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Toll-like receptors in innate immunity and infectious diseases

Min-Hao WU, Ping ZHANG, Xi HUANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 385-393 doi: 10.1007/s11684-010-0600-x

摘要： The protective ability of host defense system is largely dependent on germ-line encoded pattern-recognition receptors (PRRs). These PRRs respond to a variety of exogenous pathogens or endogenous danger signals, by recognizing some highly conserved structures such as pathogen-associated molecular patterns (PAMPs) and danger/damage associated molecular patterns (DAMPs). The most studied PRRs are Toll-like receptors (TLRs). Activation of TLRs triggers production of inflammatory cytokines and type I interferons (IFNs) via myeloid differentiation primary response gene 88 (MyD88)-dependent or-independent signaling respectively, thereby modulating innate and adaptive immunity, as well as inflammatory responses. This review introduces the classification, structure, and specific ligands of TLRs, and focuses on their signal pathways and biological activities, as well as clinical relevance. These studies of TLRs in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases, including tuberculosis (TB), microbial keratitis, and hepatitis B and C.

关键词： Toll-like receptors     innate immunity     infectious disease     inflammation    

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Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the Toll-like

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

《医学前沿（英文）》 2021年 第15卷 第2期   页码 292-301 doi: 10.1007/s11684-020-0806-5

摘要： The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA+LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor- B (NF- B), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the anti-inflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and . B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, I Bα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.

关键词： bioactive hyaluronan     lipopolysaccharide     inflammatory cytokines     TLR4     human macrophages    

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Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 288-303 doi: 10.1007/s11684-015-0412-0

摘要：

Toll-like receptors (TLRs), which are found in innate immune cells, are essential mediators of rapid inflammatory responses and appropriate T-cell activation in response to infection and tissue damage. Accumulating evidence suggests that TLR signaling is involved in normal hematopoiesis and specific hematologic pathologies. Particular TLRs and their downstream signaling mediators are expressed not only in terminally differentiated innate immune cells but also in early hematopoietic progenitors. Sterile activation of TLR signaling is required to generate early embryonic hematopoietic progenitor cells. In adult animals, TLR signaling directly or indirectly promotes differentiation of myeloid cells at the expense of that of lymphoid cells and the self-renewal of hematopoietic stem cells during infection and tissue damage. Activating mutations of the MyD88 gene, which codes for a key adaptor involved in TLR signaling, are commonly detected in B-cell lymphomas and other B-cell hematopathologies. Dysregulated TLR signaling contributes to the pathogenesis of many hematopoietic disorders, including bone marrow failure, myelodysplastic syndrome, and acute myeloid leukemia. Complete elucidation of the molecular mechanisms by which TLR signaling mediates the regulation of both normal and pathogenic hematopoiesis will prove valuable to the development of targeted therapies and strategies for improved treatment of hematopoietic disorders.

关键词： TLR     MyD88     hematopoiesis     bone marrow failure     leukemia     myelodysplastic syndrome    

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Group III metabotropic glutamate receptors and drug addiction

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 445-451 doi: 10.1007/s11684-013-0291-1

摘要：

Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction. Accumulating data have demonstrated roles of ionotropic glutamate receptors and group I and II metabotropic glutamate receptors (mGluRs) in this event. Emerging evidence also identifies Gαi/o-coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as direct substrates of drugs of abuse and active regulators of drug action. Auto- and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways, respectively. These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis. In response to operant administration of common addictive drugs, such as psychostimulants (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior. As a result, a loss-of-function mutation (knockout) of individual group III receptor subtypes often promotes drug seeking. This review summarizes the data from recent studies on three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs (psychostimulants, alcohol, and opiates).

关键词： group III metabotropic glutamate receptors     cocaine     amphetamine     alcohol     opiate    

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Expression of protease-activated receptors on platelets in healthy individuals

Rui ZHU, Lin SHEN

《医学前沿（英文）》 2009年 第3卷 第2期   页码 236-239 doi: 10.1007/s11684-009-0040-7

摘要： This study aimed to investigate the expression of protease-activated receptors (PARs) on platelets in healthy individuals and preliminarily elucidate physiological functions of PARs. Thirty healthy volunteers, who did not take any anticoagulants and antiplatelet agents within 10 days before the examination, were recruited. Fasting venous blood (5 mL) was taken from the medial cubital vein in each individual and platelet-rich plasma (PRP) was prepared. The expression of PAR1 mRNA and PAR4 mRNA in PRP was determined by RT-PCR analysis. The results showed that the average levels of PAR1 mRNA and PAR4 mRNA on platelets in healthy individuals were 0.1601 ± 0.0269 and 0.1073 ± 0.0194 respectively. In combination with literature analysis, it was concluded that the thrombin signaling pathway plays a vital role in the development of hemostasis and thrombosis, and the selective PARs antagonist has the potential for extensive application in clinical practice.

关键词： protease-activated receptors     platelet    

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Implementation of a flexible Major Vacation Toll-free Program for small passenger vehicles in China

Meng XU, Ziyou GAO

《工程管理前沿（英文）》 2017年 第4卷 第4期   页码 498-499 doi: 10.15302/J-FEM-2017111

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High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

《医学前沿（英文）》 2019年 第13卷 第1期   页码 69-82 doi: 10.1007/s11684-018-0677-1

摘要：

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1157–165 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-g and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.

关键词： cytokine-activated T cells     high-affinity T cell receptor     cancer immunotherapy     TCR-CAT    

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Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced segmental and systemic analgesia

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 465-472 doi: 10.1007/s11684-016-0482-7

摘要：

Previous studies have demonstrated the effects of different afferent fibers on electroacupuncture (EA)-induced analgesia. However, contributions of functional receptors expressed on afferent fibers to the EA analgesia remain unclear. This study investigates the roles of acid-sensing ion channel 3 (ASIC3) and transient receptor potential vanilloid 1 (TRPV1) receptors in EA-induced segmental and systemic analgesia. Effects of EA at acupoint ST36 with different intensities on the C-fiber reflex and mechanical and thermal pain thresholds were measured among the ASIC3−/−, TRPV1−/−, and C57BL/6 mice. Compared with C57BL/6 mice, the ipsilateral inhibition of EA with 0.8 C-fiber threshold (0.8Tc) intensity on C-fiber reflex was markedly reduced in ASIC3−/− mice, whereas the bilateral inhibition of 1.0 and 2.0Tc EA was significantly decreased in TRPV1−/− mice. The segmental increase in pain thresholds induced by 0.3 mA EA was significantly reduced in ASIC3−/− mice, whereas the systemic enhancement of 1.0 mA EA was markedly decreased in TRPV1−/− mice. Thus, segmental analgesia of EA with lower intensity is partially mediated by ASIC3 receptor on Aβ-fiber, whereas systemic analgesia induced by EA with higher intensity is more likely induced by TRPV1 receptor on Ad- and C-fibers.

关键词： electroacupuncture     analgesia     ASIC3     TRPV1     C-fiber reflex    

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Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell

《医学前沿（英文）》 doi: 10.1007/s11684-023-1017-7

摘要： The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS3) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

关键词： single-cell RNA-seq     glioma     radial glia     primitive oligodendrocyte precursor cell     immune escape    

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Self-sacrificial templating synthesis of flower-like nickel phyllosilicates and its application as high-performance

《化学科学与工程前沿（英文）》 2022年 第16卷 第4期   页码 484-497 doi: 10.1007/s11705-021-2074-6

摘要： The nanocomposites of flower-like nickel phyllosilicate particles incorporated into epoxy resin were fabricated via an in-situ mixing process. The flower-like nickel phyllosilicate particles were firstly synthesized using a mild self-sacrificial templating method, and the morphology and lamellar structure were examined carefully. Several properties of mechanical, thermal and tribological responses of epoxy nanocomposites were performed. It was demonstrated that adequate flower-like nickel phyllosilicate particles dispersed well in the matrix, and the nanocomposites displayed enhanced tensile strength and elastic modulus but decreased elongation at break as expected. In addition, friction coefficient and wear rate were increased first and then decreased along with the particle content, and showed the lowest values at a mass fraction of 5%. Nevertheless, the incorporated flower-like nickel phyllosilicate particles resulted in the continuously increasing thermal stability of epoxy resin (EP) nanocomposites. This study revealed the giant potential of flower-like particles in preparing high-quality EP nanocomposites.

关键词： nickel phyllosilicate     flow-like structure     mechanical property     thermal stability     tribological performance    

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嵌合抗原受体和调节性T细胞——移植中人类白细胞抗原特异性免疫抑制的潜力 Review

Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa

《工程（英文）》 2022年 第10卷 第3期   页码 30-43 doi: 10.1016/j.eng.2021.10.018

摘要：

嵌合抗原受体（CAR）是基因工程领域的一项突破，它彻底改变了过继细胞疗法（ACT）领域。表达这些受体的细胞通过在合成的CAR构建体中包含抗原特异性结合区域而被重新定向到预定的靶点。程序化特异性细胞在肿瘤学领域的优势已被临床证明，与同类未修饰的细胞相比，这种细胞具有更高的准确性、效力与更少的脱靶效应。与常规T细胞（Tconvs）不同，调节性T细胞（Treg）在抑制免疫激活和调节宿主免疫反应方面发挥着重要作用。Treg 中CAR的表达被认为是治疗自身免疫和炎症性疾病、移植物抗宿主病（GVHD）和器官移植排斥反应的一种方法。在后者中，它们作为同种异体移植受者免疫耐受的介质具有巨大的潜力。然而，目前对CAR-Treg 工程的研究非常有限，并且关于治疗用途的最佳设计存在不确定性。本文综述了CAR-Treg 发展的理论基础、其对人类移植的意义、潜在的设计、安全性考虑因素，以及迄今为止CAR-Treg在移植模型中的对比。

关键词： 嵌合抗原受体（CAR）     调节性T细胞     异性免疫     CAR设计     基因编辑    

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Dispersion of “guava-like” silica/polyacrylate nanocomposite particles in polyacrylate matrix

QI Dongming, YANG Lei, WU Minghua, SHAO Jianzhong, BAO Yongzhong

《化学科学与工程前沿（英文）》 2008年 第2卷 第2期   页码 127-134 doi: 10.1007/s11705-008-0033-0

摘要： A series of “guava-like” silica/polyacrylate nanocomposite particles with close silica content and different grafting degrees were prepared via mini-emulsion polymerization using 3-(trimethoxysilyl)propyl methacrylate (TSPM) modified silica/acrylate dispersion. The silica/polyacrylate composite particles were melt-mixed with unfilled polyacrylate (PA) resin to prepare corresponding silica/polyacrylate molded composites and the dispersion mechanism of these silica particles from the “guava-like” composite particles into polyacrylate matrix was studied. It was calculated that about 110 silica particles were accumulated in the bulk of every silica/polyacrylate composite latex particle. Both the solubility tests of silica/polyacrylate composite latex particles in tetrahydrofuran (THF) and the section transmission electron microscope (TEM) micrographs of silica/polyacrylate molded composites indicated that the grafting degree of silica particles played a crucial role in the dispersion of silica/polyacrylate composite particles into the polyacrylate matrix. When the grafting degree of polyacrylate onto silica was in a moderate range (ca. 20%–70%), almost all of silica particles in these “guava-like” composite particles were dispersed into the polyacrylate matrix in a primary-particle-level. However, at a lower grafting degree, massive silica aggregations were found in molded composites because of the lack of steric protection. At a greater grafting degree (i.e., 200%), a cross-linked network was formed in the silica/polyacrylate composite particles, which prevented the dispersion of composite particles in THF and polyacrylate matrix as primary particles.

关键词： silica/polyacrylate composite     cross-linked network     –70     guava-like     TEM    

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Layer-like FAU-type zeolites: A comparative view on different preparation routes

Bastian Reiprich, Tobias Weissenberger, Wilhelm Schwieger, Alexandra Inayat

《化学科学与工程前沿（英文）》 2020年 第14卷 第2期   页码 127-142 doi: 10.1007/s11705-019-1883-3

摘要： The creation of intergrown layer-like zeolite crystals is one route to form hierarchical zeolites. Faujasite-type (FAU-type) zeolites are among the industrially most important zeolites and the implementation of hierarchical porosity is a promising way to optimise their catalytic and adsorptive performance. After a short general survey into routes for the preparation of hierarchical pore systems in FAU, we will review the currently existing strategies for the synthesis of FAU with layer-like morphology. Those strategies are mainly based on the presence of morphology modifying agents in the synthesis mixture. However, a very recent approach is the synthesis of layer-like FAU-type zeolite crystals assembled in an intergrown manner in the absence of such additives, just by finely adjusting the crystallization temperature. This additive-free preparation route for layer-like FAU, which appears very attractive from an ecological as well as economic point of view, is highlighted in this review. Concluding, a comparison, including powder X-ray diffraction, scanning and transmission electron microscopy, nitrogen physisorption and elemental analysis, between conventional FAU and three layer-like FAU obtained by different synthesis routes was carried out to show the structural, morphological and textural differences and similarities of these materials.

关键词： FAU     hierarchical zeolite     layer-like morphology    

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Synthesis and characterization of well-defined comb-like branched polymers

LI Aixiang, LU Zaijun, LÜ Zijian

《化学科学与工程前沿（英文）》 2008年 第2卷 第4期   页码 407-411 doi: 10.1007/s11705-008-0064-6

摘要： Well-defined comb-like branched polymers having one branch in each repeating unit have been successfully synthesized by the coupling reaction of living polystyrene (PS) and polyisoprene (PI) anions with 1, 1-diphenylethenyl (DPE) groups along PS backbone prepared via atom transfer radical polymerization (ATRP) of 4-vinylbenzyloxy benzophenone (Sc) followed by Wittig reaction. The resulting comb-like branched polymers were characterized by IR, H-NMR, gel permeation chromatography (GPC) and static light scattering (SLS) in detail. The effect of living chains and DPE group molar ratio on grafting efficiency was discussed. The results show the coupling reaction of living chains and DPE groups was highly effective, and the coupling efficiency can be controlled via the feed molar ratios of living chains and DPE groups. Moreover, the effect of molecular weights of backbone (PSe) and PSLi or PILi on grafting efficiency was also discussed. The results show that when excess living polymers were used, the almost quantitative grafting efficiency could be achieved.

关键词： grafting efficiency     polyisoprene     quantitative grafting     effective     molecular    

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Novel synthetic approaches and TWC catalytic performance of flower-like Pt/CeO

Zongcheng ZHAN,Xiaojun LIU,Dongzhu MA,Liyun SONG,Jinzhou LI,Hong HE,Hongxing DAI

《环境科学与工程前沿（英文）》 2014年 第8卷 第4期   页码 483-495 doi: 10.1007/s11783-013-0595-z

摘要： A novel Ultrasonic Assisted Membrane Reduction (UAMR)-hydrothermal method was used to prepare flower-like Pt/CeO catalysts. The texture, physical/chemical properties, and reducibility of the flower-like Pt/CeO catalysts were characterized by X-Ray Diffraction (XRD), Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), N adsorption, and hydrogen temperature programmed reduction (H -TPR) techniques. The catalytic performance of the catalysts for treating automobile emission was studied relative to samples prepared by the conventional wetness impregnation method. The Pt/CeO catalysts fabricated by this novel method showed high specific surface area and metal dispersion, excellent three-way catalytic activity, and good thermal stability. The strong interaction between the Pt nanoparticles and CeO improved the thermal stability. The Ce ions were incorporated into the surfactant chains and the Pt nanoparticles were stabilized through an exchange reaction of the surface hydroxyl groups. The SEM results demonstrated that the Pt/CeO catalysts had a typical three-dimensional (3D) hierarchical porous structure, which was favorable for surface reaction and enhanced the exposure degree of the Pt nanoparticles. In brief, the flower-like Pt/CeO catalysts prepared by UAMR-hydrothermal method exhibited a higher Pt metal dispersion, smaller particle size, better three-way catalytic activity, and improved thermal stability versus conventional materials.

关键词： three-way catalyst     flower-like     Ultrasonic Assisted Membrane Reduction (UAMR)     Pt nanoparticles    

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标题 作者 时间 类型 操作

Toll-like receptors in innate immunity and infectious diseases

Min-Hao WU, Ping ZHANG, Xi HUANG,

期刊论文

Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the Toll-like

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

期刊论文

Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

null

期刊论文

Group III metabotropic glutamate receptors and drug addiction

null

期刊论文

Expression of protease-activated receptors on platelets in healthy individuals

Rui ZHU, Lin SHEN

期刊论文

Implementation of a flexible Major Vacation Toll-free Program for small passenger vehicles in China

Meng XU, Ziyou GAO

期刊论文

High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

期刊论文

Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced segmental and systemic analgesia

null

期刊论文

Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell

期刊论文

Self-sacrificial templating synthesis of flower-like nickel phyllosilicates and its application as high-performance

期刊论文

嵌合抗原受体和调节性T细胞——移植中人类白细胞抗原特异性免疫抑制的潜力

Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa

期刊论文

Dispersion of “guava-like” silica/polyacrylate nanocomposite particles in polyacrylate matrix

QI Dongming, YANG Lei, WU Minghua, SHAO Jianzhong, BAO Yongzhong

期刊论文

Layer-like FAU-type zeolites: A comparative view on different preparation routes

Bastian Reiprich, Tobias Weissenberger, Wilhelm Schwieger, Alexandra Inayat

期刊论文

Synthesis and characterization of well-defined comb-like branched polymers

LI Aixiang, LU Zaijun, LÜ Zijian

期刊论文

Novel synthetic approaches and TWC catalytic performance of flower-like Pt/CeO

Zongcheng ZHAN,Xiaojun LIU,Dongzhu MA,Liyun SONG,Jinzhou LI,Hong HE,Hongxing DAI

期刊论文