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Neutrophils in cancer—unresolved questions

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Science China(Life Sciences) 2021年第11期64卷 1829-1841页

作者： Melissa S.F.Ng Leonard Tan Quanbo Wang charles r.Mackay Lai Guan Ng Singapore Immunology Network(SIgN) A*STAR(Agency for ScienceTechnology and Research)Biopolis 138648Singapore School of Pharmaceutical Sciences Shandong Analysis and Test CenterQilu University of Technology(Shandong Academy of Sciences)Jinan 250014China State Key Laboratory of Experimental Hematology Institute of HematologyChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

There is growing recognition that neutrophils play an important role in cancer initiation, progression and metastasis. Although they are typically characterized as short-lived effector cells, neutrophils have been shown to acquire immunosuppressive and pro-tumorigenic functions that promote tumor progression and escape. As such, inhibition of their function or depletion of neutrophils are being explored as potential cancer therapies. However, growing evidence of neutrophil diversification in cancer and their potential anti-tumor roles raise many unresolved questions. Here, we review recent advances that address the definition,origin and function of neutrophils in cancer, and elaborate on obstacles that make the study of neutrophils challenging. We envision that this review will provide the groundwork for focused design of therapeutics that will specifically target "tumorreprogrammed" neutrophils while sparing normal neutrophils to improve patient outcomes.

关键词： neutrophils cancer myeloid-derived suppressor cells(MDSCs) immunotherapy

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ABCD^(2) risk score does not predict the presence of cerebral microemboli in patients with hyper-acute symptomatic critical carotid artery stenosis

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Stroke & Vascular Neurology 2017年第2期2卷 41-46页

作者： Mahmud Saedon charles E Hutchinson Christopher H E Imray Donald r J Singer Warwick Medical School University of WarwickCoventryUK University Hospitals Coventry Warwickshire NHS Trust CoventryUK Fellowship of Postgraduate Medicine LondonUK Yale School of Medicine New HavenConnecticutUSA

Introduction:ABCD^(2) risk score and cerebral microemboli detected by transcranial Doppler(TCD)have been separately shown to the predict risk of recurrent acute *** studied whether ABCD2 risk score predicts cerebral microemboli in patients with hyper-acute symptomatic carotid artery *** and methods:We studied 206 patients presenting within 2 weeks of transient ischaemic attack or minor stroke and found to have critical carotid artery stenosis(≥50% ).86 patients(age 70±1(SEM:years),58 men,83 Caucasian)had evidence of microemboli;72(84% )of these underwent carotid endarterectomy(CEA).120 patients(age 72±1 years,91 men,113 Caucasian)did not have microemboli detected;102(85% )of these underwent *** were analysed using X2 and Mann–Whitney U tests and receiver operating characteristic(rOC)***:140/206(68% :95% CI 61.63 to 74.37)patients with hyper-acute symptomatic critical carotid stenosis had an ABCD2 risk score≥*** was no significant difference in the NICE red flag criterion for early assessment(ABCD^(2) risk score≥4)for patients with cerebral microemboli versus those without microemboli(59/86 vs 81/120 patients:Or 1.05 ABCD2 risk score≥4(95% CI 0.58 to 1.90,p=0.867)).The ABCD2 risk score wasrebral *** adjusting for pre-neurological event antiplatelet treatment(APT),area under the curve(AUC)of rOC for ABCD2 risk score showed no prediction of cerebral microemboli(no pre-event APT,n=57:AUC 0.45(95% CI 0.29 to 0.60,p=0.531);preevent APT,n=147:AUC 0.51(95% CI 0.42 to 0.60,p=0.804)).Conclusions:The ABCD2 score did not predict the presence of cerebral microemboli or carotid disease in over one-quarter of patients with symptomatic critical carotid artery *** the basis of NICE guidelines(refer early if ABCD2≥4),assessment of high stroke risk based on ABCD2 scoring may lead to inappropriate delay in urgent treat

关键词： patients cerebral emboli

A Historical Perspective on Development of Systems Engineering Discipline:A review and Analysis

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Journal of Systems Science and Systems Engineering 2020年第1期29卷 1-35页

作者： Niamat Ullah Ibne Hossain raed M.Jaradat Michael A.Hamilton charles B.Keating Simon r.Goerger Department of Industrial and Systems Engineering Mississippi State UniversityPO Box 9542Mississippi State 39762USA Department of Industrial and Systems Engineering Mississippi State UniversityPO Box 9542Mississippi State39762USA Institute for Systems Engineering research(ISEr) Mississippi State University 3909 Halls Ferry RdVicksburgMS 39180 Department of Engineering Management&Systems Engineering Old Dominion UniversityNorfolkVA 23529 eInstitute for Systems Engineering research(ISEr) U.S Army Engineer Research Development Center(ERDC)3909 Halls Ferry RdVicksburgMS 39180

Since its inception,Systems Engineering(SE)has developed as a distinctive discipline,and there has been significant progress in this field in the past two *** to other engineering disciplines,SE is not affirmed by a set of underlying fundamental propositions,instead it has emerged as a set of best practices to deal with intricacies stemming from the stochastic nature of engineering complex systems and addressing their *** the existing methodologies and paradigms(dominant patterns of thought and concepts)of SE are very diverse and somewhat *** appears to create some confusion regarding the design,deployment,operation,and application of *** purpose of this paper is 1)to delineate the development of SE from 1926-2017 based on insights derived from a histogram analysis,2)to discuss the different paradigms and school of thoughts related to SE,3)to derive a set of fundamental attributes of SE using advanced coding techniques and analysis,and 4)to present a newly developed instrument that could assess the performance of systems *** than Two hundred and fifty different sources have been reviewed in this research in order to demonstrate the development trajectory of the SE discipline based on the frequency of publication.

关键词： Systems Engineering(SE) history development systems engineering attributes performance measures

Current evidence on potential of adipose derived stem cells to enhance bone regeneration and future projection

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World Journal of Stem Cells 2021年第9期13卷 1248-1277页

作者： Quang Le Vedavathi Madhu Joseph M Hart charles r Farber Eli r Zunder Abhijit S Dighe Quanjun Cui Department of Orthopaedic Surgery University of Virginia School of MedicineCharlottesvilleVA 22908United States Orthopaedic Surgery research Thomas Jefferson UniversityPhiladelphiaPA 19107United States Center for Public Health Genomics University of VirginiaCharlottesvilleVA 22908United States Departments of Public Health Sciences and Biochemistry and Molecular Genetics University of VirginiaCharlottesvilleVA 22908United States Department of Biomedical Engineering University of VirginiaCharlottesvilleVA 22908United States

Injuries to the postnatal skeleton are naturally repaired through successive stepsinvolving specific cell types in a process collectively termed “bone regeneration”.Although complex, bone regeneration occurs through a series of well-orchestratedstages wherein endogenous bone stem cells play a central role. In most situations,bone regeneration is successful;however, there are instances when it fails andcreates non-healing injuries or fracture nonunion requiring surgical or therapeuticinterventions. Transplantation of adult or mesenchymal stem cells (MSCs) definedby the International Society for Cell and Gene Therapy (ISCT) as CD105+-CD90+CD73+CD45-CD34-CD14orCD11b-CD79αorCD19-HLA-Dr- is beinginvestigated as an attractive therapy for bone regeneration throughout the *** isolated from adipose tissue, adipose-derived stem cells (ADSCs), aregaining increasing attention since this is the most abundant source of adult stemcells and the isolation process for ADSCs is straightforward. Currently, there isnot a single Food and Drug Administration (FDA) approved ADSCs product forbone regeneration. Although the safety of ADSCs is established from their usagein numerous clinical trials, the bone-forming potential of ADSCs and MSCs, ingeneral, is highly controversial. Growing evidence suggests that the ISCT definedphenotype may not represent bona fide osteoprogenitors. Transplantation of bothADSCs and the CD105- sub-population of ADSCs has been reported to induce bone regeneration. Most notably, cells expressing other markers such as CD146,AlphaV, CD200, PDPN, CD164, CXCr4, and PDGFrα have been shown torepresent osteogenic sub-population within ADSCs. Amongst other strategies toimprove the bone-forming ability of ADSCs, modulation of VEGF, TGF-β1 andBMP signaling pathways of ADSCs has shown promising results. The U.S. FDAreveals that 73% of Investigational New Drug applications for stem cell-basedproducts rely on CD105 expression as the “positive” marker for adult stem cell

关键词： Mesenchymal stem cells Adipose-derived stem cells Endogenous stem cells Skeletal stem cells Bone regeneration

The Global Boundary Stratotype Section and Point （GSSP） for the base of Changhsingian Stage （Upper Permian）

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Episodes 2006年第3期29卷 175-182页

作者： Yugan Jin Yue Wang charles Henderson Bruce r. Wardlaw Shuzhong Shen Changqun Cao State Key Laboratory of Palaeobiology and Stratigraphy Nanjing Institute of Geology and Palaeontology Chinese Academy of Sciences 39 East Beijing Road Nanjing 210008 China Department of Geology and Geophysics University of Calgary Calgary Alberta Canada T2N 1N4 U.S. Geological Survey Reston 12201 Sunrise Valley Drive National Center VA 22092 USA

The Global Stratotype Section and Point （GSSP） for the base-Changhsingian Stage is defined at the First Appearance Datum （FAD） of the conodont Clarkina wangi within the lineage from C. longicuspidata to C. wangi at a point 88 cm above the base of the Changxing Limestone in the lower part of Bed 4 （base of 4α-2） at Meishan D section, Changxing County, Zhejiang Province, South China. This level is consistent with the first appearance of Changhsingian index fusulinid Palaeofusulina sinensis and tapashanitid ammonoids. The speciation event from Clarkina longicuspidata to C. wangi occurs just above the flooding surface of the second parasequence in the Changxing Limestone. In addition, the boundary interval is clearly recognizable by the depletion of isotopic carbon ratios and the normal polarity zone appearing above the Late Wuchiapingian reversed polarity zone. Section C, about 300 m to the west of Section D, exposes more of the upper.longtan Formation. It clearly shows the transitional nature of deposition across the longtan/Changxing formational boundary, and thus is described as a supplementary reference section.

关键词：二叠纪石灰石全球界线层型剖面和节点沉积作用牙形石

Genetic Dissection of Low Phosphorus Tolerance related Traits Using Selected Introgression Lines in rice

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rice science 2015年第6期22卷 264-274页

作者： XIANG Chao rEN Jie ZHAO Xiu-qin DING Zai-song ZHANG Jing WANG Chao ZHANG Jun-wei charles Augustino JOSEPH ZHANG Qiang PANG Yun-long GAO Yong-ming SHI Ying-yao Institute of Crop Science Chinese Academy of Agricultural Sciences College of Agronomy Anhui Agricultural University Agricultural Bureau of Deqing

To dissect the genetic basis of low phosphorus tolerance （LPT）, 114 BC2F4 introgression lines （ILs） were developed from Shuhui 527 and Minghui 86 （recurrent parents）, and Yetuozai （donor parent）. The progenies were tested for 11 quantitative traits under three treatments including normal fertilization in normal soil （as control）, normal fertilization in barren soil and low phosphorus stress in barren soil in Langfang, Hebei Province, China. Moreover, the ILs were investigated at the seedling stage using nutrient solution culture method in greenhouse in Beijing, China. A total of 49 main-effect quantitative trait loci （QTLs） underlying yield related traits were identified in Langfang, and their contributions to phenotypic variations ranged from 6.7% to 16.5%. Among them, 25 （51.0%） QTLs had favorable alleles from donor parent. A total of 48 main-effect QTLs were identified for LPT-related traits in Beijing, and their contributions to phenotypic variations ranged from 7.7% to 16.6%. Among them, 21 （43.8%） QTLs had favorable alleles from donor parent. About 79.6% of the QTLs can be detected repeatedly under two or more treatments, especially QTLs associated with spikelet number per panicle, spikelet fertility and 1000-grain weight, displaying consistent phenotypic effects. Among all the detected QTLs, eight QTLs were simultaneously identified under low phosphorus stress across two environments. These results can provide useful information for the genetic dissection of LPT in rice.

关键词： rice phosphorus tolerance yield introgression line quantitative trait locus

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PHGDH as a mechanism for resistance in metabolically-driven cancers

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Cancer Drug resistance 2020年第4期3卷 762-774页

作者： richa rathore charles r.Schutt Brian A.Van Tine Division of Medical Oncology Washington University in St.LouisSt.LouisMO 63110USA Siteman Cancer Center St.LouisMO 63110USA

At the forefront of cancer research is the rapidly evolving understanding of metabolic reprogramming within cancer *** expeditious adaptation to metabolic inhibition allows cells to evolve and acquire resistance to targeted treatments,which makes therapeutic exploitation complex but achievable.3-phosphoglycerate dehydrogenase(PHGDH)is the rate-limiting enzyme of de novo serine biosynthesis and is highly expressed in a variety of cancers,including breast cancer,melanoma,and Ewing’s *** review will investigate the role of PHGDH in normal biological processes,leading to the role of PHGDH in the progression of *** an understanding of the molecular mechanisms by which PHGDH expression advances cancer growth,we will highlight the known mechanisms of resistance to cancer therapeutics facilitated by PHGDH biology and identify avenues for combatting PHGDH-driven resistance with inhibitors of PHGDH to allow for the development of effective metabolic therapies.

关键词： PHGDH cancer metabolism serine one-carbon metabolism folate cycle drug resistance

The reversal of antineoplastic drug resistance in cancer cells by β-elemene

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癌症 2015年第11期34卷 488-495页

作者： Guan-Nan Zhang charles r.Ashby Jr. Yun-Kai Zhang Zhe-Sheng Chen Huiqin Guo Department of Pharmaceutical Sciences College of Pharmacy and Health Sciences St. John’s University Department of Thoracic Surgery Peking Union Medical College Hospital

Multidrug resistance(MDr), deined as the resistance of cancer cells to compounds with diverse structures and mechanisms of actions, signiicantly limits the eicacy of antitumor drugs. A major mechanism that mediates MDr in cancer is the overexpression of adenosine triphosphate(ATP)?binding cassette transporters. These transporters bind to their respective substrates and catalyze their elux from cancer cells, thereby lowering the intracellular concentra?tions of the substrates and thus attenuating or even abolishing their eicacy. In addition, cancer cells can become resistant to drugs via mechanisms that attenuate apoptosis and cell cycle arrest such as alterations in the p53, check point kinase, nuclear factor kappa B, and the p38 mitogen?activated protein kinase pathway. In this review, we discuss the mechanisms by which β?elemene, a compound extracted from rhizoma zedoariae that has clinical antitumor eicacy, overcomes drug resistance in cancer.

关键词： rhizoma zedoariae β?Elemene Multidrug resistance

Characteristic model based all-coefficient adaptive control of an AMB suspended energy storage flywheel test rig

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Science China(Information Sciences) 2018年第11期61卷 113-127页

作者： Xujun LYU long DI Zongli LIN Yefa HU Huachun WU School of Mechanical and Electronic Engineering Wuhan University of Technology Hubei Provincial Engineering Technology research Center for Magnetic Suspension ASML-HMI 1762 Automation Pkwy 4. Charles L.Brown Department of Electrical and Computer Engineering University of Virginia

Feedback control of active magnetic bearing(AMB) suspended energy storage flywheel systems is critical in the operation of the systems and has been well studied. Both the classical proportional-integralderivative(PID) control design method and modern control theory, such as H∞ control and μ-synthesis,have been explored. PID control is easy to implement but is not effective in handling complex rotordynamics. Modern control design methods usually require a plant model and an accurate characterization of the uncertainties. In each case, few experimental validation results on the closed-loop performance are available because of the costs and the technical challenges associated with the construction of experimental test *** this paper, we apply the characteristic model based all-coefficient adaptive control(ACAC) design method for the stabilization of an AMB suspended flywheel test rig we recently constructed. Both simulation and experimental results demonstrate strong closed-loop performance in spite of the simplicity of the control design and implementation.

关键词： adaptive control characteristic modeling energy storage flywheels active magnetic bearings