Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derive...Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.展开更多
Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neur...Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neural circuits without the need for permanent structural alterations to the brain.Initially developed as a treatment for movement disorders such as Parkinson's disease(PD),DBS has expanded to encompass various neurological and psychiatric disorders.展开更多
Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomatern...Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomaternal communication,supporting early embryonic development.This study aimed to:(i)compare the protein cargo of uterine fluid EVs(UF-EVs)from CYCLIC and PREGNANT heifers;(ii)characterize the protein profile of conditioned medium(CM)-EVs from endometrial explants cultured alone(EXPL)or co-cultured with five d 7 blastocysts(EXPL+EMB)in vitro;and(iii)compare the EV protein cargo between the in vivo and in vitro models(i.e.,EXPL vs.CYCLIC and EXPL+EMB vs.PREGNANT).Results We identified 1,459 and 1,752 proteins in the UF-EVs of CYCLIC and PREGNANT heifers,respectively.Among these,12 were exclusive to CYCLIC,and 18 were exclusive to PREGNANT.Among the 1,329 proteins identified in both groups,16 were differently abundant;ten were more abundant,and six were less abundant in UF-EVs from PREGNANT heifers.In vivo,the changes in UF-EV protein cargo induced by the presence of a blastocyst were related to inflammatory and immune responses,endometrial receptivity,and support of early embryonic development by promoting cell polarity,cell–cell adhesion,and stem cell differentiation.In vitro,we identified 1,501 proteins in the CM-EVs from EXPL,1,975 in the CM-EVs from EXPL+EMB,and 82 in the CM-EVs from EMB.Additionally,50 proteins were unique to EXPL+EMB,and another 33 were differentially abundant due to the synergistic interaction between the embryo and the endometrium.These proteins are involved in embryonic development,regulation of stem cell differentiation,establishment and maintenance of cell polarity,interferon tau(IFNT)-mediated cell signaling,endometrial receptivity,and immune modulation.Although there are qualitative and quantitative differences between in vivo and in vitro-derived EVs,UF-EVs from CYCLIC heifers compared to CM-EVs from EXPL,as well as UFEVs from PREGNANT heifers compared to CM-EVs from EXPL+EMB shared common proteins.Conclusions These findings highlight the pivotal role of EVs in embryo-maternal communication,suggesting that their protein cargo may actively contribute to the modulation of the uterine environment to support early embryonic development.Understanding these molecular interactions could provide valuable insights into the mechanisms of implantation and pregnancy establishment.展开更多
Disorders of consciousness(DoC),including coma,vegetative state,and minimally conscious state,present a spectrum of conditions characterized by impaired awareness and responsiveness due to severe brain injury.Conventi...Disorders of consciousness(DoC),including coma,vegetative state,and minimally conscious state,present a spectrum of conditions characterized by impaired awareness and responsiveness due to severe brain injury.Conventional interventions for DoC primarily focus on promoting conditions conducive to spontaneous neurological recovery including pharmacological treatments such as dopaminergic agents(e.g.,amantadine)and rehabilitative strategies including sensory stimulation programs and physical therapy.展开更多
The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifact...The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.展开更多
The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. Th...The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.展开更多
Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse event...Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse events,and earlier revision.Therefore,it is essential to try to avoid LLD when implanting a THA.Several studies focus on this issue,including the following:Accelerometer-based portable navigation system,preoperative digital templating,robot-assisted surgery,the anatomical marker positioning method(shoulder-to-shoulder)and the artificial intelligence-based three-dimensional planning software system.The aforementioned methods should be familiar to surgeons who perform THA procedures,as a fundamental objective of this surgical intervention is to avoid LLD.展开更多
Smartphone-based electrocardiograms(ECGs)are increasingly utilized for monitoring atrial fibrillation(AF)recurrence after catheter ablation(CA),referred to as smartphone AF burden(SMURDEN).The SMURDEN data often exhib...Smartphone-based electrocardiograms(ECGs)are increasingly utilized for monitoring atrial fibrillation(AF)recurrence after catheter ablation(CA),referred to as smartphone AF burden(SMURDEN).The SMURDEN data often exhibit complex patterns of zero AF episodes,which may arise from either true AF-free status(structural zeros)or missed AF episodes due to intermittent monitoring(random zeros).Such a mixture of AF-free and at-risk patients can lead to zero-inflation in the data.The authors propose a novel zero-inflation test for binomial regression models to identify recurrence-free AF populations.Unlike traditional approaches requiring fully specified zero-inflated models,the proposed test utilizes a weighted average of the discrepancies between observed and expected zero proportions,with weights determined by binomial sizes.A closed-form test statistic is developed,and its asymptotic distribution is derived using estimating equations.Simulations demonstrate superior performance over existing methods,and real-world AF monitoring data validate the practical utility of our proposed test.展开更多
Objectives:Glioblastoma multiforme(GBM)is a highly aggressive brain tumor characterized by extensive transcriptional and epigenetic dysregulation.Brother of the Regulator of Imprinted Sites(BORIS/CTCFL)has been implic...Objectives:Glioblastoma multiforme(GBM)is a highly aggressive brain tumor characterized by extensive transcriptional and epigenetic dysregulation.Brother of the Regulator of Imprinted Sites(BORIS/CTCFL)has been implicated in oncogenic transcriptional programs in several cancers,but its role in GBM remains poorly defined.This study aimed to characterize BORIS-associated transcriptional programs in GBM and to assess their functional relevance using integrative computational and experimental approaches.Methods:Transcriptomic data from The Cancer Genome Atlas(TCGA)-GBM and Genotype-Tissue Expression(GTex)brain cortex were analyzed following batch correction,differential expression analysis,and gene ontology enrichment.TCGA-GBM samples were stratified into BORIS-high and BORIS-low expression quartiles to identify BORIS-associated gene signatures.BORIS chromatin occupancy was examined by Chromatin immunoprecipitation combined with sequencing(ChIP-seq)in U87MG cells,followed by functional annotation of BORIS-bound genes.Experimental validation included BORIS overexpression,RT-qPCR,immunoblotting,ChIP-qPCR,and functional assays assessing proliferation,clonogenic survival,and migration.Results:BORIS was significantly upregulated in GBM compared with normal brain tissue and was associated with transcriptional programs related to development,metabolism,and cell signaling.Quartilebased analysis identified BORIS-associated differentially expressed genes,including CD36 and FBN2.ChIP-seq revealed BORIS binding at promoter-proximal regions,with ChIP-qPCR confirming occupancy at CD36 and FBN2 regulatory regions.BORIS overexpression increased CD36 and FBN2 expression and was associated with reduced proliferation,enhanced clonogenic survival,and increased migratory capacity.Conclusion:These findings indicate that BORIS is associated with transcriptional and phenotypic programs linked to GBM aggressiveness and may represent a candidate for further investigation as a biomarker or therapeutic target in GBM.展开更多
Aquatic plants have been widely used for lake ecological restoration.The effect of aquatic plants on lake biogeochemical cycling has been investigated intensively,however,plants’effect on biodegradation of dissolved ...Aquatic plants have been widely used for lake ecological restoration.The effect of aquatic plants on lake biogeochemical cycling has been investigated intensively,however,plants’effect on biodegradation of dissolved organic carbon(DOC)is rarely studied.Here we designed an indoor incubation experiment to explore the priming effect(PE)of aquatic plant leaching solution on DOC in shallow lakes,referring to as the input of active dissolved organic matter(DOM)that would arouse changes in the degradation rate of original refractory DOM.Waters from 20 urban lakes of different tropic states were incubated to study their PE on DOC by adding leaching solutions from two submerged freshwater plants,Hydrilla(H)and Vallisneria(V).The study showed a clear influence of aquatic plants on PE with varying directions and intensities.The H incubation group showed a PE range of-6.19%–9.79%,with an average of 2.15%±2.70%,whereas the V incubation group exhibited a PE range of-10.03%to 3.60%,with an average of-0.65%±3.11%.The positive and negative PEs by the two plant species indicate a key role of plants over trophic states on organic carbon dynamics in freshwater lakes.From the perspective of plant leaching input,our results reveal that planting aquatic plants whose leaching solution can reduce PE like V could be used to enhance carbon storage and constrain carbon emission.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accoun...Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accounting for 80%of the overall noncutaneous melanomas.Clinically,it remains silent in about 30%of the cases;when symptomatic,it generally causes metamorphopsia(painless loss or distortion of vision)and/or photopsia(flashing or flickering of light in the visual field).Discoloration of the iris,astigmatism,glaucoma,and even blindness are other,less common clinical manifestations.Several pathophysiological mechanisms underlie the development of UM.Genetic mutations,involving especially the G protein subunit alpha q(GNAQ),guanine nucleotide-binding protein subunit alpha-11(GNA11),BRCA1 associated deubiquitinase 1(BAP1),splicing factor 3b subunit 1(SF3B1),and eukaryotic translation initiation factor 1A,X-linked(EIF1AX)genes as well as the MAPK/ERK signaling pathway genes,have been largely associated with the development of UM.Chromosomal aberrations,inflammatory and immunological alterations are often concurrent factors for the development and progression of UM.Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs.This review aims to present the latest advances in the clinical molecular pathology of UM,along with the resulting targeted,immunological,and other therapies that have been introduced or are currently under investigation.展开更多
Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This st...Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This study proposes a novel end-to-end disparity estimation model to address these challenges.Our approach combines a Pseudo-Siamese neural network architecture with pyramid dilated convolutions,integrating multi-scale image information to enhance robustness against lighting interferences.This study introduces a Pseudo-Siamese structure-based disparity regression model that simplifies left-right image comparison,improving accuracy and efficiency.The model was evaluated using a dataset of stereo endoscopic videos captured by the Da Vinci surgical robot,comprising simulated silicone heart sequences and real heart video data.Experimental results demonstrate significant improvement in the network’s resistance to lighting interference without substantially increasing parameters.Moreover,the model exhibited faster convergence during training,contributing to overall performance enhancement.This study advances endoscopic image processing accuracy and has potential implications for surgical robot applications in complex environments.展开更多
Obesity is characterized by both central and peripheral alterations,increasing the risk for neurological and metabolic disorders.Recent evidence indicate that obesity can disrupt the glymphatic system and impair the c...Obesity is characterized by both central and peripheral alterations,increasing the risk for neurological and metabolic disorders.Recent evidence indicate that obesity can disrupt the glymphatic system and impair the clearance of cerebrospinal fluid(CSF).This can lead to the build of neurotoxic molecules,potentially explaining obesity’s risk for neurodegeneration and cognitive decline.Given that glymphatic flow is tightly regulated by sleep,and that sleep disturbances are seen in obesity,melatonin emerges as a promising candidate to target glymphatic dysfunction in obesity.In both clinical and preclinical models,exogenous melatonin improves sleep quality and enhances slow-wave sleep,which is the sleep stage when glymphatic clearance is most active.This perspective aims to explore the mechanistic links between obesity and glymphatic dysfunction,highlighting melatonin as a novel therapeutic to mitigate cognitive and neurological consequences associated with obesity through the restoration of the glymphatic system.展开更多
This study explores the use of black soldier fly larvae protein as a bio-based adhesive to produce particleboards from sugarcane bagasse.A comprehensive evaluation was conducted,including rheological characterization ...This study explores the use of black soldier fly larvae protein as a bio-based adhesive to produce particleboards from sugarcane bagasse.A comprehensive evaluation was conducted,including rheological characterization of the adhesive and physical–mechanical testing of the panels according to European standards.The black soldier fly larvae-based adhesive exhibited gel-like viscoelastic behavior,rapid partial structural recovery after shear,and favorable application properties.Particleboards manufactured with this adhesive and sugarcane bagasse achieved promising mechanical performance,with modulus of rupture and modulus of elasticity values of 30.2 and 3500 MPa,respectively.Internal bond strength exceeded 0.4 MPa,complying with European standard 312-3 specifications.For comparative purposes,a panel made with Eucalyptus grandis particles was also produced under the same conditions to demonstrate the versatility of the adhesive system.Compared to other bio-based and synthetic adhesives,this bio-based system showed competitive performance and derives from the bioconversion of organic residues.Protein adhesives were synthesized fromHermetia illucens larvae grown commercially on agriculturalwaste frompotato chip production,emphasizing the renewable origin of both the biomass and the final adhesive.These results highlight the potential of insect proteins as sustainable and circular alternatives for the wood panel industry.展开更多
Mobile communications are reaching out to every aspect of our daily life,necessitating highefficiency data transmission and support for diverse data types and communication scenarios.Polar codes have emerged as a prom...Mobile communications are reaching out to every aspect of our daily life,necessitating highefficiency data transmission and support for diverse data types and communication scenarios.Polar codes have emerged as a promising solution due to their outstanding error-correction performance and low complexity.Unequal error protection(UEP)involves nonuniform error safeguarding for distinct data segments,achieving a fine balance between error resilience and resource allocation,which ultimately enhancing system performance and efficiency.In this paper,we propose a novel class of UEP rateless polar codes.The codes are designed based on matrix extension of polar codes,and elegant mapping and duplication operations are designed to achieve UEP property while preserving the overall performance of conventional polar codes.Superior UEP performance is attained without significant modifications to conventional polar codes,making it straightforward for compatibility with existing polar codes.A theoretical analysis is conducted on the block error rate and throughput efficiency performance.To the best of our knowledge,this work provides the first theoretical performance analysis of UEP rateless polar codes.Simulation results show that the proposed codes significantly outperform existing polar coding schemes in both block error rate and throughput efficiency.展开更多
In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a to...In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a total of 19,126 solar flares were observed regardless the class: 3548 flares in solar cycle 23 (SC23) and 15,668 flares in solar cycle 24 (SC24). Our findings show that the cycle 23 has observed the highest occurrences of M-class and X-class flares, whereas cycle 24 has pointed out a predominance of B-class and C-class flares throughout its different phases. The results indicate that the cycle 23 was magnetically more intense than cycle 24, leading to more powerful solar flares and more frequent geomagnetic storms, capable of generating significant electromagnetic emissions that can affect satellites and GPS signals. The decrease in intense solar flares during cycle 24 compared to cycle 23 reflects an evolution in solar activity patterns over time.展开更多
Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-in...Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.展开更多
Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excess...Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excessive optical surfaces,reduced light throughput,and instrumental polarization.To address these limitations,we propose an embedded solar adaptive optics telescope(ESAOT)that intrinsically incorporates the solar AO(SAO)subsystem within the telescope's optical train,featuring a co-designed correction chain with a single Hartmann-Shack full-wavefront sensor(HS f-WFS)and a deformable secondary mirror(DSM).The HS f-WFS uses temporal-spatial hybrid sampling technique to simultane-ously resolve tip-tilt and high-order aberrations,while the DSM performs real-time compensation through adaptive modal optimization.This unified architecture achieves symmetrical polarization suppression and high system throughput by min-imizing optical surfaces.A 600 mm ESAOT prototype incorporating a 12×12 micro-lens array HS f-WFS and 61-actuator piezoelectric DSM has been developed and successfully conducted on-sky photospheric observations.Validations in-cluding turbulence simulations,optical bench testing,and practical observations at the Lijiang observatory collectively confirm the system's capability to maintain aboutλ/10 wavefront error during active region tracking.This architectural breakthrough of the ESAOT addresses long-standing SAO integration challenges in solar astronomy and provides scala-bility analyses confirming direct applicability to the existing and future large solar observation facilities.展开更多
基金supported by project Emerging Infectious Diseases One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,INF-ACT,Spoke 1 and Spoke 5,Project number PE00000007,CUP B53C20040570005(to PP and DN).
文摘Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.
文摘Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neural circuits without the need for permanent structural alterations to the brain.Initially developed as a treatment for movement disorders such as Parkinson's disease(PD),DBS has expanded to encompass various neurological and psychiatric disorders.
基金supported by research projects:PID2019-111641RB-I00 and PID2023-149027OB-I00 funded by MCIN/AEI/10.13039/501100011033/to DR and PRE2020-094452 to RM。
文摘Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomaternal communication,supporting early embryonic development.This study aimed to:(i)compare the protein cargo of uterine fluid EVs(UF-EVs)from CYCLIC and PREGNANT heifers;(ii)characterize the protein profile of conditioned medium(CM)-EVs from endometrial explants cultured alone(EXPL)or co-cultured with five d 7 blastocysts(EXPL+EMB)in vitro;and(iii)compare the EV protein cargo between the in vivo and in vitro models(i.e.,EXPL vs.CYCLIC and EXPL+EMB vs.PREGNANT).Results We identified 1,459 and 1,752 proteins in the UF-EVs of CYCLIC and PREGNANT heifers,respectively.Among these,12 were exclusive to CYCLIC,and 18 were exclusive to PREGNANT.Among the 1,329 proteins identified in both groups,16 were differently abundant;ten were more abundant,and six were less abundant in UF-EVs from PREGNANT heifers.In vivo,the changes in UF-EV protein cargo induced by the presence of a blastocyst were related to inflammatory and immune responses,endometrial receptivity,and support of early embryonic development by promoting cell polarity,cell–cell adhesion,and stem cell differentiation.In vitro,we identified 1,501 proteins in the CM-EVs from EXPL,1,975 in the CM-EVs from EXPL+EMB,and 82 in the CM-EVs from EMB.Additionally,50 proteins were unique to EXPL+EMB,and another 33 were differentially abundant due to the synergistic interaction between the embryo and the endometrium.These proteins are involved in embryonic development,regulation of stem cell differentiation,establishment and maintenance of cell polarity,interferon tau(IFNT)-mediated cell signaling,endometrial receptivity,and immune modulation.Although there are qualitative and quantitative differences between in vivo and in vitro-derived EVs,UF-EVs from CYCLIC heifers compared to CM-EVs from EXPL,as well as UFEVs from PREGNANT heifers compared to CM-EVs from EXPL+EMB shared common proteins.Conclusions These findings highlight the pivotal role of EVs in embryo-maternal communication,suggesting that their protein cargo may actively contribute to the modulation of the uterine environment to support early embryonic development.Understanding these molecular interactions could provide valuable insights into the mechanisms of implantation and pregnancy establishment.
文摘Disorders of consciousness(DoC),including coma,vegetative state,and minimally conscious state,present a spectrum of conditions characterized by impaired awareness and responsiveness due to severe brain injury.Conventional interventions for DoC primarily focus on promoting conditions conducive to spontaneous neurological recovery including pharmacological treatments such as dopaminergic agents(e.g.,amantadine)and rehabilitative strategies including sensory stimulation programs and physical therapy.
文摘The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.
文摘The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.
文摘Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse events,and earlier revision.Therefore,it is essential to try to avoid LLD when implanting a THA.Several studies focus on this issue,including the following:Accelerometer-based portable navigation system,preoperative digital templating,robot-assisted surgery,the anatomical marker positioning method(shoulder-to-shoulder)and the artificial intelligence-based three-dimensional planning software system.The aforementioned methods should be familiar to surgeons who perform THA procedures,as a fundamental objective of this surgical intervention is to avoid LLD.
基金supported by the Fundamental Research Funds for the Central Universities in UIBE under Grant No.CXTD14-05。
文摘Smartphone-based electrocardiograms(ECGs)are increasingly utilized for monitoring atrial fibrillation(AF)recurrence after catheter ablation(CA),referred to as smartphone AF burden(SMURDEN).The SMURDEN data often exhibit complex patterns of zero AF episodes,which may arise from either true AF-free status(structural zeros)or missed AF episodes due to intermittent monitoring(random zeros).Such a mixture of AF-free and at-risk patients can lead to zero-inflation in the data.The authors propose a novel zero-inflation test for binomial regression models to identify recurrence-free AF populations.Unlike traditional approaches requiring fully specified zero-inflated models,the proposed test utilizes a weighted average of the discrepancies between observed and expected zero proportions,with weights determined by binomial sizes.A closed-form test statistic is developed,and its asymptotic distribution is derived using estimating equations.Simulations demonstrate superior performance over existing methods,and real-world AF monitoring data validate the practical utility of our proposed test.
基金supported by the Secretaría de Ciencia,Humanidades,Tecnología e Innovación(SECIHTI),Fondo Ciencia Básica y de Frontera 2025(CBF-2025-G-97)to E.Soto-Reyes and PRODEP(511/2023-3066-1599)SECIHTI,Fondo de Ciencia de Frontera 2023(CF-2023-G398)to C.Sámano+2 种基金supported by the Departamen to de Ciencias Naturales(DCN),División de Ciencias Naturales e Ingeniería(DCNI),UAM,Unidad Cuajimalpa,through Divisional Project Number 101S243-23 to E.Soto-Reyes and 123 S289-25 to C.Sámanoa master student from Programa de Maestría y Doctorado en Ciencias Bio-químicas,Universidad Nacional Autónoma deMéxico(UNAM)and received a fellowship(CVU number 1184475)fromSecretaría de Ciencia,Humanidades,Tecnología e Innovación(SECIHTI),Mexicoa postdoctoral fellow at the Universidad Autónoma Metropolitana-Cuajimalpa(UAM-C)and received a fellowship(CVU number 588333)from SECIHTI,Mexico.
文摘Objectives:Glioblastoma multiforme(GBM)is a highly aggressive brain tumor characterized by extensive transcriptional and epigenetic dysregulation.Brother of the Regulator of Imprinted Sites(BORIS/CTCFL)has been implicated in oncogenic transcriptional programs in several cancers,but its role in GBM remains poorly defined.This study aimed to characterize BORIS-associated transcriptional programs in GBM and to assess their functional relevance using integrative computational and experimental approaches.Methods:Transcriptomic data from The Cancer Genome Atlas(TCGA)-GBM and Genotype-Tissue Expression(GTex)brain cortex were analyzed following batch correction,differential expression analysis,and gene ontology enrichment.TCGA-GBM samples were stratified into BORIS-high and BORIS-low expression quartiles to identify BORIS-associated gene signatures.BORIS chromatin occupancy was examined by Chromatin immunoprecipitation combined with sequencing(ChIP-seq)in U87MG cells,followed by functional annotation of BORIS-bound genes.Experimental validation included BORIS overexpression,RT-qPCR,immunoblotting,ChIP-qPCR,and functional assays assessing proliferation,clonogenic survival,and migration.Results:BORIS was significantly upregulated in GBM compared with normal brain tissue and was associated with transcriptional programs related to development,metabolism,and cell signaling.Quartilebased analysis identified BORIS-associated differentially expressed genes,including CD36 and FBN2.ChIP-seq revealed BORIS binding at promoter-proximal regions,with ChIP-qPCR confirming occupancy at CD36 and FBN2 regulatory regions.BORIS overexpression increased CD36 and FBN2 expression and was associated with reduced proliferation,enhanced clonogenic survival,and increased migratory capacity.Conclusion:These findings indicate that BORIS is associated with transcriptional and phenotypic programs linked to GBM aggressiveness and may represent a candidate for further investigation as a biomarker or therapeutic target in GBM.
基金supported by the funding from Wuhan Institute of Technology to Dr.Siyue Li(Nos.24QD26 and 21QD02).
文摘Aquatic plants have been widely used for lake ecological restoration.The effect of aquatic plants on lake biogeochemical cycling has been investigated intensively,however,plants’effect on biodegradation of dissolved organic carbon(DOC)is rarely studied.Here we designed an indoor incubation experiment to explore the priming effect(PE)of aquatic plant leaching solution on DOC in shallow lakes,referring to as the input of active dissolved organic matter(DOM)that would arouse changes in the degradation rate of original refractory DOM.Waters from 20 urban lakes of different tropic states were incubated to study their PE on DOC by adding leaching solutions from two submerged freshwater plants,Hydrilla(H)and Vallisneria(V).The study showed a clear influence of aquatic plants on PE with varying directions and intensities.The H incubation group showed a PE range of-6.19%–9.79%,with an average of 2.15%±2.70%,whereas the V incubation group exhibited a PE range of-10.03%to 3.60%,with an average of-0.65%±3.11%.The positive and negative PEs by the two plant species indicate a key role of plants over trophic states on organic carbon dynamics in freshwater lakes.From the perspective of plant leaching input,our results reveal that planting aquatic plants whose leaching solution can reduce PE like V could be used to enhance carbon storage and constrain carbon emission.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
文摘Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accounting for 80%of the overall noncutaneous melanomas.Clinically,it remains silent in about 30%of the cases;when symptomatic,it generally causes metamorphopsia(painless loss or distortion of vision)and/or photopsia(flashing or flickering of light in the visual field).Discoloration of the iris,astigmatism,glaucoma,and even blindness are other,less common clinical manifestations.Several pathophysiological mechanisms underlie the development of UM.Genetic mutations,involving especially the G protein subunit alpha q(GNAQ),guanine nucleotide-binding protein subunit alpha-11(GNA11),BRCA1 associated deubiquitinase 1(BAP1),splicing factor 3b subunit 1(SF3B1),and eukaryotic translation initiation factor 1A,X-linked(EIF1AX)genes as well as the MAPK/ERK signaling pathway genes,have been largely associated with the development of UM.Chromosomal aberrations,inflammatory and immunological alterations are often concurrent factors for the development and progression of UM.Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs.This review aims to present the latest advances in the clinical molecular pathology of UM,along with the resulting targeted,immunological,and other therapies that have been introduced or are currently under investigation.
基金Supported by Sichuan Science and Technology Program(2023YFSY0026,2023YFH0004)Supported by the Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korean government(MSIT)(No.RS-2022-00155885,Artificial Intelligence Convergence Innovation Human Resources Development(Hanyang University ERICA)).
文摘Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This study proposes a novel end-to-end disparity estimation model to address these challenges.Our approach combines a Pseudo-Siamese neural network architecture with pyramid dilated convolutions,integrating multi-scale image information to enhance robustness against lighting interferences.This study introduces a Pseudo-Siamese structure-based disparity regression model that simplifies left-right image comparison,improving accuracy and efficiency.The model was evaluated using a dataset of stereo endoscopic videos captured by the Da Vinci surgical robot,comprising simulated silicone heart sequences and real heart video data.Experimental results demonstrate significant improvement in the network’s resistance to lighting interference without substantially increasing parameters.Moreover,the model exhibited faster convergence during training,contributing to overall performance enhancement.This study advances endoscopic image processing accuracy and has potential implications for surgical robot applications in complex environments.
文摘Obesity is characterized by both central and peripheral alterations,increasing the risk for neurological and metabolic disorders.Recent evidence indicate that obesity can disrupt the glymphatic system and impair the clearance of cerebrospinal fluid(CSF).This can lead to the build of neurotoxic molecules,potentially explaining obesity’s risk for neurodegeneration and cognitive decline.Given that glymphatic flow is tightly regulated by sleep,and that sleep disturbances are seen in obesity,melatonin emerges as a promising candidate to target glymphatic dysfunction in obesity.In both clinical and preclinical models,exogenous melatonin improves sleep quality and enhances slow-wave sleep,which is the sleep stage when glymphatic clearance is most active.This perspective aims to explore the mechanistic links between obesity and glymphatic dysfunction,highlighting melatonin as a novel therapeutic to mitigate cognitive and neurological consequences associated with obesity through the restoration of the glymphatic system.
基金supported by the Consejo Nacional de Investigaciones Cientificas y Tecnicas(CONICET)via grant Proyectos de Investigacion Plurianuales(PIP 2021:2894)Agencia I+D+i via grant Proyectos de Investigacion Cientifica y Tecnologica(PICT-2021-I-A-00294).
文摘This study explores the use of black soldier fly larvae protein as a bio-based adhesive to produce particleboards from sugarcane bagasse.A comprehensive evaluation was conducted,including rheological characterization of the adhesive and physical–mechanical testing of the panels according to European standards.The black soldier fly larvae-based adhesive exhibited gel-like viscoelastic behavior,rapid partial structural recovery after shear,and favorable application properties.Particleboards manufactured with this adhesive and sugarcane bagasse achieved promising mechanical performance,with modulus of rupture and modulus of elasticity values of 30.2 and 3500 MPa,respectively.Internal bond strength exceeded 0.4 MPa,complying with European standard 312-3 specifications.For comparative purposes,a panel made with Eucalyptus grandis particles was also produced under the same conditions to demonstrate the versatility of the adhesive system.Compared to other bio-based and synthetic adhesives,this bio-based system showed competitive performance and derives from the bioconversion of organic residues.Protein adhesives were synthesized fromHermetia illucens larvae grown commercially on agriculturalwaste frompotato chip production,emphasizing the renewable origin of both the biomass and the final adhesive.These results highlight the potential of insect proteins as sustainable and circular alternatives for the wood panel industry.
基金supported by National Natural Science Foundation of China(No.62301008)China Postdoctoral Science Foundation(No.2022M720272)New Cornerstone Science Foundation through the XPLORER PRIZE。
文摘Mobile communications are reaching out to every aspect of our daily life,necessitating highefficiency data transmission and support for diverse data types and communication scenarios.Polar codes have emerged as a promising solution due to their outstanding error-correction performance and low complexity.Unequal error protection(UEP)involves nonuniform error safeguarding for distinct data segments,achieving a fine balance between error resilience and resource allocation,which ultimately enhancing system performance and efficiency.In this paper,we propose a novel class of UEP rateless polar codes.The codes are designed based on matrix extension of polar codes,and elegant mapping and duplication operations are designed to achieve UEP property while preserving the overall performance of conventional polar codes.Superior UEP performance is attained without significant modifications to conventional polar codes,making it straightforward for compatibility with existing polar codes.A theoretical analysis is conducted on the block error rate and throughput efficiency performance.To the best of our knowledge,this work provides the first theoretical performance analysis of UEP rateless polar codes.Simulation results show that the proposed codes significantly outperform existing polar coding schemes in both block error rate and throughput efficiency.
文摘In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a total of 19,126 solar flares were observed regardless the class: 3548 flares in solar cycle 23 (SC23) and 15,668 flares in solar cycle 24 (SC24). Our findings show that the cycle 23 has observed the highest occurrences of M-class and X-class flares, whereas cycle 24 has pointed out a predominance of B-class and C-class flares throughout its different phases. The results indicate that the cycle 23 was magnetically more intense than cycle 24, leading to more powerful solar flares and more frequent geomagnetic storms, capable of generating significant electromagnetic emissions that can affect satellites and GPS signals. The decrease in intense solar flares during cycle 24 compared to cycle 23 reflects an evolution in solar activity patterns over time.
基金supported by grants from the Knut and Alice Wallenberg foundation(P-OB,JRZ,and AK)the Swedish Research Council(JRZ and AK),Centrum för idrottsforskning(AK and JRZ)+7 种基金the NovoNordisk Foundation Metabolic Stress Associated Molecules(MSAM)consortium NNF15SA0018346 and Metabolite-related Inflammation and Disease(MeRIAD)consortium Grant number 0064142(AK)the Swedish Diabetes Foundation(AK and JRZ)the European Foundation for the Study of Diabetes(JRZ and AK)the Region Stockholm(ALF project)(JRZ and KC)the Strategic Research Program in Diabetes at Karolinska Institutet(JRZ and AK)supported by the Strategic Research Programme in Diabetes(SRP Diabetes)for use of the Seahorse flux analyzer.Human islets were made possible through the Juvenile Diabetes Research Foundation(JDRF)award 31-2008-416(European Coordinating Infrastructure for Islet Transplantation(ECIT),Islet for Basic Research program)AK holds a Distinguished Investigator Grant within Endocrinology and Metabolism from the Novo Nordisk Foundation(NNF24OC0088739)JRZ received the 2024 European Association for the Study of Diabetes(ESAD)-Novo Nordisk Foundation Diabetes Prize for Excellence(NNF24SA0092609).
文摘Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.
基金support from the National Science Foundation of China(NSFC)(Grants No.12293031 and No.61905252)the National Science Foundation for Distinguished Young Scholars(Grant No.12022308)the National Key R&D Program of China(Grants No.2021YFC2202200 and No.2021YFC2202204).
文摘Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excessive optical surfaces,reduced light throughput,and instrumental polarization.To address these limitations,we propose an embedded solar adaptive optics telescope(ESAOT)that intrinsically incorporates the solar AO(SAO)subsystem within the telescope's optical train,featuring a co-designed correction chain with a single Hartmann-Shack full-wavefront sensor(HS f-WFS)and a deformable secondary mirror(DSM).The HS f-WFS uses temporal-spatial hybrid sampling technique to simultane-ously resolve tip-tilt and high-order aberrations,while the DSM performs real-time compensation through adaptive modal optimization.This unified architecture achieves symmetrical polarization suppression and high system throughput by min-imizing optical surfaces.A 600 mm ESAOT prototype incorporating a 12×12 micro-lens array HS f-WFS and 61-actuator piezoelectric DSM has been developed and successfully conducted on-sky photospheric observations.Validations in-cluding turbulence simulations,optical bench testing,and practical observations at the Lijiang observatory collectively confirm the system's capability to maintain aboutλ/10 wavefront error during active region tracking.This architectural breakthrough of the ESAOT addresses long-standing SAO integration challenges in solar astronomy and provides scala-bility analyses confirming direct applicability to the existing and future large solar observation facilities.
