The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNA...The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.展开更多
The emergence of beyond 5G networks has the potential for seamless and intelligent connectivity on a global scale.Network slicing is crucial in delivering services for different,demanding vertical applications in this...The emergence of beyond 5G networks has the potential for seamless and intelligent connectivity on a global scale.Network slicing is crucial in delivering services for different,demanding vertical applications in this context.Next-generation applications have time-sensitive requirements and depend on the most efficient routing path to ensure packets reach their intended destinations.However,the existing IP(Internet Protocol)over a multi-domain network faces challenges in enforcing network slicing due to minimal collaboration and information sharing among network operators.Conventional inter-domain routing methods,like Border Gateway Protocol(BGP),cannot make routing decisions based on performance,which frequently results in traffic flowing across congested paths that are never optimal.To address these issues,we propose CoopAI-Route,a multi-agent cooperative deep reinforcement learning(DRL)system utilizing hierarchical software-defined networks(SDN).This framework enforces network slicing in multi-domain networks and cooperative communication with various administrators to find performance-based routes in intra-and inter-domain.CoopAI-Route employs the Distributed Global Topology(DGT)algorithm to define inter-domain Quality of Service(QoS)paths.CoopAI-Route uses a DRL agent with a message-passing multi-agent Twin-Delayed Deep Deterministic Policy Gradient method to ensure optimal end-to-end routes adapted to the specific requirements of network slicing applications.Our evaluation demonstrates CoopAI-Route’s commendable performance in scalability,link failure handling,and adaptability to evolving topologies compared to state-of-the-art methods.展开更多
The mobility and connective capabilities of unmanned aerial vehicles(UAVs)are becoming more and more important in defense,commercial,and research domains.However,their open communication makes UAVs susceptible toundes...The mobility and connective capabilities of unmanned aerial vehicles(UAVs)are becoming more and more important in defense,commercial,and research domains.However,their open communication makes UAVs susceptible toundesirablepassive attacks suchas eavesdroppingor jamming.Recently,the inefficiencyof traditional cryptography-based techniques has led to the addition of Physical Layer Security(PLS).This study focuses on the advanced PLS method for passive eavesdropping in UAV-aided vehicular environments,proposing a solution to complement the conventional cryptography approach.Initially,we present a performance analysis of first-order secrecy metrics in 6G-enabled UAV systems,namely hybrid outage probability(HOP)and secrecy outage probability(SOP)over 2×2 Nakagami-m channels.Later,we propose a novel technique for mitigating passive eavesdropping,which considers first-order secrecy metrics as an optimization problem and determines their lower and upper bounds.Finally,we conduct an analysis of bounded HOP and SOP using the interactive Nakagami-m channel,considering the multiple-input-multiple-output configuration of the UAV system.The findings indicate that 2×2 Nakagami-mis a suitable fadingmodel under constant velocity for trustworthy receivers and eavesdroppers.The results indicate that UAV mobility has some influence on an eavesdropper’s intrusion during line-of-sight-enabled communication and can play an important role in improving security against passive eavesdroppers.展开更多
In reptiles,such as the red-eared slider turtle(Trachemys scripta elegans),gonadal sex determination is highly dependent on the environmental temperature during embryonic stages.This complex process,which leads to dif...In reptiles,such as the red-eared slider turtle(Trachemys scripta elegans),gonadal sex determination is highly dependent on the environmental temperature during embryonic stages.This complex process,which leads to differentiation into either testes or ovaries,is governed by the finely tuned expression of upstream genes,notably the testis-promoting gene Dmrt1 and the ovary-promoting gene Foxl2.Recent studies have identified epigenetic regulation as a crucial factor in testis development,with the H3K27me3 demethylase KDM6B being essential for Dmrt1 expression in T.s.elegans.However,whether KDM6B alone can induce testicular differentiation remains unclear.In this study,we found that overexpression of Kdm6b in T.s.elegans embryos induced the male development pathway,accompanied by a rapid increase in the gonadal expression of Dmrt1 at 31°C,a temperature typically resulting in female development.Notably,this sex reversal could be entirely rescued by Dmrt1 knockdown.These findings demonstrate that Kdm6b is sufficient for commitment to the male pathway,underscoring its role as a critical epigenetic regulator in the sex determination of the red-eared slider turtle.展开更多
In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisi...In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.展开更多
BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The informat...BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.展开更多
Volatile organic compounds(VOC)gas detection devices based on semiconductor sensors have become a common method due to their low cost,simple principle,and small size.However,with the continuous development of material...Volatile organic compounds(VOC)gas detection devices based on semiconductor sensors have become a common method due to their low cost,simple principle,and small size.However,with the continuous development of materials science,various new materials have been applied in the fabrication of gas sensors,but these new materials have more stringent requirements for operating temperature,which cannot be met by existing sensor modules on the market.Therefore,this paper proposes a temperature-adjustable sensor module and designs an environmental monitoring system based on the STM32F103RET6 microprocessor.This system primarily utilizes multiple semiconductor gas sensors to monitor and record the concentrations of various harmful gases in different environments.It can also monitor real-time temperature,humidity,and latitude and longitude in the current environment,and upload the data to the Internet of Things via 4G communication.This system has the advantages of small size,portability,and low cost.Experimental results show that the sensor module can achieve precise control of operating temperature to a certain extent,with an average temperature error of approximately 3%.The monitoring system demonstrates a certain level of accuracy in detecting target gases and can promptly upload the data to a cloud platform for storage and processing.A comparison with professional testing equipment shows that the sensitivity curves of each sensor exhibit similarity.This study provides engineering and technical references for the application of VOC gas sensors.展开更多
Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with ...Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.展开更多
基金funded by Notingham University and the Neuroscience Support Group Charity,UK(to HMK)supported by a CONACYT PhD scholarshipMD?was supported by the Postdoctoral Research Fellowship Program of TUBITAK。
文摘The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.
文摘The emergence of beyond 5G networks has the potential for seamless and intelligent connectivity on a global scale.Network slicing is crucial in delivering services for different,demanding vertical applications in this context.Next-generation applications have time-sensitive requirements and depend on the most efficient routing path to ensure packets reach their intended destinations.However,the existing IP(Internet Protocol)over a multi-domain network faces challenges in enforcing network slicing due to minimal collaboration and information sharing among network operators.Conventional inter-domain routing methods,like Border Gateway Protocol(BGP),cannot make routing decisions based on performance,which frequently results in traffic flowing across congested paths that are never optimal.To address these issues,we propose CoopAI-Route,a multi-agent cooperative deep reinforcement learning(DRL)system utilizing hierarchical software-defined networks(SDN).This framework enforces network slicing in multi-domain networks and cooperative communication with various administrators to find performance-based routes in intra-and inter-domain.CoopAI-Route employs the Distributed Global Topology(DGT)algorithm to define inter-domain Quality of Service(QoS)paths.CoopAI-Route uses a DRL agent with a message-passing multi-agent Twin-Delayed Deep Deterministic Policy Gradient method to ensure optimal end-to-end routes adapted to the specific requirements of network slicing applications.Our evaluation demonstrates CoopAI-Route’s commendable performance in scalability,link failure handling,and adaptability to evolving topologies compared to state-of-the-art methods.
基金funded by Taif University,Taif,Saudi Arabia,Project No.(TUDSPP-2024-139).
文摘The mobility and connective capabilities of unmanned aerial vehicles(UAVs)are becoming more and more important in defense,commercial,and research domains.However,their open communication makes UAVs susceptible toundesirablepassive attacks suchas eavesdroppingor jamming.Recently,the inefficiencyof traditional cryptography-based techniques has led to the addition of Physical Layer Security(PLS).This study focuses on the advanced PLS method for passive eavesdropping in UAV-aided vehicular environments,proposing a solution to complement the conventional cryptography approach.Initially,we present a performance analysis of first-order secrecy metrics in 6G-enabled UAV systems,namely hybrid outage probability(HOP)and secrecy outage probability(SOP)over 2×2 Nakagami-m channels.Later,we propose a novel technique for mitigating passive eavesdropping,which considers first-order secrecy metrics as an optimization problem and determines their lower and upper bounds.Finally,we conduct an analysis of bounded HOP and SOP using the interactive Nakagami-m channel,considering the multiple-input-multiple-output configuration of the UAV system.The findings indicate that 2×2 Nakagami-mis a suitable fadingmodel under constant velocity for trustworthy receivers and eavesdroppers.The results indicate that UAV mobility has some influence on an eavesdropper’s intrusion during line-of-sight-enabled communication and can play an important role in improving security against passive eavesdroppers.
基金supported by the National Natural Science Foundation of China(32325049,U22A20529,32303000)Zhejiang Provincial Natural Science Foundation(LQ24C190009)+1 种基金Ningbo Natural Science Foundation(2022J192)Zhejiang Provincial Top Key Discipline of Biological Engineering(1741000592)。
文摘In reptiles,such as the red-eared slider turtle(Trachemys scripta elegans),gonadal sex determination is highly dependent on the environmental temperature during embryonic stages.This complex process,which leads to differentiation into either testes or ovaries,is governed by the finely tuned expression of upstream genes,notably the testis-promoting gene Dmrt1 and the ovary-promoting gene Foxl2.Recent studies have identified epigenetic regulation as a crucial factor in testis development,with the H3K27me3 demethylase KDM6B being essential for Dmrt1 expression in T.s.elegans.However,whether KDM6B alone can induce testicular differentiation remains unclear.In this study,we found that overexpression of Kdm6b in T.s.elegans embryos induced the male development pathway,accompanied by a rapid increase in the gonadal expression of Dmrt1 at 31°C,a temperature typically resulting in female development.Notably,this sex reversal could be entirely rescued by Dmrt1 knockdown.These findings demonstrate that Kdm6b is sufficient for commitment to the male pathway,underscoring its role as a critical epigenetic regulator in the sex determination of the red-eared slider turtle.
文摘In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.
基金Supported by the Ministry of Science and Higher Education of the Russian Federation,No.075-15-2022-301.
文摘BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.
文摘Volatile organic compounds(VOC)gas detection devices based on semiconductor sensors have become a common method due to their low cost,simple principle,and small size.However,with the continuous development of materials science,various new materials have been applied in the fabrication of gas sensors,but these new materials have more stringent requirements for operating temperature,which cannot be met by existing sensor modules on the market.Therefore,this paper proposes a temperature-adjustable sensor module and designs an environmental monitoring system based on the STM32F103RET6 microprocessor.This system primarily utilizes multiple semiconductor gas sensors to monitor and record the concentrations of various harmful gases in different environments.It can also monitor real-time temperature,humidity,and latitude and longitude in the current environment,and upload the data to the Internet of Things via 4G communication.This system has the advantages of small size,portability,and low cost.Experimental results show that the sensor module can achieve precise control of operating temperature to a certain extent,with an average temperature error of approximately 3%.The monitoring system demonstrates a certain level of accuracy in detecting target gases and can promptly upload the data to a cloud platform for storage and processing.A comparison with professional testing equipment shows that the sensitivity curves of each sensor exhibit similarity.This study provides engineering and technical references for the application of VOC gas sensors.
基金Supported by The European Union-NextGenerationEU,Through The National Recov-ery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.
