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NF-κB in biology and targeted therapy:new insights and translational implications

Signal Transduction and Targeted Therapy 2024年第4期9卷 1322-1358页

作者： Qing Guo Yizi jin Xinyu Chen Xiaomin Ye Xin Shen Mingxi Lin Cheng Zeng Teng Zhou Jian Zhang Department of Medical Oncology Fudan University Shanghai Cancer CenterNo.270Dong'an RoadShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina State Key Laboratory of Oncogenes and Related Genes Renj-Med-X Stem Cell Research CenterShanghai Cancer Institute&Department of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127PR China Department of Cardiology the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan 2nd RoadGuangzhou 510080China Department of Neurology Rujin HospitalShanghai JiaoTong University Schoolof MedicineShanghaiChina

NF-κB signaling has been discovered for nearly 40 ***,NF-κB signaling was identified as a pivotal pathway in mediating inflammatory ***,with extensive and in-depth investigations,researchers have discovered that its role can be expanded to a variety of signaling mechanisms,biological processes,human diseases,and treatment *** this review,we first scrutinize the research process of NF-κB signaling,and summarize the composition,activation,and regulatory mechanism of NF-κB *** investigate the interaction of NF-κB signaling with other important pathways,including PI3K/AKT,MAPK,JAK-STAT,TGF-β,Wnt,Notch,Hedgehog,and TLR *** physiological and pathological states of NF-κB signaling,as well as its intricate involvement in inflammation,immune regulation,and tumor microenvironment,are also ***,we illustrate how NF-κB signaling is involved in a variety of human diseases,including cancers,inflammatory and autoimmune diseases,cardiovascular diseases,metabolic diseases,neurological diseases,and ***,we discuss the therapeutic approaches targeting NF-κB signaling,including IKK inhibitors,monoclonal antibodies,proteasome inhibitors,nuclear translocation inhibitors,DNA binding inhibitors,TKls,non-coding RNAs,immunotherapy,and ***,we provide an outlook for research in the field of NF-κB *** hope to present a stereoscopic,comprehensive NF-κB signaling that will inform future research and clinical practice.

关键词： PI3K/AKT diseases involvement

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Nusinersen for spinal muscular atrophy types Ⅱ and Ⅲ:a retrospective single-center study in South Korea

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World Journal of Pediatrics 2023年第5期19卷 450-459页

作者： Hui jin Shin Ji-Hoon Na Hyunjoo lee young-Mock lee Department of Pediatrics Gangnam Severance HospitalYonsei University College of Medicine211 Eonju-RoGangnam-GuSeoul135-720Korea

Background This study investigated the efficacy and safety of nusinersen,an antisense oligonucleotide,in patients with spinal muscular atrophy(SMA)types II(OMIM:253,550)or III(OMIM:253,400),including those with severe scoliosis or requiring respiratory support via mechanical *** Data from 40 patients with genetically confirmed SMA who were treated with nusinersen at our institute from March 2019 to April 2022 were retrospectively *** these,30 patients with an age of onset<3 years and not on permanent ventilation were *** and genetic characteristics were investigated,and motor function was evaluated based on the Hammersmith Functional Motor Scale-Expanded(HFMSE)*** The mean age of symptom onset was 1.2 *** patients were diagnosed with SMA type II(27/30,90%).Nusinersen was administered via computed tomography-guided or direct intrathecal injection in 87%(26/30)and 13%(4/30)of the patients,*** the 6-,14-,22-,and 26-month follow-ups,72%,71%,88%,and 86%of patients showed motor improvement,respectively,with mean changes in HFMSE scores of 2.10,2.88,4.21,and 5.29,*** analysis showed that the use of noninvasive ventilation was associated with poorer outcomes of motor *** Patients with SMA type II or III who received nusinersen treatment showed significant improvement in motor function.A longer treatment duration led to a higher number of patients with improved motor *** significant side effects of nusinersen were *** with SMA,even those with severe scoliosis or on respiratory support,can be safely treated using nusinersen.

关键词： Hammersmith Functional Motor Scale Expanded Motor function Nusinersen South Korea Spinal muscular atrophy

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Revealing the role of electrode potential micro-environments in single Mn atoms for carbon dioxide and oxygen electrolysis

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Nano Research 2024年第9期17卷 7957-7966页

作者： Pengcheng Liu anyi Liu Kaili Wang Shuai Shi Mengmeng jin jingxiu Liu Tao Qin Qian Liu Xijun Liu Jia He Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion School of Chemistry and Chemical EngineeringInstitute of New-Energy Materials and Low-Carbon TechnologiesSchool of Materials Science and EngineeringTianjin University of TechnologyTianjin 300384China School of Chemistry and Chemical Engineering and Environmental Engineering Weifang UniversityWeifang 261061China Department of Electrical Engineering and Automation Luoyang Institute of Science and TechnologyLuoyang 471023China Institute for Advanced Study Chengdu UniversityChengdu 610106China State Key Laboratory of Featured Metal Materials and Life-cycle Safety for Composite Structures Guangxi Key Laboratory of Processing for Non-ferrous Metals and Featured MaterialsSchool of ResourcesEnvironment and MaterialsGuangxi UniversityNanning 530004China

Elucidation the relationship between electrode potentials and heterogeneous electrocatalytic reactions has attracted widespread *** we construct the well-defined Mn single-atom(MnSA)catalyst with four N-coordination through a simple thermal pyrolysis preparation method to investigate the electrode potential micro-environments effect on carbon dioxide reduction reactions(CO_(2)RR)and oxygen reduction reactions(ORR).MnSA catalysts generate higher CO production Faradaic efficiency of exceeding 90%at-0.9 V for CO_(2)RR and higher H_(2)O_(2)yield from 0.1 to 0.6 V with excellent ORR *** functional theory(DFT)calculations based on constant potential models were performed to study the mechanism of MnSA on CO_(2)*** thermodynamic energy barrier of CO_(2)RR is lowest at-0.9 V *** hydrogen electrode(RHE).Similar DFT calculations on the H_(2)O_(2)yield of ORR showed that the H_(2)O_(2)yield at 0.2 V was *** study provides a reasonable explanation for the role of electrode potential micro-environments.

关键词： electrode potential micro-environments Mn single-atom catalyst carbon dioxide reduction reaction oxygen reduction reaction constant potential models

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Highly efficient ternary organic solar cells with excellent open-circuit voltage and fill factor via precisely tuning molecular stacking and morphology

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Science China Chemistry 2024年第3期67卷 963-972页

作者： Dinghong Sun Zhenyu Chen Jianfeng Zhang Wei Song jingyu Shi jintao Zhu Yuanyuan Meng Fei jin Shuncheng Yang Ziyi Ge Faculty of Electrical Engineering and Computer Science Ningbo UniversityNingbo 315211China Faculty of Material Science and Chemical Engineering Ningbo UniversityNingbo 315211China Zhejiang Provincial Engineering Research Center of Energy Optoelectronic Materials and Devices Ningbo Institute of Materials Technology&EngineeringChinese Academy of SciencesNingbo 315201China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences Beijing 100049China Department of Chemical and Environmental Engineering University of Nottingham NingboNingbo 315100China

The micro-morphology and molecular stacking play a key role in determining the charge transport process and nonradiative energy loss, thus impacting the performances of organic solar cells(OSCs). To address this issue, a non-fullerene acceptor PhC6-IC-F with alkylbenzene side-chain, possessing optimized molecular stacking, complementary absorption spectra and forming a cascade energy level alignment in the PM6:BTP-eC9 blend, is introduced as guest acceptor to improve efficiency of ternary OSCs. The bulky phenyl in the side-chain can regulate crystallinity and optimizing phase separation between receptors in ternary blend films, resulting in the optimal phase separations in the ternary films. As a result, high efficiencies of 18.33% as photovoltaic layer are obtained for PhC6-IC-F-based ternary devices with excellent fill factor(FF) of 78.92%. Impressively, the ternary system produces a significantly improved open circuit voltage(V_(oc)) of 0.857 V compared with the binary device,contributing to the reduced density of trap states and suppressed non-radiative recombination result in lower energy loss. This work demonstrates an effective approach for adjusting the aggregation, molecular packing and fine phase separation morphology to increase V_(oc) and FF, paving the way toward high-efficiency OSCs.

关键词： alkylbenzene side-chain morphology regulation ternary blends organic solar cells

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Engineering self-catabolic DNAzyme nanospheres for synergistic anticancer therapy

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Science China Chemistry 2024年第7期67卷 2412-2422页

作者： Yu Chen Yu Guo Jiaoli Wang Ruiting Liu Xiaohai Yang Kemin Wang Ying Pu Hui Shi jin Huang Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical EngineeringKey Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan ProvinceHunan UniversityChangsha 410082China National Clinical Research Center for Geriatric Disorders Department of GeriatricsXiangya HospitalCentral South UniversityChangsha 410008China

DNAzyme-based gene therapy faces some challenges including cell penetration,activity limitation,and co-delivery ***-assembled DNA nanomedicine has attracted widespread attention due to its many *** is urgent to develop a universal DNA degradation strategy for precise programmable drug ***,we reported a self-catabolic DNAzyme nanospheres(SCNS),which could simultaneously achieve cell penetration,activity enhancement,and co-delivery *** SCNS were assembled through Y-DNA stepwise hybridization with each other,which were then loaded with aptamer(Apt),doxorubicin(Dox),and zinc oxide nanoparticles(ZnO NPs).The acid-triggered dissociation of ZnO NPs leads to the generation of Zn^(2+)ions cofactors for immediately self-catabolic DNAzyme *** the disassembly of the SCNS,three types of anticancer treatments would be activated,which include Zn^(2+)involved reactive oxygen species(ROS),Dox-induced chemotherapy,and DNAzyme-based gene *** experimental results show that the nanoplatform(Apt-SCNS-Dox-ZnO)has a good tumor-killing effect and minimal side *** a smart self-driven drug delivery nanoplatform,it is anticipated to displace extraordinary potential in biomedicine and bioengineering.

关键词： DNAzyme nanosphere ZnO NPs ROS Dox anticancer therapy

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Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

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Acta Pharmaceutica Sinica B 2024年第2期14卷 821-835页

作者： Liping Bai jin Yang Siting Yu Zhongzheng Xiang Yuanyuan Zeng Meiling Shen Xiaorong Kou Qinjie Wu Changyang Gong Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor ***,RT-induced antitumor immunologic responses are sporadic and insufficient against cancer ***,we construct multifunctional self-sufficient nanoparticles(MARS) with dual-enzyme activity(GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic *** addition to limiting the Warburg effect to actualize starvation therapy,MARS catalyzes glucose to produce hydrogen peroxide(H_(2)O_(2)),which is then used in the Cu^(+)-mediated Fenton-like reaction and RT *** and chemodynamic therapy produce reactive oxygen species in the form of radical storms,which have a robust ICD impact on mobilizing the immune ***,when MARS is combined with RT,potent systemic antitumor immunity can be generated by activating antigen-presenting cells,promoting dendritic cells maturation,increasing the infiltration of cytotoxic T lymphocytes,and reprogramming the immuno suppre ssive tumor ***,the synergistic therapy of RT and MARS effectively suppresses local tumor growth,increases mouse longevity,and results in a 90% reduction in lung metastasis and postoperative ***,we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

关键词： Dual-enzyme activity Radiotherapy Chemodynamic therapy Fenton-likereaction Radical storms Immunogeniccell death Tumormicroenvironment Systemicimmunity

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Unveiling the emerging role of curcumin to alleviate ochratoxin A-induced muscle toxicity in grass carp(Ctenopharyngodon idella):in vitro and in vivo studies

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1638-1656页

作者： Piao Zhao Lin Feng Weidan Jiang Pei Wu Yang Liu Hongmei Ren Xiaowan jin Lu Zhang Haifeng Mi Xiaoqiu Zhou Animal Nutrition Institute Sichuan Agricultural UniversityChengdu 611130SichuanChina Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province Sichuan Agricultural UniversityChengdu 611130SichuanChina Key Laboratory of Animal Disease‑Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan ProvinceChengdu 611130SichuanChina Tongwei Co. Ltd.Healthy Aquaculture Key Laboratory of Sichuan ProvinceChengdu 610041SichuanChina

Background Ochratoxin A(OTA),a globally abundant and extremely hazardous pollutant,is a significant source of contamination in aquafeeds and is responsible for severe food *** developmental toxicity of OTA and the potential relieving strategy of natural products remain *** study screened the substance curcumin(Cur),which had the best effect in alleviating OTA inhibition of myoblast proliferation,from 96 natural products and investigated its effect and mechanism in reducing OTA myotoxicity in vivo and in *** A total of 720 healthy juvenile grass carp,with an initial average body weight of 11.06±0.05 g,were randomly assigned into 4 groups:the control group(without OTA and Cur),1.2 mg/kg OTA group,400 mg/kg Cur group,and 1.2 mg/kg OTA+400 mg/kg Cur *** treatment consisted of 3 replicates(180 fish)for 60 *** Firstly,we cultured,purified,and identified myoblasts using the tissue block culture *** preliminary screening and re-screening of 96 substances,we examined cell proliferation-related indicators such as cell viability and ultimately found that Cur had the best ***,Cur could alleviate OTA-inhibited myoblast differentiation and myofibrillar development-related proteins(Myo G and MYHC)in vivo and in vitro and improve the growth performance of grass ***,Cur could also promote the expression of OTA-inhibited protein synthesis-related proteins(S6K1 and TOR),which was related to the activation of the AKT/TOR signaling ***,Cur could downregulate the expression of OTA-enhanced protein degradation-related genes(murf1,foxo3a,and ub),which was related to the inhibition of the Fox O3a signaling *** In summary,our data demonstrated the effectiveness of Cur in alleviating OTA myotoxicity in vivo and in *** study confirms the rapidity,feasibility,and effectiveness of establishing a natural product screening method targeting myoblasts to alleviate fungal toxin toxicity.

关键词： Curcumin Grass carp Myotoxic Ochratoxin A Protein deposition

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Analytical Channel Modeling: From MIMO to Extra Large-Scale MIMO

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Chinese Journal of Electronics 2024年

作者： Jiachen TIAN Yu HAN Shi jin Jun ZHANG Jue WANG National Mobile Communication Research Laboratory Southeast University Jiangsu Key Laboratory of Wireless Communications Nanjing University of Posts and Telecommunications School of Information Science and Technology Nantong University

Multiple antenna technologies, from traditional multiple-input multiple-output(MIMO) to massive MIMO and the emerging extra large-scale MIMO, have consistently played a pivotal role in enhancing transmission rates by increasing the number of antennas. To guide the design of transmission strategies, channel models, especially analytical ones, are always significant tools, which can also reveal the performance improvements brought about by multiple antenna technologies. Analytical channel models have enjoyed significant success in traditional MIMO and massive MIMO systems. Nevertheless, due to the extended size of the array in an extra large-scale MIMO system, the distance between the receiver and the transmitter decreases and new channel properties, which did not manifest in massive MIMO systems, begin to kick in. To model the channel tailored for extra large-scale MIMO systems analytically, it is crucial to conduct a comprehensive review of traditional analytical MIMO channel models, which serves as a foundational step in understanding the fundamental characteristics of multi-antenna channels. In this paper, we first provide a survey on the state-of-the-art analytical MIMO channel models from the perspective of spatial correlation and signal propagation. Subsequently, we summarize the new properties of extra large-scale MIMO systems, i.e.,near-field properties and spatial non-stationarities, and their influences on analytical channel modeling. Our objective is to elucidate how these novel properties affect the analytical MIMO channel models, and ultimately facilitate the development of precise analytical channel models well-suited to the extra large-scale MIMO systems.

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Feasibility of Scaling up the Cost-Competitive and Clean Electrolytic Hydrogen Supply in China

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Engineering 2024年第8期39卷 154-165页

作者： Guangsheng Pan Wei Gu Zhongfan Gu jin Lin Suyang Zhou Zhi Wu Shuai Lu School of Electrical Engineering Southeast UniversityNanjing 210096China Department of Electrical Engineering Tsinghua UniversityBeijing 100084China

Scaling up clean hydrogen supply in the near future is critical to achieving China’s hydrogen development *** study established an electrolytic hydrogen development mechanism considering the generation mix and operation optimization of power systems with access to *** on the incremental cost principle,we quantified the provincial and national clean hydrogen production cost performance levels in *** results indicated that this mechanism could effectively reduce the production cost of clean hydrogen in most provinces,with a national average value of less than 2 USDkg1 at the 40-megaton hydrogen supply *** cooperation via power transmission lines could further reduce the production cost to 1.72 USD·kg^(-1).However,performance is affected by the potential distribution of hydrogen *** the supply side,competitiveness of the mechanism is limited to clean hydrogen production,while from the demand side,it could help electrolytic hydrogen fulfil a more significant *** study could provide a solution for the ambitious development of renewables and the hydrogen economy in China.

关键词： Low-carbon energy system Electrolytic hydrogen Renewables Cost optimization and analysis

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Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

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Zoological Research 2024年第2期45卷 367-380页

作者： Rui-Xue Jiang Nan Hu Yu-Wei Deng Long-Wei Hu Hao Gu Nan Luo jin Wen Xin-Quan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Stomatology Shanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai 200125China Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China

Osteoporosis(OP)is a prevalent metabolic bone *** drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted *** a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone *** showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone *** not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and ***,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and *** the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of *** findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening *** study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular *** their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

关键词： Osteoporosis Spermine Rac1 Zebrafish Mice

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