Advanced Science最新文献_第5页

Suppressed Protein Translation Caused by MSP-8 Deficiency Determines Fungal Multidrug Resistance with Fitness Cost.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202412514

Mi Zhou, Pengju Yu, Chengcheng Hu, Wenxia Fang, Cheng Jin, Shaojie Li, Xianyun Sun

{"title":"Suppressed Protein Translation Caused by MSP-8 Deficiency Determines Fungal Multidrug Resistance with Fitness Cost.","authors":"Mi Zhou, Pengju Yu, Chengcheng Hu, Wenxia Fang, Cheng Jin, Shaojie Li, Xianyun Sun","doi":"10.1002/advs.202412514","DOIUrl":"https://doi.org/10.1002/advs.202412514","url":null,"abstract":"Antifungal resistance, particularly the rise of multidrug-resistance strains, poses a significant public health threat. In this study, the study identifies a novel multidrug-resistance gene, msp-8, encoding a helicase, through experimental evolution with Neurospora crassa as a model. Deletion of msp-8 conferred multidrug resistance in N. crassa, Aspergillus fumigatus, and Fusarium verticillioides. However, the transcript levels of genes encoding known drug targets or efflux pumps remain unaltered with msp-8 deletion. Interestingly, MSP-8 interacted with ribosomal proteins, and this mutant displays compromised ribosomal function, causing translational disturbance. Notably, inhibition of protein translation enhances resistance to azoles, amphotericin B, and polyoxin B. Furthermore, MSP-8 deficiency or inhibition of translation reduces intracellular ketoconazole accumulation and membrane-bound amphotericin B content, directly causing antifungal resistance. Additionaly, MSP-8 deficiency induces cell wall remodeling, and decreases intracellular ROS levels, further contributing to resistance. The findings reveal a novel multidrug resistance mechanism independent of changes in drug target or efflux pump, while MSP-8 deficiency suppresses protein translation, thereby facilitating the development of resistance with fitness cost. This study provides the first evidence that MSP-8 participates in protein translation and that translation suppression can cause multidrug resistance in fungi, offering new insights into resistance mechanisms in clinical and environmental fungal strains.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2412514"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Artificial Neural Network for Image Classification Inspired by the Aversive Olfactory Learning Neural Circuit in Caenorhabditis elegans. 受草履虫逆嗅觉学习神经回路启发的图像分类人工神经网络

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202410637

Xuebin Wang, Chunxiuzi Liu, Meng Zhao, Ke Zhang, Zengru Di, He Liu

{"title":"An Artificial Neural Network for Image Classification Inspired by the Aversive Olfactory Learning Neural Circuit in Caenorhabditis elegans.","authors":"Xuebin Wang, Chunxiuzi Liu, Meng Zhao, Ke Zhang, Zengru Di, He Liu","doi":"10.1002/advs.202410637","DOIUrl":"https://doi.org/10.1002/advs.202410637","url":null,"abstract":"This study introduces an artificial neural network (ANN) for image classification task, inspired by the aversive olfactory learning neural circuit in Caenorhabditis elegans (C. elegans). Although artificial neural networks (ANNs) have demonstrated remarkable performance in various tasks, they still encounter challenges including excessive parameterization, high training costs and limited generalization capabilities, etc. C. elegans, boasting a simple nervous system consisting of merely 302 neurons, is capable of exhibiting complex behaviors such as aversive olfactory learning. This research pinpoints key neural circuit related to aversive olfactory learning in C. elegans by means of behavioral experiment and high-throughput RNA sequencing, and then translates it into an architecture of ANN for image classification. Furthermore, other ANNs for image classification with different architectures are constructed for comparative performance analysis to underscore the advantages of the bio-inspired designed architecture. The results show that the ANN inspired by the aversive olfactory learning neural circuit in C. elegans attains higher accuracy, greater consistency and faster convergence rate in the image classification task, particularly when dealing with more complex classification challenges. This study not only demonstrates the potential of bio-inspired design in improving the capabilities of ANNs but also offers a novel perspective and methodology for future ANNs design.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2410637"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reversing Persistent PTEN Activation after Traumatic Brain Injury Fuels Long-Term Axonal Regeneration via Akt/mTORC1 Signaling Cascade.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202410136

Ziyu Shi, Leilei Mao, Shuning Chen, Zhuoying Du, Jiakun Xiang, Minghong Shi, Yana Wang, Yuqing Wang, Xingdong Chen, Zhi-Xiang Xu, Yanqin Gao

{"title":"Reversing Persistent PTEN Activation after Traumatic Brain Injury Fuels Long-Term Axonal Regeneration via Akt/mTORC1 Signaling Cascade.","authors":"Ziyu Shi, Leilei Mao, Shuning Chen, Zhuoying Du, Jiakun Xiang, Minghong Shi, Yana Wang, Yuqing Wang, Xingdong Chen, Zhi-Xiang Xu, Yanqin Gao","doi":"10.1002/advs.202410136","DOIUrl":"https://doi.org/10.1002/advs.202410136","url":null,"abstract":"Traumatic brain injury (TBI) often leads to enduring axonal damage and persistent neurological deficits. While PTEN's role in neuronal growth is recognized, its long-term activation changes post-TBI and its effects on sensory-motor circuits are not well understood. Here, it is demonstrated that the neuronal knockout of PTEN (PTEN-nKO) significantly enhances both structural and functional recovery over the long term after TBI. Importantly, in vivo, DTI-MRI revealed that PTEN-nKO promotes white matter repair post-TBI. Additionally, calcium imaging and electromyographic recordings indicated that PTEN-nKO facilitates cortical remapping and restores sensory-motor pathways. Mechanistically, PTEN negatively regulates the Akt/mTOR pathway by inhibiting Akt, thereby suppressing mTOR. Raptor is a key component of mTORC1 and its suppression impedes axonal regeneration. The restoration of white matter integrity and the improvements in neural function observed in PTEN-nKO TBI-treated mice are reversed by a PTEN/Raptor double knockout (PTEN/Raptor D-nKO), suggesting that mTORC1 acts as a key mediator. These findings highlight persistent alterations in the PTEN/Akt/mTORC1 axis are critical for neural circuit remodeling and cortical remapping post-TBI, offering new insights into TBI pathophysiology and potential therapeutic targets.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2410136"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Schwann Cell-Specific Ablation of Beclin 1 Impairs Myelination and Leads to Motor and Sensory Neuropathy in Mice.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202308965

Lisa Gambarotto, Loris Russo, Silvia Bresolin, Luca Persano, Rachele D'Amore, Giulia Ronchi, Federica Zen, Luisa Muratori, Alice Cani, Samuele Negro, Aram Megighian, Sonia Calabrò, Paola Braghetta, Dario Bizzotto, Matilde Cescon

{"title":"Schwann Cell-Specific Ablation of Beclin 1 Impairs Myelination and Leads to Motor and Sensory Neuropathy in Mice.","authors":"Lisa Gambarotto, Loris Russo, Silvia Bresolin, Luca Persano, Rachele D'Amore, Giulia Ronchi, Federica Zen, Luisa Muratori, Alice Cani, Samuele Negro, Aram Megighian, Sonia Calabrò, Paola Braghetta, Dario Bizzotto, Matilde Cescon","doi":"10.1002/advs.202308965","DOIUrl":"https://doi.org/10.1002/advs.202308965","url":null,"abstract":"The core component of the class III phosphatidylinositol 3-kinase complex, Beclin 1, takes part in different protein networks, thus switching its role from inducing autophagy to regulating autophagosomal maturation and endosomal trafficking. While assessed in neurons, astrocytes, and microglia, its role is far less investigated in myelinating glia, including Schwann cells (SCs), responsible for peripheral nerve myelination. Remarkably, the dysregulation in endosomal trafficking is emerging as a pathophysiological mechanism underlying peripheral neuropathies, such as demyelinating Charcot-Marie-Tooth (CMT) diseases. By knocking out Beclin 1 in SCs here a novel mouse model (Becn1 cKO) is generated, developing a severe and progressive neuropathy, accompanied by involuntary tremors, body weight loss, and premature death. Ultrastructural analysis revealed abated myelination and SCs displaying enlarged cytoplasm with progressive accumulation of intracellular vesicles. Transcriptomic and histological analysis from sciatic nerves of 10-day and 2-month-old mice revealed pro-mitotic gene deregulation and increased SCs proliferation at both stages with axonal loss and increased immune infiltration in adults, well reflecting the progressive motor and sensory functional impairment that characterizes Becn1 cKO mice, compared to controls. The study establishes a further step in understanding key mechanisms in SC development and points to Beclin 1 and its regulated pathways as targets for demyelinating CMT forms.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2308965"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diverse N-Oxidation of Primary Aromatic Amines Controlled by Engineered P450 Peroxizyme Variants Facilitated by Dual-Functional Small Molecule.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202412100

Jie Chen, Fuquan Yao, Yiping Jiang, Xiangquan Qin, Mo Xian, Yingang Feng, Zhiqi Cong

{"title":"Diverse N-Oxidation of Primary Aromatic Amines Controlled by Engineered P450 Peroxizyme Variants Facilitated by Dual-Functional Small Molecule.","authors":"Jie Chen, Fuquan Yao, Yiping Jiang, Xiangquan Qin, Mo Xian, Yingang Feng, Zhiqi Cong","doi":"10.1002/advs.202412100","DOIUrl":"https://doi.org/10.1002/advs.202412100","url":null,"abstract":"Amine oxidation is an important organic reaction for the production of high-value N-containing compounds. However, it is still challenging to control the reactivity of active N-centered radicals to selectively access N-oxidation products. Herein, this study reports the engineering of cytochrome P450BM3 into multifunctional N-oxidizing enzymes with the assistance of dual-functional small molecules (DFSM) to selectively produce N-oxygenation (i.e., p-nitrosobenzene, p-nitrobenzene, and azoxybenzene) and one-electron oxidation products (i.e., oligomeric quinones and azobenzene) from aromatic amines. The best mutant, F87A/T268V/V78T/A82T, exclusively gives p-nitrosobenzene (up to 98% selectivity), whereas the selectivity for p-nitrobenzene is >99% using the mutant F87A/T268V/A82T/I263L. Crystal structure analysis reveals that key mutations and DFSM exert synergistic effects on catalytic promiscuity by controlling the substrate orientation in active center. This study highlights the potential of DFSM-facilitated P450 peroxygenase and peroxidase for the synthesis of N-containing compounds via the controllable oxidation of aromatic amines, substantially expanding the chemical space of P450 enzymes.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2412100"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted Delivery of c(RGDfk)-Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy. 通过体内 "搭便车 "的中性粒细胞将c(RGDfk)修饰脂质体靶向输送到骨髓，用于多发性骨髓瘤治疗。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202409895

Huiwen Liu, Bo Zhang, Hongrui Chen, Honglan Wang, Xifeng Qin, Chunyan Sun, Zhiqing Pang, Yu Hu

{"title":"Targeted Delivery of c(RGDfk)-Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy.","authors":"Huiwen Liu, Bo Zhang, Hongrui Chen, Honglan Wang, Xifeng Qin, Chunyan Sun, Zhiqing Pang, Yu Hu","doi":"10.1002/advs.202409895","DOIUrl":"https://doi.org/10.1002/advs.202409895","url":null,"abstract":"Multiple myeloma (MM) is a prevalent bone marrow disorder. The challenges in managing MM include selecting chemotherapy regimens that effectively modulate the myeloma microenvironment and delivering them to the bone marrow with high efficacy and minimal toxicity. Herein, a novel bone marrow targeting strategy using c(RGDfk) peptide-modified liposomes loaded with chemotherapeutics is developed, which can specifically recognize and hitchhike neutrophils following systemic administration, capitalizing on their natural aging process to facilitate precise drug delivery to the bone marrow, thus minimizing off-target effects. On the one hand, c(RGDfk)-functionalized liposomes containing carfilzomib (CRLPs) successfully transformed macrophages from M2 phenotype to M1 phenotype, enhancing immunotherapeutic responses. On the other hand, c(RGDfk)-functionalized liposomes encapsulating BMS-202 (BRLPs), a small molecule checkpoint inhibitor, interrupted the PD-1/PD-L1 axis and promoted the infiltration of cytotoxic T cells. The co-administration of CRLPs and BRLPs successfully delivered drugs to bone marrow, leading to significant modulation of the myeloma microenvironment, reduced tumor growth, and improved survival time of MM-bearing mouse models. These findings introduced an alternative approach to modulating the myeloma microenvironment and underscored the efficacy of hitchhiking neutrophils for bone marrow drug delivery. This strategy show advantages over traditional drug delivery methods in terms of improved efficacy and lowered toxicity.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2409895"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Constructing Quasi-Localized High-Concentration Solvation Structures to Stabilize Battery Interfaces in Nonflammable Phosphate-Based Electrolyte. 构建准局部高浓度溶解结构，稳定不易燃磷酸盐电解液中的电池界面

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202411826

Chenyang Shi, Mengran Wang, Zari Tehrani, Bo Hong, Mengnan Wang, Rui Tan, Serena Margadonna, Yanqing Lai, Maria Magdalena Titirici

{"title":"Constructing Quasi-Localized High-Concentration Solvation Structures to Stabilize Battery Interfaces in Nonflammable Phosphate-Based Electrolyte.","authors":"Chenyang Shi, Mengran Wang, Zari Tehrani, Bo Hong, Mengnan Wang, Rui Tan, Serena Margadonna, Yanqing Lai, Maria Magdalena Titirici","doi":"10.1002/advs.202411826","DOIUrl":"https://doi.org/10.1002/advs.202411826","url":null,"abstract":"Flame-retardant phosphate-based electrolytes effectively enhance lithium-ion battery safety but suffer from poor compatibility with graphite anodes and high-voltage cathodes, hindering scalability. Fluorinated phosphates, though widely used, increase interfacial resistance at the anode, degrading performance. In this work, carbonate solvents with strong polarity are introduced to prevent tris(2,2,2-trifluoroethyl) phosphate (TFEP) from participating in the solvation structure of lithium ions. This strategy forms a quasi-localized high-concentration solvation structure, thereby restricting the reduction of TFEP and its impact on the graphite anode. The LiNi0.8Mn0.1Co0.1O2 (NCM811) | Graphite (Gr) pouch cell with optimized electrolyte exhibits a capacity retention rate of 80.1% after 370 cycles at 0.5C, which is much more stable than the electrolyte with TFEP-involved solvation structure (capacity retention rate: 47.1% after 300 cycles). The corresponding pouch cell with cut-off voltage to 4.5 V exhibits a capacity retention rate of 82.8% after 125 cycles, significantly outperforming cells employing commercial carbonate electrolytes (capacity retention rate: 56.9% after 125 cycles). Thus, the developed quasi-localized high-concentration solvation structure can effectively stabilize the electrode interface, greatly enhancing the cycling performance of phosphate-based flame-retardant electrolytes.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2411826"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cis-Regulation of an m⁶A Eraser by an Insertion Variant Associated with Survival of Patients With Non-Small Cell Lung Carcinoma. 插入变体对 m6A 清除剂的顺式调控与非小细胞肺癌患者的存活率有关。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202407652

Lei Cheng, Qiangsheng Hu, Yanan Wang, Wei Nie, Haijiao Lu, Bo Zhang, Genming Zhao, Shiyun Ding, Feng Pan, Yinchen Shen, Runbo Zhong, Ruoxin Zhang

{"title":"Cis-Regulation of an m6A Eraser by an Insertion Variant Associated with Survival of Patients With Non-Small Cell Lung Carcinoma.","authors":"Lei Cheng, Qiangsheng Hu, Yanan Wang, Wei Nie, Haijiao Lu, Bo Zhang, Genming Zhao, Shiyun Ding, Feng Pan, Yinchen Shen, Runbo Zhong, Ruoxin Zhang","doi":"10.1002/advs.202407652","DOIUrl":"https://doi.org/10.1002/advs.202407652","url":null,"abstract":"N6-methyladenosine (m6A) serves as one of the crucial RNA modifications for genes involved in cancer progression. Here, 7273 expression quantitative trait loci potentially regulating 30 m6A pathway genes are identified from the GTEx database, with 69 single nucleotide polymorphisms significantly associated with survival of non-small cell lung carcinoma (NSCLC) patients (n = 1523) from the ongoing genome-wide association study after false positive probability tests. Notably, the rs151198415 locus, situated in a potential enhancer region, demonstrated a prolonged survival effect with the C>CCACG insertion, which is validated in an independent prospective cohort (n = 237), yielding a pooled hazard ratio of 0.72 (p = 0.007). Mechanistically, the rs151198415 C>CCACG insertion engaged in long-range interaction with the promoter of m6A eraser ALKBH5, promoting ALKBH5 transcription by the creation of an EGR1 binding site. Then, ALKBH5 upregulated FBXL5 expression by m6A demethylation, which is dependent on the ALKBH5 H204 amino acid site and specific m6A sites on FBXL5 mRNA. Finally, the ALKBH5-FBXL5 axis reduces intracellular reactive oxygen species levels, leading to PI3K/AKT and NF-kB pathway inhibition and consequently suppresses NSCLC proliferation and metastasis in vitro and in vivo. Triggered by an insertion variant, this remote cis-regulation of m6A eraser and the downstream molecular events modulate the survival of NSCLC patients.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2407652"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Heparan Sulfate Mimetic RAFT Copolymer Inhibits SARS-CoV-2 Infection and Ameliorates Viral-Induced Inflammation.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202411737

Jiaxin Ling, Åke Lundkvist, Marco Guerrini, Vito Ferro, Jin-Ping Li, Jinlin Li

{"title":"A Heparan Sulfate Mimetic RAFT Copolymer Inhibits SARS-CoV-2 Infection and Ameliorates Viral-Induced Inflammation.","authors":"Jiaxin Ling, Åke Lundkvist, Marco Guerrini, Vito Ferro, Jin-Ping Li, Jinlin Li","doi":"10.1002/advs.202411737","DOIUrl":"https://doi.org/10.1002/advs.202411737","url":null,"abstract":"The high transmissibility and mutation ability of coronaviruses enable them to easily escape existing immune protection and also pose a challenge to existing antiviral drugs. Moreover, drugs only targeting viruses cannot always attenuate the \"cytokine storm\". Herein, a synthetic heparan sulfate (HS) mimetic, HMSA-06 is reported, that exhibited antiviral activities against both the SARS-CoV-2 prototype and Omicron strains by targeting viral entry and replication. Of particular note, HMSA-06 demonstrated more potent anti-SARS-CoV-2 effects than PG545 and Roneparstat. SARS-CoV-2 is reported to hijack autophagy to facilitate its replication, therefore boosting autophagy can attenuate SARS-CoV-2 infection. It is revealed that HMSA-06, but not a similar HS mimetic that failed to inhibit SARS-CoV-2, can upregulate cellular autophagy flux. In addition, HMSA-06 was found to robustly block the NLRP3-mediated inflammatory reaction in SARS-CoV-2 infected THP-1 derived macrophages as evidenced by a reduction in inflammasome formation and the subsequent decreased secretion of mature caspase-1 and IL-1β. The HMSA-06's inflammation inhibitory function is further confirmed using a LPS/ATP-stimulated THP-1 macrophage model. Altogether, this study has identified a promising HS mimetic to combat SARS-CoV-2-associated diseases by inhibiting viral infection and attenuating viral-induced inflammatory reaction, providing insights into the development of novel anti-coronavirus drugs in the future.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2411737"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arginine-Loaded Nano-Calcium-Phosphate-Stabilized Lipiodol Pickering Emulsions Potentiates Transarterial Embolization-Immunotherapy. 精氨酸负载的纳米磷酸钙稳定脂碘皮克林乳剂能增强经动脉栓塞-免疫疗法的效果。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2024-12-16 DOI: 10.1002/advs.202410484

Duo Wang, Lei Zhang, Wei-Hao Yang, Lin-Zhu Zhang, Chao Yu, Juan Qin, Liang-Zhu Feng, Zhuang Liu, Gao-Jun Teng

{"title":"Arginine-Loaded Nano-Calcium-Phosphate-Stabilized Lipiodol Pickering Emulsions Potentiates Transarterial Embolization-Immunotherapy.","authors":"Duo Wang, Lei Zhang, Wei-Hao Yang, Lin-Zhu Zhang, Chao Yu, Juan Qin, Liang-Zhu Feng, Zhuang Liu, Gao-Jun Teng","doi":"10.1002/advs.202410484","DOIUrl":"https://doi.org/10.1002/advs.202410484","url":null,"abstract":"Transarterial chemoembolization (TACE) continues to stand as a primary option for treating unresectable hepatocellular carcinoma (HCC). However, the increased tumor hypoxia and acidification will lead to the immunosuppressive tumor microenvironment (TME) featuring exhausted T cells, limiting the effectiveness of subsequent therapies following TACE. Herein, a stable water-in-oil lipiodol Pickering emulsion by employing calcium phosphate nanoparticles (CaP NPs) as stabilizers is developed and used to encapsulate L-arginine (L-Arg), which is known for its ability to modulate T-cell metabolism. The obtained L-Arg-loaded CaP-stabilized lipiodol Pickering emulsion (L-Arg@CaPL) with great emulsion stability can not only neutralize the tumor acidity via reaction of CaP NPs with protons but also enable the release of L-Arg, thereby synergistically promoting the reinvigoration of exhausted CD8+ T cells and effectively reversing tumor immunosuppression. As a result, TACE therapy with L-Arg@CaPL shows greatly improved therapeutic responses as demonstrated in an orthotopic liver tumor model in rats. This study highlights an effective yet simple nanoparticle-stabilized Pickering emulsion strategy to promote TACE therapy via modulation of the immunosuppressive TME, presenting great potential for clinical translation.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2410484"},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0