Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B(CHB).However,antiviral resistance remains an important challenge for long-term CHB therapy.All of the clinical...Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B(CHB).However,antiviral resistance remains an important challenge for long-term CHB therapy.All of the clinically available oral antiviral agents are nucleoside or nucleotide analogues that target the activity of viral reverse transcriptase(RT),and all are reported to have resistant mutations.Since the hepatitis B virus(HBV)RT,like other viral polymerases,lacks proofreading activity,the emergence of drug-resistance occurs readily under selective pressure from the administration of antiviral agents.The molecular diagnosis of drug-resistant HBV is based on sequence variations,and current diagnostic methods include sequencing,restriction fragment polymorphism analysis,and hybridization.Here,we will discuss the currently available molecular diagnosis tools,in vitro phenotypic assays for validation of drug-resistant HBV,and treatment options for drug-resistant HBV.展开更多
Noise is known that the physical risk factors defined as any unwanted sound. It can induce the health problems such as hearing loss or annoyance. The objective of this study was to assess the occupational noise exposu...Noise is known that the physical risk factors defined as any unwanted sound. It can induce the health problems such as hearing loss or annoyance. The objective of this study was to assess the occupational noise exposure of nine groups for twenty peoples according to job characteristics and to compare the noise level by different variables. Personal noise levels were measured for three times using by dosimeters for each participant in Korea. The mean time weighted average noise level (TWA) of total was 73.2 ± 11.5 dBA by American conference of governmental industrial hygienists (ACGIH) standard. Especially, Korean classical music students were highly exposed to 93.2 ± 6.2 dBA but, office workers were 63.2 ± 6.6 dBA. In case of peak sound pressure level (Lpeak), Korean classical music students and firefighters were exposed to the highest level of 151.8 dBC and 145.8 dBC during playing and dispatching, respectively. The analysis of noise level showed that Leq had positive correlations between TWA by ministry of employment and labour (MOEL) (r = 0.98, p < 0.01) and TWA by ACGIH (r = 0.98, p < 0.01). Unlikely other groups, the noise exposure level of the Korean classical music students were exceeded the ACGIH standard. These results suggest that Korean classical music students were exposed high noise level and some solutions are need to reduce the noise exposure level such as using hearing protect device.展开更多
Background: The temperature preferences of cold-blooded animals are different for different groups of animals and are closely related to their evolutionary status and level of adaptive capabilities. The range of prefe...Background: The temperature preferences of cold-blooded animals are different for different groups of animals and are closely related to their evolutionary status and level of adaptive capabilities. The range of preferred temperatures for reptiles (28°C - 32°C) coincides with the zone of temperature-dependent increase in the rate of the M-cholinergic reaction in the brain, which was previously found in warm-blooded neurons. The growth of the M-cholinergic process contributes to the transition of adaptive behavior to a higher level. Of the cold-blooded, only reptiles actively use thermoregulatory behavior as a tool to achieve a temperature optimum. This paper is devoted to the study of the behavior of red-eared turtles aimed at reaching the range of preferred temperatures. Temperature conditions necessary for the survival of different groups of cold-blooded animals are compared and the reason for temperature preferences is discussed. Methods: The behavior of turtles was studied under conditions of variable solar radiation and in a 3-section terrarium with gradual temperature ranges: 23°C - 24°C;28°C - 31°C and 45°C - 50°C. Results: It was found that prolonged (up to 1.5 hours) heating at a temperature of 45°C - 50°C was the best way to achieve the preferred temperatures. This method of heating results in increasing the temperature of the shell to an average of 37°C, followed by a very slow decrease during 4 - 6 hours within the limits that closely coincided with the preferred level. Conclusion: The results obtained demonstrate that the main function of the turtle shell is to accumulate heat and keep it for a long time in a variable climate. The preferred temperature achieved in this case is necessary for the temperature-dependent transition of the rate of the M-cholinergic reaction in the brain to a higher level, which creates more significant adaptive capabilities. The temperature range of the M-cholinergic process has two inflection points at 27°C - 29°C and 34°C - 36°C. In accordance with these values, the temperature preferences of cold-blooded animals are divided into three groups: 0°C - 28°C (fish and amphibians);28°C - 32°C (reptiles) and 34°C - 36°C (dinosaurs). Different ranges of preferred temperatures correspond to three stages of adaptive development.展开更多
The purpose of this study was to investigate the differences in the sensory threshold between the paretic and nonparetic sides of hemiplegic patients. 28 patients who were hemiplegic post-stroke (14 men and 14 women) ...The purpose of this study was to investigate the differences in the sensory threshold between the paretic and nonparetic sides of hemiplegic patients. 28 patients who were hemiplegic post-stroke (14 men and 14 women) participated in the electrical sensory and pain thresholds study;22 patients who were hemiplegic post-stroke (13 men, 9 women) participated in a study measureing the sensory threshold with light touch. Electrical sensory and pain thresholds were measured in the forearm via transcutaneous electrical nerve stimulation. The light-touch threshold was measured in the forearm using monofilaments. The light-touch, electrical sensory, and pain thresholds for the paretic side were significantly higher than for the nonparetic side in our population, respectively. In both the nonparetic and paretic sides, the male group generally showed higher thresholds for pain and sensation than did the female group. These results suggest that the different evaluations of sensory thresholds performed in this study for healthy rehabilitation will be a valuable clinical tool in hemiplegic patients after stroke.展开更多
Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize ...Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize neuroscientifically-informed strategies of postlesional rehabilitation,and ultimately to develop innovative neuro-regenerative therapies.The term‘plasticity’,initially referring to the intrinsic propensity of neurons to modulate their synaptic transmission in a learning situation,was progressively transposed to brain injury research and clinical neurosciences.Indeed,in the event of brain damage,adaptive mechanisms of compensation allow a partial reshaping of the structure and activities of the central nervous system,thus permitting to some extent the maintenance of brain functions.展开更多
Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have...Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons.However,approximately 30%of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70%of patients can be alleviated but not completely removed by the current medications.Thus,new strategies for the treatment of epilepsy are in urgent demand.Over the past decades,with the increase in knowledge on the role of glia in the genesis and development of epilepsy,glial cells are receiving renewed attention.In a normal brain,glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function.In epilepsy,however,the supportive roles of glial cells are compromised,and their interaction with neurons is altered,which disrupts brain function.In this review,we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity,with the major focus on the dysfunction of astroglial potassium channels,water channels,gap junctions,glutamate transporters,purinergic signaling,synaptogenesis,on the roles of microglial inflammatory cytokines,microglia-astrocyte interactions in epilepsy,and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain.These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.展开更多
Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarctio...Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction.Currently,it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration.To understand how interstitial cells behave during this process,we performed single-cell RNA sequencing of regenerating zebrafish hearts.Using a combination of immunohistochemistry,chemical inhibition,and novel transgenic animals,we were able to investigate the role of cell type-specific mechanisms during cardiac regeneration.This approach allowed us to identify a number of important regenerative processes within the interstitial cell populations.Here,we provide detailed insight into how interstitial cells behave during cardiac regeneration,which will serve to increase our understanding of how this process could eventually be induced in humans.展开更多
In contrast to mammals and birds,fish display an amazing diversity of genetic sex determination systems,with frequent changes during evolution possibly associated with the emergence of new sex chromosomes and sex-dete...In contrast to mammals and birds,fish display an amazing diversity of genetic sex determination systems,with frequent changes during evolution possibly associated with the emergence of new sex chromosomes and sex-determining genes.To better understand the molecular and evolutionary mechanisms driving this diversity,several fish models are studied in parallel.Besides the medaka(Oryzias latipes Temminck and Schlegel,1846)for which the master sex-determination gene has been identified,one of the most advanced models for studying sex determination is the Southern platyfish(Xiphophorus maculatus,Günther 1966).Xiphophorus maculatus belongs to the Poeciliids,a family of live-bearing freshwater fish,including platyfish,swordtails and guppies that perfectly illustrates the diversity of genetic sex-determination mechanisms observed in teleosts.For X.maculatus,bacterial artificial chro-mosome contigs covering the sex-determination region of the X and Y sex chromosomes have been constructed.Initial molecular analysis demonstrated that the sex-determination region is very unstable and frequently undergoes duplications,deletions,inversions and other rearrangements.Eleven gene candidates linked to the master sex-determining gene have been identified,some of them corresponding to pseudogenes.All putative genes are present on both the X and the Y chromosomes,suggesting a poor degree of differentiation and a young evolutionary age for platyfish sex chromosomes.When compared with other fish and tetrapod genomes,syntenies were detected only with autosomes.This observation supports an independent origin of sex chromosomes,not only in different vertebrate lineages but also between different fish species.展开更多
Dear Editor, Plants secrete nectar to attract mutualistic animals, which predominantly function as pollinators, as in the case of flo- ral nectar, or defenders against herbivores, as in the case of extrafloral nectar...Dear Editor, Plants secrete nectar to attract mutualistic animals, which predominantly function as pollinators, as in the case of flo- ral nectar, or defenders against herbivores, as in the case of extrafloral nectar （Nicolson et al., 2007）. Because nectars usu- ally represent aqueous solutions containing sugars and other nutrient metabolites （Baker and Baker, 1983）, they are sus- ceptible to infestation by microbial organisms, which can use the nectar-secreting tissues as entry sites to infect the plant. Nectar-secreting tissues thus require an efficient shield against pathogen infections. To date, our knowledge about the way that plants protect their nectar from microorganisms is rather limited. Several reports have focused on ＇defensive chemicals＇,展开更多
文摘Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B(CHB).However,antiviral resistance remains an important challenge for long-term CHB therapy.All of the clinically available oral antiviral agents are nucleoside or nucleotide analogues that target the activity of viral reverse transcriptase(RT),and all are reported to have resistant mutations.Since the hepatitis B virus(HBV)RT,like other viral polymerases,lacks proofreading activity,the emergence of drug-resistance occurs readily under selective pressure from the administration of antiviral agents.The molecular diagnosis of drug-resistant HBV is based on sequence variations,and current diagnostic methods include sequencing,restriction fragment polymorphism analysis,and hybridization.Here,we will discuss the currently available molecular diagnosis tools,in vitro phenotypic assays for validation of drug-resistant HBV,and treatment options for drug-resistant HBV.
文摘Noise is known that the physical risk factors defined as any unwanted sound. It can induce the health problems such as hearing loss or annoyance. The objective of this study was to assess the occupational noise exposure of nine groups for twenty peoples according to job characteristics and to compare the noise level by different variables. Personal noise levels were measured for three times using by dosimeters for each participant in Korea. The mean time weighted average noise level (TWA) of total was 73.2 ± 11.5 dBA by American conference of governmental industrial hygienists (ACGIH) standard. Especially, Korean classical music students were highly exposed to 93.2 ± 6.2 dBA but, office workers were 63.2 ± 6.6 dBA. In case of peak sound pressure level (Lpeak), Korean classical music students and firefighters were exposed to the highest level of 151.8 dBC and 145.8 dBC during playing and dispatching, respectively. The analysis of noise level showed that Leq had positive correlations between TWA by ministry of employment and labour (MOEL) (r = 0.98, p < 0.01) and TWA by ACGIH (r = 0.98, p < 0.01). Unlikely other groups, the noise exposure level of the Korean classical music students were exceeded the ACGIH standard. These results suggest that Korean classical music students were exposed high noise level and some solutions are need to reduce the noise exposure level such as using hearing protect device.
文摘Background: The temperature preferences of cold-blooded animals are different for different groups of animals and are closely related to their evolutionary status and level of adaptive capabilities. The range of preferred temperatures for reptiles (28°C - 32°C) coincides with the zone of temperature-dependent increase in the rate of the M-cholinergic reaction in the brain, which was previously found in warm-blooded neurons. The growth of the M-cholinergic process contributes to the transition of adaptive behavior to a higher level. Of the cold-blooded, only reptiles actively use thermoregulatory behavior as a tool to achieve a temperature optimum. This paper is devoted to the study of the behavior of red-eared turtles aimed at reaching the range of preferred temperatures. Temperature conditions necessary for the survival of different groups of cold-blooded animals are compared and the reason for temperature preferences is discussed. Methods: The behavior of turtles was studied under conditions of variable solar radiation and in a 3-section terrarium with gradual temperature ranges: 23°C - 24°C;28°C - 31°C and 45°C - 50°C. Results: It was found that prolonged (up to 1.5 hours) heating at a temperature of 45°C - 50°C was the best way to achieve the preferred temperatures. This method of heating results in increasing the temperature of the shell to an average of 37°C, followed by a very slow decrease during 4 - 6 hours within the limits that closely coincided with the preferred level. Conclusion: The results obtained demonstrate that the main function of the turtle shell is to accumulate heat and keep it for a long time in a variable climate. The preferred temperature achieved in this case is necessary for the temperature-dependent transition of the rate of the M-cholinergic reaction in the brain to a higher level, which creates more significant adaptive capabilities. The temperature range of the M-cholinergic process has two inflection points at 27°C - 29°C and 34°C - 36°C. In accordance with these values, the temperature preferences of cold-blooded animals are divided into three groups: 0°C - 28°C (fish and amphibians);28°C - 32°C (reptiles) and 34°C - 36°C (dinosaurs). Different ranges of preferred temperatures correspond to three stages of adaptive development.
文摘The purpose of this study was to investigate the differences in the sensory threshold between the paretic and nonparetic sides of hemiplegic patients. 28 patients who were hemiplegic post-stroke (14 men and 14 women) participated in the electrical sensory and pain thresholds study;22 patients who were hemiplegic post-stroke (13 men, 9 women) participated in a study measureing the sensory threshold with light touch. Electrical sensory and pain thresholds were measured in the forearm via transcutaneous electrical nerve stimulation. The light-touch threshold was measured in the forearm using monofilaments. The light-touch, electrical sensory, and pain thresholds for the paretic side were significantly higher than for the nonparetic side in our population, respectively. In both the nonparetic and paretic sides, the male group generally showed higher thresholds for pain and sensation than did the female group. These results suggest that the different evaluations of sensory thresholds performed in this study for healthy rehabilitation will be a valuable clinical tool in hemiplegic patients after stroke.
文摘Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize neuroscientifically-informed strategies of postlesional rehabilitation,and ultimately to develop innovative neuro-regenerative therapies.The term‘plasticity’,initially referring to the intrinsic propensity of neurons to modulate their synaptic transmission in a learning situation,was progressively transposed to brain injury research and clinical neurosciences.Indeed,in the event of brain damage,adaptive mechanisms of compensation allow a partial reshaping of the structure and activities of the central nervous system,thus permitting to some extent the maintenance of brain functions.
基金supported by the Ministry of Education,Science and Technological Development of Republic of Serbia,Nos.451-03-68/2022-14/200007 and 451-03-68/2022-14/200053(to LN and JBP),Grants from European Commission(H2020 MSCA-ITN EU-GliaPhD No.72205)(to PN)Agence Nationale de la Recherche,Nos.ANR-19-CE16-0018-03 and ANR-20CE16-0003-02(to PN)+1 种基金Grants from Science and Technology Department of Zhejiang Province,China,No.2021RC051(to WS)Scientific Research Foundation for Returned Scholars of Hangzhou City,China,No.2019(to WS).
文摘Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons.However,approximately 30%of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70%of patients can be alleviated but not completely removed by the current medications.Thus,new strategies for the treatment of epilepsy are in urgent demand.Over the past decades,with the increase in knowledge on the role of glia in the genesis and development of epilepsy,glial cells are receiving renewed attention.In a normal brain,glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function.In epilepsy,however,the supportive roles of glial cells are compromised,and their interaction with neurons is altered,which disrupts brain function.In this review,we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity,with the major focus on the dysfunction of astroglial potassium channels,water channels,gap junctions,glutamate transporters,purinergic signaling,synaptogenesis,on the roles of microglial inflammatory cytokines,microglia-astrocyte interactions in epilepsy,and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain.These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.
基金MRI is supported by the French National Research Agency(ANR-10-INBS-04,‘Investments for the future')MGX acknowledges financial support from France Génomique National infrastrusture,funded as part of Investissement d‘Avenir’program managed by Agence National pour la Recherche(ANR-10-INBS-09)+2 种基金The Jopling lab is part of the Laboratory of Excellence lon Channel Science and Therapeutics supported by a grant from the ANRWork in the Jopling lab is supported by grants from the‘la Fondation Leducq'and from the ANR(ANR-20-CE14-003 MetabOx-Heart)A.H.was supported by European Research Area Network on Cardiovascular Diseases(ERA-CVD,ANR-18-ECVD-0006)awarded to T.M.-M.
文摘Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction.Currently,it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration.To understand how interstitial cells behave during this process,we performed single-cell RNA sequencing of regenerating zebrafish hearts.Using a combination of immunohistochemistry,chemical inhibition,and novel transgenic animals,we were able to investigate the role of cell type-specific mechanisms during cardiac regeneration.This approach allowed us to identify a number of important regenerative processes within the interstitial cell populations.Here,we provide detailed insight into how interstitial cells behave during cardiac regeneration,which will serve to increase our understanding of how this process could eventually be induced in humans.
文摘In contrast to mammals and birds,fish display an amazing diversity of genetic sex determination systems,with frequent changes during evolution possibly associated with the emergence of new sex chromosomes and sex-determining genes.To better understand the molecular and evolutionary mechanisms driving this diversity,several fish models are studied in parallel.Besides the medaka(Oryzias latipes Temminck and Schlegel,1846)for which the master sex-determination gene has been identified,one of the most advanced models for studying sex determination is the Southern platyfish(Xiphophorus maculatus,Günther 1966).Xiphophorus maculatus belongs to the Poeciliids,a family of live-bearing freshwater fish,including platyfish,swordtails and guppies that perfectly illustrates the diversity of genetic sex-determination mechanisms observed in teleosts.For X.maculatus,bacterial artificial chro-mosome contigs covering the sex-determination region of the X and Y sex chromosomes have been constructed.Initial molecular analysis demonstrated that the sex-determination region is very unstable and frequently undergoes duplications,deletions,inversions and other rearrangements.Eleven gene candidates linked to the master sex-determining gene have been identified,some of them corresponding to pseudogenes.All putative genes are present on both the X and the Y chromosomes,suggesting a poor degree of differentiation and a young evolutionary age for platyfish sex chromosomes.When compared with other fish and tetrapod genomes,syntenies were detected only with autosomes.This observation supports an independent origin of sex chromosomes,not only in different vertebrate lineages but also between different fish species.
文摘Dear Editor, Plants secrete nectar to attract mutualistic animals, which predominantly function as pollinators, as in the case of flo- ral nectar, or defenders against herbivores, as in the case of extrafloral nectar （Nicolson et al., 2007）. Because nectars usu- ally represent aqueous solutions containing sugars and other nutrient metabolites （Baker and Baker, 1983）, they are sus- ceptible to infestation by microbial organisms, which can use the nectar-secreting tissues as entry sites to infect the plant. Nectar-secreting tissues thus require an efficient shield against pathogen infections. To date, our knowledge about the way that plants protect their nectar from microorganisms is rather limited. Several reports have focused on ＇defensive chemicals＇,
