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.(...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.展开更多
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,neuropro...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.展开更多
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...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.展开更多
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 a...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
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.Bioactiv...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.展开更多
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 inflamm...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.展开更多
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 unders...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.展开更多
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 ...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.展开更多
基金supported by the open fund of State Key Laboratory of Southwestern Chinese Medicine Resources(No.SCMR202103)to Jian LiTibet Autonomous Region Science and Technology Plan(high-tech social development)project(No.XZ202201ZY0031G)to Yi-Xi YangAnti-infective Agent Creation Engineering Research Centre of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of pharmacy,Chengdu University(No.AAC2023002)to Qiu-Xia Lu.
文摘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.
基金supported by the open fund of State Key Laboratory of Southwestern Chinese Medicine Resources(No.SCMR202103)to Jian LiTibet Autonomous Region Science and Technology Plan(high-tech social development)project(No.XZ202201ZY0031G)to Yang YXAnti-infective Agent Creation Engineering Research Centre of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of pharmacy,Chengdu University(No.AAC2023002)to Lu QX.
文摘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.
基金Project supported by the Fundamental Research Funds for the National Key Research and Development Program, China (Grant No. 2020YFB1807403)the National Natural Science Foundation of China (Grant Nos. 62174125, 62188102, and 62131014)。
文摘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.
基金financially supported by the National Natural Science Foundation of China(No.21975163)Natural Science Foundation of Guangdong Province of China(2020A1515011165)Shenzhen Sci-ence and Technology Program(No.KQTD20190929173914967)and(No.JCYJ20220818100004009)。
文摘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.
基金Supported by the National Key Research and Development Program of China under Grant Nos 2018YFA0305700 and2016YFA0401804the National Natural Science Foundation of China under Grant Nos 11574323,11704387,11874362,11804344,11804341,61774136,11605276 and U1632275+3 种基金the Major Program of Development Foundation of Hefei Center for Physical Science and Technology under Grant No 2018ZYFX002the Users with Excellence Project of Hefei Science Center of Chinese Academy of Sciences under Grant No 2018HSC-UE012the Natural Science Foundation of Anhui Province under Grant Nos 1808085MA06,1908085QA18 and 1708085QA19the Director’s Fund of Hefei Institutes of Physical Science of Chinese Academy of Sciences under Grant No YZJJ201621
文摘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.
基金founded by Zhengzhou Finance Bureau (No.201974).
文摘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.
基金supported in part by Beijing Natural Science Foundation(7192226,7222011)Beijing Chao-Yang Hospital Golden Seeds Foundation(CYJZ202148)+3 种基金National Key Research and Development Program(2021YFC2400500)National Natural Science Foundation of China(51903013,51973021,51932002,52173275)Beijing Hospitals Authority Youth Programme(QML20210402)the Beijing Municipal Health Commission(PXM 2020_026275_000002,BMHC-2021-6,BMHC-2019-9).
文摘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.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82174202,No.32270407 and No.82074428)Natural Science Foundation of Sichuan Province(Grant No.2022NSFSC0726)+2 种基金Innovative Team Projects of Shanghai Municipal Commission of Health(Grant No.2022CX001)Innovation Foundation of the Affiliated Hospital of Chengdu University(Grant No.CDFYCX202209)Major Research and Development Plan of Xizang Autonomous Region(Grant No.XZ202201ZY0031G).
文摘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.
基金the National Natural Science Foundation of China(21834001,21906054,and 82100377)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-1-12M-006)Beijing Nova Program(Z211100002121046),ZhiShan Scholar Program of Southeast University,and programs for high-level entrepreneurial and innovative talents introduction of Jiangsu Province.
文摘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.
基金financially supported by the National Natural Science Foundation of China (Nos. 62074018 and 61704011)the China Postdoctoral Science Foundation Funded Project (Nos. 2019M652176 and 2019M661680)+4 种基金the Developing Project of Science and Technology of Jilin Province (Nos. 20200301052RQ, 20200201266JC, 20190701029GH, 20180519017JH and 20180520177JH)the Project of Education Department of Jilin Province (No. JJKH20210831KJ)the Natural Science Foundation of Guangdong Province (No. 2020A1515010868)Shenzhen Fundamental Research Fund (No. JCYJ20180307151538972)supported by R&D project of Collighter Co., Ltd。
文摘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.