Critical transitions and tipping phenomena between two meta-stable states in stochastic dynamical systems are a scientific issue.In this work,we expand the methodology of identifying the most probable transition pathw...Critical transitions and tipping phenomena between two meta-stable states in stochastic dynamical systems are a scientific issue.In this work,we expand the methodology of identifying the most probable transition pathway between two meta-stable states with Onsager±Machlup action functional,to investigate the evolutionary transition dynamics between two meta-stable invariant sets with Schrödinger bridge.In contrast to existing methodologies such as statistical analysis,bifurcation theory,information theory,statistical physics,topology,and graph theory for early warning indicators,we introduce a novel framework on Early Warning Signals (EWS) within the realm of probability measures that align with the entropy production rate.To validate our framework,we apply it to the Morris±Lecar model and investigate the transition dynamics between a meta-stable state and a stable invariant set (the limit cycle or homoclinic orbit) under various conditions.Additionally,we analyze real Alzheimer’s data from the Alzheimer’s Disease Neuroimaging Initiative database to explore EWS indicating the transition from healthy to pre-AD states.This framework not only expands the transition pathway to encompass measures between two specified densities on invariant sets,but also demonstrates the potential of our early warning indicators for complex diseases.展开更多
The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenes...The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin(SOST) that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influencea A osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or "osteokines"from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin(OCN) secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2(LCN2) is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain.We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.展开更多
L-茶氨酸(L-Theanine,LTA)是茶叶中独特的游离氨基酸,是茶汤鲜爽味的主要来源,具有多种生物活性,属于新食品原料。本文基于Citespace和VOSviewer对Web of Science核心数据库和中国知网数据库,对2014~2024年LTA相关文献进行可视化分析,...L-茶氨酸(L-Theanine,LTA)是茶叶中独特的游离氨基酸,是茶汤鲜爽味的主要来源,具有多种生物活性,属于新食品原料。本文基于Citespace和VOSviewer对Web of Science核心数据库和中国知网数据库,对2014~2024年LTA相关文献进行可视化分析,其中关键词密度和贡献图谱结果显示LTA相关研究集中在茶叶类型、胁迫反应、LTA的生物活性等方面。因此,本文综述了茶叶LTA含量的影响因素,并重点阐述LTA生物活性作用机制,包括抗氧化、抗热应激、抗抑郁、调节代谢、抗癌、调节免疫、调节肠道菌群、保护神经系统、保护肝脏和保护肠道的作用机制,发现LTA主要通过调控核因子κB(Nuclear factor kappa B,NF-κB)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、信号传导及转录激活因子(Signal transducer and activator of transcription,STAT)和丝裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)等信号通路发挥生物活性功能,并总结了当前LTA在食品产业中的实际应用。本文可为LTA的研究和发展提供方向,并为开发LTA功能性食品提供一定的参考。展开更多
Dietary restriction(DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver funct...Dietary restriction(DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet(HFD)(34% of energy), then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group. Rats in control group were fed routinely. After DR for 5 weeks, the average body weight, liver weight, liver index, serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group(P〈0.05 or P〈0.01), so did alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH) levels and the ratio of LDL-C/HDL-C in the DR50% group(P〈0.05 or P〈0.01). Histopathology examination of liver tissues further proved ameliorative effect of DR on liver function. Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1(SIRT1) in liver and adipose, while notably decreased the expression of peroxisome proliferators-activated receptors-gamma(PPARγ) in adipose(P〈0.05 or P〈0.01). The increase of SIRT1 and decrease of PPARγ may be a mechanism by which DR reduces blood lipids and ameliorates liver function.展开更多
Aim: To evaluate the joint action of phoxim and fenvalerate on the reproductive function in male Sprague-Dawley rats. Methods: The 2×2 factorial analysis experiment was used in the study. The pesticides were oral...Aim: To evaluate the joint action of phoxim and fenvalerate on the reproductive function in male Sprague-Dawley rats. Methods: The 2×2 factorial analysis experiment was used in the study. The pesticides were orally given at daily doses of phoxim (Pho) 8.2 nig/kg, fenvalerate (Fen) 3.3 mg/kg and Pho 8.2+Fen 3,3 mg/kg (Pho:Fen = 5:2), 5 days a week for 60 days. Sperm motility was measured with computer-assisted sperm motility analysis (CASA) and daily sperm production estimated. Immunoenzymatic method and electron microscopy were used to evaluate the serum testosterone and the testicular morphology, respectively. Results: There were significant decreases in sperm motility parameters in the treated animals, including straight line velocity (VSL), beat cross frequency (BCF), linearity (LIN) and straightness (STR). After treated with Fen, significant decreases in VSL, LIN and STR were demonstrated. Significant decreases of daily sperm production were seen in animals treated with Pho and Pho+Fen in comparison with the controls. Serum testosterone levels were not significantly changed in the treated groups. Factorial ANOVA showed that no significant interactions were noted between Pho and Fen in sperm motility, sperm production and serum testosterone. Both the single and mixed pesticides caused various degrees of testicular lesions, involving vacuolation of endoplasmic reticulum and necrosis of Sertoli cells. Conclusion: The pesticides may cause sperm motility changes and testicular lesions in male rats. The action of Pho and Fen may be additive.展开更多
When watching someone performs an action, mirror neurons are activated in a way that is very similar to the activation that occurs when actually performing that action. Previous single-sample case studies indicate tha...When watching someone performs an action, mirror neurons are activated in a way that is very similar to the activation that occurs when actually performing that action. Previous single-sample case studies indicate that hand-action observation training may lead to activation and remodeling of mirror neuron systems, which include important language centers, and may improve language function in aphasia patients. In this randomized-block-design experiment, we recruited 24 aphasia patients from, Zhongda Hospital, Southeast University, China. The patients were divided into three groups where they underwent hand-action observation and repetition, dynamic-object observation and repetition, or conventional speech therapy. Training took place 5 days per week, 35 minutes per day, for 2 weeks. We assessed language function via picture naming tests for objects and actions and the Western Aphasia Battery. Among the participants, one patient, his wife and four healthy student volunteers underwent functional magnetic resonance imaging to analyze changes in brain activation during hand-action observation and dynamic-object observation. Results demonstrated that, compared with dynamic-object observation, hand-action observation led to greater performance with respect to the aphasia quotient and affiliated naming sub-tests and a greater Western Aphasia Battery test score. The overall effect was similar to that of conventional aphasia training, yet hand-action observation had advantages compared with conventional training in terms of vocabulary extraction and spontaneous speech. Thus, hand-action observation appears to more strongly activate the mirror neuron system compared with dynamic-object observation. The activated areas included Broca's area, Wernicke's area, and the supramarginal gyrus. These results suggest that hand-action observation combined with repetition might better improve language function in aphasia patients compared with dynamic-object observation combined with repetition. The therapeutic mechanism of this intervention may be associated with activation of additional mirror neuron systems, and may have implications for the possible repair and remodeling of damaged nerve networks. The study protocol was approved by the Ethical Committee of Nanjing Medical University, China(approval number: 2011-SRFA-086) on March 11, 2011. This trial has been registered in the ISRCTN Registry(ISRCTN84827527).展开更多
基金National Key Research and Development Program of China,Grant/Award Number:2021ZD0201300National Natural Science Foundation of China,Grant/Award Numbers:12401233,12141107+2 种基金Guangdong Provincial Key Laboratory of Mathematical and Neural Dynamical Systems,Grant/Award Number:2024B1212010004Cross Disciplinary Research Team on Data Science and Intelligent Medicine,Grant/Award Number:2023KCXTD054Guangdong-Dongguan Joint Research,Grant/Award Number:2023A1515140016。
文摘Critical transitions and tipping phenomena between two meta-stable states in stochastic dynamical systems are a scientific issue.In this work,we expand the methodology of identifying the most probable transition pathway between two meta-stable states with Onsager±Machlup action functional,to investigate the evolutionary transition dynamics between two meta-stable invariant sets with Schrödinger bridge.In contrast to existing methodologies such as statistical analysis,bifurcation theory,information theory,statistical physics,topology,and graph theory for early warning indicators,we introduce a novel framework on Early Warning Signals (EWS) within the realm of probability measures that align with the entropy production rate.To validate our framework,we apply it to the Morris±Lecar model and investigate the transition dynamics between a meta-stable state and a stable invariant set (the limit cycle or homoclinic orbit) under various conditions.Additionally,we analyze real Alzheimer’s data from the Alzheimer’s Disease Neuroimaging Initiative database to explore EWS indicating the transition from healthy to pre-AD states.This framework not only expands the transition pathway to encompass measures between two specified densities on invariant sets,but also demonstrates the potential of our early warning indicators for complex diseases.
基金supported in part by grants from 973 Program from the Chinese Ministry of Science and Technology (MOST) (2014CB964704 and 2015CB964503)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB19000000)the National Natural Science Foundation of China (NSFC) (31371463, 81672119, and 81725010)
文摘The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin(SOST) that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influencea A osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or "osteokines"from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin(OCN) secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2(LCN2) is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain.We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.
文摘L-茶氨酸(L-Theanine,LTA)是茶叶中独特的游离氨基酸,是茶汤鲜爽味的主要来源,具有多种生物活性,属于新食品原料。本文基于Citespace和VOSviewer对Web of Science核心数据库和中国知网数据库,对2014~2024年LTA相关文献进行可视化分析,其中关键词密度和贡献图谱结果显示LTA相关研究集中在茶叶类型、胁迫反应、LTA的生物活性等方面。因此,本文综述了茶叶LTA含量的影响因素,并重点阐述LTA生物活性作用机制,包括抗氧化、抗热应激、抗抑郁、调节代谢、抗癌、调节免疫、调节肠道菌群、保护神经系统、保护肝脏和保护肠道的作用机制,发现LTA主要通过调控核因子κB(Nuclear factor kappa B,NF-κB)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、信号传导及转录激活因子(Signal transducer and activator of transcription,STAT)和丝裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)等信号通路发挥生物活性功能,并总结了当前LTA在食品产业中的实际应用。本文可为LTA的研究和发展提供方向,并为开发LTA功能性食品提供一定的参考。
基金supported by a grant from the Social Development Research Program of Science and Technology Agency of Jiangsu Province(No.BE2015646)
文摘Dietary restriction(DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet(HFD)(34% of energy), then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group. Rats in control group were fed routinely. After DR for 5 weeks, the average body weight, liver weight, liver index, serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group(P〈0.05 or P〈0.01), so did alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH) levels and the ratio of LDL-C/HDL-C in the DR50% group(P〈0.05 or P〈0.01). Histopathology examination of liver tissues further proved ameliorative effect of DR on liver function. Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1(SIRT1) in liver and adipose, while notably decreased the expression of peroxisome proliferators-activated receptors-gamma(PPARγ) in adipose(P〈0.05 or P〈0.01). The increase of SIRT1 and decrease of PPARγ may be a mechanism by which DR reduces blood lipids and ameliorates liver function.
文摘Aim: To evaluate the joint action of phoxim and fenvalerate on the reproductive function in male Sprague-Dawley rats. Methods: The 2×2 factorial analysis experiment was used in the study. The pesticides were orally given at daily doses of phoxim (Pho) 8.2 nig/kg, fenvalerate (Fen) 3.3 mg/kg and Pho 8.2+Fen 3,3 mg/kg (Pho:Fen = 5:2), 5 days a week for 60 days. Sperm motility was measured with computer-assisted sperm motility analysis (CASA) and daily sperm production estimated. Immunoenzymatic method and electron microscopy were used to evaluate the serum testosterone and the testicular morphology, respectively. Results: There were significant decreases in sperm motility parameters in the treated animals, including straight line velocity (VSL), beat cross frequency (BCF), linearity (LIN) and straightness (STR). After treated with Fen, significant decreases in VSL, LIN and STR were demonstrated. Significant decreases of daily sperm production were seen in animals treated with Pho and Pho+Fen in comparison with the controls. Serum testosterone levels were not significantly changed in the treated groups. Factorial ANOVA showed that no significant interactions were noted between Pho and Fen in sperm motility, sperm production and serum testosterone. Both the single and mixed pesticides caused various degrees of testicular lesions, involving vacuolation of endoplasmic reticulum and necrosis of Sertoli cells. Conclusion: The pesticides may cause sperm motility changes and testicular lesions in male rats. The action of Pho and Fen may be additive.
基金supported by the National Natural Science Foundation of China,No.81472163,81874035(to CLS)the General Project of University Philosophy and Social Science Research of China,No.2016SJB740015(to QY)+1 种基金the Science and Technology Plan Project of Zhangjiagang city of China in 2016,No.ZKS1615(to WLC)the Youth Science and Technology Project of Suzhou Health Development through Scientific Research and Education in 2018,No.KJXW2018059(to WLC)
文摘When watching someone performs an action, mirror neurons are activated in a way that is very similar to the activation that occurs when actually performing that action. Previous single-sample case studies indicate that hand-action observation training may lead to activation and remodeling of mirror neuron systems, which include important language centers, and may improve language function in aphasia patients. In this randomized-block-design experiment, we recruited 24 aphasia patients from, Zhongda Hospital, Southeast University, China. The patients were divided into three groups where they underwent hand-action observation and repetition, dynamic-object observation and repetition, or conventional speech therapy. Training took place 5 days per week, 35 minutes per day, for 2 weeks. We assessed language function via picture naming tests for objects and actions and the Western Aphasia Battery. Among the participants, one patient, his wife and four healthy student volunteers underwent functional magnetic resonance imaging to analyze changes in brain activation during hand-action observation and dynamic-object observation. Results demonstrated that, compared with dynamic-object observation, hand-action observation led to greater performance with respect to the aphasia quotient and affiliated naming sub-tests and a greater Western Aphasia Battery test score. The overall effect was similar to that of conventional aphasia training, yet hand-action observation had advantages compared with conventional training in terms of vocabulary extraction and spontaneous speech. Thus, hand-action observation appears to more strongly activate the mirror neuron system compared with dynamic-object observation. The activated areas included Broca's area, Wernicke's area, and the supramarginal gyrus. These results suggest that hand-action observation combined with repetition might better improve language function in aphasia patients compared with dynamic-object observation combined with repetition. The therapeutic mechanism of this intervention may be associated with activation of additional mirror neuron systems, and may have implications for the possible repair and remodeling of damaged nerve networks. The study protocol was approved by the Ethical Committee of Nanjing Medical University, China(approval number: 2011-SRFA-086) on March 11, 2011. This trial has been registered in the ISRCTN Registry(ISRCTN84827527).