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The role of proteasomes in tumorigenesis

Genes & Diseases 2024年第4期11卷 155-169页

作者： Xiangyi Zhou Ruqing Xu yue wu Li Zhou Tingxiu Xiang Department of Oncology The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China

Protein homeostasis is the basis of normal life activities,and the proteasomefamily plays an extremely important function in this process.The proteasome 2os is a concentric circle structure with twoαrings and twoβrings overlapped.The proteasome 2os can perform both ATP-dependent and non-ATP-dependent ubiquitination proteasome degradation by binding to various subunits(such as 19S,11S,and 200 PA),which is performed by its active subunitβ1,β2,andβ5.The proteasome can degrade misfolded,excess proteins tomaintain homeostasis.At the same time,it can be utilized by tumors to degrade over-proliferate and unwanted proteins to support their growth.Proteasomes can affect the development of tumors from several aspects including tumor signaling pathways such as NF-kB and p53,cell cycle,immune regulation,and drug resistance.Proteasome-encoding genes have been found to be overexpressed in a variety of tumors,providing a potential novel target for cancer therapy.In addition,proteasome inhibitors such as bortezomib,carfilzomib,and ixazomib have been put into clinical application as the first-line treatment of multiple myeloma.More and more studies have shown that it also has different therapeutic effects in other tumors such as hepatocellular carcinoma,non-small cell lung cancer,glioblastoma,and neuroblastoma.However,proteasome inhibitors are not much effective due to their tolerance and singleness in other tumors.Therefore,further studies on their mechanisms of action and drug interactions are needed to investigate their therapeutic potential.

关键词： Bortezomib Cancer therapy Immunoproteasome Multiplemyeloma Proteasome 20S Proteasome inhibitor Thymoproteasom

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Refractory autoimmune hemolytic anemia in a patient with systemic lupus erythematosus and ulcerative colitis:A case report

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World Journal of Clinical Cases 2024年第13期12卷 2286-2292页

作者： Dai-Xing Chen yue wu Sui-Feng Zhang Xiao-Jun Yang Department of Digestive System Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

BACKGROUND Ulcerative colitis(UC)and systemic lupus erythematosus(SLE)are both systemic immunoreactive diseases,and their pathogenesis depends on the interaction between genes and environmental factors.There are no reports of UC with SLE in China,but six cases of SLE with UC have been reported in China.The combination of these two diseases has distinct effects on the pathogenesis of both diseases.CASE SUMMARY A female patient(30 years old)came to our hospital due to dull umbilical pain,diarrhea and mucous bloody stool in August 2018 and was diagnosed with UC.The symptoms were relieved after oral administration of mesalazine(1 g po tid)or folic acid(5 mg po qd),and the patient were fed a control diet.On June 24,2019,the patient was admitted for treatment due to anemia and tinnitus.During hospitalization,the patient had repeated low-grade fever and a progressively decreased Hb level.Blood tests revealed positive antinuclear antibody test,positive anti-dsDNA antibody,0.24 g/L C3(0.9-1.8 g/L),0.04 g/L C4(0.1-0.4 g/L),32.37 g/L immunoglobulin(8-17 g/L),and 31568.1 mg/24 h total 24-h urine protein(0-150 mg/24 h).The patient was diagnosed with SLE involving the joints,kidneys and blood system.Previously reported cases of SLE were retrieved from PubMed to characterize clinicopathological features and identify prognostic factors for SLE.CONCLUSION The patient was discharged in remission after a series of treatments,such as intravenous methylprednisolone sodium succinate,intravenous human immunoglobulin,cyclophosphamide injection,and plasma exchange.After discharge,the patient took oral prednisone acetate tablets,cyclosporine capsules,hydroxychloroquine sulfate tablets and other treatments for symptoms and was followed up regularly for 1 month,after which the patient's condition continued to improve and stabilize.

关键词： Plasma exchange Autoimmune hemolytic anemia Systemic lupus erythematosus Ulcerative colitis Case report

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Deep tectonics and seismogenic mechanisms of the seismic source zone of the Jishishan M_(s)6.2 earthquake on December 18,2023,at the northeast margin of the Tibetan Plateau

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Earth and Planetary Physics 2024年第3期8卷 514-521页

作者： Qiong Wang ShuYu Li XinYi Li yue wu PanPan Zhao Yuan Gao Key Laboratory of Earthquake Prediction Institute of Earthquake ForecastingChina Earthquake AdministrationBeijing 100036China Institute of Geophysics China Earthquake AdministrationBeijing 100081China

On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong ea

关键词： Jishishan M_(s)6.2 earthquake crustal structure anisotropy stress and strain seismogenic mechanism northeast margin of the Tibetan Plateau

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Rational design of new in situ reduction of Ni(II)catalytic system for low-cost and large-scale preparation of porous aromatic frameworks

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Carbon Energy 2024年第5期6卷 105-113页

作者： Shanshan Wang yue wu Wenxiang Zhang Hao Ren Guangshan Zhu Heping Ma School of Chemical Engineering and Technology Xi'an Jiaotong UniversityXi'anChina State Key Laboratory of Inorganic Synthesis and Preparative Chemistry College of ChemistryJilin UniversityChangchunChina College of Chemistry Northeast Normal UniversityChangchunChina

Porous aromatic framework 1(PAF-1)is an extremely representative nanoporous organic framework owing to its high stability and exceptionally high surface area.Currently,the synthesis of PAF-1 is catalyzed by the Ni(COD)2/COD/bpy system,suffering from great instability and high cost.Herein,we developed an in situ reduction of the Ni(II)catalytic system to synthesize PAF-1 in low cost and high yield.The active Ni(0)species produced from the NiCl_(2)/bpy/NaI/Mg catalyst system can effectively catalyze homocoupling of tetrakis(4-bromophenyl)methane at the room temperature to form PAF-1 with high Brunauer-Emmett-Teller(BET)-specific surface area up to 4948 m^(2) g^(−1)(Langmuir surface area,6785 m2 g−1).The possible halogen exchange and dehalogenation coupling mechanisms for this new catalytic process in PAF's synthesis are discussed in detail.The efficiency and universality of this innovative catalyst system have also been demonstrated in other PAFs'synthesis.This work provides a cheap,facile,and efficient method for scalable synthesis of PAFs and explores their application for high-pressure storage of Xe and Kr.

关键词： adsorption carbon material nickel catalysis porous aromatic framework porous organic polymer

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Hypermethylation of the ALOX12 and CBS promoters in osteoporosis:Potential biomarkers for early diagnosis

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Genes & Diseases 2024年第1期11卷 30-33页

作者： Shang Guo yue wu Weekai Chia Peichun Hsu Hongwei Wang Yunliang Wang Biao Zhong Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200023China Institute of Translational Medicine Shanghai General HospitalShanghai Jiao Tong University School of Medicine(SJTU-SM)Shanghai 200025China The University of Chicago Department of MedicineChicagoIL 60637USA Department of Neurology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450014China

As a bone-confined chronic degenerative disorder,the progression of osteoporosis is characterized by abnormal crosstalk between osteoblasts and osteoclasts,leading to an imbalance of bone remodeling in adults.1 Several studies reported that arachidonic acid ester 12 lipoxygenase(ALOX12)acts as a regulator in bone genesis by participating in the activation of the peroxisome proliferatoractivated receptor(PPARG)pathway through its reaction product.

关键词： osteoporosis diagnosis remodeling

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Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease

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General Psychiatry 2024年第1期37卷 53-63页

作者： Xingqi wu Yibing Yan Panpan Hu Lu Wang yue wu Pan wu Zhi Geng Guixian Xiao Shanshan Zhou Gongjun Ji Bensheng Qiu Ling Wei Yanghua Tian Hesheng Liu Kai Wang Department of Neurology First ffiliated Hospital of Anhui Medical UniversityHefeiAnhuiChina School of Mental Health and Psychological Sciences Anhui Medical UniversityHefeiAnhuiChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhuiChina Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health HefeiAnhuiChina Department of Psychology and Sleep Medicine The Second Affliated Hospital of Anhui Medical UniversityHefeiAnhuiChina Center for Biomedical Imaging University of Science and Technology of ChinaHefeiAnhuiChina institute of Artificial Intlligence Hefei Comprehensive National Science CenterHefeiAnhuiChina Department of Neuroscience Medical University of South CarolinaCharlestonSouth CarolinaUSA

Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD.However,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD areunknown.Aims We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.Methods In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every 13weeks.Measurements included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the hippocampus.Patients were evaluated at baseline and after follow-up.The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time.Results The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale changes.The baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up.Moreover,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)changes.Conclusions DLPFC-iTBS maybe a feasible and easy-to-implement

关键词： stimulation Alzheimer maintained

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Effect of chemical regulators on the recovery of leaf physiology,dry matter accumulation and translocation,and yield-related characteristics in winter wheat following dry-hot wind

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Journal of Integrative Agriculture 2024年第1期23卷 108-121页

作者： Yanan Xu yue wu Yan Han Jiqing Song Wenying Zhang Wei Han Binhui Liu Wenbo Bai Institute of Environment and Sustainable Development in Agriculture Chinese Academy of Agricultural SciencesBeijing 100081China Institute of Dryland Farming Research Hebei Academy of Agriculture and Forestry SciencesHengshui 053000China Shandong General Station of Agricultural Technology Extension Jinan 250100China

Dry-hot wind stress causes losses in wheat productivity in major growing regions worldwide,especially winter wheat in the Huang-Huai-Hai Plain of China,and both the occurrence and severity of such events are likely to increase with global climate change.To investigate the recovery of physiological functions and yield formation using a new noncommercial chemical regulator(NCR)following dry-hot wind stress,we conducted a three-year field experiment(2018-2021)with sprayed treatments of tap water(control),monopotassium phosphate(CKP),NCR at both the jointing and flowering stages(CFS),and NCR only at the jointing stage(FSJ)or flowering stage(FSF).The leaf physiology,biomass accumulation and translocation,grain-filling process,and yield components in winter wheat were assessed.Among the single spraying treatments,the FSJ treatment was beneficial for the accumulation of dry matter before anthesis,as well as larger increases in the maximum grain-filling rate and mean grain-filling rate.The FSF treatment performed better in maintaining a high relative chlorophyll content as indicated by the SPAD value,and a low rate of excised leaf water loss in flag leaves,promoting dry matter accumulation and the contribution to grain after anthesis,prolonging the duration of grain filling,and causing the period until the maximum grain-filling rate reached earlier.The CFS treatment was better than any other treatments in relieving the effects of dry-hot wind.The exogenous NCR treatments significantly increased grain yields by 12.45-18.20% in 2018-2019,8.89-13.82% in 2019-2020,and 8.10-9.00% in 2020-2021.The conventional measure of the CKP treatment only increased grain yield by 6.69% in 2020-2021.The CFS treatment had the greatest mitigating effect on yield loss under dry-hot wind stress,followed by the FSF and FSJ treatments,and the CKP treatment only had a minimal effect.In summary,the CFS treatment could be used as the main chemical control measure for wheat stress resistance and yield stability in areas with a high incidence of dry-

关键词： preparation stress foliar spraying grain-filling remobilization

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Genome editing of PAR2 through targeted delivery of CRISPR-Cas9 system for alleviating acute lung inflammation via ERK/NLRP3/IL-1β and NO/iNOS signalling

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1441-1456页

作者： Xin Zhuo yue wu Xiujuan Fu Jianbin Li Yuxin Xiang Xiaoyu Liang Canquan Mao Yuhong Jiang Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue damages.It is an urgent need to explore potential drug strategies for mitigating lung inflammation.Protease-activated receptor 2(PAR2)as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction.However,it has been rarely reported about the role of PAR2 in lung inflammation.This study applied CRISPR-Cas9 system encoding Cas9 and sg RNA(p Cas9-PAR2)for PAR2 knockout and fabricated an anionic human serum albuminbased nanoparticles to deliver p Cas9-PAR2 with superior inflammation-targeting efficiency and stability(TAP/p Cas9-PAR2).TAP/p Cas9-PAR2 robustly facilitated p Cas9-PAR2 to enter and transfect inflammatory cells,eliciting precise gene editing of PAR2 in vitro and in vivo.Importantly,PAR2 deficiency by TAP/p Cas9-PAR2 effectively and safely promoted macrophage polarization,suppressed proinflammatory cytokine releases and alleviated acute lung inflammation,uncovering a novel value of PAR2.It also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/p Cas9-PAR2was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/i NOS signalling.Therefore,this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.

关键词： Protease-activated receptor 2(PAR2) CRISPR-Cas9 Gene editing Inflammation Acute lung inflammation NLRP3 Nanoparticles Drug delivery

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Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

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Neural Regeneration Research 2025年第2期20卷 326-342页

作者： Yi Ji Chaoyi Yang Xuerui Pang Yibing Yan yue wu Zhi Geng Wenjie Hu Panpan Hu Xingqi wu Kai Wang Department of Neurology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhui ProvinceChina Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health HefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina Department of Psychology and Sleep Medicine The Second Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

关键词： Alzheimer’s disease amyloid deposition apoptotic mechanisms biomarker neural regeneration neurodegeneration repetitive transcranial magnetic stimulation synaptic plasticity

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Fine-mapping of a candidate gene for web blotch resistance in Arachis hypogaea L.

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Journal of Integrative Agriculture 2024年第5期23卷 1494-1506页

作者： Xiaohui wu Mengyuan Zhang Zheng Zheng Ziqi Sun Feiyan Qi Hua Liu Juan Wang Mengmeng Wang Ruifang Zhao yue wu Xiao Wang Hongfei Liu Wenzhao Dong Xinyou Zhang College of Agronomy Henan Agricultural UniversityZhengzhou 450046China Henan Academy of Agricultural Sciences/Henan Academy of Crop Molecular Breeding/Key Laboratory of Oil Crops in Huang-Huai-Hai Plain Ministry of Agriculture and Rural Affairs/Henan Provincial Key Laboratory for Oil Crop ImprovementZhengzhou 450002China The Shennong Laboratory Zhengzhou 450002China Shangqiu Academy of Agricultural and Forestry Sciences Shangqiu 476000China

Peanut(Arachis hypogaea L.)is a globally important oil crop.Web blotch is one of the most important foliar diseases affecting peanut,which results in serious yield losses worldwide.Breeding web blotch-resistant peanut varieties is the most effective and economically viable method for minimizing yield losses due to web blotch.In the current study,a bulked segregant analysis with next-generation sequencing was used to analyze an F2:3 segregating population and identify candidate loci related to web blotch resistance.Based on the fine-mapping of the candidate genomic interval using kompetitive allele-specific PCR(KASP)markers,we identified a novel web blotch resistance-related locus spanning approximately 169 kb on chromosome 16.This region included four annotated genes,of which only Arahy.35VVQ3 had a non-synonymous single nucleotide polymorphism in the coding region between the two parents.Two markers(Chr.16.12872635 and Chr.16.12966357)linked to this gene were shown to be co-segregated with the resistance of peanut web blotch by 72 randomly selected recombinant inbred lines(RIL),which could be used in marker-assisted breeding of resistant peanut varieties.

关键词： peanut web blotch bulked segregant analysis KAsP markers resistant gene

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