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.

Advancements in enhancing corrosion protection of Mg alloys:A comprehensive review on the synergistic effects of combining inhibitors with PEO coating

Magnesium(Mg)alloys are lightweight materials with excellent mechanical properties,making them attractive for various applications,including aerospace,automotive,and biomedical industries.However,the practical application of Mg alloys is limited due to their high susceptibility to corrosion.Plasma electrolytic oxidation(PEO),or micro-arc oxidation(MAO),is a coating method that boosts Mg alloys'corrosion resistance.However,despite the benefits of PEO coatings,they can still exhibit certain limitations,such as failing to maintain long-term protection as a result of their inherent porosity.To address these challenges,researchers have suggested the use of inhibitors in combination with PEO coatings on Mg alloys.Inhibitors are chemical compounds that can be incorporated into the coating or applied as a post-treatment to further boost the corrosion resistance of the PEO-coated Mg alloys.Corrosion inhibitors,whether organic or inorganic,can act by forming a protective barrier,hindering the corrosion process,or modifying the surface properties to reduce susceptibility to corrosion.Containers can be made of various materials,including polyelectrolyte shells,layered double hydroxides,polymer shells,and mesoporous inorganic materials.Encapsulating corrosion inhibitors in containers fully compatible with the coating matrix and substrate is a promising approach for their incorporation.Laboratory studies of the combination of inhibitors with PEO coatings on Mg alloys have shown promising results,demonstrating significant corrosion mitigation,extending the service life of Mg alloy components in aggressive environments,and providing self-healing properties.In general,this review presents available information on the incorporation of inhibitors with PEO coatings,which can lead to improved performance of Mg alloy components in demanding environments.

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.

240 nm AlGaN-based deep ultraviolet micro-LEDs:size effect versus edge effect

240 nm AlGaN-based micro-LEDs with different sizes are designed and fabricated.Then,the external quantum efficiency(EQE)and light extraction efficiency(LEE)are systematically investigated by comparing size and edge effects.Here,it is revealed that the peak optical output power increases by 81.83%with the size shrinking from 50.0 to 25.0μm.Thereinto,the LEE increases by 26.21%and the LEE enhancement mainly comes from the sidewall light extraction.Most notably,transversemagnetic(TM)mode light intensifies faster as the size shrinks due to the tilted mesa side-wall and Al reflector design.However,when it turns to 12.5μm sized micro-LEDs,the output power is lower than 25.0μm sized ones.The underlying mechanism is that even though protected by SiO2 passivation,the edge effect which leads to current leakage and Shockley-Read-Hall(SRH)recombination deteriorates rapidly with the size further shrinking.Moreover,the ratio of the p-contact area to mesa area is much lower,which deteriorates the p-type current spreading at the mesa edge.These findings show a role of thumb for the design of high efficiency micro-LEDs with wavelength below 250 nm,which will pave the way for wide applications of deep ultraviolet(DUV)micro-LEDs.

Experimental study on the effect of water absorption level on rockburst occurrence of sandstone

To investigate the mechanism of rockburst prevention by spraying water onto the surrounding rocks,15 experiments are performed considering different water absorption levels on a single face.High-speed photography and acoustic emission(AE)system are used to monitor the rockburst process.The effect of water on sandstone rockburst and the prevention mechanism of water on sandstone rockburst are analyzed from the perspective of energy and failure mode.The results show that the higher the ab-sorption degree,the lower the intensity of the rockburst after absorbing water on single side of sand-stone.This is reflected in the fact that with the increase in the water absorption level,the ejection velocity of rockburst fragments is smaller,the depth of the rockburst pit is shallower,and the AE energy is smaller.Under the water absorption level of 100%,the magnitude of rockburst intensity changes from medium to slight.The prevention mechanism of water on sandstone rockburst is that water reduces the capacity of sandstone to store strain energy and accelerates the expansion of shear cracks,which is not conducive to the occurrence of plate cracking before rockburst,and destroys the conditions for rockburst incubation.

Evaluation of the intracellular lipid-lowering effect of polyphenols extract from highland barley in HepG2 cells

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.

Achieving oxidation protection effect for strips hot rolling via Al_(2)O_(3) nanofluid lubrication

It was discovered the application of Al_(2)O_(3) nanofluid as lubricant for steel hot rolling could synchronously achieve oxidation protection of strips surface.The underlying mechanism was investigated through hot rolling tests and molecular dynamics (MD) simulations.The employment of Al_(2)O_(3) nanoparticles contributed to significant enhancement in the lubrication performance of lubricant.The rolled strip exhibited the best surface topography that the roughness reached lowest with the sparsest surface defects.Besides,the oxide scale generated on steel surface was also thinner,and the ratio of Fe_(2)O_(3) among various iron oxides became lower.It was revealed the above oxidation protection effect of Al_(2)O_(3) nanofluid was attributed to the deposition of nanoparticles on metal surface during hot rolling.A protective layer in the thickness of about 193 nm was formed to prevent the direct contact between steel matrix and atmosphere,which was mainly composed of Al_(2)O_(3) and sintered organic molecules.MD simulations confirmed the diffusion of O_(2) and H_(2)O could be blocked by the Al_(2)O_(3) layer through physical absorption and penetration barrier effect.

High responsivity photodetectors based on graphene/WSe_(2) heterostructure by photogating effect

Graphene, with its zero-bandgap electronic structure, is a highly promising ultra-broadband light absorbing material.However, the performance of graphene-based photodetectors is limited by weak absorption efficiency and rapid recombination of photoexcited carriers, leading to poor photodetection performance. Here, inspired by the photogating effect, we demonstrated a highly sensitive photodetector based on graphene/WSe_(2) vertical heterostructure where the WSe_(2) layer acts as both the light absorption layer and the localized grating layer. The graphene conductive channel is induced to produce more carriers by capacitive coupling. Due to the strong light absorption and high external quantum efficiency of multilayer WSe_(2), as well as the high carrier mobility of graphene, a high photocurrent is generated in the vertical heterostructure. As a result, the photodetector exhibits ultra-high responsivity of 3.85×10~4A/W and external quantum efficiency of 1.3 × 10~7%.This finding demonstrates that photogating structures can effectively enhance the sensitivity of graphene-based photodetectors and may have great potential applications in future optoelectronic devices.

Engineering Strategies for Suppressing the Shuttle Effect in Lithium–Sulfur Batteries

Lithium–sulfur(Li–S)batteries are supposed to be one of the most potential next-generation batteries owing to their high theoretical capacity and low cost.Nevertheless,the shuttle effect of firm multi-step two-electron reaction between sulfur and lithium in liquid electrolyte makes the capacity much smaller than the theoretical value.Many methods were proposed for inhibiting the shuttle effect of polysulfide,improving corresponding redox kinetics and enhancing the integral performance of Li–S batteries.Here,we will comprehensively and systematically summarize the strategies for inhibiting the shuttle effect from all components of Li–S batteries.First,the electrochemical principles/mechanism and origin of the shuttle effect are described in detail.Moreover,the efficient strategies,including boosting the sulfur conversion rate of sulfur,confining sulfur or lithium polysulfides(LPS)within cathode host,confining LPS in the shield layer,and preventing LPS from contacting the anode,will be discussed to suppress the shuttle effect.Then,recent advances in inhibition of shuttle effect in cathode,electrolyte,separator,and anode with the aforementioned strategies have been summarized to direct the further design of efficient materials for Li–S batteries.Finally,we present prospects for inhibition of the LPS shuttle and potential development directions in Li–S batteries.

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.

Carbon Emission Effects Driven by Evolution of Chinese Dietary Structure from 1987 to 2020

Exploring carbon emission effects based on the evolution of residents’ dietary structure to achieve the carbon neutrality goal and mitigate climate change is an important task.This study took China as the research object(data excluding Hong Kong,Macao and Taiwan) and used the carbon emission coefficient method to quantitatively measure the food carbon emissions from 1987–2020,then analyzed the carbon emission effects under the evolution of dietary structure.The results showed that during the study period,the Chinese dietary structure gradually changed to a high-carbon consumption pattern.The dietary structure of urban residents developed to a balanced one,while that of rural residents developed to a high-quality one.During the study period,the per capita food carbon emissions and total food consumption of Chinese showed an increasing trend.The per capita food carbon emissions of residents in urban and rural showed an overall upward trend.The total food carbon emissions in urban increased significantly,while that in rural increased first and then decreased.The influence of beef and mutton on carbon emissions is the highest in dietary structure.Compared with the balanced dietary pattern,the food carbon emissions of Chinese residents had not yet reached the peak,but were evolving to a high-carbon consumption pattern.

“Buckets effect”in the kinetics of electrocatalytic reactions

In this study,we systematically investigated the effect of proton concentration on the kinetics of the oxygen reduction reaction(ORR)on Pt(111)in acidic solutions.Experimental results demonstrate a rectangular hyperbolic relationship,i.e.,the ORR current excluding the effect of other variables increases with proton concentration and then tends to a constant value.We consider that this is caused by the limitation of ORR kinetics by the trace oxygen concentration in the solution,which determines the upper limit of ORR kinetics.A model of effective concentration is further proposed for rectangular hyperbolic relationships:when the reactant concentration is high enough to reach a critical saturation concentration,the effective reactant concentration will become a constant value.This could be due to the limited concentration of a certain reactant for reactions involving more than one reactant or the limited number of active sites available on the catalyst.Our study provides new insights into the kinetics of electrocatalytic reactions,and it is important for the proper evaluation of catalyst activity and the study of structureperformance relationships.

Protective effects of baffles with different positions,row spacings,heights on debris flow impact

The baffle effectively slowed down debris flow velocity,reduced its kinetic energy,and significantly shortened the distance of debris flow movement.Consequently,they are widely used for protection against natural hazards such as landslides and mudslides.This study,based on the threedimensional DEM(Discrete Element Method),investigated the impact of different baffle positions on debris flow protection.Debris flow velocity and kinetic energy variations were studied through single-factor experiments.Suitable baffle positions were preliminarily selected by analyzing the influence of the first-row baffle position on the impact force and accumulation mass of debris flow.Subsequently,based on the selected baffle positions and four factors influencing the effectiveness of baffle protection(baffle position(P),baffle height(h),row spacing(S_(r)),and angle of transit area(α)),an orthogonal design was employed to further explore the optimal arrangement of baffles.The research results indicate that the use of a baffle structure could effectively slow down the motion velocity of debris flows and dissipate their energy.When the baffle is placed in the transit area,the impact force on the first-row baffle is greater than that when the baffle is placed in the deposition area.Similarly,when the baffle is placed in the transit area,the obstruction effect on debris flow mass is also greater than that when the baffle is placed in the deposition area.Through orthogonal experimental range analysis,when the impact on the first row of baffles is used as the evaluation criterion,the importance of each influencing factor is ranked asα>P>S_(r)>h.When the mass of debris flow behind the baffle is regarded as the evaluation criterion,the rank is changed to P>α>S_(r)>h.The experimental simulation results show that the optimal baffle arrangement is:P_(5),S_(r)=16,α=35°,h=9.

Understanding the Relationship Between Shrinking Cities and Land Prices:Spatial Pattern,Effectiveness,and Policy Implications

Urban shrinkage has emerged as a widespread phenomenon globally and has a significant impact on land,particularly in terms of land use and price.This study focuses on 2851 county-level cities in China in 2005–2018(excluding Hong Kong,Macao,Taiwan,and‘no data’areas in Qinhai-Tibet Plateau)as the fundamental units of analysis.By employing nighttime light(NTL)data to identify shrinking cities,the propensity score matching(PSM)model was used to quantitatively examine the impact of shrinking cities on land prices,and evaluate the magnitude of this influence.The findings demonstrate the following:1)there were 613 shrinking cities in China,with moderate shrinkage being the most prevalent and severe shrinkage being the least.2)Regional disparities are evident in the spatial distribution of shrinking cities,especially in areas with diverse terrain.3)The spatial pattern of land price exhibits a significant correlated to the economic and administrative levels.4)Shrinking cities significantly negatively impact on the overall land price(ATT=–0.1241,P<0.05).However,the extent of the effect varies significantly among different spatial regions.This study contributes novel insights into the investigation of land prices and shrinking cities,ultimately serving as a foundation for government efforts to promote the sustainable development of urban areas.

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.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Ambroxol,the cough expectorant with neuroprotective effects

Ambroxol hydrochloride(2-amino-3,5-dibromo-N-methylbenzylamine hydrochloride)has been used as a mucolytic agent in the treatment of respiratory diseases since the late 1970s.Its effects on mucus membranes such as mucus disruption,increased mucus production,and low toxicity profile were addressed in its original German patent in 1966.These first described properties have kept Ambroxol available worldwide and over the counter in the pharmaceutical market to this day.

Anticancer effects of exercise:Insights from single-cell analysis

A recent special topic in the Journal of Sport and Health Science reported the health benefits conferred by traditional and innovative m-health exercise and multimodal programs with respect to several types of cancer.1 A possible mechanism behind this protective effect could be enhanced cancer immunosurveillance.

Acute Toxicity of Jinchuan Formula Plum Wine Extract and Its Protective Effect on Mice with Liver Injury

[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.

More tree growth reduction due to consecutive drought and its legacy effect for a semiarid larch plantation in Northwest China

Extreme climate has increasingly led to negative impacts on forest ecosystems globally,especially in semiarid areas where forest ecosystems are more vulnerable.However,it is poorly understood how tree growth is affected by different drought events.In 2006–2009,the larch plantations in the semiarid areas of Northwest China were negatively affected by four consecutive dry years,which was a very rare phenomenon that may occur frequently under future climate warming.In this study,we analyzed the effect of these consecutive dry years on tree growth based on the data of the tree rings in the dominant layer of the forest canopy on a larch plantation.We found that the tree-ring width index(RWI)in dry years was lower than that in normal years,and it experienced a rapidly decreasing trend from 2006 to 2009(slope=-0.139 year^(-1),r=-0.94)due to water supply deficits in those dry years.Drought induced legacy effects of tree growth reduction,and consecutive dry years corresponded with greater growth reductions and legacy effects.Growth reductions and legacy effects were significantly stronger in the third and fourth consecutive dry years than that of single dry year(p<0.05),which might have been due to the cumulative stress caused by consecutive dry years.Our results showed that larch trees experienced greater tree growth reduction due to consecutive dry years and their legacy effect,and the trees had lower recovery rates after consecutive dry years.Our results highlight that consecutive dry years pose a new threat to plantations under climate warming,and thus,the effect of climate extremes on tree growth should be considered in growth models in semiarid areas.