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Mesenchymal stem cell therapy for acute radiation syndrome: Innovative medical approaches in military medicine

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Journal of Medical Colleges of PLA(China) 2014年第3期29卷 186-195页

作者： Erik B.Eaton Jr. Timothy R.Varney United States Army Medical Research Institute of Chemical Defense 3100 Ricketts Point Road Aberdeen Proving GroundMaryland 21010 US United States Army Medical Research Institute of Chemical Defense 3100 Ricketts Point Road Aberdeen Proving Ground Maryland 21010 US

After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.

关键词： Acute radiation syndrome Mesenchymal stem cell Cel

Silk fibroin as an additive for cell-free protein synthesis

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Synthetic and Systems Biotechnology 2020年第3期5卷 145-154页

作者： Marilyn S.Lee Chia-Suei Hung Daniel A.Phillips Chelsea C.Buck Maneesh K.Gupta Matthew W.Lux US Army Combat Capabilities Development Command Chemical and Biological Center 8567 Ricketts Point RoadAberdeen Proving GroundMD21010USA US Air Force Research Laboratory 217912th St.B652/R122 Wright-Patterson Air Force BaseOH45433USA US Naval Research Laboratory Center for Bio/Molecular Science and Engineering Bldg.42Room 3034555 Overlook Ave.WashingtonDC 20375UES Inc.4401 Dayton Xenia Rd.BeavercreekOH 45432USA

Cell-free systems contain many proteins and metabolites required for complex functions such as transcription and translation or multi-step metabolic conversions.Research into expanding the delivery of these systems by drying or by embedding into other materials is enabling new applications in sensing,point-of-need manufacturing,and responsive materials.Meanwhile,silk fibroin from the silk worm,Bombyx mori,has received attention as a protective additive for dried enzyme formulations and as a material to build biocompatible hydrogels for controlled localization or delivery of biomolecular cargoes.In this work,we explore the effects of silk fibroin as an additive in cell-free protein synthesis(CFPS)reactions.Impacts of silk fibroin on CFPS activity and stability after drying,as well as the potential for incorporation of CFPS into hydrogels of crosslinked silk fibroin are assessed.We find that simple addition of silk fibroin increased productivity of the CFPS reactions by up to 42%,which we attribute to macromolecular crowding effects.However,we did not find evidence that silk fibroin provides a protective effects after drying as previously described for purified enzymes.Further,the enzymatic crosslinking transformations of silk fibroin typically used to form hydrogels are inhibited in the presence of the CFPS reaction mixture.Crosslinking attempts did not impact CFPS activity,but did yield localized protein aggregates rather than a hydrogel.We discuss the mechanisms at play in these results and how the silk fibroin-CFPS system might be improved for the design of cell-free devices.

关键词： Cell-free systems Cell-free protein synthesis CFPS Silk fibroin Preservation

Growing seismicity in the Sichuan Basin and its association with industrial activities

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Science China Earth Sciences 2020年第11期63卷 1633-1660页

作者： Xinglin LEI Jinrong SU Zhiwei WANG Geological Survey of Japan National Institute of Advanced Industrial Science and Technology(AIST)Higashi 1-1-1TsukubaIbaraki 305-8567JapanChengdu 610041China Earthquake Monitoring Centre Sichuan Earthquake Administration State Key Laboratory of Earthquake Dynamics Institute of GeologyChina Earthquake AdministrationBeiing 100029China

In the Sichuan Basin,seismic activity has been low historically,but in the past few decades,a series of moderate to strong earthquakes have occurred.Especially since 2015,earthquake activity has seen an unprecedented continuous growth trend,and the magnitude of events is increasing.Following the M5.7 Xingwen earthquake on 18 Dec.2018,which was suggested to be induced by shale gas hydraulic fracturing,a swarm of earthquakes with a maximum magnitude up to M6.0 struck Changning and the surrounding counties.Questions arose about the possible involvement of industrial actions in these destructive events.In fact,underground fluid injection in salt mine fields has been occurring in the Sichuan Basin for more than70 years.Disposal of wastewater in natural gas fields has also continued for about 40 years.Since 2008,injection for shale gas development in the southern Sichuan Basin has increased rapidly.The possible link between the increasing seismicity and increasing injection activity is an important issue.Although surrounded by seismically active zones to the southwest and northwest,the Sichuan Basin is a rather stable region with a wide range of geological settings.First,we present a brief review of earthquakes of magnitude 5 or higher since 1600 to obtain the long-term event rate and explore the possible link between the rapidly increasing trend of seismic activity and industrial injection activities in recent decades.Second,based on a review of previous research results,combined with the latest data,we describe a comprehensive analysis of the characteristics and occurrence conditions of natural and injection-induced major seismic clusters in the Sichuan Basin since 1700.Finally,we list some conclusions and insights,which provide a better understanding of why damaging events occur so that they can either be avoided or mitigated,point out scientific questions that need urgent research,and propose a general framework based on geomechanics for assessment and management of earthquake-related risks.

关键词： Induced seismicity Fluid injection Sichuan Basin Shale gas Wastewater disposal Salt mine

Possible link between long-term and short-term water injections and earthquakes in salt mine and shale gas site in Changning,south Sichuan Basin, China

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Earth and Planetary Physics 2019年第6期3卷 510-525页

作者： XingLin Lei ZhiWei Wang JinRong Su Geological Survey of Japan AISTIbaraki 305-8567Japan State Key Laboratory of Earthquake Dynamics Institute of GeologyChina Earthquake AdministrationBeijing 100029China Earthquake Monitoring Centre Sichuan Earthquake AdministrationChengdu 610041China

Late at night on 17 June 2019,a magnitude 6.0 earthquake struck Shuanghe Town and its surrounding area in Changning County,Sichuan,China,becoming the largest earthquake recorded within the southern Sichuan Basin.A series of earthquakes with magnitudes up to 5.6 occurred during a short period after the mainshock,and we thus refer to these earthquakes as the Changning M6 earthquake sequence(or swarm).The mainshock was located very close to a salt mine,into which for^3 decades fresh water had been extensively injected through several wells at a depth of 2.7–3 km.It was also near(within^15 km)the epicenter of the 18 December 2018 M5.7 Xingwen earthquake,which is thought to have been induced by shale gas hydraulic fracturing(HF),prompting questions about the possible involvement of industrial activities in the M6 sequence.Following previous studies,this paper focuses on the relationship between injection and seismicity in the Shuanghe salt field and its adjacent Shangluo shale gas block.Except for a period of serious water loss after the start of cross-well injection in 2005–2006,the frequency of earthquakes shows a slightly increasing tendency.Overall,there is a good correlation between the event rate in the Shuanghe area and the loss of injected water.More than 400 M≥3 earthquakes,including 40 M≥4 and 5 M≥5 events,had been observed by the end of August 2019.Meanwhile,in the Shangluo area,seismicity has increased during drilling and HF operations(mostly in vertical wells)since about 2009,and dramatically since the end of 2014,coincident with the start of systematic HF in the area.The event rate shows a progressively increasing background with some fluctuations,paralleling the increase in HF operations.More than 700 M≥3 earthquakes,including 10 M≥4 and 3 M≥5 in spatially and temporally clustered seismic events,are correlated closely with active fracturing platforms.Well-resolved centroid moment tensor results for M≥4 earthquakes were shown to occur at very shallow depths around shale formations with active HF,in agree

关键词： Changning earthquake injection-induced earthquake deep well injection hydraulic fracturing salt well mine shale gas

Study on anisotropy of Longmaxi shale using hydraulic fracturing experiment

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Science China Earth Sciences 2021年第2期64卷 260-277页

作者： Hongyu ZHAI Xu CHANG Wei ZHU Xinglin LEI Ziqiu XUE Institute of Geophysics China Earthquake AdministrationBeijing 100081China Key Laboratory of Petroleum Resources Research Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China Innovation Academy for Earth Science Chinese Academy of SciencesBeijing 100029China State Key Laboratory of Petroleum Resources and Prospecting China University of Petroleum-BeijingBeijing 102249China Geological Survey of Japan National Institute of Advanced Industrial Science and Technology(AIST)Ibaraki 305-8567Japan Research Institute of Innovative Technology for the Earth Kyoto 619-0292Japan

Hydraulic fracturing reservoir reconstruction technology is crucial in the development of shale gas exploitation techniques.Large quantities of high-pressure fluids injected into shale reservoirs significantly alter compressional(P)and shear(S)wave velocities,rock mechanical parameters,and anisotropic characteristics.In this study,differentiated hydraulic fracturing petrophysical experiments were carried out on Longmaxi Formation shale under pseudo-triaxial stress loading conditions.The effects of stress loading methods,and water-rock physical and chemical reactions on P-and S-wave velocities and rock mechanical parameters were compared.The experimental results showed that isotropic stress loading may increase the P-and Swave velocities and Young’s modulus of dry shale kldnsample.Furthermore,it may lead to a weakening of the corresponding anisotropy.In contrast,differential stress loading was able to improve the anisotropy of Young’s modulus and accelerate the decrease in the compressive strength of shale in the vertical bedding direction.The water-rock physical and chemical reactions prompted by hydraulic fracturing was found to"soften"shale samples and reduce Young’s modulus.The influence of this"soften"effect on the compressional and shear wave velocities of shale was negligible,whilst there was a significant decrease in the anisotropy characteristics of Thomsen parameters,Young’s modulus,and Poisson’s ratio.The negative linear relationship between the Poisson’s ratios of the shale samples was also observed to lose sensitivity to stress loading,as a result of the"soften"effect of fracturing fluid on shale.The results of this study provide a reliable reference point and data support for future research on the mechanical properties of Longmaxi shale rocks.

关键词： Longmaxi shale Anisotropic parameters Hydraulic fracturing experiment

Nine requirements for the origin of Earth’s life:Not at the hydrothermal vent, but in a nuclear geyser system

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Geoscience Frontiers 2019年第4期10卷 1337-1357页

作者： Shigenori Maruyama Ken Kurokawa Toshikazu Ebisuzaki Yusuke Sawaki Konomi Suda M. Santosh Earth-Life Science Institute Tokyo Institute of Technology2-12-1 O-okayamaMeguro-kuTokyo 152-8551Japan Kochi University Kochi 780-8520Japan Novosibirsk State University Pirogova 1630090Russia Genome Evolution Laboratory National Institute of Genetics1111 YataMishimaShizuoka 411-8540Japan RIKEN 2-1 HirosawaWakoSaitama351-0198Japan Department of Earth and Planetary Sciences Graduate School of Science and EngineeringTokyo Institute of Technology2-12-1 OokayamaMeguro-kuTokyo 152-8550Japan Department of Earth Science and Astronomy Graduate School of Arts and Sciences The University of Tokyo3-8-1 KomabaMeguro-kuTokyo 153-8902Japan Geomicrobiology Research Group Institute for Geo-Resources and EnvironmentNational Institute of Advanced Industrial Science and Technology (AIST)Central 71-1-1 HigashiTsukubaIbaraki 305-8567Japan Centre for Tectonics Resources and ExplorationDepartment of Earth SciencesUniversity of AdelaideSA 5005Australia School of Earth Sciences and Resources China University of Geosciences (Beijing)29 Xueyuan RoadBeijing 100083China

The origin of life on Earth remains enigmatic with diverse models and debates.Here we discuss essential requirements for the first emergence of life on our planet and propose the following nine requirements:(1)an energy source(ionizing radiation and thermal energy);(2)a supply of nutrients(P.K.REE.etc.);(3)a supply of life-constituting major elements;(4)a high concentration of reduced gases such as CH4,HCN and NH3;(5)dry-wet cycles to create membranes and polymerize RNA;(6)a non-toxic aqueous environment;(7)Na-poor water;(8)highly diversified environments,and(9)cyclic conditions,such as dayto-night,hot-to-cold etc.Based on these nine requirements,we evaluate previously proposed locations for the origin of Earth’s life,including:(1)Darwin’s"warm little pond",leading to a"prebiotic soup"for life;(2)panspermia or Neo-panspermia(succession model of panspermia);(3)transportation from/through Mars;(4)a deepsea hydrothermal system;(5)an on-land subduct ion-zone hot spring,and(6)a geyser systems driven by a natural nuclear reactor.We conclude that location(6)is the most ideal candidate for the o rigin point for Earth’s life because of its efficiency in continuously supplying both the energy and the necessary materials for life,thereby maintaining the essential"cradle"for its initial development.We also emphasize that falsifiable working hypothesis provides an important tool to evaluate one of the biggest mysteries of the universe-the origin of life.

关键词： Origin of Earth's life Nuclear geyser system Emergence and evolution of life Falsifiability