A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

Assessing the corrosion protection property of coatings loaded with corrosion inhibitors using the real-time atmospheric corrosion monitoring technique

The atmospheric corrosion monitoring(ACM)technique has been widely employed to track the real-time corrosion behavior of metal materials.However,limited studies have applied ACM to the corrosion protection properties of organic coatings.This study compared a bare epoxy coating with one containing zinc phosphate corrosion inhibitors,both applied on ACM sensors,to observe their corrosion protection properties over time.Coatings with artificial damage via scratches were exposed to immersion and alternating dry and wet environments,which allowed for monitoring galvanic corrosion currents in real-time.Throughout the corrosion tests,the ACM currents of the zinc phosphate/epoxy coating were considerably lower than those of the blank epoxy coating.The trend in ACM current variations closely matched the results obtained from regular electrochemical tests and surface analysis.This alignment highlights the potential of the ACM technique in evaluating the corrosion protection capabilities of organic coatings.Compared with the blank epoxy coating,the zinc phosphate/epoxy coating showed much-decreased ACM current values that confirmed the effective inhibition of zinc phosphate against steel corrosion beneath the damaged coating.

Research on the overload protection reliability of moulded case circuit-breakers and its test device

This paper analyzed the reliability and put forward the reliability index of overload protection for moulded case circuit breaker. The success rate was adopted as its reliability index of overload protection. Based on the reliability index and the reli- ability level, the reliability examination plan was analyzed and a test device for the overload protection of moulded case cir- cuit-breaker was developed. In the reliability test of overload protection, two power sources were used, which reduced the time of conversion and regulation between two different test currents in the overload protection test, which made the characteristic test more accurate. The test device was designed on the base of a Windows system, which made its operation simple and friendly.

The future of artificial hibernation medicine:protection of nerves and organs after spinal cord injury

Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Efficient unequal error protection for online fountain codes

In this paper,an efficient unequal error protection(UEP)scheme for online fountain codes is proposed.In the buildup phase,the traversing-selection strategy is proposed to select the most important symbols(MIS).Then,in the completion phase,the weighted-selection strategy is applied to provide low overhead.The performance of the proposed scheme is analyzed and compared with the existing UEP online fountain scheme.Simulation results show that in terms of MIS and the least important symbols(LIS),when the bit error ratio is 10-4,the proposed scheme can achieve 85%and 31.58%overhead reduction,respectively.

Network pharmacology and subsequent experimental validation reveal the synergistic myocardial protection mechanism of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.

Objective:To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge(S.miltiorrhiza,Dan Shen)and C.tinctorius L.(C.tinctorius,Hong Hua)as an herb pair through network pharmacology and subsequent experimental validation.Methods:Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of s.miltiorrhiza and C.tinctorius as herb pair.Molecular docking was used to verify the binding of the components of these herbs and their potential targets.An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects,which were evaluated using the combination index.Western blot was performed to detect the protein expression of these targets.Results:Network pharmacology analysis revealed 5 pathways and 8 core targets of s.miltiorrhiza and C.tinctorius in myocardial protection.Five of the core targets were enriched in the hypoxia-inducible factor-1(HIF-1)signaling pathway.S.miltiorrhiza-C.tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway.As an upstream gene of the HIF-1 pathway,STAT3 can be activated by the active ingredients cryptotanshinone(Ctan),salvianolic acid B(Sal.B),and myricetin(Myric).Cell experiments revealed that Myric,Sal.B,and Ctan also exhibited synergistic myocardial protective activity.Molecular docking verified the strong binding of Myric,Sal.B,and Ctan to STAT3.Western blot further showed that the active ingredients synergistically upregulated the protein expressionof STAT3.Conclusion:The pharmacodynamic transmission analysis revealed that the active ingredients of S.miltiorrhiza and C.tinctorius can synergistically resist ischemia through various targets and pathways.This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function

Mechanical overloading and aging are two essential factors for osteoarthritis(OA)development.Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology,but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated.

Composite armor philosophy(CAP):Holistic design methodology of multi-layered composite protection systems for armored vehicles

A philosophy for the design of novel,lightweight,multi-layered armor,referred to as Composite Armor Philosophy(CAP),which can adapt to the passive protection of light-,medium-,and heavy-armored vehicles,is presented in this study.CAP can serve as a guiding principle to assist designers in comprehending the distinct roles fulfilled by each component.The CAP proposal comprises four functional layers,organized in a suggested hierarchy of materials.Particularly notable is the inclusion of a ceramic-composite principle,representing an advanced and innovative solution in the field of armor design.This paper showcases real-world defense industry applications,offering case studies that demonstrate the effectiveness of this advanced approach.CAP represents a significant milestone in the history of passive protection,marking an evolutionary leap in the field.This philosophical approach provides designers with a powerful toolset with which to enhance the protection capabilities of military vehicles,making them more resilient and better equipped to meet the challenges of modern warfare.

Self-actuating protection mechanisms for safer lithium-ion batteries

Safety issue is still a problem nowadays for the large-scale application of lithium-ion batteries(LIBs)in electric vehicles and energy storage stations.The unsafe behaviors of LIBs arise from the thermal run-away,which is intrinsically triggered by the overcharging and overheating.To improve the safety of LIBs,various protection strategies based on self-actuating reaction control mechanisms(SRCMs)have been proposed,including redox shuttle,polymerizable monomer additive,potential-sensitive separator,thermal shutdown separator,positive-temperature-coefficient electrode,thermally polymerizable addi-tive,and reversible thermal phase transition electrolyte.As build-in protection mechanisms,these meth-ods can sensitively detect either the temperature change inside battery or the potential change of the electrode,and spontaneously shut down the electrode reaction at risky conditions,thus preventing the battery from going into thermal runaway.Given their advantages in enhancing the intrinsic safety of LIBs,this paper overviews the research progresses of SRCMs after a brief introduction of thermal runaway mechanism and limitations of conventional thermal runaway mitigating measures.More importantly,the current states and issues,key challenges,and future developing trends of SRCTs are also discussed and outlined from the viewpoint of practical application,aiming at providing insights and guidance for developing more effective SRCMs for LIBs.

Investigations of the mechanical response of dummy HTPB propellant grain under ultrahigh acceleration overload conditions using onboard flight-test measurements

In this paper,to study the mechanical responses of a solid propellant subjected to ultrahigh acceleration overload during the gun-launch process,specifically designed projectile flight tests with an onboard measurement system were performed.Two projectiles containing dummy HTPB propellant grains were successfully recovered after the flight tests with an ultrahigh acceleration overload value of 8100 g.The onboard-measured time-resolved axial displacement,contact stress and overload values were successfully obtained and analysed.Uniaxial compression tests of the dummy HTPB propellant used in the gunlaunched tests were carried out at low and intermediate strain rates to characterize the propellant's dynamic properties.A linear viscoelastic constitutive model was employed and applied in finite-element simulations of the projectile-launching process.During the launch process,the dummy propellant grain exhibited large deformation due to the high acceleration overload,possibly leading to friction between the motor case and propellant grain.The calculated contact stress showed good agreement with the experimental results,though discrepancies in the overall displacement of the dummy propellant grain were observed.The dynamic mechanical response process of the dummy propellant grain was analysed in detail.The results can be used to estimate the structural integrity of the analysed dummy propellant grain during the gun-launch process.

SiO_(2) Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

Enhancing Identity Protection in Metaverse-Based Psychological Counseling System

Non-face-to-face psychological counseling systems rely on network technologies to anonymize information regard-ing client identity.However,these systems often face challenges concerning voice data leaks and the suboptimal communication of the client’s non-verbal expressions,such as facial cues,to the counselor.This study proposes a metaverse-based psychological counseling system designed to enhance client identity protection while ensuring efficient information delivery to counselors during non-face-to-face counseling.The proposed systemincorporates a voicemodulation function that instantlymodifies/masks the client’s voice to safeguard their identity.Additionally,it employs real-time client facial expression recognition using an ensemble of decision trees to mirror the client’s non-verbal expressions through their avatar in the metaverse environment.The system is adaptable for use on personal computers and smartphones,offering users the flexibility to access metaverse-based psychological counseling across diverse environments.The performance evaluation of the proposed system confirmed that the voice modulation and real-time facial expression replication consistently achieve an average speed of 48.32 frames per second or higher,even when tested on the least powerful smartphone configurations.Moreover,a total of 550 actual psychological counseling sessions were conducted,and the average satisfaction rating reached 4.46 on a 5-point scale.This indicates that clients experienced improved identity protection compared to conventional non-face-to-face metaverse counseling approaches.Additionally,the counselor successfully addressed the challenge of conveying non-verbal cues from clients who typically struggled with non-face-to-face psychological counseling.The proposed systemholds significant potential for applications in interactive discussions and educational activities in the metaverse.

What If the Protection against Oxidation of Chromia-Forming Alloys Was Not Always Due to the Chromia Layer?

Chromia-forming alloys have good resistance to oxidizing agents such as O2, CO2, … It is accepted that the protection of these alloys is always due to the chromia layer formed at the surface of the alloys, which acts as a barrier between the oxidizing gases and the alloy substrates, forming a diffusion zone that limits the overall reaction rate and leads to parabolic kinetics. But this was not verified in the study devoted to Inconel®625 the oxidation in CO2 that was followed by TGA, with characterizations by XRD, EDS and FIB microscopy. Contrary to what was expected and accepted in similar studies on other chromia-forming alloys, it was shown that the diffusion step that governs the overall reaction rate is not located inside the chromia layer but inside the alloy, precisely inside a zone just beneath the interface alloy/chromia, this zone being depleted in chromium. The chromia layer, therefore, plays no kinetic role and does not directly protect the underlying alloy. This result was demonstrated using a simple test that consisted in removing the chromia layer from the surface of samples partially oxidized and then to continue the thermal treatment: insofar as the kinetics continued without any change in rate, this proved that this surface layer of oxide did not protect the substrate. Based on previous work on many chromia-forming alloys, the possibility of a similar reaction mechanism is discussed. If the chromia layer is not the source of protection for a number of chromia-forming alloys, as is suspected, this might have major consequences in terms of industrial applications.

Formation and ecological response of sand patches in the protection system of Shapotou section of the Baotou-Lanzhou railway,China

The development of bare patches typically signifies a process of ecosystem degradation.Within the protection system of Shapotou section of the Baotou-Lanzhou railway,the extensive emergence of bare sand patches poses a threat to both stability and sustainability.However,there is limited knowledge regarding the morphology,dynamic changes,and ecological responses associated with these sand patches.Therefore,we analyzed the formation and development process of sand patches within the protection system and its effects on herbaceous vegetation growth and soil nutrients through field observation,survey,and indoor analysis methods.The results showed that sand patch development can be divided into three stages,i.e.,formation,expansion,and stabilization,which correspond to the initial,actively developing,and semi-fixed sand patches,respectively.The average dimensions of all sand patch erosional areas were found to be 7.72 m in length,3.91 m in width,and 0.32 m in depth.The actively developing sand patches were the largest,and the initial sand patches were the smallest.Throughout the stage of formation and expansion,the herbaceous community composition changed,and the plant density decreased by more than 50.95%.Moreover,the coverage and height of herbaceous plants decreased in the erosional area and slightly increased in the depositional lobe;and the fine particles and nutrients of soils in the erosional area and depositional lobe showed a decreasing trend.In the stabilization phases of sand patches,the area from the inlet to the bottom of sand patches becomes initially covered with crusts.Vegetation and 0-2 cm surface soil condition improved in the erosional area,but this improvement was not yet evident in the depositional lobe.Factors such as disturbance,climate change,and surface resistance to erosion exert notable influences on the formation and dynamics of sand patches.The results can provide evidence for the future treatment of sand patches and the management of the protection system of Shapotou section of the Baotou-Lanzhou railway.

Wood By-Products as UV Protection:A Consequence Review

In recent decades,the ozone layer has suffered considerable damage,increasing the entry of ultraviolet(UV)light into the atmosphere and reaching the earth’s surface,negatively affecting life.Accordingly,researchers aimed to solve this problem by synthesizing advanced UV-shielding materials.On the other hand,developing an easy and green strategy to prepare functional materials with outstanding properties based on naturally abundant and environmentally friendly raw materials is highly desirable for sustainable development.Because biomass-derived materials are sustainable and biodegradable,they present a promising substitute for petroleum-based polymers.The three main structural constituents of the plant biomass-based materials that are naturally available are cellulose,hemicellulose,and lignin.This review details current developments using wood-based products such as cellulose,hemicellulose,and lignin in UV-shielding applications.It will start with assembling the structure and chemistry of cellulose,hemicellulose,and lignin,followed by their contributions to preparing UV-shielding materials.Finally,it will briefly discuss the different processing methods for the design of UV-shielding materials.The wood by-products offer additional opportunities to use the whole tree harvest.

Redundant Data Detection and Deletion to Meet Privacy Protection Requirements in Blockchain-Based Edge Computing Environment

With the rapid development of information technology,IoT devices play a huge role in physiological health data detection.The exponential growth of medical data requires us to reasonably allocate storage space for cloud servers and edge nodes.The storage capacity of edge nodes close to users is limited.We should store hotspot data in edge nodes as much as possible,so as to ensure response timeliness and access hit rate;However,the current scheme cannot guarantee that every sub-message in a complete data stored by the edge node meets the requirements of hot data;How to complete the detection and deletion of redundant data in edge nodes under the premise of protecting user privacy and data dynamic integrity has become a challenging problem.Our paper proposes a redundant data detection method that meets the privacy protection requirements.By scanning the cipher text,it is determined whether each sub-message of the data in the edge node meets the requirements of the hot data.It has the same effect as zero-knowledge proof,and it will not reveal the privacy of users.In addition,for redundant sub-data that does not meet the requirements of hot data,our paper proposes a redundant data deletion scheme that meets the dynamic integrity of the data.We use Content Extraction Signature(CES)to generate the remaining hot data signature after the redundant data is deleted.The feasibility of the scheme is proved through safety analysis and efficiency analysis.

Spatiotemporal patterns and driving factors of soil protection in the wind-water erosion area of Chinese Loess Plateau

As one of typical areas in the world,northern Chinese Loess Plateau experiences serious wind-water erosion,which leads to widespread land degradation.During the past decades,an ecological engineering was implemented to reduce soil erosion and improve soil protection in this area.Thus,it is necessary to recognize the basic characteristics of soil protection for sustainable prevention and wind-water erosion control in the later stage.In this study,national wind erosion survey model and revised universal soil loss equation were used to analyze the spatiotemporal evolution and driving forces of soil protection in the wind-water erosion area of Chinese Loess Plateau during 2000–2020.Results revealed that:(1)during 2000–2020,total amount of soil protection reached up to 15.47×10^(8) t,which was realized mainly through water and soil conservation,accounting for 63.20%of the total;(2)soil protection was improved,with increases in both soil protection amount and soil retention rate.The amounts of wind erosion reduction showed a decrease trend,whereas the retention rate of wind erosion reduction showed an increase trend.Both water erosion reduction amount and retention rate showed increasing trends;and(3)the combined effects of climate change and human activities were responsible for the improvement of soil protection in the wind-water erosion area of Chinese Loess Plateau.The findings revealed the spatiotemporal patterns and driving forces of soil protection,and proposed strategies for future soil protection planning in Chinese Loess Plateau,which might provide valuable references for soil erosion control in other wind-water erosion areas of the world.

Recent Advances in Bronchopulmonary Dysplasia Protection and Therapy

For preterm infants, bronchopulmonary dysplasia (BPD) is usually caused by abnormal lung development due to various factors during prenatal and postnatal process. One of the reasons for death and bad prognosis of preterm infants is to have BPD. Up to now, there are no unified strategies or drugs to treat BPD. In clinical, many intervention treatments have been applied to achieve BPD therapy, mainly including preterm protection, protective ventilation strategies, and delivery of corticosteroids, pulmonary vasodilators, and antioxidants. This review summarizes the current advances in BPD protection and treatment, and notes that gut microbiota and mesenchymal stem cells (MSCs) can be the promising strategy for protecting and treating BPD in the future.