas...AIM:To investigate the effect of pharmacological pupil alterations on intraocular lens(IOL)power calculations.METHODS:A systematic review and Meta-analysis of studies published before December 2023 in the PubMed,Embase,and Cochrane library databases on the accuracy of pharmacological pupil changes on IOL power calculation was performed.The primary outcome was the results of IOL power calculations before and after the use of medications.Subgroup analyses were performed based on participants’basic characteristics,such as age,axial length(AL),and whether miosis or mydriasis were used as classification criteria for further analyses.Each eligible study was evaluated for potential risk of bias by the AHRQ assessment scale.The study was registered on PROSPERO(CRD 42024497535).RESULTS:A total of 3062 eyes from 21 studies were eligible.There was no significant difference in the IOL power calculation before and after pharmacological pupil changes using any of the Hoffer Q(WMD=0.055,95%CI=-0.046–0.156;P=0.29),SRK/T(WMD=0.003,95%CI=-0.073–0.080;P=0.93),Haigis(WMD=-0.030,95%CI=-0.176–0.116;P=0.69),Holladay 2(WMD=-0.042,95%CI=-0.366–0.282;P=0.80),and Barrett Universal Ⅱ(WMD=0.033,95%CI=-0.061–0.127;P=0.49)formulas.On the measurement of parameters related to IOL power calculation,for either miosis or mydriasis AL(P=0.98 and 0.29,respectively),lens thickness(P=0.96 and 0.13,respectively),and mean keratometry(P=0.90 and 0.86,respectively)did not present significant differences,while anterior chamber depth(P=0.07 and<0.01,respectively)and white-to-white distance(P=0.01 and 0.04,respectively)changed significantly between the two measurements prior and posterior.At the same time,despite there being some participants with the difference between the before and after calculations greater than 0.5 diopter,there was no significant difference in the incidence rate between these formulas.CONCLUSION:There is no significant effect of pharmacological pupil changes on the IOL power calculation.It will considerably reduce the visit time burden for patients who require cataract surgery.展开更多
With the escalating global prevalence of diabetes mellitus,diabetes-related complications have become a significant public health challenge[1].Studies highlight the pivotal role of gut microbiota alterations in the de...With the escalating global prevalence of diabetes mellitus,diabetes-related complications have become a significant public health challenge[1].Studies highlight the pivotal role of gut microbiota alterations in the development and progression of diabetes and its related complications[2–4].This insight emphasizes the modulation of gut microbiota as a leading focus in nursing research,offering a promising approach to enhance cognitive function in diabetic patients and advance nursing interventions[5].展开更多
文摘Chronic low-level lead (Pb) exposure in children is known to cause a deficit in learning and memory. In vitro studies have demonstrated that Pb altered protein kinase C (PKC) activityt Especially, hippocampal PKC has been correlated with performance in several learning tasks. The effects of Pb exposure on hippocampal PKC were investigated during development at various postnatal ages: postnatal day (PN) 7, 14, 28, and 56. Two-tenth % Pb acetate was administered to pregnant and lactating dams and then administered to weanling rats in drinking water. PKC activity was measured in both membrane and cytosolic fractions from the hippocampi of the controls and Pb-exposed animals. Pb-induced increase in PKC activity in the cytosolic fraction was obsereved in the PN56 rats. In contrast, PKC activity was decreased by Pb at PN7 in the membrane fraction. Furthermore, a significant decrease in the ratio of membrane to cytosolic PKC activity which is representative of PKC distribution was observed in the PN28 and PN56 Pb-exposed rats relative to the same-age controls. This study indicates that chronic Pb exposure during development influences hippocampal PKC activity and distribution. These changes may be involved in the subclinical neurotoxicity of chronic Pb exposure in young children.
基金supported by the National Basic Research Development Program of China [2012CB518200]the National Natural Science Foundation of China [31271223 and 31071002]
文摘Chronic intermittent hypobaric hypoxia (CIHH) is a treatment of moderate hypoxia that simulates high altitude interrupted by normoxia. Growing evidence shows that CIHH has multiple beneficial effects on
基金supported by the National Natural Science Fund of China (No.30872088)Technology Development Plan of Shandong Province(No.2012GSF11854)
文摘To study biomarker of acrylamide （ACR） induced neuropathy, Wistar rats received 20 or 40 mg/kg of ACR by ip injection and the levels of light neurofilament （NF-L）, middle NF （NF-M）, heavy NF （NF-H）, β-actin, α-tubulin, and β-tubulin proteins in serum were evaluated using both SDS-PAGE and Western blotting. Compared to controls, NF-L and NF-M decreased,
文摘Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution’in our environment[1]and subject living organisms to various sources of electromagnetic emissions.These emissions include;microwaves.
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 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 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supported by the National Health and Medical Research Council of Australia(No.APP1176298).
文摘The primary clinical manifestation of osteoarthritis (OA) is pain, yet considerable variability exists in the pain experience among OA patients. This narrative review aims to explore the mechanisms driving OA pain heterogeneity to inform the development of targeted interventions that improve treatment efficacy and patient outcomes. A comprehensive literature search was conducted across multiple databases (PubMed, Scopus, and Google Scholar) for papers published between January 1, 2020, and December 31, 2024. Inclusion criteria focused on studies addressing pain mechanisms and therapeutic interventions in OA. This review identifies key mechanisms of OA pain, including joint alterations, angiogenesis, nervous system involvement, peripheral and central sensitization, and psychosocial factors. It highlights the underlying distinct mechanisms in OA pain, which contribute to the variability in individuals’ responses to treatment. It was suggested that interactions between neuroimmune and neurovascular systems are key contributors to chronic pain in OA. This narrative review emphasizes the complexity of OA pain, highlighting the importance of thoroughly understanding the underlying mechanisms for developing personalized and effective pain management strategies. Additional research is required to refine treatment approaches and explore long-term effects.
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.
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.
基金Supported by Beijing Natural Science Foundation from Beijing Municipal Government(No.7202030).
文摘AIM:To investigate the effect of pharmacological pupil alterations on intraocular lens(IOL)power calculations.METHODS:A systematic review and Meta-analysis of studies published before December 2023 in the PubMed,Embase,and Cochrane library databases on the accuracy of pharmacological pupil changes on IOL power calculation was performed.The primary outcome was the results of IOL power calculations before and after the use of medications.Subgroup analyses were performed based on participants’basic characteristics,such as age,axial length(AL),and whether miosis or mydriasis were used as classification criteria for further analyses.Each eligible study was evaluated for potential risk of bias by the AHRQ assessment scale.The study was registered on PROSPERO(CRD 42024497535).RESULTS:A total of 3062 eyes from 21 studies were eligible.There was no significant difference in the IOL power calculation before and after pharmacological pupil changes using any of the Hoffer Q(WMD=0.055,95%CI=-0.046–0.156;P=0.29),SRK/T(WMD=0.003,95%CI=-0.073–0.080;P=0.93),Haigis(WMD=-0.030,95%CI=-0.176–0.116;P=0.69),Holladay 2(WMD=-0.042,95%CI=-0.366–0.282;P=0.80),and Barrett Universal Ⅱ(WMD=0.033,95%CI=-0.061–0.127;P=0.49)formulas.On the measurement of parameters related to IOL power calculation,for either miosis or mydriasis AL(P=0.98 and 0.29,respectively),lens thickness(P=0.96 and 0.13,respectively),and mean keratometry(P=0.90 and 0.86,respectively)did not present significant differences,while anterior chamber depth(P=0.07 and<0.01,respectively)and white-to-white distance(P=0.01 and 0.04,respectively)changed significantly between the two measurements prior and posterior.At the same time,despite there being some participants with the difference between the before and after calculations greater than 0.5 diopter,there was no significant difference in the incidence rate between these formulas.CONCLUSION:There is no significant effect of pharmacological pupil changes on the IOL power calculation.It will considerably reduce the visit time burden for patients who require cataract surgery.
文摘With the escalating global prevalence of diabetes mellitus,diabetes-related complications have become a significant public health challenge[1].Studies highlight the pivotal role of gut microbiota alterations in the development and progression of diabetes and its related complications[2–4].This insight emphasizes the modulation of gut microbiota as a leading focus in nursing research,offering a promising approach to enhance cognitive function in diabetic patients and advance nursing interventions[5].
