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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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Quantitative multiparametric magnetic resonance imaging can aid non-alcoholic steatohepatitis diagnosis in a japanese cohort

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World journal of Gastroenterology 2021年第7期27卷 609-623页

作者： Kento Imajo Louise Tetlow Andrea Dennis Elizabeth Shumbayawonda Sofia Mouchti timothy j kendall Eve Fryer Shogi Yamanaka Yasushi Honda Takaomi Kessoku Yuji Ogawa Masato Yoneda Satoru Saito Catherine Kelly Matt D Kelly Rajarshi Banerjee Atsushi Nakajima Department of Gastroenterology and Hepatology Yokohama City University School of MedicineYokohama 236-0004Japan Innovation PerspectumOxford OX42LLUnited Kingdom Centre for Inflammation Research University of EdinburghEdinburghUnited KingdomEdinburgh EH164TJUnited Kingdom Department of Cellular Pathology Oxford University Hospitals NHS Foundation TrustOxford OX39DUUnited Kingdom Anatomic and Clinical Pathology Department Yokohoma City University HospitalYokohoma 236-0004Japan Department of Gastroenterology Yokohama City University Graduate School of MedicineYokohama 236-0004Japan

BACKGROUND Non-invasive assessment of non-alcoholic steatohepatitis(NASH)is increasing in desirability due to the invasive nature and costs associated with the current form of assessment;liver *** multiparametric magnetic resonance imaging(mpMRI)to measure liver fat(proton density fat fraction)and fibroinflammatory disease[iron-corrected T1(cT1)],as well as elastography techniques[vibration-controlled transient elastography(VCTE)liver stiffness measure],magnetic resonance elastography(MRE)and 2D Shear-Wave elastography(SWE)to measure stiffness and fat(controlled attenuated parameter,CAP)are emerging alternatives which could be utilised as safe surrogates to liver *** To evaluate the agreement of non-invasive imaging modalities with liver biopsy,and their subsequent diagnostic accuracy for identifying NASH *** From january 2019 to February 2020,japanese patients suspected of NASH were recruited onto a prospective,observational study and were screened using noninvasive imaging techniques;mpMRI with LiverMultiScan®,VCTE,MRE and *** were subsequently biopsied,and samples were scored by three independent *** diagnostic performances of the non-invasive imaging modalities were assessed using area under receiver operating characteristic curve(AUC)with the median of the histology scores as the gold standard *** between all three independent pathologists was further explored using Krippendorff’s alpha(a)from weighted kappa *** N=145 patients with mean age of 60(SD:13 years.),39%females,and 40%with body mass index≥30 kg/m2 were included in the *** identifying patients with NASH,MR liver fat and cT1 were the strongest performing individual measures(AUC:0.80 and 0.75 respectively),and the mpMRI metrics combined(cT1 and MR liver fat)were the overall best non-invasive test(AUC:0.83).For identifying fibrosis≥1,MRE performed best(AUC:0.97),compared to VCTE-liver stiffness measure(AU

关键词： Corrected T1 Fibro-inflammation Non-invasive imaging Non-alcoholic steatohepatitis Multiparametric magnetic resonance imaging Non-alcoholic fatty liver disease

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Kinetics of glyphosate and aminomethylphosphonic acid sorption onto montmorillonite clays in soil and their translocation to genetically modified corn

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journal of Environmental Sciences 2024年第1期135卷 669-680页

作者： Meichen Wang Kelly j Rivenbark timothy D Phillips Veterinary Physiology and Pharmacology College of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityTX 77845USA

The co-occurrence of glyphosate(GLP)and aminomethylphosphonic acid(AMPA)in contaminated water,soil,sediment and plants is a cause for concern due to potential threats to the ecosystem and human health.A major route of exposure is through contact with contaminated soil and consumption of crops containing GLP and AMPA ***,clay-based sorption strategies for mixtures of GLP and AMPA in soil,plants and garden produce have been very *** this study,in vitro soil and in vivo genetically modified corn models were used to establish the proof of concept that the inclusion of clay sorbents in contaminated soils will reduce the bioavailability of GLP and AMPA in soils and their adverse effects on plant *** of chemical concentration(1–10 mg/kg),sorbent dose(0.5%-3%in soil and 0.5%-1%in plants)and duration(up to 28 days)on sorption kinetics were *** time course results showed a continuous GLP degradation to *** inclusion of calcium montmorillonite(CM)and acid processed montmorillonite(APM)clays at all doses significantly and consistently reduced the bioavailability of both chemicals from soils to plant roots and leaves in a dose-and time-dependent manner without detectable *** treated with 0.5%and 1%APM inclusion showed the highest growth rate(p≤0.05)and lowest chemical bioavailability with up to 76%reduction in roots and57%reduction in *** indicated that montmorillonite clays could be added as soil supplements to reduce hazardous mixtures of GLP and AMPA in soils and plants.

关键词： Glyphosate AMPA Adsorption Soil remediation Plant Hydroponic system

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Machine learning-guided accelerated discovery of structure-property correlations in lean magnesium alloys for biomedical applications

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journal of Magnesium and Alloys 2024年第6期12卷 2267-2283页

作者： Sreenivas Raguraman Maitreyee Sharma Priyadarshini Tram Nguyen Ryan McGovern Andrew Kim Adam j.Griebel Paulette Clancy timothy P.Weihs Department of Materials Science and Engineering Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A Hopkins Extreme Materials Institute Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A Department of Chemical and Biomolecular Engineering Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A Translational Tissue Engineering Center Johns Hopkins School of Medicine400 N BroadwayBaltimore21231MDU.S.A Department of Biomedical Engineering Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A Research and Development Fort Wayne Metals Research ProductsLLC9609 Ardmore AveFort Wayne46809INU.S.A Department of Mechanical Engineering Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A

Magnesium alloys are emerging as promising alternatives to traditional orthopedic implant materials thanks to their biodegradability,biocompatibility,and impressive mechanical ***,their rapid in-vivo degradation presents challenges,notably in upholding mechanical integrity over *** study investigates the impact of high-temperature thermal processing on the mechanical and degradation attributes of a lean Mg-Zn-Ca-Mn alloy,*** rapid,cost-efficient characterization methods like X-ray diffraction and optical microscopy,we swiftly examine microstructural changes post-thermal *** Pearson correlation coefficient analysis,we unveil the relationship between microstructural properties and critical targets(properties):hardness and corrosion ***,leveraging the least absolute shrinkage and selection operator(LASSO),we pinpoint the dominant microstructural factors among closely correlated *** findings underscore the significant role of grain size refinement in strengthening and the predominance of the ternary Ca_(2)Mg_(6)Zn_(3)phase in corrosion *** suggests that achieving an optimal blend of strength and corrosion resistance is attainable through fine grains and reduced concentration of ternary *** thorough investigation furnishes valuable insights into the intricate interplay of processing,structure,and properties in magnesium alloys,thereby advancing the development of superior biodegradable implant materials.

关键词： Magnesium alloys Machine learning Corrosion Mechanical properties Rapid characterization

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The Regional Economic Impacts of Coal Mining: A Case Study of Signal Peak Energy

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Natural Resources 2024年第8期15卷 211-223页

作者： timothy j. Considine School of Energy Resources University of Wyoming Laramie USA

This paper quantifies the regional economic contributions of coal exports from the US using a case study of Signal Peak Energy in Montana. Two methods of estimating economic contributions are compared, contribution and impact analysis. The latter is adopted because the industry impact analysis is more accurate, especially since it is based upon accounting records from Signal Peak. Our estimates of regional economic and fiscal impacts do not vary significantly with the price of coal because we explicitly account for swings in royalty income. Our analysis finds that Signal Peak Energy supports 678 jobs, over $55 million in tax revenues, more than $90 million in royalties, $111.7 million in value added, and $62.3 million in labor income. Curtailing or halting Signal Peak’s coal production for environmental reasons as some environmental groups have argued would eliminate these economic contributions.

关键词： Coal Regional Economic Exports Fiscal

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In vivo measurement of NADH fluorescence lifetime in skeletal muscle via -ber-coupled time-correlated single photon counting

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journal of Innovative Optical Health Sciences 2024年第1期17卷 121-134页

作者： Kathryn M.Priest jacob V.Schluns Nathania Nischal Colton L.Gattis jeffrey C.Wolchok timothy j.Muldoon Department of Biomedical Engineering University of Arkansas FayettevilleARUSA

Nicotinamide adenine dinucleotide(NADH)is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis,the tricarboxylic acid cycle,and oxidative phosphorylation(OXPHOS).NADH is autofluorescent,and itsfluorescence lifetime can be used to infer metabolic dynamics in living ***-coupled time-correlated single photon counting(TCSPC)equipped with an implantable needle probe can be used to measure NADH lifetime in vivo,enabling investigation of changing metabolic demand during muscle contraction or tissue *** study illustrates a proof of concept for point-based,minimally-invasive NADHfluorescence lifetime measurement in *** muscle loss(VML)injuries were created in the left tibialis anterior(TA)muscle of male Sprague Dawley *** lifetime measurements were collected before,during,and after a 30 s tetanic contraction in the injured and uninjured TA muscles,which was subsequently-t to a biexponential decay model to yield a metric of NADH utilization(cytoplasmic vs protein-bound NADH,the A11/A22 ratio).On average,this ratio was higher during and after contraction in uninjured muscle compared to muscle at rest,suggesting higher levels of free NADH in contracting and recovering muscle,indicating increased rates of *** injured muscle,this ratio was higher than uninjured muscle overall but decreased over time,which is consistent with current knowledge of inflammatory response to injury,suggesting tissue regeneration has *** data suggest that-ber-coupled TCSPC has the potential to measure changes in NADH binding in vivo in a minimally invasive manner that requires further investigation.

关键词： Glycolysis oxidative phosphorylation energy metabolism volumetric muscle loss

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Bulking Up the Bay-Position Substituents Enables Enhanced Selectivity of C_(s)‑Symmetric Boron Subphthalocyanine−Subnaphthalocyanine Hybrids

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Precision Chemistry 2024年第4期2卷 161-181页

作者： Nina F.Farac Alan j.Lough timothy P.Bender Department of Chemical Engineering and Applied Chemistry University of TorontoTorontoOntario M5S 3E5Canada Department of Chemistry University of TorontoTorontoOntario M5S 3H6Canada Department of Materials Science and Engineering University of TorontoTorontoOntario M5S 3E4Canada Department of Mechanical and Industrial Engineering University of TorontoTorontoOntario M5S 3G8Canada

The precise synthesis of subporphyrinoid hybrids withπ-expanded topologies and unique material properties plays a promising role in the design of functional ***,selective,and controllable routes to boron subphthalocyanine−subnaphthalocyanine hybrids,Bsub(Pc_(3‑p)-Nc_(p))s,are desirable for this purpose yet synthetically challenging due to random mixtures of C_(s-),C_(3v-),and,in some cases,C_(1)-symmetric compounds that form during traditional statistical mixed ***,we addressed this issue by developing a sterically driven mixed cyclotrimerization with enhanced selectivity for the targeted C_(s)-symmetric hybrid and complete suppression of sterically crowded macrocyclic *** process,coupled with a rationally designed precursor bearing bulky phenyl substituents,enabled the synthesis and characterization of bay-position phenylated Ph_(2)-(R_(p))_(8)Bsub(Pc_(2)-Nc_(1))hybrids with halogens(Rp=Cl or F)in their peripheral isoindole *** selectivity ranged between 59 and 72%with remarkable yields,significantly higher than that of conventional mixed *** findings were augmented by theoretical calculations on precursor Lewis basicity as guiding principles into hybrid macrocycle ***,the incorporation of unfused phenyl groups and halogen atoms into the hybrid framework resulted in fine-tuned optical,structural,electronic,and electrochemical *** straightforward approach achieved improved selectivity and controlled narrowing of the product distribution,affording the efficient synthesis of structurally sophisticated Bsub(Pc_(2)-Nc_(1))*** then expands the library of 3-dimensionalπ-extended macrocycles for use in a range of applications,such as in optoelectronic devices with precisely tailored optical properties.

关键词： subphthalocyanine hybrids low-symmetry aromatic macrocycle selective cyclotrimerization sterically driven chemistry broad absorption material properties

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Effect of age on the standardized ileal amino acid digestibility of soybean meal and canola meal in broilers

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Animal Nutrition 2024年第1期16卷 11-22页

作者： Mukti Barua M.Reza Abdollahi Faegheh Zaefarian timothy j.Wester Channarayapatna K.Girish Peter V.Chrystal Velmurugu Ravindran Monogastric Research Center School of Agriculture and Environment Massey University Department of Animal Science and Nutrition Faculty of Veterinary Medicine Chattogram Veterinary and Animal Sciences University Nutrition and Care Animal NutritionEvonik (SEA) Pte. Ltd Complete Feed Solutions

Standardized ileal digestibility coefficients (SIDC) of nitrogen (N) and amino acids (AA) in two protein sources (soybean meal [SBM] and canola meal [CM]) were investigated at six broiler ages (d 7, 14, 21, 28, 35, and 42). Two assay diets were formulated to contain either SBM (413 g/kg) or CM (553 g/kg) as the sole dietary AA source. Titanium dioxide (5 g/kg) was added as an indigestible marker. A total of 696 male broilers at 1 d old were allotted to 12 replicate cages per age group. Each assay diet was offered to birds for 4 d prior to the ileal digesta collection on d 7 (14 birds/cage), 14 (12 birds/cage), 21 (10 birds/cage), 28 (8 birds/cage), 35 (8 birds/cage) and 42 (6 birds/cage), respectively. The apparent digestibility coefficients were standardized using age-specific basal endogenous AA flows. In the SBM group, though the SIDC of N tended to be influenced (quadratic; P=0.075) by age, no linear or quadratic response of age effect was observed on the average SIDC of indispensable (IAA) and total AA (TAA). An age effect (quadratic; P<0.05) was observed on the average SIDC of dispensable AA (DAA) in SBM with the highest value recorded at d 7, followed by a decrease from d 14 to 28, which increased beyond d 35. The SIDC of some individual AA (Arg, Thr, Trp, Cys, Pro) were affected (P<0.05 or P<0.001) in a quadratic manner by age. In the CM, the SIDC of N, average SIDC of IAA, DAA and TAA were influenced (quadratic; P<0.05 or P<0.001) by age. The SIDC of N and average SIDC of DAA and TAA were higher from d 7 to 14, declined at d 21, and then increased beyond d 28. The average SIDC of IAA was low between d 7 and 28 and increased thereafter. The SIDC of individual AA were affected (linear or quadratic; P<0.05 or P<0.001) by different magnitudes by age. The age influence on the SIDC AA was variable, depending on the protein source and AA. The results demonstrate that age-specific SIDC AA data might need consideration in broiler feed formulations.

关键词： Age Amino acid Broiler Digestibility Protein source

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Overlooked interaction between redox-mediator and bisphenol-A in permanganate oxidation

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Environmental Science and Ecotechnology 2024年第5期21卷 248-255页

作者： Honglong Zhang Qiaoqiao Zhao Kangbao Zhong Ruopeng Bai jiaojiao Dong jun Ma jing Zhang timothy j.Strathmann School of Environment Harbin Institute of TechnologyHarbin150090PR China Institute of Nuclear and New Energy Technology Tsinghua UniversityBeijing100084PR China School of Chemistry and Chemical Engineering Chongqing Key Laboratory of Chemical Theory and MechanismChongqing UniversityChongqing401331PR China College of Environment and Ecology Chongqing UniversityChongqing400045PR China Department of Civil and Environmental Engineering Colorado School of Mines1500 Illinois StreetGoldenCO80401United States

Research efforts on permanganate(Mn(VII))combined with redox-mediator(RM),have received increasing attention due to their significant performance for bisphenol-A(BPA)***,the mechanisms underpinning BPA degradation remain *** we show the overlooked interactions between RM and BPA during permanganate oxidation by introducing an RMdN-hydroxyphthalimide(NHPI).We discovered that the concurrent generation of MnO_(2) and phthalimide-N-oxyl(PINO)radical significantly enhances BPA oxidation within the pH range of *** detection of radical cross-coupling products between PINO radicals and BPA or its derivatives corroborates the pivotal role of radical cross-coupling in BPA ***,we observed the formation of an NHPI-BPA complex,which undergoes preferential oxidation by Mn(VII),marked by the emergence of an electronrich domain in *** findings unveil the underlying mechanisms in the Mn(VII)/RM system and bridge the knowledge gap concerning BPA transformation via *** research paves the way for further exploration into optimizing complexation sites and RM dosage,significantly enhancing the system's efficiency in water treatment applications.

关键词： Permanganate Redox-mediator Bisphenol-A Radical cross-coupling Complexation

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Cultural Exclusion and the Transformation of the Cultural Landscape: The Origins of Anti-Chinese Racism in Canada

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Social Sciences in China 2024年第3期45卷 181-202页

作者： timothy j.Stanley Faculty of Education University of Ottawa

Anti-Chinese racism in Canada is a social structure of racialized exclusion that over time came to be built into the settler colonialism that continues to shape the *** of European,and especially of British and French origins,have consequently created the cultural landscapes that constitute the country(i.e.,its material constructions and dominant cultural overlays).When read against these landscapes,people of Chinese origins and members of other racialized groups continue to be positioned as aliens who do not belong in the country in way in which people racialized as white are *** on British Columbia(BC),Canada's westernmost province,and the historical activity of people of Chinese origins,this paper traces the history of anti-Chinese racism and its links to Anglo-Canadian settler *** has long been linked to China,and the Chinese entered BC at the same time as Europeans before the country *** this,Chinese people have repeatedly been positioned as threats to Anglo-Canadian dominance,and especially to control over the land and its *** Canadian resistance to racist exclusions,along with that of other groups,has led to the elimination of legislated ***,historic exclusions continue to shape cultural landscapes and popular understandings of who belongs and who does *** these landscapes requires an antiracist project of pursuing common projects that cross over racialized differences to remake the territory in ways that affirm the presence of all the peoples of Canada.

关键词： Chinese Canadians cultural exclusion white supremacy racism

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