First the research is conducted on the design of the two-phase sinusoidal power clock generator in this paper. Then the design of the new adiabatic logic circuit adopting the two-phase sinusoidal power clocks--Clocked...First the research is conducted on the design of the two-phase sinusoidal power clock generator in this paper. Then the design of the new adiabatic logic circuit adopting the two-phase sinusoidal power clocks--Clocked Transmission Gate Adiabatic Logic （CTGAL） circuit is presented. This circuit makes use of the clocked transmission gates to sample the input signals, then the output loads are charged and discharged in a fully adiabatic manner by using bootstrapped N-Channel Metal Oxide Semiconductor （NMOS） and Complementary Metal Oxide Semiconductor （CMOS） latch structure. Finally, with the parameters of Taiwan Semiconductor Manufacturing Company （TSMC） 0.25um CMOS device, the transient energy consumption of CTGAL, Bootstrap Charge-Recovery Logic （BCRL） and Pass-transistor Adiabatic Logic （PAL） including their clock generators is simulated. The simulation result indicates that CTGAL circuit has the characteristic of remarkably low energy consumption.展开更多
Clock synchronization has important applications in multi-agent collaboration(such as drone light shows,intelligent transportation systems,and game AI),group decision-making,and emergency rescue operations.Synchroniza...Clock synchronization has important applications in multi-agent collaboration(such as drone light shows,intelligent transportation systems,and game AI),group decision-making,and emergency rescue operations.Synchronization method based on pulse-coupled oscillators(PCOs)provides an effective solution for clock synchronization in wireless networks.However,the existing clock synchronization algorithms in multi-agent ad hoc networks are difficult to meet the requirements of high precision and high stability of synchronization clock in group cooperation.Hence,this paper constructs a network model,named DAUNet(unsupervised neural network based on dual attention),to enhance clock synchronization accuracy in multi-agent wireless ad hoc networks.Specifically,we design an unsupervised distributed neural network framework as the backbone,building upon classical PCO-based synchronization methods.This framework resolves issues such as prolonged time synchronization message exchange between nodes,difficulties in centralized node coordination,and challenges in distributed training.Furthermore,we introduce a dual-attention mechanism as the core module of DAUNet.By integrating a Multi-Head Attention module and a Gated Attention module,the model significantly improves information extraction capabilities while reducing computational complexity,effectively mitigating synchronization inaccuracies and instability in multi-agent ad hoc networks.To evaluate the effectiveness of the proposed model,comparative experiments and ablation studies were conducted against classical methods and existing deep learning models.The research results show that,compared with the deep learning networks based on DASA and LSTM,DAUNet can reduce the mean normalized phase difference(NPD)by 1 to 2 orders of magnitude.Compared with the attention models based on additive attention and self-attention mechanisms,the performance of DAUNet has improved by more than ten times.This study demonstrates DAUNet’s potential in advancing multi-agent ad hoc networking technologies.展开更多
The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given th...The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.展开更多
The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA P...The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE4(RhSPL4)positively regulates flowering time in rose.Transient silencing or overexpression transgenic rose plants of RhSPL4 exhibited delayed or early flowering,respectively.Analysis of transcriptome data from transgenic lines overexpressing RhSPL4 compared to the wild type indicated that differentially expressed genes were significantly enriched in the circadian rhythm pathway.Among the proteins encoded by these genes,RhSPL4 binds to the promoter of PSEUDO-RESPONSE REGULATOR 5-LIKE(RhPRR5L),as revealed in yeast one-hybrid,dual-Luciferase/Renilla luciferase reporter,chromatin immunoprecipitation-quantitative PCR and electrophoretic mobility shift assay.Furthermore,RhSPL4 specifically binds to the478 to441 bp region of the RhPRR5L promoter and activates its transcription.The silencing of RhPRR5L delayed flowering time in rose,resembling the phenotype of RhSPL4-silenced plants.Together,these results indicate that the RhSPL4-RhPRR5L module positively regulates flowering time in rose,laying the foundation for the genetic improvement of flowering time in this important horticultural crop.展开更多
Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals an...Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.展开更多
Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were ra...Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.展开更多
The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately...The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately 24-h cycle of endocrine and metabolic rhythms within cells and tissues.While circadian clocks regulate metabolic processes and related physiology,emerging evidence indicates that metabolism and circadian rhythm are intimately intertwined.In this review,we highlight the concept of metabolites,including lipids and other polar metabolites generated from intestinal microbial metabolism and nutrient intake,as time cues that drive changes in circadian rhythms,which in turn influence metabolism and aging.Furthermore,we discuss the roles of functional metabolites as circadian cues,paving a new direction on potential intervention targets of circadian disruption,pathological aging,as well as metabolic diseases that are clinically important.展开更多
One sunny morning,students are in a classroom Jake shows his smart watch,"It tells time,the heart rate,and the weather!""It's easy to know the time now,"Ms.Lee walks in,with a smile on her face...One sunny morning,students are in a classroom Jake shows his smart watch,"It tells time,the heart rate,and the weather!""It's easy to know the time now,"Ms.Lee walks in,with a smile on her face."But how did people know the time in ancient times?"展开更多
A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulat...A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulation.Epigenetic clocks,which estimate biological age based on DNA methylation patterns,have been extensively utilized to evaluate general health status and the risk of various diseases.Despite their broad application,the utility of epigenetic clocks in assessing female reproductive health remains only partially characterized.This minireview consolidates recent advancements in the application of epigenetic clocks to evaluate the functional status of the female reproductive system.The objective is to investigate their potential for quantifying and predicting the biological age of reproductive tissues,thereby establishing a theoretical basis for clinical applications in reproductive medicine.To date,no comprehensive minireview has systematically examined multi-tissue epigenetic clock models in the context of female reproductive aging,positioning this minireview as a novel contribution to the field.展开更多
问题导读下课后,李华找到英语老师,带着疑惑问道:“老师,您上次给我的作文写的批注是‘Selfdoubt gnawed at my confidence.’这个句子中的动词过于夸张,并且‘The clock watched me struggle.’中的拟人手法运用不当。这中间的界限到...问题导读下课后,李华找到英语老师,带着疑惑问道:“老师,您上次给我的作文写的批注是‘Selfdoubt gnawed at my confidence.’这个句子中的动词过于夸张,并且‘The clock watched me struggle.’中的拟人手法运用不当。这中间的界限到底在哪里呢?在读后续写中,我该如何使用无灵主语,让语言更加生动、自然呢?”展开更多
The plant circadian clock temporally drives gene expression throughout the day and coordinates various physiological processes with diurnal environmental changes. It is essential for conferring plant fitness and compe...The plant circadian clock temporally drives gene expression throughout the day and coordinates various physiological processes with diurnal environmental changes. It is essential for conferring plant fitness and competitive advantages to survive and thrive under natural conditions through the circadian control of gene transcription. Chinese cabbage(Brassica rapa ssp. pekinensis) is an economically important vegetable crop worldwide, although there is little information concerning its circadian clock system. Here we found that gene expression patterns are affected bycircadian oscillators at both the transcriptional and post-transcriptional levels in Chinese cabbage. Time-course RNA-seq analyses were conducted on two short-period lines(SPcc-1 and SPcc-2) and two long-period lines(LPcc-1 and LPcc-2) under constant light. The results showed that 32.7–50.5% of the genes were regulated bythe circadian oscillator and the expression peaks of cycling genes appeared earlier in short-period lines than long-period lines. In addition, approximately 250 splicing events exhibited circadian regulation, with intron retention(IR) accounting for a large proportion. Rhythmically spliced genes included the clock genes LATE ELONGATEDHYPOCOTYL(BrLHY), REVEILLE 2(BrRVE2) and EARLY FLOWERING 3(BrELF3). We also found that thecircadian oscillator could notably influence the diurnal expression patterns of genes that are associated with glucose metabolism via photosynthesis, the Calvin cycle and the tricarboxylic acid(TCA) cycle at both the transcriptional andpost-transcriptional levels. The collective results of this study demonstrate that circadian-regulated physiological processes contribute to Chinese cabbage growth and development.展开更多
The circadian system of mammals is composed of a hierarchical network of oscillators,including a core clock and peripheral clocks.The core clock receives an external photic signal and transmits it to the peripheral cl...The circadian system of mammals is composed of a hierarchical network of oscillators,including a core clock and peripheral clocks.The core clock receives an external photic signal and transmits it to the peripheral clocks,which,in turn,feed back to the core clock.Aging affects various functions of organisms including the circadian system.Entrainment displays the adaptability of the circadian system to changes in the external environment.However,there is currently no systematic study on the effects of aging on the entrainment capability.To explore the influencing mechanism,we develop a mathematical model of two populations of Goodwin oscillators,which represent the core clock and peripheral clocks.Based on numerical simulations,we conduct a detailed study on the impact of three aging-related factors on the entrainment capability represented by the entrainment range,entrainment time,and entrainment phase.The results indicate that the decrease in the sensitivity of suprachiasmatic nucleus(SCN)to light and the coupling strength from the SCN to the peripheral clocks due to aging increase the phase difference between the core and peripheral clocks,narrow the entrainment range,and prolong the entrainment time.A reduction in the coupling strength within the SCN has little effect on the three aspects mentioned above but increases the entrainment phase.Overall,aging reduces the circadian system's adaptability to the external environment,and the increased entrainment phase may lead to corresponding sleep problems.We also show that modulating the internal coupling strength in the peripheral clocks can mitigate aging effects;this provides an idea for using peripheral clocks to adjust the core clock,while also revealing new insights into the interaction between aging and the elasticity of the circadian system.This mechanism provides theoretical support for treating or alleviating circadian system disorders or sleep problems caused by aging.展开更多
During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many...During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many edible plants,can ameliorate obesity by activating adipose tissue browning,but its effect on circadian clock in this process remains poorly understood.Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet(HFD)-fed wild-type(WT)mice.Moreover,dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period,which was similar to the LU-increased hepatic PER2 expressions.Hepatic peroxisome proliferators-activated receptorsα(PPARα)/recombinant retinoid X receptorα(RXRα)/fibroblast growth factor 21(FGF21)pathway was rhythmically elevated by dietary LU in HFD-fed WT mice,whereas the promotion was inhibited in Per2^(-/-)mice.Meanwhile,Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice.Further,LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^(-/-)mice.Taken together,the deletion of the core clock component Per2 impedes LUinduced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice,providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.展开更多
基金Supported by the National Natural Science Foundation of China (No. 60273093)the Natural Science Foundation of Zhejinag Province(No. Y104135) the Student Sci-entific Research Foundation of Ningbo university (No.C38).
文摘First the research is conducted on the design of the two-phase sinusoidal power clock generator in this paper. Then the design of the new adiabatic logic circuit adopting the two-phase sinusoidal power clocks--Clocked Transmission Gate Adiabatic Logic （CTGAL） circuit is presented. This circuit makes use of the clocked transmission gates to sample the input signals, then the output loads are charged and discharged in a fully adiabatic manner by using bootstrapped N-Channel Metal Oxide Semiconductor （NMOS） and Complementary Metal Oxide Semiconductor （CMOS） latch structure. Finally, with the parameters of Taiwan Semiconductor Manufacturing Company （TSMC） 0.25um CMOS device, the transient energy consumption of CTGAL, Bootstrap Charge-Recovery Logic （BCRL） and Pass-transistor Adiabatic Logic （PAL） including their clock generators is simulated. The simulation result indicates that CTGAL circuit has the characteristic of remarkably low energy consumption.
文摘Clock synchronization has important applications in multi-agent collaboration(such as drone light shows,intelligent transportation systems,and game AI),group decision-making,and emergency rescue operations.Synchronization method based on pulse-coupled oscillators(PCOs)provides an effective solution for clock synchronization in wireless networks.However,the existing clock synchronization algorithms in multi-agent ad hoc networks are difficult to meet the requirements of high precision and high stability of synchronization clock in group cooperation.Hence,this paper constructs a network model,named DAUNet(unsupervised neural network based on dual attention),to enhance clock synchronization accuracy in multi-agent wireless ad hoc networks.Specifically,we design an unsupervised distributed neural network framework as the backbone,building upon classical PCO-based synchronization methods.This framework resolves issues such as prolonged time synchronization message exchange between nodes,difficulties in centralized node coordination,and challenges in distributed training.Furthermore,we introduce a dual-attention mechanism as the core module of DAUNet.By integrating a Multi-Head Attention module and a Gated Attention module,the model significantly improves information extraction capabilities while reducing computational complexity,effectively mitigating synchronization inaccuracies and instability in multi-agent ad hoc networks.To evaluate the effectiveness of the proposed model,comparative experiments and ablation studies were conducted against classical methods and existing deep learning models.The research results show that,compared with the deep learning networks based on DASA and LSTM,DAUNet can reduce the mean normalized phase difference(NPD)by 1 to 2 orders of magnitude.Compared with the attention models based on additive attention and self-attention mechanisms,the performance of DAUNet has improved by more than ten times.This study demonstrates DAUNet’s potential in advancing multi-agent ad hoc networking technologies.
基金supported by a grant from the French Society of Sleep Research and Medicine(to LS)The China Scholarship Council(to HL)The CNRS,INSERM,Claude Bernard University Lyon1(to LS)。
文摘The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.
基金supported by Yunnan Province Agricultural Joint Key Project(Grant No.202401BD070001-016)the National Natural Science Foundation of China(Grant No.32202530)+3 种基金Talent Introduction and Training Project of Yunnan Academy of Agricultural Sciences(Grant No.2024RCYP-09)Fundamental Research Project(Grant No.202401CF070046)Xingdian Talent support program(XDYC-QNRC-2023-0457)Yunnan Technology Innovation Center of Flower Technique.
文摘The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE4(RhSPL4)positively regulates flowering time in rose.Transient silencing or overexpression transgenic rose plants of RhSPL4 exhibited delayed or early flowering,respectively.Analysis of transcriptome data from transgenic lines overexpressing RhSPL4 compared to the wild type indicated that differentially expressed genes were significantly enriched in the circadian rhythm pathway.Among the proteins encoded by these genes,RhSPL4 binds to the promoter of PSEUDO-RESPONSE REGULATOR 5-LIKE(RhPRR5L),as revealed in yeast one-hybrid,dual-Luciferase/Renilla luciferase reporter,chromatin immunoprecipitation-quantitative PCR and electrophoretic mobility shift assay.Furthermore,RhSPL4 specifically binds to the478 to441 bp region of the RhPRR5L promoter and activates its transcription.The silencing of RhPRR5L delayed flowering time in rose,resembling the phenotype of RhSPL4-silenced plants.Together,these results indicate that the RhSPL4-RhPRR5L module positively regulates flowering time in rose,laying the foundation for the genetic improvement of flowering time in this important horticultural crop.
基金Supported by American Diabetes AssociationAmerican Heart Association+3 种基金NIH NIEHSNIH NIANIH NINDSand NIH ARRA.
文摘Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.
文摘Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.
基金supported by grants from the Chinese Academy of Sciences(XDB39050800)the Major Project of Guangzhou National Laboratory(GZNL2024A03013)the National Natural Science Foundation of China(92357308 and 32321004)。
文摘The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately 24-h cycle of endocrine and metabolic rhythms within cells and tissues.While circadian clocks regulate metabolic processes and related physiology,emerging evidence indicates that metabolism and circadian rhythm are intimately intertwined.In this review,we highlight the concept of metabolites,including lipids and other polar metabolites generated from intestinal microbial metabolism and nutrient intake,as time cues that drive changes in circadian rhythms,which in turn influence metabolism and aging.Furthermore,we discuss the roles of functional metabolites as circadian cues,paving a new direction on potential intervention targets of circadian disruption,pathological aging,as well as metabolic diseases that are clinically important.
文摘One sunny morning,students are in a classroom Jake shows his smart watch,"It tells time,the heart rate,and the weather!""It's easy to know the time now,"Ms.Lee walks in,with a smile on her face."But how did people know the time in ancient times?"
文摘A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulation.Epigenetic clocks,which estimate biological age based on DNA methylation patterns,have been extensively utilized to evaluate general health status and the risk of various diseases.Despite their broad application,the utility of epigenetic clocks in assessing female reproductive health remains only partially characterized.This minireview consolidates recent advancements in the application of epigenetic clocks to evaluate the functional status of the female reproductive system.The objective is to investigate their potential for quantifying and predicting the biological age of reproductive tissues,thereby establishing a theoretical basis for clinical applications in reproductive medicine.To date,no comprehensive minireview has systematically examined multi-tissue epigenetic clock models in the context of female reproductive aging,positioning this minireview as a novel contribution to the field.
文摘问题导读下课后,李华找到英语老师,带着疑惑问道:“老师,您上次给我的作文写的批注是‘Selfdoubt gnawed at my confidence.’这个句子中的动词过于夸张,并且‘The clock watched me struggle.’中的拟人手法运用不当。这中间的界限到底在哪里呢?在读后续写中,我该如何使用无灵主语,让语言更加生动、自然呢?”
基金supported by the Science and Technology Program of Hebei Province, China (236Z2903G)the Innovative Research Group Project of Hebei Natural Science Foundation, China (C2024204246)+1 种基金the Hebei International Joint Research Center of Vegetable Functional Genomicsthe International Joint R&D Center of Hebei Province in Modern Agricultural Biotechnology for supporting this work。
文摘The plant circadian clock temporally drives gene expression throughout the day and coordinates various physiological processes with diurnal environmental changes. It is essential for conferring plant fitness and competitive advantages to survive and thrive under natural conditions through the circadian control of gene transcription. Chinese cabbage(Brassica rapa ssp. pekinensis) is an economically important vegetable crop worldwide, although there is little information concerning its circadian clock system. Here we found that gene expression patterns are affected bycircadian oscillators at both the transcriptional and post-transcriptional levels in Chinese cabbage. Time-course RNA-seq analyses were conducted on two short-period lines(SPcc-1 and SPcc-2) and two long-period lines(LPcc-1 and LPcc-2) under constant light. The results showed that 32.7–50.5% of the genes were regulated bythe circadian oscillator and the expression peaks of cycling genes appeared earlier in short-period lines than long-period lines. In addition, approximately 250 splicing events exhibited circadian regulation, with intron retention(IR) accounting for a large proportion. Rhythmically spliced genes included the clock genes LATE ELONGATEDHYPOCOTYL(BrLHY), REVEILLE 2(BrRVE2) and EARLY FLOWERING 3(BrELF3). We also found that thecircadian oscillator could notably influence the diurnal expression patterns of genes that are associated with glucose metabolism via photosynthesis, the Calvin cycle and the tricarboxylic acid(TCA) cycle at both the transcriptional andpost-transcriptional levels. The collective results of this study demonstrate that circadian-regulated physiological processes contribute to Chinese cabbage growth and development.
基金Project supported by the graduate training funds of Shanghai Ocean University in China。
文摘The circadian system of mammals is composed of a hierarchical network of oscillators,including a core clock and peripheral clocks.The core clock receives an external photic signal and transmits it to the peripheral clocks,which,in turn,feed back to the core clock.Aging affects various functions of organisms including the circadian system.Entrainment displays the adaptability of the circadian system to changes in the external environment.However,there is currently no systematic study on the effects of aging on the entrainment capability.To explore the influencing mechanism,we develop a mathematical model of two populations of Goodwin oscillators,which represent the core clock and peripheral clocks.Based on numerical simulations,we conduct a detailed study on the impact of three aging-related factors on the entrainment capability represented by the entrainment range,entrainment time,and entrainment phase.The results indicate that the decrease in the sensitivity of suprachiasmatic nucleus(SCN)to light and the coupling strength from the SCN to the peripheral clocks due to aging increase the phase difference between the core and peripheral clocks,narrow the entrainment range,and prolong the entrainment time.A reduction in the coupling strength within the SCN has little effect on the three aspects mentioned above but increases the entrainment phase.Overall,aging reduces the circadian system's adaptability to the external environment,and the increased entrainment phase may lead to corresponding sleep problems.We also show that modulating the internal coupling strength in the peripheral clocks can mitigate aging effects;this provides an idea for using peripheral clocks to adjust the core clock,while also revealing new insights into the interaction between aging and the elasticity of the circadian system.This mechanism provides theoretical support for treating or alleviating circadian system disorders or sleep problems caused by aging.
文摘During the development of diet-induced obesity,the change of energy matebolism is closely related to the function of the circadian clock in mammals.Luteolin(LU),one of the most common natural flavonoids riched in many edible plants,can ameliorate obesity by activating adipose tissue browning,but its effect on circadian clock in this process remains poorly understood.Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet(HFD)-fed wild-type(WT)mice.Moreover,dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period,which was similar to the LU-increased hepatic PER2 expressions.Hepatic peroxisome proliferators-activated receptorsα(PPARα)/recombinant retinoid X receptorα(RXRα)/fibroblast growth factor 21(FGF21)pathway was rhythmically elevated by dietary LU in HFD-fed WT mice,whereas the promotion was inhibited in Per2^(-/-)mice.Meanwhile,Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice.Further,LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^(-/-)mice.Taken together,the deletion of the core clock component Per2 impedes LUinduced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice,providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.
