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Lycium barbarum L.-Derived miR162a Functions on Osteoporosis Through Directly Promoting Osteoblast Formation

Chunyan Gu,Xichao Yu,Xiaozhu Tang,Leilei Gong,Jingquan Tan,Yuanjiao Zhang,Huili Zheng,Ze Wang,Chenqian Zhang,Yejin Zhu,Zuojian Zhou,Heming Yu,Kai Xu,Jinao Duan,Xiaosong Gu,Ye Yang,

《工程（英文）》 doi: 10.1016/j.eng.2023.09.007

摘要： Traditional Chinese medicine (TCM) can help prevent or treat diseases; however, there are few studies on the active substances of TCM. For example, Lycium barbarum L. has been proven to be effective in treating osteoporosis for thousands of years, but its active substance remains to be unknown. Prompted by the efforts to modernize TCM, the present study focused on the novel active substance of Lycium barbarum L. to reinforce kidney essence to produce bone marrow. Illumina deep sequencing analysis and stem-loop polymerase chain reaction (PCR) assay revealed that miR162a, a Lycium barbarum L.-derived microRNA, can pass through the gastrointestinal tract to target the bone marrow in mice. Immunofluorescence staining showed that miR162a was absorbed through systemic RNA interference defective transmembrane family member 1 (SIDT1) in the stomach. Bioinformatics prediction and luciferase reporter assay identified that miR162a targeted nuclear receptor corepressor (NcoR). Alizarin red staining and micro-computed tomography (microCT) confirmed that miR162a promoted osteogenic differentiation in bone marrow mesenchymal stem cells, zebrafish, and a mouse model of osteoporosis. In addition, transgenic Nicotiana benthamiana (N. benthamiana) leaves overexpressing miR162a were developed by agrobacterium infiltration method. microCT and tartrate-resistant acid phosphatase staining confirmed that transgenic N. benthamiana leaves effectively protected against osteoporosis in mice. Our study mechanistically explains how Lycium barbarum L. improves osteoporosis and supports that Lycium barbarum L. reinforces kidney essence, thereby strengthening the bone. miR162a expressed by transgenic plants may represent a novel and safe treatment for human osteoporosis.

关键词： Traditional Chinese medicine Lycium barbarum L miR162a Osteoporosis Nuclear receptor corepressor Transgenic plants

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Nicotinic acetylcholine receptor α7 subunit: a novel therapeutic target for cardiovascular diseases

null

《医学前沿（英文）》 2012年第6卷第1期页码 35-40 doi: 10.1007/s11684-012-0171-0

摘要：

Inflammation is important in the pathogenesis and development of cardiovascular diseases. Recent studies show that vagus nerve stimulation inhibits pro-inflammatory cytokine production through “the cholinergic anti-inflammatory pathway,” more specifically via the α7 nicotinic acetylcholine receptor (α7nAChR). In the current study, the role of the cholinergic anti-inflammatory pathway during septic shock, hypertension, and myocardial infarction is reviewed, and its possible clinical implications in cardiovascular diseases are discussed.

关键词： α7 nicotinic acetylcholine receptor cardiovascular diseases baroreflex sensitivity

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Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

《医学前沿（英文）》 2015年第9卷第2期页码 134-138 doi: 10.1007/s11684-015-0396-9

摘要：

Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

关键词： targeted therapy drug resistance receptor tyrosine kinases cancer

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Special issue: innovative nuclear energy technology

《能源前沿（英文）》 2021年第15卷第4期页码 791-792 doi: 10.1007/s11708-021-0794-4

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Overcoming resistance to endocrine therapy in hormone receptor-positive human epidermal growth factorreceptor 2-negative (HR

Wenjie Zhu, Binghe Xu

《医学前沿（英文）》 2021年第15卷第2期页码 208-220 doi: 10.1007/s11684-020-0795-4

摘要： New targeted therapies have been developed to overcome resistance to endocrine therapy (ET) and improve the outcome of HR /HER2 advanced breast cancer (ABC). We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR /HER2 ABC. PUBMED and EMBASE databases were searched for eligible trials. Hazard ratios (HRs) for progression-free survival (PFS), odds ratios (ORs) for objective response rate (ORR), clinical benefit rate (CBR), and toxicity were meta-analyzed. Twenty-six studies with data on 10 347 patients were included and pooled. The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS (pooled HR= 0.547, <0.001), overall survival (pooled HR= 0.755, <0.001), and tumor response rates (ORR, pooled OR= 1.478, <0.001; CBR, pooled OR= 1.201, <0.001) with manageable toxicities (pooled OR= 3.280, <0.001). The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients. Moderate improvement in PFS (pooled HR= 0.686, <0.001) yet pronounced toxicities (pooled OR= 2.154, <0.001) were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant. Future studies are warranted to optimize the population and the dosing sequence of these available options.

关键词： endocrine-resistant HR⁺/HER2^- advanced breast cancer randomized clinical trials meta-analysis targeted therapy

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microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor

《医学前沿（英文）》 2023年第17卷第4期页码 699-713 doi: 10.1007/s11684-022-0972-8

摘要： Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%–50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

关键词： anti-CD19 chimeric antigen receptor T immunotherapy diffuse large B cell lymphoma tumor microenvironment tumor-associated macrophage metabolism

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An old issue and a new challenge for nuclear reactor safety

F. D’AURIA

《能源前沿（英文）》 2021年第15卷第4期页码 854-859 doi: 10.1007/s11708-021-0729-0

摘要： Nuclear reactor safety (NRS) and the branch accident analysis (AA) constitute proven technologies: these are based on, among the other things, long lasting research and operational experience in the area of water cooled nuclear reactors (WCNR). Large break loss of coolant accident (LBLOCA) has been, so far, the orienting scenario within AA and a basis for the design of reactors. An incomplete vision for those technologies during the last few years is as follows: Progress in fundamentals was stagnant, namely in those countries where the WCNR were designed. Weaknesses became evident, noticeably in relation to nuclear fuel under high burn-up. Best estimate plus uncertainty (BEPU) techniques were perfected and available for application. Electronic and informatics systems were in extensive use and their impact in case of accident becomes more and more un-checked (however, quite irrelevant in case of LBLOCA). The time delay between technological discoveries and applications was becoming longer. The present paper deals with the LBLOCA that is inserted into the above context. Key conclusion is that regulations need suitable modification, rather than lowering the importance and the role of LBLOCA. Moreover, strengths of emergency core cooling system (ECCS) and containment need a tight link.

关键词： large break loss of coolant accident (LBLOCA) nuclear reactor safety (NRS) licensing perspectives basis for design of water cooled nuclear reactors (WCNR)

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Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

《医学前沿（英文）》 2020年第14卷第6期页码 701-710 doi: 10.1007/s11684-020-0763-z

摘要： Abstract Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.

关键词： acute myeloid leukemia CAR T immunotherapy

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Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

《医学前沿（英文）》 2019年第13卷第1期页码 57-68 doi: 10.1007/s11684-019-0683-y

摘要：

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-g, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.

关键词： chimeric antigen receptor T cells epidermal growth factor receptor lung cancer immunotherapy tumor immunology

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Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages

LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao

《医学前沿（英文）》 2008年第2卷第2期页码 166-170 doi: 10.1007/s11684-008-0030-1

摘要： This study aims to demonstrate that blocking the receptor-interacting protein2 (Rip2) expression can decrease inflammatory cytokine production by macrophage and protect mice from endotoxin lethality. Murine Rip2 small interfering RNA (siRNA) plasmids were constructed and transfected into macrophage and Rip2 expression was detected with reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Cell proliferation was assayed with MTT. TNF-? concentration was assayed with ELISA and high-mobility group box 1 protein (HMGB1) level with semi-quantitative western blot after lipopolysaccharide (LPS) stimulation. LPS challenge was given after the plasmids were injected into mice and the survival rate was calculated. Rip2 siRNA plasmid could block the mRNA and protein expression of Rip2 and promote cell proliferation. Blocking Rip2 could attenuate LPS-induced TNF-? and HMGB1 production. The HMGB1 expression in the liver decreased to (40.21 ± 11.03) pg/g, and serum TNF-? level decreased to (300.43 ± 59.26) ng/L ( < 0.05). The survival rate of mice from endotoxemia was also improved ( < 0.05). The results demonstrate that Rip2 siRNA plasmid can block the expression of Rip2, decrease the production of TNF-? and HMGB1 and protect mice from fatal endotoxemia.

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让核技术为国家可持续发展再创辉煌

杜祥琬

《中国工程科学》 2008年第10卷第1期页码 9-11

摘要：

概述了对核科学技术发展及应用方向的认识，包括核技术与能源、核技术与医疗卫生、核分析技术、核辐射技术、宇航与航海核动力等5个方面，讨论了它们对国家可持续发展的意义。概括了核科学技术发展的三部曲及发展前景。

关键词：核科学核技术核工程可持续发展

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Reliability prediction and its validation for nuclear power units in service

Jinyuan SHI,Yong WANG

《能源前沿（英文）》 2016年第10卷第4期页码 479-488 doi: 10.1007/s11708-016-0425-7

摘要： In this paper a novel method for reliability prediction and validation of nuclear power units in service is proposed. The equivalent availability factor is used to measure the reliability, and the equivalent availability factor deducting planed outage hours from period hours and maintenance factor are used for the measurement of inherent reliability. By statistical analysis of historical reliability data, the statistical maintenance factor and the undetermined parameter in its numerical model can be determined. The numerical model based on the maintenance factor predicts the equivalent availability factor deducting planed outage hours from period hours, and the planed outage factor can be obtained by using the planned maintenance days. Using these factors, the equivalent availability factor of nuclear power units in the following 3 years can be obtained. Besides, the equivalent availability factor can be predicted by using the historical statistics of planed outage factor and the predicted equivalent availability factor deducting planed outage hours from period hours. The accuracy of the reliability prediction can be evaluated according to the comparison between the predicted and statistical equivalent availability factors. Furthermore, the reliability prediction method is validated using the nuclear power units in North American Electric Reliability Council (NERC) and China. It is found that the relative errors of the predicted equivalent availability factors for nuclear power units of NERC and China are in the range of –2.16% to 5.23% and –2.15% to 3.71%, respectively. The method proposed can effectively predict the reliability index in the following 3 years, thus providing effective reliability management and maintenance optimization methods for nuclear power units.

关键词： nuclear power units in service reliability reliability prediction equivalent availability factors

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Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis

Changlin Cao, Jingxian Gu, Jingyao Zhang

《医学前沿（英文）》 2017年第11卷第2期页码 169-177 doi: 10.1007/s11684-017-0505-z

摘要： Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation by activating the TREM-1/DAP12 pathway. This pathway is triggered by the interaction of TREM-1 with ligands or stimulation by bacterial lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be directly tested in human body fluids and well-known biomarker for infectious diseases. sTREM-1 level can be potentially used for the early diagnosis and prognosis prediction of some infectious diseases, including infectious pleural effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g., Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g., infection), and burn-related infections. sTREM-1 is a more sensitive and specific biomarker than traditional indices, such as C-reactive protein and procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a feasible biomarker for the targeted therapy and rapid and early diagnosis of infectious diseases.

关键词： soluble triggering receptor expressed on myeloid cells-1 infectious diseases diagnosis and prognosis biomarker

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中法关于核能与环境的联合研究 Feature Article

赵宪庚, 叶其蓁, Sébastien Candel, Dominique Vignon, Robert Guillaumont

《工程（英文）》 2023年第26卷第7期页码 159-172 doi: 10.1016/j.eng.2023.04.011

摘要：

本文聚焦核能的环境影响问题，将解决如下核能发电相关的主要环境问题：①控制正常运行条件下核设施的放射性排放，评估其非放射性环境影响（取水与非放射性水的排放）；②乏燃料与放射性废物的长期管理，主要是通过地质处置库处理的乏燃料或放射性废物；③防止和缓解严重核事故以及核事故的放射性释放；④改善核安全水平，以限制核能的环境影响，提升公众的核能接受度。核能的温室气体排放水平非常低，可以根据需求供应大规模、可调度电力，在此方面核能具有独特的优势。在正常运行工况下，核电站每年释放到周围公众的有效辐射剂量可以忽略不计。国际社会已经开展了大量的努力，以确定可持续管理地质处置条件下高放长寿命放射性废物的方法。过去几次严重核事故中获得的经验为核能生产相关的安全问题提供了经验，也促成了重要的安全改进，其中包括反应堆的设计和运行管理方面的改善以及事故管理指导方针的制定等。事实证明，这些经验是非常宝贵的。严重事故的环境风险已经被大幅降低，相关的规约也已经建立起来，以最大限度地减少严重核事故条件下放射性物质的释放，并避免大规模的人员疏散。还需要继续采取措施，改善反应堆的安全性，提升核工业与核监管机构的透明度，以进一步降低核能的环境影响。

关键词：核能环境影响放射性废物管理严重核事故核安全

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中国核电的可持续发展

赵仁恺

《中国工程科学》 2000年第2卷第10期页码 33-41

摘要：

文章阐述了核能是可持续发展的能源，是我国未来国民经济发展的重要支柱的论点，分析了国际核电发展现状，我国核电发展的方针政策、技术路线、现状以及共同关心的几个问题：铀资源问题、核安全问题、核废料问题和核电国产化问题，展望了我国核电发展的前景，并提出了建议：我国核电站应以现有压水堆核电站为基础，实现国产化、标准化、系列化；快中子增殖堆在我国核电建设中占有十分重要的地位，应大力支持、促进；尽快开始乏燃料后处理厂及其配套设施的建设。

关键词：核能铀资源核安全核废料国产化

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标题作者时间类型操作

Lycium barbarum L.-Derived miR162a Functions on Osteoporosis Through Directly Promoting Osteoblast Formation

Chunyan Gu,Xichao Yu,Xiaozhu Tang,Leilei Gong,Jingquan Tan,Yuanjiao Zhang,Huili Zheng,Ze Wang,Chenqian Zhang,Yejin Zhu,Zuojian Zhou,Heming Yu,Kai Xu,Jinao Duan,Xiaosong Gu,Ye Yang,

期刊论文

Nicotinic acetylcholine receptor α7 subunit: a novel therapeutic target for cardiovascular diseases

null

期刊论文

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

期刊论文

Special issue: innovative nuclear energy technology

期刊论文

Overcoming resistance to endocrine therapy in hormone receptor-positive human epidermal growth factorreceptor 2-negative (HR

Wenjie Zhu, Binghe Xu

期刊论文