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| 1 | Bone Morphogenetic Protein (BMP) signaling in development and human diseases显示文摘Bone Morphogenetic Proteins(BMPs)are a group of signaling molecules that belongs to the Transforming Growth Factor-b(TGF-b)superfamily of proteins.Initially discovered for their ability to induce bone formation,BMPs are now known to play crucial roles in all organ systems.BMPs are important in embryogenesis and development,and also in maintenance of adult tissue homeostasis.Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects,highlighting the essential functions of BMPs.In this review,we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development.A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling. | Richard N.Wang Jordan Green Zhongliang Wang Youlin Deng Min Qiao Michael Peabody Qian Zhang Jixing Ye Zhengjian Yan Sahitya Denduluri Olumuyiwa Idowu Melissa Li Christine Shen Alan Hu Rex C.Haydon Richard Kang James Mok Michael J.Lee Hue L.Luu Lewis L.Shi | 2014 | Genes & Diseases2014，1，1： | 47 |
| 2 | An antibody against Siglec-15 promotes bone formation and fracture healing by increasing TRAP^(+)mononuclear cells and PDGF-BB secretion显示文摘Osteoporosis(OP)is a common age-related disease characterized by a deterioration of bone mass and structure that predisposes patients to fragility fractures.Pharmaceutical therapies that promote anabolic bone formation in OP patients and OP-induced fracture are needed.We investigated whether a neutralizing antibody against Siglec-15 can simultaneously inhibit bone resorption and stimulate bone formation.We found that the multinucleation of osteoclasts was inhibited in SIGLEC-15 conditional knockout mice and mice undergoing Siglec-15 neutralizing antibody treatment.The secretion of platelet-derived growth factor-BB(PDGF-BB),the number of tartrate-resistant acid phosphatase-positive(TRAP+)mononuclear cells,and bone formation were significantly increased in the SIGLEC-15 conditional knockout mice and antibody-treated mice.The anabolic effect of the Siglec-15 neutralizing antibody on bone formation was blunted in mice with Pdgfb deleted in TRAP-1'cells.These findings showed that the anabolic effect of the Siglec-15 neutralizing antibody was mediated by elevating PDGF-BB production of TRAP4 mononuclear cells.To test the therapeutic potential of the Siglec-15 neutralizing antibody,we injected the antibody in an ovariectomy-induced osteoporotic mouse model,which mimics postmenopausal osteoporosis in women,and in two fracture healing models because fracture is the most serious health consequence of osteoporosis.The Siglec-15 neutralizing antibody effectively reduced bone resorption and stimulated bone formation in estrogen deficiency-induced osteoporosis.Of note,the Siglec-15 neutralizing antibody promoted intramembranous and endochondral ossification at the damaged area of cortical bone in fracture healing mouse models.Thus,the Siglec-15 neutralizing antibody shows significant translational potential as a novel therapy for OP and bone fracture. | Gehua Zhen Yang Dan Ruomei Wang Ce Dou Qiaoyue Guo Melissa Zarr Linda N.Liu Lieping Chen Ruoxian Deng Yusheng Li Zengwu Shao Xu Cao | 2021 | Bone Research2021，9，4： | 6 |
| 3 | Palliative surgery for Krukenberg tumors—12-year experience and review of the literature显示文摘AIM To determine the clinical characteristics of patients undergoing palliative surgery for Krukenberg tumors,including disease presentation,outcomes,and prognostic factors.METHODS This was a retrospective clinical study of all patients who underwent palliative surgery for Krukenberg tumors between January 2004 and December 2015.Patient information was obtained from inpatient and outpatient case notes as well as the hospital electronic records.Patients who underwent potential y curative resection,and patients with Krukenberg tumors who did not undergo surgery were also excluded from the study.Palliative surgery was defined as those performed for either alleviation of symptoms or for asymptomatic patients for whom surgical removal of the tumors were deemed necessary following a multidisciplinary consensus.Tumors were diagnosed pre-operatively by computed tomography scans and all had histologic confirmation of the surgical specimens.RESULTS Over the study duration,38 female patients underwent palliative surgery for Krukenberg tumors at our institution.Mean age was 54.2±11.7 years.The colon was the most frequent primary source of metastases(n=21)followed by the stomach(n=4).Prophylactic palliative surgery was performed for eight(21.1%)asymptomatic patients.Median post-operative length of stay was 8 d(IQR 6-12 d).Five patients(13.2%)experienced postoperative complications,although high grade morbidity was only seen in one patient(2.6%).Median overall survival from surgery was 17 mo(95%CI:12.1-21.9)at a median follow-up duration of 12 mo(IQR 8-17mo).The median survival was shorter for patients who underwent emergency surgery,younger patients,those with a colorectal primary,larger tumors,or synchronous peritoneal or hepatic metastases.CONCLUSION Pal iative surgery for Krukenberg tumors can be performed safely with acceptable complication rates.Bilateral oophorectomy should be performed to prevent the risk of symptomatic contralateral tumors. | Isaac Seow-En Gwen Hwarng Grace Hwei Ching Tan Leonard Ming Li Ho Melissa Ching Ching Teo | 2018 | World Journal of Clinical Oncology2018，9，1： | 5 |
| 4 | Sustained high level transgene expression in mammalian cells mediated by the optimized piggyBac transposon system显示文摘Sustained,high level transgene expression in mammalian cells is desired in many cases for studying gene functions.Traditionally,stable transgene expression has been accomplished by using retroviral or lentiviral vectors.However,such viral vector-mediated transgene expression is often at low levels and can be reduced over time due to low copy numbers and/or chromatin remodeling repression.The piggyBac transposon has emerged as a promising nonviral vector system for efficient gene transfer into mammalian cells.Despite its inherent advantages over lentiviral and retroviral systems,piggyBac system has not been widely used,at least in part due to their limited manipulation flexibilities.Here,we seek to optimize piggyBac-mediated transgene expression and generate a more efficient,user-friendly piggyBac system.By engineering a panel of versatile piggyBac vectors and constructing recombinant adenoviruses expressing piggyBac transposase(PBase),we demonstrate that adenovirusmediated PBase expression significantly enhances the integration efficiency and expression level of transgenes in mesenchymal stem cells and osteosarcoma cells,compared to that obtained from co-transfection of the CMV-PBase plasmid.We further determine the drug selection timeline to achieve optimal stable transgene expression.Moreover,we demonstrate that the transgene copy number of piggyBac-mediated integration is approximately 10 times higher than that mediated by retroviral vectors.Using the engineered tandem expression vector,we show that three transgenes can be simultaneously expressed in a single vector with high efficiency.Thus,these results strongly suggest that the optimized piggyBac system is a valuable tool for making stable cell lines with sustained,high transgene expression. | Xiang Chen Jing Cui Zhengjian Yan Hongmei Zhang Xian Chen Ning Wang Palak Shah Fang Deng Chen Zhao Nisha Geng Melissa Li Sahitya K.Denduluri Rex C.Haydon Hue H.Luu Russell R.Reid Tong-Chuan He | 2015 | Genes & Diseases2015，2，1： | 5 |
| 5 | Dysfunctional stem and progenitor cells impair fracture healing with age显示文摘Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature;mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging;a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly. | Diane R Wagner Sonali Karnik Zachary J Gunderson Jeffery J Nielsen Alanna Fennimore Hunter J Promer Jonathan W Lowery M Terry Loghmani Philip S Low Todd O McKinley Melissa A Kacena Matthias Clauss Jiliang Li | 2019 | World Journal of Stem Cells2019，11，6： | 3 |
| 6 | Agricultural Risk Factors Influence Microbial Ecology in Honghu Lake显示文摘Agricultural activities, including stock-farming, planting industry, and fish aquaculture,can affect the physicochemical and biological characters of freshwater lakes. However, the effects of pollution producing by agricultural activities on microbial ecosystem of lakes remain unclear.Hence, in this work, we selected Honghu Lake as a typical lake that is influenced by agriculture activities. We collected water and sediment samples from 18 sites, which span a wide range of areas from impacted and less-impacted areas. We performed a geospatial analysis on the composition of microbial communities associated with physicochemical properties and antibiotic pollution of samples. The co-occurrence networks of water and sediment were also built and analyzed. Our results showed that the microbial communities of impacted and less-impacted samples of water were largely driven by the concentrations of TN, TP, NO_3^--N, and NO_2^--N, while those of sediment were affected by the concentrations of Sed-OM and Sed-TN. Antibiotics have also played important roles in shaping these microbial communities: the concentrations of oxytetracycline and tetracycline clearly reflected the variance in taxonomic diversity and predicted functional diversity between impacted and less-impacted sites in water and sediment samples, respectively. Furthermore, for samples from both water and sediment, large differences of network topology structures between impacted and less-impacted were also observed. Our results provide compelling evidence that the microbial community can be used as a sentinel of eutrophication and antibiotics pollution risk associated with agricultural activity; and that proper monitoring of this environment is vital to maintain a sustainable environment in Honghu Lake. | Maozhen Han Melissa Dsouza Chunyu Zhou Hongjun Li Junqian Zhang Chaoyun Chen Qi Yao Chaofang Zhong Hao Zhou Jack A Gilbert Zhi Wang Kang Ning | 2019 | Genomics, Proteomics & Bioinformatics2019，17，1： | 3 |
| 7 | PNAS:科学家首次鉴别出让寨卡病毒如此致命的关键蛋白显示文摘当寨卡病毒横空出世时科学家们对其知之甚少。在过去一年里研究者们通过深入研究来阐明寨卡病毒为何会引发一系列危险的健康问题。包括新生儿缺陷等,比如小头畸型和神经性问题(格--巴二氏综合征等)。但研究者们并不知道寨卡病毒哪种蛋白会让其变得具有杀伤性。当然他们也不清楚这些蛋白质的作用机理是什么。 | Ge Li Melissa Poulsen Csaba Fenyvuesvolgyi Yoko Yashiroda Minoru Yoshida J. Marc Simard Robert C. Gallo Richard Y. Zhao | 2017 | 现代生物医学进展2017，17，3： | 2 |
| 8 | Synthe- sis, antifungal activity, and structure-activity relation- ships of coruscanone A analogues显示文摘 | BABU K B LI X C MELISSA R J | 2006 | J Med Chem2006，49，26： | 1 |
| 9 | small molecule oligonu cleotide-based telomerase template inhibition in combination with cytolytic therapy in an vitro androgen-independent prostate cancer model显示文摘 | Benjamin KC Li Y Melissa T | 2006 | Urol Oncol2006，24，2： | 1 |
| 10 | Imaging of subsquamous Barrett’s epithelium with ultrahigh-resolution optical coherence tomography: a histologic correlation study显示文摘 | Michael J. Cobb Joo Ha Hwang Melissa P. Upton Yuchuan Chen Brant K. Oelschlager Douglas E. Wood Michael B. Kimmey Xingde Li | 2010 | Gastrointestinal Endoscopy2010，，： | 1 |
| 11 | A novel mouse model of in-stent restenosis显示文摘 | Luis Rodriguez-Menocal Yuntao Wei Si M. Pham Melissa St-Pierre Sen Li Keith Webster Pascal Goldschmidt-Clermont Roberto I. Vazquez-Padron | 2009 | Atherosclerosis2009，，2： | 1 |
| 12 | Lack of a meaningful effect of anacetrapib on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects显示文摘 | Rajesh Krishna Daria Stypinski Melissa Ali Amit Garg Josee Cote Andrea Maes Bruce DeGroot Yang Liu Susie Li Sandra M. Connolly John A. Wagner S. Aubrey Stoch | 2012 | British Journal of Clinical Pharmacology2012，，1： | 1 |
| 13 | A metastatic colon cancer model using nonoperative transanal rectal injection显示文摘 | Melissa Donigan Bryan D. Loh Laurie S. Norcross Shuan Li Paul R. Williamson Samuel DeJesus Andrea Ferrara Joseph T. Gallagher Cheryl H. Baker | 2010 | Surgical Endoscopy2010，，3： | 1 |
| 14 | CRISPR clear? Dimeric Cas9-Fok1 nucleases improve genome-editing specificity显示文摘Bacteria and archaea have been known for decades having evolved adaptive immunedefenses called clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPRassociated(Cas)systems to degrade foreign nucleic acids.Recently,these RNA-guided Cas9 nucleases derived from CRISPR/Cas systems have shown promise in transforming our ability to edit mammalian genomes.1 While zinc-finger nucleases(ZFNs)and transcription activator-like effector nucleases(TALENs)have shown similar promise,the ease of producing targeting RNAs over the generation of unique sequence-directed nucleases to guide site-specific modifications makes the CRISPR/Cas9 system an appealing method forgenome editing.A short guideRNA(sgRNA)can direct Cas9 to a specific genomic sequence where it induces doublestrand breaks that,when imperfectly repaired,yield mutations.1 Cas9 can also catalyze gene replacement through homologous recombination. | Hongmei Zhang Zhengjian Yan Melissa Li Michael Peabody Tong-Chuan He | 2014 | Genes & Diseases2014，1，1： | 1 |
| 15 | Genotypic and phenotypic characterization of genetic differentiation and diversity in the USDA rice mini-core collection显示文摘 | Xiaobai Li Wengui Yan Hesham Agrama Biaolin Hu Limeng Jia Melissa Jia Aaron Jackson Karen Moldenhauer Anna McClung Dianxing Wu | 2010 | Genetica2010，，： | 1 |
| 16 | Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features显示文摘 | Chad JC Li XX Melissa L | 2009 | PNAS2009，106，13： | 1 |
| 17 | Use of toll-like receptor assays to detect and identify microbial contaminants in biological products 显示文摘 | Li YH James LD Melissa Z | 2009 | J Clin Microbio12009，47，11： | 1 |
| 18 | Lower cost strategies for triage of human papillomavirus DNA‐positive women显示文摘 | You‐Lin Qiao Jose Jeronimo Fang‐Hui Zhao Johannes Schweizer Wen Chen Melissa Valdez Peter Lu Xun Zhang Le‐Ni Kang Pooja Bansil Proma Paul Charles Mahoney Marthe Berard‐Bergery Ping Bai Roger Peck Jing Li Feng Chen Mark H. Stoler Philip E. Castle | 2014 | Int. J. Cancer2014，，12： | 1 |
| 19 | Interaction of the Cyto- chrome P4501A2, SULT1A1 and NAT gane polymorphisms with smoking and dietary mutagen intake in modification of the risk of pan- creatic cancer显示文摘 | Hideo Suzuki Jeffrey S Morris Yanan Li Mark A Doll David W Hein Jun Liu Li ]ian Manal M Hassan Rena S Day Melissa L Bondy James L Abbruzzese and Donghui Li | 2008 | Carcinogenesis2008，29，6： | 1 |
| 20 | Imaging of subsquamous Barrett’s epithelium with ultrahigh-resolution optical coherence tomography: a histologic correlation study显示文摘 | Michael J. Cobb Joo Ha Hwang Melissa P. Upton Yuchuan Chen Brant K. Oelschlager Douglas E. Wood Michael B. Kimmey Xingde Li | 2010 | Gastrointestinal Endoscopy2010，，2： | 1 |
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