During aging,the spine undergoes degenerative changes,particularly with vertebral endplate bone expansion and sclerosis,that are associated with nonspecific low back pain.We report that parathyroid hormone(PTH)treatme...During aging,the spine undergoes degenerative changes,particularly with vertebral endplate bone expansion and sclerosis,that are associated with nonspecific low back pain.We report that parathyroid hormone(PTH)treatment reduced vertebral endplate sclerosis and improved pain behaviors in three mouse models of spinal degeneration(aged,SM/J,and young lumbar spine instability mice).Aberrant innervation in the vertebral body and endplate during spinal degeneration was decreased with PTH treatment as quantified by PGP9.5^(+)and CGRP^(+)nerve fibers,as well as CGRP expression in dorsal root ganglia.The neuronal repulsion factor Slit3 significantly increased in response to PTH treatment mediated by transcriptional factor FoxA2.PTH type 1 receptor and Slit3 deletion in osteocalcin-expressing cells prevented PTH-reduction of endplate porosity and improvement in behavior tests.Altogether,PTH stimulated osteoblast production of Slit3,decreased aberrant sensory nerve innervation,and provided symptomatic relief of LBP associated with mouse spinal degeneration.展开更多
Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patien...Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.展开更多
The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral bloo...The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.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
Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.展开更多
Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)...Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)introduced the Single Tremelimumab Regular Interval Durvalumab(STRIDE)regimen,an immunotherapy-based approach that achieved a median overall survival(OS)of 16.43 months compared to 13.77 months with sorafenib.While statistically significant,this~2.7 months OS gain warrants scrutiny in light of STRIDE’s increased immune-related toxicity and cost.This commentary evaluates STRIDE’s impact within the broader landscape of first-line systemic therapy for unresectable HCC,alongside other regimens such as atezolizumab plus bevacizumab and nivolumab plus ipilimumab.We explore STRIDE’s mechanism of action,safety profile,modest progression-free survival(PFS)improvement,and implementation challenges,incorporating insights from 2023-2025 research.In addition,we discussed its limitations in non-viral HCC and Child-Pugh B patients,the role of emerging biomarkers,and the potential of radiation to enhance immunotherapy efficacy.As a dual immune checkpoint inhibitor(ICI)strategy,STRIDE offers an important advance that may not only extend survival but also open the door to future curative approaches.However,optimizing its use will require refined patient selection and further investigation of synergistic combination therapies.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In th...Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In this study,we investigated the potential therapeutic effects of MCC950,a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor,on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats.Our results showed that chronic administration of MCC950(10 mg/kg)to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation,thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors,including interleukin-1βand-18.A decrease in astrocytic and microglial activation was also observed.We also found that MCC950 significantly inhibited autophagy.More importantly,behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function,which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain,such as blood‒brain barrier breakdown,white matter damage,and endothelial dysfunction.Thus,our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.展开更多
This study presents a comprehensive phylogenetic analysis on Batrachospermaceae based on key taxonomic identifiers(rbcL,psaA,psbA,and COI-5P)from some genera.To systematically explore the phylogenetic relationships an...This study presents a comprehensive phylogenetic analysis on Batrachospermaceae based on key taxonomic identifiers(rbcL,psaA,psbA,and COI-5P)from some genera.To systematically explore the phylogenetic relationships and taxonomy within Batrachospermaceae,we integrated molecular and morphological data,and explored the phylogeny,character evolution,and ancestral geographical origin and provided a theoretical support for the classification and geographic origination of Batrachospermaceae.Our findings reveal distinct relationships within the phylogenetic tree.Notably,10 genera(Sirodotia,Batrachospermum,Tuomeya,Volatus,Lympha,Nothocladus,Torularia,Sheathia,Nocturama,and Petrohua)are closely associated in the rbcL phylogenetic tree.Additionally,four genera(Kumanoa,Hoefkenia,Notohesperus,and Virescentia)exhibit high support ratios,indicating their close interrelations.Other genera,including Paludicola,Visia,Acarposporophycos,Macrosporophycos,Visioidea,Balliopsis,and Psilosiphon,exhibit clustering traits.Furthermore,the multigene sequences provide a robust support for Montagnia that forms a monophyletic group.Ancestral reconstruction of morphological characters identifies nine primitive character states,including whorl,fascicle length,cortical cells,secondary fascicles,the shape of carpogonical branch,spermatangia,carposporophyte,carpogonium and trichogyne,with Visia likely representing ancestral traits in Batrachospermaceae.Furthermore,geographical origin maps suggest a potential common ancestral of Batrachospermaceae origin in the American continent.Additional to conventional analyses,including evolutionary and ancestral reconstruction investigations into key morphological characters,we attempt to reconstruct the biogeography within the Batrachospermaceae,thus contributing to a nuanced understanding of its origin.展开更多
Background:As an important indicator of subjective well-being(SWB),decent work is a key guarantee for the sustainable development of teachers and their psychological health and work quality.Faced with the rapid develo...Background:As an important indicator of subjective well-being(SWB),decent work is a key guarantee for the sustainable development of teachers and their psychological health and work quality.Faced with the rapid development of artificial intelligence and the global labor market,vocational college teachers are facing challenges such as workload pressure and limited career development,which may harm their well-being.This study aims to localize the measurement method of decent work in Chinese vocational education based on the theory of the Psychology of Working Theory,and explore the relationship mechanism between organizational support,career adaptability,decent work,and job satisfaction among vocational college teachers.Methods:A cross-sectional survey was conducted with 422 HVCU teachers in China(202 male,220 female)using the localized Perceived Organizational Support Scale,Career Adaptability Scale,Decent Work Scale,and Job Satisfaction Scale.Results:The overall level of HVCU teachers’decent work was above the median(Mean=4.09,SD=0.69),laying a foundation for their SWB.Decent work significantly and positively predicted job satisfaction(β=0.620,p<0.001).Organizational support(r=0.58,p<0.001)and career adaptability(r=0.82,p<0.001)can positively affect decent work,and further improve job satisfaction(collective R2 rising from 38.3%to 41.1%).Bootstrap analysis confirmed these mediating effects were robust.Conclusions:This study confirms that the combined effects of organizational support and career adaptability can enhance decent work,further improving teachers’job satisfaction and subsequent subjective well-being.Besides,this study provides an empirical basis for improving the well-being of higher vocational teachers and the sustainable development of vocational education,and has practical significance for improving the teacher incentive policy.展开更多
Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulat...Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.展开更多
Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is importan...Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.展开更多
Background:We aimed to study physician attitudes toward ultrasound-guided procedures and possible improvements.We hypothesized that the usage of ultrasound in procedures may be limited by a high barrier of entry and t...Background:We aimed to study physician attitudes toward ultrasound-guided procedures and possible improvements.We hypothesized that the usage of ultrasound in procedures may be limited by a high barrier of entry and that most physicians would choose to adopt software that provides real-time image guidance if accessible.Methods:A voluntary,cross-sectional survey of physicians at a single site was conducted using a five-point Likert scale.Data analysis included both descriptive and inferential statistical analyses and stratified by categorical descriptors,including variables of formal training,years of experience,and specialty of practice.Results:One hundred sixteen physicians responded to the survey.The majority disagreed that there was a steep learning curve(57.5%)and that they need more time to identify structures under ultrasound(85.0%).Overall attitudes were mixed about the use of additional software to improve ease of use,but most(55.4%)had positive opinions toward the addition of real-time 3D reconstruction.Respondents without formal training were significantly more likely to agree that additional software would improve ease of ultrasound-guided procedures(p=0.0389).Radiologists were significantly more likely to perceive a steeper learning curve and less likely to advocate for supplemental software compared to emergency medicine physicians,surgeons,or anesthesiologists.Conclusions:Surveyed physicians demonstrated comfort with ultrasound-guided procedures and a mixed stance toward the use of additional software to assist with procedures.Those without formal training had significantly more positive attitudes toward the use of additional technology to augment ultrasound-guided procedures,suggesting a knowledge gap that may benefit from such technology.展开更多
Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics cl...Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.展开更多
BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical...BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.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
BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investi...BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.展开更多
Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes...Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes with non-traditional forms of teaching and learning,and increased work pressure leading to an increase in the rate of teachers leaving the profession.Therefore,this study aims to explore the mechanism of the career calling on job burnout through career adaptability and work engagement.Methods:This study conducted a cross-sectional survey of 465 primary and secondary school teachers(PSST)in China's Mainland from the perspective of work adjustment and used structural equation modeling(SEM)to examine the mediating roles of career adaptability and work engagement in the relationship between teachers’career calling and job burnout.Results:The results show that PSSTs are above average in career calling,career adaptability,and work engagement,while job burnout is below average.A significant positive or negative correlation exists between career calling,career adaptability,work engagement,and job burnout.The result of path analysis indicates that career adaptability and work engagement exert an indirect influence on the job burnout of PSST through three paths:namely,the independent intermediary role of career adaptability(EV=−0.144),the independent intermediary role of work engagement(EV=0.172)and the chain intermediary role of the two(EV=0.176).Conclusion:This study emphasizes the importance of career adaptability and work engagement in teacher development in regulating career calling and job burnout.Therefore,on the one hand,we think that if managers want to reduce teachers’job burnout,they need to pay more attention to teachers’career adaptability and work engagement,rather than relying solely on teachers’career calling.On the other hand,it is to remind teachers not to rely on their adjustment to adapt to the work,but also to need outside help as much as possible.展开更多
Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously...Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].展开更多
Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulati...Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).展开更多
基金supported by the U.S.Department of Health&Human Services NIH National Institute on Aging under Award Number P01AG066603(to J.C.)。
文摘During aging,the spine undergoes degenerative changes,particularly with vertebral endplate bone expansion and sclerosis,that are associated with nonspecific low back pain.We report that parathyroid hormone(PTH)treatment reduced vertebral endplate sclerosis and improved pain behaviors in three mouse models of spinal degeneration(aged,SM/J,and young lumbar spine instability mice).Aberrant innervation in the vertebral body and endplate during spinal degeneration was decreased with PTH treatment as quantified by PGP9.5^(+)and CGRP^(+)nerve fibers,as well as CGRP expression in dorsal root ganglia.The neuronal repulsion factor Slit3 significantly increased in response to PTH treatment mediated by transcriptional factor FoxA2.PTH type 1 receptor and Slit3 deletion in osteocalcin-expressing cells prevented PTH-reduction of endplate porosity and improvement in behavior tests.Altogether,PTH stimulated osteoblast production of Slit3,decreased aberrant sensory nerve innervation,and provided symptomatic relief of LBP associated with mouse spinal degeneration.
基金supported by the Canadian Institutes of Health Research(DFD-181599)the National Institutes of Health(T32AG058527)to RJB and R0190106435 to VM.
文摘Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.
基金supported by Department of Defense grant HT9425-24-1-0030 a grant from the Stanley Medical Research Institute(to SS).
文摘The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.
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funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
文摘Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)introduced the Single Tremelimumab Regular Interval Durvalumab(STRIDE)regimen,an immunotherapy-based approach that achieved a median overall survival(OS)of 16.43 months compared to 13.77 months with sorafenib.While statistically significant,this~2.7 months OS gain warrants scrutiny in light of STRIDE’s increased immune-related toxicity and cost.This commentary evaluates STRIDE’s impact within the broader landscape of first-line systemic therapy for unresectable HCC,alongside other regimens such as atezolizumab plus bevacizumab and nivolumab plus ipilimumab.We explore STRIDE’s mechanism of action,safety profile,modest progression-free survival(PFS)improvement,and implementation challenges,incorporating insights from 2023-2025 research.In addition,we discussed its limitations in non-viral HCC and Child-Pugh B patients,the role of emerging biomarkers,and the potential of radiation to enhance immunotherapy efficacy.As a dual immune checkpoint inhibitor(ICI)strategy,STRIDE offers an important advance that may not only extend survival but also open the door to future curative approaches.However,optimizing its use will require refined patient selection and further investigation of synergistic combination therapies.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金supported by the National Natural Science Foundation of China,No.82201626(to CC)the Natural Science Foundation of LiaoningProvince,No.2022-MS-442(to CC)the Dalian Municipal Medical Key Specialty Climbing Project,No.2024ZZ040(to MZ).
文摘Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In this study,we investigated the potential therapeutic effects of MCC950,a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor,on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats.Our results showed that chronic administration of MCC950(10 mg/kg)to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation,thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors,including interleukin-1βand-18.A decrease in astrocytic and microglial activation was also observed.We also found that MCC950 significantly inhibited autophagy.More importantly,behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function,which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain,such as blood‒brain barrier breakdown,white matter damage,and endothelial dysfunction.Thus,our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.
基金Supported by the National Natural Science Foundation of China(No.32170204)。
文摘This study presents a comprehensive phylogenetic analysis on Batrachospermaceae based on key taxonomic identifiers(rbcL,psaA,psbA,and COI-5P)from some genera.To systematically explore the phylogenetic relationships and taxonomy within Batrachospermaceae,we integrated molecular and morphological data,and explored the phylogeny,character evolution,and ancestral geographical origin and provided a theoretical support for the classification and geographic origination of Batrachospermaceae.Our findings reveal distinct relationships within the phylogenetic tree.Notably,10 genera(Sirodotia,Batrachospermum,Tuomeya,Volatus,Lympha,Nothocladus,Torularia,Sheathia,Nocturama,and Petrohua)are closely associated in the rbcL phylogenetic tree.Additionally,four genera(Kumanoa,Hoefkenia,Notohesperus,and Virescentia)exhibit high support ratios,indicating their close interrelations.Other genera,including Paludicola,Visia,Acarposporophycos,Macrosporophycos,Visioidea,Balliopsis,and Psilosiphon,exhibit clustering traits.Furthermore,the multigene sequences provide a robust support for Montagnia that forms a monophyletic group.Ancestral reconstruction of morphological characters identifies nine primitive character states,including whorl,fascicle length,cortical cells,secondary fascicles,the shape of carpogonical branch,spermatangia,carposporophyte,carpogonium and trichogyne,with Visia likely representing ancestral traits in Batrachospermaceae.Furthermore,geographical origin maps suggest a potential common ancestral of Batrachospermaceae origin in the American continent.Additional to conventional analyses,including evolutionary and ancestral reconstruction investigations into key morphological characters,we attempt to reconstruct the biogeography within the Batrachospermaceae,thus contributing to a nuanced understanding of its origin.
基金funded by Nanjing University of Posts and Telecommunications Humanities and Social Sciences Research Fund Project(NYY222055)Special research project on teaching reform of innovation and entrepreneurship education in Nanjing University of Posts and Telecommunications(GCSJG202528)+2 种基金General Subject of Educational Science Planning in Jiangsu Province(C/2024/01/76)General project of educational science research in Shanghai(C24288)Key funded project of Shandong Vocational Education Teaching Reform Research in 2022(2022052).
文摘Background:As an important indicator of subjective well-being(SWB),decent work is a key guarantee for the sustainable development of teachers and their psychological health and work quality.Faced with the rapid development of artificial intelligence and the global labor market,vocational college teachers are facing challenges such as workload pressure and limited career development,which may harm their well-being.This study aims to localize the measurement method of decent work in Chinese vocational education based on the theory of the Psychology of Working Theory,and explore the relationship mechanism between organizational support,career adaptability,decent work,and job satisfaction among vocational college teachers.Methods:A cross-sectional survey was conducted with 422 HVCU teachers in China(202 male,220 female)using the localized Perceived Organizational Support Scale,Career Adaptability Scale,Decent Work Scale,and Job Satisfaction Scale.Results:The overall level of HVCU teachers’decent work was above the median(Mean=4.09,SD=0.69),laying a foundation for their SWB.Decent work significantly and positively predicted job satisfaction(β=0.620,p<0.001).Organizational support(r=0.58,p<0.001)and career adaptability(r=0.82,p<0.001)can positively affect decent work,and further improve job satisfaction(collective R2 rising from 38.3%to 41.1%).Bootstrap analysis confirmed these mediating effects were robust.Conclusions:This study confirms that the combined effects of organizational support and career adaptability can enhance decent work,further improving teachers’job satisfaction and subsequent subjective well-being.Besides,this study provides an empirical basis for improving the well-being of higher vocational teachers and the sustainable development of vocational education,and has practical significance for improving the teacher incentive policy.
文摘Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.
文摘Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.
文摘Background:We aimed to study physician attitudes toward ultrasound-guided procedures and possible improvements.We hypothesized that the usage of ultrasound in procedures may be limited by a high barrier of entry and that most physicians would choose to adopt software that provides real-time image guidance if accessible.Methods:A voluntary,cross-sectional survey of physicians at a single site was conducted using a five-point Likert scale.Data analysis included both descriptive and inferential statistical analyses and stratified by categorical descriptors,including variables of formal training,years of experience,and specialty of practice.Results:One hundred sixteen physicians responded to the survey.The majority disagreed that there was a steep learning curve(57.5%)and that they need more time to identify structures under ultrasound(85.0%).Overall attitudes were mixed about the use of additional software to improve ease of use,but most(55.4%)had positive opinions toward the addition of real-time 3D reconstruction.Respondents without formal training were significantly more likely to agree that additional software would improve ease of ultrasound-guided procedures(p=0.0389).Radiologists were significantly more likely to perceive a steeper learning curve and less likely to advocate for supplemental software compared to emergency medicine physicians,surgeons,or anesthesiologists.Conclusions:Surveyed physicians demonstrated comfort with ultrasound-guided procedures and a mixed stance toward the use of additional software to assist with procedures.Those without formal training had significantly more positive attitudes toward the use of additional technology to augment ultrasound-guided procedures,suggesting a knowledge gap that may benefit from such technology.
基金supported by the Neurosurgery Pain Research Institute at Johns Hopkins University and by the Lehner Family Foundation.
文摘Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.
文摘BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.
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.
文摘BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.
基金funded by Humanities and Social Sciences Foundation and Natural Science Foundation of Nanjing University of Posts and Telecommunications(NYY222055,NY224176)General Subject of Educational Science Planning in Jiangsu Province(C/2024/01/76)National Natural Science Foundation of China(62307025).
文摘Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes with non-traditional forms of teaching and learning,and increased work pressure leading to an increase in the rate of teachers leaving the profession.Therefore,this study aims to explore the mechanism of the career calling on job burnout through career adaptability and work engagement.Methods:This study conducted a cross-sectional survey of 465 primary and secondary school teachers(PSST)in China's Mainland from the perspective of work adjustment and used structural equation modeling(SEM)to examine the mediating roles of career adaptability and work engagement in the relationship between teachers’career calling and job burnout.Results:The results show that PSSTs are above average in career calling,career adaptability,and work engagement,while job burnout is below average.A significant positive or negative correlation exists between career calling,career adaptability,work engagement,and job burnout.The result of path analysis indicates that career adaptability and work engagement exert an indirect influence on the job burnout of PSST through three paths:namely,the independent intermediary role of career adaptability(EV=−0.144),the independent intermediary role of work engagement(EV=0.172)and the chain intermediary role of the two(EV=0.176).Conclusion:This study emphasizes the importance of career adaptability and work engagement in teacher development in regulating career calling and job burnout.Therefore,on the one hand,we think that if managers want to reduce teachers’job burnout,they need to pay more attention to teachers’career adaptability and work engagement,rather than relying solely on teachers’career calling.On the other hand,it is to remind teachers not to rely on their adjustment to adapt to the work,but also to need outside help as much as possible.
基金supported by the Hyperbaric Med School of the Department of Biomedical Sciences at the University of Padova,the Italian Air Force,and the Institute of Clinical Physiology(Milan)-National Research Council(IFC-CNR).
文摘Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].
基金supported by the Merkin PNNR Center(23-DF/C2/261)(to HS).
文摘Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).