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Natural products and drug discovery

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National Science Review 2022年第11期9卷 37-57页

作者： david j.Newman NIH Special Volunteer

This review covers the recent history of a series of very important natural products and their derivatives that are currently in use or under evaluation in the areas of anti-infectives, important cancer treatments that include antibody drug conjugates, followed by a discussion of type 2 diabetes(T2DM) drugs and angiotensin converting enzyme inhibitors. The current structures of the agents are shown, though in the case of some peptides used in T2DM drugs the standard single leTher abbreviation for an amino acid is used.

关键词： artemisinin glycopeptides anthracyclines dolastatin diabetes 2 ACE inhibitors

Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

Analysis of ancient mass extinction recoveries in marine environments: generating strategies for managing outcomes of the current mass extinction

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National Science Review 2024年第1期11卷 8-10页

作者： david j.Bottjer Department of Earth Sciences University of Southern California

The defining feature of a mass extinction and its associated recovery is the global amount of extinction that occurred[1]. However, there is finer-scale detail to the story, as seen in the ongoing modern mass extinction(the sixth mass extinction), which exhibits variable effects among marine ecosystems and environments, and hence geographic areas [1].

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Positron emission particle tracking——Application and labelling techniques

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Particuology 2008年第1期6卷 16-23页

作者： david j. Parker School of Physics and Astronomy the University of Birmingham Edgbaston Birmingham B15 2TT UK

The positron emission particle tracking （PEPT） technique has been widely used in science and engineering to obtain detailed information on the motion and flow fields of fluids or granular materials in multiphase systems, for example, fluids in rock cracks, chemical reactors and food processors; dynamic behaviour of granular materials in chemical reactors, granulators, mixers, dryers, rotating kilns and ball mills. The information obtained by the PEPT technique can be used to optimise the design, operational conditions for a wide range of industrial process systems, and to evaluate modelling work. The technique is based on tracking radioactively labelled particles （up to three particles） by detecting the pairs of backto-back 511 keV γ-rays arising from annihilation of emitted positrons. It therefore involves a positron camera, location algorithms for calculating the tracer location and speed, and tracer labelling techniques. This paper will review the particle tracking technique from tracking algorithm, tracer labelling to their application.

关键词： PEPT Tracer Algorithm Tracking

Zircon age depth-profiling sheds light on the early Caledonian evolution of the Seve Nappe Complex in west-central j?mtland

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Geoscience Frontiers 2022年第2期13卷 460-470页

作者： Katarzyna Walczak Christopher j.Barnes jaroslaw Majka david G.Gee Iwona Klonowska AGH University of Science and Technology Faculty of GeologyGeophysics and Environmental Protectional.Mickiewicza 3030-059 KrakówPoland Uppsala University Department of Earth SciencesVillavagen 16752-36 UppsalaSweden

The Scandinavian Caledonides comprise nappe stacks of far-travelled allochthons that record closure of the Iapetus Ocean and subsequent continental collision of Baltica and *** Seve Nappe Complex(SNC)of the Scandinavian Caledonides includes relics of the outermost Baltoscandian passive margin that were subducted to mantle *** earliest of the deep subduction events has been dated to ca.500-480 *** of this event has been reported from the northern exposures of the *** south in the central and southern segments of the SNC,(ultra)high-pressure rocks have yielded younger ages in the range of ca.470-440 *** study provides the first record of the early Caledonian event in the southern *** evidence has been obtained by depth profiling of zircon grains that were extracted from the Tv?r?klumparna microdiamond-bearing *** zircon grains preserve eclogite facies overgrowths that crystallized at 482.6±3.8 Ma.A second,chemically-distinct zircon overgrowth records granulite facies metamorphism at 439.3±3.6 Ma,which corroborates previous geochronological evidence for granulite facies metamorphism at this *** on these results,we propose that the entire outer margin of Baltica was subducted in the late Cambrian to early Ordovician,but the record of this event may be almost entirely eradicated in the vast majority of lithologies by pervasive late Ordovician to early Silurian metamorphism.

关键词： Caledonian Orogeny Seve Nappe Complex Zircon geochronology Depth profiling HP/UHP metamorphism Double dunking

Ca2+ signaling during vertebrate somitogenesis

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Acta Pharmacologica Sinica 2006年第7期27卷 781-790页

作者： Sarah E webb Andrew L MILLER Department of Biology the Hong Kong University of Science and TechnologyClear Water BayHong Kong SARChina

A variety of Ca2+signals,in the form of intercellular pulses and waves,have beenreported to be associated with the various sequential stages of somitogenesis:from convergent extension and the formation of the paraxial mesoderm;during thepatterning of the paraxial mesoderm to establish segmental units;throughout theformation of the morphological boundaries that delineate the segmental units,andfinally from within the maturing somites as they undergo subsequent develop-ment and *** to both the technical challenges presented in imag-ing intact,developing embryos,and the subtle nature of the Ca2+transientsgenerated,they have proved to be difficult to ***,a combinationof cultured cell preparations and improvements in explant and whole embryo im-aging techniques has begun to reveal a new and exciting class of developmentalCa2+*** this chapter,we review the small,but expanding,number ofreports in the literature and attempt to identify common characteristics of thesomitogenic Ca2+transients,such as their mode of generation,as well as theirspatial and temporal *** may help to elucidate the significance andfunction of these intriguing Ca2+transients and thus integrate them into the com-plex signaling networks that orchestrate early developmental events.

关键词： Ca2+ signaling somitogenesis zebrafish Xenopus mouse chick

Vlendelian randomization： loosening the Gordian knot of testosterone and male ageing

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Asian journal of Andrology 2013年第5期15卷 579-581页

作者： david j Handelsman ANZAC Research Institute University of SydneySydney NSW 2139 Australia

It is unknown whether the reduced blood testosterone among unselected older men （＂andropause＂） compared to healthy younger men is due to ageing per se or as a non-specific adaptive reaction to chronic diseases acc... 详细信息

关键词： Mendelian randomization loosening male ageing

Pico-washing:simultaneous liquid addition and removal for continuous-flow washing of microdroplets

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Microsystems & Nanoengineering 2022年第2期8卷 249-261页

作者： Michael j.Siedlik david Issadore Department of Bioengineering University of PennsylvaniaPhiladelphiaPA 19104United States

Droplet microfluidics is based on a toolbox of several established unit operations,including droplet generation,incubation,mixing,pico-injection,and *** the last two decades,the development of droplet microfluidic systems,which incorporate these multiple unit operations into a workflow,has demonstrated unique capabilities in fields ranging from single-cell transcriptomic analyses to materials *** unit operation that is sorely underdeveloped in droplet microfluidics is washing,exchange of the fluid in a droplet with a different ***,we demonstrate what we name the"pico-washer,"a unit operation capable of simultaneously adding fluid to and removing fluid from droplets in flow while requiring only a small footprint on a microfluidic *** describe the fabrication strategy,device architecture,and process parameters required for stable operation of this technology,which is capable of operating with kHz droplet ***,we provide an image processing workflow to characterize the washing process with microsecond and micrometer ***,we demonstrate the potential for integrated droplet workflows by arranging two of these unit operations in series with a droplet generator,describe a design rule for stable operation of the pico-washer when integrated into a system,and validate this design rule *** anticipate that this technology will contribute to continued development of the droplet microfluidics toolbox and the realization of novel droplet-based,multistep biological and chemical assays.

关键词： operations simultaneous removing

Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown Rafael j.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute