The flavonoids from Pentorum chinense Pursh.mediates ferroptosis to alleviate sorafenib-induced liver injury in BRL-3A cells

Background:Drug-induced liver damage is a severe medical issue that affects people all over the world.Sorafenib has some side effects that cause liver injury.A dietary medicinal plant called Penthorum chinense Pursh.(PCP)has hepatoprotective properties.There are currently few reports on PCP’s protective impact and mechanism against sorafenib-induced liver injury.Methods:To create a liver injury model,sorafenib was administered to BRL-3A cells.Cell viability assays,immunofluorescence tests,Western blotting,real-time quantitative PCR,and high-content imaging systems were utilized to examine PCP’s effect and mechanism.Results:In this study,PCP treatment mitigated the liver damage caused by sorafenib by enhancing cell survival,lowering lipid reactive oxygen species and malondialdehyde levels,and elevating glutathione levels.In addition,PCP can enhance the protein expression of cystine/glutamate transporter xCT and glutathione peroxidase 4,reduce iron content and alleviate mitochondrial toxicity.Further mechanism studies revealed that PCP inhibited ferroptosis by promoting the production of nuclear factor E2-related factor 2 nuclear translocation and subsequently affecting target genes(HO-1 and NQO1).Conclusion:Together,PCP regulates the nuclear factor E2-related factor 2 pathway,which helps to lessen ferroptosis brought on by sorafenib.

Luteolin alleviates sorafenib-induced ferroptosis of BRL-3A cells through modulation of the Nrf2/GPX4 signaling pathway

Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.

Low-damage interface enhancement-mode AlN/GaN high electron mobility transistors with 41.6% PAE at 30 GHz

This paper reports a low-damage interface treatment process for Al N/Ga N high electron mobility transistor(HEMT)and demonstrates the excellent power characteristics of radio-frequency(RF) enhancementmode(E-mode) Al N/Ga N HEMT. An RF E-mode device with 2.9-nm-thick Al N barrier layer fabricated by remote plasma oxidation(RPO) treatment at 300℃. The device with a gate length of 0.12-μm has a threshold voltage(Vth) of 0.5 V, a maximum saturation current of 1.16 A/mm, a high Ion/Ioff ratio of 1×108, and a 440-m S/mm peak transconductance. During continuous wave(CW) power testing, the device demonstrates that at 3.6 GHz, a power added efficiency is 61.9% and a power density is 1.38 W/mm, and at 30 GHz, a power added efficiency is 41.6% and a power density is 0.85 W/mm. Furthermore, the RPO treatment improves the mobility of RF E-mode Al N/Ga N HEMT. All results show that the RPO processing method has good applicability to scaling ultrathin barrier E-mode Al N/Ga N HEMT for 5G compliable frequency ranging from sub-6 GHz to Ka-band.

Unraveling the relationship between Sr stoichiometry in Sr_(x)Fe_(1.5)Mo_(0.5)O_(6)-σ and its catalytic performance for high-temperature CO_(2) electrolysis

The solid oxide electrolytic cell(SOEC)is one of the most promising energy conversion and storage devices,which could convert CO_(2) to CO with high Faradaic efficiency and production rate.However,the lack of active and stable cathode materials impedes their practical applications.Here we focus on the promising perovskite oxide cathode material Sr_(2)Fe_(1.5)Mo_(0.5)O_(6)-σ,with the aim of understanding how A-atom stoichiometry and catalytic performance are linked.We find that increasing the strontium content in the perovskite improves the chemisorption of CO_(2) on its surface,forming a SrCO_(3) phase.This hinders the charge transfer and oxygen exchange processes.Simulta-neously,strontoium segregation to the cathode surface facilitates coking of the surface during CO_(2) electrolysis,which poisons the electrode.Consequently,a small number of Sr deficiencies are optimal for both electrochemical performance and long-term stability.Our results provide new insights for designing high-performance CO_(2) electrolysis cathode materials.

Pressure-Induced Metallization Accompanied by Elongated S–S Dimer in Charge Transfer Insulator NiS2

The insulator-metal transition triggered by pressure in charge transfer insulator NiS2 is investigated by combining high-pressure electrical transport,synchrotron x-ray diffraction and Raman spectroscopy measurements up to40-50 GPa.Upon compression,we show that the metallization firstly appears in the low temperature region at^3.2 GPa and then extends to room temperature at^8.0 GPa.During the insulator-metal transition,the bond length of S-S dimer extracted from the synchrotron x-ray diffraction increases with pressure,which is supported by the observation of abnormal red-shift of the Raman modes between 3.2 and 7.1 GPa.Considering the decreasing bonding-antibonding splitting due to the expansion of S-S dimer,the charge gap between the S-ppπ* band and the upper Hubbard band of Ni-3 d eg state is remarkabl.y decreased.These results consistently indicate that the elongated S-S dimer plays a predominant role in the insulator-metal transition under high pressure,even though the p-d hybridization is enhanced simultaneously,in accordance with a scenario of charge-gap-controlled type.

Age-related changes for the predictors of benign prostatic hyperplasia in Chinese men aged 40 years or older

A cross-sectional study was conducted to estimate the age-stratified normal levels and age-related changes in the risk predictors of benign prostatic hyperplasia(BPH)progression.A total of 4706 male participants aged 40 years or older in Zhengzhou(China)were enrolled.The values of the International Prostate Symptom Score(IPSS),prostate-specific antigen(PSA),prostate volume(PV),and postvoid residual urine volume(PVR)significantly increased with age.Nonlinear relationships between age and IPSS scores≥8(P for nonlinearity=0.046),PSA level≥1.6 ng ml^(-1),PV≥31 ml,or PVR≥39 ml(all P for nonlinearity<0.001)were observed.After the age of 61 years,the risk indicators related to BPH progression were positively correlated with age(odds ratio[OR]>1),regardless of the predictors of the IPSS score,PSA level,PV,or PVR;and the OR values increased gradually.Therefore,after the age of 61 years,the risk predictors related to BPH progression were positively correlated with age.

Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulatingβ-catenin via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway

Osteosarcoma(OS)therapy faces many challenges,especially the poor survival rate once metastasis occurs.Therefore,it is crucial to explore new OS treatment strategies that can efficiently inhibit OS metastasis.Bioactive nanoparticles such as zinc oxide nanoparticles(ZnO NPs)can efficiently inhibit OS growth,however,the effect and mechanisms of them on tumor metastasis are still not clear.In this study,we firstly prepared well-dispersed ZnO NPs and proved that ZnO NPs can inhibit OS metastasis-related malignant behaviors including migration,invasion,and epithelial-mesenchymal transition(EMT).RNA-Seqs found that differentially expressed genes(DEGs)in ZnO NP-treated OS cells were enriched in wingless/integrated(Wnt)and hypoxia-inducible factor-1(HIF-1)signaling pathway.We further proved that Zn^(2+)released from ZnO NPs induced downregulation ofβ-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway.ZnO NPs combined with ICG-001,aβ-catenin inhibitor,showed a synergistic inhibitory effect on OS lung metastasis and a longer survival time.In addition,tissue microarray(TMA)of OS patients also detected much higherβ-catenin expression which indicated the role ofβ-catenin in OS development.In summary,our current study not only proved that ZnO NPs can inhibit OS metastasis by degradingβ-catenin in HIF-1α/BNIP3/LC3B-mediated mitophagy pathway,but also provided a far-reaching potential of ZnO NPs in clinical OS treatment with metastasis.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9

Objective:To explore whether the ethanol extract of Herpetospermum caudigerum Wall(EHC),a Xizang medicinal plant traditionally used for treating liver diseases,can improve imiquimod-induced psoriasis-like skin inflammation.Methods:Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice.The protein levels of interferon-γ(IFN-γ),tumor necrosis factor-a(TNF-a),and interleukin-17A(IL-17A)in mouse skin samples were examined using immunohistochemical staining.In vitro,IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1(ICAM-1)and chemokine CXC ligand 9(CXCL9)using Western blotting and reverse transcription-quantitative polymerase chain reaction.The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.Results:EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ,TNF-a,and IL-17A in psoriatic lesions.Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes.Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin–proteasome-mediated protein degradation rather than transcriptional repression.Seven primary compounds including ehletianol C,dehydrodiconiferyl alcohol,herpetrione,herpetin,herpetotriol,herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Conclusion:Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites.

Mass Spectrometry Imaging-Based Single-Cell Lipidomics Profiles Metabolic Signatures of Heart Failure

Heart failure(HF),leading as one of the main causes of mortality,has become a serious public health issue with high prevalence around the world.Single cardiomyocyte(CM)metabolomics promises to revolutionize the understanding of HF pathogenesis since the metabolic remodeling in the human hearts plays a vital role in the disease progression.Unfortunately,current metabolic analysis is often limited by the dynamic features of metabolites and the critical needs for high-quality isolated CMs.Here,high-quality CMs were directly isolated from transgenic HF mice biopsies and further employed in the cellular metabolic analysis.The lipids landscape in individual CMs was profiled with a delayed extraction mode in time-of-flight secondary ion mass spectrometry.Specific metabolic signatures were identified to distinguish HF CMs from the control subjects,presenting as possible single-cell biomarkers.The spatial distributions of these signatures were imaged in single cells,and those were further found to be strongly associated with lipoprotein metabolism,transmembrane transport,and signal transduction.Taken together,we systematically studied the lipid metabolism of single CMs with a mass spectrometry imaging method,which directly benefited the identification of HF-associated signatures and a deeper understanding of HF-related metabolic pathways.

InAs/InAsSb type-Ⅱ superlattice with near room-temperature long-wave emission through interface engineering

Ga-free InAs/InAsSb type-Ⅱ superlattices(T2SL) have extensive application prospective in infrared photodetectors. Achieving higher operation temperature is critical to its commercial applications. Here, a fractional monolayer alloy method was used to grow InAsSb alloy with better controlled alloy composition. The as-grown T2SL gave eleven satellite peaks and a first satellite peak with a narrow full-width-half-maximum (FWHM) of 20.5arcsec (1 arcsec=0.01592°). Strain mapping results indicated limited Sb diffusion through the As-Sb exchange process at the interface. Moreover, unlike interface states caused by the As-Sb exchange effect, this relatively clear interface was distinctive with localized states with higher activation energies of the non-radiative recombination process ((18±1) meV and (84±12) meV at different temperature ranges), which means that this interface state introduced by fractional monolayer alloy growth method can effectively suppress Auger recombination process in T2SL. Through this interface engineering of InAs/InAsSb Type-Ⅱ superlattice, it achieved detective photoluminescence (PL) signal with the center wavelength of 9μm at 250K.