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
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
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 clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for th...The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.展开更多
This study presents an achievement of laser cooling of alkaline-earth atoms in the Chinese Space Station’s strontium(Sr)atomic space optical clock.The system’s core components,physical unit,optical unit,and electric...This study presents an achievement of laser cooling of alkaline-earth atoms in the Chinese Space Station’s strontium(Sr)atomic space optical clock.The system’s core components,physical unit,optical unit,and electrical unit,have a total volume of 306 L and a total mass of 163.8 kg.These compact and robust units can overcome mechanical vibrations and temperature fluctuations during space launch.The laser sources of the optical unit are composed of diode lasers,and the injection locking of slave lasers is automatically performed by a program.In the experiment,a blue magneto-optical trap of cold atoms was achieved,with the atom numbers estimated to be approximately(1.50±0.13)×10^(6) for 87Sr and(8.00±0.56)×10^(6) for 88Sr.This work establishes a foundation for atomic confinement and high-precision interrogation in space-based optical clocks and expands the frontiers of cold atom physics in microgravity.展开更多
The phenomenon that a clock at a higher gravitational potential ticks faster than one at a lower potential,also known as gravitational redshift,is one of the classical tests of Einstein’s theory of general relativity...The phenomenon that a clock at a higher gravitational potential ticks faster than one at a lower potential,also known as gravitational redshift,is one of the classical tests of Einstein’s theory of general relativity.Owing to their ultra-high accuracy and stability,state-of-the-art optical lattice clocks have enabled resolving the gravitational redshift with a millimeter-scale height difference.Further reducing the vertical inter-clock separation down to the sub-millimeter level and especially shortening the required measurement time may be achieved by employing spin squeezing.Here,we theoretically investigate the spin-squeezing-enhanced differential frequency comparison between two optical clocks within a lattice-trapped cloud of^(171)Yb atoms.The numerical results illustrate that for a sample of 10^(4)atoms,the atomic-collision-limited resolution of the vertical separation between two clocks can reach 0.48 mm,corresponding to a fractional gravitational redshift at the 10^(-20)level.In addition,the required averaging time may be reduced to less than one hundredth of that of conventional clocks with independent atoms.Our work opens a door to the future spin-squeezing-enhanced test of general relativity.展开更多
We present analog clocks fitted to the Mars solar day.These clocks use the standard Earth-based second of the International System of Units(SI)as their operational unit of time,unlike current practice for Mars timekee...We present analog clocks fitted to the Mars solar day.These clocks use the standard Earth-based second of the International System of Units(SI)as their operational unit of time,unlike current practice for Mars timekeeping.We discuss the importance of preserving the SI second.On this basis,we identify the two analog clocks most suitable for public use by a future Mars population.These are a 20-hour clock with a hand motion similar to that of the standard Earth clock,and a 24-hour clock with a novel“Martian”hand motion which strikes the hour when all 3 hands converge onto that hour mark on the dial.Both clocks have Earth-day equivalents to assist learning.We also present a 24-hour“SpaceClock”,similar to the Martian clock but with no favored reference plane,hence equally readable from any viewing orientation.展开更多
The circadian clock is a highly conserved timekeeping system in organisms,which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression.Substantial clinical and experimenta...The circadian clock is a highly conserved timekeeping system in organisms,which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression.Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies.Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues,primarily manifested as a dysfunction of core clock components(particularly circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like 1(BMAL1))and the widespread dysregulation of their downstream target genes.Notably,CLOCK demonstrates non-canonical oncogenic functions,including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways.This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1,encompassing multidimensional effects such as cell cycle control,DNA damage response,metabolic reprogramming,and tumor microenvironment(TME)remodeling.Regarding the therapeutic strategies,we focus on cutting-edge approaches such as chrononutritional interventions,chronopharmacological modulation,and treatment regimen optimization,along with a discussion of future perspectives.The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology,particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.展开更多
Power Line Communications-Artificial Intelligence of Things(PLC-AIo T)combines the low cost and high coverage of PLC with the learning ability of Artificial Intelligence(AI)to provide data collection and transmission ...Power Line Communications-Artificial Intelligence of Things(PLC-AIo T)combines the low cost and high coverage of PLC with the learning ability of Artificial Intelligence(AI)to provide data collection and transmission capabilities for PLC-AIo T devices in smart parks.With the development of smart parks,their emerging services require secure and accurate time synchronization of PLC-AIo T devices.However,the impact of attackers on the accuracy of time synchronization cannot be ignored.To solve the aforementioned problems,we propose a tampering attack-aware Deep Q-Network(DQN)-based time synchronization algorithm.First,we construct an abnormal clock source detection model.Then,the abnormal clock source is detected and excluded by comparing the time synchronization information between the device and the gateway.Finally,the proposed algorithm realizes the joint guarantee of high accuracy and low delay for PLC-AIo T in smart parks by intelligently selecting the multi-clock source cooperation strategy and timing weights.Simulation results show that the proposed algorithm has better time synchronization delay and accuracy performance.展开更多
This article proposes a new physics package to enhance the frequency stability of the space cold atom clock with the advantages of a microgravity environment. Clock working processes, including atom cooling, atomic st...This article proposes a new physics package to enhance the frequency stability of the space cold atom clock with the advantages of a microgravity environment. Clock working processes, including atom cooling, atomic state preparation,microwave interrogation, and transition probability detection, are integrated into the cylindrical microwave cavity to achieve a high-performance and compact physics package for the space cold atom clock. We present the detailed design and ground-test results of the cold atom clock physics package in this article, which demonstrates a frequency stability of 1.2×10^(-12) τ^(-1/2) with a Ramsey linewidth of 12.5 Hz, and a better performance is predicted with a 1 Hz or a narrower Ramsey linewidth in microgravity environment. The miniaturized cold atom clock based on intracavity cooling has great potential for achieving space high-precision time-frequency reference in the future.展开更多
We construct a power enhancement cavity to form an optical lattice in an ytterbium optical clock.It is demonstrated that the intra-cavity lattice power can be increased by about 45 times,and the trap depth can be as l...We construct a power enhancement cavity to form an optical lattice in an ytterbium optical clock.It is demonstrated that the intra-cavity lattice power can be increased by about 45 times,and the trap depth can be as large as 1400Er when laser light with a power of only 0.6 W incident to the lattice cavity.Such high trap depths are the key to accurate evaluation of the lattice-induced light shift with an uncertainty down to~1×10-18.By probing the ytterbium atoms trapped in the power-enhanced optical lattice,we obtain a 4.3 Hz-linewidth Rabi spectrum,which is then used to feedback to the clock laser for the close loop operation of the optical lattice clock.We evaluate the density shift of the Yb optical lattice clock based on interleaving measurements,which is-0.46(62)mHz.This result is smaller compared to the density shift of our first Yb optical clock without lattice power enhancement cavity mainly due to a larger lattice diameter of 344μm.展开更多
Precise timing of flowering in plants is critical for their growth and reproductive processes.One factor controlling flowering time is the cycle of light and darkness within a day,known as the photoperiod.Plants are c...Precise timing of flowering in plants is critical for their growth and reproductive processes.One factor controlling flowering time is the cycle of light and darkness within a day,known as the photoperiod.Plants are classified into long-day,short-day,and day-neutral plants based on light requirements for floral initiation.Although the molecular mechanisms that govern this differentiation remain incompletely understood,studies have consistently shown that the circadian clock plays a central role in regulating photoperiod response across diverse plant species.However,there is a scarcity of reviews describing the regulatory network linking the circadian clock with photoperiodic flowering.This review summarizes that regulatory network,focusing on the distinct roles of clock genes in long-day and short-day plants.We also discuss the strategies of clock gene mutations contributing to geographic variation in longday and short-day crops.展开更多
A frequency servo system-on-chip(FS-SoC)featuring output power stabilization technology is introduced in this study for high-precision and miniaturized cesium(Cs)atomic clocks.The proposed power stabilization loop(PSL...A frequency servo system-on-chip(FS-SoC)featuring output power stabilization technology is introduced in this study for high-precision and miniaturized cesium(Cs)atomic clocks.The proposed power stabilization loop(PSL)technique,incorporating an off-chip power detector(PD),ensures that the output power of the FS-SoC remains stable,mitigating the impact of power fluctuations on the atomic clock's stability.Additionally,a one-pulse-per-second(1PPS)is employed to syn-chronize the clock with GPS.Fabricated using 65 nm CMOS technology,the measured phase noise of the FS-SoC stands at-69.5 dBc/Hz@100 Hz offset and-83.9 dBc/Hz@1 kHz offset,accompanied by a power dissipation of 19.7 mW.The Cs atomic clock employing the proposed FS-SoC and PSL obtains an Allan deviation of 1.7×10^(-11) with 1-s averaging time.展开更多
Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have un...Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.展开更多
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.
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.
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supported by grants from the National Natural Science Foundation of China(N0.82474525 and No.82074444)the Hunan Provincial Natural Outstanding Young People Science Foundation(2023JJ10032)the Hunan Province Health and High-Level Talent Medical Academic Leader Training Plan(20240304051).
文摘The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB35010202)the National Natural Science Foundation of China(Grants No.62275268)。
文摘This study presents an achievement of laser cooling of alkaline-earth atoms in the Chinese Space Station’s strontium(Sr)atomic space optical clock.The system’s core components,physical unit,optical unit,and electrical unit,have a total volume of 306 L and a total mass of 163.8 kg.These compact and robust units can overcome mechanical vibrations and temperature fluctuations during space launch.The laser sources of the optical unit are composed of diode lasers,and the injection locking of slave lasers is automatically performed by a program.In the experiment,a blue magneto-optical trap of cold atoms was achieved,with the atom numbers estimated to be approximately(1.50±0.13)×10^(6) for 87Sr and(8.00±0.56)×10^(6) for 88Sr.This work establishes a foundation for atomic confinement and high-precision interrogation in space-based optical clocks and expands the frontiers of cold atom physics in microgravity.
基金supported by CAS Project for Young Scientists in Basic Research(Grant No.YSBR-085)the National Time Service Center(Grant No.E239SC1101)+1 种基金Innovation Program for Quantum Science and Technology(Grant No.2021ZD0303200)China Postdoctoral Science Foundation(Grant No.BX2021020).
文摘The phenomenon that a clock at a higher gravitational potential ticks faster than one at a lower potential,also known as gravitational redshift,is one of the classical tests of Einstein’s theory of general relativity.Owing to their ultra-high accuracy and stability,state-of-the-art optical lattice clocks have enabled resolving the gravitational redshift with a millimeter-scale height difference.Further reducing the vertical inter-clock separation down to the sub-millimeter level and especially shortening the required measurement time may be achieved by employing spin squeezing.Here,we theoretically investigate the spin-squeezing-enhanced differential frequency comparison between two optical clocks within a lattice-trapped cloud of^(171)Yb atoms.The numerical results illustrate that for a sample of 10^(4)atoms,the atomic-collision-limited resolution of the vertical separation between two clocks can reach 0.48 mm,corresponding to a fractional gravitational redshift at the 10^(-20)level.In addition,the required averaging time may be reduced to less than one hundredth of that of conventional clocks with independent atoms.Our work opens a door to the future spin-squeezing-enhanced test of general relativity.
文摘We present analog clocks fitted to the Mars solar day.These clocks use the standard Earth-based second of the International System of Units(SI)as their operational unit of time,unlike current practice for Mars timekeeping.We discuss the importance of preserving the SI second.On this basis,we identify the two analog clocks most suitable for public use by a future Mars population.These are a 20-hour clock with a hand motion similar to that of the standard Earth clock,and a 24-hour clock with a novel“Martian”hand motion which strikes the hour when all 3 hands converge onto that hour mark on the dial.Both clocks have Earth-day equivalents to assist learning.We also present a 24-hour“SpaceClock”,similar to the Martian clock but with no favored reference plane,hence equally readable from any viewing orientation.
基金supported by the Ministry of Science and Technology of the People’s Republic of China(Nos.2020YFA0803300 and 2021YFA0805600)the National Natural Science Foundation of China(Nos.92157113,82072630,82173114,82072903,82272872,82002811,82188102,and 82030074)+2 种基金the Zhejiang Natural Science Foundation Key Project(Nos.LD22H160002 and LD21H160003)the Zhejiang Natural Science Foundation Discovery Project(No.LQ22H160023)the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2019R01001),China.
文摘The circadian clock is a highly conserved timekeeping system in organisms,which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression.Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies.Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues,primarily manifested as a dysfunction of core clock components(particularly circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like 1(BMAL1))and the widespread dysregulation of their downstream target genes.Notably,CLOCK demonstrates non-canonical oncogenic functions,including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways.This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1,encompassing multidimensional effects such as cell cycle control,DNA damage response,metabolic reprogramming,and tumor microenvironment(TME)remodeling.Regarding the therapeutic strategies,we focus on cutting-edge approaches such as chrononutritional interventions,chronopharmacological modulation,and treatment regimen optimization,along with a discussion of future perspectives.The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology,particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
基金supported by the Science and Technology Project of the State Grid Corporation of China under Grant Number 5400202199541A-0-5-ZN。
文摘Power Line Communications-Artificial Intelligence of Things(PLC-AIo T)combines the low cost and high coverage of PLC with the learning ability of Artificial Intelligence(AI)to provide data collection and transmission capabilities for PLC-AIo T devices in smart parks.With the development of smart parks,their emerging services require secure and accurate time synchronization of PLC-AIo T devices.However,the impact of attackers on the accuracy of time synchronization cannot be ignored.To solve the aforementioned problems,we propose a tampering attack-aware Deep Q-Network(DQN)-based time synchronization algorithm.First,we construct an abnormal clock source detection model.Then,the abnormal clock source is detected and excluded by comparing the time synchronization information between the device and the gateway.Finally,the proposed algorithm realizes the joint guarantee of high accuracy and low delay for PLC-AIo T in smart parks by intelligently selecting the multi-clock source cooperation strategy and timing weights.Simulation results show that the proposed algorithm has better time synchronization delay and accuracy performance.
基金Project supported by the Space Application System of China Manned Space Programthe Youth Innovation Promotion Association,CAS。
文摘This article proposes a new physics package to enhance the frequency stability of the space cold atom clock with the advantages of a microgravity environment. Clock working processes, including atom cooling, atomic state preparation,microwave interrogation, and transition probability detection, are integrated into the cylindrical microwave cavity to achieve a high-performance and compact physics package for the space cold atom clock. We present the detailed design and ground-test results of the cold atom clock physics package in this article, which demonstrates a frequency stability of 1.2×10^(-12) τ^(-1/2) with a Ramsey linewidth of 12.5 Hz, and a better performance is predicted with a 1 Hz or a narrower Ramsey linewidth in microgravity environment. The miniaturized cold atom clock based on intracavity cooling has great potential for achieving space high-precision time-frequency reference in the future.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.12334020 and 11927810)the National Key Research and Development Program of China(Grant No.2022YFB3904001).
文摘We construct a power enhancement cavity to form an optical lattice in an ytterbium optical clock.It is demonstrated that the intra-cavity lattice power can be increased by about 45 times,and the trap depth can be as large as 1400Er when laser light with a power of only 0.6 W incident to the lattice cavity.Such high trap depths are the key to accurate evaluation of the lattice-induced light shift with an uncertainty down to~1×10-18.By probing the ytterbium atoms trapped in the power-enhanced optical lattice,we obtain a 4.3 Hz-linewidth Rabi spectrum,which is then used to feedback to the clock laser for the close loop operation of the optical lattice clock.We evaluate the density shift of the Yb optical lattice clock based on interleaving measurements,which is-0.46(62)mHz.This result is smaller compared to the density shift of our first Yb optical clock without lattice power enhancement cavity mainly due to a larger lattice diameter of 344μm.
基金This work was supported by Laboratory of Lingnan Modern Agriculture Project(NZ2021001)State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources(SKICUSAa202007)+1 种基金Natural Science Foundation of Guangdong Province(2022A1515011027,2021A1515012148)the Double Firstclass Discipline Promotion Project(2023B10564004).
文摘Precise timing of flowering in plants is critical for their growth and reproductive processes.One factor controlling flowering time is the cycle of light and darkness within a day,known as the photoperiod.Plants are classified into long-day,short-day,and day-neutral plants based on light requirements for floral initiation.Although the molecular mechanisms that govern this differentiation remain incompletely understood,studies have consistently shown that the circadian clock plays a central role in regulating photoperiod response across diverse plant species.However,there is a scarcity of reviews describing the regulatory network linking the circadian clock with photoperiodic flowering.This review summarizes that regulatory network,focusing on the distinct roles of clock genes in long-day and short-day plants.We also discuss the strategies of clock gene mutations contributing to geographic variation in longday and short-day crops.
基金supported by the National Natural Science Foundation of China under Grant 62034002 and 62374026.
文摘A frequency servo system-on-chip(FS-SoC)featuring output power stabilization technology is introduced in this study for high-precision and miniaturized cesium(Cs)atomic clocks.The proposed power stabilization loop(PSL)technique,incorporating an off-chip power detector(PD),ensures that the output power of the FS-SoC remains stable,mitigating the impact of power fluctuations on the atomic clock's stability.Additionally,a one-pulse-per-second(1PPS)is employed to syn-chronize the clock with GPS.Fabricated using 65 nm CMOS technology,the measured phase noise of the FS-SoC stands at-69.5 dBc/Hz@100 Hz offset and-83.9 dBc/Hz@1 kHz offset,accompanied by a power dissipation of 19.7 mW.The Cs atomic clock employing the proposed FS-SoC and PSL obtains an Allan deviation of 1.7×10^(-11) with 1-s averaging time.
基金supported by National Council of Science and Technology(CONACYT)(grants FC 2016/2672 and FOSISS 272757),INMEGEN(09/2017/I)the Ministry of Education,Science,Technology and Innovation of Mexico City(SECTEI)(grant 228/2021).
文摘Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.
