Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian cloc...Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.展开更多
Lung transplantation(LT)is now an accepted therapy for end stage lung disease in appropriate patients.Atrial arrhythmias(AA)can occur after LT.Early AA after LT are most often atrial fibrillation,whereas late arrhythm...Lung transplantation(LT)is now an accepted therapy for end stage lung disease in appropriate patients.Atrial arrhythmias(AA)can occur after LT.Early AA after LT are most often atrial fibrillation,whereas late arrhythmias which occur many months or years after LT are often atrial tachycardia.The causes of AA are multifactorial.The review begins with a brief history of LT and AA.This review further describes the pathophysiology of the AA.The risk factors,incidence,recipient characteristics including intra-operative factors are elaborated on.Since there are no clear and specific guidelines on the management of atrial arrhythmia following LT,the recommended guidelines on the management of AA in general are often extrapolated and used in the setting of post LT arrhythmia.The strategy of rate control vs rhythm control is discussed.The pros and cons of various drug regimen,need for direct current cardioversion and catheter ablation therapies are considered.Possible methods to prevent or reduce the incidence of AA after LT are considered.The impact of AA on the short-term and long-term outcomes following LT is discussed.展开更多
Takotsubo syndrome(TTS),also known as stress cardiomyopathy,occurs in approximately 2%of all patients presenting with suspected acute coronary syndrome.[1]The in-hospital mortality rate of pati-ents with TTS is report...Takotsubo syndrome(TTS),also known as stress cardiomyopathy,occurs in approximately 2%of all patients presenting with suspected acute coronary syndrome.[1]The in-hospital mortality rate of pati-ents with TTS is reported to be approximately 4%-5%.[2]This condition is commonly associated with various rhythm and conduction disturbances,such as atrial fibrillation(5%-15%),ventricular arrhythmias(4%-9%),and rarely sinus node dysfunction(1.3%).展开更多
Musical rhythms are represented as sequences of symbols. The sequences may be composed of binary symbols denoting either silent or monophonic sounded pulses, or ternary symbols denoting silent pulses and two types of ...Musical rhythms are represented as sequences of symbols. The sequences may be composed of binary symbols denoting either silent or monophonic sounded pulses, or ternary symbols denoting silent pulses and two types of sounded pulses made up of low-pitched (dum) and high-pitched (tak) sounds. Experiments are described that compare the effectiveness of the many-to-many minimum-weight matching between two sequences to serve as a measure of similarity that correlates well with human judgements of rhythm similarity. This measure is also compared to the often used edit distance and to the one-to-one minimum-weight matching. New results are reported from experiments performed with three widely different datasets of real- world and artificially generated musical rhythms (including Afro-Cuban rhythms), and compared with results previously reported with a dataset of Middle Eastern dum-tak rhythms.展开更多
Major depressive disorder(MDD)affects people all over the world,and yet,its etiology is complex and remains incompletely understood.In this review,we aim to assess recent advances in understanding depression and its r...Major depressive disorder(MDD)affects people all over the world,and yet,its etiology is complex and remains incompletely understood.In this review,we aim to assess recent advances in understanding depression and its regulation,as well as its interaction with circadian rhythms.Circadian rhythms are internalized representations of the periodic daily light and dark cycles.Accumulating evidence has shown that MDD and the related mental disorders are associated with disrupted circadian rhythms.In particular,depression has often been linked to abnormalities in circadian rhythms because dysregulation of the circadian system increases susceptibility to MDD.The fact that several rhythms are disrupted in depressed patients suggests that these disruptions are not restricted to any one rhythm but rather involve the molecular circadian clock core machinery.The sleep-wake cycle is one rhythm that is often disrupted in depression,which often leads to disturbances in other rhythms.The circadian disruptions manifested in depressed patients and the effectiveness and fast action of chronobiologically based treatments highlight the circadian system as a key therapeutic target in the treatment of depression.This review assesses the evidence on rising depression rates and examines their contributing factors,including circadian misalignment.We discuss key hypotheses underlying depression pathogenesis,potential etiology,and relevant animal models,and underscore potential mechanisms driving depression's growing burden and how understanding these factors is critical for improving prevention and treatment strategies.展开更多
Traditional Chinese medicine(TCM)has a comprehensive and thorough understanding of biological rhythm.Biological rhythm is an inherent connotation of“harmony between human and nature”,one of the thoughts in TCM.TCM d...Traditional Chinese medicine(TCM)has a comprehensive and thorough understanding of biological rhythm.Biological rhythm is an inherent connotation of“harmony between human and nature”,one of the thoughts in TCM.TCM discusses emphatically circadian rhythm,syzygial rhythm and seasonal rhythm,and particularly circadian and seasonal rhythms.Theories of Yin Yang and Five Elements are the principles and methods,with which TCM understands biological rhythms.Based on theories in TCM,biological rhythm in essence is a continuous variation of the human body state synchronized with natural rhythms,and theories of Yin Yang and Five Elements are both language tools to describe this continuous variation and theoretical tools for its investigation and application.The understandings of biological rhythm in TCM can be applied to etiology,health care,disease control and treatment.Many understandings in TCM have been confirmed by modern research and clinical reports,but there are still some pending issues.TCM is distinguished for its holistic viewpoint on biological rhythms.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
A heart attack disrupts the normal flow of blood to the heart muscle,potentially causing severe damage or death if not treated promptly.It can lead to long-term health complications,reduce quality of life,and signific...A heart attack disrupts the normal flow of blood to the heart muscle,potentially causing severe damage or death if not treated promptly.It can lead to long-term health complications,reduce quality of life,and significantly impact daily activities and overall well-being.Despite the growing popularity of deep learning,several drawbacks persist,such as complexity and the limitation of single-model learning.In this paper,we introduce a residual learning-based feature fusion technique to achieve high accuracy in differentiating abnormal cardiac rhythms heart sound.Combining MobileNet with DenseNet201 for feature fusion leverages MobileNet lightweight,efficient architecture with DenseNet201,dense connections,resulting in enhanced feature extraction and improved model performance with reduced computational cost.To further enhance the fusion,we employed residual learning to optimize the hierarchical features of heart abnormal sounds during training.The experimental results demonstrate that the proposed fusion method achieved an accuracy of 95.67%on the benchmark PhysioNet-2016 Spectrogram dataset.To further validate the performance,we applied it to the BreakHis dataset with a magnification level of 100X.The results indicate that the model maintains robust performance on the second dataset,achieving an accuracy of 96.55%.it highlights its consistent performance,making it a suitable for various applications.展开更多
This paper presents a novel rehabilitation robot designed to address the challenges of Passive Range of Motion(PROM)exercises for frozen shoulder patients by integrating advanced scapulohumeral rhythm stabilization.Fr...This paper presents a novel rehabilitation robot designed to address the challenges of Passive Range of Motion(PROM)exercises for frozen shoulder patients by integrating advanced scapulohumeral rhythm stabilization.Frozen shoulder is characterized by limited glenohumeral motion and disrupted scapulohumeral rhythm,with therapist-assisted interventions being highly effective for restoring normal shoulder function.While existing robotic solutions replicate natural shoulder biomechanics,they lack the ability to stabilize compensatory movements,such as shoulder shrugging,which are critical for effective rehabilitation.Our proposed device features a 6 Degrees of Freedom(DoF)mechanism,including 5 DoF for shoulder motion and an innovative 1 DoF Joint press for scapular stabilization.The robot employs a personalized two-phase operation:recording normal shoulder movement patterns from the unaffected side and applying them to guide the affected side.Experimental results demonstrated the robot’s ability to replicate recorded motion patterns with high precision,with Root Mean Square Error(RMSE)values consistently below 1 degree.In simulated frozen shoulder conditions,the robot effectively suppressed scapular elevation,delaying the onset of compensatory movements and guiding the affected shoulder to move more closely in alignment with normal shoulder motion,particularly during arm elevation movements such as abduction and flexion.These findings confirm the robot’s potential as a rehabilitation tool capable of automating PROM exercises while correcting compensatory movements.The system provides a foundation for advanced,personalized rehabilitation for patients with frozen shoulders.展开更多
Objective:Circadian rhythm disruption(CRD)is a risk factor that correlates with poor prognosis across multiple tumor types,including hepatocellular carcinoma(HCC).However,its mechanism remains unclear.This study aimed...Objective:Circadian rhythm disruption(CRD)is a risk factor that correlates with poor prognosis across multiple tumor types,including hepatocellular carcinoma(HCC).However,its mechanism remains unclear.This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.Methods:To quantify CRD,the HCC CRD score(HCCcrds)was developed.Using machine learning algorithms,we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort(n=369),and the robustness of this method was validated.Furthermore,we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.Results:We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis.The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis,higher pathological grade,and advanced clinical stages,while the CRD-related subtype with low HCCcrds had better clinical outcomes.We also identified novel biomarkers for each subtype,such as nicotinamide nmethyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.Conclusion:We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers.Within these groups greater HCCcrds was associated with worse prognosis.This approach has the potential to improve prediction of an individual’s prognosis,guide precision treatments,and assist clinical decision making for HCC patients.展开更多
Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patie...Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patients’blood pressure,they were divided into group A,group B,and group C,and all the data of hypertension patients in this study were collected,including age,gender,BMI,smoking,drinking,basic diseases(diabetes,cerebrovascular disease,hyperlipidemia,etc.),fasting blood glucose,ambulatory blood pressure(24-hour mean systolic pressure,24-hour mean diastolic pressure,daytime mean systolic pressure and daytime mean diastolic pressure).Results:There were significant differences in mean systolic blood pressure and mean diastolic blood pressure at night among group A,group B and group C(P<0.05).Age,hyperlipidemia and fasting blood glucose were risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium was a protective factor for circadian rhythm abnormality(P<0.05).Conclusion:Age,hyperlipidemia and fasting blood glucose are risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium is a protective factor for circadian rhythm abnormality(P<0.05).展开更多
Objective: To investigate the effect of a self-developed balance rhythm dance program on the rehabilitation of motor function and the reduction of fall risk in elderly women with diminished balance function. Methods: ...Objective: To investigate the effect of a self-developed balance rhythm dance program on the rehabilitation of motor function and the reduction of fall risk in elderly women with diminished balance function. Methods: Fifty elderly women with reduced balance function, admitted to the Qingbar Elderly Care Center of Chongqing Medical University from December 2022 to December 2023, were randomly selected and divided into two groups. The aerobic exercise group (25 patients) received traditional treatment and rehabilitation nursing, while the balance rhythm dance intervention group (25 patients) received the balance rhythm dance intervention in addition to traditional treatment and rehabilitation nursing. The Unified Parkinson’s Disease Rating Scale (UPDRS) and Berg Balance Scale (BBS) were used as evaluation indicators to compare the intervention effects between the two groups. Results: The data revealed that the balance rhythm dance intervention significantly improved the motor ability and balance function of elderly women in the intervention group (P < 0.01), with statistically significant differences observed. Conclusion: The balance rhythm dance program plays a critical role in promoting the rehabilitation of motor function and balance ability in elderly women, effectively enhancing their quality of life.展开更多
The ability of natural conception decreases with age,leading many advanced-age women with fertility desire begin to attempt in vitro fertilization and embryo transfer(IVF-ET)technique nowadays.Traditional Chinese medi...The ability of natural conception decreases with age,leading many advanced-age women with fertility desire begin to attempt in vitro fertilization and embryo transfer(IVF-ET)technique nowadays.Traditional Chinese medicine(TCM)believes that human body undergoes periodic changes corresponding to the natural rhythms.Women exhibit distinct physiological lunar rhythms of the thoroughfare vessel and the conception vessel,as well as pathological rhythms during the menstrual cycle and IVF-ET cycle.Based on the theory of TCM temporal rhythm,this paper discusses the pathogenesis characteristics of infertility in advanced-age women at different stages.It believes that acupuncture intervention should comply with the following ideas:determining main acupoints based on disease differentiation,with a preference for the acupoints on the thoroughfare vessel,the conception vessel,spleen meridian and kidney meridian,as well as the back-shu points of the liver,spleen and kidney;determining the supplementary acupoints based on syndrome differentiation and symptoms;determining the supplementary acupoints based on time differentiation of lunar rhythm of the thoroughfare vessel and the conception vessel,and integrating both reinforcing and reducing techniques.During the process of intervention,the physical and mental states were balanced simultaneously.展开更多
Rhythm,as a prominent characteristic of auditory experiences such as speech and music,is known to facilitate attention,yet its contribution to working memory(WM)remains unclear.Here,human participants temporarily reta...Rhythm,as a prominent characteristic of auditory experiences such as speech and music,is known to facilitate attention,yet its contribution to working memory(WM)remains unclear.Here,human participants temporarily retained a 12-tone sequence presented rhythmically or arrhythmically in WM and performed a pitch change-detection task.Behaviorally,while having comparable accuracy,rhythmic tone sequences showed a faster response time and lower response boundaries in decision-making.Electroencephalographic recordings revealed that rhythmic sequences elicited enhanced non-phase-locked beta-band(16 Hz–33 Hz)and theta-band(3 Hz–5 Hz)neural oscillations during sensory encoding and WM retention periods,respectively.Importantly,the two-stage neural signatures were correlated with each other and contributed to behavior.As beta-band and theta-band oscillations denote the engagement of motor systems and WM maintenance,respectively,our findings imply that rhythm facilitates auditory WM through intricate oscillation-based interactions between the motor and auditory systems that facilitate predictive attention to auditory sequences.展开更多
Closed-loop neuromodulation,especially using the phase of the electroencephalography(EEG)rhythm to assess the real-time brain state and optimize the brain stimulation process,is becoming a hot research topic.Because t...Closed-loop neuromodulation,especially using the phase of the electroencephalography(EEG)rhythm to assess the real-time brain state and optimize the brain stimulation process,is becoming a hot research topic.Because the EEG signal is non-stationary,the commonly used EEG phase-based prediction methods have large variances,which may reduce the accuracy of the phase prediction.In this study,we proposed a machine learning-based EEG phase prediction network,which we call EEG phase prediction network(EPN),to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data.We verified the performance of EPN on pre-recorded data,simulated EEG data,and a real-time experiment.Compared with widely used state-of-the-art models(optimized multi-layer filter architecture,auto-regress,and educated temporal prediction),EPN achieved the lowest variance and the greatest accuracy.Thus,the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.展开更多
Background:The prevalence of circadian misalignment,particularly social jetlag(SJL),contributes significantly to the epidemic of metabolic disorders.However,the precise impact of SJL on the liver has remained poorly e...Background:The prevalence of circadian misalignment,particularly social jetlag(SJL),contributes significantly to the epidemic of metabolic disorders.However,the precise impact of SJL on the liver has remained poorly elucidated.Methods:The rhythmicity of circulating prolactin(PRL)was evaluated in subjects with SJL and mice under SJL.The causative mechanism of SJL on fatty liver was explored using jetlag model in wild-type and PrI^(-/-) mice.Luciferase reporter assay,electrophoretic mobility shift assay,and chromatin immunoprecipitation analysis were used to study the transcriptional mechanism of retinoic acid receptor-related orphan receptor α on PRL.RNA-sequencing(RNA-seq)on human and mice liver as well as circadian analysis were used to study the mechanism of SJL-associated desynchronized PRL on hepatic lipid metabolism.The therapeutic effect of PRL intervention on SJL-induced mice at different time points was compared.Results:SJL increases the risk of metabolic dysfunction-associated steatotic liver disease(MASLD),mediated by the disruption of the rhythmicity of serum PRL.In particular,SJL inhibits the rhythmic transcription of PRL in the pituitary,leading to desynchronized PRL levels in circulation.Under jetlag conditions,the rhythmicity of the hepatic PRL signaling pathway was significantly dampened,which resulted in increased lipogenesis via inhibited hepatic mitogen-activated protein kinase/cyclin D1 expressions.Notably,PRL treatment at PRL nadir in jetlagged mice decreased hepatic lipid content and liver injury markers to a greater extent compared with conventional PRL administration.Conclusions:Reprogrammed hepatic PRL signaling pathway with concomitant dysregulated lipid metabolism homeostasis was the causative mechanism of fatty liver under SJL,which was mediated through derailed serum PRL rhythm.Restoration of PRL rhythm could effectively alleviate SJL-induced fatty liver,providing new insight into treating MASLD.展开更多
BACKGROUND Diabetic gastrointestinal autonomic neuropathy(DGAN)often affects the patients’quality of life.Thus,research on influencing factors of DGAN may promote DGAN prevention and decrease the incidence rate.This ...BACKGROUND Diabetic gastrointestinal autonomic neuropathy(DGAN)often affects the patients’quality of life.Thus,research on influencing factors of DGAN may promote DGAN prevention and decrease the incidence rate.This study used electrogastrogram(EGG)to assess the relationship between metabolic dysfunction-associated steatotic liver disease(MASLD)and DGAN.AIM To analyze the changes of EGG in patients with MASLD and type 2 diabetes mellitus(T2DM),and to elucidate whether ultrasound-diagnosed MASLD is an independent risk factor for diabetic gastric motility disorders(DGMD).METHODS A total of 272 patients with T2DM hospitalized at the Second Affiliated Hospital of Soochow University from December 2020 to December 2021 and the Affiliated Suqian Hospital of Xuzhou Medical University from November 2023 to June 2024 were included in the cross-sectional study.General information,clinical data,and medical history of all study subjects,including name,age,gender,body mass index,and duration of diabetes were collected.Laboratory tests included biochemical parameters,glycosylated hemoglobin(HbA1c),fasting C-peptide,2h postprandial C-peptide and 25-hydroxyvitamin D[25(OH)D].EGG,fundus examination and carotid artery ultrasonography were performed and results were recorded.According to the results of EGG,the subjects were divided into the DGMD group and non-DGMD group.RESULTS The duration of diabetes,fasting blood glucose(FBG),HbA1c,25(OH)D and the prevalence of MASLD were significantly higher in the DGMD group(P<0.05).Multiple logistic regression analysis showed that the duration,FBG,25(OH)D and the presence of MASLD were independent influencing factors.CONCLUSION MASLD is strongly associated with an increased incidence of DGMD.Timely treatment of MASLD is effective to prevent diabetic gastroparesis.展开更多
The volatile compounds from ash-leaf maple (Acer negundo L.) were examined by adsorption-thermodesorption and GC-MS. Thirty-two compounds, including alcohols, ketones, aldehydes, esters, terpenoids, carboxylic acids, ...The volatile compounds from ash-leaf maple (Acer negundo L.) were examined by adsorption-thermodesorption and GC-MS. Thirty-two compounds, including alcohols, ketones, aldehydes, esters, terpenoids, carboxylic acids, etc. were identified. The analysis revealed that the diurnal rhythm of release of volatile compounds from maple differed in July and in August. In July, the releasing of most volatile compounds reached the peak at 14 o'clock, when in August, the emission of volatile compounds reached the peak at 10 o'clock. Besides diurnal rhythm, there also existed other differences in the releasing of volatiles and their relative contents in July and in August. A possible explanation for this phenomenon is the maturation of leaves, since the sampling conditions were the same both in July and August. At the same time, the response of Anoplophora glabrpennis Motschulsky to volatiles was examined with field bioassay with traps. cis-3-hexen-1-ol was found to be more effective to attract A. glabrpennis than other volatiles released by ash-leaf maple tree in field trapping test. A mixture of 1-butanol, 1-pentanol and 2-pentanol was tested to be the most attractive to A. glabripennis among all tested volatiles. More field trapping tests should be conducted.展开更多
In July 2006, the diurnal activity rhythms of 13 heads of captive Qinling golden takin were observed in Shaanxi Provincial Centre for the Breeding and Conservation of Rare Wildlife （SPCBCRW） at daylight （from 9：00...In July 2006, the diurnal activity rhythms of 13 heads of captive Qinling golden takin were observed in Shaanxi Provincial Centre for the Breeding and Conservation of Rare Wildlife （SPCBCRW） at daylight （from 9：00 am to 4：00 pm in July）. The behavioral ethnogram was identified through observation at the sampling site, with the behaviors of golden takin recorded at 5 min interval using instantaneous scannable sampling method. The results indicated that the resting of golden takin took an important part in the daylight activities. Meanwhile, drinking and urinating and defecating were 1.92 and 0.54 and 0.92 times per head per day. Ambient temperature had a strong effect on the diurnal activity rhythms of golden takin. The diurnal activity rhymes were affected by ages of the animals effectively, which was expressed through differentiation of the time budgets. Moreover, different individuals in the same population showed some non-synchronously activity rhythms.展开更多
基金supported in part by grants from the National Key R&D Program of China(2021YFC2400400/04 to L.L.C.)the National Natural Science Foundation of China for Key Program Projects(82030070 to L.L.C.)+2 种基金the National Natural Science Foundation of China for Distinguished Young Scholars(22025102 to Q.W.)the National Natural Science Foundation of China(82271036 to Y.F.W.,22277033 to J.Z.,22177034 to L.K.M.)the Young Elite Scientist Sponsorship Program by CAST(2022QNRC001 to Y.F.W.)。
文摘Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.
文摘Lung transplantation(LT)is now an accepted therapy for end stage lung disease in appropriate patients.Atrial arrhythmias(AA)can occur after LT.Early AA after LT are most often atrial fibrillation,whereas late arrhythmias which occur many months or years after LT are often atrial tachycardia.The causes of AA are multifactorial.The review begins with a brief history of LT and AA.This review further describes the pathophysiology of the AA.The risk factors,incidence,recipient characteristics including intra-operative factors are elaborated on.Since there are no clear and specific guidelines on the management of atrial arrhythmia following LT,the recommended guidelines on the management of AA in general are often extrapolated and used in the setting of post LT arrhythmia.The strategy of rate control vs rhythm control is discussed.The pros and cons of various drug regimen,need for direct current cardioversion and catheter ablation therapies are considered.Possible methods to prevent or reduce the incidence of AA after LT are considered.The impact of AA on the short-term and long-term outcomes following LT is discussed.
文摘Takotsubo syndrome(TTS),also known as stress cardiomyopathy,occurs in approximately 2%of all patients presenting with suspected acute coronary syndrome.[1]The in-hospital mortality rate of pati-ents with TTS is reported to be approximately 4%-5%.[2]This condition is commonly associated with various rhythm and conduction disturbances,such as atrial fibrillation(5%-15%),ventricular arrhythmias(4%-9%),and rarely sinus node dysfunction(1.3%).
文摘Musical rhythms are represented as sequences of symbols. The sequences may be composed of binary symbols denoting either silent or monophonic sounded pulses, or ternary symbols denoting silent pulses and two types of sounded pulses made up of low-pitched (dum) and high-pitched (tak) sounds. Experiments are described that compare the effectiveness of the many-to-many minimum-weight matching between two sequences to serve as a measure of similarity that correlates well with human judgements of rhythm similarity. This measure is also compared to the often used edit distance and to the one-to-one minimum-weight matching. New results are reported from experiments performed with three widely different datasets of real- world and artificially generated musical rhythms (including Afro-Cuban rhythms), and compared with results previously reported with a dataset of Middle Eastern dum-tak rhythms.
基金supported by the National Natural Science Foundation of China(No.81701347,31961133026,81570171,31871187,and 81070455)the National Key R&D Program of China(No.2019YFA0802400)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions。
文摘Major depressive disorder(MDD)affects people all over the world,and yet,its etiology is complex and remains incompletely understood.In this review,we aim to assess recent advances in understanding depression and its regulation,as well as its interaction with circadian rhythms.Circadian rhythms are internalized representations of the periodic daily light and dark cycles.Accumulating evidence has shown that MDD and the related mental disorders are associated with disrupted circadian rhythms.In particular,depression has often been linked to abnormalities in circadian rhythms because dysregulation of the circadian system increases susceptibility to MDD.The fact that several rhythms are disrupted in depressed patients suggests that these disruptions are not restricted to any one rhythm but rather involve the molecular circadian clock core machinery.The sleep-wake cycle is one rhythm that is often disrupted in depression,which often leads to disturbances in other rhythms.The circadian disruptions manifested in depressed patients and the effectiveness and fast action of chronobiologically based treatments highlight the circadian system as a key therapeutic target in the treatment of depression.This review assesses the evidence on rising depression rates and examines their contributing factors,including circadian misalignment.We discuss key hypotheses underlying depression pathogenesis,potential etiology,and relevant animal models,and underscore potential mechanisms driving depression's growing burden and how understanding these factors is critical for improving prevention and treatment strategies.
基金This work is supported by a grant from National Science Foundation of China(No.81574098).
文摘Traditional Chinese medicine(TCM)has a comprehensive and thorough understanding of biological rhythm.Biological rhythm is an inherent connotation of“harmony between human and nature”,one of the thoughts in TCM.TCM discusses emphatically circadian rhythm,syzygial rhythm and seasonal rhythm,and particularly circadian and seasonal rhythms.Theories of Yin Yang and Five Elements are the principles and methods,with which TCM understands biological rhythms.Based on theories in TCM,biological rhythm in essence is a continuous variation of the human body state synchronized with natural rhythms,and theories of Yin Yang and Five Elements are both language tools to describe this continuous variation and theoretical tools for its investigation and application.The understandings of biological rhythm in TCM can be applied to etiology,health care,disease control and treatment.Many understandings in TCM have been confirmed by modern research and clinical reports,but there are still some pending issues.TCM is distinguished for its holistic viewpoint on biological rhythms.
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A heart attack disrupts the normal flow of blood to the heart muscle,potentially causing severe damage or death if not treated promptly.It can lead to long-term health complications,reduce quality of life,and significantly impact daily activities and overall well-being.Despite the growing popularity of deep learning,several drawbacks persist,such as complexity and the limitation of single-model learning.In this paper,we introduce a residual learning-based feature fusion technique to achieve high accuracy in differentiating abnormal cardiac rhythms heart sound.Combining MobileNet with DenseNet201 for feature fusion leverages MobileNet lightweight,efficient architecture with DenseNet201,dense connections,resulting in enhanced feature extraction and improved model performance with reduced computational cost.To further enhance the fusion,we employed residual learning to optimize the hierarchical features of heart abnormal sounds during training.The experimental results demonstrate that the proposed fusion method achieved an accuracy of 95.67%on the benchmark PhysioNet-2016 Spectrogram dataset.To further validate the performance,we applied it to the BreakHis dataset with a magnification level of 100X.The results indicate that the model maintains robust performance on the second dataset,achieving an accuracy of 96.55%.it highlights its consistent performance,making it a suitable for various applications.
基金supported in part by the Technology Innovation Program(20017345)funded by the Ministry of Trade,Industry and Energy(MOTIE),Republic of Korea.
文摘This paper presents a novel rehabilitation robot designed to address the challenges of Passive Range of Motion(PROM)exercises for frozen shoulder patients by integrating advanced scapulohumeral rhythm stabilization.Frozen shoulder is characterized by limited glenohumeral motion and disrupted scapulohumeral rhythm,with therapist-assisted interventions being highly effective for restoring normal shoulder function.While existing robotic solutions replicate natural shoulder biomechanics,they lack the ability to stabilize compensatory movements,such as shoulder shrugging,which are critical for effective rehabilitation.Our proposed device features a 6 Degrees of Freedom(DoF)mechanism,including 5 DoF for shoulder motion and an innovative 1 DoF Joint press for scapular stabilization.The robot employs a personalized two-phase operation:recording normal shoulder movement patterns from the unaffected side and applying them to guide the affected side.Experimental results demonstrated the robot’s ability to replicate recorded motion patterns with high precision,with Root Mean Square Error(RMSE)values consistently below 1 degree.In simulated frozen shoulder conditions,the robot effectively suppressed scapular elevation,delaying the onset of compensatory movements and guiding the affected shoulder to move more closely in alignment with normal shoulder motion,particularly during arm elevation movements such as abduction and flexion.These findings confirm the robot’s potential as a rehabilitation tool capable of automating PROM exercises while correcting compensatory movements.The system provides a foundation for advanced,personalized rehabilitation for patients with frozen shoulders.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(grant number:242300421283)+1 种基金Henan Province Science and Technology Research and Development(grant number:242102311176)Henan Province medical science and technology research project(grant number:SBGJ202403038)。
文摘Objective:Circadian rhythm disruption(CRD)is a risk factor that correlates with poor prognosis across multiple tumor types,including hepatocellular carcinoma(HCC).However,its mechanism remains unclear.This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.Methods:To quantify CRD,the HCC CRD score(HCCcrds)was developed.Using machine learning algorithms,we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort(n=369),and the robustness of this method was validated.Furthermore,we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.Results:We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis.The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis,higher pathological grade,and advanced clinical stages,while the CRD-related subtype with low HCCcrds had better clinical outcomes.We also identified novel biomarkers for each subtype,such as nicotinamide nmethyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.Conclusion:We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers.Within these groups greater HCCcrds was associated with worse prognosis.This approach has the potential to improve prediction of an individual’s prognosis,guide precision treatments,and assist clinical decision making for HCC patients.
文摘Objective:To analyze the characteristics of ambulatory blood pressure in elderly patients with hypertension and find out the risk factors of abnormal circadian rhythm.Methods:According to the circadian rhythm of patients’blood pressure,they were divided into group A,group B,and group C,and all the data of hypertension patients in this study were collected,including age,gender,BMI,smoking,drinking,basic diseases(diabetes,cerebrovascular disease,hyperlipidemia,etc.),fasting blood glucose,ambulatory blood pressure(24-hour mean systolic pressure,24-hour mean diastolic pressure,daytime mean systolic pressure and daytime mean diastolic pressure).Results:There were significant differences in mean systolic blood pressure and mean diastolic blood pressure at night among group A,group B and group C(P<0.05).Age,hyperlipidemia and fasting blood glucose were risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium was a protective factor for circadian rhythm abnormality(P<0.05).Conclusion:Age,hyperlipidemia and fasting blood glucose are risk factors for circadian rhythm abnormality(P<0.05),and 24-hour urinary sodium is a protective factor for circadian rhythm abnormality(P<0.05).
基金Chongqing Sports Scientific Research Project“Research and Development of Balance Rhythm Dance and Its Application in Reducing Fall Risk in Older Women”(Project No.D202209)Chongqing Nursing Vocational College College-level Project“Research on the Talent Training Model of Field Engineers in the Intelligent Health Care Sector Based on Rehabilitation Assistive Devices under the‘Integration of Science and Education’Approach”(Project No.Y202307)+1 种基金Chongqing Science and Technology Bureau Research Project“Investigating the Impact of Electro-acupuncture Applied to Antagonist Muscles on Walking Ability in Stroke Patients with Hemiplegia Based on the Principle of Reciprocal Inhibition”(Project No.CSTC2019JXJL130019)Chongqing Traditional Chinese Medicine Hospital Research Project“The Alterations in the Pelvic Floor Muscle Group Following Acupuncture Treatment for Postpartum Stress Urinary Incontinence Were Evaluated Using SWE Technology”(Project No.jxyn2021-2-23)。
文摘Objective: To investigate the effect of a self-developed balance rhythm dance program on the rehabilitation of motor function and the reduction of fall risk in elderly women with diminished balance function. Methods: Fifty elderly women with reduced balance function, admitted to the Qingbar Elderly Care Center of Chongqing Medical University from December 2022 to December 2023, were randomly selected and divided into two groups. The aerobic exercise group (25 patients) received traditional treatment and rehabilitation nursing, while the balance rhythm dance intervention group (25 patients) received the balance rhythm dance intervention in addition to traditional treatment and rehabilitation nursing. The Unified Parkinson’s Disease Rating Scale (UPDRS) and Berg Balance Scale (BBS) were used as evaluation indicators to compare the intervention effects between the two groups. Results: The data revealed that the balance rhythm dance intervention significantly improved the motor ability and balance function of elderly women in the intervention group (P < 0.01), with statistically significant differences observed. Conclusion: The balance rhythm dance program plays a critical role in promoting the rehabilitation of motor function and balance ability in elderly women, effectively enhancing their quality of life.
基金Supported by Beijing University of Chinese Medicine First Class Discipline Construction:90010961020079。
文摘The ability of natural conception decreases with age,leading many advanced-age women with fertility desire begin to attempt in vitro fertilization and embryo transfer(IVF-ET)technique nowadays.Traditional Chinese medicine(TCM)believes that human body undergoes periodic changes corresponding to the natural rhythms.Women exhibit distinct physiological lunar rhythms of the thoroughfare vessel and the conception vessel,as well as pathological rhythms during the menstrual cycle and IVF-ET cycle.Based on the theory of TCM temporal rhythm,this paper discusses the pathogenesis characteristics of infertility in advanced-age women at different stages.It believes that acupuncture intervention should comply with the following ideas:determining main acupoints based on disease differentiation,with a preference for the acupoints on the thoroughfare vessel,the conception vessel,spleen meridian and kidney meridian,as well as the back-shu points of the liver,spleen and kidney;determining the supplementary acupoints based on syndrome differentiation and symptoms;determining the supplementary acupoints based on time differentiation of lunar rhythm of the thoroughfare vessel and the conception vessel,and integrating both reinforcing and reducing techniques.During the process of intervention,the physical and mental states were balanced simultaneously.
基金supported by the National Natural Science Foundation of China(12171373)supported by the Fundamental Research Funds for the Central Universities of China(GK202207018).
文摘Rhythm,as a prominent characteristic of auditory experiences such as speech and music,is known to facilitate attention,yet its contribution to working memory(WM)remains unclear.Here,human participants temporarily retained a 12-tone sequence presented rhythmically or arrhythmically in WM and performed a pitch change-detection task.Behaviorally,while having comparable accuracy,rhythmic tone sequences showed a faster response time and lower response boundaries in decision-making.Electroencephalographic recordings revealed that rhythmic sequences elicited enhanced non-phase-locked beta-band(16 Hz–33 Hz)and theta-band(3 Hz–5 Hz)neural oscillations during sensory encoding and WM retention periods,respectively.Importantly,the two-stage neural signatures were correlated with each other and contributed to behavior.As beta-band and theta-band oscillations denote the engagement of motor systems and WM maintenance,respectively,our findings imply that rhythm facilitates auditory WM through intricate oscillation-based interactions between the motor and auditory systems that facilitate predictive attention to auditory sequences.
基金supported by the Key Collaborative Research Program of the Alliance of International Science Organizations(ANSO-CR-KP-2022-10)Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project(2021ZD0200200)+2 种基金Natural Science Foundation of China(82151307,82202253,and 31620103905)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32030207)Science Frontier Program of the Chinese Academy of Sciences(QYZDJ-SSW-SMCO19).
文摘Closed-loop neuromodulation,especially using the phase of the electroencephalography(EEG)rhythm to assess the real-time brain state and optimize the brain stimulation process,is becoming a hot research topic.Because the EEG signal is non-stationary,the commonly used EEG phase-based prediction methods have large variances,which may reduce the accuracy of the phase prediction.In this study,we proposed a machine learning-based EEG phase prediction network,which we call EEG phase prediction network(EPN),to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data.We verified the performance of EPN on pre-recorded data,simulated EEG data,and a real-time experiment.Compared with widely used state-of-the-art models(optimized multi-layer filter architecture,auto-regress,and educated temporal prediction),EPN achieved the lowest variance and the greatest accuracy.Thus,the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.
基金supported by the National Natural Science Foundation of China(82030026,81900787,81770819,82300877,and 82450002)the Key Project supported by Medical Science and technology development Foundation,Nanjing Department of Health(YKK24104)+1 种基金the Medical Research Program of Jiangsu Provincial Health Committe(M2024050)the China Postdoctoral Science Foundation(2023M731628).
文摘Background:The prevalence of circadian misalignment,particularly social jetlag(SJL),contributes significantly to the epidemic of metabolic disorders.However,the precise impact of SJL on the liver has remained poorly elucidated.Methods:The rhythmicity of circulating prolactin(PRL)was evaluated in subjects with SJL and mice under SJL.The causative mechanism of SJL on fatty liver was explored using jetlag model in wild-type and PrI^(-/-) mice.Luciferase reporter assay,electrophoretic mobility shift assay,and chromatin immunoprecipitation analysis were used to study the transcriptional mechanism of retinoic acid receptor-related orphan receptor α on PRL.RNA-sequencing(RNA-seq)on human and mice liver as well as circadian analysis were used to study the mechanism of SJL-associated desynchronized PRL on hepatic lipid metabolism.The therapeutic effect of PRL intervention on SJL-induced mice at different time points was compared.Results:SJL increases the risk of metabolic dysfunction-associated steatotic liver disease(MASLD),mediated by the disruption of the rhythmicity of serum PRL.In particular,SJL inhibits the rhythmic transcription of PRL in the pituitary,leading to desynchronized PRL levels in circulation.Under jetlag conditions,the rhythmicity of the hepatic PRL signaling pathway was significantly dampened,which resulted in increased lipogenesis via inhibited hepatic mitogen-activated protein kinase/cyclin D1 expressions.Notably,PRL treatment at PRL nadir in jetlagged mice decreased hepatic lipid content and liver injury markers to a greater extent compared with conventional PRL administration.Conclusions:Reprogrammed hepatic PRL signaling pathway with concomitant dysregulated lipid metabolism homeostasis was the causative mechanism of fatty liver under SJL,which was mediated through derailed serum PRL rhythm.Restoration of PRL rhythm could effectively alleviate SJL-induced fatty liver,providing new insight into treating MASLD.
基金Supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0507200The Suqian Sci Tech Program,No.Z2023106+2 种基金National Natural Science Foundation of China,No.82071234,No.31400947 and No.82170836Gusu Talent Program,No.GSWS2022030The Clinical Research Center of Neurological Disease of The Second Affiliated Hospital of Soochow University,No.ND2024A02.
文摘BACKGROUND Diabetic gastrointestinal autonomic neuropathy(DGAN)often affects the patients’quality of life.Thus,research on influencing factors of DGAN may promote DGAN prevention and decrease the incidence rate.This study used electrogastrogram(EGG)to assess the relationship between metabolic dysfunction-associated steatotic liver disease(MASLD)and DGAN.AIM To analyze the changes of EGG in patients with MASLD and type 2 diabetes mellitus(T2DM),and to elucidate whether ultrasound-diagnosed MASLD is an independent risk factor for diabetic gastric motility disorders(DGMD).METHODS A total of 272 patients with T2DM hospitalized at the Second Affiliated Hospital of Soochow University from December 2020 to December 2021 and the Affiliated Suqian Hospital of Xuzhou Medical University from November 2023 to June 2024 were included in the cross-sectional study.General information,clinical data,and medical history of all study subjects,including name,age,gender,body mass index,and duration of diabetes were collected.Laboratory tests included biochemical parameters,glycosylated hemoglobin(HbA1c),fasting C-peptide,2h postprandial C-peptide and 25-hydroxyvitamin D[25(OH)D].EGG,fundus examination and carotid artery ultrasonography were performed and results were recorded.According to the results of EGG,the subjects were divided into the DGMD group and non-DGMD group.RESULTS The duration of diabetes,fasting blood glucose(FBG),HbA1c,25(OH)D and the prevalence of MASLD were significantly higher in the DGMD group(P<0.05).Multiple logistic regression analysis showed that the duration,FBG,25(OH)D and the presence of MASLD were independent influencing factors.CONCLUSION MASLD is strongly associated with an increased incidence of DGMD.Timely treatment of MASLD is effective to prevent diabetic gastroparesis.
文摘The volatile compounds from ash-leaf maple (Acer negundo L.) were examined by adsorption-thermodesorption and GC-MS. Thirty-two compounds, including alcohols, ketones, aldehydes, esters, terpenoids, carboxylic acids, etc. were identified. The analysis revealed that the diurnal rhythm of release of volatile compounds from maple differed in July and in August. In July, the releasing of most volatile compounds reached the peak at 14 o'clock, when in August, the emission of volatile compounds reached the peak at 10 o'clock. Besides diurnal rhythm, there also existed other differences in the releasing of volatiles and their relative contents in July and in August. A possible explanation for this phenomenon is the maturation of leaves, since the sampling conditions were the same both in July and August. At the same time, the response of Anoplophora glabrpennis Motschulsky to volatiles was examined with field bioassay with traps. cis-3-hexen-1-ol was found to be more effective to attract A. glabrpennis than other volatiles released by ash-leaf maple tree in field trapping test. A mixture of 1-butanol, 1-pentanol and 2-pentanol was tested to be the most attractive to A. glabripennis among all tested volatiles. More field trapping tests should be conducted.
基金The project was sponsored by the Scientific Re-search Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (1999-363).
文摘In July 2006, the diurnal activity rhythms of 13 heads of captive Qinling golden takin were observed in Shaanxi Provincial Centre for the Breeding and Conservation of Rare Wildlife （SPCBCRW） at daylight （from 9：00 am to 4：00 pm in July）. The behavioral ethnogram was identified through observation at the sampling site, with the behaviors of golden takin recorded at 5 min interval using instantaneous scannable sampling method. The results indicated that the resting of golden takin took an important part in the daylight activities. Meanwhile, drinking and urinating and defecating were 1.92 and 0.54 and 0.92 times per head per day. Ambient temperature had a strong effect on the diurnal activity rhythms of golden takin. The diurnal activity rhymes were affected by ages of the animals effectively, which was expressed through differentiation of the time budgets. Moreover, different individuals in the same population showed some non-synchronously activity rhythms.
