Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to cont...Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.展开更多
Malnutrition is present in the majority of patients presenting for surgical management of gastrointestinal malignancies,due to the effects of the tumour and preoperative anti-neoplastic treatments.The traditional prac...Malnutrition is present in the majority of patients presenting for surgical management of gastrointestinal malignancies,due to the effects of the tumour and preoperative anti-neoplastic treatments.The traditional practice of fasting patients until the resumption of bowel function threatens to further contribute to the malnutrition experienced by these patients.Furthermore,the rationale behind this traditional practice has been rendered obsolete through developments in anaesthetic agents and changes to postoperative analgesia practices.Conversely,there is a growing body of literature that consistently demonstrates that providing oral or tube feeding proximal to the anastomosis within 24 h postoperatively,is not only safe,but might be associated with significant benefits to the postoperative course.Early post operative feeding should therefore be adopted as a standard of care in oncology patients undergoing gastrointestinal resections.展开更多
Background:Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province,China and is under consideration in other countries,including the United States.As China begins to i...Background:Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province,China and is under consideration in other countries,including the United States.As China begins to implement DMD newborn screening (DMD-NBS),there is ongoing discussion regarding the steps forward for follow up care of positively identified patients as well as false positive and false negative results.Data sources:Relevant papers related to DMD-NBS,and NBS in China were reviewed in PubMed.Results:The current state of DMD-NBS is discussed,along with the steps needed to effectively screen infants for this disease in China,recommendations for establishment of follow up care in patients with positive and negative screens,and measurement of patient outcomes.Conclusions:Zhejiang Province,China is ready to implement DMD-NBS.Future challenges that exist for this program,and other countries,include the ability to track patients,assist with access to care,and ensure adequate follow-up care according to evidence-based guidelines.In addition,China's large rural population,lack of specialty providers,and difficulty in educating patients regarding the benefits of treatment create challenges that will need to be addressed.展开更多
Genetic variation ranging from single-nucleotide polymorphisms to large structural variants (SVs) can cause variation of gene content among individuals within the same species. There is an increasing appreciation that...Genetic variation ranging from single-nucleotide polymorphisms to large structural variants (SVs) can cause variation of gene content among individuals within the same species. There is an increasing appreciation that a single reference genome is insufficient to capture the full landscape of genetic diversity of a species. Pan-genome analysis offers a platform to evaluate the genetic diversity of a species via investigation of its entire genome repertoire. Although a recent wave of pan-genomic studies has shed new light on crop diversity and improvement using advanced sequencing technology, the potential applications of crop pan-genomics in crop improvement are yet to be fully exploited. In this review, we highlight the progress achieved in understanding crop pan?genomics, discuss biological activities that cause SVs, review important agronomical traits affected by SVs, and present our perspective on the application of pan-genomics in crop improvement.展开更多
Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of ...Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of the military.Vision loss is commonly associated with traumatic brain injuries of all severities and can leave patients permanently disabled.This vision loss can be caused by injury to the visual system at multiple levels,including the eyes,optic nerves,and many different sites in the brain and brainstem(Sen,2017).Despite the far-reaching effects of visual impairment after traumatic brain injury,its incidence after traumatic brain injury is not well measured,and few successful treatments have been identified or implemented.展开更多
Bacterial wilt （BW） caused by Ralstonia solanacearum is an important constraint to peanut （Arachis hypogaea L.） production in several Asian and African countries, and planting BW-resistant cultivars is the most fe...Bacterial wilt （BW） caused by Ralstonia solanacearum is an important constraint to peanut （Arachis hypogaea L.） production in several Asian and African countries, and planting BW-resistant cultivars is the most feasible method for controlling the disease. Although several BW-resistant peanut germplasm accessions have been identified, the genetic diversity among these has not been properly investigated, which has impeded efficient utilization. In this study, the genetic relationships of 31 peanut genotypes with various levels of resistance to BW were assessed based on SSR and AFLP analyses. Twenty-nine of 78 SSR primers and 32 of 126 AFLP primer combinations employed in this study were polymorphic amongst the peanut genotypes tested. The SSR primers amplified 91 polymorphic loci in total with an average of 3.14 alleles per primer, and the AFLP primers amplified 72 polymorphic loci in total with an average of 2.25 alleles per primer. Four SSR primers （14H06, 7G02, 3A8, 16C6） and one AFLP primer （P1M62） were found to be most efficient in detecting diversity. The genetic distance between pairs of genotypes ranged from 0.12 to 0.94 with an average of 0.53 in the SSR data and from 0.06 to 0.57 with an average of 0.25 in the AFLP data. The SSR-based estimates of the genetic distance were generally larger than that based on the AFLP data. The genotypes belonging to subsp, fastigiata possessed wider diversity than that of subsp, hypogaea. The clustering of genotypes based on the SSR and AFLP data were similar but the SSR clustering was more consistent with morphological classification ofA. hypogaea. Optimum diverse genotypes of both subsp, hypogaea and subsp.fastigiata can be recommended based on this analysis for developing mapping populations and breeding for high yielding and resistant cultivars.展开更多
Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress.Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating ...Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress.Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances.In this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells.SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1.Consistent with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1.Finally,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter.These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway.Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases.展开更多
Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via endoscopes.Miniaturized endoscopic probes are necessary for imaging small luminal or delicate or...Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via endoscopes.Miniaturized endoscopic probes are necessary for imaging small luminal or delicate organs without causing trauma to tissue.However,current fabrication methods limit the imaging performance of highly miniaturized probes,restricting their widespread application.To overcome this limitation,we developed a novel ultrathin probe fabrication technique that utilizes 3D microprinting to reliably create side-facing freeform micro-optics(<130μm diameter)on single-mode fibers.Using this technique,we built a fully functional ultrathin aberration-corrected optical coherence tomography probe.This is the smallest freeform 3D imaging probe yet reported,with a diameter of 0.457 mm,including the catheter sheath.We demonstrated image quality and mechanical flexibility by imaging atherosclerotic human and mouse arteries.The ability to provide microstructural information with the smallest optical coherence tomography catheter opens a gateway for novel minimally invasive applications in disease.展开更多
This review aims to familiarize the radiologist with the common types of sinus surgery including their indications and techniques.We also illustrate how surgeons interpret 3D sinus anatomy when evaluating computed tom...This review aims to familiarize the radiologist with the common types of sinus surgery including their indications and techniques.We also illustrate how surgeons interpret 3D sinus anatomy when evaluating computed tomography(CT)studies.Preoperative evaluation by CT is mandatory for all patients undergoing functional endoscopic sinus surgery(FESS).In the past decade in particular,CT of the paranasal sinuses has become a roadmap for FESS.The radiologist's goal is to report on five key points:the extent of sinus opacification,opacification of sinus drainage pathways,anatomical variants,critical variants,and condition of surrounding soft tissues of the neck,brain and orbits.We present a systematic approach to the use of coronal,axial,and sagittal images in CT evaluation before FESS.展开更多
AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One...AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haemato- chemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS: The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O3-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (P <0.05 at 12 months). None of the treated patients experienced a loss in visual acuity in their study eye at 6 and 12 months, compared to 16% and 40 % of patients in the control group who lost 2 lines or more at 6 months and 12 months respectively (P <0.05 treated vs control group)). Major ozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, P <0.05) and an increase in Biological Antioxidant Po展开更多
Background:Physical activity(PA)in the early years is associated with a range of positive health outcomes.Fundamental motor skill(FMS)competence is associated with PA and is theorized to be driven by PA in the early y...Background:Physical activity(PA)in the early years is associated with a range of positive health outcomes.Fundamental motor skill(FMS)competence is associated with PA and is theorized to be driven by PA in the early years and vice versa in mid to late childhood.However,to date,no studies have meta-analyzed the association between PA and FMS in the early years.Methods:Six electronic databases were searched for articles published up to April 2019.Cross-sectional and longitudinal studies were included if they targeted children(ages 3-6 year)as the population of the study and assessed the association between objectively measured PA and FMS.Total FMS,total physical activity(TPA),and moderate-to-vigorous physical activity(MVPA)data were meta-analyzed using a random effects model.Results:We identified 24,815 titles and abstracts.In total,19 studies met the inclusion criteria,including 14 cross-sectional and 4 longitudinal studies,as well as 1 study with cross-sectional and longitudinal analysis.There was a significant but small positive association between FMS and MVPA(r=0.20,95%confidence interval(CI):0.13-0.26)and TPA(r=0.20,95%CI:0.12-0.28).Findings from longitudinal studies revealed that PA drives FMS in early childhood.Mediation was explored in 1 study,which found that perceived motor competence did not mediate the association between FMS and PA.Conclusion:Using a meta-analysis,this study is the first to show a positive association between FMS,MVPA,and TPA in the early years of childhood,suggesting that the association begins at an early age.Limited evidence from longitudinal studies supports the theory that PA drives FMS in the early years of childhood.More evidence is needed from large studies to track PA and FMS until mid to late childhood and to explore the mediators of this association.展开更多
Herd immunity is often considered a measure to protect a whole community or population from disease if the vaccination threshold is met. Using the demographic and COVID-19 infection data from the state of Pennsylvania...Herd immunity is often considered a measure to protect a whole community or population from disease if the vaccination threshold is met. Using the demographic and COVID-19 infection data from the state of Pennsylvania, United States, the study aimed to determine if herd immunity by vaccination is an effective way to reduce the spread of the COVID-19 virus. The Pennsylvania counties were split into two groups based on qualification of herd immunity: counties that met the COVID-19 herd immunization rate of 70% and counties that did not. The ANOVA test was used to analyze the difference between the groups with and without herd immunity by the COVID-19 vaccine. The results demonstrated that there was no significant statistical difference between counties that did achieve and those that did not achieve the herd immunity threshold for the COVID-19 vaccine. On the other hand, it was observed that there had been a significant decrease in positive cases between 2020 and 2023. This decline can be attributed to the overall protection by the vaccination and adaptability to the disease, not specifically due to herd immunity alone. Ultimately, these outcomes suggest that herd immunity cannot reduce the risk of contracting COVID-19. Increased efforts to get vaccinated should be implemented to protect the general community and a wider scope of age.展开更多
Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity c...Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity can improve memory and spatial cognition,reduce age-related cognitive decline,and preserve brain volume,but the mechanisms are not fully understood.Accordingly,we investigated whether any detrimental effects of high-fat diet(HFD)-induced obesity on cognition,motor behavior,adult hippocampal neurogenesis,and brain-derived neurotrophic factor(BDNF)could be mitigated by voluntary exercise training in male C57Bl/6 mice.HFD-induced impairment of motor function was not reversed by exercise.Importantly,voluntary wheel running improved long-term memory and increased hippocampal neurogenesis,suggesting that regular physical activity may prevent cognitive decline in obesity.展开更多
Research of autonomous manufacturing systems is motivated both by the new technical possibilities of cyber-physical systems and by the practical needs of the industry.Autonomous operation in semi-structured industrial...Research of autonomous manufacturing systems is motivated both by the new technical possibilities of cyber-physical systems and by the practical needs of the industry.Autonomous operation in semi-structured industrial environments can now be supported by advanced sensor technologies,digital twins,artificial intelligence and novel communication techniques.These enable real-time monitoring of production processes,situation recognition and prediction,automated and adaptive(re)planning,teamwork and performance improvement by learning.This paper summarizes the main requirements towards autonomous industrial robotics and suggests a generic workflow for realizing such systems.Application case studies will be presented from recent practice at HUN-REN SZTAKI in a broad range of domains such as assembly,welding,grinding,picking and placing,and machining.The various solutions have in common that they use a generic digital twin concept as their core.After making general recommendations for realizing autonomous robotic solutions in the industry,open issues for future research will be discussed.展开更多
Ischemia-reperfusion injury(IRI)remains an unresolved and complicated situation in clinical practice,especially in the case of organ transplantation.Several factors contribute to its complexity;the depletion of energy...Ischemia-reperfusion injury(IRI)remains an unresolved and complicated situation in clinical practice,especially in the case of organ transplantation.Several factors contribute to its complexity;the depletion of energy during ischemia and the induction of oxidative stress during reperfusion initiate a cascade of pathways that lead to cell death and finally to severe organ injury.Recently,the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases has gained increasing attention from researchers,due to their involvement in the modulation of a wide variety of cellular functions.There are seven mammalian sirtuins and,among them,the nuclear/cytoplasmic sirtuin 1(SIRT1)and the mitochondrial sirtuin 3(SIRT3)are ubiquitously expressed in many tissue types.Sirtuins are known to play major roles in protecting against cellular stress and in controlling metabolic pathways,which are key processes during IRI.In this review,we mainly focus on SIRT1 and SIRT3 and examine their role in modulating pathways against energy depletion during ischemia and their involvement in oxidative stress,apoptosis,microcirculatory stress and inflammation during reperfusion.We present evidence of the beneficial effects of sirtuins against IRI and emphasize the importance of developing new strategies by enhancing their action.展开更多
Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without th...Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.展开更多
基金Supported by The Association for International Cancer Research(AICRto Dr.Al-Hassi HO)+6 种基金ScotlandFunded by the AICRgrant No.120234a BBSRC Strategic Research Grant(to English N and Knight SCWMNIP33458)the St Mark’s Hospital FoundationUnited Kingdom
文摘Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.
文摘Malnutrition is present in the majority of patients presenting for surgical management of gastrointestinal malignancies,due to the effects of the tumour and preoperative anti-neoplastic treatments.The traditional practice of fasting patients until the resumption of bowel function threatens to further contribute to the malnutrition experienced by these patients.Furthermore,the rationale behind this traditional practice has been rendered obsolete through developments in anaesthetic agents and changes to postoperative analgesia practices.Conversely,there is a growing body of literature that consistently demonstrates that providing oral or tube feeding proximal to the anastomosis within 24 h postoperatively,is not only safe,but might be associated with significant benefits to the postoperative course.Early post operative feeding should therefore be adopted as a standard of care in oncology patients undergoing gastrointestinal resections.
基金Muscular Dystrophy Association,unrestricted grants from Sarepta and Marathon,PerkinElmer,National High Technology Research and Development Program(863 Program,2015AA020513)Zhejiang Provincial Natural Science Foundation of China(LY16H0900007).
文摘Background:Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province,China and is under consideration in other countries,including the United States.As China begins to implement DMD newborn screening (DMD-NBS),there is ongoing discussion regarding the steps forward for follow up care of positively identified patients as well as false positive and false negative results.Data sources:Relevant papers related to DMD-NBS,and NBS in China were reviewed in PubMed.Results:The current state of DMD-NBS is discussed,along with the steps needed to effectively screen infants for this disease in China,recommendations for establishment of follow up care in patients with positive and negative screens,and measurement of patient outcomes.Conclusions:Zhejiang Province,China is ready to implement DMD-NBS.Future challenges that exist for this program,and other countries,include the ability to track patients,assist with access to care,and ensure adequate follow-up care according to evidence-based guidelines.In addition,China's large rural population,lack of specialty providers,and difficulty in educating patients regarding the benefits of treatment create challenges that will need to be addressed.
文摘Genetic variation ranging from single-nucleotide polymorphisms to large structural variants (SVs) can cause variation of gene content among individuals within the same species. There is an increasing appreciation that a single reference genome is insufficient to capture the full landscape of genetic diversity of a species. Pan-genome analysis offers a platform to evaluate the genetic diversity of a species via investigation of its entire genome repertoire. Although a recent wave of pan-genomic studies has shed new light on crop diversity and improvement using advanced sequencing technology, the potential applications of crop pan-genomics in crop improvement are yet to be fully exploited. In this review, we highlight the progress achieved in understanding crop pan?genomics, discuss biological activities that cause SVs, review important agronomical traits affected by SVs, and present our perspective on the application of pan-genomics in crop improvement.
基金supported by NIH grant HD001097(to NKE)by a Cincinnati Children’s Hospital Procter Scholar Award(to NKE)
文摘Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of the military.Vision loss is commonly associated with traumatic brain injuries of all severities and can leave patients permanently disabled.This vision loss can be caused by injury to the visual system at multiple levels,including the eyes,optic nerves,and many different sites in the brain and brainstem(Sen,2017).Despite the far-reaching effects of visual impairment after traumatic brain injury,its incidence after traumatic brain injury is not well measured,and few successful treatments have been identified or implemented.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(No.30070521 and 30270840).
文摘Bacterial wilt （BW） caused by Ralstonia solanacearum is an important constraint to peanut （Arachis hypogaea L.） production in several Asian and African countries, and planting BW-resistant cultivars is the most feasible method for controlling the disease. Although several BW-resistant peanut germplasm accessions have been identified, the genetic diversity among these has not been properly investigated, which has impeded efficient utilization. In this study, the genetic relationships of 31 peanut genotypes with various levels of resistance to BW were assessed based on SSR and AFLP analyses. Twenty-nine of 78 SSR primers and 32 of 126 AFLP primer combinations employed in this study were polymorphic amongst the peanut genotypes tested. The SSR primers amplified 91 polymorphic loci in total with an average of 3.14 alleles per primer, and the AFLP primers amplified 72 polymorphic loci in total with an average of 2.25 alleles per primer. Four SSR primers （14H06, 7G02, 3A8, 16C6） and one AFLP primer （P1M62） were found to be most efficient in detecting diversity. The genetic distance between pairs of genotypes ranged from 0.12 to 0.94 with an average of 0.53 in the SSR data and from 0.06 to 0.57 with an average of 0.25 in the AFLP data. The SSR-based estimates of the genetic distance were generally larger than that based on the AFLP data. The genotypes belonging to subsp, fastigiata possessed wider diversity than that of subsp, hypogaea. The clustering of genotypes based on the SSR and AFLP data were similar but the SSR clustering was more consistent with morphological classification ofA. hypogaea. Optimum diverse genotypes of both subsp, hypogaea and subsp.fastigiata can be recommended based on this analysis for developing mapping populations and breeding for high yielding and resistant cultivars.
基金supported by funds from the Spanish Ministry of Economy and Competitiveness(SAF2015-64146-R and RTI2018-093999-B-100)and the“FundacióLa Maratóde TV3”to M.V.-C.
文摘Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress.Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances.In this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells.SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1.Consistent with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1.Finally,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter.These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway.Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases.
基金funded by the Australian Research Council(CE140100003)a Premier’s Research and Industry Fund grant provided by the South Australian Government Department for Industry and Skills+5 种基金BMBF PRINTOPTICS(13N14096,13N14097),Baden-Wurttemberg(BW)Stiftung OPTERIAL,European Research Council Advanced Grant COMPLEXPLAS,European Research Council Proof of Concept 3DPrintedOptics,and German Research Foundation(DFG)Integrated quantum science and technology(IQST)the National Health and Medical Research Council(NHMRC,Principle Research Fellowship 1111630)the National Heart Foundation(Lin Huddleston Senior Fellowship,and Postdoctoral Fellowship 102093)the University of Adelaide(Faculty of Health and Medical Sciences Emerging Leadership Program grant and Research Travel Award)Australia-Germany Joint Research Co-operation Scheme(UA-DAAD).
文摘Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via endoscopes.Miniaturized endoscopic probes are necessary for imaging small luminal or delicate organs without causing trauma to tissue.However,current fabrication methods limit the imaging performance of highly miniaturized probes,restricting their widespread application.To overcome this limitation,we developed a novel ultrathin probe fabrication technique that utilizes 3D microprinting to reliably create side-facing freeform micro-optics(<130μm diameter)on single-mode fibers.Using this technique,we built a fully functional ultrathin aberration-corrected optical coherence tomography probe.This is the smallest freeform 3D imaging probe yet reported,with a diameter of 0.457 mm,including the catheter sheath.We demonstrated image quality and mechanical flexibility by imaging atherosclerotic human and mouse arteries.The ability to provide microstructural information with the smallest optical coherence tomography catheter opens a gateway for novel minimally invasive applications in disease.
文摘This review aims to familiarize the radiologist with the common types of sinus surgery including their indications and techniques.We also illustrate how surgeons interpret 3D sinus anatomy when evaluating computed tomography(CT)studies.Preoperative evaluation by CT is mandatory for all patients undergoing functional endoscopic sinus surgery(FESS).In the past decade in particular,CT of the paranasal sinuses has become a roadmap for FESS.The radiologist's goal is to report on five key points:the extent of sinus opacification,opacification of sinus drainage pathways,anatomical variants,critical variants,and condition of surrounding soft tissues of the neck,brain and orbits.We present a systematic approach to the use of coronal,axial,and sagittal images in CT evaluation before FESS.
文摘AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haemato- chemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS: The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O3-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (P <0.05 at 12 months). None of the treated patients experienced a loss in visual acuity in their study eye at 6 and 12 months, compared to 16% and 40 % of patients in the control group who lost 2 lines or more at 6 months and 12 months respectively (P <0.05 treated vs control group)). Major ozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, P <0.05) and an increase in Biological Antioxidant Po
文摘Background:Physical activity(PA)in the early years is associated with a range of positive health outcomes.Fundamental motor skill(FMS)competence is associated with PA and is theorized to be driven by PA in the early years and vice versa in mid to late childhood.However,to date,no studies have meta-analyzed the association between PA and FMS in the early years.Methods:Six electronic databases were searched for articles published up to April 2019.Cross-sectional and longitudinal studies were included if they targeted children(ages 3-6 year)as the population of the study and assessed the association between objectively measured PA and FMS.Total FMS,total physical activity(TPA),and moderate-to-vigorous physical activity(MVPA)data were meta-analyzed using a random effects model.Results:We identified 24,815 titles and abstracts.In total,19 studies met the inclusion criteria,including 14 cross-sectional and 4 longitudinal studies,as well as 1 study with cross-sectional and longitudinal analysis.There was a significant but small positive association between FMS and MVPA(r=0.20,95%confidence interval(CI):0.13-0.26)and TPA(r=0.20,95%CI:0.12-0.28).Findings from longitudinal studies revealed that PA drives FMS in early childhood.Mediation was explored in 1 study,which found that perceived motor competence did not mediate the association between FMS and PA.Conclusion:Using a meta-analysis,this study is the first to show a positive association between FMS,MVPA,and TPA in the early years of childhood,suggesting that the association begins at an early age.Limited evidence from longitudinal studies supports the theory that PA drives FMS in the early years of childhood.More evidence is needed from large studies to track PA and FMS until mid to late childhood and to explore the mediators of this association.
文摘Herd immunity is often considered a measure to protect a whole community or population from disease if the vaccination threshold is met. Using the demographic and COVID-19 infection data from the state of Pennsylvania, United States, the study aimed to determine if herd immunity by vaccination is an effective way to reduce the spread of the COVID-19 virus. The Pennsylvania counties were split into two groups based on qualification of herd immunity: counties that met the COVID-19 herd immunization rate of 70% and counties that did not. The ANOVA test was used to analyze the difference between the groups with and without herd immunity by the COVID-19 vaccine. The results demonstrated that there was no significant statistical difference between counties that did achieve and those that did not achieve the herd immunity threshold for the COVID-19 vaccine. On the other hand, it was observed that there had been a significant decrease in positive cases between 2020 and 2023. This decline can be attributed to the overall protection by the vaccination and adaptability to the disease, not specifically due to herd immunity alone. Ultimately, these outcomes suggest that herd immunity cannot reduce the risk of contracting COVID-19. Increased efforts to get vaccinated should be implemented to protect the general community and a wider scope of age.
基金supported by an NHMRC Investigator Grant(APP1194141)supported by project grants from the NHMRC(APP1042465,APP1041760,and APP1156511).
文摘Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity can improve memory and spatial cognition,reduce age-related cognitive decline,and preserve brain volume,but the mechanisms are not fully understood.Accordingly,we investigated whether any detrimental effects of high-fat diet(HFD)-induced obesity on cognition,motor behavior,adult hippocampal neurogenesis,and brain-derived neurotrophic factor(BDNF)could be mitigated by voluntary exercise training in male C57Bl/6 mice.HFD-induced impairment of motor function was not reversed by exercise.Importantly,voluntary wheel running improved long-term memory and increased hippocampal neurogenesis,suggesting that regular physical activity may prevent cognitive decline in obesity.
基金supported by the European Union within the framework of the“National Laboratory for Autonomous Systems”(No.RRF-2.3.1-212022-00002)the Hungarian“Research on prime exploitation of the potential provided by the industrial digitalisation(No.ED-18-2-2018-0006)”the“Research on cooperative production and logistics systems to support a competitive and sustainable economy(No.TKP2021-NKTA-01)”。
文摘Research of autonomous manufacturing systems is motivated both by the new technical possibilities of cyber-physical systems and by the practical needs of the industry.Autonomous operation in semi-structured industrial environments can now be supported by advanced sensor technologies,digital twins,artificial intelligence and novel communication techniques.These enable real-time monitoring of production processes,situation recognition and prediction,automated and adaptive(re)planning,teamwork and performance improvement by learning.This paper summarizes the main requirements towards autonomous industrial robotics and suggests a generic workflow for realizing such systems.Application case studies will be presented from recent practice at HUN-REN SZTAKI in a broad range of domains such as assembly,welding,grinding,picking and placing,and machining.The various solutions have in common that they use a generic digital twin concept as their core.After making general recommendations for realizing autonomous robotic solutions in the industry,open issues for future research will be discussed.
基金Supported by AGAUR,No.2012FI_B00382,Generalitat de Catalunya,Barcelona,Spain,to Pantazi ECSIC for the development program to Bejaoui M,No.I-COOP0005The Fondo de Investigaciones Sanitarias,No.FIS PI12/00519
文摘Ischemia-reperfusion injury(IRI)remains an unresolved and complicated situation in clinical practice,especially in the case of organ transplantation.Several factors contribute to its complexity;the depletion of energy during ischemia and the induction of oxidative stress during reperfusion initiate a cascade of pathways that lead to cell death and finally to severe organ injury.Recently,the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases has gained increasing attention from researchers,due to their involvement in the modulation of a wide variety of cellular functions.There are seven mammalian sirtuins and,among them,the nuclear/cytoplasmic sirtuin 1(SIRT1)and the mitochondrial sirtuin 3(SIRT3)are ubiquitously expressed in many tissue types.Sirtuins are known to play major roles in protecting against cellular stress and in controlling metabolic pathways,which are key processes during IRI.In this review,we mainly focus on SIRT1 and SIRT3 and examine their role in modulating pathways against energy depletion during ischemia and their involvement in oxidative stress,apoptosis,microcirculatory stress and inflammation during reperfusion.We present evidence of the beneficial effects of sirtuins against IRI and emphasize the importance of developing new strategies by enhancing their action.
文摘Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.
