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A SteMNess perspective of survival motor neuron function： splicing factors in stem cell biology and disease

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Frontiers in Biology 2015年第4期10卷 297-309页

作者： Stuart J. Grice Ji-Long Liu MRC Functional Genomics Unit Department of Physiology Anatomy and Genetics University of Oxford South Parks RoadOxford OX1 3PT UK

Genome-wide analyses of metazoan messenger RNA （mRNA） species are unveiling the extensive transcriptional diversity generated by alternative splicing （AS）. Research is also beginning to identify the splicing factors and AS events required to maintain the balance between stem cell renewal （i.e stemness properties） and differentiation. One set of proteins at the center of spliceosome biogenesis are the survival motor neuron （SMN） complex constituents, which have a critical role in the assembly of spliceosomal small nuclear ribonucleoproteins （snRNPs） in all cells. In this review we discuss what is currently known about how AS controls pluripotency and cell fate and consider how an increased requirement for splicing factors, including SMN, helps to maintain an enrichment of stem cell-specific AS events. Furthermore, we highlight studies showing that mutations in specific splicing factors can lead to the aberrant development, and cause targeted degeneration of the nervous system. Using SMN as an example, we discuss the perspective of how stem cell-specific changes in splicing factors can lead to developmental defects and the selective degeneration of particular tissues. Finally we consider the expanding role of SMN, and other splicing factors, in the regulation of gene expression in stem cell biology, thereby providing insight into a number of debilitating diseases.

关键词： stem cells splicing survival motor neuron (SMN) spinal muscular atrophy (SMA)

Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China

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World Journal of Psychiatry 2024年第4期14卷 523-532页

作者： Jing-Wen Xu Xiao-Bo Guan Xue-Ying Wang Yang Feng Qi Zhang Jun-Juan Zhu Jian-Hua Chen Department of Medicine Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China The Fourth Sick Ward Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Psychotic DisordersShanghai 200030China The First Sick Ward Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China

BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is *** To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS *** This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric *** plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid *** patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were *** Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female *** and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 *** male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total *** Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

关键词： Antipsychotics Risperidone 9-hydroxyrisperidone Plasma drug concentration monitoring Chronic schizophrenia

Dual prognostic role of 2-oxoglutarate-dependent oxygenases in ten cancer types:implications for cell cycle regulation and cell adhesion maintenance

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Cancer Communications 2019年第1期39卷 214-227页

作者： Wai Hoong Chang Donall Forde Alvina G.Lai Nuffield Department of Medicine University of OxfordOld Road CampusOxford OX37FZUK

Background: Tumor hypoxia is associated with metastasis and resistance to chemotherapy and radiotherapy. Genes involved in oxygen-sensing are clinically relevant and have significant implications for prognosis. In this study, we examined the pan-cancer prognostic significance of oxygen-sensing genes from the 2-oxoglutarate-dependent oxygenase family. Methods: A multi-cohort, retrospective study of transcriptional profiles of 20,752 samples of 25 types of cancer was performed to identify pan-cancer prognostic signatures of 2-oxoglutarate-dependent oxygenase gene family (a family of oxygen-dependent enzymes consisting of 61 genes). We defined minimal prognostic gene sets using three independent pancreatic cancer cohorts (n = 681). We identified two signatures, each consisting of 5 genes. The ability of the signa-tures in predicting survival was tested using Cox regression and receiver operating characteristic (ROC) curve analyses. Results: Signature 1 (KDM8, KDM6B, P4HTM, ALKBH4, ALKBH7) and signature 2 (KDM3A, P4HA1, ASPH, PLOD1, PLOD2) were associated with good and poor prognosis. Signature 1 was prognostic in 8 cohorts representing 6 cancer types (n = 2627): bladder urothelial carcinoma (P = 0.039), renal papillary cell carcinoma (P = 0.013), liver cancer (P = 0.033 and P = 0.025), lung adenocarcinoma (P = 0.014), pancreatic adenocarcinoma (P 9 cancer types (n = 4134): bladder urothelial carcinoma (P = 0.039), cervical squamous cell carcinoma and endocervical adenocar-cinoma (P = 0.035), head and neck squamous cell carcinoma (P = 0.038), renal clear cell carcinoma (P = 0.012), renal papillary cell carcinoma (P = 0.002), liver cancer (P ox regression confirmed independen

关键词： oxygen-sensing gene 2-oxoglutarate-dependent oxygenase Pan-cancer Prognosis Hypoxia KDM8 HNF4A

Interactions of complement proteins C1q and factor H with lipid A and Escherichia coli:further evidence that factor H regulates the classical complement pathway

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Protein & Cell 2011年第4期2卷 320-332页

作者： Lee Aun Tan Andrew C.Yang Uday Kishore Robert B.Sim Medical Research Council Immunochemistry Unit Department of BiochemistryUniversity of OxfordSouth Parks RoadOxford OX13QUUK Present address:Department of Immunology Faculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W120NNUK St Peter’s College New Inn Hall St.Oxford OX12DLUK Present address:SUNY Downstate College of Medicine 450 Clarkson Avenue BrooklynNY 11203USA Weatherall Institute of Molecular Medicine John Radcliffe HospitalUniversity of OxfordHeadingtonOxford OX39DSUK Present address:Center for Infection Immunity and Disease MechanismsBiosciencesSchool of Health Sciences and Social CareBrunel UniversityUxbridge UB83PH West LondonUK Present address:Department of Pharmacology University of OxfordMansfield RoadOxford OX13QTUK

Proteins of the complement system are known to interact with many charged *** recently characterized binding of C1q and factor H to immobilized and liposomal anionic *** H inhibited C1q binding to anionic phospholipids,suggesting a role for factor H in regulating activation of the complement classical pathway by anionic *** extend this finding,we examined interactions of C1q and factor H with lipid A,a well-characterized activator of the classical *** report that C1q and factor H both bind to immobilized lipid A,lipid A liposomes and intact Escherichia coli *** H competes with C1q for binding to these ***,increasing the factor H:C1q molar ratio in serum diminished C4b fixation,indicating that factor H diminishes classical pathway *** recombinant forms of the Cterminal,globular heads of C1q A,B and C chains bound to lipid A and *** in a manner qualitatively similar to native C1q,confirming that C1q interacts with these targets via its globular head *** observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain *** is distinct from its role as an alternative pathway *** suggest that under physiological conditions,factor H may serve as a downregulator of bacterially-driven inflammatory responses,thereby finetuning and balancing the inflammatory response in infections with Gram-negative bacteria.

关键词： complement lipid A bacteria factor H C1q

Photocontrolled polymer adhesives facilitate the assembly of hydrogels for soft robotics

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Science China Chemistry 2024年第10期67卷 3184-3186页

作者： Diling Yang Hao Zhang Hongbo Zeng School of Materials and Environmental Engineering Hunan University of HumanitiesScience and TechnologyLoudi 417000China Department of Chemical and Materials Engineering University of AlbertaEdmontonAlberta T6G 1H9Canada

Both Sun Wukong in eastern mythology and Transformers in western science fiction animation have profoundly inspired the design of deformable materials and modern *** application scope of intelligent materials,also known as smart materials,which are capable of responding to external stimuli to achieve shape changes,structural reorganization,and functional reconfiguration,is wide-ranging,and it covers areas such as soft robotics and flexible electronics[1–3],4D printing[4,5],biomedical equipment[6,7],sensing devices[8],and energy harvesting systems[9].

关键词： printing harvesting smart

PROTEIN SEPARATION USING ULTRAFILTRATION-AN EXAMPLE OF MULTI-SCALE COMPLEX SYSTEMS

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China Particuology 2005年第6期3卷 343-348页

作者： Zhanfeng Cui Department of Engineering Science University of Oxford Parks Road Oxford OX1 3P J UK

In this mini-review, the complexity of protein fractionation using ultrafiltration is discussed. The coupling of the system hydrodynamics, boundary Layer transport, membrane permeation, electrostatic and hydrophobic interactions and its effects on protein transmission and membrane selectivity are analysed. Although ultrafiltration is promising for larger scale protein purification and also with outstanding advantages both technically and economically, much needs to be done to derive the general guidance for membrane selection, process design and system operation. With fine tuning of operational and physiochemical conditions, the process can be greatly improved in terms of process productivity and protein purity. A coupled multi-scale approach might provide a way forward to analyse this complex system and improve the confidence in applying such a promising technology and predictability of the outcome.

关键词： protein purification protein fractionation ultrafiltration membrane separation multi-scale analysis

Magnetic control： Switchable ultrahigh magnetic gradients at Fe3O4 nanoparticles to enhance solution-phase mass transport

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Nano Research 2015年第10期8卷 3293-3306页

作者： Kamonwad Ngamchuea Kristina Tschulik Richard G. Compton DepartmentofChemistry Physical&TheoreticalChemistryLaboratoryUniversityofOxfordSouthParksRoadOxfordOX13QZUK

Enhancing mass transport to electrodes is desired in almost all types of electrochemical sensing, electrocatalysis, and energy storage or conversion. Here, a method of doing so by means of the magnetic gradient force generated at magnetic-nanoparticle-modified electrodes is presented. It is shown using Fe3O4-nanoparticle-modified electrodes that the ultrahigh magnetic gradients （〉10^8 T·m^- 1） established at the magnetized Fe3O4 nanoparticles speed up the transport of reactants and products at the electrode surface. Using the Fe（Ⅲ）/ Fe（Ⅱ）-hexacyanoferrate redox couple, it is demonstrated that this mass transport enhancement can conveniently and repeatedly be switched on and off by applying and removing an external magnetic properties of magnetite nanoparticles field, owing to the superparamagnetic Thus, it is shown for the first time that magnetic nanoparticles can be used to control mass transport in electrochemical systems. Importantly, this approach does not require any means of mechanical agitation and is therefore particularly interesting for application in micro- and nanofluidic systems and devices.

关键词： superparamagneficmagnetite nanoparficles nanoparticle-modifiedelectrodes magnetic field effects magnetoelectrochemistry

Unveiling anomalous lattice shrinkage induced by Pi-backbonding in Prussian blue analogues

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Journal of Energy Chemistry 2022年第7期31卷 121-128,I0004页

作者： Ju-Hyeon Lee Jin-Gyu Bae Hyeon Jeong Lee Ji Hoon Lee School of Materials Science and Engineering Kyungpook National UniversityDaegu 41566Republic of Korea Department of Materials University of OxfordOxford OX13PHUnited Kingdom

Transition-metal(TM)-based Prussian blue and its analogues(TM-PBAs) have attracted considerable attention as cathode materials owing to their versatile ion storage capability with tunable working voltages. TM-PBAs with different crystal structures, morphologies, and TM combinations can exhibit excellent electrochemical properties because of their unique and robust host frameworks with well-defined ionic diffusion channels. Nonetheless, there is still a lack of understanding regarding the performance dependence of TM-PBAs on structural changes during charging/discharging processes. In this study, in situ X-ray diffraction and X-ray absorption fine structure analyses elucidate the TMdependent structural changes in a series of TM-PBAs during the charging and discharging *** the discharging process, the lattice volume of Fe-PBA increased while those of Ni-and Cu-PBAs decreased. This discrepancy is attributed to the extent of size reduction of the cyanometallate complex([Fe(CN)_(6)]) via pi-backbonding from Fe to C due to redox flips of the low-spin Fe^(3+/2+) ion. This study presents a comprehensive understanding of how TM selection affects capacity acquisition and phase transition in TM-PBAs, a promising class of cathode materials.

关键词： Prussian blue analogues X-ray diffraction X-ray absorption fine structure Pi-backdonation Cyanides

Numerical Simulation of Microcarrier Motion in a Rotating Wall Vessel Bioreactor

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Biomedical and Environmental Sciences 2006年第3期19卷 163-168页

作者： ZHI-HAO JU TIAN-QING LIU XUE-Hu MA ZHAN-FENG CUI State Key Laboratory of Fine Chemical Engineering Stem Cells ＆ Tissue Engineering Laboratory Dalian University of Technology Dalian 116012 Liaoning China Department of Engineering Science Oxford University Oxford OX1 3PJ UK

Objective To analyze the forces of rotational wall vessel （RWV） bioreactor on small tissue pieces or microcarrier particles and to determine the tracks of microcarrier particles in RWV bioreactor. Methods The motion of the microcarrier in the rotating wall vessel （RWV） bioreactor with both the inner and outer cylinders rotating was modeled by numerical simulation. Results The continuous trajectory of microcarrier particles, including the possible collision with the wall was obtained. An expression between the minimum rotational speed difference of the inner and outer cylinders and the microcarrier particle or aggregate radius could avoid collisions with either wall. The range of microcarrier radius or tissue size, which could be safely cultured in the RWV bioreactor, in terms of shear stress level, was determined. Conclusion The model works well in describing the trajectory of a heavier microcarrier particle in rotating wall vessel.

关键词： Tissue engineering Bioreactor Rotating wall vessel Numerical simulation