Mitochondrial dysfunction and quality control lie at the heart of subarachnoid hemorrhage

The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.

Competitive oxidation behavior of Ni-based superalloy GH4738 at extreme temperature

A high thrust-to-weight ratio poses challenges to the high-temperature performance of Ni-based superalloys. The oxidation behavior of GH4738 at extreme temperatures has been investigated by isothermal and non-isothermal experiments. As a result of the competitive diffusion of alloying elements, the oxide scale included an outermost porous oxide layer (OOL), an inner relatively dense oxide layer (IOL), and an internal oxide zone (IOZ), depending on the temperature and time. A high temperature led to the formation of large voids at the IOL/IOZ interface. At 1200℃, the continuity of the Cr-rich oxide layer in the IOL was destroyed, and thus, spallation occurred. Extension of oxidation time contributed to the size of Al-rich oxide particles with the increase in the IOZ. Based on this finding,the oxidation kinetics of GH4738 was discussed, and the corresponding oxidation behavior at 900-1100℃ was predicted.

Generation of mitochondrial replacement monkeys by female pronucleus transfer

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA diseases.While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously reported.In this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear transfer.These individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during development.The successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration

Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy production.They are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.

Role of methoxy and C_(α)-based substituents in electrochemical oxidation mechanisms and bond cleavage selectivity of β-O-4 lignin model compounds

In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.

Latest assessment methods for mitochondrial homeostasis in cognitive diseases

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).

Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

Effect of Ti and Ta content on the oxidation resistance of Co-Ni-based superalloys

Co-Ni-based superalloys are known for their capability to function at elevated temperatures and superior hot corrosion and thermal fatigue resistance.Therefore,these alloys show potential as crucial high-temperature structural materials for aeroengine and gas turbine hot-end components.Our previous work elucidated the influence of Ti and Ta on the high-temperature mechanical properties of alloys.However,the intricate interaction among elements considerably affects the oxidation resistance of alloys.In this paper,Co-35Ni-10Al-2W-5Cr-2Mo-1Nb-xTi-(5−x)Ta alloys(x=1,2,3,4)with varying Ti and Ta contents were designed and compounded,and their oxidation resistance was investigated at the temperature range from 800 to 1000℃.After oxidation at three test conditions,namely,800℃for 200 h,900℃for 200 h,and 1000℃for 50 h,the main structure of the oxide layer of the alloy consisted of spinel,Cr_(2)O_(3),and Al_(2)O_(3)from outside to inside.Oxides consisting of Ta,W,and Mo formed below the Cr_(2)O_(3)layer.The interaction of Ti and Ta imparted the highest oxidation resistance to 3Ti2Ta alloy.Conversely,an excessive amount of Ti or Ta resulted in an adverse effect on the oxidation resistance of the alloys.This study reports the volatilization of W and Mo oxides during the oxidation process of Co-Ni-based cast superalloys with a high Al content for the first time and explains the formation mechanism of holes in the oxide layer.The results provide a basis for gaining insights into the effects of the interaction of alloying elements on the oxidation resistance of the alloys they form.

Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

Maternal zinc alleviates tert-butyl hydroperoxide-induced mitochondrial oxidative stress on embryonic development involving the activation of Nrf2/PGC-1αpathway

Background Mitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species(ROS)damages embryonic development and leads to growth arrest.Objective The purpose of this study is to elucidate whether maternal zinc(Zn)exert protective effect on oxidative stress targeting mitochondrial function using an avian model.Result In ovo injected tert-butyl hydroperoxide(BHP)increases(P<0.05)hepatic mitochondrial ROS,malondialdehyde(MDA)and 8-hydroxy-2-deoxyguanosine(8-OHdG),and decreases(P<0.05)mitochondrial membrane potential(MMP),mitochondrial DNA(mtDNA)copy number and adenosine triphosphate(ATP)content,contributing to mitochondrial dysfunction.In vivo and in vitro studies revealed that Zn addition enhances(P<0.05)ATP synthesis and metallothionein 4(MT4)content and expression as well as alleviates(P<0.05)the BHP-induced mitochondrial ROS generation,oxidative damage and dysfunction,exerting a protective effect on mitochondrial function by enhancing antioxidant capacity and upregulating the mRNA and protein expressions of Nrf2 and PGC-1α.Conclusions The present study provides a new way to protect offspring against oxidative damage by maternal Zn supplementation through the process of targeting mitochondria involving the activation of Nrf2/PGC-1αsignaling.

Cosmetic or Dietary Vegetable Oils Sampled in the Cameroonian Market May Not Expose Consumers to Lipid Oxidation Products Generating Oxidative Stress and Inflammation

Vegetable oils are a source of energy, essential fatty acids, antioxidants and fat-soluble vitamins useful for human health care and development. These oils also contribute to organoleptic quality of their products’ derivatives. However, their chemical and physical properties can be modified by the mode of their extraction, storage and distribution. These modifications might negatively affect the nutritional quality of the oils. The goals of this study were to: sample different vegetable oils for cosmetic or dietary use marketed in Cameroon, and verify purity and oxidation states of each kind of oil through determination of its acidity, iodine, peroxide, saponification, refractive indexes and the conformity of the labeling. The carotene content, the level of polar components and specific absorbance were also determined. As the result, six oils namely palm, palm kernel, coconut, black cumin, peanut and shea butter were collected. Apart from labeling, chemicals and physicals parameters analyzed were generally in accordance with the Cameroonian and Codex Alimentarius standard. This study suggests that vegetable oils sampled in the Cameroonian market may not expose consumers to lipid oxidation products generating pathological oxidative stress and inflammation. However, efforts in application of existing standard need to be done as far as labeling are concerned.

Mitochondrial therapeutics and mitochondrial transfer for neurodegenerative diseases and aging

Mitochondrial dysfunction and neurodegeneration:Progressive neurodegenerative diseases affect a significant proportion of the population;in a single year,there are as many as 276 million disabilities and 9 million deaths as a result of neurological diseases.

The Fang’s hypoglycemic formula improves insulin resistance in type 2 diabetes mellitus by regulating mitochondrial autophagy

Background:To investigate the pharmacological effects of Fangshi Jiangtang decoction(FSJT)on type 2 diabetes mellitus(T2DM)model rats and explore its mechanism of action from the perspective of mitochondrial autophagy.Methods:Sixty Sprague Dawley rats were randomly divided into six groups after one week of adaptive feeding:Control group,T2DM model group,metformin group(0.2 g/kg by gavage),and FSJT low,medium,and high dose groups(9.5,19,38 g/kg by gavage).Except for the Control group,the other five groups were given a high-fat diet.The treatment lasted for 8 weeks,and blood glucose levels were measured weekly.Eight weeks later,blood samples were collected from the rats,and serum was separated for the determination of HbA1c,oral glucose tolerance test,and homeostatic model assessment for insulin resistance index.The pancreas of the rats was collected,weighed,and fixed.The same part of the pancreas was used for hematoxylin-eosin.Kits were used to detect triglycerides,total cholesterol,interleukin-1β,interleukin-6,tumor necrosis factor-α,malondialdehyde,glutathione peroxidase,and superoxide dismutase in pancreatic tissue to assess the effects of FSJT on inflammation and oxidative stress in T2DM rats.Western blot analysis was performed to detect the expression of VDAC1,TOM20,COXⅣ,PINK1,Parkin,beclin1,light chain 3,and selective autophagy adaptor protein P62 to evaluate the effects of FSJT on mitochondrial autophagy in T2DM model rats.Results:Compared with the T2DM model group,FSJT intervention significantly reduced blood glucose,HbA1c,oral glucose tolerance test,and homeostatic model assessment for insulin resistance index in T2DM model rats,alleviated pancreatic tissue lesions,reduced levels of total cholesterol,triglycerides,interleukin-1β,interleukin-6,tumor necrosis factor-α,and malondialdehyde,increased glutathione peroxidase and superoxide dismutase activities,downregulated the expression of VDAC1,TOM20,COXⅣ,and P62 proteins,and upregulated the expression of PINK1,Parkin,Beclin1,and light chain 3 proteins.Conclusion:FSJT can improve insulin resistance in T2DM by promoting the activation of mitochondrial autophagy.

Mitochondrial genomes of Tapes dorsatus and Cardita variegata:insights into Heteroconchia phylogeny

Heteroconchia,a widespread and abundant aquatic invertebrate,is an important clade of bivalve mollusks.The relationship between the three branches of Heteroconchia,Palaeoheterodonta,Archiheterodonta,and Euheterodonta has become a main controversy in molecular studies of the relationships between bivalves.In the present study,we assembled the complete mitochondrial genomes of Tapes dorsatus(Veneridae)and Cardita variegata(Carditidae)using high-throughput sequencing.C.variegata is the first mitochondrial genome belonging to the family Carditidae to be reported.We used 12 protein coding genes(excluding atp8)from the complete mitochondrial genomes of 146 species to recover the internal relationships of Heteroconchia.Our results support the traditional view of early branching of Palaeoheterodonta and the recovery of the monophyly of Palaeoheterodonta,Anomalodesmata,Imparidentia.Rearrangement analysis show that gene arrangement within Venerida was highly variable.Time-calibrated phylogenetic studies based on a relaxed molecular clock model suggested that Veneridae originated approximately 337.62 million years ago(Ma)and split into two major clades,whereas Carditidae originated approximately 510.09 Ma.Our results provide evidence of the internal relationships of Heteroconchia.

Gene characterization and phylogenetic analysis of four mitochondrial genomes in Caenogastropoda

Caenogastropoda is a highly diverse group,containing~60%of all existing gastropods.Species in this subclass predominantly inhabit marine environments and have a high ecological and economic value.Owing to the increase in relevant phylogenetic studies,our understanding of between species relatedness in Caenogastropoda has improved.However,the biodiversity,taxonomic status,and phylogenetic relationships of this group remain unclear.In the present study,we performed next-generation sequencing of four complete mitochondrial genomes from three families(Buccinidae,Columbellidae,and Cypraeidae)and the four mitogenomes were classical circular structures,with a length of 16177 bp in Volutharpa ampullacea,16244 bp in Mitrella albuginosa,16926bp in Mauritia arabica asiatica and 15422 bp in Erronea errones.Base composition analysis indicated that whole sequences were biased toward A and T.Then compared them with 171 complete mitochondrial genomes of Caenogastropoda.The phylogenetic relationship of Caenogastropoda derived from Maximum Likelihood(ML)and Bayesian Inference(BI)trees constructed based on CDS sequences was consistent with the results of traditional morphological analysis,with all three families showing close relationships.This study supported Caenogastropoda at the molecular level as a separate clade of Mollusca.According to our divergence time estimations,Caenogastropoda was formed during the middle Triassic period(~247.2–237 Ma).Our novel mitochondrial genomes provide evidence for the speciation of Caenogastropoda in addition to elucidating the mitochondrial genomic evolution of this subclass.

Tuning the reactivity of TiO_(2)layer with uniform distribution of Sub-5 nm Fe_(2)O_(3)particles via in situ voltage-assisted oxidation for robust catalytic reduction

The trade-off between efficiency and stability has limited the application of TiO_(2)as a catalyst due to its poor surface reactivity.Here,we present a modification of a TiO_(2)layer with highly stable Sub-5 nm Fe_(2)O_(3)nanoparticles(NP)by modulating its structure-surface reactivity relationship to attain efficiency-stability balance via a voltage-assisted oxidation approach.In situ simultaneous oxidation of the Ti substrate and Fe precursor using high-energy plasma driven by high voltage resulted in uniform distribution of Fe_(2)O_(3)NP embedded within porous TiO_(2)layer.Comprehensive surface characterizations with density functional theory demonstrated an improved electronic transition in TiO_(2)due to the presence of surface defects from reactive oxygen species and possible charge transfer from Ti to Fe;it also unexpectedly increased the active site in the TiO_(2)layer due to uncoordinated electrons in Sub-5 nm Fe_(2)O_(3)NP/TiO_(2)catalyst,thereby enhancing the adsorption of chemical functional groups on the catalyst.This unique embedded structure exhibited remarkable improvement in reducing 4-nitrophenol to 4-aminophenol,achieving approximately 99%efficiency in 20 min without stability decay after 20 consecutive cycles,outperforming previously reported TiO_(2)-based catalysts.This finding proposes a modified-electrochemical strategy enabling facile construction of TiO_(2)with nanoscale oxides extandable to other metal oxide systems.

Electrochemical anodic oxidation assisted fabrication of memristors

Owing to the advantages of simple structure,low power consumption and high-density integration,memristors or memristive devices are attracting increasing attention in the fields such as next generation non-volatile memories,neuromorphic computation and data encryption.However,the deposition of memristive films often requires expensive equipment,strict vacuum conditions,high energy consumption,and extended processing times.In contrast,electrochemical anodizing can produce metal oxide films quickly(e.g.10 s) under ambient conditions.By means of the anodizing technique,oxide films,oxide nanotubes,nanowires and nanodots can be fabricated to prepare memristors.Oxide film thickness,nanostructures,defect concentrations,etc,can be varied to regulate device performances by adjusting oxidation parameters such as voltage,current and time.Thus memristors fabricated by the anodic oxidation technique can achieve high device consistency,low variation,and ultrahigh yield rate.This article provides a comprehensive review of the research progress in the field of anodic oxidation assisted fabrication of memristors.Firstly,the principle of anodic oxidation is introduced;then,different types of memristors produced by anodic oxidation and their applications are presented;finally,features and challenges of anodic oxidation for memristor production are elaborated.

Boosted Electrocatalytic Glucose Oxidation Reaction on Noble-Metal-Free MoO_(3)-Decorated Carbon Nanotubes

Electrocatalytic glucose oxidation reaction(GOR)has attracted much attention owing to its crucial role in biofuel cell fabrication.Herein,we load MoO_(3)nanoparticles on carbon nanotubes(CNTs)and use a discharge process to prepare a noblemetal-free MC-60 catalyst containing MoO_(3),Mo_(2)C,and a Mo_(2)C–MoO_(3)interface.In the GOR,MC-60 shows activity as high as 745μA/(mmol/L cm^(2)),considerably higher than those of the Pt/CNT(270μA/(mmol/L cm^(2)))and Au/CNT catalysts(110μA/(mmol/L cm^(2))).In the GOR,the response minimum on MC-60 is as low as 8μmol/L,with a steady-state response time of only 3 s.Moreover,MC-60 has superior stability and anti-interference ability to impurities in the GOR.The better performance of MC-60 in the GOR is attributed to the abundant Mo sites bonding to C and O atoms at the MoO_(3)–Mo_(2)C interface.These Mo sites create active sites for promoting glucose adsorption and oxidation,enhancing MC-60 performance in the GOR.Thus,these results help to fabricate more effi cient noble-metal-free catalysts for the fabrication of glucose-based biofuel cells.

Resveratrol combats chronic diseases through enhancing mitochondrial quality

Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammation and anti-oxidation functions,and improving mitochondrial quality.Chronic diseases as non-communicable diseases are mainly caused by multiple factors,such as physiological decline and dysfunction in the body,and have become a significant challenge on public health worldwide.It is worth noting that chronic diseases such as Alzheimer's disease(AD),Parkinson's disease(PD),muscle atrophy,cardiovascular disease,obesity,and cancer are accompanied by abnormal mitochondrial function.Therefore,targeted regulation of mitochondria may be a meaningful way to prevent and treat chronic diseases.Increasing evidence has confirmed that RSV is actively involved in regulating mitochondria,and it has become an essential consideration to prevent and treat chronic diseases through targeting mitochondria and improving corresponding functions.In this article,current studies on RSV to optimize mitochondrial quality for preventing and alleviating chronic disease are systematically summarized,which can provide a theoretical reference for the development of functional foods or drugs to combat chronic diseases.