Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by memory and cognitive impairments.The two primary pathological hallmarks of AD include the accumulation ofβ-amyloid(Aβ)plaques and formation of...Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by memory and cognitive impairments.The two primary pathological hallmarks of AD include the accumulation ofβ-amyloid(Aβ)plaques and formation of neurofibrillary tangles(NFTs)composed predominantly of hyperphosphorylated tau protein(Zhang et al.,2023).Moreover,synaptic dysfunction is considered another crucial factor in AD pathogenesis and is closely associated with cognitive decline.Notably,synaptic damage,loss,and dysfunction manifest earlier than the pathological features of Aβplaques and NFTs(Knopman et al.,2021).Therefore,understanding the mechanisms underlying synaptic dysfunction in AD is vital for providing insights into disease mechanisms and developing novel therapeutic strategies.展开更多
MicroRNAs （miRNAs） are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ag...MicroRNAs （miRNAs） are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ageing. Recently, extracellular miRNAs have been discovered in the bloodstream and bodily fluids. These miRNAs are shown to be secreted and circulating in microvesicles （MVs）, or in complex with other factors such as RNA-binding proteins and high-density lipoprotein （HDL） particles. These cell-free, circulating miRNAs can be taken into and function as negative regulators of target genes in recipient cells. Here we review the biogenesis and uptake of circulating miRNAs as well as their profiles in ageing and ageing-related diseases. We discuss the emerging role of circulating miRNAs as biomarkers and therapeutic targets.展开更多
The degeneration of cholinergic neurons and cholinergic hypofunction are pathologies associated with Alzheimer＇s disease （AD）. Muscarinic acetylcholine receptors （mAChRs） mediate acetylcholine-induced neurotransm...The degeneration of cholinergic neurons and cholinergic hypofunction are pathologies associated with Alzheimer＇s disease （AD）. Muscarinic acetylcholine receptors （mAChRs） mediate acetylcholine-induced neurotransmission and five mAChR subtypes （M1-M5） have been identified. Among them, M1 mAChR is widely expressed in the central nervous system and has been implicated in many physiological and pathological brain functions. In addition, M1 mAChR is postulated to be an important therapeutic target for AD and several other neurodegenerative diseases. In this article, we review recent progress in understanding the functional involvement of M1 mAChR in AD pathology and in developing M1 mAChR agonists forAD treatment.展开更多
Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,...Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.展开更多
DEAR EDITOR,Extracellular vesicles(EVs)are important for the transport of biologically active materials and for intercellular communication.As an exposed mucosa,amphibian skin participates in many essential physiologi...DEAR EDITOR,Extracellular vesicles(EVs)are important for the transport of biologically active materials and for intercellular communication.As an exposed mucosa,amphibian skin participates in many essential physiological processes.To date,however,little is known about EVs in amphibian skin.Here,we successfully isolated EVs from the skin secretions of Bombina maxima,and characterized the EVs using nanoparticle tracking,western blotting,and electron microscopy.展开更多
Heat shock proteins(Hsps)are a family of abundantly expressed ATP-dependent chaperone proteins.Hsp90 is an eminent member of Hsp family.Thus far,two primary functions have been described for Hsp90:first,as a regulator...Heat shock proteins(Hsps)are a family of abundantly expressed ATP-dependent chaperone proteins.Hsp90 is an eminent member of Hsp family.Thus far,two primary functions have been described for Hsp90:first,as a regulator of conformational change of some protein kinases and nuclear hormone receptors,and the other as an indispensable factor in cellular stress response.Hsp90 has an essential number of interaction proteins since it participates in almost every biological process and its importance is self-evident.Hsp90 has an inextricable relationship in the pathogenesis of cancer,especially in the proliferation and irradiation of cancer cells,thus being a notable cancer target.Since the discovery of geldanamycin,the first inhibitor of Hsp90,from the bacterial species Streptomyces hygroscopicus,even more attention has been focused toward Hsp90.Many structure-based inhibitors of Hsp90 have been designed to develop an innovative method to defeat cancer.However,already designed inhibitors have various deficiencies,such as hepatotoxicity,poor aqueous solubility,instability,and non-ideal oral bioavailability.Based on the aforementioned reasons and to achieve an optimal performance and fewer side effects,we designed a novel inhibitor of Hsp90,called FS5,and resolved the crystal structure of the Hsp90^N-FS5 complex(1.65 A°,PDB code 5XRB).Furthermore,we compared the complexes Hsp90^N,Hsp90^N-GDM,and Hsp90^N-ATP and suggest that the inhibitor FS5 may compete with ATP for binding to Hsp90,which can be regarded as a potential strategy for the development of novel cancer drugs in the future.展开更多
Diagnosis of mitochondrial DNA（mt DNA）disorders has traditionally been focused on the presence of point mutations and large deletions.However,deviations in mitochondrial abundance or mt DNA copy number can also be a...Diagnosis of mitochondrial DNA（mt DNA）disorders has traditionally been focused on the presence of point mutations and large deletions.However,deviations in mitochondrial abundance or mt DNA copy number can also be associated with many physiological and pathological conditions（Bai and Wong,2005）.展开更多
Autism spectrum disorder（ASD） is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication de？cits, and repetitive behavior. Although the mechanisms underlying its...Autism spectrum disorder（ASD） is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication de？cits, and repetitive behavior. Although the mechanisms underlying its etiology and manifestations are poorly understood,several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin（OXT） and arginine-vasopressin（AVP）, as these neuropeptides modulate various aspects of mammalian social behavior. As far as we know, there is no comprehensive review of the roles of the OXT and AVP systems in the development of ASD from the genetic aspect. In this review, we summarize the current knowledge regarding associations between ASD and single-nucleotide variants of the human OXT-AVP pathway genes OXT, AVP, AVP receptor 1a（AVPR1a）, OXT receptor（OXTR）, theoxytocinase/vasopressinase（LNPEP）, and ADP-ribosyl cyclase（CD38）.展开更多
DEAR EDITOR,Pore-forming proteins(PFPs)are widely distributed among all kingdoms of life and can oligomerize to form pores/channels in membrane systems.Extracellular vesicles(EVs)circulate in all biological fluids and...DEAR EDITOR,Pore-forming proteins(PFPs)are widely distributed among all kingdoms of life and can oligomerize to form pores/channels in membrane systems.Extracellular vesicles(EVs)circulate in all biological fluids and can trigger biological responses at a distance,thus emerging as an additional means of intercellular communication through the release of cellular cargo,such as lipids,nucleic acids,metabolites,and proteins.To date,however,the mechanism by which EV contents are released into extracellular space remains unclear.In our previous study on toads(Bombina maxima),we identified a PFP and trefoil factor complexβγ-CAT(βγ-crystallin fused aerolysin-like protein(α-subunit)and trefoil factor(β-subunit)complex,hence namedβγ-CAT),which assembled under strict regulation in response to environmental cues.Here,we observed that the PFPβγ-CAT colocalized with EVs in the skin of B.maxima in vivo.Using small EVs(sEVs)isolated from B.maxima dermal fibroblast cells and murine fibroblast cells,we found thatβγ-CAT could specifically target and oligomerize on purified EVs,rather than disrupt membrane integrity,and promote the release of different metabolites.Our analysis revealed that a secretory PFP drove metabolite release from EVs through channel formation,providing novel clues for the delivery of EV content into extracellular space.展开更多
The mitochondrial organelle is crucial to the energy metabolism of the eukaryotic cell. Defects in mitochondrial function lie at the core of a wide range of disorders, including both rare primary mitochondrial disorde...The mitochondrial organelle is crucial to the energy metabolism of the eukaryotic cell. Defects in mitochondrial function lie at the core of a wide range of disorders, including both rare primary mitochondrial disorders and more common conditions such as Parkinson＇s disease and diabetes. Inherited defects in mitochondrial function can be found in both the nuclear genome and the mitochondrial genome, with the latter creating unique challenges in the treatment and understanding of disease passed on through the mitochondrial genome. In this review, we will describe the limited treatment regimens currently used to alleviate primary mitochondrial disorders, as well as the potential for emerging technologies（in particular, those involving direct manipulation of the mitochondrial genome） to more decisively treat this class of disease. We will also emphasize the critical parallels between primary mitochondrial disorders and more common ailments such as cancer and diabetes.展开更多
We have read the article entitled "Galen’s place in Avicenna’s The Canon of Medicine: Respect, confirmation and criticism."(online available: 15 November 2019) [1]. We want to congratulate the authors for ...We have read the article entitled "Galen’s place in Avicenna’s The Canon of Medicine: Respect, confirmation and criticism."(online available: 15 November 2019) [1]. We want to congratulate the authors for this successful review article and make some contributions.The article explains that Avicenna mentioned Galen in his famous medical book—The Cannon of Medicine, in detail.展开更多
Delphinium denudatum Wall.is one of the important medicinal herbs of traditional Persian medicine and is known as Jadwar.Medicinal plants are the most widely used drugs in traditional Persian medicine and has been use...Delphinium denudatum Wall.is one of the important medicinal herbs of traditional Persian medicine and is known as Jadwar.Medicinal plants are the most widely used drugs in traditional Persian medicine and has been used for various diseases since earlier times.The medicinal uses of Delphinium denudatum Wall.date back to over 1,000 years ago.Rhazes(845–925 C.E.)was the first Persian physician and scientist who reported the use of Delphinium denudatum Wall.as a herbal remedy.During the following centuries,the usages of Delphinium denudatum Wall.in the treatment of various diseases has been mentioned in the books and references of traditional Persian medicine for cures to various diseases such as neurologic and psychiatric disease,gastrointestinal disease,fever,pain,and poisoning.According to modern studies,the dried roots of Delphinium denudatum Wall.have antipyretic,antimicrobial,anticonvulsant,hepatoprotective,antioxidant,and pain-relieving properties.Biomolecules from roots of Delphinium denudatum Wall.were also identified as potential cures for central nervous system diseases as well as for the amelioration of morphine addiction.Delphinium denudatum Wall.,with its properties involving the prevention of mitochondrial dysfunction,reduction of oxidative stress,and inflammation and immune dysregulation,can be utilized in curing inflammatory disorders.The effective therapeutic influence of root extract of Delphinium denudatum Wall.against several diseases needs to be confirmed through controlled clinical trials.This article reviews the different features of Delphinium denudatum Wall.and focuses on the well-known therapeutic effects of this herbal drug on various human disorders and animal disease models.展开更多
Microarray technology has been widely applied in biomedical research.The key to microarray study is to develop efficient immobilization method.In this study,we designed a new reversible microarray immobilization metho...Microarray technology has been widely applied in biomedical research.The key to microarray study is to develop efficient immobilization method.In this study,we designed a new reversible microarray immobilization method based on thiol-quinone reaction.A quinone-functionalized slide was fabricated through H_(2)O_(2)treatment of dopamine-coated slides.Various thiol-containing molecules can be anchored onto the quinone-functionalized slides via thioether linker,which could be cleaved under H_(2)O_(2) treatment to regenerate quinone groups on the surface.The highly versatile approach can be widely used for immobilization of various thiol-containing molecules.展开更多
With a rapidly ageing population in Singapore, older adults and their family members face challenges of age-related diseases, caregiver stress, and increasing demand for caregiving services. To address this pressing i...With a rapidly ageing population in Singapore, older adults and their family members face challenges of age-related diseases, caregiver stress, and increasing demand for caregiving services. To address this pressing issue, this pilot study aims to introduce online health coaching for older adults in Singapore and evaluate its effectiveness on maintenance of personal healthcare. In the midst of the COVID-19 outbreak, older adults’ activities were largely restricted by measures on social distancing. The online health coaching provided a solution for older adults to achieve a healthy lifestyle in a contactless manner. In this pilot study, 18 older adults (≥55 years old) who were willing to be coached by trained health coaches (n = 10) for 8 weeks (once a week) were recruited. Pre- and post-surveys with older adults were conducted. Furthermore, health coaching booklet was used to control the quality of coaching and to record diet and exercise plans. The pilot study demonstrated that the health coaching provided older adults with knowledge of nutrition and exercise, raised their awareness of well-being in terms of daily meals and regular exercise, and provided an alternative to maintain a healthy lifestyle amidst global pandemic. Additionally, we also identified that the older adults’ satisfactions with health coaching were positively associated with educational levels (R<sup>2</sup> = 0.31). Lastly, this pilot study highlighted that health coaching standardization process for older adults is critical for researchers and healthcare practitioners in the future.展开更多
Alzheimer's disease(AD),the leading cause of dementia,is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain.This condition casts a significant shadow on global health due...Alzheimer's disease(AD),the leading cause of dementia,is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain.This condition casts a significant shadow on global health due to its complex and multifactorial nature.In addition to genetic predispositions,the development of AD is influenced by a myriad of risk factors,including aging,systemic inflammation,chronic health conditions,lifestyle,and environmental exposures.Recent advancements in understanding the complex pathophysiology of AD are paving the way for enhanced diagnostic techniques,improved risk assessment,and potentially effective prevention strategies.These discoveries are crucial in the quest to unravel the complexities of AD,offering a beacon of hope for improved management and treatment options for the millions affected by this debilitating disease.展开更多
Leaf senescence is a complex but tightly regulated developmental process involving a coordinated sequence of multiple molecular events, which ultimately leads to death of the leaf. Efforts to understand the mechanisti...Leaf senescence is a complex but tightly regulated developmental process involving a coordinated sequence of multiple molecular events, which ultimately leads to death of the leaf. Efforts to understand the mechanistic principles underlying leaf senescence have been largely made by transcriptomic, proteomic, and metabolomic studies over the past decade. This review focuses on recent milestones in leaf senes- cence research obtained using multi-omics technologies, as well as future endeavors toward systems understanding of leaf senescence processes. In particular, we discuss recent advances in understanding molecular events during leaf senescence through genome-wide transcriptome analyses in Arabidopsis. We also describe comparative transcriptome analyses used to unveil the commonality and diversity of regulatory mechanisms governing leaf senescence in the plant kingdom. Finally, we provide current illustrations of epigenomic, proteomic, and metabolomic landscapes of leaf senescence. We envisage that integration of multi-omics leaf senescence data will enable us to address unresolved questions regarding leaf senescence, including determining the molecular principles that coordinate concurrent and ordered changes in biological events during leaf senescence.展开更多
Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human dise...Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.展开更多
Polycystic ovary syndrome(PCOS),a common endocrine disorder with metabolic and reproductive consequences,affects a significant percentage of women of reproductive age.Because of its complexity and impact on the qualit...Polycystic ovary syndrome(PCOS),a common endocrine disorder with metabolic and reproductive consequences,affects a significant percentage of women of reproductive age.Because of its complexity and impact on the quality of life,PCOS requires timely diagnosis and screening for complications.The most common clinical manifestations of PCOS are hirsutism,hyperandrogenism,acne,irregular cycles,amenorrhea,and anovulation.Although PCOS has different clinical manifestations in women,hyperandrogenism,and anovulation are the most common symptoms.A good medical history,examination,blood tests,and ultrasound findings facilitate the diagnosis of PCOS.Novel treatments have also undergone clinical trials to improve the symptoms of PCOS.However,comprehensive review articles investigating the different communities of this disease are limited,and this review aimed to collect data on the different etiologies of PCOS along with the latest diagnostic methods and the most common and up-to-date treatments for this disease.展开更多
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by memory and cognitive impairments.The two primary pathological hallmarks of AD include the accumulation ofβ-amyloid(Aβ)plaques and formation of neurofibrillary tangles(NFTs)composed predominantly of hyperphosphorylated tau protein(Zhang et al.,2023).Moreover,synaptic dysfunction is considered another crucial factor in AD pathogenesis and is closely associated with cognitive decline.Notably,synaptic damage,loss,and dysfunction manifest earlier than the pathological features of Aβplaques and NFTs(Knopman et al.,2021).Therefore,understanding the mechanisms underlying synaptic dysfunction in AD is vital for providing insights into disease mechanisms and developing novel therapeutic strategies.
基金supported by the grants from the National Institutes of Health(AG17242 and GM 104459)(to Y.S.)a grant from KRIBB Research Initiative Program(to Y.S.)
文摘MicroRNAs （miRNAs） are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ageing. Recently, extracellular miRNAs have been discovered in the bloodstream and bodily fluids. These miRNAs are shown to be secreted and circulating in microvesicles （MVs）, or in complex with other factors such as RNA-binding proteins and high-density lipoprotein （HDL） particles. These cell-free, circulating miRNAs can be taken into and function as negative regulators of target genes in recipient cells. Here we review the biogenesis and uptake of circulating miRNAs as well as their profiles in ageing and ageing-related diseases. We discuss the emerging role of circulating miRNAs as biomarkers and therapeutic targets.
基金supported by grants from the National Institutes of Health,USA(R01AG038710,R01AG021173,R01AG044420 and R01NS046673)the Alzheimer’s Association,the National Natural Science Foundation of China(91332112,81225008 and 81161120496)+1 种基金Fundamental Research Funds for the Central Universities of Chinathe Fok Ying Tung Education Foundation
文摘The degeneration of cholinergic neurons and cholinergic hypofunction are pathologies associated with Alzheimer＇s disease （AD）. Muscarinic acetylcholine receptors （mAChRs） mediate acetylcholine-induced neurotransmission and five mAChR subtypes （M1-M5） have been identified. Among them, M1 mAChR is widely expressed in the central nervous system and has been implicated in many physiological and pathological brain functions. In addition, M1 mAChR is postulated to be an important therapeutic target for AD and several other neurodegenerative diseases. In this article, we review recent progress in understanding the functional involvement of M1 mAChR in AD pathology and in developing M1 mAChR agonists forAD treatment.
基金supported by the National Natural Science Foundation of China (U21A20361 and 82130039 to Y.W.Z.)Fundamental Research Funds for the Central Universities (20720220133 to Y.W.Z.)+2 种基金Natural Science Foundation of Fujian Province (2021J02057 to Q.L.M.)Science and Technology Plan Projects of Fujian Province (2020Y2015 to Z.X.W.)2020 Joint Support of Key Projects on Health Care (3502Z20209005 to Z.X.W.)。
文摘Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.
基金supported by the National Natural Science Foundation of China(31572268,U1602225,31872226)Yunling Scholar Program to Y.Z.,and the Basic Research of Yunnan Province(202101AT070292)to X.L.G.
文摘DEAR EDITOR,Extracellular vesicles(EVs)are important for the transport of biologically active materials and for intercellular communication.As an exposed mucosa,amphibian skin participates in many essential physiological processes.To date,however,little is known about EVs in amphibian skin.Here,we successfully isolated EVs from the skin secretions of Bombina maxima,and characterized the EVs using nanoparticle tracking,western blotting,and electron microscopy.
基金supported by the Open Project of Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases,Ministry of Education(No.XN201904)Gannan Medical University(No.QD201910)+1 种基金the National Natural Science Foundation of China(Nos.31770795 and 31971043)the Jiangxi Province Natural Science Foundation(No.20181ACB20014)
文摘Heat shock proteins(Hsps)are a family of abundantly expressed ATP-dependent chaperone proteins.Hsp90 is an eminent member of Hsp family.Thus far,two primary functions have been described for Hsp90:first,as a regulator of conformational change of some protein kinases and nuclear hormone receptors,and the other as an indispensable factor in cellular stress response.Hsp90 has an essential number of interaction proteins since it participates in almost every biological process and its importance is self-evident.Hsp90 has an inextricable relationship in the pathogenesis of cancer,especially in the proliferation and irradiation of cancer cells,thus being a notable cancer target.Since the discovery of geldanamycin,the first inhibitor of Hsp90,from the bacterial species Streptomyces hygroscopicus,even more attention has been focused toward Hsp90.Many structure-based inhibitors of Hsp90 have been designed to develop an innovative method to defeat cancer.However,already designed inhibitors have various deficiencies,such as hepatotoxicity,poor aqueous solubility,instability,and non-ideal oral bioavailability.Based on the aforementioned reasons and to achieve an optimal performance and fewer side effects,we designed a novel inhibitor of Hsp90,called FS5,and resolved the crystal structure of the Hsp90^N-FS5 complex(1.65 A°,PDB code 5XRB).Furthermore,we compared the complexes Hsp90^N,Hsp90^N-GDM,and Hsp90^N-ATP and suggest that the inhibitor FS5 may compete with ATP for binding to Hsp90,which can be regarded as a potential strategy for the development of novel cancer drugs in the future.
文摘Diagnosis of mitochondrial DNA（mt DNA）disorders has traditionally been focused on the presence of point mutations and large deletions.However,deviations in mitochondrial abundance or mt DNA copy number can also be associated with many physiological and pathological conditions（Bai and Wong,2005）.
基金supported by a fund from University of Ulm-Peking University Health Science Center Joint Center for Neuroscience(BMU20160563)
文摘Autism spectrum disorder（ASD） is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication de？cits, and repetitive behavior. Although the mechanisms underlying its etiology and manifestations are poorly understood,several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin（OXT） and arginine-vasopressin（AVP）, as these neuropeptides modulate various aspects of mammalian social behavior. As far as we know, there is no comprehensive review of the roles of the OXT and AVP systems in the development of ASD from the genetic aspect. In this review, we summarize the current knowledge regarding associations between ASD and single-nucleotide variants of the human OXT-AVP pathway genes OXT, AVP, AVP receptor 1a（AVPR1a）, OXT receptor（OXTR）, theoxytocinase/vasopressinase（LNPEP）, and ADP-ribosyl cyclase（CD38）.
基金supported by the National Natural Science Foundation of China (31572268, U1602225, 31872226)Yunling Scholar Program to Y.Z.Basic Research of Yunnan Province(202101AT070292) to X.L.G.
文摘DEAR EDITOR,Pore-forming proteins(PFPs)are widely distributed among all kingdoms of life and can oligomerize to form pores/channels in membrane systems.Extracellular vesicles(EVs)circulate in all biological fluids and can trigger biological responses at a distance,thus emerging as an additional means of intercellular communication through the release of cellular cargo,such as lipids,nucleic acids,metabolites,and proteins.To date,however,the mechanism by which EV contents are released into extracellular space remains unclear.In our previous study on toads(Bombina maxima),we identified a PFP and trefoil factor complexβγ-CAT(βγ-crystallin fused aerolysin-like protein(α-subunit)and trefoil factor(β-subunit)complex,hence namedβγ-CAT),which assembled under strict regulation in response to environmental cues.Here,we observed that the PFPβγ-CAT colocalized with EVs in the skin of B.maxima in vivo.Using small EVs(sEVs)isolated from B.maxima dermal fibroblast cells and murine fibroblast cells,we found thatβγ-CAT could specifically target and oligomerize on purified EVs,rather than disrupt membrane integrity,and promote the release of different metabolites.Our analysis revealed that a secretory PFP drove metabolite release from EVs through channel formation,providing novel clues for the delivery of EV content into extracellular space.
文摘The mitochondrial organelle is crucial to the energy metabolism of the eukaryotic cell. Defects in mitochondrial function lie at the core of a wide range of disorders, including both rare primary mitochondrial disorders and more common conditions such as Parkinson＇s disease and diabetes. Inherited defects in mitochondrial function can be found in both the nuclear genome and the mitochondrial genome, with the latter creating unique challenges in the treatment and understanding of disease passed on through the mitochondrial genome. In this review, we will describe the limited treatment regimens currently used to alleviate primary mitochondrial disorders, as well as the potential for emerging technologies（in particular, those involving direct manipulation of the mitochondrial genome） to more decisively treat this class of disease. We will also emphasize the critical parallels between primary mitochondrial disorders and more common ailments such as cancer and diabetes.
文摘We have read the article entitled "Galen’s place in Avicenna’s The Canon of Medicine: Respect, confirmation and criticism."(online available: 15 November 2019) [1]. We want to congratulate the authors for this successful review article and make some contributions.The article explains that Avicenna mentioned Galen in his famous medical book—The Cannon of Medicine, in detail.
文摘Delphinium denudatum Wall.is one of the important medicinal herbs of traditional Persian medicine and is known as Jadwar.Medicinal plants are the most widely used drugs in traditional Persian medicine and has been used for various diseases since earlier times.The medicinal uses of Delphinium denudatum Wall.date back to over 1,000 years ago.Rhazes(845–925 C.E.)was the first Persian physician and scientist who reported the use of Delphinium denudatum Wall.as a herbal remedy.During the following centuries,the usages of Delphinium denudatum Wall.in the treatment of various diseases has been mentioned in the books and references of traditional Persian medicine for cures to various diseases such as neurologic and psychiatric disease,gastrointestinal disease,fever,pain,and poisoning.According to modern studies,the dried roots of Delphinium denudatum Wall.have antipyretic,antimicrobial,anticonvulsant,hepatoprotective,antioxidant,and pain-relieving properties.Biomolecules from roots of Delphinium denudatum Wall.were also identified as potential cures for central nervous system diseases as well as for the amelioration of morphine addiction.Delphinium denudatum Wall.,with its properties involving the prevention of mitochondrial dysfunction,reduction of oxidative stress,and inflammation and immune dysregulation,can be utilized in curing inflammatory disorders.The effective therapeutic influence of root extract of Delphinium denudatum Wall.against several diseases needs to be confirmed through controlled clinical trials.This article reviews the different features of Delphinium denudatum Wall.and focuses on the well-known therapeutic effects of this herbal drug on various human disorders and animal disease models.
基金the financial support from the Research Grants Council of Hong Kong(Nos.11102719,11304118 and 14306317)Shenzhen Basic Research Project(No.JCYJ20160601173218804)+1 种基金National Natural Science Foundation of China(No.21778044)the Shandong University of Technology Ph.D.Startup Foundation(No.420033)。
文摘Microarray technology has been widely applied in biomedical research.The key to microarray study is to develop efficient immobilization method.In this study,we designed a new reversible microarray immobilization method based on thiol-quinone reaction.A quinone-functionalized slide was fabricated through H_(2)O_(2)treatment of dopamine-coated slides.Various thiol-containing molecules can be anchored onto the quinone-functionalized slides via thioether linker,which could be cleaved under H_(2)O_(2) treatment to regenerate quinone groups on the surface.The highly versatile approach can be widely used for immobilization of various thiol-containing molecules.
文摘With a rapidly ageing population in Singapore, older adults and their family members face challenges of age-related diseases, caregiver stress, and increasing demand for caregiving services. To address this pressing issue, this pilot study aims to introduce online health coaching for older adults in Singapore and evaluate its effectiveness on maintenance of personal healthcare. In the midst of the COVID-19 outbreak, older adults’ activities were largely restricted by measures on social distancing. The online health coaching provided a solution for older adults to achieve a healthy lifestyle in a contactless manner. In this pilot study, 18 older adults (≥55 years old) who were willing to be coached by trained health coaches (n = 10) for 8 weeks (once a week) were recruited. Pre- and post-surveys with older adults were conducted. Furthermore, health coaching booklet was used to control the quality of coaching and to record diet and exercise plans. The pilot study demonstrated that the health coaching provided older adults with knowledge of nutrition and exercise, raised their awareness of well-being in terms of daily meals and regular exercise, and provided an alternative to maintain a healthy lifestyle amidst global pandemic. Additionally, we also identified that the older adults’ satisfactions with health coaching were positively associated with educational levels (R<sup>2</sup> = 0.31). Lastly, this pilot study highlighted that health coaching standardization process for older adults is critical for researchers and healthcare practitioners in the future.
基金supported by the National Key R&D Program of China(2021ZD0202402 and 2021YFA1101401 to X.W.)the National Natural Science Foundation of China(82325018 and U21A20358 to X.W.,82271451 to Q.Z.)+2 种基金the Natural Science Foundation of Fujian Province of China(2021J02004 to X.W.)the Guangdong Basic and Applied Basic Research Foundation(2021B1515120081 to X.W.)the Fundamental Research Funds for the Chinese Central Universities(20720230070 to X.W.and Q.Z.,20720220052 to Q.Z.)。
文摘Alzheimer's disease(AD),the leading cause of dementia,is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain.This condition casts a significant shadow on global health due to its complex and multifactorial nature.In addition to genetic predispositions,the development of AD is influenced by a myriad of risk factors,including aging,systemic inflammation,chronic health conditions,lifestyle,and environmental exposures.Recent advancements in understanding the complex pathophysiology of AD are paving the way for enhanced diagnostic techniques,improved risk assessment,and potentially effective prevention strategies.These discoveries are crucial in the quest to unravel the complexities of AD,offering a beacon of hope for improved management and treatment options for the millions affected by this debilitating disease.
文摘Leaf senescence is a complex but tightly regulated developmental process involving a coordinated sequence of multiple molecular events, which ultimately leads to death of the leaf. Efforts to understand the mechanistic principles underlying leaf senescence have been largely made by transcriptomic, proteomic, and metabolomic studies over the past decade. This review focuses on recent milestones in leaf senes- cence research obtained using multi-omics technologies, as well as future endeavors toward systems understanding of leaf senescence processes. In particular, we discuss recent advances in understanding molecular events during leaf senescence through genome-wide transcriptome analyses in Arabidopsis. We also describe comparative transcriptome analyses used to unveil the commonality and diversity of regulatory mechanisms governing leaf senescence in the plant kingdom. Finally, we provide current illustrations of epigenomic, proteomic, and metabolomic landscapes of leaf senescence. We envisage that integration of multi-omics leaf senescence data will enable us to address unresolved questions regarding leaf senescence, including determining the molecular principles that coordinate concurrent and ordered changes in biological events during leaf senescence.
基金supported by the National Natural Science Foundation of China(31871380,32000500,32070730,32170756,32170804,81330008,81671377,81725010,81725010,81872874,81921006,81922027,81971312,81991512,82030041,82103167,82122024,82125009,82125011,82130044,91749126,91949101,91949207,92049302)the National Key Research and Development Program of China(2017YFA0506400,2018YFA0800200,2018YFA0800700,2018YFA0900200,2018YFC2000100,2018YFC2000400,2018YFE-0203700,20192ACB70002,2019YFA0802202,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002800,2020YFC-2002900,2021ZD0202401)+11 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100,XDA16010603,XDA16020400,XDB29020000,XDB39000000,XDB39000000,XDB39030300)the China Association for Science and Technology(2021QNRC001)the Beijing Municipal Science and Technology Commission(Z200022)the Natural Science Foundation of Shanghai(21JC1406400)the Key Programs of the Jiangxi ProvinceChina(20192ACB70002)the“Shu Guang”Project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation(19SG18)the Shanghai Sailing Program(22YF1434300)the Research Project of Joint Laboratory of University of Science and Technology of China and Anhui Mental Health Center(2019LH03)the Fundamental Research Funds for the Central Universities(WK2070210004)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(YESS20210002)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022083)。
文摘Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.
文摘Polycystic ovary syndrome(PCOS),a common endocrine disorder with metabolic and reproductive consequences,affects a significant percentage of women of reproductive age.Because of its complexity and impact on the quality of life,PCOS requires timely diagnosis and screening for complications.The most common clinical manifestations of PCOS are hirsutism,hyperandrogenism,acne,irregular cycles,amenorrhea,and anovulation.Although PCOS has different clinical manifestations in women,hyperandrogenism,and anovulation are the most common symptoms.A good medical history,examination,blood tests,and ultrasound findings facilitate the diagnosis of PCOS.Novel treatments have also undergone clinical trials to improve the symptoms of PCOS.However,comprehensive review articles investigating the different communities of this disease are limited,and this review aimed to collect data on the different etiologies of PCOS along with the latest diagnostic methods and the most common and up-to-date treatments for this disease.
