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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA present address:University of Colorado Boulder BoulderCO 80309USA present address:Dana Farber Cancer Institute BostonMA 02215USA present address:Massachusetts Institute of Technology BostonMA 02139USA present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

Modular Synthesis of Multi-substituted Cyclobutanones Enabled by Oxyallyl Cations

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Chinese Journal of Chemistry 2024年第5期42卷 459-463页

作者： Meng Wang Zhonggui Wang Ping Lu Research Center for Molecular Recognition and Synthesis Department of ChemistryFudan University220 Handan LuShanghai200433 China present address: department of Cancer biology Dana-Farber Cancer Institute department of Biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBostonMA 02115USA

Stereoselective synthesis of multi-substituted cyclobutanes with different substituents is still a daunting challenge in organic *** report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available *** substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic *** transformation to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was also explored.

关键词： Diastereoselectivity Modular synthesis Nucleophilic substitution Organohalides Oxyallyl cation Precision functionalization Strained molecules 1,2,3,4-Tetrasubstituted cyclobutanes

The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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Molecular plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni department of plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel present address:department of Cell and Metabolic biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA department of Botany and plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

TRP Channels in Stroke

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Neuroscience Bulletin 2024年第8期40卷 1141-1159页

作者： Pengyu Zong Cindy XLi Jianlin Feng Mara Cicchetti Lixia Yue department of Cell biology Calhoun Cardiology CenterSchool of Medicine(UConn Health)University of ConnecticutFarmingtonCT 06030USA Institute for the Brain and Cognitive Sciences University of Connecticut337 Mansfield RoadUnit 1272StorrsCT 06269USA present address:department of Neuroscience University of Pittsburgh4200 Fifth AvePittsburghPA 15260USA

Ischemic stroke is a devastating disease that affects millions of patients ***,there are no effective medications for mitigating brain injury after ischemic *** channels are evolutionally ancient biosensors that detect external stimuli as well as tissue or cellular *** date,many members of the TRP superfamily have been reported to contribute to ischemic brain injury,including the TRPC subfamily(1,3,4,5,6,7),TRPV subfamily(1,2,3,4)and TRPM subfamily(2,4,7).These TRP channels share structural similarities but have distinct channel functions and *** activation during ischemic stroke can be beneficial,detrimental,or even *** this review,we focus on discussing the interesting features of stroke-related TRP channels and summarizing the underlying cellular and molecular mechanisms responsible for their involvement in ischemic brain injury.

关键词： Stroke TRP channels-Neuronal death Immune cell infiltration Blood-brain barrier Glial activation

The super-pangenome of Populus unveils genomic facets for its adaptation and diversification in widespread forest trees

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Molecular plant 2024年第5期17卷 725-746页

作者： Tingting Shi Xinxin Zhang Yukang Hou Changfu Jia Xuming Dan Yulin Zhang Yuanzhong Jiang Qiang Lai Jiajun Feng Jianju Feng Tao Ma Jiali Wu Shuyu Liu Lei Zhang Zhiqin Long Liyang Chen Nathaniel R.Street Par K.Ingvarsson Jianquan Liu Tongming Yin Jing Wang Key Laboratory for Bio-Resources and Eco-Environment of Ministry of Education College of Life SciencesSichuan UniversityChengduSichuanChina College of Horticulture and Forestry Tarim UniversityAlar 843300China Umea plant Science Centre Department of Plant PhysiologyUmea UniversityUmeaVasterbottenSweden Linnean Centre for plant biology Department of Plant BiologyUppsala BioCenterSwedish University of Agricultural SciencesUppsalaSweden The Key Laboratory of Tree Genetics and Biotechnology of Jiangsu Province and Education department of China Nanjing Forestry UniversityNanjingJiangsuChina

Understanding the underlying mechanisms and links between genome evolution and adaptive innovations stands as a key goal in evolutionary ***,among the world’s most widely distributed and cultivated trees,exhibit extensive phenotypic diversity and environmental *** this study,we present a genus-level super-pangenome comprising 19 Populus genomes,revealing the likely pivotal role of private genes in facilitating local environmental and climate *** the integration of pangenomes with transcriptomes,methylomes,and chromatin accessibility mapping,we unveil that the evolutionary trajectories of pangenes and duplicated genes are closely linked to local genomic landscapes of regulatory and epigenetic architectures,notably CG methylation in gene-body *** comparative genomic analyses have enabled the identification of 142202 structural variants across species that intersect with a significant number of genes and contribute substantially to both phenotypic and adaptive *** have experimentally validated a∼180-bp presence/absence variant affecting the expression of the CUC2 gene,crucial for leaf serration ***,we developed a user-friendly web-based tool encompassing the multi-omics resources associated with the Populus super-pangenome(http://***).Together,the present pioneering super-pangenome resource in forest trees not only aids in the advancement of breeding efforts of this globally important tree genus but also offers valuable insights into potential avenues for comprehending tree biology.

关键词： Populus pangenomes whole-genome duplication structural variation genome evolution

Making the Complicated Simple:A Minimizing Carrier Strategy on Innovative Nanopesticides

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Nano-Micro Letters 2024年第10期16卷 31-46页

作者： Wenjie Shangguan Qiliang Huang Huiping Chen Yingying Zheng Pengyue Zhao Chong Cao Manli Yu Yongsong Cao Lidong Cao State Key Laboratory for biology of plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193People's Republic of China College of plant Protection China Agricultural UniversityBeijing 100193People's Republic of China State Key Laboratory of Element-Organic Chemistry Department of Chemical BiologyCollege of ChemistryNankai UniversityTianjin 300071People's Republic of China

The flourishing progress in nanotechnology offers boundless opportunities for agriculture,particularly in the realm of nanopesticides research and ***,concerns have been raised regarding the human and environmental safety issues stemming from the unrestrained use of non-therapeutic nanomaterials in *** is also important to consider whether the current development strategy of nanopesticides based on nanocarriers can strike a balance between investment and return,and if the complex material composition genuinely improves the efficiency,safety,and circularity of ***,we introduced the concept of nanopesticides with minimizing carriers(NMC)prepared through prodrug design and molecular self-assembly emerging as practical tools to address the current limitations,and compared it with nanopesticides employing non-therapeutic nanomaterials as carriers(NNC).We further summarized the current development strategy of NMC and examined potential challenges in its preparation,performance,and ***,we asserted that the development of NMC systems can serve as the innovative driving force catalyzing a green and efficient revolution in nanopesticides,offering a way out of the current predicament.

关键词： Nanopesticides Green agrochemicals Self-assembly Nanomaterial safety Sustainable development strategies

Regulation of gene-edited plants in Europe:from the valley of tears into the shining sun?

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aBIOTECH 2024年第2期5卷 231-238页

作者： Holger Puchta department of Molecular biology Joseph Gottlieb Kolreuter Institute for Plant SciencesKarlsruhe Institute of Technology(KIT)Fritz-Haber-Weg 476131 KarlsruheGermany

Some 20 years ago,the EU introduced complex regulatory rules for the growth of transgenic crops,which resulted in a de facto ban to grow these plants in fields within most European *** the rise of novel genome editing technologies,it has become possible to improve crops genetically in a directed way without the need for incorporation of foreign ***,in 2018,the European Court of Justice ruled that such gene-edited plants are to be regulated like transgenic *** then,European scientists and breeders have challenged this decision and requested a revision of this outdated ***,after 5 years,the European Commission has now published a proposal on how,in the future,to regulate crops produced by new breeding *** proposal tries to find a balance between the different interest groups in *** one side,genetically modified plants,which cannot be discerned from their natural counterparts,will exclusively be used for food and feed and are-besides a registration step-not to be regulated at *** the other side,plants expressing herbicide resistance are to be excluded from this regulation,a concession to the strong environmental associations and NGOs in ***,edited crops are to be excluded from organic farming to protect the business interests of the strong organic sector in ***,if this law passes European parliament and council,unchanged,it will present a big step forward toward establishing a more sustainable European agricultural ***,it might soon be possible to develop and grow crops that are more adapted to global warming and whose cultivation will require lower amounts of ***,there is still a long way to go until the law is *** often,the storm of arguments raised by the opponents,based on irrational fears of mutations and a naive understanding of nature,has fallen on fruitful ground in Europe.

关键词： Genetically modified organism Cisgenesis Gene editing CRISPR/Cas Regulation

Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea department of Immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka present address:Immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

Activation of stress-response genes by retrograde signaling-mediated destabilization of nuclear importin IMPα-9 and its interactor TPR2

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Molecular plant 2024年第6期17卷 884-899页

作者： Liping Zeng Maria Fernanda Gomez Mendez Jingzhe Guo Jishan Jiang Bailong Zhang Hao Chen Brandon Le Haiyan Ke Katayoon Dehesh department of Botany and plant Sciences Institute of Integrative Genome BiologyUniversity of CaliforniaRiversideRiversideCA 92521USA School of Medicine University of CaliforniaRiversideRiversideCA 92521USA

Stress-induced retrograde signal transmission from the plastids to the nucleus has long puzzled plant *** address this,we performed a suppressor screen of the ceh1 mutant,which contains elevated 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate(MEcPP)levels,and identified the gain-of-function mutant impα-9,which shows reversed dwarfism and suppressed expression of stress-response genes in the ceh1 background despite heightened *** genetic and biochemical analyses established that the accumulation of MEcPP initiates an upsurge in Arabidopsis SKP1-like 1(ASK1)abundance,a pivotal component in the proteasome degradation *** increase in ASK1 prompts the degradation of IMPα-***,we uncovered a protein-protein interaction between IMPα-9 and TPR2,a transcriptional co-suppressor and found that a reduction in IMPα-9 levels coincides with a decrease in TPR2 ***,the interaction between IMPα-9 and TPR2 was disrupted in impα-9 mutants,highlighting the critical role of a single amino acid alteration in maintaining their *** of their interaction results in the reversal of MEcPP-associated *** immunoprecipitation coupled with sequencing analyses revealed that TPR2 binds globally to stress-response genes and suggested that IMPα-9 associates with the *** function together to suppress the expression of stress-response genes under normal conditions,but this suppression is alleviated in response to stress through the degradation of the suppressing *** biological relevance of our discoveries was validated under high light stress,marked by MEcPP accumulation,elevated ASK1 levels,IMPα-9 degredation,reduced TPR2 abundance,and subsequent activation of a network of stress-response *** summary,our study collectively unveils fresh insights into plant adaptive mechanisms,highlighting intricate interactions among retrograde signaling,the proteasome,and nuclear transport machinery.

关键词： plastidial retrograde signal MEcPP ASK1 impα-9 TPR2