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Tumor organoids to study gastroesophageal cancer: a primer

Journal of Molecular cell Biology 2020年第8期12卷 593-606页

作者： Ramon U.Jin jason c.mills Division of Oncology Department of Internal MedicineWashington University School of MedicineSt.LouisMO 63130USA Division of Gastroenterology Department of Internal MedicineWashington University School of MedicineSt.LouisMO 63130USA Department of Developmental Biology Washington University School of MedicineSt.LouisMO 63130USA Department of Pathology and Immunology Washington University School of MedicineSt.LouisMO 63130USA

Gastroesophageal cancers are leading causes of cancer *** attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and *** is dear that we should no longer treat all gastroesophageal cancers as a homogeneous disease,which is what we do when we use nonspecific ***,we currently cannot monitor successful gene/pathway targeting,nor understand how/when tumors develop resistance,nor predict which patients will derive maximal *** improve outcomes,we must precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well as develop novel avenues to study and predict treatment effects in individual *** this end,patient-derived organoids,in which tumor cells from individual patients are grown in a Petri dish,are a new versatile system that allows for timely expandability,detailed molecular characterization,and genetic manipulation with the promise of enabling predictive assessment of treatment *** this review,we will explore the development and basic techniques for organoid generation,and discuss the current and potential future applications of this exciting technology to study the basic science of carcinogenesis and to predict/guide cancer patient care in the clinics.

关键词： targeted therapy precision oncology cancer model tumor heterogeneity cancer evolution personalized medicine

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Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

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Journal of Sport and Health Science 2024年第2期13卷 233-244页

作者： Xiang Ren Tan Mary c.Stephenson Sharifah Badriyah Alhadad Kelvin W.Z.Loh Tuck Wah Soong jason K.W.Lee Ivan c.c.Low Health and Social Sciences Singapore Institute of TechnologySingapore 138683Singapore Human Potential Translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore centre for Translational Magnetic Resonance Research Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117549Singapore Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117593Singapore Heat Resilience and Performance centre Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117510Singapore N.1 Institute for Health National University of SingaporeSingapore 117456Singapore campus for Research Excellence and Technological Enterprise(cREATE) Singapore 138602Singapore

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive *** heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and ***:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,*** a separate trial,blended ice was ingested before and during exercise as a cooling *** were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging ***:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive *** function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital ***,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural ***:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

关键词： Brain functional activity cognition Heat stress Hyperthermia Motor function

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Degradation and resynthesis of chlorophyll during increased oxidative stress and prolonged darkness differ between annual and perennial flax(Linum L.)

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Oil crop Science 2024年第2期9卷 121-130页

作者： Kenyon J. Nisbett Abida Alokozai Su Hyun Elizabeth Ko G. Adam Mott jason c.L. Browna Department of Biological Sciences University of Toronto ScarboroughTorontoONCanada Department of cell&Systems Biology University of TorontoTorontoONCanada centre for the Analysis of Genome Evolution&Function University of TorontoTorontoONCanada

Among plants,there is considerable variation in lifespan:annuals live less than one year,whereas perennials live for several years,with the longest-living perennial having survived 43,600 *** proposed by the Disposable Soma Theory,this lifespan variation among plants likely reflects differential investment of limited energy and nutrient resources,with perennials investing more energy and nutrients into biomolecular maintenance compared to annuals in order to ensure persistence over multiple *** differential investment may be particularly important during periods of exogenous stress,which are known to accelerate biomolecular *** present study evaluated this hypothesis using annual and perennial flax(Linum L.)subjected to two exogenous stressors—increased oxidative stress(i.e.,foliar H2O2spraying)and complete prolonged *** chlorophyll has been shown to exhibit degradation in response to changes in environmental conditions,we utilized changes in chlorophyll levels during and after periods of exogenous stress to evaluate our *** predicted that i)perennials would exhibit a slower rate of chlorophyll degradation during exposure to exogenous stressors compared to annuals,and ii)perennials would exhibit a faster rate of chlorophyll resynthesis following such exposure compared to *** levels before,during,and after exposure to both exogenous stressors were measured in two separate trails,once using image colour analysis and once using *** chlorophyll degradation rates in response to oxidative stress did not differ between annuals and perennials,contrary to our predictions,chlorophyll resynthesis rates following such exposure were significantly higher in perennials,as *** plants were subjected to complete prolonged darkness,chlorophyll degradation rates were significantly lower in perennials than annuals,as predicted;however,when plants were subsequently reintroduced to natural photoperiod,ch

关键词： Ageing Life history Maximum lifespan Oxidative stress Somatic maintenance

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Artificial light at night(ALAN) pollution alters bat lunar chronobiology:insights from broad-scale long-term acoustic monitoring

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Ecological Processes 2024年第1期13卷 176-187页

作者： Han Li Pauline Allen Saige Boris Samantha Lagrama Jade Lyons christina mills Pauline Moussi casey Nichols carter Tacosik Mc Kenzie Tsaousis Nyzaya Livingston Wilson John F.Grider Kevin A.Parker Matina c.Kalcounis-Rueppell Department of Biology University of Nebraska Omaha Department of Biology University of North Carolina Greensboro colorado Parks and Wild-life Parker Ecology LLc Department of Biological Sciences University of Alberta

Background The timing of behavior and habitat use of nocturnal animals can be influenced by the lunar cycle in nature. The prevalence of artificial light at night(ALAN) has been recognized as a source of environmental pol-lution. The interaction between ALAN and the lunar cycle on bat behavior is important for understanding anthro-pogenic effects on bats. We utilized a decade(2012–2022) of acoustic monitoring data collected in North carolina, United States, to investigate the relationship between bat activity, lunar cycle, and light pollution. We examined whether the amount of lunar illumination affected species-specific nightly activity and whether hourly bat activity patterns varied between nights with different moon phases. We further investigated if the relationship between bat activity and the lunar cycle might be altered by light *** We found that seven bat species showed activity variation across nights in relation to the amount of moon illumination when ALAN was absent. In general, bats were less active on full moon nights compared to new moon nights. Light pollution interacted with the bat–lunar relationship in five of the seven species, masking the effect of the lunar cycle. We identified delayed bat activity patterns on nights with a full or waxing moon in seven species, and light pollution altered that pattern in four species. Overall, ALAN was associated with decreased bat activity inde-pendent of lunar cycle *** Our study demonstrated that at a broad spatial scale, ALAN negatively affected many North American temperate bat species and altered their lunar chronobiology. As light pollution is spreading to historically dark areas and habitats, ALAN might couple with other threats, such as the white-nose syndrome or climate change, to cause cascading damage in the environment that depends on ecosystem services such as pest control provided by bats. We argue that further research and conservation actions are needed to mitigate

关键词： Artificial light at night ALAN Bats chiroptera chronobiology Light pollution Lunar cycle Moonlight

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Unifying concepts in methanogenic,aerobic,and anammox sludge granulation

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Environmental Science and Ecotechnology 2024年第1期17卷 17-30页

作者： Simon mills Anna christine Trego Marco Prevedello Jo De Vrieze Vincent O’Flaherty Piet N.L.Lens Gavin collins Microbial communities Laboratory School of Biological and Chemical SciencesNational University of Ireland GalwayUniversity RoadGalwayH91 TK33Ireland Microbial Ecology Laboratory School of Biological and chemical Sciences University of GalwayUniversity RoadGalwayH91 TK33Ireland center for Microbial Ecology and Technology(cMET) Ghent UniversityCoupure Links 653B-9000GentBelgium University of Galway University RoadGalwayH91 TK33Ireland

The retention of dense and well-functioning microbial biomass is crucial for effective pollutant removal in several biological wastewater treatment *** solids retention is often achieved through aggregation of microbial communities into dense,spherical aggregates known as granules,which were initially discovered in the *** granules have since been widely applied in upflow anaerobic digesters for waste-to-energy ***,granular biomass has been applied in aerobic wastewater treatment and anaerobic ammonium oxidation(anammox)*** mechanisms underpinning the formation of methanogenic,aerobic,and anammox granules are the subject of ongoing *** each granule type has been extensively studied in isolation,there has been a lack of comparative studies among these granulation *** is likely that there are some unifying concepts that are shared by all three sludge *** these unifying concepts could allow a unified theory of granulation to be ***,we review the granulation mechanisms of methanogenic,aerobic,and anammox granular sludge,highlighting several common concepts,such as the role of extracellular polymeric substances,cations,and operational parameters like upflow velocity and shear *** have then identified some unique features of each granule type,such as different internal structures,microbial compositions,and quorum sensing ***,we propose that future research should prioritize aspects of microbial ecology,such as community assembly or interspecies interactions in individual granules during their formation and growth.

关键词： Granule Granulation Anaerobic digestion Anammox Aerobic granule

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construction of a novel six-gene signature to predict tumour response to induction chemotherapy and overall survival in locoregionally advanced laryngeal and hypopharyngeal carcinoma

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Genes & Diseases 2024年第3期11卷 148-150页

作者： chen Tan Lingwa Wang Yifan Yang Shizhi He George G.chen jason YK.chan Michael cF.Tong c.A.van Hasselt Wenbin Xu Ling Feng Ru Wang Jugao Fang Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Key Laboratory of Otolaryngology Head and Neck Surgery(Ministry of Education of china) Beijing Institute of OtolaryngologyBeijing 100730China Department of Otorhinolaryngology Head and Neck SurgeryThe Chinese University of Hong KongPrince of Wales HospitalHongKong SAR999077China Department of Medical Genetics Institute of Basic Medical ScienceChinese Academy of Medical Science&Peking Union Medical CollageBeijing 100730China

Locoregionally advanced laryngeal and hypopharyngeal cancers(LA-LHcs)are traditionally treated with surgery followed by postoperative radiotherapy,which impairs speech and swallowing functions and reduces the quality of life.^(1,2)The use of induction chemotherapy(Ic)as a larynxpreserving approach for LA-LHcs has been verified and refined.^(3)However,the short-term tumor response to Ic varies,non-responders usually show poor survival and little benefit.

关键词： chemotherapy laryngeal surgery

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Synthesis,disorder and Ising anisotropy in a new spin liquid candidate PrMgAl_(11)O_(19)

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Materials Futures 2024年第3期3卷 148-156页

作者： Yantao cao Huanpeng Bu Zhendong Fu Jinkui Zhao jason S Gardner Zhongwen Ouyang Zhaoming Tian Zhiwei Li Hanjie Guo Key Lab for Magnetism and Magnetic Materials of the Ministry of Education Lanzhou UniversityLanzhou 730000People’s Republic of China Songshan Lake Materials Laboratory DongguanGuangdong 523808People’s Republic of China Institute of Physics Chinese Academy of SciencesBeijing 100190People’s Republic of China Materials Science and Technology Division Oak Ridge National LaboratoryOak RidgeTN 37831United States of America School of Physics and Wuhan National High Magnetic Field center Huazhong University of Science and TechnologyWuhan 430074People’s Republic of China

Here we report the successful synthesis of large single crystals of triangular frustrated PrMgAl_(11)O_(19)using the optical floating zone *** crystal x-ray diffraction(XRD)measurements unveiled the presence of quenched disorder within the mirror plane,specifically~7%of Pr ions deviating from the ideal 2d site towards the 6h *** susceptibility measurements revealed an Ising anisotropy with the c-axis being the easy *** a large spin–spin interaction that develops below~10 K and considerable site disorder,the spins do not order or freeze down to at least 50 *** availability of large single crystals offers a distinct opportunity to investigate the exotic magnetic state on a triangular lattice with an easy axis out of the plane.

关键词： spin liquid disorder frustration triangular lattice Ising anisotropy

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Systematic Radio Telescope Alignment Using Portable Fringe Projection Profilometry

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Nanomanufacturing and Metrology 2024年第1期7卷 75-85页

作者： Joel Berkson Justin Hyatt Nathan Julicher Byeongjoon Jeong Isaac Pimienta Rachel Ball Wyatt Ellis jason Voris Diego Torres‑Barajas Daewook Kim James c.Wyant college of Optical Sciences University of Arizona1630 E.University Blvd.TucsonAZ 85721USA Department of Astronomy at Steward Observatory University of Arizona933 N Cherry Ave.TucsonAZ 85721USA

In 2019,the Event Horizon Telescope(EHT)released the first-ever image of a black hole event *** are now aiming for higher angular resolutions of distant targets,like black holes,to understand more about the fundamental laws of gravity that govern our *** achieve this higher resolution and increased sensitivity,larger radio telescopes are needed to operate at higher frequencies and in larger *** like the next-generation Very Large Array(ngVLA)and the Square-Kilometer Array(SKA)require building hundreds of telescopes with diameters greater than 10 ms over the next *** has a twofold *** telescope surfaces need to be more accurate to operate at higher frequencies,and the logistics involved in maintaining a radio telescope need to be simplified to support them properly in large *** of these problems can be solved with improved methods for surface metrology that are faster and more accurate with a higher *** leads to faster and more accurate panel alignment and,therefore,a more productive *** this paper,we present the use of binocular fringe projection profilometry as a solution to this problem and demonstrate it by aligning two panels on a 3-m radio telescope *** measurement takes only 10 min and directly delivers feedback on the tip,tilt,and piston of each panel to create the ideal reflector shape.

关键词： Metrology Fringe projection profilometry Off-axis alignment Radio astronomy Radio antenna

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng connie chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex c.Haydon Hue H.Luu Sherwin Ho Michael J.Lee jason Strelzow Russell R.Reid Tong-chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-catenin cancer canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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Unintended targeting of Dmp1-cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice

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Bone Research 2017年第1期5卷 41-48页

作者： Joohyun Lim Joseph Burclaff Guangxu He jason c.mills Fanxin Long Department of Orthopaedic Surgery Washington University School of MedicineSt.LouisMOUSA Division of Gastroenterology Departments of Medicine and Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA Department of Orthopedics The Second Xiangya HospitalCentral South UniversityHunan 410011China Department of Developmental Biology Washington University School of MedicineSt.LouisMOUSA

cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of cre expression. The Dmpl- cre mouse, expressing cre from a 14-kb DNA fragment of the mouse Dmpl gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon cre recombination, we find that in 2-month-old mice, Dmpl-cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, Dmpl-cre marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express Pdgfra. confirming the utility of Dmpl-cre in the gastrointestinal mesenchyme, deletion of Bmprla with Dmpl-cre causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when using Dmpl-cre because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.

关键词： gene cell bone Unintended targeting of Dmp1-cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice Figure

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