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Chinese Journal of Natural Medicines 2024年第1期22卷 1-3页

作者： ZHANG Lele lu jinjian School of Basic Medical Sciences Chengdu UniversityChengdu 610106China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical ***,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.

关键词： Unresectable hepatocellular carcinoma Combination strategies Immunotherapy PD-1/PD-L1 Natural products

Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells

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Chinese Journal of Natural Medicines 2023年第11期21卷 842-851页

作者： HE Xinyu FU Jiarui LYU Wenyu HUANG Muyang MO Jianshan CHENG Yaxin XU Yulian ZHENG Lijun ZHANG Xiaolei QI lu ZHANG Lele ZHENG Ying HUANG Mingqing NI Lin lu jinjian State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China College of Plant Protection Fujian Agriculture and Forestry UniversityFuzhou 350002China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation Guangdong Key Laboratory of Chiral Molecule and Drug DiscoverySchool of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhou 510006China College of Life Sciences China Jiliang UniversityHangzhou 310018China Department of Pharmacy Fujian Medical University Union HospitalFuzhou 350100China Department of Pathology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China School of Basic Medical Sciences Chengdu UniversityChengdu 610106China College of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350003China Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research University of MacaoMacao 999078China

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 μmol·L^(−1), respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD’s role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.

关键词： Cancer Natural products Bulbocodin D Bulbocodin C STAT3 ERK

Engineering biomimetic nanosystem targeting multiple tumor radioresistance hallmarks for enhanced radiotherapy

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Science China(Life Sciences) 2024年第7期67卷 1398-1412页

作者： Shuxiang Wang Hongmei Cao Cui-Cui Zhao Qian Wang Dianyu Wang jinjian Liu Lijun Yang Jianfeng Liu State Key Laboratory of Advanced Medical Materials and Devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear MedicineKey Laboratory of Radiopharmacokinetics for Innovative DrugsTianjin Institutes of Health ScienceInstitute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy(Tianjin)Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationTianjin 300060China

Tumor cells establish a robust self-defense system characterized by hypoxia,antioxidant overexpression,DNA damage repair,and so forth to resist *** one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under ***,we herein developed an engineering biomimetic nanosystem(M@HHPt)masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens(O_(2))and cisplatin prodrugs(Pt(Ⅳ))to target multiple tumor radioresistance hallmarks for enhanced *** administration,M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O_(2)and Pt(Ⅳ).O_(2)introduction induced hypoxia alleviation cooperated with Pt(Ⅳ)reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative ***,the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA ***,M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7%.Overall,this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.

关键词： biomimetic nanosystem hypoxia alleviation glutathione consumption oxidative stress amplification DNA damage fixation radiosensitization

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Tuning the exciton binding energy of covalent organic frameworks for efficient photocatalysis

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Chinese Chemical Letters 2024年第2期35卷 577-583页

作者： Zhangjie Gu Zhen Shan Yulan Wang jinjian Wang Tongtong Liu Xiaoming Li Zhiyang Yu Jian Su Gen Zhang Key Laboratory for Soft Chemistry and Functional Materials of Ministry of Education School of Chemistry and Chemical EngineeringNanjing University of Science and TechnologyNanjing 210094China State Key Laboratory of Photocatalysis on Energy and Environment College of ChemistryFuzhou UniversityFuzhou 350002China MIIT Key Laboratory of Advanced Display Material and Devices School of Materials Science and EngineeringNanjing University of Science and TechnologyNanjing 210094China Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China

Owing to the large exciton binding energy(>100 meV)of most organic materials,the process of exciton dissociation into free electrons and holes is seriously hindered,which plays a key role in the photocatalytic *** this study,a series of chalcogen(S,Se)-substituted mesoporous covalent organic frameworks(COFs)have been synthesized for enhanced photocatalytic organic *** measurements indicate that the introduction of semi-metallic Se atom and the enlargement of conjugation degree can not only reduce the exciton binding energy accelerating the charge separation,but also reduce the band gap of *** a result,the COF-NUST-36 with the lowest exciton binding energy(39.5 meV)shows the highest photocatalytic performance for selective oxidation of amines(up to 98%*** 97.5%Sel.).This work provides a feasible method for designing COFs with high photocatalytic activity by adjusting exciton binding energy.

关键词： Covalent organic frameworks Exciton binding energy Atom substitution Extended conjugation Photocatalysis

Interaction between internal solitary waves and the seafloor in the deep sea

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Deep Underground Science and Engineering 2024年第2期3卷 149-162页

作者： Zhuangcai Tian jinjian Huang Jiaming Xiang Shaotong Zhang Jinran Wu Xiaolei Liu Tingting luo Jianhua Yue State Key Laboratory of Intelligent Construction and Healthy Operation and Maintenance of Deep Underground Engineering China University of Mining and TechnologyXuzhouChina Research Center for Deep Ocean Science and Underwater Engineering China University of Mining and TechnologyXuzhouChina Frontiers Science Center for Deep Ocean Multispheres and Earth System Key Lab of Submarine Geosciences and Prospecting TechniquesMOECollege of Marine GeosciencesOcean University of ChinaQingdaoChina Institute for Learning Sciences&Teacher Education Australian Catholic UniversityBrisbaneQueenslandAustralia Shandong Provincial Key Laboratory of Marine Environment and Geological Engineering Ocean University of ChinaQingdaoChina Department of Chemical and Biomolecular Engineering National University of SingaporeSingaporeSingapore School of Resources and Geosciences China University of Mining and TechnologyXuzhouChina

Internal solitary wave(ISW),as a typical marine dynamic process in the deep sea,widely exists in oceans and marginal seas *** interaction between ISW and the seafloor mainly occurs in the bottom boundary *** the seabed boundary layer of the deep sea,ISW is the most important dynamic *** study analyzed the current status,hotspots,and frontiers of research on the interaction between ISW and the seafloor by *** on the action of ISW on the seabed,such as transformation and reaction,a large amount of research work and results were systematically analyzed and *** this basis,this study analyzed the wave–wave interaction and interaction between ISW and the bedform or slope of the seabed,which provided a new perspective for an in‐depth understanding of the interaction between ISW and the ***,the latest research results of the bottom boundary layer and marine engineering stability by ISW were introduced,and the unresolved problems in the current research work were *** study provides a valuable reference for further research on the hazards of ISW to marine engineering geology.

关键词： bottom boundary layer interaction internal solitary wave seafloor sediment

Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp.c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1a/XBP-1s axis and JNK signaling

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Acta Pharmaceutica Sinica B 2024年第1期14卷 304-318页

作者： Yong Rao Rui Su Chenyan Wu Xingxing Chai jinjian Li Guanyu Yang Junjie Wu Tingting Fu Zhongping Jiang Zhikai Guo Congjun Xu Ling Huang Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikou 570200China Hainan Key Laboratory of Tropical Microbe Resources Institute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural Sciences&Key Laboratory for Biology and Genetic Resources of Tropical Crops of Hainan ProvinceHainan Institute for Tropical Agricultural ResourcesHaikou 571101China School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510275China Laboratory Animal Center of Guangdong Medical University Dongguan 523808China

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease(MAFLD).However,there are few reported lipotoxicity ***,we identified a natural anti-lipotoxicity candidate,HN-001,from the marine fungus Aspergillus ***-001 dose-and time-dependently reversed palmitic acid(PA)-induced hepatocyte *** protection was associated with IRE-1a-mediated XBP-1 splicing inhibition,which resulted in suppression of XBP-1s nuclear translocation and transcriptional *** of XBP-1s attenuated lipotoxicity,but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown ***,the ER stress and lipotoxicity amelioration was associated with *** HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity,reduced lysophosphatidylcholine(LPC)level,subsequently ameliorated *** contrast,overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of ***,HN-001 treatment suppressed the downstream pro-apoptotic JNK *** vivo,chronic administration of HN-001(i.p.)in mice alleviated all manifestations of MAFLD,including hepatic steatosis,liver injury,inflammation,and *** effects were correlated with PLA2/IRE-1a/XBP-1s axis and JNK signaling *** data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity,and provide a natural structural basis for developing anti-MAFLD candidates.

关键词： Lipotoxicity MAFLD ER stress IRE-1a XBP-1s JNK PLA2

Neuroprotective effect of Naochuxue prescription (脑出血方) on intracerebral hemorrhage: inhibition of autophagy via downregulating high mobility group box-1

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Journal of Traditional Chinese Medicine 2024年

作者： JIN Hong WANG Xinna WANG Ruonan LI jinjian YU Junchao ZHAO Dexi ZHAI lu Department of Encephalopathy the Affiliated Hospital of Changchun University of Chinese Medicine College of Nursing Changchun University of Chinese Medicine College of Chinese Medicine Changchun University of Chinese Medicine Research Center of Traditional Chinese Medicine the First Affiliated Hospital of Changchun University of Chinese Medicine

OBJECTIVE: To determine the molecular mechanisms underlying the neuroprotective effects of Naochuxue prescription (脑出血方，NCXP) in rats with intracerebral hemorrhage (ICH). METHODS: Sprague–Dawley rats were injected with collagenase to generate ICH models， which were then randomly divided into six groups， including control， sham， model， and three intervention groups. The intervention groups received different doses of NCXP (0.13， 0.26， and 0.52 g/kg) daily for 10 d. High-performance liquid chromatography (HPLC) was used to analyze the chemical characteristics of NCXP. The neurobehavioral outcomes of the rats were evaluated using neurological deficit scores (Zea Longa 5) and the corner turn test. Pathomorphological changes in perihematomal tissues after ICH were observed using hematoxylin and eosin staining. Immunohistochemistry (IHC) was used to detect the inflammation expression of interleukin 6 (IL-6) and toll-like receptor 4 (TLR4). High mobility group box-1 (HMGB1)， Beclin1， microtubule-associated protein 1 light chain 3 beta (LC3)， and sequestosome 1 (p62) were detected using real-time quantitative polymerase chain reaction and Western blotting in perihematomal tissues. RESULTS: HPLC showed that the NCXP had good stability. Rats with ICH had severe neurological function deficits compared to the control group. IHC results showed that NCXP significantly downregulated the expression of the inflammatory proteins IL-6 and TLR4. ICH rats treated with NCXP showed less neurological injury than the model group， accompanied by a significantly decreased expression of HMGB1， Beclin1， and LC3 and an increased expression of p62. CONCluSIONS: The neuroprotective effect of NCXP alleviated inflammation and autophagy possibly by downregulating HMGB1 expression. However， further research on the signaling pathways is required to verify this hypothesis.

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基于深度学习的超大直径盾构姿态预测研究

中南大学学报（自然科学版） 2024年第4期55卷 1477-1491页

作者：丰土根胡锦健张箭河海大学岩土力学与堤坝工程教育部重点实验室江苏南京210098

传统的盾构姿态纠偏措施多是在盾构机实际轴线已经偏离设计轴线之后采取的被动控制措施,具有一定的滞后性,而盾构姿态纠偏不及时会给施工过程和完成后的隧道本身带来严重的危害。为了准确预测盾构姿态偏差,为提前纠偏提供决策支持,本文... 详细信息

传统的盾构姿态纠偏措施多是在盾构机实际轴线已经偏离设计轴线之后采取的被动控制措施,具有一定的滞后性,而盾构姿态纠偏不及时会给施工过程和完成后的隧道本身带来严重的危害。为了准确预测盾构姿态偏差,为提前纠偏提供决策支持,本文依托江阴—靖江长江隧道超大直径盾构施工项目,提出一种基于CNN-EMD-LSTM的深度学习模型,该模型既能捕捉时间序列的维度特征和时变特征,又能提高盾构姿态数据分解重构方法的预测精度;通过消融实验对CNN-EMD-LSTM模型中每个部分的重要性进行探讨,并对CNN-EMD-LSTM模型在不同窗口长度、不同滑动步长下的预测效果进行对比。研究结果表明:CNN-EMD-LSTM模型对超大直径盾构姿态的预测效果较好;可以通过调节不同推进区间的压力进行盾构姿态纠偏;CNN-EMD-LSTM模型中各个部分按重要性从大到小排序依次为EMD、CNN、LSTM;窗口长度过大或过小都会增大模型预测误差,而滑动步长越小模型的预测效果越好。

关键词：超大直径盾构姿态预测姿态纠偏消融实验 CNN-EMD-LSTM

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中药药理规范研究的思考

世界科学技术-中医药现代化 2019年第9期21卷 1846-1854页

作者：汪选斌陆金健湖北医药学院附属人民医院生物医药研究院湖北医药学院武当特色中药研究湖北省重点实验室十堰442000 澳门大学中华医药研究院中药质量研究国家重点实验室澳门特别行政区999078

用现代科学技术与方法对中药的药效、活性成分及作用机制进行研究始于上世纪20年代,从最初采用经典的植物化学模式对单味药进行研究,逐渐拓展到对药性理论、中药复方、配伍规律、治法治则及中医药理论的探讨,希望揭示中医药防治疾病的... 详细信息

用现代科学技术与方法对中药的药效、活性成分及作用机制进行研究始于上世纪20年代,从最初采用经典的植物化学模式对单味药进行研究,逐渐拓展到对药性理论、中药复方、配伍规律、治法治则及中医药理论的探讨,希望揭示中医药防治疾病的科学内涵,实现指导临床合理安全用药、发现新药、丰富和发展中医药理论的作用。近一个世纪以来,中药药理研究在理论、方法和技术上不规范,虽然取得了重要进展和大量研究成果,但也存在许多亟待解决的科学问题。本文试通过系统地梳理中药药理研究的成功经验和存在的问题,提出中药药理规范研究的定义,及其两个创新(思想创新和理论创新)和两个规范(方法规范和技术规范)。中药药理规范研究是创新前提下的规范以及规范基础上的创新辩证统一体,是创新-规范-再创新的不断循环发展。中药药理规范研究的提出希望能推动中药药理学学科向着更加规范、合理、科学的方向发展。

关键词：中药药理学规范研究思考 DNA模型

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预警装备组网协同探测预案设计流程研究

现代雷达 2020年第12期42卷 24-29页

作者：周芬吕金建张翼空军预警学院武汉430019 解放军95028部队武汉430000

针对资源灵活管控和体系效能提升的双重需求,基于组网协同探测预案设计的概念,文中从理论基础、核心要义、关键思路和最终目的四个角度剖析了预案设计的内涵,提出了"纵向分层+横向分解"的预案设计流程,并对流程中每个环节的实现过程进... 详细信息

针对资源灵活管控和体系效能提升的双重需求,基于组网协同探测预案设计的概念,文中从理论基础、核心要义、关键思路和最终目的四个角度剖析了预案设计的内涵,提出了"纵向分层+横向分解"的预案设计流程,并对流程中每个环节的实现过程进行了具体阐述,最后结合典型反导预警场景下的设计实例验证了流程的有效性。研究成果为预警装备组网协同探测预案的制作提供了技术支撑和方法指导。

关键词：组网协同探测预案设计认知决策粒度分层