Increased accumulation and/or impaired utilization of fatty acid in extra-adipose tissues are implicated in the pathogenesis of insulin resistance and type 2 diabetes. Pyruvate dehydrogenase kinase 4 （Pdk4） is a key...Increased accumulation and/or impaired utilization of fatty acid in extra-adipose tissues are implicated in the pathogenesis of insulin resistance and type 2 diabetes. Pyruvate dehydrogenase kinase 4 （Pdk4） is a key enzyme involved in fatty oxidation and energy expenditure, and its expression can be repressed by pro-inflammatory stimuli. Previously, we have shown that class II transactivator （CIITA） mediates the adverse effect of interferon gamma （IFN-7） in skeletal muscle cells by cooperating with hypermethylated in cancer 1 （HIC1） to repress silent informa- tion regulator 1 （SIRT1） transcription. Building upon this finding, we report here that CIITA interacted with HIC1 via the GTP-binding domain （GBD） while HIC1 interacted with CIITA via the BTB/POZ domain. The GBD domain was required for CIITA to repress SIRT1 transcription probably acting as a bridge for CIITA to bind to HIC1 and consequently to bind to the SIRT1 promoter. IFN-7 stimulation, CIITA over-expression, or HIC1 over- expression repressed Pdk4 promoter activity while silencing either CIITA or HIC1 normalized Pdk4 expression in the presence of IFN-7. An increase in SIRT1 expression or activity partially rescued Pdk4 expression in the pre- sence of CIITA, but SIRT1 inhibition abrogated Pdk4 normalization even in the absence of CIITA. Taken together, our data have identified a HIC1-CIITA-SIRT1 axis that regulates Pdk4 transcription in response to IFN-7 stimula- tion.展开更多
Tumor necrosis factor alpha(TNF-a) is a cytokine that can potently stimulate the synthesis of a range of proinflammatory mediators in macrophages. The underlying epigenetic mechanism, however, is underexplored. Here w...Tumor necrosis factor alpha(TNF-a) is a cytokine that can potently stimulate the synthesis of a range of proinflammatory mediators in macrophages. The underlying epigenetic mechanism, however, is underexplored. Here we report that the transcriptional modulator megakaryocytic leukemia 1(MKL1) is associated with a histone H3 K4 methyltransferase activity. Re-ChIP assay suggests that MKL1 interacts with and recruits WDR5, a component of the COMPASS complex responsible for H3 K4 methylation, to the promoter regions of pro-inflammatory genes in macrophages treated with TNF-α. WDR5 enhances the ability of MKL1 to stimulate the promoter activities of proinflammatory genes. In contrast, silencing of WDR5 attenuates TNF-a induced production of pro-inflammatory mediators and erases the H3 K4 methylation from the gene promoters. Of interest, the chromatin remodeling protein BRG1 also plays an essential role in maintaining H3 K4 methylation on MKL1 target promoters by interacting with WDR5. MKL1 knockdown disrupts the interaction between BRG1 and WDR5. Together, our data illustrate a role for MKL1 in moderating the crosstalk between BRG1 and WDR5 to activate TNF-a induced pro-inflammatory transcription in macrophages.展开更多
Expression of P-selectin in injured or activated endothelia cells serves as a permissive step towards leukocyte recruitment and perpetuation of inflammation in the pathogenesis of atherosclerosis.P-selectin can be ind...Expression of P-selectin in injured or activated endothelia cells serves as a permissive step towards leukocyte recruitment and perpetuation of inflammation in the pathogenesis of atherosclerosis.P-selectin can be induced by pro-inflammatory stimuli via the transcription factor NF-κB,but the epigenetic mechanisms remain incompletely understood.Previously we reported that myocardin-related transcription factor A（MRTF-A）mediates the transactivation of a slew of adhesion molecules by oxidized low-density lipoprotein（oxLDL）,likely through a crosstalk with brahma-related gene 1（BRGl）,a chromatin remodeling protein.Here,we show that MRTF-A was both sufficient and necessary for the transactivation of P-selectin gene in endothelial cells treated with TNF-α.Depletion of MRTF-A using small interfering RNA（siRNA）abrogated the binding of BRGl on the P-selectin promoter.Overexpression of BRG1 up-regulated the activity of P-selectin promoter activity while BRGl knockdown attenuated P-selectin expression.Finally,BRGl silencing suppressed the accumulation of acetylated histone H3 and methylated histone H3K4,and altered the binding of NF-κB on the P-selectin promoter.Therefore,our data demonstrate an essential role for MRTF-A and BRGl in P-selectin transactivation in endothelial cells.展开更多
The resistance of cancer cells to the anti-cancer drugs is the most important reason that affecting the efficacy of the non-small cell lung cancer(NSCLC)chemotherapy;thus,to explore the underlyingmechanismof drug resi...The resistance of cancer cells to the anti-cancer drugs is the most important reason that affecting the efficacy of the non-small cell lung cancer(NSCLC)chemotherapy;thus,to explore the underlyingmechanismof drug resistance ofNSCLC medications is urgently needed for improving the therapeutic efficacy of current anti-NSCLC chemotherapies.The aim of the present study is to explore the roles of exosomes in the chemosensitivity of A549 cells and the related mechanism.A549 cells and cisplatin resistant cell line A549/DDP derived exosomes were isolated,and the expressions of CXCR4 were compared.Then,after cisplatin treatment,A549 cells were treated with exosomes,and the proliferation,apoptosis,migration,and invasion of the cells were examined.Finally,the tumorigenic effect of A549/DDP derived exosomes were also evaluated by cisplatin treated xenograft tumor mice models in vivo.We found that A549/DDP derived exosomes increased the proliferation,migration,and invasion,and inhibited the apoptosis and cisplatin sensitivity of A549 cells.CXCR4 was also significantly increased in cells treated with A549/DDP derived exosomes.Furthermore,A549/DDP derived exosomes may also decrease the chemosensitivity of NSCLC cells to cisplatin in vivo.Our data suggested that A549/DDP derived exosomes can affect the chemosensitivity of A549 cells to cisplatin,possibly by transporting CXCR4 to A549 cells.Our data may provide novel evidence for the investigation of drug resistance of NSCLC.展开更多
Multiple reflections in seismic exploration data severely degrade subsurface imaging accuracy and interpretation reliability.Traditional multiple attenuation methods exhibit limited performance under complex geologica...Multiple reflections in seismic exploration data severely degrade subsurface imaging accuracy and interpretation reliability.Traditional multiple attenuation methods exhibit limited performance under complex geological conditions,while existing deep learning approaches struggle to simultaneously suppress high-energy multiples and preserve the structural continuity and amplitude fidelity of primary reflections.This paper proposes an enhanced U-Net architecture termed Seismic-CBAM-UNet,employing a two-stage cascaded strategy of“frequency-domain preprocessing+attention-enhanced network”.The method first applies spectral subtraction in the frequency domain to preprocess raw seismic data,specifically targeting multiples concentrated in the low-frequency band.Subsequently,Convolutional Block Attention Modules are embedded within the network architecture,integrating both channel and spatial attention mechanisms to enable adaptive focusing on geologically significant reflection events.Experimental results demonstrate that our method outperforms Wiener filtering and wavelet thresholding across multiple evaluation metrics:achieving 1.62 dB SNR improvement,61.3%multiple attenuation rate,92.10%primary preservation rate,and 0.798 structural similarity index.The proposed approach effectively suppresses multiple interference while precisely maintaining geological structure continuity and amplitude characteristics,providing reliable technical support for high-precision imaging in complex seismic environments.展开更多
In commercial lithium-ion batteries(LIBs),the uncontrolled Li plating on graphite anodes under fast charging presents critical challenges to cycling stability and safety.Here,we introduce a silicalite-1@SnO_(2) hollow...In commercial lithium-ion batteries(LIBs),the uncontrolled Li plating on graphite anodes under fast charging presents critical challenges to cycling stability and safety.Here,we introduce a silicalite-1@SnO_(2) hollow sphere(SHS)capsule additive incorporated into graphite anodes to inhibit and regulate Li plating under fast-charging conditions.This additive achieves a two-stage strategy to address Li plating issues:(1)Before Li plating initiates,the silicalite-1 component of SHS enhances lithium-ion(Li^(+))diffusion throughout the electrode,reducing charge transfer polarization and suppressing the onset of dendritic Li deposition.(2)When the anode potential drops below 0 V(vs Li/Li^(+))during fast charging,the SnO_(2) hollow sphere within SHS acts as a lithiophilic site,guiding Li deposition into its internal cavity.Benefiting from this two-stage strategy,the LiNi0.8Co0.1Mn0.1O_(2)||graphite pouch cell(180μm thickness,5 wt%SHS addition)achieves an 82%state of charge at 6 C and retains 80%capacity over 255 cycles,significantly outperforming counterparts degraded by dendritic Li plating during fast charging.This work provides a holistic strategy to address Li plating challenges in fastcharging,high-energy LIBs by integrating kinetic optimization and structural confinement.展开更多
As the world enters into the era of electrifying transportation for cleaner energy,lithium-ion battery(LIB)-powered electric vehicles have drawn great attention in recent years.However,the fast-charging capability of ...As the world enters into the era of electrifying transportation for cleaner energy,lithium-ion battery(LIB)-powered electric vehicles have drawn great attention in recent years.However,the fast-charging capability of LIBs has long been regarded as the technological obstacle to the wider adoption of battery electric vehicles(BEVs)in the market.A substantial challenge associated with fast charging is the formation of Li plating on the graphite anode as it is the major contributor of side reactions during cell operations.In this review,the fundamentals of Li plating and corresponding influencing factors(including state of charge[SOC],charging current density,temperature,and N/P ratio)for the Li-ion intercalation process are first elucidated under fast-charging conditions.Furthermore,conventional strategies to suppress Li plating by enhancing ion transport kinetics between interface and electrode through anode engineering and electrolyte design are also summarized and analyzed.Then,innovative strategies for achieving ultrahigh SOC of anodes by regulating Li plating morphology on host materials to construct hybrid anode storage are discussed in detail.Two types of strategies are compared in terms of cell performance,process simplicity,and safety concerns.Last,we highlight some research orientations and perspectives pertaining to the development of hybrid anode storage,providing effective approaches to address Li plating issues for fast-charging LIBs.展开更多
基金supported,in part,by the National Natural Science Foundation of China(31200645)the Natural Science Foundation of Jiangsu Province(BK20141498)a grant from Jiangsu Jiankang Vocational University(JK201405)
文摘Increased accumulation and/or impaired utilization of fatty acid in extra-adipose tissues are implicated in the pathogenesis of insulin resistance and type 2 diabetes. Pyruvate dehydrogenase kinase 4 （Pdk4） is a key enzyme involved in fatty oxidation and energy expenditure, and its expression can be repressed by pro-inflammatory stimuli. Previously, we have shown that class II transactivator （CIITA） mediates the adverse effect of interferon gamma （IFN-7） in skeletal muscle cells by cooperating with hypermethylated in cancer 1 （HIC1） to repress silent informa- tion regulator 1 （SIRT1） transcription. Building upon this finding, we report here that CIITA interacted with HIC1 via the GTP-binding domain （GBD） while HIC1 interacted with CIITA via the BTB/POZ domain. The GBD domain was required for CIITA to repress SIRT1 transcription probably acting as a bridge for CIITA to bind to HIC1 and consequently to bind to the SIRT1 promoter. IFN-7 stimulation, CIITA over-expression, or HIC1 over- expression repressed Pdk4 promoter activity while silencing either CIITA or HIC1 normalized Pdk4 expression in the presence of IFN-7. An increase in SIRT1 expression or activity partially rescued Pdk4 expression in the pre- sence of CIITA, but SIRT1 inhibition abrogated Pdk4 normalization even in the absence of CIITA. Taken together, our data have identified a HIC1-CIITA-SIRT1 axis that regulates Pdk4 transcription in response to IFN-7 stimula- tion.
基金the National Natural Science Foundation of China (81570420) supported by the Qinglan Project of the Education Commission of Jiangsu Province
文摘Tumor necrosis factor alpha(TNF-a) is a cytokine that can potently stimulate the synthesis of a range of proinflammatory mediators in macrophages. The underlying epigenetic mechanism, however, is underexplored. Here we report that the transcriptional modulator megakaryocytic leukemia 1(MKL1) is associated with a histone H3 K4 methyltransferase activity. Re-ChIP assay suggests that MKL1 interacts with and recruits WDR5, a component of the COMPASS complex responsible for H3 K4 methylation, to the promoter regions of pro-inflammatory genes in macrophages treated with TNF-α. WDR5 enhances the ability of MKL1 to stimulate the promoter activities of proinflammatory genes. In contrast, silencing of WDR5 attenuates TNF-a induced production of pro-inflammatory mediators and erases the H3 K4 methylation from the gene promoters. Of interest, the chromatin remodeling protein BRG1 also plays an essential role in maintaining H3 K4 methylation on MKL1 target promoters by interacting with WDR5. MKL1 knockdown disrupts the interaction between BRG1 and WDR5. Together, our data illustrate a role for MKL1 in moderating the crosstalk between BRG1 and WDR5 to activate TNF-a induced pro-inflammatory transcription in macrophages.
基金supported by the Natural Science Foundation of Jiangsu Province(BK20141498)a grant from Jiangsu Jiankang Vocational University(JKC201505)
文摘Expression of P-selectin in injured or activated endothelia cells serves as a permissive step towards leukocyte recruitment and perpetuation of inflammation in the pathogenesis of atherosclerosis.P-selectin can be induced by pro-inflammatory stimuli via the transcription factor NF-κB,but the epigenetic mechanisms remain incompletely understood.Previously we reported that myocardin-related transcription factor A（MRTF-A）mediates the transactivation of a slew of adhesion molecules by oxidized low-density lipoprotein（oxLDL）,likely through a crosstalk with brahma-related gene 1（BRGl）,a chromatin remodeling protein.Here,we show that MRTF-A was both sufficient and necessary for the transactivation of P-selectin gene in endothelial cells treated with TNF-α.Depletion of MRTF-A using small interfering RNA（siRNA）abrogated the binding of BRGl on the P-selectin promoter.Overexpression of BRG1 up-regulated the activity of P-selectin promoter activity while BRGl knockdown attenuated P-selectin expression.Finally,BRGl silencing suppressed the accumulation of acetylated histone H3 and methylated histone H3K4,and altered the binding of NF-κB on the P-selectin promoter.Therefore,our data demonstrate an essential role for MRTF-A and BRGl in P-selectin transactivation in endothelial cells.
基金supported by The Fundamental Research Funds for the Central Universities[No.WK9110000071]Youth Fund of Anhui Cancer Hospital[Nos.2018YJQN019,2020YJQN007].
文摘The resistance of cancer cells to the anti-cancer drugs is the most important reason that affecting the efficacy of the non-small cell lung cancer(NSCLC)chemotherapy;thus,to explore the underlyingmechanismof drug resistance ofNSCLC medications is urgently needed for improving the therapeutic efficacy of current anti-NSCLC chemotherapies.The aim of the present study is to explore the roles of exosomes in the chemosensitivity of A549 cells and the related mechanism.A549 cells and cisplatin resistant cell line A549/DDP derived exosomes were isolated,and the expressions of CXCR4 were compared.Then,after cisplatin treatment,A549 cells were treated with exosomes,and the proliferation,apoptosis,migration,and invasion of the cells were examined.Finally,the tumorigenic effect of A549/DDP derived exosomes were also evaluated by cisplatin treated xenograft tumor mice models in vivo.We found that A549/DDP derived exosomes increased the proliferation,migration,and invasion,and inhibited the apoptosis and cisplatin sensitivity of A549 cells.CXCR4 was also significantly increased in cells treated with A549/DDP derived exosomes.Furthermore,A549/DDP derived exosomes may also decrease the chemosensitivity of NSCLC cells to cisplatin in vivo.Our data suggested that A549/DDP derived exosomes can affect the chemosensitivity of A549 cells to cisplatin,possibly by transporting CXCR4 to A549 cells.Our data may provide novel evidence for the investigation of drug resistance of NSCLC.
基金supported by Fundamental Research Program of Shanxi Province(Grant No.202303021211245).
文摘Multiple reflections in seismic exploration data severely degrade subsurface imaging accuracy and interpretation reliability.Traditional multiple attenuation methods exhibit limited performance under complex geological conditions,while existing deep learning approaches struggle to simultaneously suppress high-energy multiples and preserve the structural continuity and amplitude fidelity of primary reflections.This paper proposes an enhanced U-Net architecture termed Seismic-CBAM-UNet,employing a two-stage cascaded strategy of“frequency-domain preprocessing+attention-enhanced network”.The method first applies spectral subtraction in the frequency domain to preprocess raw seismic data,specifically targeting multiples concentrated in the low-frequency band.Subsequently,Convolutional Block Attention Modules are embedded within the network architecture,integrating both channel and spatial attention mechanisms to enable adaptive focusing on geologically significant reflection events.Experimental results demonstrate that our method outperforms Wiener filtering and wavelet thresholding across multiple evaluation metrics:achieving 1.62 dB SNR improvement,61.3%multiple attenuation rate,92.10%primary preservation rate,and 0.798 structural similarity index.The proposed approach effectively suppresses multiple interference while precisely maintaining geological structure continuity and amplitude characteristics,providing reliable technical support for high-precision imaging in complex seismic environments.
基金supported by the National Key R&D Program of China(grant no.2021YFB2400300)the Henan Silane Technology Development(grant no.22H010101201)the Henan Newmight Company(grant no.21H010201546).
文摘In commercial lithium-ion batteries(LIBs),the uncontrolled Li plating on graphite anodes under fast charging presents critical challenges to cycling stability and safety.Here,we introduce a silicalite-1@SnO_(2) hollow sphere(SHS)capsule additive incorporated into graphite anodes to inhibit and regulate Li plating under fast-charging conditions.This additive achieves a two-stage strategy to address Li plating issues:(1)Before Li plating initiates,the silicalite-1 component of SHS enhances lithium-ion(Li^(+))diffusion throughout the electrode,reducing charge transfer polarization and suppressing the onset of dendritic Li deposition.(2)When the anode potential drops below 0 V(vs Li/Li^(+))during fast charging,the SnO_(2) hollow sphere within SHS acts as a lithiophilic site,guiding Li deposition into its internal cavity.Benefiting from this two-stage strategy,the LiNi0.8Co0.1Mn0.1O_(2)||graphite pouch cell(180μm thickness,5 wt%SHS addition)achieves an 82%state of charge at 6 C and retains 80%capacity over 255 cycles,significantly outperforming counterparts degraded by dendritic Li plating during fast charging.This work provides a holistic strategy to address Li plating challenges in fastcharging,high-energy LIBs by integrating kinetic optimization and structural confinement.
基金financially supported by the National Key R&D Program of China(2021YFB2400300)Fundamental Research Funds for the Central Universities(22X010201631 and 23X010301599)“Xiaomi Young Scholar”Funding Project,and CATL Future Energy Research Institute(22H010102023).
文摘As the world enters into the era of electrifying transportation for cleaner energy,lithium-ion battery(LIB)-powered electric vehicles have drawn great attention in recent years.However,the fast-charging capability of LIBs has long been regarded as the technological obstacle to the wider adoption of battery electric vehicles(BEVs)in the market.A substantial challenge associated with fast charging is the formation of Li plating on the graphite anode as it is the major contributor of side reactions during cell operations.In this review,the fundamentals of Li plating and corresponding influencing factors(including state of charge[SOC],charging current density,temperature,and N/P ratio)for the Li-ion intercalation process are first elucidated under fast-charging conditions.Furthermore,conventional strategies to suppress Li plating by enhancing ion transport kinetics between interface and electrode through anode engineering and electrolyte design are also summarized and analyzed.Then,innovative strategies for achieving ultrahigh SOC of anodes by regulating Li plating morphology on host materials to construct hybrid anode storage are discussed in detail.Two types of strategies are compared in terms of cell performance,process simplicity,and safety concerns.Last,we highlight some research orientations and perspectives pertaining to the development of hybrid anode storage,providing effective approaches to address Li plating issues for fast-charging LIBs.
