Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public hea...Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.展开更多
In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition syste...In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition systems that initiate the so-called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), both of which are accompanied by a set of induced defenses that usually repel pathogen attacks. Here we discuss the complex network of signaling pathways occurring during PTI, focusing on the involvement of mitogen-activated protein kinases.展开更多
Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardia...Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardial infarction(MI)by inducing angiogenesis.Methods:Male,adult Sprague-Dawley rats were randomly divided into 5 groups(n=12 in each group):sham group(S),sedentary MI group(MI),MI+resistance exercise group(MR),MI+adeno-associated virus(AAV)-FSTL1 injection group(MA),and MI+AAV-FSTL1 injection+resistance exercise group(MAR).The AAV-FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle.The MI model was established by ligation of the left anterior descending coronary artery.Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder.Heart function was evaluated by hemodynamic measures.Collagen volume fraction of myocardium was observed and analyzed by Masson’s staining.Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-b receptor 1(TGFbR1)inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1.Angiogenesis,cell proliferation,and disco interacting protein 2 homolog A(DIP2A)location were observed by immunofluorescence staining.The expression of FSTL1,DIP2A,and the activation of signaling pathways were detected by Western blotting.Angiogenesis of endothelial cells was observed by tubule experiment.One-way analysis of variance and Student’s t test were used for statistical analysis.Results:Resistance exercise stimulated the secretion of skeletal muscle FSTL1,which promoted myocardial angiogenesis,inhibited pathological remodeling,and protected cardiac function in MI rats.Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart.Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A,while TGFbR1 inhibitor intervention down-regulated the phosphorylation level of Smad2/3 and the expression of vascular endothelial growth factor-A,which was not conducive to angiogenesis.FSTL1 bound to the receptor,DIP2A,to regulate angiogenesis mainly through the Smad2/3 signaling pathway.FSTL1-DIP2A directly activated Smad2/3 and was not affected by TGFbR1.Conclusion:Dynamic resistance exercise stimulates the expression of skeletal muscle-derived FSTL1,which could supplement the insufficiency of cardiac FSTL1 and promote cardiac rehabilitation through the DIP2A-Smad2/3 signaling pathway in MI rats.展开更多
As sessile organisms plants must ronmental conditions. To survive cope with ever changing enviplants have evolved elaborate mechanisms to perceive and rapidly respond to a diverse range of abiotic and biotic stresses....As sessile organisms plants must ronmental conditions. To survive cope with ever changing enviplants have evolved elaborate mechanisms to perceive and rapidly respond to a diverse range of abiotic and biotic stresses. Central to this response is the ability to modulate gene expression at both the transcriptional and posttranscriptional levels. This review will focus on recent progress that has been made towards understanding the rapid reprogramming of the transcriptome that occurs in response to stress as well as emerging mechanisms underpinning the reprogramming of gene expression in response to stress,展开更多
Bradykinin is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at the site of tissue damage or inflammation
Objective To investigate the mechanisms through which kidney-tonifying herbs(KTHs) and liver-clearing herbs(LCHs) in Dingjing Decoction(DJD) regulate premature ovarian failure(POF). Methods One hundred and fif...Objective To investigate the mechanisms through which kidney-tonifying herbs(KTHs) and liver-clearing herbs(LCHs) in Dingjing Decoction(DJD) regulate premature ovarian failure(POF). Methods One hundred and fifty Sprague-Dawley rats were randomly divided into five groups such as control, model, KTHs, LCHs, and DJD groups. POF-related biological molecules were examined. Factor analysis was performed to investigate the regulatory networks and key biomolecules involved in mediating POF after treatment with KTHs and LCHs. Results The master regulatory factors in the reproductive endocrine network associated with KTHs intervention included four molecules in the pituitary-ovarian axis, cortisol(CORT) in the target gland of pituitary-adrenal axis, and some molecules in the hypothalamus. In contrast, the master regulatory factors associated with LCHs intervention included four molecules in the pituitary-ovarian axis and some molecules in the hypothalamus; No biomolecules in the pituitary-adrenal axis were involved in the LCH-mediated mechanisms.Gonadotropin-releasing hormone(Gn RH), which was identified as a common biological molecule in the hypothalamus, was involved in regulating the reproductive endocrine network in association with KTHs intervention. Conclusion KTHs directly regulates biological molecules in the pituitary-adrenal axis and indirectly regulates those in the pituitary-adrenal axis through the hypothalamus, while the LCHs only exert its effects indirectly. Gn RH is the key biological molecule associated with KTHs intervention.展开更多
Metastases,or migration of cancers,are common and severe cancer complications.Although the 5-year survival rates of primary tumors have greatly improved,those of metastasis remain below 30%,highlighting the importance...Metastases,or migration of cancers,are common and severe cancer complications.Although the 5-year survival rates of primary tumors have greatly improved,those of metastasis remain below 30%,highlighting the importance of investigating specific mechanisms and therapeutic approaches for metastasis.Microfluidic devices have emerged as a powerful platform for drug target identification and drug response screening and allow incorporation of complex interactions in the metastatic microenvironment as well as manipulation of individual factors.In this work,we review microfluidic devices that have been developed to study cancer cell migration and extravasation in response to mechanical(section‘Microfluidic investigation of mechanical factors in cancer cell migration’),biochemical(section‘Microfluidic investigation of biochemical signals in cancer cell invasion’),and cellular(section‘Microfluidic metastasis-on-a-chip models for investigation of cancer extravasation’)signals.We highlight the device characteristics,discuss the discoveries enabled by these devices,and offer perspectives on future directions for microfluidic investigations of cancer metastasis,with the ultimate aim of identifying the essential factors for a‘metastasis-on-a-chip’platform to pursue more efficacious treatment approaches for cancer metastasis.展开更多
Leaf shape is highly variable within and among plant species,ranging from slender to oval shaped.This is largely determined by the proximodistal axis of growth.However,little is known about how proximal–distal growth...Leaf shape is highly variable within and among plant species,ranging from slender to oval shaped.This is largely determined by the proximodistal axis of growth.However,little is known about how proximal–distal growth is controlled to determine leaf shape.Here,we show that Arabidopsis leaf and sepal proximodistal growth is tuned by two phytohormones.Two class A AUXIN RESPONSE FACTORs(ARFs),ARF6 and ARF8,activate the transcription of DWARF4,which encodes a key brassinosteroid(BR)biosynthetic enzyme.At the cellular level,the phytohormones promote more directional cell expansion along the proximodistal axis,as well as final cell sizes.BRs promote the demethyl-esterification of cell wall pectins,leading to isotropic in-plane cell wall loosening.Notably,numerical simulation showed that isotropic cell wall loosening could lead to directional cell and organ growth along the proximodistal axis.Taken together,we show that auxin acts through biosynthesis of BRs to determine cell wall mechanics and directional cell growth to generate leaves of variable roundness.展开更多
基金supported by the Natural Science Foundation of Beijing,China(7214223,7212027)the Beijing Hospitals Authority Youth Programme(QML20210601)+3 种基金the Chinese Scholarship Council(CSC)scholarship(201706210415)the National Key Research and Development Program of China(2017YFC0908800)the Beijing Municipal Health Commission(PXM2020_026272_000002,PXM2020_026272_000014)the National Natural Science Foundation of China(82070293).
文摘Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.
文摘In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition systems that initiate the so-called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), both of which are accompanied by a set of induced defenses that usually repel pathogen attacks. Here we discuss the complex network of signaling pathways occurring during PTI, focusing on the involvement of mitogen-activated protein kinases.
基金supported this research:The National Natural Science Foundation of China(No.31671240 to ZT,No.31900828 to YX).
文摘Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardial infarction(MI)by inducing angiogenesis.Methods:Male,adult Sprague-Dawley rats were randomly divided into 5 groups(n=12 in each group):sham group(S),sedentary MI group(MI),MI+resistance exercise group(MR),MI+adeno-associated virus(AAV)-FSTL1 injection group(MA),and MI+AAV-FSTL1 injection+resistance exercise group(MAR).The AAV-FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle.The MI model was established by ligation of the left anterior descending coronary artery.Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder.Heart function was evaluated by hemodynamic measures.Collagen volume fraction of myocardium was observed and analyzed by Masson’s staining.Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-b receptor 1(TGFbR1)inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1.Angiogenesis,cell proliferation,and disco interacting protein 2 homolog A(DIP2A)location were observed by immunofluorescence staining.The expression of FSTL1,DIP2A,and the activation of signaling pathways were detected by Western blotting.Angiogenesis of endothelial cells was observed by tubule experiment.One-way analysis of variance and Student’s t test were used for statistical analysis.Results:Resistance exercise stimulated the secretion of skeletal muscle FSTL1,which promoted myocardial angiogenesis,inhibited pathological remodeling,and protected cardiac function in MI rats.Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart.Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A,while TGFbR1 inhibitor intervention down-regulated the phosphorylation level of Smad2/3 and the expression of vascular endothelial growth factor-A,which was not conducive to angiogenesis.FSTL1 bound to the receptor,DIP2A,to regulate angiogenesis mainly through the Smad2/3 signaling pathway.FSTL1-DIP2A directly activated Smad2/3 and was not affected by TGFbR1.Conclusion:Dynamic resistance exercise stimulates the expression of skeletal muscle-derived FSTL1,which could supplement the insufficiency of cardiac FSTL1 and promote cardiac rehabilitation through the DIP2A-Smad2/3 signaling pathway in MI rats.
文摘As sessile organisms plants must ronmental conditions. To survive cope with ever changing enviplants have evolved elaborate mechanisms to perceive and rapidly respond to a diverse range of abiotic and biotic stresses. Central to this response is the ability to modulate gene expression at both the transcriptional and posttranscriptional levels. This review will focus on recent progress that has been made towards understanding the rapid reprogramming of the transcriptome that occurs in response to stress as well as emerging mechanisms underpinning the reprogramming of gene expression in response to stress,
文摘Bradykinin is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at the site of tissue damage or inflammation
基金National Natural Science Foundation of China(No.81073073,No.81403153)
文摘Objective To investigate the mechanisms through which kidney-tonifying herbs(KTHs) and liver-clearing herbs(LCHs) in Dingjing Decoction(DJD) regulate premature ovarian failure(POF). Methods One hundred and fifty Sprague-Dawley rats were randomly divided into five groups such as control, model, KTHs, LCHs, and DJD groups. POF-related biological molecules were examined. Factor analysis was performed to investigate the regulatory networks and key biomolecules involved in mediating POF after treatment with KTHs and LCHs. Results The master regulatory factors in the reproductive endocrine network associated with KTHs intervention included four molecules in the pituitary-ovarian axis, cortisol(CORT) in the target gland of pituitary-adrenal axis, and some molecules in the hypothalamus. In contrast, the master regulatory factors associated with LCHs intervention included four molecules in the pituitary-ovarian axis and some molecules in the hypothalamus; No biomolecules in the pituitary-adrenal axis were involved in the LCH-mediated mechanisms.Gonadotropin-releasing hormone(Gn RH), which was identified as a common biological molecule in the hypothalamus, was involved in regulating the reproductive endocrine network in association with KTHs intervention. Conclusion KTHs directly regulates biological molecules in the pituitary-adrenal axis and indirectly regulates those in the pituitary-adrenal axis through the hypothalamus, while the LCHs only exert its effects indirectly. Gn RH is the key biological molecule associated with KTHs intervention.
基金financial support by the Natural Sciences and Engineering Research Council of Canada via Discovery Grants to LDY and YS and by the Canada Research Chairs Program.
文摘Metastases,or migration of cancers,are common and severe cancer complications.Although the 5-year survival rates of primary tumors have greatly improved,those of metastasis remain below 30%,highlighting the importance of investigating specific mechanisms and therapeutic approaches for metastasis.Microfluidic devices have emerged as a powerful platform for drug target identification and drug response screening and allow incorporation of complex interactions in the metastatic microenvironment as well as manipulation of individual factors.In this work,we review microfluidic devices that have been developed to study cancer cell migration and extravasation in response to mechanical(section‘Microfluidic investigation of mechanical factors in cancer cell migration’),biochemical(section‘Microfluidic investigation of biochemical signals in cancer cell invasion’),and cellular(section‘Microfluidic metastasis-on-a-chip models for investigation of cancer extravasation’)signals.We highlight the device characteristics,discuss the discoveries enabled by these devices,and offer perspectives on future directions for microfluidic investigations of cancer metastasis,with the ultimate aim of identifying the essential factors for a‘metastasis-on-a-chip’platform to pursue more efficacious treatment approaches for cancer metastasis.
基金supported by the National Natural Science Foundation of China(NSFC)grants 31825002 and 31861143021the Key Research Project of the Frontier Science of CAS grant ZDBS-LY-SM012,and the Strategic Priority Research Program of CAS grant XDA24020203.Y.W.acknowledges the National Key R&D Program of China grant 2019YFA0903902 and NSFC grant 31871245.F.D.was supported by a Young Scientists Fund of NSFC(grant 32000507).C.T.was supported by NSFC grants 31961133010 and 31970805the Youth Innovation Promotion Association of CAS(award 2017139).
文摘Leaf shape is highly variable within and among plant species,ranging from slender to oval shaped.This is largely determined by the proximodistal axis of growth.However,little is known about how proximal–distal growth is controlled to determine leaf shape.Here,we show that Arabidopsis leaf and sepal proximodistal growth is tuned by two phytohormones.Two class A AUXIN RESPONSE FACTORs(ARFs),ARF6 and ARF8,activate the transcription of DWARF4,which encodes a key brassinosteroid(BR)biosynthetic enzyme.At the cellular level,the phytohormones promote more directional cell expansion along the proximodistal axis,as well as final cell sizes.BRs promote the demethyl-esterification of cell wall pectins,leading to isotropic in-plane cell wall loosening.Notably,numerical simulation showed that isotropic cell wall loosening could lead to directional cell and organ growth along the proximodistal axis.Taken together,we show that auxin acts through biosynthesis of BRs to determine cell wall mechanics and directional cell growth to generate leaves of variable roundness.