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Regulating the morphology of fluorinated non-fullerene acceptor and polymer donor via binary solvent mixture for high efficiency polymer solar cells

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Science china chemistry 2019年第9期62卷 1221-1229页

作者： Mengxue chen Zhuohan Zhang Wei li Jinlong cai Jiangsheng Yu emma l. K. Spooner Rachel c. Kilbride Donghui li Baocai Du Robert S. Gurney Dan liu Weihua Tang David G. lidzey Tao Wang School of Materials Science and Engineering Wuhan University of Technology Wuhan 430070 China State Key laboratory of Silicate Materials for Architectures Wuhan University of Technology Wuhan 430070 China School of chemical Engineering Nanjing University of Science and Technology Nanjing 210094 China Department of Physics and Astronomy University of Sheffield Sheffield S3 7RH UK

Fluorinated non-fullerene acceptors(NFAs) usually have planar backbone and a higher tendency to crystallize compared to their non-fluorinated counterparts, which leads to enhanced charge mobility in organic solar cells(OScs). However, this selforganization behavior may result in excessive phase separation with electron donors and thereby deteriorate device ***, we demonstrate an effective approach to tune the molecular organization of a fluorinated NFA(INPIc-4 F), and its phase separation with the donor PBDB-T, by varying the casting solvent. A prolonged film drying time encourages the crystallization of INPIc-4 F into spherulites and consequently results in excessive phase separation, leading to a low device power conversion efficiency(PcE) of 8.1%. contrarily, a drying time leads to fine mixed domains with inefficient charge transport properties,resulting in a moderate device PcE of 11.4%. An intermediate film drying time results in the formation of face-on π-π stacked PBDB-T and INPIc-4 F domains with continuous phase-separated networks, which facilitates light absorption, exciton dissociation as well as balanced charge transport towards the electrode, and achieves a remarkable PcE of 13.1%. This work provides a rational guide for optimizing the molecular ordering of NFAs and electron donors for high device efficiency.

关键词： organic solar cells non-fullerene acceptors solvent morphology efficiency

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Inflammatory response to coronary artery bypass surgery: Does the heme-oxygenase-1 gene microsatellite polymorphism play a role?

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chinese Medical Journal 2005年第15期118卷 1285-1290页

作者： lI Ping Jules Sanders emma Hawe David Brull Hugh Montgomery Steve Humphries cardiovascular Department Second Affiliated Hospital of Jiangxi Medical College Nanchang 330006 China centre for cardiovascular Genetics British Heart Foundation Laboratories Department of Medicine Royal Free ＆ University College London Medical School Rayne Building 5 University Street London WC1E 6JF UK

Background Heme-oxygenase 1 （HO-1） is a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide （cO） and may have significant anti-inflammatory function. The HO-1 gene promoter region shows microsatellite polymorphism with different （GT）n repeats, reported to differently induce gene expression, with the short allele associated with higher gene expression. We measured the acute inflammatory response using coronary artery bypass surgery （cABG） as a well-characterized and uniform stimulus and examined the correlation between levels of Il-6, c-reactive protein （cRP） and fibrinogen and their relationship to HO-1 genotype. Methods Two hundred and seventy-five consecutive patients undergoing cABG were genotyped for the HO-1 promoter polymorphism using PcR and automated DNA capillary sequencer. Il-6, cRP and fibrinogen were measured at baseline and 6, 24, 48, 72, 96 and 120 hours after cABG. Results complete Il-6, cRP and fibrinogen measures were available in 220 patients. Before surgery Il-6 levels showed a strong correlation with cRP and fibrinogen （ r = 0. 48, P 〈 0. 0001 ; r = 0. 41, P 〈 0. 0001 respectively）, with a significant correlation between cRP and fibrinogen （r=0. 61, P 〈 0. 0001 ）. All three acute phase reactants showed a significant increase after cABG. After surgery, peak Il-6 was strongly correlated with peak cRP （r=0. 34, P =0.0009） but not with peak fibrinogen （r=0. 15, P =0. 13 ）, while peak cRP and peak fibrinogen were significantly correlated （r = 0. 15, P 〈 0. 0001 ）. HO-1 allelic repeats ranged from 22- 42, with （GT）25 and （GT）32 being the two most common alleles, and subsequently divided into three groups according to previous published work：〈 30 （GT） n were designated as S （short） , 30 - 37 （GT） n as M （middle） and long repeats with 〉 37 （GT） n as l （long） ; allele frequency 0. 35, 0. 58 and 0.07 respectively. Baseline cRP differed by genotype： those carrying at least one long allele having higher cRP than those

关键词： heine oxygenase polymorphism inflammation bypass surgery

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Assessing vulnerability to panic:a systematic review of psychological and physiological responses to biological challenges as prospective predictors of panic attacks and panic disorder

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General Psychiatry 2019年第6期32卷 297-303页

作者： Donald J Robinaugh Meredith J Ward emma R Toner Mackenzie l Brown Olivia M losiewicz Eric Bui Scott P Orr Department of Psychiatry Massachusetts General HospitalBostonMassachusettsUSA Department of Psychiatry Harvard Medical SchoolBostonMassachusettsUSA

Background cognitive-behavioural theories of panic disorder posit that panic attacks arise from a positive feedback loop between arousal-related bodily sensations and perceived *** a recently develope computational model formalising these theories of pani attacks,it was observed that the response to a simulate perturbation to arousal provided a strong indicator of vulnerability to panic attacks and panic *** this/review,we evaluate whether this observation is borne o in the empirical literature that has examined responses biological challenge(eg,c02 inhalation)and their relatio to subsequent panic attacks and panic *** We searched PubMed,Web of Science and PsycINFO using keywords denoting provocation agents(eg,sodium lactate)and procedures(eg,infusion)combined with keywords relevant to panic disorder(eg,panic).Articles were eligible if they used response to a biologic challenge paradigm to prospectively predict panic attac or panic *** We identified four eligible *** effect sizes suggest that there is biological challenge response a moderate prospective association with subsequent pani attacks,but no prospective relationship with panic disorde conclusions These findings provide support for the prediction derived from cognitive-behavioural theories an some preliminary evidence that response to a biological challenge may have clinical utility as a marker of vulnerab to panic attacks pending further research and developme Trial registration number 135908.

关键词： behaviour subsequent sizes

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characterisation of colonic dysplasia-like epithelial atypia in murine colitis

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World Journal of Gastroenterology 2016年第37期22卷 8334-8348页

作者： Sarron Randall-Demllo Ruchira Fernando Terry Brain Sukhwinder Singh Sohal Anthony l cook Nuri Guven Dale Kunde Kevin Spring Rajaraman Eri School of Health Sciences University of Tasmania LauncestonLaunceston TAS 7250 Australia Department of Pathology Launceston General Hospital LauncestonLaunceston TAS 7250 Australia Wicking Dementia Research and Educatio ceutre University of Tasmania Hobart TAS 7005 Australia Division of Pharmacy School of Medicine University of Tasmania Hobart TAS 7005 Australia Breathe Well centre of Research Excellence for chronic Respiratory Disease and lung Ageing School of Medicine University of TasmaniaHobart TAS 7005Australia Medical Oncology Ingham Institute for Applied Medical Research LiverpoolLiverpool NSW 2753 Australia liverpool clinical School Western Sydney University South West Sydney NSW 2052 Australia South West Sydney clinical School University of New South WalesSydney NSW 2052 Australia

AIM To determine if exacerbation of pre-existing chronic colitis in Winnie(Muc2 mutant) mice induces colonic *** Winnie mice and c57Bl6 as a genotype control, were administered 1% w/v dextran sulphate sodium(DSS) orally, followed by drinking water alone in weeklong cycles for a total of three cycles. After the third cycle, mice were killed and colonic tissue collected for histological and immunohistochemical evaluation. Inflammation and severity of dysplasia in the colonic mucosa were assessed in H&E sections of the colon. Epithelial cell proliferation was assessed using Ki67 and aberrant β-catenin signalling assessed with enzyme-based immunohistochemistry. Extracted RNA from colonic segments was used for the analysis of gene expression using real-time quantitative PcR. Finally, the distribution of cxcl5 was visualised using *** compared to controls, Winnie mice exposed to three cycles of DSS displayed inflammation mostly confined to the distal-mid colon with extensive mucosal hyperplasia and regenerative atypia resembling epithelial dysplasia. Dysplasia-like changes were observed in 100% of Winnie mice exposed to DSS, with 55% of these animals displaying changes similar to high-grade dysplasia, whereas high-grade changes were absent in wild-type mice. Occasional penetration of the muscularis mucosae by atypical crypts was observed in 27% of Winnie mice after DSS. Atypical crypts however displayed no evidence of oncogenic nuclear β-catenin accumulation, regardless of histological severity. Expression of cav1, Trp53 was differentially regulated in the distal colon of Winnie relative to wild-type mice. Expression of Myc and ccl5 was increased by DSS treatment in Winnie only. Furthermore, increased ccl5 expression correlated with increased complexity in abnormal crypts. While no overall difference in cxcl5 mucosal expression was observed between treatment groups, epithelial cxcl5 protein appeared to be diminished in the atypical e

关键词： Mice Mucin-2 colon colitis Dysplasia Dextran sulphate sodium

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Advanced bioactive glue tethering lubricin/PRG4 to promote integrated healing of avascular meniscus tears

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Bioactive Materials 2023年第10期28卷 61-73页

作者： Solaiman Tarafder Jaskirti Ghataure David langford Rachel Brooke Ryunhyung Kim Samantha lewis Eyen Julian Bensadoun Jeffrey T.Felix James l.cook chang H.lee Regenerative Engineering laboratory Columbia University Medical Center630 W.168 St.-VC12-212New YorkNY10032USA Thompson laboratory for Regenerative Orthopaedics Missouri Orthopedic InstituteUniversity of Missouri1100 Virginia AvenueColumbi1MO65212USA

Meniscus injuries are extremely common with approximately one million patients undergoing surgical treatment annually in the U.S. alone, but no regenerative therapy exist. Previously, we showed that controlled applications of connective tissue growth factor (cTGF) and transforming growth factor beta 3 (TGFβ3) via fibrin-based bio-glue facilitate meniscus healing by inducing recruitment and stepwise differentiation of synovial mesenchymal stem/progenitor cells. Here, we first explored the potential of genipin, a natural crosslinker, to enhance fibrin-based glue’s mechanical and degradation properties. In parallel, we identified the harmful effects of lubricin on meniscus healing and investigated the mechanism of lubricin deposition on the injured meniscus surface. We found that the pre-deposition of hyaluronic acid (HA) on the torn meniscus surface mediates lubricin deposition. Then we implemented chemical modifications with heparin conjugation and cD44 on our bioactive glue to achieve strong initial bonding and integration of lubricin pre-coated meniscal tissues. Our data suggested that heparin conjugation significantly enhances lubricin-coated meniscal tissues. Similarly, cD44, exhibiting a strong binding affinity to lubricin and hyaluronic acid (HA), further improved the integrated healing of HA/lubricin pre-coated meniscus injuries. These findings may represent an important foundation for developing a translational bio-active glue guiding the regenerative healing of meniscus injuries.

关键词： Knee meniscus Bioactive glue Stem cell recruitment lubricin

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Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis

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World Journal of Diabetes 2022年第3期13卷 260-271页

作者： Mary M Barker Francesco Zaccardi Emer M Brady Gaurav S Gulsin Andrew P Hall Joseph Henson Zin ZinHtike Kamlesh Khunti Gerald P Mccann emma l Redman David R Webb emma G Wilmot Tom Yates Jian Yeo Melanie J Davies Jack A Sargeant Diabetes Research centre University of LeicesterLeicester General HospitalLeicester LE54PWUnited Kingdom Department of cardiovascular Sciences Glenfield HospitalUniversity of LeicesterLeicester LE39QPUnited Kingdom The Hanning Sleep laboratory University Hospitals of Leicester NHS TrustUniversity of LeicesterLeicester LE54PWUnited Kingdom National Institute for Health Research Leicester Biomedical Research CentreLeicester LE54PWUnited Kingdom leicester Diabetes centre University Hospitals of Leicester NHS TrustLeicester LE54PWUnited Kingdom National Institute for Health Research Applied Research Collaboration East MidlandsLeicester LE54PWUnited Kingdom Department of Diabetes University Hospitals of Derby and Burton NHS Foundation TrustDerby DE223NEUnited Kingdom

BAcKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger *** To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with *** A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 *** and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood *** and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk *** A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in *** diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older *** results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(cI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%cI:0.10-0.25)and 0.32 cm higher waist circumference(95%cI:0.14-0.49),after adjustment for duration of diabetes and other *** age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and *** The diagnosis of T2D earlier in life is associated with a worse cardi

关键词： Type 2 diabetes mellitus Early-onset adult type 2 diabetes Age of onset cardiovascular risk Young adults Glycaemic control Obesity

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IgH locus suicide recombination does not depend on NHEJ in contrast to cSR in B cells

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cellular & Molecular Immunology 2019年第2期16卷 201-202页

作者： Hend Boutouil François Boyer Jeanne cook-Moreau Michel cogné Sophie Péron cRIBl UMR CNRS 7276 INSERM U126287000 LimogesFrance Institut Universitaire de France 75000 ParisFrance

IgH locus suicide recombination(lSR)occurs in activated Blymphocytes and may result in the death of the concerned B cell,justifying the name“locus suicide recombination”.1 lSR,as for immunoglobulin(Ig)class switch recombination(cSR),is an intrachromosomal recombination in the Ig heavy chain(IgH)***,lSR somehow appears to be the detrimental counterpart of cSR in activated B cells,since cSR intends for cells to actively participate in immune responses while lSR eliminates B ***,an important question to address is the regulation and the exact molecular mechanism of lSR.

关键词： cSR eliminate concerned

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Acrylamide fragment inhibitors that induce unprecedented conformational distortions in enterovirus 713c and SARS-coV-2 main protease

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3924-3933页

作者： Bo Qin Gregory B.craven Pengjiao Hou Julian chesti Xinran lu emma S.child Rhodri M.l.Morgan Wenchao Niu lina Zhao Alan Armstrong David J.Mann Sheng cui NHc Key laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100076China Department of life Sciences Imperial College LondonSouth Kensington CampusLondon SW72AZUK Department of chemistry Imperial College LondonMolecular Sciences Research HubWhite City CampusWood LaneLondon W120BZUK cAS Key laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsUniversity of Chinese Academy of SciencesBeijing 100049China

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional *** of these proteases exhibit a similar fold and contain an essential catalytic cysteine,offering the opportunity to inhibit these enzymes with electrophilic small *** we describe the successful application of quantitative irreversible tethering(qIT)to identify acrylamide fragments that target the active site cysteine of the 3c protease(3cpro)of Enterovirus 71,the causative agent of hand,foot and mouth disease in humans,altering the substrate binding ***,we re-purpose these hits towards the main protease(Mpro)of SARS-coV-2 which shares the 3c-like fold and a similar active *** hit fragments covalently link to the catalytic cysteine of Mpro to inhibit its *** demonstrate that targeting the active site cysteine of Mpro can have profound allosteric effects,distorting secondary structures to disrupt the active dimeric unit.

关键词： SARS-coV-2 Protease inhibitors covalent fragments Allosteric inhibition EV71

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Molecular analysis of γ1, γ3, and α class switch recombination junctions in APOBEc3-deficient mice using high-throughput sequencing

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cellular & Molecular Immunology 2020年第4期17卷 418-420页

作者： Hussein Issaoui Mélissa Ferrad Nour Ghazzaui Sandrine lecardeur Jeanne cook-Moreau François Boyer Yves Denizot UMR cNRS 7276 INSERM U1262Equipe Labellisée LIGUE 2018University of LimogesCBRSrue Pr.Descottes87025 LimogesFrance

Activation-induced deaminase(AID)is required for immunoglobulin(Ig)class switch recombination(cSR),in which the constant(c)μgene of IgM is substituted with c_(γ),c_(ε),or c_(α),thereby generating IgG,IgE,and IgA antibodies,respectively,with new effector functions but the same antigenic specificity.1 AID targets specific DNA switch(S)regions preceding c regions except for cδ.2 Sμis usually the donor region,while Sγ,ε,αare the acceptor *** deaminates c into U on single-stranded DNA by targeting the WRcY(W=A/T,R=A/G,and Y=c/T)hot motif and,to a lesser extent,the SYc(S=G/c,Y=c/T)cold motif.3,4 AID is a member of the apolipoprotein B editing complex(APOBEc)*** APOBEc genes,a family of evolutionarily conserved cytidine deaminases,APOBEc3 is implicated in diverse cell functions including innate immunity against retroviruses.4 The DNA-editing APOBEc3 enzymes have recently attracted attention due to their involvement in cancer and potential applications in gene editing.5–7 While a single copy of each APOBEc3 gene is present in rodents,seven copies of each APOBEc3 gene are found in humans.

关键词： immunity involvement thereby

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Using induced pluripotent stem cells as a tool for modelling carcinogenesis

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World Journal of Stem cells 2015年第2期7卷 461-469页

作者： emma l curry Mohammad Moad craig N Robson Rakesh Heer Northern Institute for cancer Research Paul O’Gorman BuildingMedical SchoolNewcastle University

cancer is a highly heterogeneous group of diseases that despite improved treatments remain prevalent accounting for over 14 million new cases and 8.2 million deaths per year. Studies into the process of carcinogenesis are limited by lack of appropriate models for the development and pathogenesis of the disease based on human tissues. Primary culture of patient samples can help but is difficult to grow for a number of tissues. A potential opportunity to overcome these barriers is based on the landmark study by Yamanaka which demonstrated the ability of four factors;Oct4, Sox2, Klf4, and c-Myc to reprogram human somatic cells in to pluripotency. These cells were termed induced pluripotent stem cells(i PScs) and display characteristic properties of embryonic stem cells. This technique has a wide range of potential uses including disease modelling, drug testing and transplantation studies. Interestingly i PScs also share a number of characteristics with cancer cells including self-renewal and proliferation, expression of stem cell markers and altered metabolism. Recently, i PScs have been generated from a number of human cancer cell lines and primary tumour samples from a range of cancers in an attempt to recapitulate the development of cancer and interrogate the underlying mechanisms involved. This review will outline the similarities between the reprogramming process and carcinogenesis, and how these similarities have been exploited to generate i PSc models for a number of cancers.

关键词： Induced pluripotent stem cells cancer Model Reprogramming

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