Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at...Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.展开更多
Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson...Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.展开更多
This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a ...This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a general part covering the grand lines and more in-depth views of more recent tannin,lignin,carbohydrate and soy bioadhesives,somemix of the other bio raw materials with soy protein and soy flour and some other differently sourced bioadhesives for wood,this review presents a more in-depth part on starch-based wood adhesives and a more indepth part covering plant protein-based adhesives.It must be kept in mind that the review is focused on completely or almost completely biosourced adhesives,the fashionable adhesives derived from mixes of biosourced materials with synthetic resins having been intentionally excluded.This choice was made as the latter constitute only an intermediate interval,possibly temporary if even for a somewhat long times,towards a final full bioeconomy of scale in this field.This review also focuses on more recent results,mainly obtained in the last 10–20 years,thus on adhesive formulations really innovative and sometimes even non-traditional.In all these fields there is still a lot of possibility of innovation for relevant formulation as this field is still in rapid growth.展开更多
BACKGROUND Cardiac resynchronization therapy(CRT)has been a major therapeutic advancement for patients with heart failure and electrical dyssynchrony.While CRT improves symptoms,reduces hospitalizations,and enhances s...BACKGROUND Cardiac resynchronization therapy(CRT)has been a major therapeutic advancement for patients with heart failure and electrical dyssynchrony.While CRT improves symptoms,reduces hospitalizations,and enhances survival,the role of implantable cardioverter-defibrillators(ICDs)alongside CRT in patients with non-ischemic cardiomyopathy(NICM)remains controversial.To evaluate and compare the outcomes of CRT with ICD(CRT-D)versus CRT with pacemaker-only(CRT-P)in individuals diagnosed with NICM,with a specific focus on the elderly.METHODS A comprehensive search of PubMed,Embase,and the Cochrane Central Register of Controlled Trials was conducted in January 2024.Studies comparing CRT-D and CRT-P in patients with NICM were included,with subgroup analyses focusing on patients aged 75 years and older.RESULTS Twelve studies,including two randomized clinical trials,with a total of 62,145 patients and 16,754 pooled death events(9,171 in CRT-D and 7,583 in CRT-P),were analyzed.CRT-D was associated with a significantly lower risk of all-cause mortality compared to CRT-P(pooled OR=0.72;95%CI:0.61-0.85;P<0.01),with significant heterogeneity(I2=83%).RCT subgroup analysis,was not statistically significant(pooled OR=0.82;95%CI:0.64-1.06;P=0.41;I2=0%).In patients older than 75 years,no significant difference in mortality risk was observed(pooled OR 0.96;95%CI:0.81-1.15;I2=39%).CONCLUSION Our meta-analysis suggests that the addition of ICD therapy to CRT in patients with NICM significantly reduces all-cause mortality.However,this benefit does not extend to cardiovascular mortality,likely due to the primary role of ICDs in preventing sudden cardiac death rather than other causes such as progressive heart failure.The survival advantage of CRT-D is most pronounced in younger patients,with those over 75 years of age deriving less benefit.This highlights the importance of careful patient selection,considering age and comorbidities,when deciding on ICD implantation in NICM patients.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
The integration of digital tools and effective knowledge management practices is critical for enhancing administrative efficiency and institutional continuity in higher education. This study investigates the relations...The integration of digital tools and effective knowledge management practices is critical for enhancing administrative efficiency and institutional continuity in higher education. This study investigates the relationships between knowledge modeling, institutional memory, leadership styles, technology, and administrative efficiency at the University of Cape Coast (UCC). The study sought to identify the challenges and opportunities in integrating digital tools into administrative processes and to provide actionable recommendations for improvement. A mixed-methods research design was employed, combining quantitative analysis using Partial Least Squares Structural Equation Modeling (PLS-SEM) with qualitative thematic analysis of interviews. The findings revealed key challenges, including resistance to change, fragmented knowledge repositories, and inadequate funding, alongside opportunities such as centralized knowledge systems, cost-effective open-source tools, and capacity-building initiatives. The study highlights the importance of strategic leadership, robust policies, and investments in digital infrastructure to enhance administrative practices. Policy implications include the need for clear digital transformation guidelines and leadership training to foster innovation and collaboration. Recommendations include investing in scalable digital tools, implementing comprehensive capacity-building programs, and promoting stakeholder engagement to drive successful digital integration. These insights provide a roadmap for UCC and similar institutions seeking to optimize administrative efficiency through digital transformation.展开更多
Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief int...Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief introduction to the current state-of-the-art for neuroectoderm brain organoid development,emphasizing their biggest advantages in comparison with classical two-dimensional cell cultures and animal models.However,despite their usefulness for developmental studies,a major limitation for most brain organoid models is the absence of contributing cell types from endodermal and mesodermal origin.As such,current research is highly investing towards the incorporation of a functional vasculature and the microglial immune component.In this review,we will specifically focus on the development of immune-competent brain organoids.By summarizing the different approaches applied to incorporate microglia,it is highlighted that immune-competent brain organoids are not only important for studying neuronal network formation,but also offer a clear future as a new tool to study inflammatory responses in vitro in 3D in a brainlike environment.Therefore,our main focus here is to provide a comprehensive overview of assays to measure microglial phenotype and function within brain organoids,with an outlook on how these findings could better understand neuronal network development or restoration,as well as the influence of physical stress on microglia-containing brain organoids.Finally,we would like to stress that even though the development of immune-competent brain organoids has largely evolved over the past decade,their full potential as a pre-clinical tool to study novel therapeutic approaches to halt or reduce inflammation-mediated neurodegeneration still needs to be explored and validated.展开更多
Object detection in occluded environments remains a core challenge in computer vision(CV),especially in domains such as autonomous driving and robotics.While Convolutional Neural Network(CNN)-based twodimensional(2D)a...Object detection in occluded environments remains a core challenge in computer vision(CV),especially in domains such as autonomous driving and robotics.While Convolutional Neural Network(CNN)-based twodimensional(2D)and three-dimensional(3D)object detection methods havemade significant progress,they often fall short under severe occlusion due to depth ambiguities in 2D imagery and the high cost and deployment limitations of 3D sensors such as Light Detection and Ranging(LiDAR).This paper presents a comparative review of recent 2D and 3D detection models,focusing on their occlusion-handling capabilities and the impact of sensor modalities such as stereo vision,Time-of-Flight(ToF)cameras,and LiDAR.In this context,we introduce FuDensityNet,our multimodal occlusion-aware detection framework that combines Red-Green-Blue(RGB)images and LiDAR data to enhance detection performance.As a forward-looking direction,we propose a monocular depth-estimation extension to FuDensityNet,aimed at replacing expensive 3D sensors with a more scalable CNN-based pipeline.Although this enhancement is not experimentally evaluated in this manuscript,we describe its conceptual design and potential for future implementation.展开更多
BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitiv...BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.展开更多
BACKGROUND Major adverse cardiovascular(CV)events(MACEs)are the primary cause of morbidity and mortality in kidney transplantation(KT)recipients.The risk for MACEs is impacted by an array of traditional and transplant...BACKGROUND Major adverse cardiovascular(CV)events(MACEs)are the primary cause of morbidity and mortality in kidney transplantation(KT)recipients.The risk for MACEs is impacted by an array of traditional and transplant-related non-traditional CV risk factors.AIM To investigate the association between potential CV risk factors related to KT and MACEs,and their potential modification by hyperuricemia(HU).METHODS The relationship between CV risk factors related to KT and MACEs was examined in a cohort of 545 patients who underwent transplantation between 2008 and 2019.The mean age of patients at KT was 55.0 years±14.2 years(range 15.0–89.0 years).Univariate and multivariate logistic regression models were constructed to identify risk factors influencing MACEs.To explore the potential effect modification by uric acid(UA),patients were categorized into groups based on UA levels:(1)Low(<356μmol/L);(2)Normal(356–416μmol/L);(3)High(416–475μmol/L);and(4)Very high(>475μmol/L).RESULTS MACEs occurred in 145 of 545(26.6%)KT recipients.The most prevalent comorbidities were hypertension(87%),dyslipidemia(78%),secondary hyperparathyroidism(68%),HU(63%)and anemia(33%).In the multivariate logistic regression model,the most significant factors associated with MACEs were previous CV events[odds ratio(OR)=70.6,95%CI:24.9–200.1],left ventricular hypertrophy(LVH)(OR=12.6,95%CI:2.7–58.3),HU treatment(OR=4.3,95%CI:2.4–7.6),and anemia(OR=5.3,95%CI:2.9–9.8).Effect modification by the presence of HU revealed that independent factors associated with MACEs were age(OR=1.03,95%CI:1.0–1.1),previous CV events(OR=41.7,95%CI:13.6–127.6),LVH(OR=15.3,95%CI:2.0–116.6),HU treatment(OR=2.5,95%CI:1.3–4.6)and anemia(OR=5.4,95%CI:2.8–10.5).Effect modification by UA levels dichotomized at 475μmol/L(very high level of UA)revealed that HU treatment was not associated with MACEs in groups with or without very high UA levels.CONCLUSION A very high level of UA was observed to act as an effect-modifying factor for MACEs,especially when combined with other risk factors such as age,previous CV events,LVH,and anemia.展开更多
The present study investigates the wavespace of Highly Contrasted Structures(HCS)and Highly Dissipative Structures(HDS)by wave-based models.The Asymptotic Homogenization Method(AHM),exploits the asymptotic Zig-Zag mod...The present study investigates the wavespace of Highly Contrasted Structures(HCS)and Highly Dissipative Structures(HDS)by wave-based models.The Asymptotic Homogenization Method(AHM),exploits the asymptotic Zig-Zag model and homogenization technique to compute the bending wavenumbers via a 6th-order equation.The General Laminate Model(GLM)employs Mindlin’s displacement field to establish displacement-constraint relationships and resolves a quadratic Eigenvalue Problem(EVP)of the dispersion relation.The Wave Finite Element(WFE)scheme formulates the Nonlinear Eigenvalue Problem(NEP)for waves in varying directions and tracks complex wavenumbers using Weighted Wave Assurance Criteria(WWAC).Two approaches are introduced to estimate the Damping Loss Factor(DLF)of HDS,with the average DLF calculated by the modal density at various angles where non-homogeneity is present.Evaluation of robustness and accuracy is made by comparing the wavenumbers and DLF obtained from AHM and GLM with WFE.WFE is finally extended to a sandwich metastructure with a non-homogeneous core,and the Power Input Method(PIM)with Finite Element Method(FEM)data is employed to assess the average DLF,demonstrating an enhanced DLF compared to layered configurations with the same material portion,indicating increased energy dissipation due to the bending-shear coupling effects.展开更多
Alzheimer’s dementia(AD)and type 2 diabetes(T2D)are interrelated global public health problems,and the current epidemics of both AD and T2D are insulin resistance diseases.Thus,AD and T2D may share common risk factor...Alzheimer’s dementia(AD)and type 2 diabetes(T2D)are interrelated global public health problems,and the current epidemics of both AD and T2D are insulin resistance diseases.Thus,AD and T2D may share common risk factors such as an unhealthy diet,lifestyle,and obesity.Meat products is an important part of the diet of consumers worldwide.This systematic review and meta-analysis aims to assess and estimate the effect of meat products consumption on AD and T2D in humans.Web of Science,MEDLINE,PubMed,Cochrane Library,and Embase were searched from January 2012 to April 2024.29 articles reported 32 cohort studies with 1785769 subjects,with 3546 AD cases and 91092 T2D cases that met the inclusion criteria and were included in our analysis.Consumption of various meat products increased the risk of T2D(hazard ratios(HR)=1.19,95%confidence intervals(CI):1.13−1.26,P=0.000;I2=88.5%),consumption of smoked,grilled/roasted and fried meat products was more likely to induce T2D(HR=1.24,95%CI:1.18−1.30,P=0.000;I2=76.1%),but was borderline significant for the risk of AD(HR=1.11,95%CI:0.98−1.25,P=0.094;I2=58.8%),with consumption of mainly livestock and poultry products increasing the risk(HR=1.21,95%CI:1.03−1.42,P=0.017;I2=66.8%).The association between meat products consumption and AD risk was influenced by meat type and sample size,while the risk of T2D was influenced by meat type,follow-up and sex.A daily intake of 27,123 and 170 g of livestock products increased the risk of T2D by 10%,51%and 70%respectively,whereas the risk of T2D was reduced when the intake of various meat products was less than 23 g/day.展开更多
Schistosomiasis is a neglected tropical disease (NTD) widespread in sub-Saharan Africa and mostly affects school going children. Côte d’Ivoire is one of the most vulnerable countries to schistosomiasis, and its ...Schistosomiasis is a neglected tropical disease (NTD) widespread in sub-Saharan Africa and mostly affects school going children. Côte d’Ivoire is one of the most vulnerable countries to schistosomiasis, and its prevalence varies by region. This cross-sectional survey was conducted in schools in the Upper Sassandra region to determine the knowledge, attitude, and practices of school children regarding schistosomiasis. In total, 354 students participated in the survey. Our results showed that, compared to the girls, the boys had a higher level of knowledge about schistosomiasis OR = 1.605 and p = 0.05. Regarding the signs, symptoms, and modes of transmission and prevention of schistosomiasis, the participants reported a low level of knowledge p > 0.05 and OR 1. In conclusion, it is important to target health messages in schools to reach the most vulnerable students effectively. This initiative aims to provide children with basic knowledge and skills in the transmission of schistosomiasis.展开更多
Doping plays a pivotal role in enhancing the performance of organic semiconductors(OSCs)for advanced optoelectronic and thermoelectric applications.In this study,we systematically investigated the doping performance a...Doping plays a pivotal role in enhancing the performance of organic semiconductors(OSCs)for advanced optoelectronic and thermoelectric applications.In this study,we systematically investigated the doping performance and applicability of the ionic dopant 4-isopropyl-4′-methyldiphenyliodonium tetrakis(penta-fluorophenyl-borate)(DPI-TPFB)as a p-dopant for OSCs.Using the p-type OSC PBBT-2T as a model system,we demonstrated that DPI-TPFB shows significant doping effect,as confirmed by ESR spectra,ultraviolet-visible-near-infrared(UV-vis-NIR)absorption,and work function analysis,and enhances the electronic conductivity of PBBT-2T films by over four orders of magnitude.Furthermore,DPI-TPFB exhibited broad doping applicability,effectively doping various p-type OSCs and even imparting p-type characteristics to the n-type OSC N2200,transforming its intrinsic n-type behavior into p-type.The application of DPI-TPFB-doped PBBT-2T films in organic thermoelectric devices(OTEs)was also explored,achieving a power factor of approximately 10μW·m^(-1)·K^(-2).These findings highlight the potential of DPI-TPFB as a versatile and efficient dopant for integration into organic optoelectronic and thermoelectric devices.展开更多
The bidirectional convergence of artificial intelligence and nanophotonics drives photonic technologies toward unprecedented levels of intelligence and efficiency,fundamentally reshaping their design paradigms and app...The bidirectional convergence of artificial intelligence and nanophotonics drives photonic technologies toward unprecedented levels of intelligence and efficiency,fundamentally reshaping their design paradigms and application boundaries.With its powerful data-driven and nonlinear optimization capabilities,artificial intelligence has become a powerful tool for optical design,enabling the inverse design of nanophotonics devices while accelerating the forward computation of electromagnetic responses.Conversely,nanophotonics provides a wave-based computational platform,giving rise to novel optical neural networks that achieve high-speed parallel computing and efficient information processing.This paper reviews the latest progress in the bidirectional field of artificial intelligence and nanophotonics,analyzes the basic principles of various applications from a universal perspective,comprehensively evaluates the advantages and limitations of different research methods,and makes a forwardlooking outlook on the bidirectional integration of artificial intelligence and nanophotonics,focusing on analyzing future development trends,potential applications,and challenges.The deep integration of artificial intelligence and nanophotonics is ushering in a new era for photonic technologies,offering unparalleled opportunities for fundamental research and industrial applications.展开更多
During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their el...During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.展开更多
Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
Unlike primary metabolites,secondary metabolites serve critical ecological functions,including plant protection,stress tolerance,and symbiosis.This review focuses on extracting,separating,and identifying the major cla...Unlike primary metabolites,secondary metabolites serve critical ecological functions,including plant protection,stress tolerance,and symbiosis.This review focuses on extracting,separating,and identifying the major classes of secondary metabolites,including alkaloids,terpenoids,phenolics,glycosides,saponins,and coumarins.It describes optimized methods regarding plant selection,extraction by solvents,and purification of the metabolites,highlighting the latest advancements in chromatographic and spectroscopic techniques.The review also describes some of the most important problems,such as the instability of the compounds or diversity of the structures,and discusses emerging technologies that solve these issues.Moreover,it examines the secondary roles of these metabolites in medicine,such as anticancer and antimicrobial drugs,sustainable agriculture biopesticides,and environmental ecology-also known as allelopathy and bioindicators.It combines traditional ethnobotanical approaches with contem-porary science,demonstrating the vital need to protect biodiversity in key ecosystems such as tropical rainforests,mountain regions,coral reefs,and arid zones as a foundation for anticipatory bio-discoveries.It organizes the methodological frameworks and outlines the steps needed to enhance the extraction of bioactive compounds from natural sources.展开更多
GaN diodes for high energy(64.8 MeV)proton detection were fabricated and investigated.A comparison of the performance of GaN diodes with different structures is presented,with a focus on sapphire and on GaN substrates...GaN diodes for high energy(64.8 MeV)proton detection were fabricated and investigated.A comparison of the performance of GaN diodes with different structures is presented,with a focus on sapphire and on GaN substrates,Schottky and pin diodes,and different active layer thicknesses.Pin diodes fabricated on a sapphire substrate are the best choice for a GaN proton detector working at 0 V bias.They are sensitive(minimum detectable proton beam<1 pA/cm^(2)),linear as a function of proton current and fast(<1 s).High proton current sensitivity and high spatial resolution of GaN diodes can be exploited in the future for proton imaging of patients in proton therapy.展开更多
This work investigates the potential of low-pressure,medium-speed dual-fuel engines for cleaner maritime transportation.The thermodynamic performance of these engines is explored using three alternative fuels:liquefie...This work investigates the potential of low-pressure,medium-speed dual-fuel engines for cleaner maritime transportation.The thermodynamic performance of these engines is explored using three alternative fuels:liquefied natural gas(LNG),methanol,and ammonia.A parametric analysis examines the effect of adjustments to key engine parameters(compression ratio,boost pressure,and air-fuel ratio)on performance.Results show an initial improvement in performance with an increase in compression ratio,which reaches a peak and then declines.Similarly,increases in boost pressure and air-fuel ratio lead to linear performance gains.However,insufficient cooling reduces the amount of fuel burned,which hinders performance.Exergy analysis reveals significant exergy destruction within the engine,which ranges from 69.96%(methanol)to 78.48%(LNG).Notably,the combustion process is the leading cause of exergy loss.Among the fuels tested,methanol exhibits the lowest combustion-related exergy destruction(56.41%),followed by ammonia(62.12%)and LNG(73.77%).These findings suggest that methanol is a promising near-term alternative to LNG for marine fuel applications.展开更多
基金supported by Postdoc Fellowship from the Foundation for Angelman Syndrome Therapeutics(FT2022-005 to JM,PD2023-001 to XY,and FT2024-001 to YAH)STTR R41 MH118747(to JM)。
文摘Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.
基金supported by the Spanish Ministry of Science and Innovation via a doctoral grant[FPU22/03656].supported by the Spanish Ministry of Science and Innovation(PID2022-137963OB-I00)Generalitat de Catalunya(2021-SGR-00635 AGAUR)+1 种基金CERCA Programme(Generalitat de Catalunya)by ICREA,ICREA-Academia 2020(to SV)。
文摘Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.
文摘This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a general part covering the grand lines and more in-depth views of more recent tannin,lignin,carbohydrate and soy bioadhesives,somemix of the other bio raw materials with soy protein and soy flour and some other differently sourced bioadhesives for wood,this review presents a more in-depth part on starch-based wood adhesives and a more indepth part covering plant protein-based adhesives.It must be kept in mind that the review is focused on completely or almost completely biosourced adhesives,the fashionable adhesives derived from mixes of biosourced materials with synthetic resins having been intentionally excluded.This choice was made as the latter constitute only an intermediate interval,possibly temporary if even for a somewhat long times,towards a final full bioeconomy of scale in this field.This review also focuses on more recent results,mainly obtained in the last 10–20 years,thus on adhesive formulations really innovative and sometimes even non-traditional.In all these fields there is still a lot of possibility of innovation for relevant formulation as this field is still in rapid growth.
文摘BACKGROUND Cardiac resynchronization therapy(CRT)has been a major therapeutic advancement for patients with heart failure and electrical dyssynchrony.While CRT improves symptoms,reduces hospitalizations,and enhances survival,the role of implantable cardioverter-defibrillators(ICDs)alongside CRT in patients with non-ischemic cardiomyopathy(NICM)remains controversial.To evaluate and compare the outcomes of CRT with ICD(CRT-D)versus CRT with pacemaker-only(CRT-P)in individuals diagnosed with NICM,with a specific focus on the elderly.METHODS A comprehensive search of PubMed,Embase,and the Cochrane Central Register of Controlled Trials was conducted in January 2024.Studies comparing CRT-D and CRT-P in patients with NICM were included,with subgroup analyses focusing on patients aged 75 years and older.RESULTS Twelve studies,including two randomized clinical trials,with a total of 62,145 patients and 16,754 pooled death events(9,171 in CRT-D and 7,583 in CRT-P),were analyzed.CRT-D was associated with a significantly lower risk of all-cause mortality compared to CRT-P(pooled OR=0.72;95%CI:0.61-0.85;P<0.01),with significant heterogeneity(I2=83%).RCT subgroup analysis,was not statistically significant(pooled OR=0.82;95%CI:0.64-1.06;P=0.41;I2=0%).In patients older than 75 years,no significant difference in mortality risk was observed(pooled OR 0.96;95%CI:0.81-1.15;I2=39%).CONCLUSION Our meta-analysis suggests that the addition of ICD therapy to CRT in patients with NICM significantly reduces all-cause mortality.However,this benefit does not extend to cardiovascular mortality,likely due to the primary role of ICDs in preventing sudden cardiac death rather than other causes such as progressive heart failure.The survival advantage of CRT-D is most pronounced in younger patients,with those over 75 years of age deriving less benefit.This highlights the importance of careful patient selection,considering age and comorbidities,when deciding on ICD implantation in NICM patients.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
文摘The integration of digital tools and effective knowledge management practices is critical for enhancing administrative efficiency and institutional continuity in higher education. This study investigates the relationships between knowledge modeling, institutional memory, leadership styles, technology, and administrative efficiency at the University of Cape Coast (UCC). The study sought to identify the challenges and opportunities in integrating digital tools into administrative processes and to provide actionable recommendations for improvement. A mixed-methods research design was employed, combining quantitative analysis using Partial Least Squares Structural Equation Modeling (PLS-SEM) with qualitative thematic analysis of interviews. The findings revealed key challenges, including resistance to change, fragmented knowledge repositories, and inadequate funding, alongside opportunities such as centralized knowledge systems, cost-effective open-source tools, and capacity-building initiatives. The study highlights the importance of strategic leadership, robust policies, and investments in digital infrastructure to enhance administrative practices. Policy implications include the need for clear digital transformation guidelines and leadership training to foster innovation and collaboration. Recommendations include investing in scalable digital tools, implementing comprehensive capacity-building programs, and promoting stakeholder engagement to drive successful digital integration. These insights provide a roadmap for UCC and similar institutions seeking to optimize administrative efficiency through digital transformation.
基金funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant agreement No.813263(PMSMat Train,granted to UF,PP,MV,and DP)provided by the Fund for Scientific Research Flanders(FWO-Vlaanderen)of the Flemish Government(FWO sabbatical bench fee K800224N granted to PP)and ERA-NET Re Park(granted to PP)。
文摘Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief introduction to the current state-of-the-art for neuroectoderm brain organoid development,emphasizing their biggest advantages in comparison with classical two-dimensional cell cultures and animal models.However,despite their usefulness for developmental studies,a major limitation for most brain organoid models is the absence of contributing cell types from endodermal and mesodermal origin.As such,current research is highly investing towards the incorporation of a functional vasculature and the microglial immune component.In this review,we will specifically focus on the development of immune-competent brain organoids.By summarizing the different approaches applied to incorporate microglia,it is highlighted that immune-competent brain organoids are not only important for studying neuronal network formation,but also offer a clear future as a new tool to study inflammatory responses in vitro in 3D in a brainlike environment.Therefore,our main focus here is to provide a comprehensive overview of assays to measure microglial phenotype and function within brain organoids,with an outlook on how these findings could better understand neuronal network development or restoration,as well as the influence of physical stress on microglia-containing brain organoids.Finally,we would like to stress that even though the development of immune-competent brain organoids has largely evolved over the past decade,their full potential as a pre-clinical tool to study novel therapeutic approaches to halt or reduce inflammation-mediated neurodegeneration still needs to be explored and validated.
文摘Object detection in occluded environments remains a core challenge in computer vision(CV),especially in domains such as autonomous driving and robotics.While Convolutional Neural Network(CNN)-based twodimensional(2D)and three-dimensional(3D)object detection methods havemade significant progress,they often fall short under severe occlusion due to depth ambiguities in 2D imagery and the high cost and deployment limitations of 3D sensors such as Light Detection and Ranging(LiDAR).This paper presents a comparative review of recent 2D and 3D detection models,focusing on their occlusion-handling capabilities and the impact of sensor modalities such as stereo vision,Time-of-Flight(ToF)cameras,and LiDAR.In this context,we introduce FuDensityNet,our multimodal occlusion-aware detection framework that combines Red-Green-Blue(RGB)images and LiDAR data to enhance detection performance.As a forward-looking direction,we propose a monocular depth-estimation extension to FuDensityNet,aimed at replacing expensive 3D sensors with a more scalable CNN-based pipeline.Although this enhancement is not experimentally evaluated in this manuscript,we describe its conceptual design and potential for future implementation.
基金Supported by Beijing Bethune Charitable Foundation and Provincial Natural Science Foundation of Liaoning,No.2022-MS-190.
文摘BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.
文摘BACKGROUND Major adverse cardiovascular(CV)events(MACEs)are the primary cause of morbidity and mortality in kidney transplantation(KT)recipients.The risk for MACEs is impacted by an array of traditional and transplant-related non-traditional CV risk factors.AIM To investigate the association between potential CV risk factors related to KT and MACEs,and their potential modification by hyperuricemia(HU).METHODS The relationship between CV risk factors related to KT and MACEs was examined in a cohort of 545 patients who underwent transplantation between 2008 and 2019.The mean age of patients at KT was 55.0 years±14.2 years(range 15.0–89.0 years).Univariate and multivariate logistic regression models were constructed to identify risk factors influencing MACEs.To explore the potential effect modification by uric acid(UA),patients were categorized into groups based on UA levels:(1)Low(<356μmol/L);(2)Normal(356–416μmol/L);(3)High(416–475μmol/L);and(4)Very high(>475μmol/L).RESULTS MACEs occurred in 145 of 545(26.6%)KT recipients.The most prevalent comorbidities were hypertension(87%),dyslipidemia(78%),secondary hyperparathyroidism(68%),HU(63%)and anemia(33%).In the multivariate logistic regression model,the most significant factors associated with MACEs were previous CV events[odds ratio(OR)=70.6,95%CI:24.9–200.1],left ventricular hypertrophy(LVH)(OR=12.6,95%CI:2.7–58.3),HU treatment(OR=4.3,95%CI:2.4–7.6),and anemia(OR=5.3,95%CI:2.9–9.8).Effect modification by the presence of HU revealed that independent factors associated with MACEs were age(OR=1.03,95%CI:1.0–1.1),previous CV events(OR=41.7,95%CI:13.6–127.6),LVH(OR=15.3,95%CI:2.0–116.6),HU treatment(OR=2.5,95%CI:1.3–4.6)and anemia(OR=5.4,95%CI:2.8–10.5).Effect modification by UA levels dichotomized at 475μmol/L(very high level of UA)revealed that HU treatment was not associated with MACEs in groups with or without very high UA levels.CONCLUSION A very high level of UA was observed to act as an effect-modifying factor for MACEs,especially when combined with other risk factors such as age,previous CV events,LVH,and anemia.
基金supported by the Natural Sciences and Engineering Research Council of Canada-Discovery Grant(individual)Program(No.NSEC-DG#355433-2009)funded by the LabEx CeLyA(Centre Lyonnais d’Acoustique,No.ANR-10-LABX-0060)of Universite?de Lyon。
文摘The present study investigates the wavespace of Highly Contrasted Structures(HCS)and Highly Dissipative Structures(HDS)by wave-based models.The Asymptotic Homogenization Method(AHM),exploits the asymptotic Zig-Zag model and homogenization technique to compute the bending wavenumbers via a 6th-order equation.The General Laminate Model(GLM)employs Mindlin’s displacement field to establish displacement-constraint relationships and resolves a quadratic Eigenvalue Problem(EVP)of the dispersion relation.The Wave Finite Element(WFE)scheme formulates the Nonlinear Eigenvalue Problem(NEP)for waves in varying directions and tracks complex wavenumbers using Weighted Wave Assurance Criteria(WWAC).Two approaches are introduced to estimate the Damping Loss Factor(DLF)of HDS,with the average DLF calculated by the modal density at various angles where non-homogeneity is present.Evaluation of robustness and accuracy is made by comparing the wavenumbers and DLF obtained from AHM and GLM with WFE.WFE is finally extended to a sandwich metastructure with a non-homogeneous core,and the Power Input Method(PIM)with Finite Element Method(FEM)data is employed to assess the average DLF,demonstrating an enhanced DLF compared to layered configurations with the same material portion,indicating increased energy dissipation due to the bending-shear coupling effects.
基金supported by the Agricultural Science and Technology Innovation Program,Institute of Food Science and Technology,Chinese Academy of Agricultural Sciences under Grant CAAS-ASTIP-2023-IFSTGuangdong Provincial Key R&D Programme(2023B0202080003).
文摘Alzheimer’s dementia(AD)and type 2 diabetes(T2D)are interrelated global public health problems,and the current epidemics of both AD and T2D are insulin resistance diseases.Thus,AD and T2D may share common risk factors such as an unhealthy diet,lifestyle,and obesity.Meat products is an important part of the diet of consumers worldwide.This systematic review and meta-analysis aims to assess and estimate the effect of meat products consumption on AD and T2D in humans.Web of Science,MEDLINE,PubMed,Cochrane Library,and Embase were searched from January 2012 to April 2024.29 articles reported 32 cohort studies with 1785769 subjects,with 3546 AD cases and 91092 T2D cases that met the inclusion criteria and were included in our analysis.Consumption of various meat products increased the risk of T2D(hazard ratios(HR)=1.19,95%confidence intervals(CI):1.13−1.26,P=0.000;I2=88.5%),consumption of smoked,grilled/roasted and fried meat products was more likely to induce T2D(HR=1.24,95%CI:1.18−1.30,P=0.000;I2=76.1%),but was borderline significant for the risk of AD(HR=1.11,95%CI:0.98−1.25,P=0.094;I2=58.8%),with consumption of mainly livestock and poultry products increasing the risk(HR=1.21,95%CI:1.03−1.42,P=0.017;I2=66.8%).The association between meat products consumption and AD risk was influenced by meat type and sample size,while the risk of T2D was influenced by meat type,follow-up and sex.A daily intake of 27,123 and 170 g of livestock products increased the risk of T2D by 10%,51%and 70%respectively,whereas the risk of T2D was reduced when the intake of various meat products was less than 23 g/day.
文摘Schistosomiasis is a neglected tropical disease (NTD) widespread in sub-Saharan Africa and mostly affects school going children. Côte d’Ivoire is one of the most vulnerable countries to schistosomiasis, and its prevalence varies by region. This cross-sectional survey was conducted in schools in the Upper Sassandra region to determine the knowledge, attitude, and practices of school children regarding schistosomiasis. In total, 354 students participated in the survey. Our results showed that, compared to the girls, the boys had a higher level of knowledge about schistosomiasis OR = 1.605 and p = 0.05. Regarding the signs, symptoms, and modes of transmission and prevention of schistosomiasis, the participants reported a low level of knowledge p > 0.05 and OR 1. In conclusion, it is important to target health messages in schools to reach the most vulnerable students effectively. This initiative aims to provide children with basic knowledge and skills in the transmission of schistosomiasis.
基金supported by the Fundamental Research Program of Shanxi Province(Nos.202303021212159 and 202303021222190)the National Natural Science Foundation of China(No.62222403)+2 种基金the Higher Education Institutions Science and Technology Innovation Program of Shanxi Province(No.2023L160)the Scientific Research Fund of Hunan Provincial Education Department(No.23B0842)the Natural Science Foundation of Shanxi Normal University(Nos.JCYJ2024017 and JCYJ2023015)。
文摘Doping plays a pivotal role in enhancing the performance of organic semiconductors(OSCs)for advanced optoelectronic and thermoelectric applications.In this study,we systematically investigated the doping performance and applicability of the ionic dopant 4-isopropyl-4′-methyldiphenyliodonium tetrakis(penta-fluorophenyl-borate)(DPI-TPFB)as a p-dopant for OSCs.Using the p-type OSC PBBT-2T as a model system,we demonstrated that DPI-TPFB shows significant doping effect,as confirmed by ESR spectra,ultraviolet-visible-near-infrared(UV-vis-NIR)absorption,and work function analysis,and enhances the electronic conductivity of PBBT-2T films by over four orders of magnitude.Furthermore,DPI-TPFB exhibited broad doping applicability,effectively doping various p-type OSCs and even imparting p-type characteristics to the n-type OSC N2200,transforming its intrinsic n-type behavior into p-type.The application of DPI-TPFB-doped PBBT-2T films in organic thermoelectric devices(OTEs)was also explored,achieving a power factor of approximately 10μW·m^(-1)·K^(-2).These findings highlight the potential of DPI-TPFB as a versatile and efficient dopant for integration into organic optoelectronic and thermoelectric devices.
基金supported by the National Key R&D Program of China(Grant No.2024YFB3614600)the National Natural Science Foundation of China(Grant No.52402185)+1 种基金Guangzhou Basic and Applied Basic Research Foundation(Grant No.2025A1515011800)Shenzhen Science and Technology Program(Grant No.JCYJ20241202123712017)。
文摘The bidirectional convergence of artificial intelligence and nanophotonics drives photonic technologies toward unprecedented levels of intelligence and efficiency,fundamentally reshaping their design paradigms and application boundaries.With its powerful data-driven and nonlinear optimization capabilities,artificial intelligence has become a powerful tool for optical design,enabling the inverse design of nanophotonics devices while accelerating the forward computation of electromagnetic responses.Conversely,nanophotonics provides a wave-based computational platform,giving rise to novel optical neural networks that achieve high-speed parallel computing and efficient information processing.This paper reviews the latest progress in the bidirectional field of artificial intelligence and nanophotonics,analyzes the basic principles of various applications from a universal perspective,comprehensively evaluates the advantages and limitations of different research methods,and makes a forwardlooking outlook on the bidirectional integration of artificial intelligence and nanophotonics,focusing on analyzing future development trends,potential applications,and challenges.The deep integration of artificial intelligence and nanophotonics is ushering in a new era for photonic technologies,offering unparalleled opportunities for fundamental research and industrial applications.
基金supported by Catalan Government,Nos.2014SGR344(to JT),2017SGR704(to JT),2021SGR01214(to MAL)MCIN/AEI/10.13039/501100011033/by“ERDF A way of making Europe,”Nos.SAF2015-67143(to JT),PID2019-106332GB-I00(to JT and MAL)and PID2022-141252NB-I00(to MAL).
文摘During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
文摘Unlike primary metabolites,secondary metabolites serve critical ecological functions,including plant protection,stress tolerance,and symbiosis.This review focuses on extracting,separating,and identifying the major classes of secondary metabolites,including alkaloids,terpenoids,phenolics,glycosides,saponins,and coumarins.It describes optimized methods regarding plant selection,extraction by solvents,and purification of the metabolites,highlighting the latest advancements in chromatographic and spectroscopic techniques.The review also describes some of the most important problems,such as the instability of the compounds or diversity of the structures,and discusses emerging technologies that solve these issues.Moreover,it examines the secondary roles of these metabolites in medicine,such as anticancer and antimicrobial drugs,sustainable agriculture biopesticides,and environmental ecology-also known as allelopathy and bioindicators.It combines traditional ethnobotanical approaches with contem-porary science,demonstrating the vital need to protect biodiversity in key ecosystems such as tropical rainforests,mountain regions,coral reefs,and arid zones as a foundation for anticipatory bio-discoveries.It organizes the methodological frameworks and outlines the steps needed to enhance the extraction of bioactive compounds from natural sources.
基金support from MATRIX(ANR-22-CE92-0047)with financial support from ITMI Cancer of Aviesan within the framework of the 2021−2030 Cancer Control Strategy,on funds administrated by INSERM through the project NECTAR.Matilde Siviero acknowledges funding from the French−German University/Saarbrücken(contract CDOC-06-2022).
文摘GaN diodes for high energy(64.8 MeV)proton detection were fabricated and investigated.A comparison of the performance of GaN diodes with different structures is presented,with a focus on sapphire and on GaN substrates,Schottky and pin diodes,and different active layer thicknesses.Pin diodes fabricated on a sapphire substrate are the best choice for a GaN proton detector working at 0 V bias.They are sensitive(minimum detectable proton beam<1 pA/cm^(2)),linear as a function of proton current and fast(<1 s).High proton current sensitivity and high spatial resolution of GaN diodes can be exploited in the future for proton imaging of patients in proton therapy.
文摘This work investigates the potential of low-pressure,medium-speed dual-fuel engines for cleaner maritime transportation.The thermodynamic performance of these engines is explored using three alternative fuels:liquefied natural gas(LNG),methanol,and ammonia.A parametric analysis examines the effect of adjustments to key engine parameters(compression ratio,boost pressure,and air-fuel ratio)on performance.Results show an initial improvement in performance with an increase in compression ratio,which reaches a peak and then declines.Similarly,increases in boost pressure and air-fuel ratio lead to linear performance gains.However,insufficient cooling reduces the amount of fuel burned,which hinders performance.Exergy analysis reveals significant exergy destruction within the engine,which ranges from 69.96%(methanol)to 78.48%(LNG).Notably,the combustion process is the leading cause of exergy loss.Among the fuels tested,methanol exhibits the lowest combustion-related exergy destruction(56.41%),followed by ammonia(62.12%)and LNG(73.77%).These findings suggest that methanol is a promising near-term alternative to LNG for marine fuel applications.
