Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.

Deep tectonics and seismogenic mechanisms of the seismic source zone of the Jishishan M_(s)6.2 earthquake on December 18,2023,at the northeast margin of the Tibetan Plateau

On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.

Ultrasmall CoS nanoparticles embedded in heteroatom-doped carbon for sodium-ion batteries and mechanism explorations via synchrotron X-ray techniques

Transition metal sulfides have been regarded as promising anode materials for sodium-ion batteries(SIB).However,they face the challenges of poor electronic conductivity and large volume change,which result in capacity fade and low rate capability.In this work,a composite containing ultrasmall CoS(~7 nm)nanoparticles embedded in heteroatom(N,S,and O)-doped carbon was synthesized by an efficient one-step sulfidation process using a Co(Salen)precursor.The ultrasmall CoS nanoparticles are beneficial for mechanical stability and shortening Na-ions diffusion pathways.Furthermore,the N,S,and O-doped defect-rich carbon provides a robust and highly conductive framework enriched with active sites for sodium storage as well as mitigates volume expansion and polysulfide shuttle.As anode for SIB,CoS@HDC exhibits a high initial capacity of 906 mA h g^(-1)at 100 mA g^(-1)and a stable long-term cycling life with over 1000 cycles at 500 mA g^(-1),showing a reversible capacity of 330 mA h g^(-1).Meanwhile,the CoS@HDC anode is proven to maintain its structural integrity and compositional reversibility during cycling.Furthermore,Na-ion full batteries based on the CoS@HDC anode and Na_(3)V_(2)(PO_(4))_(3)cathode demonstrate a stable cycling behavior with a reversible specific capacity of~200 m A h g^(-1)at least for 100 cycles.Moreover,advanced synchrotron operando X-ray diffraction,ex-situ X-ray absorption spectroscopy,and comprehensive electrochemical tests reveal the structural transformation and the Co coordination chemistry evolution of the CoS@HDC during cycling,providing fundamental insights into the sodium storage mechanism.

Flexible transparent wood enabled by epoxy resin and ethylene glycol diglycidyl ether

Transparent wood has potential application in intelligent building,solar cell,electronics,and other advanced materials,while its single functionability hinders its further development.Flexible transparent wood(FTW)was prepared by alkaline pretreatment and bleaching treat-ment of paulownia wood followed by impregnation of epoxy resin and ethylene glycol diglycidyl ether(EDGE).The eff ect of delignifi cation degree on the optical and mechani-cal properties of FTW was studied,and the infl uence of the epoxy/EDGE ratio on the fl exibility and mechanical proper-ties of FTW was also investigated.The results showed that higher delignifi cation degree resulted in higher transmit-tance of FTW.More EDGE addition led to better fl exibility of FTW,while overmuch addition of EDGE will reduce the mechanical properties.The optimal FTW sample resulted in a high transmittance of 89%and an ultrahigh haze value of 97%with outstanding fl exibility and excellent mechanical properties.The investigation of FTW broadens the research fi eld of transparent wood,and provides great possibility for its application in fl exible wearable devices and fl exible materials.

Numerical Investigations on Supercritical Heat Transfer Characteristics of Environmental Friendly Refrigerants

The heat transfer of supercritical fluids is a vastly growing field, specifically to find suitable alternatives to replace conventional R134a, which can be beneficial for climate change. Most of the experimental and numerical investigations have been conducted to explore supercritical water, carbon dioxide and R134a as heat transfer working fluids. Hydrofluoroolefin (HFO) and refrigerants blends have been considered the most environment-friendly refrigerants to replace Chlorofluorocarbons (CFCs), Hydrochlorofluoro-carbons (HCFCs) and Hydrofluorocarbons (HFCs). Their main advantage of zero Ozone Depletion Potential (ODP) and comparatively lower Global Warming Potential (GWP) have attracted growing amount of attention to mitigate environmental issues. This work adopts the computational method and takes the environmentally friendly refrigerants to investigate the heat transfer characteristics under widely used shear-stress transport (SST) model. A comprehensive comparison was performed at reduced pressure of 1.10 for supercritical fluids R515A, R1234ze(E) and R134a. The peaks of heat transfer coefficient occurred in the vicinity of pseudo critical temperature for all of these considered fluids;however, R134a resulted in higher heat transfer coefficient, Reynolds number and Prandtl number in comparison with R515A and R1234ze(E). The higher heat transfer coefficient of supercritical fluid R134a is owing to its thermophysical properties and the specific heat plays crucial role in the heat transfer of supercritical fluids. Owing to environmental issues, R515A can be a considerable replacement of R134a. R1234ze(E) is also promising alternative to R134a;however, safety issues should thoroughly concern its mild flammable characteristics.

Thermophysical Properties and Supercritical Heat Transfer Characteristics of R515A

The heat transfer of supercritical fluids is a vastly growing field, specifically to find suitable alternative to replace conventional R134a, which can be beneficial for climate change. A considerable suggestion is R515A which possesses considerably lower global warming potential. The present simulations are designed to study supercritical fluid R515A under cooling conditions in horizontal position. The effect of pressure, mass flux, heat flux and tube diameter were considered for horizontal tube in the vicinity of pseudo critical temperature. Numerical investigations on heat transfer characteristics of supercritical fluid R515A were performed using widely used shear-stress transport (SST) model. Moreover, heat transfer correlations were developed and suggested to accurately predict Nusselt number within 10% accuracy. The simulation results showed about 3.98% average absolute deviation.

Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT,p38 MAPK/NF-κB pathways

Alcoholic liver disease(ALD)is the most frequent liver disease worldwide,resulting in severe harm to personal health and posing a serious burden to public health.Based on the reported antioxidant and anti-inflammatory capacities of scutellarin(SCU),this study investigated its protective role in male BALB/c mice with acute alcoholic liver injury after oral administration(10,25,and 50 mg/kg).The results indicated that SCU could lessen serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels and improve the histopathological changes in acute alcoholic liver;it reduced alcohol-induced malondialdehyde(MDA)content and increased glutathione peroxidase(GSH-Px),catalase(CAT),and superoxide dismutase(SOD)activity.Furthermore,SCU decreased tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1βmessenger RNA(mRNA)expression levels,weakened inducible nitric oxide synthase(iNOS)activity,and inhibited nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome activation.Mechanistically,SCU suppressed cytochrome P450 family 2 subfamily E member 1(CYP2E1)upregulation triggered by alcohol,increased the expression of oxidative stress-related nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)pathways,and suppressed the inflammation-related degradation of inhibitor of nuclear factor-κB(NF-κB)-α(IκBα)as well as activation of NF-κB by mediating the protein kinase B(AKT)and p38 mitogen-activated protein kinase(MAPK)pathways.These findings demonstrate that SCU protects against acute alcoholic liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and suppressing inflammation by regulating the AKT,p38 MAPK/NF-κB pathways.

Nanoscale chemical segregation to twin interfaces in τ-MnAl-C and resulting effects on the magnetic properties

In this study,aberration-corrected scanning transmission electron microscopy coupled with electron energy-loss spectroscopy(STEM-EELS)was used to investigate the atomistic structure and chemical com-position of true twin and order twin boundaries in ferromagneticτ-MnAl-C.True twins and order twins were distinguished based on the diffraction patterns using TEM.No elemental segregation was observed at the coherent true twin boundary but some Mn enrichment within a region of about 1.5-2 nm was found at the incoherent true twin boundary.A transition region with Mn enrichment about 4-6 nm wide was found at the order twin boundary.A carbon cluster with a size of around 5 nm was also found at the twin boundary.Micromagnetic simulations were conducted to study the effect of this chemical seg-regation at twin interfaces on the magnetic properties.The results showed that the coercivity tends to increase with increasing structural and chemical disorder at the interface.

Ameliorative effect of scutellarin on acute alcohol brain injury in mice

Drinking culture has high significance in both China and the world,whether in the entertainment sector or in social occasions;according to the World Health Organization's 2018 Global Alcohol and Health Report,about 3 million people died from excessive drinking in 2016,accounting for 5.3%of the total global deaths that year.Oxidative stress and inflammation are the most common pathological phenomena caused by alcohol abuse(Snyder et al.,2017).

Aeromonas sobria regulates proinflammatory immune response in mouse macrophages via activating the MAPK,AKT,and NF-κB pathways

Aeromonas sobria,a Gram-negative bacterium that can colonize both humans and animals,is found in a variety of environments,including water,seafood,meat,and vegetables(Cahill,1990;Galindo et al.,2004;Song et al,2019).Aeromonas spp.are conditionally pathogenic bacteria in aquaculture,which can rapidly proliferate,causing disease and even death in fish,especially when the environment is degraded(Neamat-Allah et al,2020,2021a,2021b).In developing countries,Aeromonas spp.have been associated with a wide spectrum of infections in humans,including gastroen-teritis,wound infections,septicemia,and lung infections(San Joaquin and Pickett,1988;Wang et al,2009;Su et al,2013).Infections caused by Aeromonas spp.are usually more severe in immunocompromised individuals(Miyamoto et al,2017).

Extracting local nucleation fields in permanent magnets using machine learning

Microstructural features play an important role in the quality of permanent magnets.The coercivity is greatly influenced by crystallographic defects,like twin boundaries,as is well known for MnAl-C.It would be very useful to be able to predict the macroscopic coercivity from microstructure imaging.Although this is not possible now,in the present work we examine a related question,namely the prediction of simulated nucleation fields of a quasi-three-dimensional(rescaled and extruded)system constructed from a two-dimensional image.