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| 1 | Ionomycin ameliorates hypophosphatasia via rescuing alkaline phosphatase deficiency-mediated L-type Ca^(2+) channel internalization in mesenchymal stem cells显示文摘The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or secondary teeth, osteoporosis, bone pain,chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused a reduction in intracellular Ca2+ influx, resulting in an osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse bone marrow mesenchymal stem cells(BMSCs). Increasing the intracellular level of calcium in BMSCs by ionomycin treatment rescued the osteoporotic phenotype in alpl+/- mice and BMSC-specific(Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL was found to be required for the maintenance of intracellular Ca2+ influx, which it achieves by regulating L-type Ca2+ channel trafficking via binding to the α2δsubunits to regulate the internalization of the L-type Ca2+ channel. Decreased Ca2+ flux inactivates the Akt/GSK3β/β-catenin signaling pathway, which regulates lineage differentiation of BMSCs. This study identifies a previously unknown role of the ectoenzyme ALPL in the maintenance of calcium channel trafficking to regulate stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channels by ionomycin treatment may be a promising therapeutic approach for adult patients with HPP. | Bei Li Xiaoning He Zhiwei Dong Kun Xuan Wei Sun Li Gao Shiyu Liu Wenjia Liu Chenghu Hu Yimin Zhao Songtao Shi Yan Jin | 2020 | Bone Research2020，8，2： | 4 |
| 2 | Achieving efficient RNAi therapy: progress and challenges显示文摘RNA interference(RNAi)has been harnessed to produce a new class of drugs for treatment of various diseases.This review summarizes the most important parameters that govern the silencing efficiency and duration of the RNAi effect such as small interfering RNA(siRNA)stability and modification,the type of delivery system and particle sizing methods.It also discusses the predominant barriers for siRNA delivery,such as off-target effects and introduces internalization,endosomal escape and mathematical modeling in RNAi therapy and combinatorial RNAi.At present,effective delivery of RNAi therapeutics in vivo remains a challenge although significant progress has been made in this field. | Kun Gao Leaf Huang | 2013 | Acta Pharmaceutica Sinica B2013，3，4： | 3 |
| 3 | Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers显示文摘The benefcial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate.Moreover,the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only infuencing their pharmacokinetic and pharmacodynamic properties but also bioavailability,therapeutic effcacy and toxicity.Therefore,an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential.In order to direct nanoparticles towards specifc sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated.These include particle size,shape and surface charge/chemistry.Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways.Similarly,a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria,endoplasmic reticulum(ER)and Golgi.This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization.Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specifc endocytic pathway. | Samrat Mazumdar Deepak Chitkara Anupama Mittal | 2021 | Acta Pharmaceutica Sinica B2021，11，4： | 1 |
| 4 | Endostatin specifically targets both tumor blood vessels and lymphatic vessels显示文摘Endostatin,a 20 kDa C-terminal fragment of collagen XVIII,was first identified as a potent angiogenic inhibitor.The anti-angiogenic function of endostatin has been well documented during the past decade.Recently,several studies demonstrated that endostatin also inhibits tumor lymphangiogenesis and lymphatic metastasis.However,the exact mechanism that endostatin executes its anti-angiogenic and anti-lymphangiogenic functions remains elusive.In the current mini-review,we briefly summarize recent novel findings,including the functions of endostatin targeting not only angiogenesis but also lymphangiogenesis,and the underlying mechanism by which endostatin internalization regulates its biological functions. | Wei Zhuo Yang Chen Xiaomin Song Yongzhang Luo | 2011 | Frontiers of Medicine2011，5，4： | 1 |
| 5 | Generation of recombinant rabies virus ERA strain applied to virus tracking in cell infection显示文摘The mechanism of rabies virus (RABV) infection still needs to be further characterized. RABV particle with self-fluorescent is a powerful viral model to visualize the viral infection process in cells. Herein, based on a reverse genetic system of the Evelyn-Rokitnicki-Abelseth (rERA) strain, we generated a recombinant RABV rERA-N/mCherry strain that stably expresses an additional ERA nucleoprotein that fuses with the red fluorescent protein mCherry (N/mCherry). The rERA-N/mCherry strain retained growth property similar to the parent strain rERA in vitro. The N/mCherry expression showed genetic stability during passage into mouse neuroblastoma (NA) cells and did not change the virulence of the vector. The rERA-N/mCherry strain was then utilized as a visual viral model to study the RABV-cell binding and internalization. We directly observed the red self-fluorescence of rERA-N/mCherry particles binding to the cell surface, and further co-localizing with clathrin in the early stage of infection in NA cells by fluorescence microscopy. Our results showed that the rERA-N/mCherry strain uses clathrin-dependent endocytosis to enter cells, which is consistent with the well-known mechanism of RABV invasion. The recombinant RABV rERA-N/mCherry thus appears to have the potential to be an effective viral model to further explore the fundamental molecular mechanism of rabies neuropathogenesis. | ZHAO Dan-dan SHUAI Lei GE Jin-ying WANG Jin-liang WEN Zhi-yuan LIU Ren-qiang WANG Chong WANG Xi-jun BU Zhi-gao | 2019 | Journal of Integrative Agriculture2019，18，10： | 1 |
| 6 | INTERNALIZATION OF GAP JUNCTIONS BETWEEN NEURON AND GLIAL CELL AND FORMATION OF ANNULAR LAMELLAR BODIES IN CHINESE LEECH Whitmania pigra显示文摘This paper reveals the formation of annular lamellar body (ALB) in the ganglion of leech by means of in situ fixation and the lanthanum nitrate tracer technique. This formation involves both wrapping and internalization of the gap junctions between glial processes themselves, as well as between neuron and glial process. The results indicate that there is probably an active process of internalization of membrane structures involving gap junctions between neuron and glial cell in the central nervous system in leech. The functions of ALB are discussed. | 朱丽霞 张人骥 | 1991 | Science China Chemistry1991，34，7： | 1 |
| 7 | Intracellular distribution and internalization pathways of guanidinylated bioresponsive poly(amido amine)s in gene delivery显示文摘Guanidinylated bioresponsive poly(amido amine)s polymers, CAR-CBA and CHL-CBA, weresynthesized by Michael-type addition reaction between guanidine hydrochloride(CAR) orchlorhexidine(CHL) and N,N-cystaminebisacrylamide(CBA). Previous studies have shownthat both polymers had high transfection efficiencies as gene delivery carriers. In this study,we investigated the nucleolus localization abilities and cellular internalization pathways ofthese two polymers in gene delivery. Each polymer condensed plasmid DNA(p DNA) andformed nanoparticle complexes, and then their transfection studies were performed inMCF-7 cells. Both complexes were found enriched in nucleolus after cellular transfection,and their transfection efficiencies were significantly improved when transfection was per-formed on MCF-7 cells arrested at M phase. The transfection efficiency of CAR-CBA-pDNAwas inhibited by chlorpromazine, and cell endosomes were disrupted after being exposedto CAR-CBA-pDNA. In regards to CHL-CBA-pDNA, its transfection efficiency was not affected by three types of endocytosis inhibitors used in the study, and CHL-CBA-pDNA showed no effect on endosomes. Cellular lactate dehydrogenase release and membrane morphology were changed after cells were transfected by the two complexes. The results indicated that both CAR-CBA and CHL-CBA polymers demonstrated good nucleolus localization abilities. It was beneficial for transfection when cells were arrested at M phase. CAR-CBA-pDNA cellular internalization was involved with clathrin-mediated endocytosis pathway, and escaping from endosomal entrapment, while the cellular uptake of CHL-CBA-pDNA occurs via clathrin-and caveolae-independent mechanism. | Jinmina Zhang Chunxi Wang Mei Lu Haonan Xing Tianzhi Yang Cuifang Cai Xiaoyun Zhao Minjie Wei Jiankun Yu Pingtian Ding | 2018 | Asian Journal of Pharmaceutical Sciences2018，13，4： | 1 |
| 8 | DNA Nanostructures as Drug Carriers for Cellular Delivery显示文摘Drug delivery systems have been widely developed for enhancing target activity and improving drug functions.Liposomes,high-molecular polymer,gold nanoparticles and carbon nanomaterials,etc.,are all the candidates of drug carriers.However,immunotoxicity,heterogeneity and low solubility generally exist and hamper their applications.As a kind of biological materials,DNA has its unique advantages in biomedical applications,including excellent biological compatibility and programmability.DNA nanostructures have been proved to possess high cellular uptake efficiency,which sheds new light on DNA-based drug delivery system.In this review,we summarize the influence factors of DNA nanostructure internalization efficiency,including cell lines,and the size and the shape of DNA nanoparticles.Uniformity of DNA nanostructures in appearance and properties ensures the stability in research,which makes DNA carriers stand out from other nanomaterials.Next,we focus on the functionalization of DNA carriers,which endows DNA nanostructures with the potential to construct integrated drug delivery platforms.We also discuss the internalization pathways of DNA nanostructures and their fate in cells.The deeply understanding about the endocytic pathways provides new sight for the further design strategy on changing the transportation routes of DNA carriers in cells.Finally,the challenges in further applications are discussed,and suggestions are proposed. | WU Na ZHAO Yongxi | 2020 | Chemical Research in Chinese Universities2020，36，2： | 0 |
| 9 | Mock Conference’s Impact on Internalizing Translating and Interpreting Learners’ Motivation显示文摘The internalization of motivation in second/foreign language(L2)learning and the use of mock conferences(MCs)to prepare translating and interpreting learners for future professional careers have been widely researched by scholars,but whether MC can facilitate the internalization of T&I learners’motivation is under-researched.Based on self-determination theory(SDT),this thesis investigates the effectiveness of MC in facilitating internalization of motivation through an empirical study which involves a 2-week long pedagogical experiment on two parallel classes of T&I learners taught by the same teacher in their 1st year of graduate study at Graduate School of Translation and Interpretation,Beijing Foreign Studies University.The research shows that compared with traditional teachercentered teaching model,MCs can better facilitate internalization of T&I learners’motivation.This article justifies the use of MCs as a situated approach in interpreting teaching and describes the design of MCs according to the psychological needs of SDT.In addition,the paper offers suggestions for further improvement of MCs design at the postgraduate level. | Minjuan Gao | 2019 | Journal of Contemporary Educational Research2019，3，3： | 0 |
| 10 | Protective effects of anti-ricin A-chain antibodies delivered intracellularly against ricin-induced cytotoxicity显示文摘AIM:To evaluate the ability of anti-ricin A-chain antibodies,delivered intracellularly,to protect against ricininduced cytotoxicity in RAW264.7 cells. METHODS:Anti-deglycosylated ricin A-chain antibody and RAC18 anti-ricin A-chain monoclonal antibody were delivered intracellularly by encapsulating in liposomes or via conjugation with the cell-penetrating MTS-transport peptide.RAW264.7 cells were incubatedwith these antibodies either before or after ricin exposure.The changes in cytotoxicity were estimated by MTT assay.Co-localization of internalized antibody and ricin was evaluated by fluorescence microscopy. RESULTS:Internalized antibodies significantly increased cell viability either before or after ricin exposure compared to the unconjugated antibodies.Fluorescence microscopy confirmed the co-localization of internalized antibodies and ricin inside the cells. CONCLUSION:Intracellular delivery of antibodies to neutralize the ricin toxin after cellular uptake supports the potential use of cell-permeable antibodies for postexposure treatment of ricin intoxication. | Frank Martiniuk Seth Pincus Sybille Müller Heinz Kohler Kam-Meng Tchou-Wong | 2010 | World Journal of Biological Chemistry2010，1，5： | 0 |
| 11 | Analysis of the Relationship between Internationalization and the Quality of Ed.D. in U.S.A显示文摘The universal phenomenon of internationalization as mainstream of higher education is often based on the assumption that there is value added to the quality of higher education systems when enhancing the international dimension of teaching,research and service(Knight,1997).Questioning the validity of the assumption,this study examined the relationship between internationalization and quality of Professional Doctorate in Education(Ed.D.)of U.S.A.Using the pre-existing data provided in the process of the course of“Comparative Education Research”instructed by Ms.Song,the study conducted the discussion and analysis from the perspective of diverse learners(Normore&Cook,2009)of doctoral students in terms of the factors included mentorship interaction,curriculums,participation,financial support and expectations,skills and quality.The results showed that the variables in internationalization were strongly related with the indicators of quality in Ed.D.education on the following extends:research and methodology capability,application and solution to problem,access of resources,management,creation and innovation,completion rates and publications. | Jiedan Wang Fei Long | 2019 | 教育研究前沿(中英文版)2019，9，4： | 0 |
| 12 | THE OFFSHORE DIRECT INVESTMENT OF HONG KONG CLOTHING FIRMS显示文摘Hong Kong clothing firms have invested overseas from as early as the late 1950s in order to evade or minimise the impact of quantitative restrictions for export to developed countries. Under global trading and production involvement, the Offshore Direct Investment (ODI) activities of Hong Kong clothing firms have actually spread and penetrated into the clothing industry of different continents in the world. This paper studies empirically on Dunning’s eclectic model for the offshore investment of Hong Kong clothing firms with emphasis on the rationale behind the shift and the locations chosen for initial and recent investments. | 区健勋 杨国荣 | 1997 | Journal of China Textile University(English Edition)1997，14，3： | 0 |
| 13 | Estimation of successful capping with complete aspiration of bladder via nephroureterostomy tube显示文摘BACKGROUND Ureteral stent and nephroureterostomy tube(NUT)are treatments of ureteral obstruction.Ureteral stent provides better quality of life.Internalization of NUT is desired whenever possible.AIM To assess outcomes of capping trial among cancer patients with complete aspiration of retained contrast from bladder via NUT.METHODS Our Institutional Review Board approved retrospective review of all NUT placement,NUT exchange and conversion of nephrostomy catheter into NUT performed during June 2013 to June 2015(n=578).Cases were excluded due to lack of imaging of bladder(n=37),incomplete aspiration of bladder(n=324),no attempt at capping NUT(n=166),and patients with confounding factors interfering with results of capping trial including non-compliant bladder,bladder outlet obstruction and catheter malposition(n=14).Study group consisted of 37 procedures in 34 patients(male 19,female 15,age 2-83 years,average 58,median 61)most with cancer(prostate 8,endometrial 5,bladder 4,colorectal 4,breast 2,gastric 2,neuroblastoma 2,cervical 1,ovarian 1,renal 1,sarcoma 1,urothelial 1 and testicular 1)and one with Crohn’s disease.Medical records were reviewed to assess outcomes of capping trial.Exact 95%confidence intervals(95%CI)were calculated.RESULTS Among patients with complete aspiration of retained contrast,30(81%,95%CI:0.65-0.92)catheters were successfully capped(range 12-94 d,average 40,median 24.5)until planned conversion to internal stent(23),routine exchange(5),removal(1)or death unrelated to catheter(1).Seven capping trials(19%,95%CI:0.08-0.35)were unsuccessful(range 2-22 d,average 12,median 10)due to leakage(3),elevated creatinine(2),fever/hematuria(1)and nausea/vomiting(1).CONCLUSION Capping trial success among patients with complete aspiration of retained contrast/urine from bladder via NUT appears high. | Majid Maybody Wesley K Shay Deborah A Fleischer Meier Hsu Chaya Moskowitz | 2020 | World Journal of Clinical Urology2020，9，1： | 0 |
| 14 | Follicle-stimulating Hormone(FSH) Induced Internalization of Porcine FSH Receptor in Cultured Porcine Granulosa Cells and Chinese Hamster Ovary Cells Transfected with Recombinant Porcine FSH Receptor cDNA显示文摘In order to study the fate of human follicle-stimulating hormone (FSH) when hormone binds to its receptor, a quick biochemical method that can differentiate between the surface-bound and internalized hormone was used to determine the internalization induced by FSH in cultured both porcine granulosa cells and Chinese hamster ovary (CHO) cells expressing recombinant porcine FSH receptor. The results showed that FSH was slowly internalized, and the internalized radioactivity (acid resistant) reached a peak 10-12 h after addition of 125 I-hFSH. It was suggested that FSHR do not get internalized rapidly under physiological circumstances precisely because the appropriate sequences are absent. | 朱长虹 田红 熊忠明 肖惠珠 | 2001 | Journal of Huazhong University of Science and Technology(Medical Sciences)2001，21，3： | 0 |
| 15 | Study on the Promoting Mechanism of Teachers'Ethics Internalization in Universities显示文摘On the basis of clarifying the teachers'Ethics internalization theory,this paper analyzes the typical dilemma in teachers'Ethics internalization.To resolve these problems,this paper construct an overall framework,including security mechanism,normative mechanism,education mechanism,evaluation mechanism and supervision mechanism,which the external conditions are used to constantly strengthen the moral needs of the subject,then enhance the consciousness of moral internalization,improve the effectiveness of teachers'moral construction. | Shan Chang | 2021 | Journal of Contemporary Educational Research2021，5，3： | 0 |
| 16 | Translocation and transformation of engineered nanomaterials in plant cells and their effect on metabolism显示文摘As the climate worsens and the demand for food grows,so does the interest in nanoagriculture.The interaction between plants and nanomaterials(NMs)has been extensively and intensively examined.However,stopping at the outcome of a phenomenon is often insufficient.Therefore,we introduce three important processes of nanoparticleplant interactions:translocation,transformation,and plant metabolism.During the migration of nanoparticles,size and surface electrical properties are the main determining factors.Additionally,the interaction of nanoparticles with cell membranes is another key aspect of research.The transformation of nanoparticles in plants is mainly due to redox substances.The way that nanoparticles affect plant metabolism may be able to shed light on the interaction of nanoparticles with plants.This review adds to the existing knowledge on the design of nanoagrochemicals and summarizes the mechanism of interaction of NMs with plants.In this way,NMs can be used for their beneficial effects and thus contribute to the maintenance of food security and sustainable development. | WEICHEN ZHAO PINGFAN ZHOU BENZHEN LOU YAQI JIANG YUANBO LI MINGSHU LI NOMAN SHAKOOR YUKUI RUI | 2023 | BIOCELL2023，47，3： | 0 |
| 17 | Multi-Dimensional Analysis of China’s“Double Reduction” Policy显示文摘Under China’s“Double Reduction”policy,although the educational pressure has somewhat reduced,the mechanism of talent selection through examinations still exists,which means competition remains,leading to the internalization of education.This article analyzes the challenges faced by the“Double Reduction”policy from historical and current perspectives.The reasons for the internalization of education are examined and four recommendations for the further implementation of the“Double Reduction”policy are presented. | Yizhe Li | 2023 | Journal of Contemporary Educational Research2023，7，12： | 0 |
| 18 | Fate of enteric pathogens in different spinach cultivars cultivated in growth chamber and field systems显示文摘between enteric pathogens and plant hosts have been shown to be multifaceted.This series of studies sought to expand our knowledge in this area and evaluate whether spinach cultivar selection may be used to curtail pathogen contamination and ultimately reduce microbiological risk associated with this crop.As a component to that assessment,potential antimicrobials that were constituents within spinach leaves were first analysed and found to be spatially non-uniform,being more concentrated on the outer edges of the leaves than in the centre of the leaves.Consequently,the entire foliage of a plant was sampled in subsequent studies examining the fate of Salmonella and Escherichia coli O157:H7 on seven cultivars of spinach.Cultivar did not affect the degree of Salmonella internalized into spinach tissue(P>0.05);however,it appeared that those Salmonella that were internalized were transient residents as the percentage of plants containing this internalized pathogen dropped within 24 h.No relationship existed between antimicrobial levels(total phenols or antioxidant capacity)of the spinach cultivars and the prevalence of plants exhibiting Salmonella internalization or the persistence of Salmonella or E.coli O157:H7 after the plants had been sprayed with the pathogen.In both growth chamber and field studies,Salmonella was more resistant than E.coli O157:H7 to inactivation.Cultivar affected the persistence of both E.coli O157:H7 and Salmonella but the ranking for each pathogen’s survival on three of those cultivars differed suggesting the difficulty in finding one cultivar that would be inhospitable to multiple pathogens. | Marilyn C.Erickson Jye-Yin Liao Alison S.Payton Peter W.Cook Henk C.Den Bakker Jesus Bautista Juan Carlos Díaz Pérez | 2018 | Food Quality and Safety2018，2，4： | 0 |
| 19 | Apply relevant theories to explain how innovation may affect the internationalisation process and performance of multinational enterprise(s)显示文摘With the rapid development of globalization nowadays,innovation has been an essential element for MNEs in competition.Multinational enterprises are tend to obtain this vital competitive advantage in their internali zation processes and performances. | 张莹 | 2016 | 科技经济导刊2016，，25： | 0 |
| 20 | Analysis on Output Teaching Mode of College English Based on Implicit Learning Theory显示文摘The application of language,to a great extant,requires learners to understand the inputted information quickly as well as automatically,and combine verbal fragments into meaningful outputted language. This type of spontaneous mechanism depends on the effective input of language and long-rang internalization of language structure,which helps to form the implicit knowledge in students' conceptual system,thus to realize the automatic use of language. Therefore,the article intends to combine implicit learning theory with the output teaching mode with a purpose of working out a practical teaching mode to enhance the teaching effect and college students' applied abilities to use English. | ZHANG Ling LIN Wen-qin | 2014 | 海外英语2014，，17： | 0 |
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