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Hepatic HDAC3 Regulates Systemic Iron Homeostasis and Ferroptosis via the Hippo Signaling Pathway

Research 2024年第3期2023卷 499-511页

作者： Hongen Meng Yingying Yu Enjun Xie Qian Wu Xiangju Yin Bin Zhao Junxia Min Fudi Wang The Second Afiliated Hospital The First Affiliated HospitalInstitute of Translational MedicineScho of Public HealthZhejiang University School of MedicineHangzhouChina institute of Emergency Management Henan Polytechnic UniversityJiaozuoChina MOE Key Laboratory of Biosystems Homeostasis and Protection Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biologyand Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou 310058China.

Histone deacetylases(HDACs)are epigenetic regulators that play an important role in determining cell fate and maintaining cellular ***,whether and how HDACs regulate iron metabolism and ferroptosis(an iron-dependent form of cell death)remain ***,the putative role of hepatic HDACs in regulating iron metabolism and ferroptosis was investigated using genetic mouse *** lacking Hdac3 expression in the liver(Hdac3-LKO mice)have significantly reduced hepatic Hamp mRNA(encoding the peptide hormone hepcidin)and altered iron *** profiling of Hdac3-LKO mice suggests that the Hippo signaling pathway may be downstream of ***,using a Hippo pathway inhibitor and overexpressing the transcriptional regulator Yap(Yes-associated protein)significantly reduced Hamp mRNA *** a promoter reporter assay,we then identified 2 Yap-binding repressor sites within the human HAMP promoter *** also found that inhibiting Hdac3 led to increased translocation of Yap to the nucleus,suggesting activation of ***,knock-in mice expressing a constitutively active form of Yap(Yap K342M)phenocopied the altered hepcidin levels observed in Hdac3-LKO ***,we show that iron-overload-induced ferroptosis underlies the liver injury that develops in Hdac3-LKO mice,and knocking down Yap expression in Hdac3-LKO mice reduces both iron-overload-and ferroptosis-induced liver *** results provide compelling evidence supporting the notion that HDAC3 regulates iron homeostasis via the Hippo/Yap pathway and may serve as a target for reducing ferroptosis in iron-overload-related diseases.

关键词： homeostasis metabolism expressing

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CRISPR-based genetic screens advance cancer immunology

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Science China Life Sciences 2024年

作者： Yuanfang Cao Xueting Li Yumu Pan Huahe Wang Siyu Yang Lingjuan Hong Lupeng Ye institute of Modern biology Nanjing University

CRISPR technologies have revolutionized research areas ranging from fundamental science to translational medicine. CRISPR-based genetic screens offer a powerful platform for unbiased screening in various fields, such as cancer immunology. Immune checkpoint blockade(ICB)therapy has been shown to strongly affect cancer treatment. However, the currently available ICBs are limited and do not work in all cancer patients. Pooled CRISPR screens enable the identification of previously unknown immune regulators that can regulate T-cell activation,cytotoxicity, persistence, infiltration into tumors, cytokine secretion, memory formation, T-cell metabolism, and CD4+T-cell *** novel targets can be developed as new immunotherapies or used with the current ICBs as new combination therapies that may yield synergistic efficacy. Here, we review the progress made in the development of CRISPR technologies, particularly technological advances in CRISPR screens and their application in novel target identification for immunotherapy.

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Gapless Genome Assembly of ZH8015 and Preliminary Multi-Omics Analysis to Investigate ZH8015's Responses Against Brown Planthopper Infestation

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Rice science 2024年第3期31卷 317-327,I0042-I0045页

作者： LI Dian DUAN Wenjing LIU Qun’en WU Weixun ZHAN Xiaodeng SUN Lianping ZHANG Yingxin CHENG Shihua State Key Laboratory of Rice biology and Breeding China National Rice Research InstituteHangzhou 310006China

Accurate genomic information is essential for advancing genetic breeding research in specific rice *** study presented a gapless genome assembly of the indica rice cultivar Zhonghui 8015(ZH8015)using Pac Bio HiFi,Hi-C,and ONT(Oxford Nanopore Technologies)ultra-long sequencing technologies,annotating 43037 gene ***,utilizing this genome along with transcriptomic and metabolomic techniques,we explored ZH8015's response to brown planthopper(BPH)*** transcriptomic sampling indicated significant changes in gene expression levels around 48 h after BPH *** analysis revealed particularly significant alterations in genes related to reactive oxygen species scavenging and cell wall *** results demonstrated marked increases in levels of several monosaccharides,which are components of the cell wall and dramatic changes in flavonoid *** association analysis identified differentially expressed genes associated with key metabolites,shedding light on ZH8015's response to BPH *** summary,this study constructed a reliable genome sequence resource for ZH8015,and the preliminary multi-omics results will guide future insect-resistant breeding research.

关键词： brown planthopper gapless genome genome assembly multi-omics Nilaparvata lugens rice

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Meningeal lymphatic vasculature,a general target for glioblastoma therapy?

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Fundamental Research 2024年第2期4卷 267-269页

作者： Changping Zhou Han Xu Jincai Luo Laboratory of Vascular biology Institute of Molecular MedicineCollege of Future TechnologyBeijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijing 100871China

Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and *** increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical *** central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this *** are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph *** the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including ***,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.

关键词： Meningeal lymphatic vessels Glioblastoma Immunity Vascular endothelial growth factor C Immune modulation

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Carbon Catabolite Repressor UvCreA is Required for Development and Pathogenicity in Ustilaginoidea virens

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Rice science 2024年第2期31卷 203-214,I0029-I0031页

作者： XIE Shuwei SHI Huanbin WEN Hui LIU Zhiquan QIU Jiehua JIANG Nan KOU Yanjun State Key Laboratory of Rice biology and Breeding China National Rice Research InstituteHangzhou 311400China

The rice false smut disease, caused by Ustilaginoidea virens, has emerged as a significantglobal threat to rice production. The mechanism of carbon catabolite repression plays a crucial role in theefficient utilization of carbon nutrients and enzyme regulation in the presence of complex nutritionalconditions. Although significant progress has been made in understanding carbon catabolite repression infungi such as Aspergillus nidulans and Magnaporthe oryzae, its role in U. virens remains unclear. Toaddress this knowledge gap, we identified UvCreA, a pivotal component of carbon catabolite repression,in U. virens. Our investigation revealed that UvCreA localized to the nucleus. Deletion of UvCreA resultedin decreased growth and pathogenicity in U. virens. Through RNA-seq analysis, it was found that theknockout of UvCreA led to the up-regulation of 514 genes and down-regulation of 640 genes. Moreover,UvCreA was found to be involved in the transcriptional regulation of pathogenic genes and genesassociated with carbon metabolism in U. virens. In summary, our findings indicated that UvCreA isimportant in fungal development, virulence, and the utilization of carbon sources through transcriptionalregulation, thus making it a critical element of carbon catabolite repression.

关键词： Ustilaginoidea virens virulence carbon catabolite repression Oryza sativa rice false smut

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Mitogenome-based phylogeny of mosquitoes(Diptera:Culicidae)

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Insect Science 2024年第2期31卷 599-612页

作者： De-Hong Chen Shu-Lin He Wen-Bo Fu Zhen-Tian Yan Yun-Jian Hu Huan Yuan Ming-Bin Wang Bin Chen Chongqing Key Laboratory of Vector Insects Institute of Entomology and Molecular BiologyChongqing Normal UniversityChongqingChina

Mosquitoes are of great medical significance as vectors of many deadly *** have been widely used in phylogenetic studies,but mitogenome knowledge within the family Culicidae is limited,and Culicidae phylogeny is far from *** this study,we surveyed the mitogenomes of 149 Culicidae species,including 7 newly sequenced *** analysis of 149 mosquito mitogenomes shows gene composition and order to be identical to that of an ancestral insect,and the AT bias,length variation,and codon usage are all consistent with that of other reported Dipteran *** analyses based on the DNA sequences of the 13 protein-coding genes from the 149 species robustly support the monophyly of the subfamily Anophelinae and the tribes Aedini,Culicini,Mansonini,Sabethini,and *** resolve ambiguous relationships between clades within the subfamily Culicinae,we performed topological tests and show that Aedini is a sister to Culicini and that Uranotaenini is a sister to(Mansonini)+(Toxorhynchitini+Sabethini).In addition,we estimated divergence times using a Bayesian relaxation clock based on the sequence data and 3 fossil calibration *** results show mosquitoes diverged during the Early Jurassic with massive Culicinae radiations during the Cretaceous,coincident with the emergence of angiosperms and the burst of mammals and ***,this study,which uses the largest number of Culicidae mitogenomes sequenced to date,comprehensively reveals the mitogenome characteristics and mitogenome-based phylogeny and divergence times of Culicidae,providing information for further studies on the mitogenome,phylogeny,evolution,and taxonomic revision of Culicidae.

关键词： characterization Culicidae evolution mitogenomes mosquitoes phylogeny

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Insights into therapeutic peptides in the cancerimmunity cycle:Update and challenges

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3818-3833页

作者： Xiaokun Zhang Ye Wu Jiayi Lin Shengxin Lu Xinchen Lu Aoyu Cheng Hongzhuan Chen Weidong Zhang Xin Luan Shanghai Frontiers Science Center for Chinese medicine Chemical biology Institute of Interdisciplinary Integrative Medicine Research and Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China institute of Medicinal Plant Development Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100193China School of Pharmacy Second Military Medical UniversityShanghai 200433China Department of Pharmacology School of PharmacyFudan UniversityShanghai 201203China

Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer *** vital biological mediators,peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies(CITs).However,physicochemical peptide features such as conformation and stability pose challenges to their on-target *** review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle(CIC),including tumor antigen presentation,immune cell regulation,and immune checkpoint *** attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical ***,possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.

关键词： Cancer-immunity cycle Oncolytic peptide Peptide neoantigen vaccine Peptide mimotope Immune checkpoint blockade Cancer immunotherapy Synthetic long peptide vaccine Peptide-major histocompatibility complex

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Establishment of microneurovascular units in alginate hydrogel microspheres to reveal the anti-hypoxic effect of salidroside

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Journal of Pharmaceutical Analysis 2024年第6期14卷 926-929页

作者： Shiyu Chen Yuxuan Li Yingrui Zhang Hongren Yao Tong Xu Yi Zhang Jin-Ming Lin Xian-Li Meng State Key Laboratory of Southwestern Chinese medicine Resources Innovative Institute of Chinese Medicine and PharmacyChengdu University of Traditional Chinese MedicineChengdu611137China Beijing Key Laboratory of Microanalytical Methods and Instrumentation Department of ChemistryKey Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology(Ministry of Education)Tsinghua UniversityBeijing100084China School of Ethnic medicine Chengdu University of Traditional Chinese MedicineChengdu611137China

Microneurovascular units(mNVUs),comprising neurons,micro-glia,and blood-brain barrier(BBB)endothelial cells,are pivotal to the central nervous system and are associated with cerebral hypoxia and brain *** hypoxia triggers microglial overactivity,causing inflammation,neuronal injury,and disruption of the BBB[1].Salidroside(Sal),a key compound in Tibetan medicine Rhodiola crenulata,mitigates hypoxia-induced metabolic disorders and neuronal damage by preserving mitochondrial function[2].

关键词： injuries preserving Tibetan

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Carotenoid isomerase regulates rice tillering and grain productivity by its biosynthesis pathway

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Journal of Integrative Plant biology 2024年第2期66卷 172-175页

作者： Chaoqing Ding Zhengji Shao Yuping Yan Guangheng Zhang Dali Zeng Li Zhu Jiang Hu Zhenyu Gao Guojun Dong Qian Qian Deyong Ren State Key Laboratory of Rice biology and Breeding ChinaNational Rice Research InstituteHangzhou 310006China

Tillers are unique inflorescence-like branches in grasses,and their number determines the panicle number,plant architecture,and yield(Shang et al.,2021).Tiller formation mainly undergoes axillary meristem(AM)initiation and tiller bud outgrowth(Wang et al.,2018;Yan et al.,2023).The rice(Oryza sativa)KNOX gene OSH1 is expressed in AMs,and an osh1 mutant produces fewer tillers(Tanaka et al.,2015).

关键词： sativa Oryza panicle

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CAR-T overdrive:harnessing inosine for metabolic rewiring and stemness induction

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2347-2348页

作者： MartíFarrera-Sal Michael Schmueck-Henneresse Berlin institute of Health(BIH)at Charité—Universitatsmedizin Berlin BIH Center for Regenerative Therapies(BCRT)Experimental ImmunotherapyAugustenburger Platz 1BerlinGermany

In a recent Cancer Cell publication,Klysz et *** the impact of inosine(INO),a catabolic product of adenosine(Ado),on Chimeric Antigen Receptor(CAR)T-cell function,stemness,and *** provided insights into T-cell exhaust... 详细信息

关键词： programming. CAR Ado

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