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  1. Article ; Online: Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits.

    Zhou, Jiao / Li, Chunxia / Lu, Meng / Jiang, Gaoyue / Chen, Shanze / Li, Huihui / Lu, Kefeng

    PLoS biology

    2024  Volume 22, Issue 3, Page(s) e3002537

    Abstract: Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which autophagy limits inflammation remain elusive. Here, we found that the pan-FGFR inhibitor LY2874455 efficiently activated autophagy and suppressed expression of ... ...

    Abstract Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which autophagy limits inflammation remain elusive. Here, we found that the pan-FGFR inhibitor LY2874455 efficiently activated autophagy and suppressed expression of proinflammatory factors in macrophages stimulated by lipopolysaccharide (LPS). Multiplex proteomic profiling identified the immunoproteasome, which is a specific isoform of the 20s constitutive proteasome, as a substrate that is degraded by selective autophagy. SQSTM1/p62 was found to be a selective autophagy-related receptor that mediated this degradation. Autophagy deficiency or p62 knockdown blocked the effects of LY2874455, leading to the accumulation of immunoproteasomes and increases in inflammatory reactions. Expression of proinflammatory factors in autophagy-deficient macrophages could be reversed by immunoproteasome inhibitors, confirming the pivotal role of immunoproteasome turnover in the autophagy-mediated suppression on the expression of proinflammatory factors. In mice, LY2874455 protected against LPS-induced acute lung injury and dextran sulfate sodium (DSS)-induced colitis and caused low levels of proinflammatory cytokines and immunoproteasomes. These findings suggested that selective autophagy of the immunoproteasome was a key regulator of signaling via the innate immune system.
    MeSH term(s) Animals ; Mice ; Lipopolysaccharides/pharmacology ; Proteomics ; Autophagy ; Inflammation ; Macrophages ; Proteasome Endopeptidase Complex
    Chemical Substances Lipopolysaccharides ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2024-03-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002537
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  2. Article: Proteomics and Autophagy Research.

    Lu, Kefeng / Li, Huihui

    Advances in experimental medicine and biology

    2021  Volume 1208, Page(s) 373–386

    Abstract: Autophagy is an evolutionarily conserved intracellular degradation process. Autophagy is closely involved in human health and diseases. In recent years, mass spectrometry-based proteomic methods have become important and powerful tools for autophagy ... ...

    Abstract Autophagy is an evolutionarily conserved intracellular degradation process. Autophagy is closely involved in human health and diseases. In recent years, mass spectrometry-based proteomic methods have become important and powerful tools for autophagy studies. These types of techniques have been especially helpful to reveal the range of degradation substrates of autophagy through large-scale, unbiased analysis of cellular proteomes. At present, a variety of mass spectrometry-based proteomics methods have been successfully applied to autophagy research.
    MeSH term(s) Autophagy ; Humans ; Mass Spectrometry ; Proteome/genetics ; Proteomics
    Chemical Substances Proteome
    Language English
    Publishing date 2021-07-14
    Publishing country United States
    Document type Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-16-2830-6_17
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  3. Article ; Online: Hardware algorithm design and validation for nuclear radiation imaging based on Monte Carlo simulation.

    Zou, Kefeng / Wang, Lei / Lu, Wei / Feng, Penglei / Chen, Junqiao / Li, Haoxuan

    Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine

    2024  Volume 206, Page(s) 111228

    Abstract: The nuclear radiation imaging technology, aimed at illustrating the position and distribution of radioactive sources, has undergone extensive research. By relying on a simulated radiation imaging system for data acquisition, we can significantly expedite ...

    Abstract The nuclear radiation imaging technology, aimed at illustrating the position and distribution of radioactive sources, has undergone extensive research. By relying on a simulated radiation imaging system for data acquisition, we can significantly expedite the development cycle of these imaging instruments. Establishing simulated experimental scenarios and radiation imaging systems is of paramount significance in obtaining output signals for algorithmic testing and validation. This study is divided into two parts: simulation and hardware algorithm. In the simulation part, precise simulation of scintillation light transport in a crystal was achieved using the GEANT4 Monte Carlo simulation toolkit. A LaBr3(Ce) detector system was simulated by digitizing photon interactions. In the hardware algorithm part, a positioning algorithm based on a fully connected neural network was implemented and optimized using a heterogeneous distributed storage approach. The system validated and assessed the FPGA-based neural network gamma camera positioning algorithm, demonstrating significant consistency with computer-generated images in capturing the shape and dispersion of radioactive sources (planar, multi-point, and ring-shaped).
    Language English
    Publishing date 2024-02-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 1142596-9
    ISSN 1872-9800 ; 0883-2889 ; 0969-8043
    ISSN (online) 1872-9800
    ISSN 0883-2889 ; 0969-8043
    DOI 10.1016/j.apradiso.2024.111228
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  4. Article: Screening for Genes Involved in Autophagy.

    Lu, Kefeng / Li, Huihui

    Advances in experimental medicine and biology

    2021  Volume 1208, Page(s) 357–371

    Abstract: Autophagy is an important intracellular lysosomal degradation process in cells, which is highly conserved from yeast to mammals. The process of autophagy is roughly divided into the following key steps: the formation of a membrane structure called ISM ( ... ...

    Abstract Autophagy is an important intracellular lysosomal degradation process in cells, which is highly conserved from yeast to mammals. The process of autophagy is roughly divided into the following key steps: the formation of a membrane structure called ISM (isolated membrane) after stimulation, the biogenesis and maturation of autophagosomes, and finally the degradation of autophagosomes. A number of proteins are required to function in the whole process of autophagy. Since the initial genetic screening in yeast cells, multiple genes that play pivotal roles in autophagy have been discovered. These molecules have been named ATG genes (AuTophaGy related genes). The screening for new key molecules involved in autophagy has greatly promoted the characterization of the mechanism of the autophagy machinery and provides multiple targets for the development of autophagy-based regulatory drugs.
    MeSH term(s) Animals ; Autophagosomes ; Autophagy/genetics ; Autophagy-Related Proteins/genetics ; Lysosomes ; Saccharomyces cerevisiae
    Chemical Substances Autophagy-Related Proteins
    Language English
    Publishing date 2021-07-14
    Publishing country United States
    Document type Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-16-2830-6_16
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  5. Article: Molecular mechanisms of exercise intervention in alleviating the symptoms of autism spectrum disorder: Targeting the structural alterations of synapse.

    Zong, Wenhao / Lu, Xiaowen / Dong, Guijun / Zhang, Li / Li, Kefeng

    Frontiers in psychiatry

    2023  Volume 14, Page(s) 1096503

    Abstract: Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder characterized by stereotyped behaviors, specific interests, and impaired social and communication skills. Synapses are fundamental structures for transmitting ... ...

    Abstract Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder characterized by stereotyped behaviors, specific interests, and impaired social and communication skills. Synapses are fundamental structures for transmitting information between neurons. It has been reported that synaptic deficits, such as the increased or decreased density of synapses, may contribute to the onset of ASD, which affects the synaptic function and neuronal circuits. Therefore, targeting the recovery of the synaptic normal structure and function may be a promising therapeutic strategy to alleviate ASD symptoms. Exercise intervention has been shown to regulate the structural plasticity of synapses and improve ASD symptoms, but the underlying molecular mechanisms require further exploration. In this review, we highlight the characteristics of synaptic structural alterations in the context of ASD and the beneficial effects of an exercise intervention on improving ASD symptoms. Finally, we explore the possible molecular mechanisms of improving ASD symptoms through exercise intervention from the perspective of regulating synaptic structural plasticity, which contributes to further optimizing the related strategies of exercise intervention promoting ASD rehabilitation in future.
    Language English
    Publishing date 2023-03-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2023.1096503
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  6. Article ; Online: Bone cement distribution may significantly affect the efficacy of percutaneous vertebroplasty in treating symptomatic Schmorl's nodes.

    Cai, Kaiwen / Jiang, Guoqiang / Lu, Bin / Zhang, Kai / Luo, Kefeng

    BMC musculoskeletal disorders

    2023  Volume 24, Issue 1, Page(s) 473

    Abstract: Purpose: Percutaneous vertebroplasty(PVP) has been widely used in treating symptomatic Schmorl's nodes(SNs). However, there were still some patients with poor pain relief. At present, there is a lack of research to analyze the reasons for poor efficacy.! ...

    Abstract Purpose: Percutaneous vertebroplasty(PVP) has been widely used in treating symptomatic Schmorl's nodes(SNs). However, there were still some patients with poor pain relief. At present, there is a lack of research to analyze the reasons for poor efficacy.
    Methods: Review the SNs patients treated with PVP in our hospital from November 2019 to June 2022, collect their baseline data. Reverse reconstruction software was used to calculate the filling rate of bone edema ring(R
    Results: A total of 26 vertebrae were included in 24 patients. When grouped according to symptoms, patients in n-RG were older, and surgical segments were tend to locate in lower lumbar spine. The proportion of Poor distribution was significantly higher. When grouped according to the cement distribution, the preoperative NRS and ODI of the three groups were comparable, but the NRS and ODI of Poor group were significantly worse than the Excellent and Good groups postoperatively and at the last follow-up.
    Conclusions: The cement distribution may significantly affect the efficacy of PVP in treating symptomatic SNs. We suggest that the bone edema ring should be filled as fully as possible to ensure the efficacy. In addition, advanced age and low lumbar lesions are also adverse factors for clinical outcomes.
    MeSH term(s) Humans ; Bone Cements/therapeutic use ; Vertebroplasty ; Treatment Outcome ; Intervertebral Disc Displacement/diagnosis ; Pain ; Spinal Fractures/diagnostic imaging ; Spinal Fractures/surgery ; Fractures, Compression/diagnostic imaging ; Fractures, Compression/surgery ; Osteoporotic Fractures/surgery ; Retrospective Studies
    Chemical Substances Bone Cements
    Language English
    Publishing date 2023-06-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041355-5
    ISSN 1471-2474 ; 1471-2474
    ISSN (online) 1471-2474
    ISSN 1471-2474
    DOI 10.1186/s12891-023-06575-8
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  7. Article: Largely Enhanced Thermoelectric Power Factor of Flexible Cu

    Zuo, Xinru / Han, Xiaowen / Lu, Yiming / Liu, Ying / Wang, Zixing / Li, Jiajia / Cai, Kefeng

    Materials (Basel, Switzerland)

    2023  Volume 16, Issue 22

    Abstract: Copper-sulfide-based materials have attracted noteworthy attention as thermoelectric materials due to rich elemental reserves, non-toxicity, low thermal conductivity, and adjustable electrical properties. However, research on the flexible thermoelectrics ...

    Abstract Copper-sulfide-based materials have attracted noteworthy attention as thermoelectric materials due to rich elemental reserves, non-toxicity, low thermal conductivity, and adjustable electrical properties. However, research on the flexible thermoelectrics of copper sulfide has not yet been reported. In this work, we developed a facile method to prepare flexible Mn-doped Cu
    Language English
    Publishing date 2023-11-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2487261-1
    ISSN 1996-1944
    ISSN 1996-1944
    DOI 10.3390/ma16227159
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  8. Article ; Online: Autophagy is regulated by endoplasmic reticulum calcium homeostasis and sphingolipid metabolism.

    Liu, Shiyan / Chen, Mutian / Wang, Yichang / Li, Huihui / Qi, Shiqian / Geng, Jia / Lu, Kefeng

    Autophagy

    2023  Volume 19, Issue 12, Page(s) 3256–3257

    Abstract: Calcium is involved in a variety of cellular processes. As the crucial components of cell membranes, sphingolipids also play important roles as signaling molecules. Intracellular calcium homeostasis, autophagy initiation and sphingolipid synthesis are ... ...

    Abstract Calcium is involved in a variety of cellular processes. As the crucial components of cell membranes, sphingolipids also play important roles as signaling molecules. Intracellular calcium homeostasis, autophagy initiation and sphingolipid synthesis are associated with the endoplasmic reticulum (ER). Recently, through genetic screening and lipidomics analysis in
    MeSH term(s) Calcium/metabolism ; Autophagy ; Sphingolipids ; Saccharomyces cerevisiae/metabolism ; Endoplasmic Reticulum/metabolism ; Calcium Channels/metabolism ; Homeostasis
    Chemical Substances Calcium (SY7Q814VUP) ; Sphingolipids ; Calcium Channels
    Language English
    Publishing date 2023-08-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2023.2249761
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  9. Article ; Online: Nanoengineering Approach toward High Power Factor Ag

    Liu, Ying / Li, Yating / Wu, Miaomiao / Lu, Yiming / Wang, Zixing / Wei, Ping / Zhao, Wenyu / Cai, Kefeng

    ACS applied materials & interfaces

    2023  Volume 15, Issue 30, Page(s) 36587–36593

    Abstract: Herein, a flexible ... ...

    Abstract Herein, a flexible Ag
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Journal Article
    ISSN 1944-8252
    ISSN (online) 1944-8252
    DOI 10.1021/acsami.3c06960
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  10. Article ; Online: PAK inhibitor FRAX486 decreases the metastatic potential of triple-negative breast cancer cells by blocking autophagy.

    Lyu, Liang / Li, Haiyan / Lu, Kefeng / Jiang, Shu / Li, Huihui

    British journal of cancer

    2023  Volume 130, Issue 3, Page(s) 394–405

    Abstract: Background: Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with a high risk of metastasis and recurrence and a poor prognosis. Epithelial-mesenchymal transition (EMT) endows epithelial cells with the ability to move to distant ... ...

    Abstract Background: Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with a high risk of metastasis and recurrence and a poor prognosis. Epithelial-mesenchymal transition (EMT) endows epithelial cells with the ability to move to distant sites, which is essential for the metastasis of TNBC to organs, including the lung. Autophagy, an intracellular degradation process that involves formation of double-layered lipid autophagosomes that transport cytosolic cargoes into lysosomes via autophagosome-lysosome fusion, is involved in various diseases, including cancer and neurodegenerative, metabolic, cardiovascular, and infectious diseases. The relationship between autophagy and cancer has become relatively clear. However, research on pharmacological drugs that block cancer EMT by targeting autophagy is still in the initial stages. Therefore, the re-evaluation of old drugs for their potential in blocking both autophagy and EMT was conducted.
    Methods: More than 2000 small molecule chemicals were screened for dual autophagy/EMT inhibitors, and FRAX486 was identified as the best candidate inhibitor of autophagy/EMT. The functions of FRAX486 in TNBC metastasis were detected by CCK-8, migration and wound healing assays. The effects of FRAX486 on autophagy and its target PAK2 were determined by immunoblotting, immunofluorescence, immunoprecipitation analysis and transmission electron microscopy. The findings were validated in mouse models.
    Results: Here, we report that FRAX486, a potent P21-activated kinase 2 (PAK2) inhibitor, facilitates TNBC suppression both in vitro and in vivo by blocking autophagy. Mechanistically, FRAX486 inhibits autophagy in TNBC cells by targeting PAK2, leading to the ubiquitination and proteasomal degradation of STX17, which mediates autophagosome-lysosome fusion. The inhibition of autophagy by FRAX486 causes upregulation of the epithelial marker protein E-cadherin and thus suppresses the migration and metastasis of TNBC cells.
    Conclusions: The effects of FRAX486 on TNBC metastasis suppression were verified to be dependent on PAK2 and autophagy inhibition. Together, our results provide a molecular basis for the application of FRAX486 as a potential treatment for inhibiting the metastasis of TNBC.
    MeSH term(s) Mice ; Humans ; Animals ; Triple Negative Breast Neoplasms/pathology ; Cell Line, Tumor ; Pyrimidines/pharmacology ; Cell Movement ; Autophagy ; Epithelial-Mesenchymal Transition ; Cell Proliferation ; Pyridones
    Chemical Substances 6-(2,4-dichlorophenyl)-8-ethyl-2-(3-fluoro-4-(piperazin-1-yl)phenylamino)pyrido(2,3-d)pyrimidin-7(8H)-one ; Pyrimidines ; Pyridones
    Language English
    Publishing date 2023-12-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-023-02523-4
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