Atherosis-associated lnc_000048 activates PKR to enhance STAT1-mediated polarization of THP-1 macrophages to M1 phenotype

Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classically activated macrophage(M1)polarization.In this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages.Flow cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048.Flow cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite effect.Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization.Moreover,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR.Immunofluorescence(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage.We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression.Taken together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Cell polarization in ischemic stroke: molecular mechanisms and advances

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Linear dichroism transition and polarization-sensitive photodetector of quasi-one-dimensional palladium bromide

Perpendicular optical reversal of the linear dichroism transition has promising applications in polarization-sensitive optoelectronic devices. We perform a systematical study on the in-plane optical anisotropy of quasi-one-dimensional PdBr_(2) by using combined measurements of the angle-resolved polarized Raman spectroscopy(ARPRS) and anisotropic optical absorption spectrum. The analyses of ARPRS data validate the anisotropic Raman properties of the PdBr_(2) flake.And anisotropic optical absorption spectrum of PdBr_(2) nanoflake demonstrates distinct optical linear dichroism reversal. Photodetector constructed by PdBr_(2) nanowire exhibits high responsivity of 747 A·W^(-1) and specific detectivity of 5.8×10^(12) Jones. And the photodetector demonstrates prominent polarization-sensitive photoresponsivity under 405-nm light irradiation with large photocurrent anisotropy ratio of 1.56, which is superior to those of most of previously reported quasi-one-dimensional counterparts. Our study offers fundamental insights into the strong optical anisotropy exhibited by PdBr_(2), establishing it as a promising candidate for miniaturization and integration trends of polarization-related applications.

Electric field and force characteristic of dust aerosol particles on the surface of high-voltage transmission line

High-voltage transmission lines play a crucial role in facilitating the utilization of renewable energy in regions prone to desertification. The accumulation of atmospheric particles on the surface of these lines can significantly impact corona discharge and wind-induced conductor displacement. Accurately quantifying the force exerted by particles adhering to conductor surfaces is essential for evaluating fouling conditions and making informed decisions. Therefore, this study investigates the changes in electric field intensity along branched conductors caused by various fouling layers and their resulting influence on the adhesion of dust particles. The findings indicate that as individual particle size increases, the field strength at the top of the particle gradually decreases and eventually stabilizes at approximately 49.22 k V/cm, which corresponds to a field strength approximately 1.96 times higher than that of an unpolluted transmission line. Furthermore,when particle spacing exceeds 15 times the particle size, the field strength around the transmission line gradually decreases and approaches the level observed on non-adhering surface. The electric field remains relatively stable. In a triangular arrangement of three particles, the maximum field strength at the tip of the fouling layer is approximately 1.44 times higher than that of double particles and 1.5 times higher compared to single particles. These results suggest that particles adhering to the transmission line have a greater affinity for adsorbing charged particles. Additionally, relevant numerical calculations demonstrate that in dry environments, the primary adhesion forces between particles and transmission lines follow an order of electrostatic force and van der Waals force. Specifically, at the minimum field strength, these forces are approximately74.73 times and 19.43 times stronger than the gravitational force acting on the particles.

Degradation analysis and doping modification optimization for high-voltage P-type layered cathode in sodium-ion batteries

Advancing high-voltage stability of layered sodium-ion oxides represents a pivotal avenue for their progress in energy storage applications.Despite this,a comprehensive understanding of the mechanisms underpinning their structural deterioration at elevated voltages remains insufficiently explored.In this study,we unveil a layer delamination phenomenon of Na_(0.67)Ni_(0.3)Mn_(0.7)O_(2)(NNM)within the 2.0-4.3 V voltage,attributed to considerable volumetric fluctuations along the c-axis and lattice oxygen reactions induced by the simultaneous Ni^(3+)/Ni^(4+)and anion redox reactions.By introducing Mg doping to diminished Ni-O antibonding,the anion oxidation-reduction reactions are effectively mitigated,and the structural integrity of the P2 phase remains firmly intact,safeguarding active sites and precluding the formation of novel interfaces.The Na_(0.67)Mg_(0.05)Ni_(0.25)Mn_(0.7)O_(2)(NMNM-5)exhibits a specific capacity of100.7 mA h g^(-1),signifying an 83%improvement compared to the NNM material within the voltage of2.0-4.3 V.This investigation underscores the intricate interplay between high-voltage stability and structural degradation mechanisms in layered sodium-ion oxides.

High-Power Raman Soliton Generation at 1.7 μm in All-Fiber Polarization-Maintaining Erbium-Doped Amplifier

An all-fiber polarization maintaining high-power laser system operating at 1.7 μm based on the Ramaninduced soliton self-frequency shifting effect is demonstrated. The entirely fiberized system is built by erbiumdoped oscillator and two-stage amplifiers with polarization maintaining commercial silica fibers and devices, which can provide robust and stable soliton generation. High-power soliton laser with the average power of 0.28 W,the repetition rate of 42.7 MHz, and pulse duration of 515 fs is generated directly from the main amplifier.Our experiment provides a feasible method for high-power all-fiber polarization maintaining femtosecond laser generation working at 1.7 μm.

Understanding the failure mechanism towards developing high-voltage single-crystal Ni-rich Co-free cathodes

Benefited from its high process feasibility and controllable costs,binary-metal layered structured LiNi_(0.8)Mn_(0.2)O_(2)(NM)can effectively alleviate the cobalt supply crisis under the surge of global electric vehicles(EVs)sales,which is considered as the most promising nextgeneration cathode material for lithium-ion batteries(LIBs).However,the lack of deep understanding on the failure mechanism of NM has seriously hindered its application,especially under the harsh condition of high-voltage without sacrifices of reversible capacity.Herein,singlecrystal LiNi_(0.8)Mn_(0.2)O_(2) is selected and compared with traditional LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM),mainly focusing on the failure mechanism of Cofree cathode and illuminating the significant effect of Co element on the Li/Ni antisite defect and dynamic characteristic.Specifically,the presence of high Li/Ni antisite defect in NM cathode easily results in the extremely dramatic H2/H3 phase transition,which exacerbates the distortion of the lattice,mechanical strain changes and exhibits poor electrochemical performance,especially under the high cutoff voltage.Furthermore,the reaction kinetic of NM is impaired due to the absence of Co element,especially at the single-crystal architecture.Whereas,the negative influence of Li/Ni antisite defect is controllable at low current densities,owing to the attenuated polarization.Notably,Co-free NM can exhibit better safety performance than that of NCM cathode.These findings are beneficial for understanding the fundamental reaction mechanism of single-crystal Ni-rich Co-free cathode materials,providing new insights and great encouragements to design and develop the next generation of LIBs with low-cost and high-safety performances.

Fully polarized Compton scattering in plane waves and its polarization transfer

Fully polarized Compton scattering from a beam of spin-polarized electrons is investigated in plane-wave backgrounds in a broad intensity region from the perturbative to the nonperturbative regimes.In the perturbative regime,polarized linear Compton scattering is considered for investigating polarization transfer from a single laser photon to a scattered photon,and in the high-intensity region,the polarized locally monochromatic approximation and locally constant field approximation are established and are employed to study polarization transfer from an incoming electron to a scattered photon.The numerical results suggest an appreciable improvement of about 10%in the scattering probability in the intermediate-intensity region if the electron’s longitudinal spin is parallel to the laser rotation.The longitudinal spin of the incoming electron can be transferred to the scattered photon with an efficiency that increases with laser intensity and collisional energy.For collision between an optical laser with frequency1 eV and a 10 GeV electron,this polarization transfer efficiency can increase from about 20%in the perturbative regime to about 50%in the nonperturbative regime for scattered photons with relatively high energy.

Unique double-layer solid electrolyte interphase formed with fluorinated ether-based electrolytes for high-voltage lithium metal batteries

Li metal batteries using high-voltage layered oxides cathodes are of particular interest due to their high energy density.However,they suffer from short lifespan and extreme safety concerns,which are attributed to the degradation of layered oxides and the decomposition of electrolyte at high voltage,as well as the high reactivity of metallic Li.The key is the development of stable electrolytes against both highvoltage cathodes and Li with the formation of robust interphase films on the surfaces.Herein,we report a highly fluorinated ether,1,1,1-trifluoro-2-[(2,2,2-trifluoroethoxy)methoxy]ethane(TTME),as a cosolvent,which not only functions as a diluent forming a localized high concentration electrolyte(LHCE),but also participates in the construction of the inner solvation structure.The TTME-based electrolyte is stable itself at high voltage and induces the formation of a unique double-layer solid electrolyte interphase(SEI)film,which is embodied as one layer rich in crystalline structural components for enhanced mechanical strength and another amorphous layer with a higher concentration of organic components for enhanced flexibility.The Li||Cu cells display a noticeably high Coulombic efficiency of 99.28%after 300 cycles and Li symmetric cells maintain stable cycling more than 3200 h at 0.5 mA/cm^(2) and 1.0m Ah/cm^(2).In addition,lithium metal cells using LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2) and Li CoO_(2) cathodes(both loadings~3.0 m Ah/cm^(2))realize capacity retentions of>85%over 240 cycles with a charge cut-off voltage of 4.4 V and 90%for 170 cycles with a charge cut-off voltage of 4.5 V,respectively.This study offers a bifunctional ether-based electrolyte solvent beneficial for high-voltage Li metal batteries.

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

Effect of electron-electron interaction on polarization process of exciton and biexciton in conjugated polymer

By using one-dimensional tight-binding model modified to include electron-electric field interaction and electron-electron interaction,we theoretically explore the polarization process of exciton and biexciton in cis-polyacetylene.The dynamical simulation is performed by adopting the non-adiabatic evolution approach.The results show that under the effect of moderate electric field,when the strength of electron-electron interaction is weak,the singlet exciton is stable but its polarization presents obvious oscillation.With the enhancement of interaction,it is dissociated into polaron pairs,the spin-flip of which can be observed through modulating the interaction strength.For the triplet exciton,the strong electron-electron interaction restrains its normal polarization,but it is still stable.In the case of biexciton,the strong electron-electron interaction not only dissociate it,but also flip its charge distribution.The yield of the possible states formed after the dissociation of exciton and biexciton is also calculated.

Polarization control of above-threshold ionization spectrum in elliptically polarized two-color laser fields

We study the above-threshold ionization(ATI)process of atoms exposed to fundamental and high-frequency lasers with arbitrary ellipticity by applying the frequency-domain theory.It is found that the angular-resolved ATI spectrum is sensitive to ellipticities of two lasers and emitted angles of the photoelectron.Particularly for the photon energy of the highfrequency laser more than atomic ionization potential,the width of plateau tends to a constant with increasing ellipticity of fundamental field,the dip structure disappears with increasing ellipticity of the high-frequency field.With the help of the quantum channel analysis,it is shown that the angular distribution depends mainly on the ellipticity of high-frequency field in the case that its frequency is high.Moreover,one can see that the maximal and minimal energies in quantum numerical results are in good agreement with the classical prediction.Our investigation may provide theoretical support for experimental research on polarization control of ionization in elliptically polarized two-color laser fields.

A 1-bit electronically reconfigurable beam steerable metasurface reflectarray with multiple polarization manipulations

A 1-bit electronically controlled metasurface reflectarray is presented to achieve beam steering with multiple polarization manipulations. A metsurface unit cell loaded by two PIN diodes is designed. By switching the two PIN diodes between ON and OFF states, the isotropic and anisotropic reflections can be flexibly achieved. For either the isotropic reflection or the anisotropic reflection, the two operation states achieve the reflection coefficients with approximately equal magnitude and 180°out of phase, thus giving rise to the isotropic/anisotropic 1-bit metasurface unit cells. With the 1-bit unit cells, a 12-by-12 metasurface reflectarray is optimally designed and fabricated. Under either y-or x-polarized incident wave illumination, the reflectarray can achieve the co-polarized and cross-polarized beam scanning, respectively, with the peak gains of 20.08 d Bi and 17.26 d Bi within the scan range of about ±50°. With the right-handed circular polarization(RHCP) excitation, the left-handed circular polarization(LHCP) radiation with the peak gain of 16.98 d Bic can be achieved within the scan range of ±50°. Good agreement between the experimental results and the simulation results are observed for 2D beam steering and polarization manipulation capabilities.

Pairing nitroxyl radical and phenazine with electron-withdrawing/-donating substituents in “water-in-ionic liquid” for high-voltage aqueous redox flow batteries

Aqueous redox-active organic materials-base electrolytes are sustainable alternatives to vanadium-based electrolyte for redoxflow batteries(RFBs)due to the advantages of high ionic conductivity,environmentally benign,safety and low cost.However,the underexplored redox properties of organic materials and the narrow thermodynamic electrolysis window of water(1.23 V)hinder their wide applications.Therefore,seeking suitable organic redox couples and aqueous electrolytes with a high output voltage is highly suggested for advancing the aqueous organic RFBs.In this work,the functionalized phenazine and nitroxyl radical with electron-donating and electron-withdrawing group exhibit redox potential of-0.88 V and 0.78 V vs.Ag,respectively,in“water-in-ionic liquid”supporting electrolytes.Raman spectra reveal that the activity of water is largely suppressed in“water-in-ionic liquid”due to the enhanced hydrogen bond interactions between ionic liquid and water,enabling an electrochemical stability window above 3 V.“Water-in-ionic liquid”supporting electrolytes help to shift redox potential of nitroxyl radical and enable the redox activity of functionalized phenazine.The assembled aqueous RFB allows a theoretical cell voltage of 1.66 V and shows a practical discharge voltage of 1.5 V in the“water-in-ionic liquid”electrolytes.Meanwhile,capacity retention of 99.91%per cycle is achieved over 500 charge/discharge cycles.A power density of 112 mW cm^(-2) is obtained at a current density of 30 mA cm^(-2).This work highlights the importance of rationally combining supporting electrolytes and organic molecules to achieve high-voltage aqueous RFBs.

Intrinsic polarization conversion and avoided-mode crossing in X-cut lithium niobate microrings

Compared with well-developed free space polarization converters, polarization conversion between TE and TM modes in the waveguide is generally considered to be caused by shape birefringence, like curvature, morphology of waveguide cross section and scattering. Here, we study the polarization conversion mechanism in 1-THz-FSR X-cut lithium niobate microrings with multiple-resonance condition, that is the conversion can be implemented by birefringence of waveguides,which will also introduce an avoided-mode crossing. In the experiment, we find that this mode crossing results in severe suppression of one sideband in local nondegenerate four-wave mixing and disrupts the cascaded four-wave mixing on this side. Simultaneously, we propose one two-dimensional method to simulate the eigenmodes(TE and TM) in X-cut microrings, and the mode crossing point. This work will provide one approach to the design of polarization converters and simulation for monolithic photonics integrated circuits, and may be helpful to the studies of missed temporal dissipative soliton formation in X-cut lithium niobate rings.

Recent progress on valley polarization and valley-polarized topological states in two-dimensional materials

Valleytronics, using valley degree of freedom to encode, process, and store information, may find practical applications in low-power-consumption devices. Recent theoretical and experimental studies have demonstrated that twodimensional(2D) honeycomb lattice systems with inversion symmetry breaking, such as transition-metal dichalcogenides(TMDs), are ideal candidates for realizing valley polarization. In addition to the optical field, lifting the valley degeneracy of TMDs by introducing magnetism is an efficient way to manipulate the valley degree of freedom. In this paper, we first review the recent progress on valley polarization in various TMD-based systems, including magnetically doped TMDs,intrinsic TMDs with both inversion and time-reversal symmetry broken, and magnetic TMD heterostructures. When topologically nontrivial bands are empowered into valley-polarized systems, valley-polarized topological states, namely valleypolarized quantum anomalous Hall effect can be realized. Therefore, we have also reviewed the theoretical proposals for realizing valley-polarized topological states in 2D honeycomb lattices. Our paper can help readers quickly grasp the latest research developments in this field.

Breaking the optical efficiency limit of virtual reality with a nonreciprocal polarization rotator

A catadioptric lens structure,also known as pancake lens,has been widely used in virtual reality(VR)displays to reduce the formfactor.However,the utilization of a half mirror(HM)to fold the optical path thrice leads to a significant optical loss.The theoretical maximum optical efficiency is merely 25%.To transcend this optical efficiency constraint while retaining the foldable characteristic inherent to traditional pancake optics,in this paper,we propose a theoretically lossless folded optical system to replace the HM with a nonreciprocal polarization rotator.In our feasibility demonstration experiment,we used a commercial Faraday rotator(FR)and reflective polarizers to replace the lossy HM.The theoretically predicted 100%efficiency can be achieved approximately by using two high-extinction-ratio reflective polarizers.In addition,we evaluated the ghost images using a micro-OLED panel in our imaging system.Indeed,the ghost images can be suppressed to undetectable level if the optics are with antireflection coating.Our novel pancake optical system holds great potential for revolutionizing next-generation VR displays with lightweight,compact formfactor,and low power consumption.

Knockout of C6orf120 in Rats Alleviates Concanavalin A-induced Autoimmune Hepatitis by Regulating Macrophage Polarization

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.

Effect of honokiol regulating SIRT3 on chronic hypoxia-induced microglia and astrocyte polarization

Objective:To investigate the effect of honokiol on microglia polarization and the underlying mechanism.Methods:Inflammatory factors were detected using ELISA to determine the optimal concentration of cobalt chloride to induce,and that of honokiol to treat chronic hypoxia(48 h)in microglia cell line BV2 cells.BV2 cells were divided into four groups:control,chronic hypoxia,chronic hypoxia+honokiol,chronic hypoxia+honokiol+3-TYP(SIRT3 inhibitor).ELISA was used to measure the concentration of supernatant TNFαand IL-1βproteins,qPCR was used to detect the expression of cellular M1 and M2 polarization markers,and biochemical assays were used to detect the level of reactive oxygen species in each group.Western Blot was used to detect protein levels of SIRT3 and upstream inflammatory molecules NLRP3 and caspase1.Results:Chronic cobalt chloride stimulation of BV2 cells at an optimal concentration of 100μmol/L significantly increased the release of inflammatory fac-tors TNFαand IL-1βafter stimulation compared with the control group(P<0.05);compared with the control group,cells in the chronic hypoxia group had down-regulation of SIRT3 protein expression,whereas the ROS levels,NLRP3 and caspase1 protein levels,the M1 polarization marker CD86,iNOS mRNA levels and CD16/32 ratio were upregulated.and honokiol(10μmol/L)significantly up-regulated the SIRT3 protein and mRNA levels of M2 markers Arg-1 and CD206 in chronic hypoxic cells(P<0.05)and down-regulated levels of ROS,NLRP3/caspase1 protein,and mRNA levels of M1 markers(P<0.05),and this anti-oxidative and anti-inflammatory effect was able to be reversed by SIRT3 inhibitor.Conclusion:Honokiol inhibits chronic hypoxia-induced microglia M1 polarization and inflammatory pathway activation,and its anti-inflammatory effects are SIRT3-de-pendent.