Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postn...Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
Wearable sensors integrated with deep learning techniques have the potential to revolutionize seamless human-machine interfaces for real-time health monitoring,clinical diagnosis,and robotic applications.Nevertheless,...Wearable sensors integrated with deep learning techniques have the potential to revolutionize seamless human-machine interfaces for real-time health monitoring,clinical diagnosis,and robotic applications.Nevertheless,it remains a critical challenge to simultaneously achieve desirable mechanical and electrical performance along with biocompatibility,adhesion,self-healing,and environmental robustness with excellent sensing metrics.Herein,we report a multifunctional,anti-freezing,selfadhesive,and self-healable organogel pressure sensor composed of cobalt nanoparticle encapsulated nitrogen-doped carbon nanotubes(CoN CNT)embedded in a polyvinyl alcohol-gelatin(PVA/GLE)matrix.Fabricated using a binary solvent system of water and ethylene glycol(EG),the CoN CNT/PVA/GLE organogel exhibits excellent flexibility,biocompatibility,and temperature tolerance with remarkable environmental stability.Electrochemical impedance spectroscopy confirms near-stable performance across a broad humidity range(40%-95%RH).Freeze-tolerant conductivity under sub-zero conditions(-20℃)is attributed to the synergistic role of CoN CNT and EG,preserving mobility and network integrity.The Co N CNT/PVA/GLE organogel sensor exhibits high sensitivity of 5.75 k Pa^(-1)in the detection range from 0 to 20 k Pa,ideal for subtle biomechanical motion detection.A smart human-machine interface for English letter recognition using deep learning achieved 98%accuracy.The organogel sensor utility was extended to detect human gestures like finger bending,wrist motion,and throat vibration during speech.展开更多
The regenerative capacity of peripheral nerve is significantly different from injury responses in the central nervous system.Regeneration of injured axons,re-myelination and functional recovery are readily observed af...The regenerative capacity of peripheral nerve is significantly different from injury responses in the central nervous system.Regeneration of injured axons,re-myelination and functional recovery are readily observed after injury to peripheral nerve.展开更多
Buildings represent a significant share of the world’s energy consumption,and the sector has drawn the attention of governments,which have adopted policies to reduce energy expenditure.The Certifications of Energy Ef...Buildings represent a significant share of the world’s energy consumption,and the sector has drawn the attention of governments,which have adopted policies to reduce energy expenditure.The Certifications of Energy Efficiency in Buildings stand out as one possible solution to achieve this goal,employed in several countries worldwide.The European Union presents advanced energy assessment programs for buildings,being a reference and model for several other regulations in the world.The Energy Certification System for Buildings(SCE)of Portugal is considered a success case,reflected in the significant number of energy certificates issued.The Brazilian Labeling Program for Building(PBE Edifica),first launched in 2009,does not find a broad application today in the Brazilian scenario.This work shows a synthesis of the European Energy Performance of Buildings Directive(EPBD)and the Brazilian and Portuguese regulations’history.A qualitative comparison is made between the SCE and the PBE Edifica to verify a European and a developing country’s regulations with a certain degree of cultural and climatic similarities.Through this comparison,proposals are made for improvements to Brazilian certification,seeking to improve its energy planning and energy policy concerning its building stock.The suggestions for improvement presented may also be appropriate for other developing countries that have started and have not yet successfully implemented their energy certification programs in buildings.展开更多
Food restriction is a strategy to improve the productive efficiency of some aquatic organisms.It is expected with the implementation of food restriction programs to first reduce the feed consumption by the cultivated ...Food restriction is a strategy to improve the productive efficiency of some aquatic organisms.It is expected with the implementation of food restriction programs to first reduce the feed consumption by the cultivated species and consequently reduce the waste load in the water.In addition,there is a lower employment of labor during periods of food restriction.However,the efficiency of the feed restriction and the compensatory gain of weight by the organisms cultivated will depend on the adaptation and the characteristics of the species in question.Several methodologies have tested forms of food restriction applied to fish farming.Some of them are addressed in this review,as well as results and comparisons made with several authors on the subject in question.The purpose of this paper was to describe the main reasons for using food restriction,its implications on fish organism and to compare results from previous studies.展开更多
Introduction: Child obesity has important consequences on the child’s health and is related to the risk of developing chronic diseases. That brings up the need for research assessing the impact of obesity-and overwei...Introduction: Child obesity has important consequences on the child’s health and is related to the risk of developing chronic diseases. That brings up the need for research assessing the impact of obesity-and overweight-reduction programs with close attention to methodology aspects and precise indicators of the impact of such programs. Goal: Assessing the impact of a physical activity program on the plasma concentrations of adiponectin, leptin, and ghrelin in overweight and obese schoolchildren. Methods: Randomized controlled trial, double-blind, with 6-to 9-year-old overweight and obese school-children. A sample of 79 schoolchildren randomly distributed into control and intervention groups was subjected to a physical activity program. The levels of adiponectin, leptin, ghrelin, body mass index, body fat percentage, anthropometry, lipid profile and glycemia were evaluated. The program’s impact was assessed through multivariate linear regression models. Result: When comparing the groups, a significant difference was found for adiponectin, which shows an increase in the proportion of subjects with higher adiponectin concentrations for the intervention group and a reduction in body mass index and body fat percentage. Conclusion: The impact of the intervention program was positive in increasing adiponectin levels associated with a reduction in body mass index and body fat percentage.展开更多
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
BACKGROUND Family caregivers of cirrhosis patients(CPs)often experience burden,stress,and depression.Investigating whether these conditions improve following the patient undergoing liver transplantation(LT)is crucial,...BACKGROUND Family caregivers of cirrhosis patients(CPs)often experience burden,stress,and depression.Investigating whether these conditions improve following the patient undergoing liver transplantation(LT)is crucial,as it would elucidate the compre-hensive benefits of the procedure and demonstrate the positive impacts not only on the patients but also on their caregivers and society.AIM To compare the levels of burden,stress and depression among family caregivers of cirrhotic and liver transplant patients.METHODS This cross-sectional observational study evaluated caregivers of CPs and LT recipients at a quaternary Brazilian hospital.Instruments included identification cards,interview scripts,the caregiver burden scale Inventory,Lipp’s Stress Symptom Inventory,and the Beck Depression Inventory-Second Edition.Psychometric analyses involved confirmatory factor analysis and calculation of McDonald’s omega and composite reliability.Factor scores were compared with the Mann-Whitney U test,with effect size as the rank-biserial correlation coefficient(r).Statistical analysis was performed with R software(P<0.05).RESULTS Seventy-seven CP caregivers and 65 LT recipient caregivers were included.Most were female(CP:85.7%vs LT:84.6%)and the patients’spouses(76.6%vs 63.1%).The median age and caregiving duration were 55.4(23.3-76.3)vs 54.6(25.7-82.1)and 3.9(1-20)vs 8(1.5-24)years,respectively(P=0.001).LT caregivers were less likely to be at risk of overload(21.5%vs 49.4%),to be under stress(33.8%vs 36.4%)and to show symptoms of depression(15.4%vs 35.1%).Compared with LT caregivers,CP caregivers had greater median factor scores for burden(general tension,P=0.012;isolation,P=0.014;disappointment,P=0.004),depression(P=0.008),and stress(P=0.047),with small to moderate effect sizes.The disappointment(r=0.240)and depression(r=0.225)dimensions had the largest effect sizes.CONCLUSION Family caregivers of LT recipients are less likely to exhibit symptoms of burden,stress,and depression,suggesting that the benefits of LT extend to the patients’family members.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in n...Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).展开更多
Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS)...Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).展开更多
Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic...Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).展开更多
Premise:The com bined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan,Sou...Premise:The com bined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan,South Korea,Europe,and North America.Since old age is the most significant predictor of dementia,global healthcare systems must rise to the challenge of providing care for those with neurodegenerative disorders.展开更多
Cancer is a major global concern due to its high mortality rate.Tumor immunotherapy has revolutionized cancer treatment.However,low response rates and immune-related complications remain challenges.Extracellular vesic...Cancer is a major global concern due to its high mortality rate.Tumor immunotherapy has revolutionized cancer treatment.However,low response rates and immune-related complications remain challenges.Extracellular vesicles(EVs),including exosomes,have emerged as promising therapeutic tools for various pathological conditions,especially cancer.Evidence indicates that changes in the quantity and composition of EVs can influence the immunosuppressive tumor microenvironment,potentially affecting the effectiveness of immunotherapy.Exploiting EVs for immune sensitization has generated significant clinical interest.This review provides an in-depth understanding of the origin of EVs,their therapeutic applications(such as drug delivery nanoplatforms and cancer immunotherapies,including vaccines),diagnostic potential as tumor biomarkers,ongoing EV-based clinical trials,and the challenges encountered in EV-based cancer immunotherapy.展开更多
Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function.While denervation-induced taste bud degeneration and subsequent re...Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function.While denervation-induced taste bud degeneration and subsequent regeneration were discovered decades ago,the mechanisms underlying these phenomena(e.g.,heterogenous cellular responses to nerve injury and the signaling pathways involved)remain poorly understood.Here,using mouse genetics,nerve injury models,pharmacologic manipulation,and taste bud organoid models,we identify a specific subpopulation of taste cells,predominantly c-Kit-expressing sweet cells,that exhibit superior resistance to nerve injury.We found the c-Kit inhibitor imatinib selectively reduced the number of residual c-Kit-expressing sweet cells at post-operation week 2,subsequently attenuating the re-emergence of other type II cells by post-operation week 4.In taste bud organoids,c-Kit-expressing cells were resistant to R-spondin withdrawal but susceptible to imatinib,while other taste cell types showed the opposite behavior.We also observed a distinct population of residual taste cells that acquired stem-like properties,generating clonal descendent cells among suprabasal keratinocytes independent of c-Kit signaling.Together,our findings reveal that c-Kit signaling confers resilience on c-Kit-expressing sweet cells and supports the broader reconstruction of taste buds during the later regenerative stage following nerve injury.展开更多
Ensuring the reliability of wind energy as a dependable source requires overcoming challenges posed by the inherent volatility and stochastic nature of wind patterns.Long-term forecasting provides strategic advantages...Ensuring the reliability of wind energy as a dependable source requires overcoming challenges posed by the inherent volatility and stochastic nature of wind patterns.Long-term forecasting provides strategic advantages in managing energy generation projects,enabling the development of effective portfolio management strategies.The primary objective of this study was the development of forecasting methods to support strategic decision-making within the scope of wind energy operations,specifically targeting the PindaíWind Complex and its commercial dispatch.The study integrated Big Data analytics,data engineering,and computational techniques through the application of machine learning algorithms:including eXtreme Gradient Boosting,Multilayer Perceptron,Support Vector Regression,Ridge Regression,and Random Forests,aiming to generate forward-looking projections of the complex’s energy production for the year 2023.To this end,five supervised machine learning techniques were modeled and implemented.These techniques were grounded in their respective mathematical and structural formulations,and the empirical foundation for modeling was provided by historical power generation data from the PindaíWind Complex,combined with high-resolution realized and forecasted meteorological data retrieved via the Open-Meteo API.The models are trained using historical monthly generation data from the PindaíWind Complex,which has an installed capacity of 79.9 MW and is located in the northeastern region of Brazil,along with meteorological data from reanalysis models,such as air temperature,relative humidity,precipitation,surface pressure,wind speed at 10 m,wind speed at 100 m,and wind gusts.These methodologies are applied to forecast monthly wind generation for the year 2023,and the outputs are systematically compared using evaluation metrics to determine the most suitable modeling approach.The results highlight the superiority of the Multilayer Perceptron,Support Vector Regression,and eXtreme Gradient Boosting models,which achieved Kling-Gupta Efficiency(KGE)of 0.89,0.89,and 0.90,mean absolute scaled error(MASE)of 0.29,0.31,and 0.18,root mean square errors(RMSE)of 0.56,0.59,and 0.35,and mean absolute errors(MAE)of 0.48,0.52,and 0.29,respectively.展开更多
Objective Atherosclerosis involves not only the narrowing of blood vessels and plaque accumulation but also changes in plaque composition and stability,all of which are critical for disease progression.Conventional im...Objective Atherosclerosis involves not only the narrowing of blood vessels and plaque accumulation but also changes in plaque composition and stability,all of which are critical for disease progression.Conventional imaging techniques such as magnetic resonance angiography(MRA)and digital subtraction angiography(DSA)primarily assess luminal narrowing and plaque size,but have limited capability in identifying plaque instability and inflammation within the vascular muscle wall.This study aimed to develop and evaluate a novel imaging approach using ligand-modified nanomagnetic contrast(lmNMC)nanoprobes in combination with molecular magnetic resonance imaging(mMRI)to visualize and quantify vascular inflammation and plaque characteristics in a rabbit model of atherosclerosis.Methods A rabbit model of atherosclerosis was established and underwent mMRI before and after administration of lmNMC nanoprobes.Radiomic features were extracted from segmented images using discrete wavelet transform(DWT)to assess spatial frequency changes and gray-level co-occurrence matrix(GLCM)analysis to evaluate textural properties.Further radiomic analysis was performed using neural network-based regression and clustering,including the application of self-organizing maps(SOMs)to validate the consistency of radiomic pattern between training and testing data.Results Radiomic analysis revealed significant changes in spatial frequency between pre-and post-contrast images in both the horizontal and vertical directions.GLCM analysis showed an increase in contrast from 0.08463 to 0.1021 and a slight decrease in homogeneity from 0.9593 to 0.9540.Energy values declined from 0.2256 to 0.2019,while correlation increased marginally from 0.9659 to 0.9708.Neural network regression demonstrated strong convergence between target and output coordinates.Additionally,SOM clustering revealed consistent weight locations and neighbor distances across datasets,supporting the reliability of the radiomic validation.Conclusion The integration of lmNMC nanoprobes with mMRI enables detailed visualization of atherosclerotic plaques and surrounding vascular inflammation in a preclinical model.This method shows promise for enhancing the characterization of unstable plaques and may facilitate early detection of high-risk atherosclerotic lesions,potentially improving diagnostic and therapeutic strategies.展开更多
Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,represents the two predominant clinical entities within this spectrum of gastrointestinal disorders.Current evidence indicates that th...Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,represents the two predominant clinical entities within this spectrum of gastrointestinal disorders.Current evidence indicates that the etiology of IBD is multifactorial,involving a complex interplay between host genetic susceptibility and environmental determinants.In recent years,non-pharmacological strategies such as physical exercise and vagus nerve stimulation have gained increasing attention as adjunctive therapeutic approaches.Vagus nerve stimulation has emerged as a promising therapeutic modality,particularly in conditions characterized by autonomic dysfunction and diminished vagal tone.Conversely,vagotomy,by disrupting vagal control,abolishes parasympathetic reflexes and may potentiate inflammatory responses and exacerbate IBD symptomatology under stress conditions.Physical exercise has likewise been investigated as a non-pharmacological intervention in Crohn’s disease and ulcerative colitis.Although the precise mechanisms remain to be fully elucidated,accumulating evidence suggests that skeletal muscle contractions promote the secretion of myokines,with recognized anti-inflammatory properties.These myokines act on the intestinal microenvironment,conferring protection against malignant transformation and modulating the composition and function of the gut microbiota.In this review,we critically examine the interplay between physical exercise,vagus nerve stimulation,and vagotomy in the pathophysiology and management of IBD,with particular emphasis on their immunomodulatory and therapeutic potential.展开更多
Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comme...Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comment on the results of a meta-analysis published by Shetty et al that shows an addictive risk for cardi-ovascular events when both pathologies are together.Patients with MASLD and T2DM have the worst prognosis related to liver disease since they have a higher risk for metabolic dysfunction-associated steatohepatitis,disease progression,and hepatocarcinoma.The meta-analysis included 370013 participants and showed that,although with high heterogeneity,there is a higher prevalence of cardio-vascular events in patients with T2DM when MASLD is diagnosed compared to those without MASLD.Hence,MASLD and T2DM may have a new interplay regarding cardiovascular outcomes in addition to the already known liver-related outcomes.展开更多
基金supported by NIH grants,Nos.R01NS125074,R01AG083164,R01NS107365,and R21NS127177(to YL),1F31NS129204-01A1(to KW)and Albert Ryan Fellowship(to KW).
文摘Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
基金supported by the Basic Science Research Program(2023R1A2C3004336,RS-202300243807)&Regional Leading Research Center(RS-202400405278)through the National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)。
文摘Wearable sensors integrated with deep learning techniques have the potential to revolutionize seamless human-machine interfaces for real-time health monitoring,clinical diagnosis,and robotic applications.Nevertheless,it remains a critical challenge to simultaneously achieve desirable mechanical and electrical performance along with biocompatibility,adhesion,self-healing,and environmental robustness with excellent sensing metrics.Herein,we report a multifunctional,anti-freezing,selfadhesive,and self-healable organogel pressure sensor composed of cobalt nanoparticle encapsulated nitrogen-doped carbon nanotubes(CoN CNT)embedded in a polyvinyl alcohol-gelatin(PVA/GLE)matrix.Fabricated using a binary solvent system of water and ethylene glycol(EG),the CoN CNT/PVA/GLE organogel exhibits excellent flexibility,biocompatibility,and temperature tolerance with remarkable environmental stability.Electrochemical impedance spectroscopy confirms near-stable performance across a broad humidity range(40%-95%RH).Freeze-tolerant conductivity under sub-zero conditions(-20℃)is attributed to the synergistic role of CoN CNT and EG,preserving mobility and network integrity.The Co N CNT/PVA/GLE organogel sensor exhibits high sensitivity of 5.75 k Pa^(-1)in the detection range from 0 to 20 k Pa,ideal for subtle biomechanical motion detection.A smart human-machine interface for English letter recognition using deep learning achieved 98%accuracy.The organogel sensor utility was extended to detect human gestures like finger bending,wrist motion,and throat vibration during speech.
文摘The regenerative capacity of peripheral nerve is significantly different from injury responses in the central nervous system.Regeneration of injured axons,re-myelination and functional recovery are readily observed after injury to peripheral nerve.
文摘Buildings represent a significant share of the world’s energy consumption,and the sector has drawn the attention of governments,which have adopted policies to reduce energy expenditure.The Certifications of Energy Efficiency in Buildings stand out as one possible solution to achieve this goal,employed in several countries worldwide.The European Union presents advanced energy assessment programs for buildings,being a reference and model for several other regulations in the world.The Energy Certification System for Buildings(SCE)of Portugal is considered a success case,reflected in the significant number of energy certificates issued.The Brazilian Labeling Program for Building(PBE Edifica),first launched in 2009,does not find a broad application today in the Brazilian scenario.This work shows a synthesis of the European Energy Performance of Buildings Directive(EPBD)and the Brazilian and Portuguese regulations’history.A qualitative comparison is made between the SCE and the PBE Edifica to verify a European and a developing country’s regulations with a certain degree of cultural and climatic similarities.Through this comparison,proposals are made for improvements to Brazilian certification,seeking to improve its energy planning and energy policy concerning its building stock.The suggestions for improvement presented may also be appropriate for other developing countries that have started and have not yet successfully implemented their energy certification programs in buildings.
文摘Food restriction is a strategy to improve the productive efficiency of some aquatic organisms.It is expected with the implementation of food restriction programs to first reduce the feed consumption by the cultivated species and consequently reduce the waste load in the water.In addition,there is a lower employment of labor during periods of food restriction.However,the efficiency of the feed restriction and the compensatory gain of weight by the organisms cultivated will depend on the adaptation and the characteristics of the species in question.Several methodologies have tested forms of food restriction applied to fish farming.Some of them are addressed in this review,as well as results and comparisons made with several authors on the subject in question.The purpose of this paper was to describe the main reasons for using food restriction,its implications on fish organism and to compare results from previous studies.
文摘Introduction: Child obesity has important consequences on the child’s health and is related to the risk of developing chronic diseases. That brings up the need for research assessing the impact of obesity-and overweight-reduction programs with close attention to methodology aspects and precise indicators of the impact of such programs. Goal: Assessing the impact of a physical activity program on the plasma concentrations of adiponectin, leptin, and ghrelin in overweight and obese schoolchildren. Methods: Randomized controlled trial, double-blind, with 6-to 9-year-old overweight and obese school-children. A sample of 79 schoolchildren randomly distributed into control and intervention groups was subjected to a physical activity program. The levels of adiponectin, leptin, ghrelin, body mass index, body fat percentage, anthropometry, lipid profile and glycemia were evaluated. The program’s impact was assessed through multivariate linear regression models. Result: When comparing the groups, a significant difference was found for adiponectin, which shows an increase in the proportion of subjects with higher adiponectin concentrations for the intervention group and a reduction in body mass index and body fat percentage. Conclusion: The impact of the intervention program was positive in increasing adiponectin levels associated with a reduction in body mass index and body fat percentage.
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
文摘BACKGROUND Family caregivers of cirrhosis patients(CPs)often experience burden,stress,and depression.Investigating whether these conditions improve following the patient undergoing liver transplantation(LT)is crucial,as it would elucidate the compre-hensive benefits of the procedure and demonstrate the positive impacts not only on the patients but also on their caregivers and society.AIM To compare the levels of burden,stress and depression among family caregivers of cirrhotic and liver transplant patients.METHODS This cross-sectional observational study evaluated caregivers of CPs and LT recipients at a quaternary Brazilian hospital.Instruments included identification cards,interview scripts,the caregiver burden scale Inventory,Lipp’s Stress Symptom Inventory,and the Beck Depression Inventory-Second Edition.Psychometric analyses involved confirmatory factor analysis and calculation of McDonald’s omega and composite reliability.Factor scores were compared with the Mann-Whitney U test,with effect size as the rank-biserial correlation coefficient(r).Statistical analysis was performed with R software(P<0.05).RESULTS Seventy-seven CP caregivers and 65 LT recipient caregivers were included.Most were female(CP:85.7%vs LT:84.6%)and the patients’spouses(76.6%vs 63.1%).The median age and caregiving duration were 55.4(23.3-76.3)vs 54.6(25.7-82.1)and 3.9(1-20)vs 8(1.5-24)years,respectively(P=0.001).LT caregivers were less likely to be at risk of overload(21.5%vs 49.4%),to be under stress(33.8%vs 36.4%)and to show symptoms of depression(15.4%vs 35.1%).Compared with LT caregivers,CP caregivers had greater median factor scores for burden(general tension,P=0.012;isolation,P=0.014;disappointment,P=0.004),depression(P=0.008),and stress(P=0.047),with small to moderate effect sizes.The disappointment(r=0.240)and depression(r=0.225)dimensions had the largest effect sizes.CONCLUSION Family caregivers of LT recipients are less likely to exhibit symptoms of burden,stress,and depression,suggesting that the benefits of LT extend to the patients’family members.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
基金supported by grants from Mission Connect, a project of the TIRR Foundation, the Glaucoma Research FoundationNIH grants R01NS112691 and R01NS076708 (to TAW)
文摘Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).
基金supported by NIH grants(R01NS125074,R01AG083164,and R21NS127177)(to YL).
文摘Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).
文摘Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).
基金funded by the Natural Sciences and Engineering Research Council of Canada(RGPIN:2016-05964&2023-04283 to JHK)the University of Manitoba Tri-Agency Bridge Funding(#57289 to JHK)the Ricard Foundation’s Baxter Bursary(to JP)。
文摘Premise:The com bined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan,South Korea,Europe,and North America.Since old age is the most significant predictor of dementia,global healthcare systems must rise to the challenge of providing care for those with neurodegenerative disorders.
文摘Cancer is a major global concern due to its high mortality rate.Tumor immunotherapy has revolutionized cancer treatment.However,low response rates and immune-related complications remain challenges.Extracellular vesicles(EVs),including exosomes,have emerged as promising therapeutic tools for various pathological conditions,especially cancer.Evidence indicates that changes in the quantity and composition of EVs can influence the immunosuppressive tumor microenvironment,potentially affecting the effectiveness of immunotherapy.Exploiting EVs for immune sensitization has generated significant clinical interest.This review provides an in-depth understanding of the origin of EVs,their therapeutic applications(such as drug delivery nanoplatforms and cancer immunotherapies,including vaccines),diagnostic potential as tumor biomarkers,ongoing EV-based clinical trials,and the challenges encountered in EV-based cancer immunotherapy.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean Government(Ministry of Science and ICT,RS-2023-00208193 to Y.T.J.)by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare(RS-2024-00403511 to D.-H.K.)by a Korea University grant(K2117151 to Y.T.J.)。
文摘Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function.While denervation-induced taste bud degeneration and subsequent regeneration were discovered decades ago,the mechanisms underlying these phenomena(e.g.,heterogenous cellular responses to nerve injury and the signaling pathways involved)remain poorly understood.Here,using mouse genetics,nerve injury models,pharmacologic manipulation,and taste bud organoid models,we identify a specific subpopulation of taste cells,predominantly c-Kit-expressing sweet cells,that exhibit superior resistance to nerve injury.We found the c-Kit inhibitor imatinib selectively reduced the number of residual c-Kit-expressing sweet cells at post-operation week 2,subsequently attenuating the re-emergence of other type II cells by post-operation week 4.In taste bud organoids,c-Kit-expressing cells were resistant to R-spondin withdrawal but susceptible to imatinib,while other taste cell types showed the opposite behavior.We also observed a distinct population of residual taste cells that acquired stem-like properties,generating clonal descendent cells among suprabasal keratinocytes independent of c-Kit signaling.Together,our findings reveal that c-Kit signaling confers resilience on c-Kit-expressing sweet cells and supports the broader reconstruction of taste buds during the later regenerative stage following nerve injury.
文摘Ensuring the reliability of wind energy as a dependable source requires overcoming challenges posed by the inherent volatility and stochastic nature of wind patterns.Long-term forecasting provides strategic advantages in managing energy generation projects,enabling the development of effective portfolio management strategies.The primary objective of this study was the development of forecasting methods to support strategic decision-making within the scope of wind energy operations,specifically targeting the PindaíWind Complex and its commercial dispatch.The study integrated Big Data analytics,data engineering,and computational techniques through the application of machine learning algorithms:including eXtreme Gradient Boosting,Multilayer Perceptron,Support Vector Regression,Ridge Regression,and Random Forests,aiming to generate forward-looking projections of the complex’s energy production for the year 2023.To this end,five supervised machine learning techniques were modeled and implemented.These techniques were grounded in their respective mathematical and structural formulations,and the empirical foundation for modeling was provided by historical power generation data from the PindaíWind Complex,combined with high-resolution realized and forecasted meteorological data retrieved via the Open-Meteo API.The models are trained using historical monthly generation data from the PindaíWind Complex,which has an installed capacity of 79.9 MW and is located in the northeastern region of Brazil,along with meteorological data from reanalysis models,such as air temperature,relative humidity,precipitation,surface pressure,wind speed at 10 m,wind speed at 100 m,and wind gusts.These methodologies are applied to forecast monthly wind generation for the year 2023,and the outputs are systematically compared using evaluation metrics to determine the most suitable modeling approach.The results highlight the superiority of the Multilayer Perceptron,Support Vector Regression,and eXtreme Gradient Boosting models,which achieved Kling-Gupta Efficiency(KGE)of 0.89,0.89,and 0.90,mean absolute scaled error(MASE)of 0.29,0.31,and 0.18,root mean square errors(RMSE)of 0.56,0.59,and 0.35,and mean absolute errors(MAE)of 0.48,0.52,and 0.29,respectively.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(Grant number:RS-2023-00248763).
文摘Objective Atherosclerosis involves not only the narrowing of blood vessels and plaque accumulation but also changes in plaque composition and stability,all of which are critical for disease progression.Conventional imaging techniques such as magnetic resonance angiography(MRA)and digital subtraction angiography(DSA)primarily assess luminal narrowing and plaque size,but have limited capability in identifying plaque instability and inflammation within the vascular muscle wall.This study aimed to develop and evaluate a novel imaging approach using ligand-modified nanomagnetic contrast(lmNMC)nanoprobes in combination with molecular magnetic resonance imaging(mMRI)to visualize and quantify vascular inflammation and plaque characteristics in a rabbit model of atherosclerosis.Methods A rabbit model of atherosclerosis was established and underwent mMRI before and after administration of lmNMC nanoprobes.Radiomic features were extracted from segmented images using discrete wavelet transform(DWT)to assess spatial frequency changes and gray-level co-occurrence matrix(GLCM)analysis to evaluate textural properties.Further radiomic analysis was performed using neural network-based regression and clustering,including the application of self-organizing maps(SOMs)to validate the consistency of radiomic pattern between training and testing data.Results Radiomic analysis revealed significant changes in spatial frequency between pre-and post-contrast images in both the horizontal and vertical directions.GLCM analysis showed an increase in contrast from 0.08463 to 0.1021 and a slight decrease in homogeneity from 0.9593 to 0.9540.Energy values declined from 0.2256 to 0.2019,while correlation increased marginally from 0.9659 to 0.9708.Neural network regression demonstrated strong convergence between target and output coordinates.Additionally,SOM clustering revealed consistent weight locations and neighbor distances across datasets,supporting the reliability of the radiomic validation.Conclusion The integration of lmNMC nanoprobes with mMRI enables detailed visualization of atherosclerotic plaques and surrounding vascular inflammation in a preclinical model.This method shows promise for enhancing the characterization of unstable plaques and may facilitate early detection of high-risk atherosclerotic lesions,potentially improving diagnostic and therapeutic strategies.
文摘Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,represents the two predominant clinical entities within this spectrum of gastrointestinal disorders.Current evidence indicates that the etiology of IBD is multifactorial,involving a complex interplay between host genetic susceptibility and environmental determinants.In recent years,non-pharmacological strategies such as physical exercise and vagus nerve stimulation have gained increasing attention as adjunctive therapeutic approaches.Vagus nerve stimulation has emerged as a promising therapeutic modality,particularly in conditions characterized by autonomic dysfunction and diminished vagal tone.Conversely,vagotomy,by disrupting vagal control,abolishes parasympathetic reflexes and may potentiate inflammatory responses and exacerbate IBD symptomatology under stress conditions.Physical exercise has likewise been investigated as a non-pharmacological intervention in Crohn’s disease and ulcerative colitis.Although the precise mechanisms remain to be fully elucidated,accumulating evidence suggests that skeletal muscle contractions promote the secretion of myokines,with recognized anti-inflammatory properties.These myokines act on the intestinal microenvironment,conferring protection against malignant transformation and modulating the composition and function of the gut microbiota.In this review,we critically examine the interplay between physical exercise,vagus nerve stimulation,and vagotomy in the pathophysiology and management of IBD,with particular emphasis on their immunomodulatory and therapeutic potential.
文摘Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comment on the results of a meta-analysis published by Shetty et al that shows an addictive risk for cardi-ovascular events when both pathologies are together.Patients with MASLD and T2DM have the worst prognosis related to liver disease since they have a higher risk for metabolic dysfunction-associated steatohepatitis,disease progression,and hepatocarcinoma.The meta-analysis included 370013 participants and showed that,although with high heterogeneity,there is a higher prevalence of cardio-vascular events in patients with T2DM when MASLD is diagnosed compared to those without MASLD.Hence,MASLD and T2DM may have a new interplay regarding cardiovascular outcomes in addition to the already known liver-related outcomes.
