A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabrica...A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabricated through fluorescence resonance energy transfer(FRET) and the electrostatic attraction between positively-charged hemicyanine molecules and negatively-charged carbon dots(CDs).Arg can be quantitatively detected in the concentration range from 6.0×10^-5 mol/L to 2.7×10^-4 mol/L.Further,due to its ability to target mitochondrion and low cytotoxicity,intracellular Arg was succes s fully tracked through ratiometric fluorescence imaging.展开更多
Hypochlorite anion is a ubiquitous reactive molecule in the terminal disinfection systems, inflammatory stress and immune systems. Thus, rapid and visual monitoring ClO^- in water and biological samples is very meanin...Hypochlorite anion is a ubiquitous reactive molecule in the terminal disinfection systems, inflammatory stress and immune systems. Thus, rapid and visual monitoring ClO^- in water and biological samples is very meaningful for water quality safety and toxicity assessment of contaminants. Herein, a colorimetric and fluorometric probe（Rh-ClO） based on rhodamine B fluorophore and thiophene-2-carbohydrazide has been unveiled and successfully utilized for ClO^- detection in water samples and HeLa cells. Upon addition of ClO^-, color changes of solution from colorless to pink were immediately visible to the nakedeyes, meanwhile, brilliant red fluorescence was observed under excited at UV light（365 nm）. Rh-ClO displayed high selectivity and sensitivity for ClO^- , and the detection limit was 7 mmol/L calculated from the fluorescence titration. With the aid of its merits including rapid response to ClO^- within 10 s, Rh-ClO and its test paper could successfully detect ClO^- in water. Additionally, HeLa cells image co-stained with Rh-ClO and Rh123 demonstrated that Rh-ClO possessed excellent and fast cell-membrane permeability and mitochondrion-targetability. It was clearly confirmed that Rh-ClO would be a promising probe for rapid tracking of ClO^- in water samples and in mitochondria of living cells.展开更多
Apoptosis plays an important role in the pathogenesis of viral infections.In this study,we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms.Annexin V-PI staining a...Apoptosis plays an important role in the pathogenesis of viral infections.In this study,we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms.Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis.HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria.The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly （ADP-ribose） polymerase,which is known to be an important substrate for activated caspase-3.Caspase-9 was activated significantly in HHV-6A-infected cells,whereas caspase-8 was not activated obviously.Moreover,HHV-6A infection upregulated Bax and downregulated Bcl-2.This is the first demonstration of mitochondrion-mediated,caspase-dependent apoptosis in HHV-6A-infected cells.展开更多
Transmission electron microscopy of the yellowfin porgy (Sparus latus Houttuyn) spermatozoa ultrastructure showed the spermatozoon as a primitive type made up of the acrosomeless head , the flagellum , and the midpiec...Transmission electron microscopy of the yellowfin porgy (Sparus latus Houttuyn) spermatozoa ultrastructure showed the spermatozoon as a primitive type made up of the acrosomeless head , the flagellum , and the midpiece , at the periphery of which was a relatively big mitochondrion with more complex structure . It was found that during spermiogenesis, only one relatively big mitochondrion occurred in both the spermatid and the spermatozoon . This is different from other teleost fishes . During spermiogenesis, the mitochondria number is one, and morphology did not change . All these are different fromthose of other fishes .展开更多
The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular an...The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.展开更多
Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intro...Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development.PPR21 is a typical P-type PPR protein targeted to mitochondria.The ppr21 mutants are arrested in embryogenesis and endosperm development,leading to embryo lethality.Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1,2,and 4 and impair the assembly and activity of mitochondrial complex I.Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns.However,our protein interaction analyses reveal that PPR21 does not interact with EMP12.Instead,both PPR21 and EMP12 interact with the small MutS-related(SMR)domain-containing PPR protein 1(PPR-SMR1)and the short P-type PPR protein 2(SPR2).PPR-SMR1 interacts with SPR2,and both proteins are required for the splicing of many introns in mitochondria,including nad2 intron 1,2,and 4.These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.展开更多
Male gametes are produced in the anthers and are essential for fertilization and seed setting.A transverse section of the anther reveals four layers:the epidermis,endothecium,middle layer,and tapetum.The tapetum,being...Male gametes are produced in the anthers and are essential for fertilization and seed setting.A transverse section of the anther reveals four layers:the epidermis,endothecium,middle layer,and tapetum.The tapetum,being the innermost layer,plays a critical role in supplying nutrients,enzymes,and protection to microspores.Detailed microscopic and ultrastructural analyses have revealed highly active and well-organized structures within the tapetum,referred to as tapetal organelles.Molecular studies have highlighted the significance of tapetal cell death and the nurturing role of the tapetum for microspores.However,the mechanisms by which these processes are mediated by tapetal organelles at the cellular level remain elusive.The discovery of mutants defective in tapetal organelles has enabled further investigations into their structure,morphology,and function.This review discusses the molecular and functional roles of various tapetal organelles,such as plastids(amyloplasts and elaioplasts),mitochondria,tapetosomes,endoplasmic reticulum,and lipid bodies.We provide an overview of their roles,highlight key organelles in the tapetum,and address recent challenges and potential applications of genes regulating tapetal organelles in enhancing crop fertility.展开更多
Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impai...Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impairing ATP production and generating reactive oxygen species(ROS).These reactive species induce mitochondrial dysfunction,leading to oxidative stress,calcium imbalance,and activation of apoptosis pathways.The mitochondrial ATP-sensitive potassium channel(mitoKATP)and mitochondrial permeability transition pore(mPTP)channels are particularly affected,contributing to membrane potential loss,cytochrome c release,and cell death.This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases,with a focus on mitochondrial impairment,ion channel dysfunction,and ROS overproduction.Additionally,we examine hypoxia-inducible factor 1-alpha(HIF-1α)as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress.Antioxidants and compounds modulating key ion channels,such as mitoKATP and mPTP,are highlighted as promising interventions for mitigating hypoxia-induced damage.Furthermore,we emphasize the potential of integrating in vitro,in vivo,and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.展开更多
In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed t...In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed to investigate the characteristics of codon bias and factors in shaping the codon usage patterns among mitochondrion, chloroplast and nuclear genes in common wheat （Triticum aestivum L.）. GC contents in nuclear genes were higher than that in mitochondrion and chloroplast genes. The neutrality and correspondence analyses indicated that the codon usage in nuclear genes would be a result of relative strong mutational bias, while the codon usage patterns of mitochondrion and chloroplast genes were more conserved in GC content and influenced by translation level. The Parity Rule 2 （PR2） plot analysis showed that pyrimidines were used more frequently than purines at the third codon position in the three genomes. In addition, using a new alterative strategy, 11, 12, and 24 triplets were defined as preferred codons in the mitochondrion, chloroplast and nuclear genes, respectively. These findings suggested that the mitochondrion, chloroplast and nuclear genes shared particularly different features of codon usage and evolutionary constraints.展开更多
神经退行性疾病是以脑和/或脊髓神经元慢性进行性退变为主要病理特征的一类疾病,其病因不清、发病机制复杂,至今尚无有效的治疗方法。近年来,线粒体定位的沉默信息调节因子(silent information regulators,SIRTs)家族成员SIRT3、SIRT4、...神经退行性疾病是以脑和/或脊髓神经元慢性进行性退变为主要病理特征的一类疾病,其病因不清、发病机制复杂,至今尚无有效的治疗方法。近年来,线粒体定位的沉默信息调节因子(silent information regulators,SIRTs)家族成员SIRT3、SIRT4、SIRT5在神经退行性疾病中的作用日益受到关注。研究表明它们通过调节线粒体功能、炎症反应等参与了神经元变性的许多重要环节。本文综述了线粒体SIRTs在阿尔茨海默病、帕金森病和肌萎缩侧索硬化症等神经退行性疾病中的研究进展,以期为阐明疾病的发病机制与防治提供新的思路。展开更多
基金National Natural Science Foundation of China(Nos.U1704161,U1504203,21601158)Zhengzhou University(No.32210431)for the financial supports。
文摘A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabricated through fluorescence resonance energy transfer(FRET) and the electrostatic attraction between positively-charged hemicyanine molecules and negatively-charged carbon dots(CDs).Arg can be quantitatively detected in the concentration range from 6.0×10^-5 mol/L to 2.7×10^-4 mol/L.Further,due to its ability to target mitochondrion and low cytotoxicity,intracellular Arg was succes s fully tracked through ratiometric fluorescence imaging.
基金supported by the National Natural Science Foundation of China (No. 21302080)Program Funded by Liaoning Province Education Administration (No. L2014010)
文摘Hypochlorite anion is a ubiquitous reactive molecule in the terminal disinfection systems, inflammatory stress and immune systems. Thus, rapid and visual monitoring ClO^- in water and biological samples is very meaningful for water quality safety and toxicity assessment of contaminants. Herein, a colorimetric and fluorometric probe（Rh-ClO） based on rhodamine B fluorophore and thiophene-2-carbohydrazide has been unveiled and successfully utilized for ClO^- detection in water samples and HeLa cells. Upon addition of ClO^-, color changes of solution from colorless to pink were immediately visible to the nakedeyes, meanwhile, brilliant red fluorescence was observed under excited at UV light（365 nm）. Rh-ClO displayed high selectivity and sensitivity for ClO^- , and the detection limit was 7 mmol/L calculated from the fluorescence titration. With the aid of its merits including rapid response to ClO^- within 10 s, Rh-ClO and its test paper could successfully detect ClO^- in water. Additionally, HeLa cells image co-stained with Rh-ClO and Rh123 demonstrated that Rh-ClO possessed excellent and fast cell-membrane permeability and mitochondrion-targetability. It was clearly confirmed that Rh-ClO would be a promising probe for rapid tracking of ClO^- in water samples and in mitochondria of living cells.
基金supported by the National Natural Science Foundationof China (No. 30771961 and No. 30901344)Science Development Foundation of Nanjing Medical University (No. 08NMUZ003)Jiangsu Province Laboratory of Pathogen Biology (No. 08bykf01)
文摘Apoptosis plays an important role in the pathogenesis of viral infections.In this study,we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms.Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis.HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria.The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly （ADP-ribose） polymerase,which is known to be an important substrate for activated caspase-3.Caspase-9 was activated significantly in HHV-6A-infected cells,whereas caspase-8 was not activated obviously.Moreover,HHV-6A infection upregulated Bax and downregulated Bcl-2.This is the first demonstration of mitochondrion-mediated,caspase-dependent apoptosis in HHV-6A-infected cells.
文摘Transmission electron microscopy of the yellowfin porgy (Sparus latus Houttuyn) spermatozoa ultrastructure showed the spermatozoon as a primitive type made up of the acrosomeless head , the flagellum , and the midpiece , at the periphery of which was a relatively big mitochondrion with more complex structure . It was found that during spermiogenesis, only one relatively big mitochondrion occurred in both the spermatid and the spermatozoon . This is different from other teleost fishes . During spermiogenesis, the mitochondria number is one, and morphology did not change . All these are different fromthose of other fishes .
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
基金supported by the National Natural Science Foundation of China(32072126 and 32230075)the Shandong Provincial Natural Science Foundation(ZR2019MC005).
文摘Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development.PPR21 is a typical P-type PPR protein targeted to mitochondria.The ppr21 mutants are arrested in embryogenesis and endosperm development,leading to embryo lethality.Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1,2,and 4 and impair the assembly and activity of mitochondrial complex I.Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns.However,our protein interaction analyses reveal that PPR21 does not interact with EMP12.Instead,both PPR21 and EMP12 interact with the small MutS-related(SMR)domain-containing PPR protein 1(PPR-SMR1)and the short P-type PPR protein 2(SPR2).PPR-SMR1 interacts with SPR2,and both proteins are required for the splicing of many introns in mitochondria,including nad2 intron 1,2,and 4.These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.
基金supported by the National Natural Science Foundation of China(Grant Nos.32272191 and 32350410428).
文摘Male gametes are produced in the anthers and are essential for fertilization and seed setting.A transverse section of the anther reveals four layers:the epidermis,endothecium,middle layer,and tapetum.The tapetum,being the innermost layer,plays a critical role in supplying nutrients,enzymes,and protection to microspores.Detailed microscopic and ultrastructural analyses have revealed highly active and well-organized structures within the tapetum,referred to as tapetal organelles.Molecular studies have highlighted the significance of tapetal cell death and the nurturing role of the tapetum for microspores.However,the mechanisms by which these processes are mediated by tapetal organelles at the cellular level remain elusive.The discovery of mutants defective in tapetal organelles has enabled further investigations into their structure,morphology,and function.This review discusses the molecular and functional roles of various tapetal organelles,such as plastids(amyloplasts and elaioplasts),mitochondria,tapetosomes,endoplasmic reticulum,and lipid bodies.We provide an overview of their roles,highlight key organelles in the tapetum,and address recent challenges and potential applications of genes regulating tapetal organelles in enhancing crop fertility.
基金supported by"Potential Medicinal Plants of Uzbekistan with Adaptogenic Effects and Their Molecular,Cellular,and Therapeutic Mechanisms"from the Innovative Development Agency under the Ministry of Higher Education,Science,and Innovation of the Republic of Uzbekistan(Grant No.FL-8323102109).
文摘Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impairing ATP production and generating reactive oxygen species(ROS).These reactive species induce mitochondrial dysfunction,leading to oxidative stress,calcium imbalance,and activation of apoptosis pathways.The mitochondrial ATP-sensitive potassium channel(mitoKATP)and mitochondrial permeability transition pore(mPTP)channels are particularly affected,contributing to membrane potential loss,cytochrome c release,and cell death.This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases,with a focus on mitochondrial impairment,ion channel dysfunction,and ROS overproduction.Additionally,we examine hypoxia-inducible factor 1-alpha(HIF-1α)as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress.Antioxidants and compounds modulating key ion channels,such as mitoKATP and mPTP,are highlighted as promising interventions for mitigating hypoxia-induced damage.Furthermore,we emphasize the potential of integrating in vitro,in vivo,and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.
基金Supported by the Sate Key Basic Research and Development Plan of China （2003CB715904） and the National Science Foundation for 0verseas Distinguished Young Scholar （30428003）
文摘In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed to investigate the characteristics of codon bias and factors in shaping the codon usage patterns among mitochondrion, chloroplast and nuclear genes in common wheat （Triticum aestivum L.）. GC contents in nuclear genes were higher than that in mitochondrion and chloroplast genes. The neutrality and correspondence analyses indicated that the codon usage in nuclear genes would be a result of relative strong mutational bias, while the codon usage patterns of mitochondrion and chloroplast genes were more conserved in GC content and influenced by translation level. The Parity Rule 2 （PR2） plot analysis showed that pyrimidines were used more frequently than purines at the third codon position in the three genomes. In addition, using a new alterative strategy, 11, 12, and 24 triplets were defined as preferred codons in the mitochondrion, chloroplast and nuclear genes, respectively. These findings suggested that the mitochondrion, chloroplast and nuclear genes shared particularly different features of codon usage and evolutionary constraints.
文摘神经退行性疾病是以脑和/或脊髓神经元慢性进行性退变为主要病理特征的一类疾病,其病因不清、发病机制复杂,至今尚无有效的治疗方法。近年来,线粒体定位的沉默信息调节因子(silent information regulators,SIRTs)家族成员SIRT3、SIRT4、SIRT5在神经退行性疾病中的作用日益受到关注。研究表明它们通过调节线粒体功能、炎症反应等参与了神经元变性的许多重要环节。本文综述了线粒体SIRTs在阿尔茨海默病、帕金森病和肌萎缩侧索硬化症等神经退行性疾病中的研究进展,以期为阐明疾病的发病机制与防治提供新的思路。
