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FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury

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Military Medical research 2024年第4期11卷 521-542页

作者： Mi Zhou Yang-Wu-Yue Liu Yu-Hang He Jing-Yu Zhang Hao Guo Hao Wang Jia-Kui Ren Yi-Xun Su Teng Yang Jia-Bo Li Wen-Hui He Peng-Jiao Ma Man-Tian Mi Shuang-Shuang Dai Department of biochemistry and molecular biology School of Basic MedicineArmy Medical UniversityChongqing 400038China research center for Nutrition and Food Safety Chongqing Key Laboratory of Nutrition and HealthInstitute of Military Preventive MedicineArmy Medical UniversityChongqing 400038China Department of Neurosurgery Daping HospitalArmy Medical UniversityChongqing 400042China Department of Trauma and Emergency Southwest HospitalArmy Medical UniversityChongqing 400038China Department of Histology and Embryology Chongqing Key Laboratory of NeurobiologyBrain and Intelligence Research Key Suyixun Laboratory of Chongqing Education CommissionArmy Medical UniversityChongqing 400038China research center Seventh Affiliated Hospital of Sun Yat-Sen UniversityShenzhen 518107GuangdongChina

Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly ***:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral *** also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout ***:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse *** of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced *** the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high *** the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression afte

关键词： Traumatic brain injury(TBI) Neutrophil Forkhead box protein O1(FOXO1) Acute stage Chronic stage

On-site rapid detection of multiple pesticide residues in tea leaves by lateral flow immunoassay

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Journal of Pharmaceutical Analysis 2024年第2期14卷 276-283页

作者： Junxia Gao Tianyi Zhang Yihua Fang Ying Zhao Mei Yang Li Zhao Ye Li Jun Huang Guonian Zhu Yirong Guo Institute of Pesticide and Environmental Toxicology Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang ProvinceMinistry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and InsectsZhejiang UniversityHangzhou310058China Tea research Institute Chinese Academy of Agricultural SciencesKey Laboratory of Tea Biology and Resources UtilizationMinistry of AgricultureHangzhou310008China Shanghai Agricultural Technology Extension Service center Shanghai201103China School of Biological and Chemical Engineering Zhejiang University of Science and TechnologyHangzhou311200China

The application of pesticides (mostly insecticides and fungicides) during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea. Thus, it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits. However, the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues. In this study, nine types of lateral flow immunochromatographic strips (LFICSs) were developed to detect the pesticides of interest (fenpropathrin, chlorpyrifos, imidacloprid, thiamethoxam, acetamiprid, carbendazim, chlorothalonil, pyraclostrobin, and iprodione). To reduce the interference of tea substrates on the assay sensitivity, the pretreatment conditions for tea samples, including the extraction solvent, extraction time, and purification agent, were optimized for the simultaneous detection of these pesticides. The entire testing procedure (including pretreatment and detection) could be completed within 30 min. The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.

关键词： Lateral flow immunoassay Rapid detection Pesticide multi-residue Tea matrix Sample rapid pretreatment

Comparative analysis between single-train passing and double-train intersection in a tunnel

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第5期25卷 429-442页

作者： Jianming DU Qian FANG Xuan ZHANG Hualao WANG Bridge and Tunnel research center Research Institute of Highway Ministry of TransportBeijing 100088China Tunnel and Underground Engineering research center of Ministry of Education Beijing Jiaotong UniversityBeijing 00044China

Aerodynamic pressure significantly impacts the scientific evaluation of tunnel service *** aerodynamic pressure of two trains running in a double-track tunnel is considerably more complicated than that of a single *** used the numerical method to investigate the difference in aerodynamic pressure between a single train and two trains running in a double-track ***,the numerical method was verified by comparing the results of numerical simulation and on-site ***,the characteristics of aerodynamic pressure were ***,the influence of various train-tunnel factors on the characteristics of aerodynamic pressure was *** results show that the aerodynamic pressure variation can be divided into stage I:irregular pressure fluctuations before the train tail leaves the tunnel exit,and stage II:periodic pressure declines after the train tail leaves the tunnel *** addition,the aerodynamic pressure simultaneously jumps positively or drops negatively for a single train or two trains running in double-track tunnel *** pressure amplitude in the two-train case is higher than that for a single *** maximum positive peak pressure difference(P_(STP))and maximum negative peak pressure difference(P_(STN))increase as train speed rises to the power from 2.256 to 2.930 in stage *** P_(STP) and P_(STN) first increase and then decrease with the increase of tunnel length in stage *** P_(STP) and P_(STN) increase as the blockage ratio rises to the power from 2.032 to 2.798 in stages I and II.

关键词： Railway tunnel Aerodynamic effect Pressure characteristic Train speed Tunnel length Blockage ratio

RNA m^(6)A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

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Genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han Andrew Small Jianhuang Xue Huilin Huang Hengyou Weng Rui Su Brandon Tan Chao Shen Wei Li Zhicong Zhao Ying Qing Xi Qin Kitty Wang Keith Leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian Xiaolan Deng Jianjun Chen Zhenhua Chen Department of Systems biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella Graduate School of Biological Sciences Beckman Research Institute of City of HopeDuarteCA 91010USA Gehr Family center for Leukemia research City of HopeDuarteCA 91010USA Sun Yat-sen University Cancer center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China Guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China Department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA Department of biochemistry and molecular biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China School of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including *** was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to ***,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in ***,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature ***,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of ***2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in ***,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词： AML miR-126 N^(6)-methyladenosine Pre-miRNA maturation YTHDF2

Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3680-3696页

作者： Yunkun Li Xiaoding Shen Haitao Ding Yuxin Zhang Dayi Pan Liping Su Yahui Wu Zaixiang Fang Jie Zhoua Qiyong Gong Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Functional and molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune ***,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)*** cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen ***,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating *** a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

关键词： Dendritic prodrug Enhanced penetration Metabolic intervention Cancer-associated fibroblasts Immunogenic cell death Chemotherapy Immunotherapy Immune microenvironment reconstitution

CSCO guidelines for colorectal cancer version 2024:Updates and discussions

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Chinese Journal of Cancer research 2024年第3期36卷 233-239页

作者： Liubo Chen Hanguang Hu Ying Yuan Shanshan Weng Department of Medical Oncology(Key Laboratory of Cancer Prevention and Intervention China National Ministry of EducationKey Laboratory of Molecular Biology in Medical SciencesZhejiang ProvinceChina)the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Zhejiang Provincial Clinical research center for CANCER Hangzhou 310009China Cancer center Zhejiang UniversityHangzhou 310058China

According to the latest global cancer statistics,colorectal cancer(CRC)is the most common malignancy of the digestive system and the second most lethal among all cancer types(1).In China,CRC is the second most prevalent cancer,following only after lung cancer(2).The first version of the Chinese Society of Clinical Oncology(CSCO)guideline was launched in 2017 and has been updated annually based on the latest findings of clinical research,drug accessibility and expert consensus(3-8).Here,we present the main updates of the 2024 version compared to the 2023 version.

关键词： CSCO colorectal cancer

Unveiling a novel entry gate:Insect foregut as an alternative infection route for fungal entomopathogens

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The Innovation 2024年第4期5卷 42-53,41页

作者： Yiling Lai Weilu Zheng Yitong Zheng Haiquan Lu Shuang Qu Lili Wang Muwang Li Sibao Wang New Cornerstone Science Laboratory CAS Key Laboratory of Insect Developmental and Evolutionary BiologyCAS Center for Excellence in Molecular Plant SciencesChinese Academy of Sciences(CAS)Shanghai 200032China CAS center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijing 100049China Sericultural research Institute Jiangsu University of Science and TechnologyZhenjiang 212000China

Insects and their natural microbial pathogens are intertwined in constant arms races,with pathogens continually seeking entry into susceptible hosts through distinct *** fungi are primarily believed to infect host insects through external cuticle ***,we report a new variety,Beauveria bassiana ***(Bbm),that can infect insects through the previously unrecognized *** routes of infection significantly accelerate insect *** pH-responsive transcription factor PacC in Bbm exhibits rapid upregulation and efficient proteolytic processing via PalC for alkaline adaptation in the *** of PalC is regulated by the adjacent downstream gene *** to non-enteropathogenic strains such as ARSEF252,Aia in Bbm lacks a 249-bp fragment,resulting in its enhanced alkaline-induced *** induction promotes PalC upregulation and facilitates PacC *** the active form of BbmPacC in ARSEF252 enables intestinal *** study uncovers the pH-responsive Aia-PalC-PacC cascade enhancing fungal alkaline tolerance for intestinal infection,laying the foundation for developing a new generation of fungal insecticides to control destructive insect pests.

关键词： alkaline seeking enable

Staying hungry:a roadmap to harnessing central regulators of symbiotic nitrogen fixation under fluctuating nitrogen availability

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aBIOTECH 2024年第1期5卷 107-113页

作者： Lijin Qiao Jieshun Lin Takuya Suzaki Pengbo Liang State Key Laboratory of Plant Environmental Resilience College of Biological SciencesChina Agricultural UniversityBeijingChina MOA Key Laboratory of Soil Microbiology Rhizobium Research CenterChina Agricultural UniversityBeijingChina Department of molecular biology and Genetics Aarhus UniversityAarhusDenmark Faculty of Life and Environmental Sciences University of TsukubaTsukubaIbarakiJapan Tsukuba Plant-Innovation research center University of TsukubaTsukubaIbarakiJapan

Legumes have evolved specific inventions to enhance nitrogen(N)acquisition by establishing symbiotic interactions with N-fixing rhizobial *** symbiotic N fixation is energetically costly,legumes have developed sophisticated mechanisms to ensure carbon-nitrogen balance,in a variable environment,both locally and at the whole plant level,by monitoring nodule number,nodule development,and nodular nitrogenase activity,as well as controlling nodule *** of the autoregulation of nodulation and regulation of nodulation by nodule inception(NIN)and NIN-LIKE PROTEINs(NLPs)have provided great insights into the genetic mechanisms underlying the nitrateinduced regulation of root nodulation for adapting to N availability in the ***,many aspects of N-induced pleiotropic regulation remain to be fully explained,such as N-triggered senescence in mature *** et *** that this process is governed by a transcriptional network regulated by NAC-type transcription *** and dissection of these soybean nitrogenassociated NAPs(SNAPs)transcription factor-mastered networks have yielded a roadmap for exploring how legumes rewire nodule functions across a range of N levels,laying the foundation for enhancing the growth of N-deprived crops in agricultural settings.

关键词： Symbiotic nitrogen fixation N-adapted nodulation Nodule senescence NIN NLPs SNAPs

Aldo-keto reductases:Role in cancer development and theranostics

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Oncology research 2024年第8期32卷 1287-1308页

作者： SIDDAVARAM NAGINI PRATHAP REDDY KALLAMADI KRANTHI KIRAN KISHORE TANAGALA GEEREDDY BHANUPRAKASH REDDY World Neem Organization Mumbai400101India Department of biochemistry ICMR-National Institute of NutritionHyderabad500007India Department of Pathology and Cell biology Columbia University Irving Medical CenterNew York10032USA

Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various *** are aberrantly expressed in a wide range of malignant *** expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to *** have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and *** of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for *** classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical *** AKR inhibitors from natural sources also exhibit anticancer *** molecule inhibitors targeting speciﬁc AKR isoforms have shown promise in preclinical *** inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to *** this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug ***,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.

关键词： Aldo-keto reductases(AKRs) Aldo-keto reductase(AKR)inhibitors Cancer Drug-resistance Xenobiotics