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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

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Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis

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Asian Journal of Pharmaceutical Sciences 2024年第3期19卷 131-145页

作者： Rui Wang Tongyao Liu Xinhong Li Enhao Lu Yiting Chen Kuankuan Luo Tao Wang Xueli Huang Zhiwen Zhang Shilin Du Xianyi Sha Key Laboratory of Smart Drug Delivery(Ministry of Education) Institutes of Integrative MedicineDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China department of Emergency medicine Shanghai Geriatric Medical CenterShanghai 201104China department of Emergency medicine Zhongshan HospitalFudan UniversityShanghai 200032China

Flare and multiple recurrences pose significant challenges in gouty *** treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent *** should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis,calling for therapeutic systems to achieve these two goals *** this study,we propose a biomimetic integrated nanozyme,HMPB-Pt@MM,comprising platinum nanozyme and hollow Prussian *** demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory ***,it rapidly targets inflamed ankles through the camouflage of macrophage ***,HMPB-Pt@MM exhibits urate oxidase-like capabilities,continuously metabolizing locally elevated uric acid concentrations,ultimately inhibiting multiple recurrences of gouty *** summary,HMPB-Pt@MM integrates ROS clearance with uric acid metabolism,offering a promising platform for the treatment of gouty arthritis.

关键词： Gouty arthritis Inflammation Nanozyme Platinum Prussian blue

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Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

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Chinese Journal of integrative medicine 2024年第6期30卷 515-524页

作者： CAO Liu-jing LIU Li-ya CHEN You-qin HAN Yu-ying WEI Li-hui YAO Meng-ying FANG Yi WU Mei-zhu CHENG Ying Thomas J.Sferra LIU Hui-xin LI Li PENG Jun SHEN A-ling Clinical Research Institute the Second Affiliated Hospital&Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhou350122China Fujian Key Laboratory of integrative medicine in Geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China department of Pediatrics Case Western Reserve University School of MedicineUH Rainbow Babies and Children’s HospitalClevelandOH44106USA Innovation and Transformation Center Fujian University of Traditional Chinese MedicineFuzhou350122China department of Health Management Fujian Provincial HospitalShengli Clinical College of Fujian Medical UniversityFuzhou000000China

ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) *** polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in *** treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

关键词： colorectal cancer Pien Tze Huang Chinese medicine partner of NOB1 proliferation p53/p21 pathway

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Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

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World Journal of Diabetes 2024年第3期15卷 502-518页

作者： Zi-Ang Ma Li-Xin Wang Hui Zhang Han-Zhou Li Li Dong Qing-Hai Wang Yuan-Song Wang Bao-ChaoPan Shu-Fang Zhang Huan-Tian Cui Shu-Quan Lv Graduate School Hebei University of Chinese MedicineShijiazhuang 050000Hebei ProvinceChina department of Endocrinology Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese MedicineCangzhou 061000Hebei ProvinceChina School of integrative medicine Tianjin University of Traditional Chinese MedicineTianjin 300000China The First School of Clinical medicine Yunnan University of Traditional Chinese MedicineKunming 065000Yunnan ProvinceChina department of Endocrinology Hebei Cangzhou Hospital of Integrative MedicineCangzhou 061000Hebei ProvinceChina

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many ***,the protective mechanism of JPGS in treating DN remains *** To evaluate the therapeutic effects and the possible mechanism of JPGS on *** We first evaluated the therapeutic potential of JPGS on a DN mouse *** then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted ***,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative *** metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were *** analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS *** related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects *** experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related *** JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in ***,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

关键词： Diabetic nephropathy Jianpi Gushen Huayu Decoction Oxidative stress Inflammation Untargeted metabolomics Toll-like receptor 4/nuclear factor-kappa B/NOD-like receptor family pyrin domain containing 3 pathway c-Jun N-terminal kinase/P38-mediated apoptosis

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The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina School of integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

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Virus-like nanoparticle vaccines for inducing long-lasting immunity against infectious diseases

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National Science Review 2024年第4期11卷 13-15页

作者： Yi-Nan Zhang Sarah Auclair Jiang Zhu department of integrative Structural and Computational Biology The Scripps Research Institute department of Immunology and Microbiology The Scripps Research Institute

Prophylactic vaccines that can generate long-lasting protective immune responses are needed for many infectious diseases. Efficient vaccination requires vaccine antigens to be retained and presented to B cells in lymp...

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Peripheral Mechanism of Cancer-Induced Bone Pain

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Neuroscience Bulletin 2024年第6期40卷 815-830页

作者： Yachen Yang Wei Yang Ruofan Zhang Yanqing Wang department of integrative medicine and Neurobiology School of Basic Medical SciencesShanghai Medical CollegeInstitute of Acupuncture ResearchInstitutes of Integrative MedicineFudan UniversityShanghai200032China Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function Shanghai Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceFudan UniversityShanghai200032China Zhongshan-Fudan Joint Innovation Center Zhongshan528437China

Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone *** constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic *** present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be ***,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic ***,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root *** nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to *** peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.

关键词： Cancer-induced bone pain Peripheral mechanism Tumor microenvironment Sensory nerve Immunocytes

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Wildfire severity alters soil microbial exoenzyme production and fungal abundances in the southern Appalachian Mountains

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Pedosphere 2024年第5期34卷 865-878页

作者： Megan L.SCHILL Richard BAIRD Shawn P.BROWN Allison M.VEACH department of integrative Biology University of Texas at San Antonio Biochemistry Molecular Biology Entomology and Plant Pathology Department Mississippi State University department of Biological Sciences The University of Memphis

Climate change has increased drought frequency and duration that are exacerbated by increased temperatures globally. This effect has, and will continue,to increase fire occurrence across many regions of North America. In the southern Appalachian Mountains, wildfires with high burn severity occurred in 2016due to increased drought and human activity. To investigate the effects of burn severity on soil physicochemical properties, microbial extracellular enzyme production, and microbial abundances in a temperate region, surface soils (0–15 cm) were collected from two sites (the Great Smoky Mountains National Park in Tennessee and the Nantahala National Forest in North Carolina, USA) spanning lightly, moderately, and severely burned areas, accompanied by adjacent unburned locations that act as controls. The soil samples were collected at three time points between 2017 and 2019 (i.e., 0.5, 1, and 2.5 years post-fire)among burn severity plots. Total hydrolytic enzyme production varied over time, with severe burn plots having significantly lower enzyme production at 2.5years post-fire. Individual enzymes varied among burn severities and across time post-fire. Light burn plots showed greater carbon-specific (β-glucosidase and β-xylosidase) and phosphorus-specific (acid phosphatase) enzyme activities at 0.5 years post-fire, but this effect was transient. At 2.5 years post-fire, theβ-xylosidase and acid phosphatase activities were lower in severe or moderate burn plots relative to the controls. In contrast, the activity of nitrogen-specific enzyme leucyl aminopeptidase was the lowest in severe burn plots at 0.5 years post-fire, but was the lowest in light burn plots at 2.5 years post-fire. The fungi:bacteria ratio declined with burn severity, indicating that fungi are sensitive or less resilient to high burn severity during recovery. These results suggest that wildfires alter trajectories for soil microbial structure and function within a 2.5-year timeframe, which potentially

关键词： 16S carbon ITS nitrogen phosphorous

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Prospects and limitations of soil amendment and irrigation techniques for the water-saving public urban greenery and ephemeral weed management in the sandy soils of the United Arab Emirates

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Journal of Arid Land 2024年第9期16卷 1288-1302页

作者： Ayesha ALAM Elke GABRIEL-NEUMANN department of integrative Agriculture College of Agriculture and Veterinary MedicineUnited Arab Emirates UniversityAl Ain 15551the United Arab Emirates ASPIRE Research Institute of Food Security in Drylands College of Agriculture and Veterinary MedicineUnited Arab Emirates UniversityAl Ain 15551the United Arab Emirates

Public urban greenery greatly contributes to the residential and tourist value of cities in the Gulf Region,but due to the hyper-arid climatic conditions,the cost of irrigation and plant maintenance is very *** strategies to reduce the monetary and ecological costs involve the cultivation of native xerophytic plantations,and/or the use of soil improvers to increase water-and nutrient-holding capacity of the sandy *** soil improvers based on mineral,organic,or synthetic materials have entered the United Arab Emirates(UAE)market in recent years,but there is considerable uncertainty about how they should best be used in combination with ornamental plant stands involving xerophytic native *** present study investigated the effect of soil amendment and deep pipe irrigation on perennial ornamental plant stands involving native plants(Tephrosia appolinea(Gel.)Link in combination with Aerva javanica(Burm.f.)*** Schult.)and native-exotic plants(*** in combination with Ruelia simplex ***)either or not topsoil and subsoil amendment with bentonite and hydrophobic sand under the irrigation water supply of less than 50%of reference evapotranspiration(ET0).After one year of cultivation,*** and ***(native ***)produced high biomass and exhibited high water use efficiency(WUE)as compared with *** and ***(native ***)combination given that no significant differences were found under the soil amendment *** stands thrived under irrigation water supply far below what is usually supplied to exotic ornamental stands in public parks of the Al Ain City,the ***,subsoil amendment in combination with deep pipe irrigation reduced the occurrence of weeds and increased the overall plant rooting *** results suggest that subsoil amendment and irrigation up to 60-80 cm depth can potentially control ephemeral weed infestation,which is a great challenge in various plant production systems of the

关键词： native and exotic plant communities competitive strength soil improvers urban plantation subsoil amendment weed management

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Vacuum-free lamination via controlled polymer adhesion for selective photogeneration and photodetection

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Carbon Energy 2024年第7期6卷 205-218页

作者： Min Soo Kim Jihyun Lim Woongsik Jang Dong Hwan Wang department of Intelligent Semiconductor Engineering Chung-Ang UniversitySeoulRepublic of Korea School of integrative Engineering Chung-Ang UniversitySeoulRepublic of Korea

This study attempts to develop a reproducible thin-film formation technique called vacuum-free(VF)lamination,which transfers thin films using elastomeric polymer-based laminating ***,by controlling the interface characteristics of the mediator based on the work of adhesion,VF lamination is successfully performed for various thicknesses(from 20 to 240 nm)of a conjugated photoactive material composed of poly[(2,6-(4,8-bis(5-(2-ethylhexyl-3-fluoro)thiophen-2-yl)-benzo[1,2-b:4,5-bʹ]dithiophene))-alt-(5,5-(1ʹ,3ʹ-di-2-thienyl-5ʹ,7ʹ-bis(2-ethylhexyl)benzo[1ʹ,2ʹ-c:4ʹ,5ʹ-cʹ]dithiophene-4,8-dione)](a polymer donor)and 2,2ʹ-((2Z,2ʹZ)-((12,13-bis(2-butyloctyl)-3,9-diundecyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2ʹʹ,3ʹʹ:4ʹ,5ʹ]thieno[2ʹ,3ʹ:4,5]pyrrolo[3,2-g]thieno[2ʹ,3ʹ:4,5]thieno[3,2-b]indole-2,10-diyl)bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile(a nonfullerene acceptor).Interestingly,the organic photovoltaic and photodetecting applications,prepared by the VF lamination process,showed superior performance compared to those of devices prepared by conventional *** is due to the overturned surface morphology,which led to enhanced charge transport ability and blocking of the externally injected ***,the reproducible VF lamination process,exploiting an adhesion-based elastomeric polymer mediator,is a promising thin-film formation technique for developing efficient next-generation organic optoelectronic materials consistent with the solution process.

关键词： conjugated nonfullerene acceptor photodetectors photovoltaics polymer vacuum-free lamination

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