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Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system

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burns & Trauma 2021年第1期9卷 558-572页

作者： Jon Hazeldine robert J.Dinsdale David N.Naumann Animesh Acharjee jonathan r.b.bishop Janet M.Lord Paul Harrison Institute of Inflammation and Ageing University of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom National Institute for Health research Surgical reconstruction and Microbiology research Centre Heritage BuildingQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Scar Free Foundation birmingham Centre for burns research University Hospital Birmingham Foundation TrustQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Academic Department of Military Surgery and Trauma Royal Centre for Defence MedicineQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Institute of Cancer and Genomic Sciences Centre for Computational BiologyUniversity of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom

background:Traumatic injury is associated with increased concentrations of cell-free DNA(cfDNA)in the circulation,which contribute to post-injury *** endonuclease deoxyribonuclease 1(DNase-1)is responsible for removing 90%of circulating ***,DNase activity was reported to be significantly reduced following major non-traumatic brain injury(TbI),but the processes responsible were not ***,it is not known how quickly following injury DNase activity is reduced and whether this also occurs after ***:At 3 post-injury time points(≤1,4–12 and 48–72 hours),blood samples were obtained from 155 adult trauma patients that had sustained an isolated TbI(n=21),TbI with accompanying extracranial injury(TbI^(+))(n=53)or an extracranial injury only(ECI)(n=81).In addition to measuring cfDNA levels and the activity and expression of DNase,circulating concentrations of monomeric globular action(G-actin),an inhibitor of DNase-1,and the actin scavenging proteins gelsolin(GSN)and vitamin D binding protein(VDbP)were determined and values compared to a cohort of healthy ***:Significantly elevated concentrations of plasma cfDNA were seen in TbI,TbI^(+)and ECI patients at all study time points when compared to healthy *** levels were significantly higher at≤1 hour post-injury in ECI patients who subsequently developed multiple organ dysfunction syndrome when compared to those who did *** DNase-1 protein was significantly elevated in all patient groups at all sampling time *** contrast,DNase enzyme activity was significantly reduced,with this impaired function evident in TbI^(+)patients within minutes of *** concentrations of G-actin were elevated in all patient cohorts in the immediate aftermath of injury and this was accompanied by a significant reduction in the levels of GSN and ***:The post-traumatic increase in circulating cfDNA that occurs following extracranial trauma and TbI

关键词： Cell-free DNA Deoxyribonuclease Extracellular actin scavenging system Pre-hospital Trauma

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DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

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Engineering 2024年第7期38卷 39-51页

作者： Kai-bo Wang Yingying Wang jonathan Dickerhoff Danzhou Yang borch Department of Medicinal Chemistry and Molecular Pharmacology College of PharmacyPurdue UniversityWest LafayetteIN 47907USA Purdue Center for Cancer research Purdue UniversityWest LafayetteIN 47907USA Department of Chemistry Purdue UniversityWest LafayetteIN 47907USA Purdue Institute for Drug Discovery Purdue UniversityWest LafayetteIN 47907USA Jiangsu Key Laboratory of bioactive Natural Product research&State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA *** structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer ***,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,bCL2,KrAS,and *** products have long been an important source of drug discovery,particularly in the fields of cancer and infectious *** progress has recently been made in the discovery of naturally occurring DNA G4-targeting *** DNA G4s,such as MYC-G4,bCL2-G4,KrAS-G4,PDGFr-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many ***,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from *** also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

关键词： G-quadruplex Natural products Alkaloids Cancer Promoter

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Local Adaptive Gradient Variance Attack for Deep Fake Fingerprint Detection

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Computers, Materials & Continua 2024年第1期78卷 899-914页

作者： Chengsheng Yuan baojie Cui Zhili Zhou Xinting Li Qingming jonathan Wu Engineering research Center of Digital Forensics Ministry of EducationNanjing University of Information Science and TechnologyNanjing210044China School of Computer Science Nanjing University of Information Science and TechnologyNanjing210044China Institute of Artificial Intelligence and blockchain Guangzhou UniversityGuangzhou510006China School of International relations National University of Defense TechnologyNanjing210039China Department of Electrical and Computer Engineering University of WindsorWindsorN9B 3P4Canada

In recent years,deep learning has been the mainstream technology for fingerprint liveness detection(FLD)tasks because of its remarkable ***,recent studies have shown that these deep fake fingerprint detection(DFFD)models are not resistant to attacks by adversarial examples,which are generated by the introduction of subtle perturbations in the fingerprint image,allowing the model to make fake *** of the existing adversarial example generation methods are based on gradient optimization,which is easy to fall into local optimal,resulting in poor transferability of adversarial *** addition,the perturbation added to the blank area of the fingerprint image is easily perceived by the human eye,leading to poor visual *** response to the above challenges,this paper proposes a novel adversarial attack method based on local adaptive gradient variance for *** ridge texture area within the fingerprint image has been identified and designated as the region for perturbation ***,the images are fed into the targeted white-box model,and the gradient direction is optimized to compute gradient ***,an adaptive parameter search method is proposed using stochastic gradient ascent to explore the parameter values during adversarial example generation,aiming to maximize adversarial attack *** results on two publicly available fingerprint datasets show that ourmethod achieves higher attack transferability and robustness than existing methods,and the perturbation is harder to perceive.

关键词： FLD adversarial attacks adversarial examples gradient optimization transferability

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Academic productivity correlates with industry earnings in foot and ankle fellowship programs in the United States:A retrospective analysis

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World Journal of Orthopedics 2024年第2期15卷 129-138页

作者： Albert T Anastasio Anthony N baumann Kempland C Walley Kyle J Hitchman Conor O’Neill jonathan Kaplan Samuel b Adams Department of Orthopedic Surgery Duke University HospitalDurhamNC 27710United States College of Medicine Northeast Ohio Medical UniversityRootstownOH 44272United States Department of Orthopedic Surgery University of MichiganAnn ArborMI 48109United States School of Osteopathic Medicine Campbell UniversityLillingtonNC 27546United States

bACKGrOUND The study investigates the connection between academic productivity and industry earnings in foot and ankle orthopedic surgery *** metrics like the H-index and Open Payments Database(OPD)data,it addresses a gap in understanding the relationship between scholarly achievements and financial outcomes,providing a basis for further exploration in this specialized medical *** To elucidate the trends between academic productivity and industry earnings across foot and ankle orthopedic surgery fellowship programs in the United *** This study is a retrospective analysis of the relationship between academic productivity and industry earnings of foot and ankle orthopedic surgery fellowships at an individual faculty and fellowship *** productivity was defined via H-index and recorded from the Scopus *** earnings were recorded from the *** Forty-eight foot and ankle orthopedic surgery fellowships(100%of fellowships)in the United States with a combined total of 165 physicians(95.9%of physicians)were *** individual physician(n=165)total life-time earnings reported on the OPD website was United States Dollar(USD)451430.30±1851084.89(range:USD 25.16-21269249.85;median:USD 27839.80).Mean physician(n=165)H-index as reported on Scopus is 14.24±12.39(range:0-63;median:11).There was a significant but weak correlation between individual physician H-index and individual physician total life-time earnings(Prman’s rho=0.334)and a significant and moderate positive correlation between combined fellowship H-index and total life-time earnings per fellowship(P=0.004,Spearman’s rho=0.409).CONCLUSION There is a significant and positive correlation between academic productivity and industry earnings at foot and ankle orthopedic surgery fellowships in the United *** observation is true on an individual physician level as well as on a fellowship level.

关键词： Sunshine act Foot and ankle Orthopedic surgery Orthopedic fellowship Industry earnings

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recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment:A longitudinal cohort study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 79-87页

作者： Jeremy P.Tervo Patricia T.Jacobson brandon J.Vilarello Tiana M.Saak Francesco F.Caruana Liam W.Gallagher Joseph b.Gary David A.Gudis Paule V.Joseph D.P.Devanand Terry E.Goldberg jonathan b.Overdevest Columbia University Vagelos College of Physicians and Surgeons New YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery New York-Presbyterian/Columbia University Irving Medical CenterNew YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery University of PittsburghPittsburghPennsylvaniaUSA Department of Otolaryngology-Head and Neck Surgery University of MinnesotaMinneapolisMinnesotaUSA National Institute of Alcohol Abuse and Alcoholism Section of Sensory Science and Metabolism&National Institute of Nursing ResearchBethesdaMarylandUSA New York-Presbyterian/Columbia University Irving Medical Center New YorkNew YorkUSA

Objectives:Persistent olfactory dysfunction(OD)following loss of smell associated with SArS-CoV-2 infection is a major feature of long *** on the prevalence of persistent OD predominantly rely on self-reported olfactory *** studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute *** anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of *** study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical ***:We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin'Sticks extended test at baseline and 1-year time *** had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not ***:baseline olfactory evaluation was completed by 122 participants,53 of whom completed the 1-year follow-up *** participants presenting with perceived OD,74.5%had confirmed psychophysical OD at baseline,with 55.1%at 1-year *** had reliable trends in self-rated versus psychophysically tested olfactory function at both time *** total threshold,discrimination,and identification(TDI)score improved by+3.25 points in the cohort with psychophysical OD(p=0.0005),with this improvement largely attributable to an increase in median threshold scores(+2.75 points;p=0.0004).Conclusions:OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19,with many demonstrating lingering deficits at *** in threshold,but not discrimination or identification,most significantly mediate improvement

关键词： long COVID olfaction post-COVID condition smell dysfunction

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biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew rawlings Marta roldo Gianluca Tozzi jonathan I.Dawson Gianluca Cidonio richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HbMSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAb)by blending human bone-ECM(b)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HbMSCs viability upon *** composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)*** inclusion of bone morphogenetic protein-2(bMP-2)with the HbMSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay bone 3D bioprinting

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Predictive Factors of renal Failure in COVID-19 Patients at the Anti-COVID Center in Lome, Togo

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Open Journal of Nephrology 2024年第2期14卷 125-135页

作者： Kossi Akomola Sabi Yoan Makafui Amekoudi Awéréou Kotosso Laune Odilon blatome badomta Dolaama Ayodélé jonathan Sabi Oscar Gnirimi Gbahbang Loutou Ahoub-Laye Affo béfa Noto-Kadou-Kaza Nephrology-Hemodialysis Department of CHU Sylvanus Olympio University of Lom Lom Togo Faculty of Health Sciences University of Lom Lom Togo Nephrology Department of the CHU Kara University of Kara Kara Togo Centre Hospitalier Universitaire Pointe--Pitre Pointe--Pitre Guadeloup

background: Angiotensin-converting enzyme 2 has been identified as the receptor that allows the entry of SarsCov2 into the human cell. Its expression in the kidney is 100 times higher than in the lung;thus, making the kidney an excellent target for SarsCov2 infection manifesting as renal failure (rF). The objective of this study was to determine the predictive factors of rF during COVID-19 in the Togolese context. Patients and Methods: This was a retrospective descriptive and analytical study conducted at the Lomé Anti-COVID Center including the records of patients hospitalized for COVID-19, of age ≥ 18 years and having performed a creatinemia. rF was defined by a GFr 2 calculated according to the MDrD formula. Patients were randomized into 2 groups according to GFrresults: 482 patients were selected for this study with a mean age of 58.02 years. Sixty-five percent of the patients were men, i.e., a sex ratio of 1.88. Fifty-two patients had rF, i.e., a frequency of 10.8%.There were 65% men (315 cases), for a sex ratio (M/F) of 1.88. risk factors for renal failure in COVID-19 were age ≥ 65 years (Ora 2.42;CIa95% [1.17 - 4.95];p = 0.016), anemia (Ora 2.49;CIa95% [1.21 - 5.26];p = 0.015), moderate (Ora 13;CIa95% [2.30 - 2.44];p = 0.017), severe (Ora 26.2;CIa95% [4.85 - 4.93];p = 0.002) and critical (Ora 108;CIa95% [16.5 - 21.76];p Conclusion: renal failure would therefore be related to the severity of COVID-19 and is the most formidable factor, conditioning the course of the disease and the patient’s vital prognosis.

关键词： COVID-19 renal Failure risk Factors Togo

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Fjord-Type AIEgens based on Inherent Through-Space Conjugation

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CCS Chemistry 2024年第7期6卷 1739-1747页

作者： Ye-Qiang Han Yuan Xie Jianyu Zhang Shiyu Tan Haoke Zhang ben Zhong Tang jonathan L.Sessler Feihe Huang Stoddart Institute of Molecular Science Department of ChemistryZhejiang UniversityHangzhou 310058 Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials ZJU-Hangzhou Global Scientific and Technological Innovation CenterZhejiang UniversityHangzhou 311215 MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310058 Center for AIE research College of Materials Science and EngineeringShenzhen UniversityShenzhen 518061 Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionThe Hong Kong University of Science and TechnologyKowloonHong Kong 999077 School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)Guangzhou 518172 Department of Chemistry The University of Texas at AustinAustinTexas 78712-1224 Green Catalysis Center and College of Chemistry Zhengzhou UniversityZhengzhou 450001

Through-space conjugation(TSC)is a noncovalently electronic interaction that is emerging as a potential complement to through-bond conjugation(TbC)-based strategies for constructing luminescent ***,the design of efficient luminogens based on TSC is currently challenging due to a lack of established structure-property *** is particularly true in the case of luminogens displaying aggregation-induced emission(AIE)*** this work,three terphenyl derivatives were prepared,and their photophysical properties were systemically *** was found that relative to the corresponding m-and p-linked analogues,the electronic interaction of TbC is weakened while the strength of TSC is commensurately enhanced in the constitutional isomer containing an o-linked fjordtype *** this set of luminogens,the presence of a fjord-type arrangement promotes a transformation from aggregation-caused quenching to *** investigations involving congeneric quaterphenyl and pentphenyl isomers support the universality of the fjord-type unit as a framework for synthesizing AIE-active luminogens(AIEgens)with inherent *** work not only provides a novel set of AIEgens but also establishes the utility of TSC in controlling the photophysical properties of nonconventional and twisted luminogens.

关键词： fjord-type through-space conjugation through-bond conjugation aggregation-induced emission luminescence twisted conformation

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Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth

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The Innovation 2024年第2期5卷 107-114页

作者： Johan Gustafsson Fariba roshanzamir Anders Hagnestål Sagar M.Patel Oseeyi I.Daudu Donald F.becker jonathan L.robinson Jens Nielsen Department of Life Sciences Chalmers University of TechnologySE-41296 GothenburgSweden Hagnesia Ab SE-43854 HindåsSweden Department of biochemistry and redox biology Center University of Nebraska-LincolnLincolnNE 68588USA bioInnovation Institute DK2200 CopenhagenDenmark

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation,but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in ***-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell ***,we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion *** addition,we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human *** combined modeling reproduced severe hypoxic conditions and the Warburg effect,and we found that limitations in enzymatic capacity contribute to cancer cells’preferential use of glutamine as a substrate to the citric acid ***,we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer *** identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts,but when limiting to metabolites previously identified to participate in such collaboration,no growth advantage was *** work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments.

关键词： metabolism effect limitations

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Encapsulated Fe(IV)Molecular Complex for Photoacoustic Imaging

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CCS Chemistry 2024年第5期6卷 1184-1197页

作者： Ye Xu Chao Li Zhong-Yu Yu Jiamin Wang Zhaoyang Liu Chao Jiang Zhen-Feng Chen Xiaoyu Wu Ming-Xing Li Hong Yang Zhao-Xi Wang jonathan L.Sessler Department of Chemistry Center for Supramolecular Chemistry and CatalysisInnovative Drug Research CenterShanghai UniversityShanghai 200444 College of Chemistry and Materials Science Shanghai Key Laboratory of Rare Earth Functional MaterialsShanghai Frontiers Science Center of Biomimetic CatalysisShanghai Normal UniversityShanghai 200234 Sijing Community Health Service Center of Songjiang District Shanghai 201601 Key Laboratory for Chemistry and Molecular Engineering of Medicinal resources Guangxi Normal UniversityGuilin 541004 Department of Chemistry The University of Texas at AustinAustinTexas 78712-1224

stable neutral Fe(IV)complex(Fe-HDCL),readily accessible on the g scale,was found to possess high water solubility and good stability(<5%degradation over 4 h upon photoirradiation).Fe-HDCL is green and absorbs light e... 详细信息

stable neutral Fe(IV)complex(Fe-HDCL),readily accessible on the g scale,was found to possess high water solubility and good stability(radation over 4 h upon photoirradiation).Fe-HDCL is green and absorbs light effectively in the visible region(500–800 nm)with aλmax at 650 nm(ɛ=7830 M^(−1)cm^(−1)).Fe-HDCL also exhibits photothermal(PT)behavior comparable to single-wall carbon nanotubes in the solid *** aqueous solution,high PT conversion(η=72.6%)is achieved,and a strong hyperthermia-based inhibition of cell growth is observed upon subjecting Fe-HDCL to near-infrared 730 nm laser *** biological studies in vitro and in vivo confirmed that Fe-HDCL is biocompatible,clears readily,and allows the visual detection of blood *** subjecting mice to intravenous injection at low doses(e.g.,50μmol·kg^(−1)),Fe-HDCL also permits the photoacoustic(PA)imaging of kidneys and the evaluation of renal fibrosis in mouse *** addition,Fe-HDCL allows PA-based imaging of brain tissues,presumably reflecting its ability to pass through the blood-brain *** thus propose that Fe-HDCL has a role to play as PT agent and as a photodiagnostic.

关键词： stable Fe(IV)complex blood-brain barrier molecular cage photoacoustic imaging renal fibrosis

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