In this editorial,a commentary on the article by Chang et al has been provided,the course of treatment of anorectal fistulas,especially complex and recurring ones,require accurate diagnostic procedures for determining...In this editorial,a commentary on the article by Chang et al has been provided,the course of treatment of anorectal fistulas,especially complex and recurring ones,require accurate diagnostic procedures for determining ideal surgical procedures.Conventional ways of imaging sometimes fall short,offering insufficient insights in aggravated instances.In this editorial,a novel application of hydrogen peroxide-enhanced magnetic resonance imaging(HP-MRI)that promises significant improvements in the imaging of anorectal fistula.Study is based on a retrospective investigation of 60 patients,contrasts the new HP-MRI with conventional diagnostic techniques such as physical examination,trans-perineal ultrasonography and poor spatial resolution MRI.The findings demonstrate HP-MRI's incredible diagnostic performance,with sensitivity and specificity rates of 96.08%and 90.91%,respectively,and unparalleled interobserver agreement(Kappa values ranging from 0.80 to 0.89).It has been a significant advancement for assessment of anorectal fistulas providing a better roadmap for surgical planning,lowering recurrence rates as well as reduced personal and financial burden on patients by reducing the need for repeated treatment and extended hospital stays.The remaining funds can be utilized for treatment of other medical need.Ultimately HP-MRI provides us a healthier&more efficient society by improvising patients well-being&optimized healthcare infrastructure.展开更多
Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A ...Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis....Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.展开更多
N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory lo...N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.展开更多
Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially...Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.展开更多
Reforestation initiatives are often limited by insufficient seeds,a problem exacerbated by natural variability in tree flowering and seed production and climate change and other environmental challenges.Innovative and...Reforestation initiatives are often limited by insufficient seeds,a problem exacerbated by natural variability in tree flowering and seed production and climate change and other environmental challenges.Innovative and adaptive solutions such as in vitro propagation are thus needed.Tissue culture can provide high-quality propagation material for tree conservation and mass propagation,but faces technical,economic,regulatory,and social barriers.Obstacles related to the academia-industry interface and to stakeholder concerns are discussed and actions suggested to overcome these barriers to realize the full potential of tree micropropagation.These include refining techniques to improve efficiency and reduce costs;establishing collaborations among researchers,industry,and foresters;and reducing points of contention and misinformation regarding genetic diversity and public perception.International collaborative initiatives,exemplified by the EU COST Action CA21157 COPYTREE,are elementary for achieving these goals.展开更多
Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian clock.The hormone is primarily synthesized by the vertebrate pinea...Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian clock.The hormone is primarily synthesized by the vertebrate pineal gland,but is ubiquitous among invertebrates,unicellular organisms,plants,and even cyanobacteria(Hattori and Suzuki,2024).Melatonin is well-conserved evolutionarily and possesses several physiological functions,such as immune response,bone and glucose metabolism,and memory formation besides regulating the circadian rhythm.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
Background Coronary atherectomy is used to treat severely calcified coronary artery lesions which are more frequent with increasing age,but its impact in older adults has not been sufficiently examined.Methods We comp...Background Coronary atherectomy is used to treat severely calcified coronary artery lesions which are more frequent with increasing age,but its impact in older adults has not been sufficiently examined.Methods We compared adults≥18 years old who underwent coronary atherectomy during inpatient PCI in 2016–2023 from the Vizient Clinical Data Base and compared outcomes in younger(<65 years),youngest-old(65–74 years),middle-old(75–84 years),and oldest-old(≥85 years)adults.Primary outcome was in-hospital mortality,and secondary outcomes included postprocedural complications.Results Among 47,337 patients who underwent coronary atherectomy,19,862(42.0%)were younger adults and 27,475(58.0%)were older adults,including 13,583 youngest-old,10,206 middle-old,and 3,686 oldest-old adults.Compared with younger adults,youngest-old adults had higher mortality(adjusted odds ratio[aOR]=1.37,P<0.001),ischemic stroke(aOR=1.35,P=0.005),gastrointestinal hemorrhage(GIH)(aOR=1.44,P<0.001),acute kidney injury(AKI)(aOR=1.43,P<0.001),tamponade(aOR=1.86,P<0.001),and pericardiocentesis(aOR=2.32,P<0.001).Middle-old adults had higher mortality(aOR=1.80,P<0.001),GIH(aOR=1.42,P=0.002),AKI(aOR=1.63,P<0.001),tamponade(aOR=2.52,P<0.001),and pericardiocentesis(aOR=3.13,P<0.001).Oldest-old adults had the highest odds for mortality(aOR=2.03,P<0.001),GIH(aOR=1.48,P=0.016),AKI(aOR=2.26,P<0.001),tamponade(aOR=3.86,P<0.001),and pericardiocentesis(aOR=4.21,P<0.001).There was a significant interaction(P-interaction=0.035)between atherectomy and age groups with regard to the odds of in-hospital mortality.Conclusions In this large claims-based study,in-hospital mortality,GIH,AKI,tamponade,and pericardiocentesis were higher in older adults compared with younger adults,in a stepwise manner by age group.展开更多
BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diag...BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.展开更多
Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot real...Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation.To address this,we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration.We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system(pMSS)with repetitive transcranial magnetic stimulation in mice.Oxytocin levels,dendritic morphology and density,and mouse behavior were measured before and after pMSS intervention.Our findings suggest that pMSS can activate oxytocinergic neurons,leading to upregulation of oxytocin secretion and neurite outgrowth.As a result,sociability was rapidly improved after a one-week pMSS treatment regimen.These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.展开更多
Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying ...Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying mice with comorbid acute neurogenic pulmonary edema(NPE),a life-threatening systemic consequence often induced by SAH,in this model is difficult without histopathological investiga-tions.Herein,we present an imaging procedure involving dual-energy X-ray absorp-tiometry(DXA)to identify NPE in a murine model of SAH.We quantified the lung lean mass(LM)and compared the relationship between micro-computed tomography(CT)evidence of Hounsfield unit(HU)values and histopathological findings of PE.Of the 85 mice with successful induction of SAH by filament perforation,16(19%)had NPE,as verified by postmortem histology.The DXA-LM values correlate well with CT-HU levels(r=0.63,p<0.0001).Regarding the relationship between LM and HU in mice with post-SAH NPE,the LM was positively associated with HU values(r2=0.43;p=0.0056).A receiver operating characteristics curve of LM revealed a sensitivity of 87%and specificity of 57%for detecting PE,with a similar area under the curve as the HU(0.79±0.06 vs.0.84±0.07;p=0.21).These data suggest that confirming acute NPE using DXA-LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is defined by the abnormal lipid deposition in hepatocytes.The prevalence of MASLD is significantly increased in the elderly population,suggest...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is defined by the abnormal lipid deposition in hepatocytes.The prevalence of MASLD is significantly increased in the elderly population,suggesting that aging may be related to the occurrence of MASLD.Emerging evidences suggest that vitamin D receptor(VDR)may be implicated in the progression of MASLD.Therefore,additional researches are warranted to elucidate whether VDR plays a role in aging-related MASLD.AIM To investigate the relationship between aging and MASLD and explore the role and related mechanisms of VDR in aging-related MASLD.METHODS Cellular senescence models were established,and the senescence phenotype of telomerase RNA component knockout mice was validated.These mice were then used as a senescence model for subsequent studies.Changes in VDR expression in the livers of aging mice were examined.VDR knockdown models,including cell knockdown models and hepatic-specific VDR knockout mice,were constructed,and MASLD was established in these models.Additionally,vitamin D(VD)-supplemented models,including senescent liver cell lines and senescent mice,were constructed.RESULTS The steatosis in senescent liver cells was more severe than in normal cells(P<0.05).Moreover,hepatic steatosis was significantly more pronounced in senescence model mice compared to control group when the MASLD model was successfully induced(P<0.05).Therefore,we concluded that aging aggravated hepatic steatosis.The hepatic expression of VDR increased after aging.VDR knockdown in senescent liver cells and senescent mice alleviated hepatic steatosis(P<0.05).When senescent liver cells were stimulated with VD,cellular steatosis was aggravated(P<0.05).However,VD supplementation had no effect on aging mice.CONCLUSION Aging can lead to increased hepatic steatosis,and the hepatic-specific knockdown of VDR alleviated aging-related MASLD.VDR could serve as a potential molecular target for aging-related MASLD.展开更多
In this letter,a commentary on the article by Xu et al has been provided.Gastrointestinal stomal tumours(GISTs)are rare tumours that originate commonly in stomach(60%-70%)and small intestine(30%-40%).The course of tre...In this letter,a commentary on the article by Xu et al has been provided.Gastrointestinal stomal tumours(GISTs)are rare tumours that originate commonly in stomach(60%-70%)and small intestine(30%-40%).The course of treatment especially oesophageal GIST is very complex and hard to diagnose because of limited availability of pathological and clinical data.Endoscopic resection(ER)is a minimally invasive approach for removing tumours from the oesophagus and digestive system that does not require open surgery and is especially successful for very small and low-risk GIST.A retrospective exami-nation of 32 patients treated with ER between 2012 and 2023 was conducted to analyse clinical and pathological characteristics,effectiveness of therapy,and long-term prognosis.The findings demonstrate en bloc resection was achieved in 96.9%of cases with an R0 resection rate of 75%with a median size of tumour was approximately 2.12 cm.Post-surgery complication like hydrothorax,post-endoscopic submucosal dissection electrocoagulation syndrome occurred in about 25%of cases which later go resolved by conservative treatment.Recurrence of GIST was approximately 9.4%primarily in high-risk cases.ER should be widely adopted in clinical practise preferably for managing low-risk oesophageal GIST because of its high success rate,low recurrence rates and excellent survival results,ensuring better patient prognosis.展开更多
Accurate,reliable,and regularly updated information is necessary for targeted management of forest stands.This information is usually obtained from sample-based field inventory data.Due to the time-consuming and costl...Accurate,reliable,and regularly updated information is necessary for targeted management of forest stands.This information is usually obtained from sample-based field inventory data.Due to the time-consuming and costly procedure of forest inventory,it is imperative to generate and use the resulting data optimally.Integrating field inventory information with remote sensing data increases the value of field approaches,such as national forest inventories.This study investigated the optimal integration of forest inventory data with aerial image-based canopy height models(CHM)for forest growing stock estimation.For this purpose,fixed-area and angle-count plots from a forest area in Austria were used to assess which type of inventory system is more suitable when the field data is integrated with aerial image analysis.Although a higher correlation was observed between remotely predicted growing stocks and field inventory values for fixed-area plots,the paired t-test results revealed no statistical difference between the two methods.The R2 increased by 0.08 points and the RMSE decreased by 7.7 percentage points(24.8m^(3)·ha^(−1))using fixed-area plots.Since tree height is the most critical variable essential for modeling forest growing stock using aerial images,we also compared the tree heights obtained from CHM to those from the typical field inventory approach.The result shows a high correlation(R^(2)=0.781)between the tree heights extracted from the CHM and those measured in the field.However,the correlation decreased by 0.113 points and the RMSE increased by 4.2 percentage points(1.04m)when the allometrically derived tree heights were analyzed.Moreover,the results of the paired t-test revealed that there is no significant statistical difference between the tree heights extracted from CHM and those measured in the field,but there is a significant statistical difference when the CHM-derived and the allometrically-derived heights were compared.This proved that image-based CHM can obtain more accurate tree height information than field inventory estimations.Overall,the results of this study demonstrated that image-based CHM can be integrated into the forest inventory data at large scales and provide reliable information on forest growing stock.The produced maps reflect the variability of growth conditions and developmental stages of different forest stands.This information is required to characterize the status and changes,e.g.,in forest structure diversity,parameters for volume,and can be used for forest aboveground biomass estimation,which plays an important role in managing and controlling forest resources in mid-term forest management.This is of particular interest to forest managers and forest ecologists.展开更多
文摘In this editorial,a commentary on the article by Chang et al has been provided,the course of treatment of anorectal fistulas,especially complex and recurring ones,require accurate diagnostic procedures for determining ideal surgical procedures.Conventional ways of imaging sometimes fall short,offering insufficient insights in aggravated instances.In this editorial,a novel application of hydrogen peroxide-enhanced magnetic resonance imaging(HP-MRI)that promises significant improvements in the imaging of anorectal fistula.Study is based on a retrospective investigation of 60 patients,contrasts the new HP-MRI with conventional diagnostic techniques such as physical examination,trans-perineal ultrasonography and poor spatial resolution MRI.The findings demonstrate HP-MRI's incredible diagnostic performance,with sensitivity and specificity rates of 96.08%and 90.91%,respectively,and unparalleled interobserver agreement(Kappa values ranging from 0.80 to 0.89).It has been a significant advancement for assessment of anorectal fistulas providing a better roadmap for surgical planning,lowering recurrence rates as well as reduced personal and financial burden on patients by reducing the need for repeated treatment and extended hospital stays.The remaining funds can be utilized for treatment of other medical need.Ultimately HP-MRI provides us a healthier&more efficient society by improvising patients well-being&optimized healthcare infrastructure.
基金supported by ANID FONDECYT No.1221178Centro Ciencia&Vida,FB210008,Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID to CTR.
文摘Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
基金supported by the Natural Science Foundation of Jilin Province(No.SKL202302002).
文摘Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.
基金supported by the National Institute on Aging(Nos.AG000723 and AG000578)(to VAB)the Fondation Sante(No.19656),Greece 2.0+1 种基金the National Recovery and Resilience Plan’s flagship program TAEDR-0535850the European Research Council(No.101077374-Synapto Mitophagy)(to KP)。
文摘N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.
基金supported by the National Key Research and Development Project(2022YFA1104500 to JX)the National Natural Science Foundation of China(82020108002 and82225005 to JX and 82370277 to HW)+1 种基金the Science and Technology Commission of Shanghai Municipality(23ZR1422900 to HW and 23410750100 to JX)supported by a Biotechnology and Biological Sciences Research Council(BBSRC)International Partnering Award。
文摘Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.
基金funded by COST Action CA21157“European Network for Innovative Woody Plant Cloning”www.cost.eusupported by COST(European Cooperation in Science and Technology)www.cost.eu。
文摘Reforestation initiatives are often limited by insufficient seeds,a problem exacerbated by natural variability in tree flowering and seed production and climate change and other environmental challenges.Innovative and adaptive solutions such as in vitro propagation are thus needed.Tissue culture can provide high-quality propagation material for tree conservation and mass propagation,but faces technical,economic,regulatory,and social barriers.Obstacles related to the academia-industry interface and to stakeholder concerns are discussed and actions suggested to overcome these barriers to realize the full potential of tree micropropagation.These include refining techniques to improve efficiency and reduce costs;establishing collaborations among researchers,industry,and foresters;and reducing points of contention and misinformation regarding genetic diversity and public perception.International collaborative initiatives,exemplified by the EU COST Action CA21157 COPYTREE,are elementary for achieving these goals.
基金supported by JSPS KAKENHI Grant Number JP22K11823 to AH and JP22J01508 to KW。
文摘Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian clock.The hormone is primarily synthesized by the vertebrate pineal gland,but is ubiquitous among invertebrates,unicellular organisms,plants,and even cyanobacteria(Hattori and Suzuki,2024).Melatonin is well-conserved evolutionarily and possesses several physiological functions,such as immune response,bone and glucose metabolism,and memory formation besides regulating the circadian rhythm.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
文摘Background Coronary atherectomy is used to treat severely calcified coronary artery lesions which are more frequent with increasing age,but its impact in older adults has not been sufficiently examined.Methods We compared adults≥18 years old who underwent coronary atherectomy during inpatient PCI in 2016–2023 from the Vizient Clinical Data Base and compared outcomes in younger(<65 years),youngest-old(65–74 years),middle-old(75–84 years),and oldest-old(≥85 years)adults.Primary outcome was in-hospital mortality,and secondary outcomes included postprocedural complications.Results Among 47,337 patients who underwent coronary atherectomy,19,862(42.0%)were younger adults and 27,475(58.0%)were older adults,including 13,583 youngest-old,10,206 middle-old,and 3,686 oldest-old adults.Compared with younger adults,youngest-old adults had higher mortality(adjusted odds ratio[aOR]=1.37,P<0.001),ischemic stroke(aOR=1.35,P=0.005),gastrointestinal hemorrhage(GIH)(aOR=1.44,P<0.001),acute kidney injury(AKI)(aOR=1.43,P<0.001),tamponade(aOR=1.86,P<0.001),and pericardiocentesis(aOR=2.32,P<0.001).Middle-old adults had higher mortality(aOR=1.80,P<0.001),GIH(aOR=1.42,P=0.002),AKI(aOR=1.63,P<0.001),tamponade(aOR=2.52,P<0.001),and pericardiocentesis(aOR=3.13,P<0.001).Oldest-old adults had the highest odds for mortality(aOR=2.03,P<0.001),GIH(aOR=1.48,P=0.016),AKI(aOR=2.26,P<0.001),tamponade(aOR=3.86,P<0.001),and pericardiocentesis(aOR=4.21,P<0.001).There was a significant interaction(P-interaction=0.035)between atherectomy and age groups with regard to the odds of in-hospital mortality.Conclusions In this large claims-based study,in-hospital mortality,GIH,AKI,tamponade,and pericardiocentesis were higher in older adults compared with younger adults,in a stepwise manner by age group.
基金Supported by the National Natural Science Foundation of China,No.82202185and Shanghai Science and Technology Development Foundation,No.22Y11911500.
文摘BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.
基金supported by the China Science and Technology Innovation 2030-Major Project(2022ZD0211700)the Major Program of the National Natural Science Foundation of China(62394312)+2 种基金the National Natural Science Foundation of China(82471536)the Wenzhou Science and Technology Projects(ZY2023006,2024R2002)Oujiang Laboratory(OJQD2022002).
文摘Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation.To address this,we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration.We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system(pMSS)with repetitive transcranial magnetic stimulation in mice.Oxytocin levels,dendritic morphology and density,and mouse behavior were measured before and after pMSS intervention.Our findings suggest that pMSS can activate oxytocinergic neurons,leading to upregulation of oxytocin secretion and neurite outgrowth.As a result,sociability was rapidly improved after a one-week pMSS treatment regimen.These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
基金supported by the Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science KAKENHI 22K09110.
文摘Murine subarachnoid hemorrhage(SAH)induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH.However,identifying mice with comorbid acute neurogenic pulmonary edema(NPE),a life-threatening systemic consequence often induced by SAH,in this model is difficult without histopathological investiga-tions.Herein,we present an imaging procedure involving dual-energy X-ray absorp-tiometry(DXA)to identify NPE in a murine model of SAH.We quantified the lung lean mass(LM)and compared the relationship between micro-computed tomography(CT)evidence of Hounsfield unit(HU)values and histopathological findings of PE.Of the 85 mice with successful induction of SAH by filament perforation,16(19%)had NPE,as verified by postmortem histology.The DXA-LM values correlate well with CT-HU levels(r=0.63,p<0.0001).Regarding the relationship between LM and HU in mice with post-SAH NPE,the LM was positively associated with HU values(r2=0.43;p=0.0056).A receiver operating characteristics curve of LM revealed a sensitivity of 87%and specificity of 57%for detecting PE,with a similar area under the curve as the HU(0.79±0.06 vs.0.84±0.07;p=0.21).These data suggest that confirming acute NPE using DXA-LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.
基金Supported by the National Natural Science Foundation of China,No.820300089.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is defined by the abnormal lipid deposition in hepatocytes.The prevalence of MASLD is significantly increased in the elderly population,suggesting that aging may be related to the occurrence of MASLD.Emerging evidences suggest that vitamin D receptor(VDR)may be implicated in the progression of MASLD.Therefore,additional researches are warranted to elucidate whether VDR plays a role in aging-related MASLD.AIM To investigate the relationship between aging and MASLD and explore the role and related mechanisms of VDR in aging-related MASLD.METHODS Cellular senescence models were established,and the senescence phenotype of telomerase RNA component knockout mice was validated.These mice were then used as a senescence model for subsequent studies.Changes in VDR expression in the livers of aging mice were examined.VDR knockdown models,including cell knockdown models and hepatic-specific VDR knockout mice,were constructed,and MASLD was established in these models.Additionally,vitamin D(VD)-supplemented models,including senescent liver cell lines and senescent mice,were constructed.RESULTS The steatosis in senescent liver cells was more severe than in normal cells(P<0.05).Moreover,hepatic steatosis was significantly more pronounced in senescence model mice compared to control group when the MASLD model was successfully induced(P<0.05).Therefore,we concluded that aging aggravated hepatic steatosis.The hepatic expression of VDR increased after aging.VDR knockdown in senescent liver cells and senescent mice alleviated hepatic steatosis(P<0.05).When senescent liver cells were stimulated with VD,cellular steatosis was aggravated(P<0.05).However,VD supplementation had no effect on aging mice.CONCLUSION Aging can lead to increased hepatic steatosis,and the hepatic-specific knockdown of VDR alleviated aging-related MASLD.VDR could serve as a potential molecular target for aging-related MASLD.
文摘In this letter,a commentary on the article by Xu et al has been provided.Gastrointestinal stomal tumours(GISTs)are rare tumours that originate commonly in stomach(60%-70%)and small intestine(30%-40%).The course of treatment especially oesophageal GIST is very complex and hard to diagnose because of limited availability of pathological and clinical data.Endoscopic resection(ER)is a minimally invasive approach for removing tumours from the oesophagus and digestive system that does not require open surgery and is especially successful for very small and low-risk GIST.A retrospective exami-nation of 32 patients treated with ER between 2012 and 2023 was conducted to analyse clinical and pathological characteristics,effectiveness of therapy,and long-term prognosis.The findings demonstrate en bloc resection was achieved in 96.9%of cases with an R0 resection rate of 75%with a median size of tumour was approximately 2.12 cm.Post-surgery complication like hydrothorax,post-endoscopic submucosal dissection electrocoagulation syndrome occurred in about 25%of cases which later go resolved by conservative treatment.Recurrence of GIST was approximately 9.4%primarily in high-risk cases.ER should be widely adopted in clinical practise preferably for managing low-risk oesophageal GIST because of its high success rate,low recurrence rates and excellent survival results,ensuring better patient prognosis.
基金supported by grants provided within the research project»EO4Forest:Use of multi-temporal Sentinel-2 and VHR Pleiades stereo data for sustainable forest monitoring and management«funded by the Austrian Federal Ministry for Climate Action,Environ-ment,Energy,Mobility,Innovation and Technology(BMK)within the FFG Austrian Space Applications Program ASAP 12(grant agreement number 854027).
文摘Accurate,reliable,and regularly updated information is necessary for targeted management of forest stands.This information is usually obtained from sample-based field inventory data.Due to the time-consuming and costly procedure of forest inventory,it is imperative to generate and use the resulting data optimally.Integrating field inventory information with remote sensing data increases the value of field approaches,such as national forest inventories.This study investigated the optimal integration of forest inventory data with aerial image-based canopy height models(CHM)for forest growing stock estimation.For this purpose,fixed-area and angle-count plots from a forest area in Austria were used to assess which type of inventory system is more suitable when the field data is integrated with aerial image analysis.Although a higher correlation was observed between remotely predicted growing stocks and field inventory values for fixed-area plots,the paired t-test results revealed no statistical difference between the two methods.The R2 increased by 0.08 points and the RMSE decreased by 7.7 percentage points(24.8m^(3)·ha^(−1))using fixed-area plots.Since tree height is the most critical variable essential for modeling forest growing stock using aerial images,we also compared the tree heights obtained from CHM to those from the typical field inventory approach.The result shows a high correlation(R^(2)=0.781)between the tree heights extracted from the CHM and those measured in the field.However,the correlation decreased by 0.113 points and the RMSE increased by 4.2 percentage points(1.04m)when the allometrically derived tree heights were analyzed.Moreover,the results of the paired t-test revealed that there is no significant statistical difference between the tree heights extracted from CHM and those measured in the field,but there is a significant statistical difference when the CHM-derived and the allometrically-derived heights were compared.This proved that image-based CHM can obtain more accurate tree height information than field inventory estimations.Overall,the results of this study demonstrated that image-based CHM can be integrated into the forest inventory data at large scales and provide reliable information on forest growing stock.The produced maps reflect the variability of growth conditions and developmental stages of different forest stands.This information is required to characterize the status and changes,e.g.,in forest structure diversity,parameters for volume,and can be used for forest aboveground biomass estimation,which plays an important role in managing and controlling forest resources in mid-term forest management.This is of particular interest to forest managers and forest ecologists.
