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Tissue distribution and tumor uptake of folate receptor–targeted epothilone folate conjugate,BMS-753493,in CD2F1 mice after systemic administration

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Acta Pharmaceutica Sinica B 2016年第5期6卷 460-467页

作者： Hong Shen Lifei Wang Weiqi Chen Krista Menard Yang Hong Yuan Tian samuel j.bonacorsi W.Griffith Humphreys Francis Y.Lee jinping Gan Pharmaceutical Candidate Optimization Bristol-Myers Squibb Research & Development Discovery Oncology Bristol-Myers Squibb Research & Development Chemistry Bristol-Myers Squibb Research & Development

To assess targeting of an epothilone folate conjugate(BMS-753493) to the folate receptor(FR)-overexpressed tumor in mice bearing both FRt and FR– tumors,a series of experiments were conducted by quantitative whole-body autoradiography(QWBA) and LC–MS/MS following *** of BMS-753493 or its active moiety,BMS-748285 in mice bearing FRt(98M109) and FR–(M109) *** showed [3H]BMS-753493–derived radioactivity was extensively distributed to various *** FR over-expressing 98M109 tumors showed consistently higher level of radioactivity than FR-negative tumors(i.e.,M109 tumors) up to 48 h post dose of [3H]BMS-753493,despite the magnitude of difference between the tumors is relatively small(generally 3 5-fold).The radioactivity level in 98M109 tumors was 2 12-fold of normal tissues except intestine/content at 48 h post *** selective radioactivity uptake into 98M109 tumors over M109 or normal tissues was observed after *** of the active epothilone,[3H]***–MS/MS measurements demonstrated that the concentrations of BMS-748285,presumably from hydrolysis of the folate conjugate,in 98M109 tumors were greater than those in M109 tumors after *** of BMS-753493(2–3-fold) whereas no differential uptake in the tumors following BMS-748285 *** data were consistent with radioactivity *** results demonstrated that the folate conjugation in BMS-753493 enabled moderately preferential distribution of the active epothilone to FR overexpressing 98M109 tumors,thereby supporting targeted delivery of cytotoxics through the folate receptor.

关键词： Folate receptor Tumor selective targeting Folate receptor–expressing tumor Epothilone folate conjugate Tissue distribution Tumor uptake

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Single-atom Pt on carbon nanotubes for selective electrocatalysis

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Carbon Energy 2024年第1期6卷 63-71页

作者： samuel S.Hardisty Xiaoqian Lin Anthony R.j.Kucernak David Zitoun Department of Chemistry Bar Ilan Institute of Nanotechnology and Advanced Materials(BINA)Bar Ilan UniversityRamat GanIsrael Department of Chemistry Molecular Science Research HubImperial College LondonLondonUK

Utilizing supported single atoms as catalysts presents an opportunity to reduce the usage of critical raw materials such as platinum,which are essential for electrochemical reactions such as hydrogen oxidation reaction(HOR).Herein,we describe the synthesis of a Pt single electrocatalyst inside single-walled carbon nanotubes(SWCNTs)via a redox *** via electron microscopy,X-ray photoelectron microscopy,and X-ray absorption spectroscopy show the single-atom nature of the *** electrochemical behavior of the sample to hydrogen and oxygen was investigated using the advanced floating electrode technique,which minimizes mass transport limitations and gives a thorough insight into the activity of the *** single-atom samples showed higher HOR activity than state-of-the-art 30%Pt/C while almost no oxygen reduction reaction activity in the proton exchange membrane fuel cell operating *** selective activity toward HOR arose as the main fingerprint of the catalyst confinement in the SWCNTs.

关键词： confinement electrocatalysis hydrogen platinum single atom catalysts

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Constrained re-calibration of two-equation Reynolds-averaged Navier–Stokes models

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Theoretical & Applied Mechanics Letters 2024年第2期14卷 82-89页

作者： Yuanwei Bin Xiaohan Hu jiaqi Li samuel j.Grauer Xiang I.A.Yang Department of Mechanical Engineering Pennsylvania State UniversityUniversity ParkPA 16802USA State Key Laboratory for Turbulence and Complex Systems Peking UniversityBeijing 100871China College of Engineering Peking UniversityBeijing 100871China

Machine-learned augmentations to turbulence models can be advantageous for flows within the training dataset but can often cause harm *** lack of generalizability arises because the constants(as well as the functions)in a Reynolds-averaged Navier–Stokes(RANS)model are coupled,and un-constrained re-calibration of these constants(and functions)can disrupt the calibrations of the baseline model,the preservation of which is critical to the model's *** safeguard the behaviors of the baseline model beyond the training dataset,machine learning must be constrained such that basic calibrations like the law of the wall are kept *** letter aims to identify such constraints in two-equation RANS models so that future machine learning work can be performed without violating these *** demonstrate that the identified constraints are not ***,they help preserve the generalizability of the baseline model.

关键词： Machine learning Turbulence modeling Reynolds-averaged Navier-Stokes

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Sustainable plasticulture in Chinese agriculture: a review of challenges and routes to achieving long-term food and ecosecurity

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Frontiers of Agricultural Science and Engineering 2024年第1期11卷 155-168页

作者： samuel j.CUSWORTH William j.DAVIES Martin R.MCAINSH Carly j.STEVENS Weilu WANG Lancaster Environment Centre Lancaster UniversityLancasterLA14YQUK The Institutes of Agricultural Science and Technology Development Yangzhou UniversityYangzhou 225009China

Plastic pollution is global concern, affecting most aspects of global food production systems. Plasticulture, a practice used in agriculture to improve crop quality and quantity, among other factors, is a significant source of plastic pollution. This review examines the extent of plasticulture in China, the implications of the practice across decades of use and the legislative instruments used to resolve those issues. It briefly assesses the effectiveness of these policies and proposes possible future innovations to promote increases in long-term food and eco-security, where sustainable plasticulture is a key agent for change. While plasticulture has increased agricultural productivity in growth-limiting conditions, plastic pollution in agricultural soils has become acute in China. Consequently, plastic pollution is having deleterious effects on soil health and in turn, crop productivity in China. Plastic pollution in agriculture is a multifaceted issue and so proposed solutions should be informed by this complexity. Current measures do not reflect a holistic approach to solving this socioecological challenge and adopt a top-down approach, with little or no supportive mechanisms. Future recommendations need to consider the particular set of conditions that influence the production, use and end-of-life management of agriplastics,specific to the environmental, economic and social conditions in each location.

关键词： Circular plastics economy crop production food security plastic pollution sustainable plasticulture

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Thermochemical co-conversion of biomass-plastic waste to biochar:a review

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Green Chemical Engineering 2024年第1期5卷 31-49页

作者： Adewale George Adeniyi Kingsley O.Iwuozor Ebuka Chizitere Emenike Oluwaseun j.Ajala samuel Ogunniyi Kabir B.Muritala Department of Chemical Engineering Faculty of Engineering and TechnologyUniversity of IlorinIlorinP.M.B.1515Nigeria Department of Chemical Engineering Landmark UniversityOmu-AranKwara StateP.M.B.1001Nigeria Department of Pure and Industrial Chemistry Nnamdi Azikiwe UniversityAwkaP.M.B.5025Nigeria Department of Chemistry Federal University of TechnologyBosso CampusMinnaNiger StateP.M.B.65Nigeria

Biomass and plastics are two of the most common municipal solid wastes globally that have continuously placed a burden on the *** is therefore important that they are properly *** coconversion offers a valuable opportunity to recycle biomass and plastics simultaneously into biochar,which reduces the time and cost of recycling them individually while producing a material with a wide range of *** study is a review of published literature that discusses the thermochemical co-processing of biomass and plastic wastes into *** was observed that co-pyrolysis and co-hydrothermal carbonization are the most commonly utilized technologies for this *** characteristics of different biomass and plastics that have been thermochemically converted into biochar were *** properties of the resulting biochar are affected by the feedstock composition,pre-treatment and blending ratio,the reactor’s configuration,reaction temperature,and the presence of a *** studies found that treating the feedstocks separately resulted in a lower yield of biochar than processing them *** biochar created by this procedure has been used as a soil additive and as an adsorbent for water *** perspectives and suggestions,such as the necessity for some technical advancement,biochar’s economic benefits,improved government participation,and raised social awareness,were also *** factors have the potential to propel this field of study to great horizons.

关键词： Biomass Co-pyrolysis Plastic Thermochemical process Valorization

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Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma

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Oncology Research 2024年第7期32卷 1163-1172页

作者： LISANNE K.A.NEIjENHUIS LEUTA L.NAUMANN SONIA A.M.FERKEL samuel j.S.RUBIN STEPHAN ROGALLA Division of Gastroenterology and Hepatology Department of MedicineSchool of MedicineStanford UniversityStanford94305USA Department of Surgery Leiden University Medical CenterLeiden2333 ZAThe Netherlands Centre for Human Drug Research Leiden2333 CLThe Netherlands Department of General VisceralVascular and Thoracic SurgeryCharite University Medicine BerlinBerlin10117Germany

Background:Osteosarcoma is the most common malignant primary bone *** prognosis for patients with disseminated disease remains very poor despite recent advancements in ***,current treatment regimens bear a signiﬁcant risk of serious side ***,there is an unmet clinical need for effective therapies with improved safety proﬁ*** is an antibacterial agent that has been shown to induce cell death in different types of cancer cell ***:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day *** were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal ***:After 35 days,mice were euthanized,and the tumors were harvested for *** mice were excluded from the analysis due to *** weight was signiﬁcantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this *** tumor weight was signiﬁcantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the *** antineoplastic effects were observed on intramuscular tumors or for intravenous administration of *** were no signiﬁcant differences in microvessel density or mitotic rate between treatment *** body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is ***:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are ***,its toxic proﬁle grants further *** these observations,further research is necessary to

关键词： Osteosarcoma Taurolidine Cancer treatment Chemotherapy Murine models

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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(P<0.001;Spearman’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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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K jacobs Steven D Morley Kay samuel Katie Morgan Lyndsey Boswell Timothy j Kendall David A Dorward jonathan A Fallowfield Peter C Hayes john N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

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An electropenetrography waveform library for the probing and ingestion behaviors of Culex tarsalis on human hands

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Insect Science 2024年第4期31卷 1165-1186页

作者： Anastasia M.W.Cooper samuel B.jameson Victoria Pickens Cameron Osborne Elaine A.Backus Kristopher Silver Dana N.Mitzel Department of Entomology Kansas State UniversityManhattanKansasUSA Department of Tropical Medicine Tulane University School of Public Health and Tropical MedicineNew OrleansLos AngelesUSA USDA Agricultural Research Service San Joaquin Valley Agricultural Sciences CenterParlierCaliforniaUSA National Bio and Agro-Defense Facility USDA Agricultural Research ServiceManhattanKansasUSA

Culex tarsalis Coquillett(Diptera:Culicidae)mosquitoes are capable of vectoring numerous pathogens affecting public and animal ***,the probing behaviors of mosquitoes are poorly understood because they occur in opaque ***(EPG)has the potential to elucidate these behaviors by recording the electrical signals generated during *** used an AC–DC EPG with variable input resistors(Ri levels)to construct a waveform library for *** feeding on human *** events associated with mosquito probing were used to characterize waveforms at four Ri levels and with two electrical current *** optimal settings for EPG recordings of *** probing on human hands was an Ri level of 10^(7)Ohms using an applied signal of 150 millivolts alternating *** for *** included those previously observed and associated with probing behaviors in Aedes aegypti L.(Diptera:Culicidae):waveform families j(surface salivation),K(stylet penetration through the skin),L(types 1 and 2,search for a blood vessel/ingestion site),M(types 1 and 2,ingestion),N(type 1,an unknown behavior which may be a resting and digestion phase),and W(withdrawal).However,we also observed variations in the waveforms not described in ***,which we named types L3,M3,M4,and *** investigation enhances our understanding of mosquito probing *** also provides a new tool for the automated calculation of peak *** work will facilitate future pathogen acquisition and transmission studies and help identify new pest and disease management targets.

关键词： AC-DC blood feeders electrical penetration graph EPG human hands mosquitoes waveform library

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Laparoscopic management of remnant gall bladder with stones: Lessons from a tertiary care centre's experience

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Laparoscopic, Endoscopic and Robotic Surgery 2024年第1期7卷 27-33页

作者： Gilbert samuel jebakumar jeevanandham Muthiah Loganathan jayapal R.Santhosh Kumar Siddhesh Tasgaonkar K.S.Santhosh Anand j.K.A.jameel Sudeepta Kumar Swain K.j.Raghunath Prasanna Kumar Reddy Tirupporur Govindaswamy Balachandar Department of Surgical Gastroenterology Apollo HospitalsChennai 600006India Department of General Surgery Apollo HospitalsChennai 600006India Department of Minimal Access Surgery Apollo HospitalsChennai 600006India

Objective:Laparoscopic cholecystectomy is currently the gold standard for treating symptomatic gallstone *** its success,approximately 10%of patients may experience persistent biliary symptoms,leading to the post-cholecystectomy syndrome.A remnant gallbladder with cystic duct or bile duct stones is one of the causes of this *** objective of this study was to shed light on the clinical manifestations,evaluation,therapeutic strategies,and outcomes associated with laparoscopic management of symptomatic remnant ***:This was a retrospective study,conducted over a five-year period(january 2017 to December 2022)at Apollo Hospitals in South *** patients who underwent laparoscopic completion cholecystectomy for a remnant gall bladder were *** following data were collected:patient demographics,symptoms,preoperative investigations,intraoperative details and post operative ***:In total,36 patients were included and *** majority of patients were male(25,69.4%),with a mean age of 50.7±12.1 *** most common presentation was pain in the upper abdomen or right upper quadrant region(24,66.7%).The laparoscopic approach was attempted in all patients,with a success rate of 94.4%.Two patients required conversion to open *** fistula to the colon was observed in one *** was observed in 7 patients(19.4%),and stone clearance was successfully achieved using endoscopic retrograde cholangiopancreatography in all patients ***:Incomplete gall bladder removal either intentionally or unintentionally leaves a remnant gall bladder that is at risk for stone formation and *** who have this clinical entity with symptoms require a redo or complete cholecystectomy,a complex procedure associated with certain *** study highlights the feasibility and safety of laparoscopic completion cholecystectomy for the management of remnant gallbladder

关键词： Remnant gall bladder Stump cholecystitis Subtotal cholecystectomy Laparoscopic completion cholecystectomy

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