Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dy...Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dysfunction.The mechanism of this process remains elusive.Using rat models of ischemia and hypoxic vascular smooth muscle cells(VSMCs),we combined transmission electron microscopy,super-resolution microscopy,and metabolic analysis to analyze the structure and function change of mitochondrial cristae.Multi-omics approaches revealed arginase 1(Arg1)upregulation in ischemic VSMCs,confirmed by in vivo and in vitro knockout models showing Arg1's protective effects on mitochondrial cristae,mitochondrial and vascular function,and limited the release of mtDNA.Mechanistically,Arg1 interacting with Mic1o led to mitochondrial cristae remodeling,together with hypoxia-induced VDAC1 lactylation resulting in the opening of MPTP and release of mtDNA of VSMCs.The released mtDNA led to PANoptosis of VSMCs via activation of the cGAS-STING pathway.ChIP-qPCR results demonstrated that lactatemediated Arg1 up-regulation was due to H3K18la upregulation.VSMCs targeted nano-material PLGA-PEl-siRNA@PM-a-SMA(NPsiArg1)significantly improved vascular dysfunction.This study uncovers a new mechanism of vascular dysfunction following ischemic/hypoxic injury:a damaging positive feedback loop mediated by lactate-regulated Arg1 expression between the nucleus and mitochondria,leading to mitochondria cristae disorder and mtDNA release,culminating in VSMCs PANoptosis.Targeting VSMCs Arg1 inhibition offers a potential therapeutic strategy to alleviate ischemia/hypoxia-induced vascular impairments.展开更多
Prohibitin is named due to the negative regulatory role of its gene products in cell proliferation. Prohibitin gene is located at q21 of chromosome 17 in human beings and the protein is found at mitochondria, nucleus...Prohibitin is named due to the negative regulatory role of its gene products in cell proliferation. Prohibitin gene is located at q21 of chromosome 17 in human beings and the protein is found at mitochondria, nucleus and cytoplasm. Due to its size and ring-shaped structure, prohibitin protein defines functional subcompartments in mitochondria. Its subunits, PHB1 and PHB2, suppress cell proliferation as in the protein itself Nevertheless, recent investigation suggests that prohibitin protein enhances cell proliferation as well. It has also been found to suppress cell apoptosis by reducing cytochrome C release via the avoidance of mitochondrial crista remodeling which is facilitated through type 1 optic atrophy protein （OPAl）. Acting as a binding site for ubiquitin, prohibitin protein regulates protein degradation by proteasome. Examples are the degradations of sperm mitochondria in a fertilized ovum or those of an abnormal sperm.展开更多
A three-dimensional numerical model of the membranous labyrinth of the semicircular canal of the inner ear was established to investigate the effects of canalithiasis of BPPV on the balance function of the inner ear.T...A three-dimensional numerical model of the membranous labyrinth of the semicircular canal of the inner ear was established to investigate the effects of canalithiasis of BPPV on the balance function of the inner ear.The movement of otolith particles in the membranous labyrinth was simulated when a person turns his head to a specific position.The effects of otolith movements on the balance function of the inner ear were simulated for different numbers,diameters,and initial positions of otoliths.The simulation results show that the otolith diameter affects the movement duration of otoliths in the membranous labyrinth.The number and diameter of otoliths,the diameter of the membranous labyrinth,and the initial position of the otoliths can cause changes in the pressure difference on both sides of the cupula of the crista ampullaris(cupula).The latent period and onset period are related to the diameter of otolith particles and the position of the head.There is also a correlation between the severity of the disease and the diameter and number of otolith particles.展开更多
Objective:To screen plant extract fractions and elucidate the components present in Caesalpinia crista(C.crista)leaves for cholinergic and anti-amyloidogenic activities for the treatment of Alzheimer's diseases.Me...Objective:To screen plant extract fractions and elucidate the components present in Caesalpinia crista(C.crista)leaves for cholinergic and anti-amyloidogenic activities for the treatment of Alzheimer's diseases.Methods:This work has been carried out to study the action of C.crista extracts from nonpolar to polar solvents toward inhibition of oxidative stress,cholinergic and amyloidosis.The antioxidant activity was studied using DPPH total antioxidant assay;cholinergic assay by Ellman's method and anti-amyloidogenic assay by thioflavin-T fluorescence and transmission electron microscopy.Results:The quantification of polyphenols was carried out following C.crista methanolic extract(CCMeOH)HPLC fingerprinting,along with LC-MS and elucidated by MS LAMPS database.GC-MS of CCMeOH was screened for potential moieties.In vitro experimental results showed that the CCMe OH was potential extract that exhibited active inhibition of antioxidant property,cholinergic enzymes acetylcholinesterase and butyrylcholinesterase.For anti-amyloidogenic evaluations,among all the extracts,the CCMe OH was found to have the potential toward inhibiting the oligomers,fibrillation of Aβ42 with good defibrillation of amyloid cascading properties.Conclusions:These results are also supported by the presence of polyphenols as the active ingredients.Multi-potent target drug therapy is a promising option in treating the Alzheimer's diseases.Methanolic extract of C.crista shows potential activity against cholinergic enzymes,Aβ42 aggregation with antioxidant activity.展开更多
Acanthosis nigricans is characterized by papillomatous brownish lesions mainly in the intertriginous areas. We used dermoscopy to examine such lesions in a family with acanthosis nigricans. The dermoscopic images show...Acanthosis nigricans is characterized by papillomatous brownish lesions mainly in the intertriginous areas. We used dermoscopy to examine such lesions in a family with acanthosis nigricans. The dermoscopic images showed an aberrant skin structure of linear crista cutis and sulcus cutis, and hyperpigmented dots in crista cutis. The hyperpigmented dots, which could not be seen with the naked eyes, may contribute to the color of the pigmented skin. Dermoscopy can be useful for evaluating disorders involving the structure of area cutanea and a change in skin color.展开更多
Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis ...Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis and development of HCs is crucial.Our current study highlights rhpn2,a member of rho-binding proteins,as essential for vestibular HC development.The rhpn2 gene is highly expressed in the crista and macula HCs.Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number,accompanied by vestibular dysfunction.Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants.Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab.Furthermore,co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA,validating the interaction of the two proteins.rhpn2 knockout leads to a decreased expression of rock2b,a canonical RhoA signaling pathway gene.Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants.This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway,providing a target for the treatment of balance disorders.展开更多
Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial...Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial membrane,forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function.In the past decade,MICOS abnormalities have been extensively linked to AD pathogenesis.In particular,dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD,often in association with hallmark pathological features such as amyloid-b plaque accumulation,neurofibrillary tangle formation,and neuronal apoptosis.Furthermore,MICOS subunits interact with several etiologically relevant proteins,significantly influencing AD progression.The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD.Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment.In the present review,we introduce current understanding of MICOS structures and functions,highlight MICOS pathogenesis in AD,and summarize the available MICOS-targeting drugs potentially useful for AD.展开更多
Mitochondrial damage,characterized by altered morphological distribution and the damage of cristae,is closely associated with mitochondrial disease.However,imaging methods for capturing mitochondrial morphology at the...Mitochondrial damage,characterized by altered morphological distribution and the damage of cristae,is closely associated with mitochondrial disease.However,imaging methods for capturing mitochondrial morphology at the nanoscale level in live samples remain unavailable,which seriously hinders the accurate evaluation and diagnosis of mitochondrial-related diseases.In response,we propose a super-resolution quantification strategy based on structured illumination microscopy(SIM)for the rapid,accurate evaluation of mitochondrial morphology.Using the strategy,we accurately captured the morphological distribution of mitochondria at the nanoscale level in a way generally applicable to checking various cell processes and identifying patients with mitochondrial disease who exhibit the SLC25A46 mutation.We also used algorithm-assisted super-resolution imaging to quantitatively analyze damage to mitochondrial cristae,which supports a novel drug screening strategy—high-resolution drug screening—for investigating drugs’pharmacodynamics on organelles in living cells.In short,our strategy improves the accurate examination of changes in mitochondrial morphology in living cells and indicates new ways in which SIM-imaging can assist in diagnosing mitochondrial disease at the single-cell level.展开更多
Besides providing energy to sustain life,mitochondria also play crucial roles in stress response and programmed cell death.The mitochondrial hallmark lipid,cardiolipin(CL),is essential to the maintenance of mitochondr...Besides providing energy to sustain life,mitochondria also play crucial roles in stress response and programmed cell death.The mitochondrial hallmark lipid,cardiolipin(CL),is essential to the maintenance of mitochondrial structure and function.However,how mitochondria and CL are involved in stress response is not as well defined in plants as in animal and yeast cells.We previously revealed a role for CL in mitochondrial fission and in heat stress response in Arabidopsis.To further determine the involvement of mitochondria and CL in plant heat response,here we treated Arabidopsis seedlings with varied lengths of acute heat stress.These treatments resulted in decreases in mitochondrial membrane potential,disruption of mitochondrial ultrastructure,accumulation of mitochondrial reactive-oxygen species(ROS),and redistribution of CL to the outer mitochondrial membrane and to a novel type of vesicle.The level of the observed changes correlated with the severeness of the heat stress,indicating the strong relevance of these processes to stress response.Our findings provide the basis for studying mechanisms underpinning the role of mitochondria and CL in plant stress response.展开更多
Objective:To develop a downloadable three-dimensional(3D)study tool of the membranous labyrinth in order to facilitate the study of benign paroxysmal positional vertigo(BPPV).Background:The diagnosis and treatment of ...Objective:To develop a downloadable three-dimensional(3D)study tool of the membranous labyrinth in order to facilitate the study of benign paroxysmal positional vertigo(BPPV).Background:The diagnosis and treatment of BPPV depend on an understanding of the anatomy of the vestibular labyrinth and its position relative to the head.To date,many illustrations have been made to explain principles of diagnosis and treatment of BPPV,but few have been based on anatomical studies of the membranous labyrinth.Methods:A previously reported 3D model of a human labyrinth was transposed to a 3D development software to allow the creation of markers along the semicircular ducts and utricle.These markers represent otoliths at different positions during movement of the model within the 3D environment.User-friendly tools were created to navigate the model,to allow clear documentation and communication of studied problems,and to study the model across relevant planes.The final model can be downloaded and is available for general useat https://bppvviewer.com/download/.Results:The model allows visualization of true membranous labyrinth anatomy in both ears simultaneously.The dependent portion of each semicircular duct,the planes of the cristae,and the position of the utricle can easily be visualized in any head position.Moveable markers can mark the expected progress of otolith debris with changes in head position and images can be captured to document simulations in various draw styles.Conclusion:This simple model could offer insights that lead to more accurate diagnosis and treatment of BPPV.It may also be useful as a tool to teach BPPV.展开更多
The phosphorylation coupling factors of the chloroplast thylakoid membranes were plucked off to form deficient membranes which were combined with crista membranes to form a fusion system. This membranes reconstituted ...The phosphorylation coupling factors of the chloroplast thylakoid membranes were plucked off to form deficient membranes which were combined with crista membranes to form a fusion system. This membranes reconstituted ATP synthesis activity in light. However, the △pH in the reaction medium was not observed.This paper is a report on some of the results obtained recently in connection with the problem. Various examinations and measurements were used and this phenomenon was repeated. Through the reconstituted system, (thylakoid membranes combined with crista membranes) the kinetic proton changes were studied. It proved that the photophosphorylation activity of this system increased with the increase of the quantity of the combined crista membranes to which, however, the △pH in medium, the effects of 9-AA fluorescence quenching, and the absorption change of neutral red in the membrane pockets were inversely proportional. For this phenomenon, analyses and discussions on the relationship between electron transport or proton transduction and ATP synthesis in the fusion membranes have been made.展开更多
A 62-year-old woman with frequent occurrence of symptomatic atrial tachycardia with a foci located at the root of the upper crista terminalis was found to have right diaphragm paresis after receiving a total of 8 radi...A 62-year-old woman with frequent occurrence of symptomatic atrial tachycardia with a foci located at the root of the upper crista terminalis was found to have right diaphragm paresis after receiving a total of 8 radiofrequency energy deliveries （40-60 W, 50-60℃） and a total duration of 540 seconds of ablation therapy （7Fr 8 mm deflectable ablation catheter）. The right diaphragm paresis remained resolved up to 14 months after the procedure as confirmed by repeated chest X-rays.展开更多
Objective:To investigate the hepatoprotective activity of ethanolic extract of leaves of Caesalpenia crista(C.crista)against paracetamol induced hepatotoxicity in rats.Methods:Paracetamol(2 g/kg body weight)was used t...Objective:To investigate the hepatoprotective activity of ethanolic extract of leaves of Caesalpenia crista(C.crista)against paracetamol induced hepatotoxicity in rats.Methods:Paracetamol(2 g/kg body weight)was used to induce hepatotoxicity in albino rats.Ethanolic extract of leaves of C.crista was administered at the dose levels of 200 and 400 mg/kg body weight orally for 7 d.Silymarin(100 mg/kg)was used as standard drug.The hepatoprotective effect of ethanolic extract was evaluated by assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase,serum glutamic pyruvic transaminase,serum alkaline phosphatase,bilirubin(total and direct),and triglycerides content.Histopathological study of rat liver was also done.Results:Administration of ethanolic extract at doses 200 mg/kg and 400 mg/kg body weight exhibited significant reduction in elevated level of serum marker enzymes,bilirubin(total and direct)and triglycerides when compared to positive control group.Conclusions:It is concluded that the ethanolic extract of C.crista leaves seems to justify the promising hepatoprotective effect on paracetamol induced liver damage in rats.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82300561,82270523,and 82305006)the Natural Science Foundation of Chongqing(No.CSTB2023NSCQ-MSX0713)+5 种基金the Chongqing Medical Young Talents Program(No.YXQN202452 and No.YXQN202415)the High-Level Military Technological Innovation Talent Program,the Chongqing Talent Program:Innovative Leading Talents(No.CSTC2024YCJH-BGZXM0011)the Sprint Program of Joint Medical Research of Chongqing Science and Chongqing Health Commission(No.2025CCXM-001)the Youth Program of Joint Medical Research of Chongqing Science and Chongqing Health Commission(No.2025QNXM038)the Special Funding for Postdoctoral Research Projects in Chongqing,the Science Foundation of State Key Laboratory of Trauma and Chemical Poisoning(No.2024K003)the Chongqing Natural Science Foundation Innovation and Development Joint Fund(Chongqing Education Commission)(No.CSTB2024NSCQLZX0079).
文摘Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dysfunction.The mechanism of this process remains elusive.Using rat models of ischemia and hypoxic vascular smooth muscle cells(VSMCs),we combined transmission electron microscopy,super-resolution microscopy,and metabolic analysis to analyze the structure and function change of mitochondrial cristae.Multi-omics approaches revealed arginase 1(Arg1)upregulation in ischemic VSMCs,confirmed by in vivo and in vitro knockout models showing Arg1's protective effects on mitochondrial cristae,mitochondrial and vascular function,and limited the release of mtDNA.Mechanistically,Arg1 interacting with Mic1o led to mitochondrial cristae remodeling,together with hypoxia-induced VDAC1 lactylation resulting in the opening of MPTP and release of mtDNA of VSMCs.The released mtDNA led to PANoptosis of VSMCs via activation of the cGAS-STING pathway.ChIP-qPCR results demonstrated that lactatemediated Arg1 up-regulation was due to H3K18la upregulation.VSMCs targeted nano-material PLGA-PEl-siRNA@PM-a-SMA(NPsiArg1)significantly improved vascular dysfunction.This study uncovers a new mechanism of vascular dysfunction following ischemic/hypoxic injury:a damaging positive feedback loop mediated by lactate-regulated Arg1 expression between the nucleus and mitochondria,leading to mitochondria cristae disorder and mtDNA release,culminating in VSMCs PANoptosis.Targeting VSMCs Arg1 inhibition offers a potential therapeutic strategy to alleviate ischemia/hypoxia-induced vascular impairments.
文摘Prohibitin is named due to the negative regulatory role of its gene products in cell proliferation. Prohibitin gene is located at q21 of chromosome 17 in human beings and the protein is found at mitochondria, nucleus and cytoplasm. Due to its size and ring-shaped structure, prohibitin protein defines functional subcompartments in mitochondria. Its subunits, PHB1 and PHB2, suppress cell proliferation as in the protein itself Nevertheless, recent investigation suggests that prohibitin protein enhances cell proliferation as well. It has also been found to suppress cell apoptosis by reducing cytochrome C release via the avoidance of mitochondrial crista remodeling which is facilitated through type 1 optic atrophy protein （OPAl）. Acting as a binding site for ubiquitin, prohibitin protein regulates protein degradation by proteasome. Examples are the degradations of sperm mitochondria in a fertilized ovum or those of an abnormal sperm.
基金This study was founded by the National Nature Science Foundation of China(11572079,11772087,31500765,11472074,11372069)。
文摘A three-dimensional numerical model of the membranous labyrinth of the semicircular canal of the inner ear was established to investigate the effects of canalithiasis of BPPV on the balance function of the inner ear.The movement of otolith particles in the membranous labyrinth was simulated when a person turns his head to a specific position.The effects of otolith movements on the balance function of the inner ear were simulated for different numbers,diameters,and initial positions of otoliths.The simulation results show that the otolith diameter affects the movement duration of otoliths in the membranous labyrinth.The number and diameter of otoliths,the diameter of the membranous labyrinth,and the initial position of the otoliths can cause changes in the pressure difference on both sides of the cupula of the crista ampullaris(cupula).The latent period and onset period are related to the diameter of otolith particles and the position of the head.There is also a correlation between the severity of the disease and the diameter and number of otolith particles.
基金Jain University,Bangalore for the financial support
文摘Objective:To screen plant extract fractions and elucidate the components present in Caesalpinia crista(C.crista)leaves for cholinergic and anti-amyloidogenic activities for the treatment of Alzheimer's diseases.Methods:This work has been carried out to study the action of C.crista extracts from nonpolar to polar solvents toward inhibition of oxidative stress,cholinergic and amyloidosis.The antioxidant activity was studied using DPPH total antioxidant assay;cholinergic assay by Ellman's method and anti-amyloidogenic assay by thioflavin-T fluorescence and transmission electron microscopy.Results:The quantification of polyphenols was carried out following C.crista methanolic extract(CCMeOH)HPLC fingerprinting,along with LC-MS and elucidated by MS LAMPS database.GC-MS of CCMeOH was screened for potential moieties.In vitro experimental results showed that the CCMe OH was potential extract that exhibited active inhibition of antioxidant property,cholinergic enzymes acetylcholinesterase and butyrylcholinesterase.For anti-amyloidogenic evaluations,among all the extracts,the CCMe OH was found to have the potential toward inhibiting the oligomers,fibrillation of Aβ42 with good defibrillation of amyloid cascading properties.Conclusions:These results are also supported by the presence of polyphenols as the active ingredients.Multi-potent target drug therapy is a promising option in treating the Alzheimer's diseases.Methanolic extract of C.crista shows potential activity against cholinergic enzymes,Aβ42 aggregation with antioxidant activity.
文摘Acanthosis nigricans is characterized by papillomatous brownish lesions mainly in the intertriginous areas. We used dermoscopy to examine such lesions in a family with acanthosis nigricans. The dermoscopic images showed an aberrant skin structure of linear crista cutis and sulcus cutis, and hyperpigmented dots in crista cutis. The hyperpigmented dots, which could not be seen with the naked eyes, may contribute to the color of the pigmented skin. Dermoscopy can be useful for evaluating disorders involving the structure of area cutanea and a change in skin color.
基金supported by grants from the Natural Science Foundation of Jiangsu Province(BK20221377 and BK20220607)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(22KJB180023)the National Natural Science Foundation of China Grants(32200783,32350017,and 92368104),and the Qing Lan Project of Jiangsu Province.
文摘Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis and development of HCs is crucial.Our current study highlights rhpn2,a member of rho-binding proteins,as essential for vestibular HC development.The rhpn2 gene is highly expressed in the crista and macula HCs.Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number,accompanied by vestibular dysfunction.Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants.Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab.Furthermore,co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA,validating the interaction of the two proteins.rhpn2 knockout leads to a decreased expression of rock2b,a canonical RhoA signaling pathway gene.Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants.This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway,providing a target for the treatment of balance disorders.
基金funded by the National Natural Science Foundation of China(No.81500858 to Xinwen Zhang,No.81700977 to Xu Yan)Natural Science Foundation of Liaoning Province(China)(No.2022-MS-231 to Xinwen Zhang)+1 种基金the Science and Technology Planning Project of Shenyang(China)(No.22-321-33-26 to Dehao Shang)Grants-in-Aid for Scientific Research(Japan)(No.22K09927 to Zhou Wu).
文摘Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial membrane,forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function.In the past decade,MICOS abnormalities have been extensively linked to AD pathogenesis.In particular,dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD,often in association with hallmark pathological features such as amyloid-b plaque accumulation,neurofibrillary tangle formation,and neuronal apoptosis.Furthermore,MICOS subunits interact with several etiologically relevant proteins,significantly influencing AD progression.The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD.Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment.In the present review,we introduce current understanding of MICOS structures and functions,highlight MICOS pathogenesis in AD,and summarize the available MICOS-targeting drugs potentially useful for AD.
基金This work was supported by the Special Project for the Shandong Provincial Key Laboratory(No.SDKL2017023)the National key R&D Plan Key Research Projects of Modernization of Traditional Chinese Medicine(No.2019 YFC1711203)+1 种基金Shandong Provincial Enterprise Project for Talents Development to P.X.L.,Key Research and Development Plan of Shandong Province(Nos.2018GSF121033,2019GSF108225,and 2019JZZY010520)Outstanding Contribution to the Shandong Middle-aged and Young Experts to F.L.,Academic promotion program of Shandong First Medical University(No.2019LJ003)to Q.X.C.We also thank Dr.Taosheng Huang for kindly gifted SLC25A46 normal and mutant cell line.
文摘Mitochondrial damage,characterized by altered morphological distribution and the damage of cristae,is closely associated with mitochondrial disease.However,imaging methods for capturing mitochondrial morphology at the nanoscale level in live samples remain unavailable,which seriously hinders the accurate evaluation and diagnosis of mitochondrial-related diseases.In response,we propose a super-resolution quantification strategy based on structured illumination microscopy(SIM)for the rapid,accurate evaluation of mitochondrial morphology.Using the strategy,we accurately captured the morphological distribution of mitochondria at the nanoscale level in a way generally applicable to checking various cell processes and identifying patients with mitochondrial disease who exhibit the SLC25A46 mutation.We also used algorithm-assisted super-resolution imaging to quantitatively analyze damage to mitochondrial cristae,which supports a novel drug screening strategy—high-resolution drug screening—for investigating drugs’pharmacodynamics on organelles in living cells.In short,our strategy improves the accurate examination of changes in mitochondrial morphology in living cells and indicates new ways in which SIM-imaging can assist in diagnosing mitochondrial disease at the single-cell level.
基金supported by the National Natural Science Foundation of China(32200231)the Zhejiang Provincial Natural Science Foundation of China(LZ23C020002)+1 种基金the National Key Research and Development Program(2022YFD1401600)to RPthe National Science Foundation(MCB 2148206)to JH.
文摘Besides providing energy to sustain life,mitochondria also play crucial roles in stress response and programmed cell death.The mitochondrial hallmark lipid,cardiolipin(CL),is essential to the maintenance of mitochondrial structure and function.However,how mitochondria and CL are involved in stress response is not as well defined in plants as in animal and yeast cells.We previously revealed a role for CL in mitochondrial fission and in heat stress response in Arabidopsis.To further determine the involvement of mitochondria and CL in plant heat response,here we treated Arabidopsis seedlings with varied lengths of acute heat stress.These treatments resulted in decreases in mitochondrial membrane potential,disruption of mitochondrial ultrastructure,accumulation of mitochondrial reactive-oxygen species(ROS),and redistribution of CL to the outer mitochondrial membrane and to a novel type of vesicle.The level of the observed changes correlated with the severeness of the heat stress,indicating the strong relevance of these processes to stress response.Our findings provide the basis for studying mechanisms underpinning the role of mitochondria and CL in plant stress response.
文摘Objective:To develop a downloadable three-dimensional(3D)study tool of the membranous labyrinth in order to facilitate the study of benign paroxysmal positional vertigo(BPPV).Background:The diagnosis and treatment of BPPV depend on an understanding of the anatomy of the vestibular labyrinth and its position relative to the head.To date,many illustrations have been made to explain principles of diagnosis and treatment of BPPV,but few have been based on anatomical studies of the membranous labyrinth.Methods:A previously reported 3D model of a human labyrinth was transposed to a 3D development software to allow the creation of markers along the semicircular ducts and utricle.These markers represent otoliths at different positions during movement of the model within the 3D environment.User-friendly tools were created to navigate the model,to allow clear documentation and communication of studied problems,and to study the model across relevant planes.The final model can be downloaded and is available for general useat https://bppvviewer.com/download/.Results:The model allows visualization of true membranous labyrinth anatomy in both ears simultaneously.The dependent portion of each semicircular duct,the planes of the cristae,and the position of the utricle can easily be visualized in any head position.Moveable markers can mark the expected progress of otolith debris with changes in head position and images can be captured to document simulations in various draw styles.Conclusion:This simple model could offer insights that lead to more accurate diagnosis and treatment of BPPV.It may also be useful as a tool to teach BPPV.
基金Project supported by the National Natural Science Foundation of China.
文摘The phosphorylation coupling factors of the chloroplast thylakoid membranes were plucked off to form deficient membranes which were combined with crista membranes to form a fusion system. This membranes reconstituted ATP synthesis activity in light. However, the △pH in the reaction medium was not observed.This paper is a report on some of the results obtained recently in connection with the problem. Various examinations and measurements were used and this phenomenon was repeated. Through the reconstituted system, (thylakoid membranes combined with crista membranes) the kinetic proton changes were studied. It proved that the photophosphorylation activity of this system increased with the increase of the quantity of the combined crista membranes to which, however, the △pH in medium, the effects of 9-AA fluorescence quenching, and the absorption change of neutral red in the membrane pockets were inversely proportional. For this phenomenon, analyses and discussions on the relationship between electron transport or proton transduction and ATP synthesis in the fusion membranes have been made.
文摘A 62-year-old woman with frequent occurrence of symptomatic atrial tachycardia with a foci located at the root of the upper crista terminalis was found to have right diaphragm paresis after receiving a total of 8 radiofrequency energy deliveries （40-60 W, 50-60℃） and a total duration of 540 seconds of ablation therapy （7Fr 8 mm deflectable ablation catheter）. The right diaphragm paresis remained resolved up to 14 months after the procedure as confirmed by repeated chest X-rays.
基金Supported by Teerthanker Mahaveer University,Delhi Road,Bagarpur,Moradabad,Uttar Pradesh,India(Grant No.TMU/TMCOP/2013-14/RES.GRANT-05/PGN).
文摘Objective:To investigate the hepatoprotective activity of ethanolic extract of leaves of Caesalpenia crista(C.crista)against paracetamol induced hepatotoxicity in rats.Methods:Paracetamol(2 g/kg body weight)was used to induce hepatotoxicity in albino rats.Ethanolic extract of leaves of C.crista was administered at the dose levels of 200 and 400 mg/kg body weight orally for 7 d.Silymarin(100 mg/kg)was used as standard drug.The hepatoprotective effect of ethanolic extract was evaluated by assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase,serum glutamic pyruvic transaminase,serum alkaline phosphatase,bilirubin(total and direct),and triglycerides content.Histopathological study of rat liver was also done.Results:Administration of ethanolic extract at doses 200 mg/kg and 400 mg/kg body weight exhibited significant reduction in elevated level of serum marker enzymes,bilirubin(total and direct)and triglycerides when compared to positive control group.Conclusions:It is concluded that the ethanolic extract of C.crista leaves seems to justify the promising hepatoprotective effect on paracetamol induced liver damage in rats.
