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Elucidating the Degradation pathways of Human Insulin in the Solid State

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Journal of Analysis and Testing 2024年第03期8卷 288-299页

作者： andrew Fagan Lorraine M.Bateman Joseph p.O'Shea Abina M.Crean SSpC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork School of pharmacy University College Cork Analytical and Biological Chemistry Research Facility (ABCRF) University College Cork School of Chemistry University College Cork

While there have been significant advances in the development of peptide oral dosage forms in recent years, highlighted by the clinical and commercial success of approved peptides such as Rybelsus?, there remain several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chemical stability inherent to their structures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution state. Using insulin as a model peptide, this work sought to contribute to the development of analytical techniques for investigating common insulin degradation pathways. Chemically denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy, reverse phase HpLC and size exclusion chromatography methods for the investigation of unfolding, chemical modifications and covalent aggregation of the insulin molecule respectively. Solid state degraded samples were prepared by heating insulin powder at 60 °C and 75% relative humidity for 1, 3, 5 and 7 d, and the degradation profiles of the samples were evaluated and compared with those observed in solution. While no unfolding was observed to occur, significant deamidation and covalent aggregation were detected. Reductive disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Biopharmaceutical analysis Covalent aggregation Deamidation Disulfide cleavage Insulin Solid state Stability

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

Some Mean Convergence Theorems for the Maximum of Normed Double Sums of Banach Space Valued Random Elements

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Acta Mathematica Sinica,English Series 2024年第7期40卷 1727-1740页

作者： andrew ROSALSKY Le Van THANH Nguyen Thi THUY Department of Statistics University of FloridaGainesvilleFL 32611-8545USA Department of Mathematics Vinh UniversityVinhNghe AnViet Nam High School for Gifted Students Vinh UniversityVinhNghe AnViet Nam

In this correspondence,we establish mean convergence theorems for the maximum of normed double sums of Banach space valued random *** of the results pertain to random elements which are *** expand and improve a number of particular cases in the literature on mean convergence of random elements in Banach *** of the main contributions of the paper is to simplify and improve a recent result of Li,presnell,and Rosalsky[Journal of Mathematical Inequalities,16,117–126(2022)].A new maximal inequality for double sums of M-dependent random elements is proved which may be of independent *** sharpness of the results is illustrated by four examples.

关键词： Double sum mean convergence Rademacher type p Banach space Banach space valued random element M-dependent random elements

Enantioselective iridium-catalyzed allylic substitution with a Reformatsky reagent: direct construction of β-stereogenic homoallylic esters

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Science China Chemistry 2024年

作者： Debasis pal Kirana D.Veeranna Yuk Fai Wong p.andrew Evans Department of Chemistry Queen's University(Canada) Xiangya School of pharmaceutical Sciences Central South University

The Reformatsky reagent derived from ethyl bromoacetate circumvents the challenge associated with the direct regio-and enantioselective iridium-catalyzed allylic alkylation with an unstabilized aliphatic ester enolate. Notably, this work represents the first example of using a Reformatsky reagent in a metal-allyl reaction, which permits the direct construction of enantioenriched β-stereogenic homoallylic esters without preactivation of the pronucleophile or post-reaction modification of the product(e.g., thermal decarboxylation of a 1,3-dicarbonyl). Moreover, the process allows the coupling of a broad range of sterically and electronically diverse electrophiles bearing aryl, heteroaryl and alkenyl derivatives, including the significantly more challenging alkyl-substituted allylic carbonates. The versatility of the ester product is exemplified by a series of functional group manipulations and the development of a concise and efficient enantioselective total synthesis of the natural product,(+)-descurainolide A. Finally, mechanistic studies indicate that the zinc enolate behaves as a soft nucleophile that undergoes outer-sphere alkylation.

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Outcomes following minimally invasive dorsal cheilectomy for hallux rigidus:A systematic review

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World Journal of Orthopedics 2024年第6期15卷 585-592页

作者： Katherine Esser James J Butler Mackenzie Roof Nathaniel p Mercer Michael C Harrington Alan p Samsonov andrew J Rosenbaum John G Kennedy Department of Orthopaedic Surgery University of Toledo Medical Center University of Toledo College of Medicine and Life SciencesToledoOH 43614United States Department of Orthopedic Surgery NYU Langone HealthNew YorkNY 10002United States Department of Orthopedic Surgery Albany Medical CenterAlbanyNY 12208United States

BACKGROUND Cheilectomy of the 1^(st)metatarsophalangeal joint(MTpJ)is one of the most common procedures for the management of hallux ***,there is no consensus regarding outcomes following minimally invasive dorsal cheilectomy(MIDC)for the management of hallux *** To evaluate outcomes following MIDC for the management of hallux *** During November 2023,the pubMed,EMBASE and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following MIDC for the management of hallux *** Six studies were *** total,348 patients(370 feet)underwent MIDC for hallux rigidus at a weighted mean follow-up of 37.9±16.5 *** distribution of patients by Coughlin and Shurna's classification was recorded in 4 studies as follows:Ⅰ(58 patients,27.1%),Ⅱ(112 patients,52.3%),Ⅲ(44 patients,20.6%).Three studies performed an additional 1^(st)MTpJ arthroscopy and debridement following *** intra-articular bone debris was observed in 100%of patients in 1 *** weighted mean American orthopedic foot and ankle society score improved from a preoperative score of 68.9±3.2 to a postoperative score of *** complication rate was 8.4%,the most common of which was persistent joint pain and ***-two failures(8.7%)were ***-three secondary procedures(8.9%)were performed at a weighted mean time of 8.6±3.2 months following the index *** This systematic review demonstrated improvements in subjective clinical outcomes together with a moderate complication rate following MIDC for the management of hallux rigidus at short-term follow-up.A moderate reoperation rate at short-term follow-up was *** marked heterogeneity between included studies and paucity of high quality comparative studies limits the generation of any robust conclusions.

关键词： Minimally invasive dorsal cheilectomy Hallux rigidus The first metatarsophalangeal joint Cheilectomy Minimally invasive surgery

Effects of organic fertilizers produced using different techniques on rice grain yield and ammonia volatilization in double-cropping rice fields

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pedosphere 2024年第1期34卷 110-120页

作者： Mingcheng HU andrew JWADE Weishou SHEN Zhenfang ZHONG Chongwen QIU Xiangui LIN Jiangsu Key Laboratory of Atmospheric Environment Monitoring and pollution Control Collaborative Innovation Center of Atmospheric Environment and Equipment Technologyand School of Environmental Science and EngineeringNanjing University of Information Science and TechnologyNanjing 210044China Department of Geography and Environmental Science University of ReadingReading RG65DWUK Haina Research Institute of Guangdong Haina Agricultural Co. Ltd.Huizhou 516000China State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China

Ammonia(NH_(3)) volatilization from rice fields contributes to poor air quality and indicates low nitrogen use efficiency. Although organic fertilizers can meet the nitrogen requirement for rice growth, the simultaneous effects of organic fertilizers on NH_(3) volatilization and rice yield in paddy fields are poorly understood and quantified. To address this gap in our knowledge, experimental field plots were established in a conventional double-cropping paddy field in the pearl River Delta region, southern China. Five fertilizer treatments were used besides the control with no fertilizer: fresh organic fertilizer, successively composted organic fertilizer, chemically composted organic fertilizer, mixture of chemically composted organic fertilizer with inorganic fertilizer, and chemical fertilizer. Ammonia volatilization was measured using a batch-type airflow enclosure method. No significant differences in grain yield were observed among organic and chemical fertilizer treatments. However, compared with chemical fertilizer, chemically composted organic fertilizer and successively composted organic fertilizer significantly decreased total NH_(3) volatilization by 70% and 68%, respectively. The ammonium-nitrogen concentration in field surface water correlated strongly(p positively with NH_(3) volatilization across fertilization treatments. Our findings demonstrate that chemically composted organic fertilizer can sustain rice yield while reducing NH_(3) volatilization. An important future step is to promote these field measurements to similar rice cultivation areas to quantify the regional-and national-scale impact on air quality and nitrogen deposition in sensitive areas, and to design and implement better fertilizer management practices.

关键词： air quality crop production manure NH_(3)emission nitrogen use efficiency

Enhanced entropy generation and heat transfer characteristics of magnetic nano-encapsulated phase change materials in latent heat thermal energy storage systems

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Applied Mathematics and Mechanics(English Edition) 2024年第6期45卷 1051-1070页

作者： p.S.REDDY p.SREEDEVI Department of Mathematics Rajeev Gandhi Memorial College of Engineering and TechnologyNandyal 518501India

The objective of the current study is to investigate the importance of entropy generation and thermal radiation on the patterns of velocity,isentropic lines,and temperature contours within a thermal energy storage device filled with magnetic nanoencapsulated phase change materials(NEpCMs).The versatile finite element method(FEM)is implemented to numerically solve the governing *** effects of various parameters,including the viscosity parameter,ranging from 1 to 3,the thermal conductivity parameter,ranging from 1 to 3,the Rayleigh parameter,ranging from 102 to 3×10^(2),the radiation number,ranging from 0.1 to 0.5,the fusion temperature,ranging from 1.0 to 1.2,the volume fraction of NEpCMs,ranging from 2%to 6%,the Stefan number,ranging from 1 to 5,the magnetic number,ranging from 0.1 to 0.5,and the irreversibility parameter,ranging from 0.1 to 0.5,are examined in detail on the temperature contours,isentropic lines,heat capacity ratio,and velocity ***,the heat transfer rates at both the cold and hot walls are analyzed,and the findings are presented *** results indicate that the time taken by the NEpCMs to transition from solid to liquid is prolonged inside the chamber region as the fusion temperatureθf ***,the contours of the heat capacity ratio Cr decrease with the increase in the Stefan number Ste.

关键词： volume fraction of nano-encapsulated phase change material(NEpCM) radiation Stefan number heat capacity ratio entropy generation

A Hybrid Optimization Approach of Single point Incremental Sheet Forming of AISI 316L Stainless Steel Using Grey Relation Analysis Coupled with principal Component Analysiss

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Journal of Wuhan University of Technology(Materials Science) 2024年第1期39卷 160-166页

作者： A Visagan p Ganesh Department of production Technology Madras Institute of TechnologyChennai-600044India

We investigated the parametric optimization on incremental sheet forming of stainless steel using Grey Relational Analysis(GRA) coupled with principal Component Analysis(pCA). AISI 316L stainless steel sheets were used to develop double wall angle pyramid with aid of tungsten carbide tool. GRA coupled with pCA was used to plan the experiment conditions. Control factors such as Tool Diameter(TD), Step Depth(SD), Bottom Wall Angle(BWA), Feed Rate(FR) and Spindle Speed(SS) on Top Wall Angle(TWA) and Top Wall Angle Surface Roughness(TWASR) have been studied. Wall angle increases with increasing tool diameter due to large contact area between tool and workpiece. As the step depth, feed rate and spindle speed increase,TWASR decreases with increasing tool diameter. As the step depth increasing, the hydrostatic stress is raised causing severe cracks in the deformed surface. Hence it was concluded that the proposed hybrid method was suitable for optimizing the factors and response.

关键词： single point incremental forming AISI 316L taguchi grey relation analysis principal component analysis surface roughness scanning electron microscopy

Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1629-1636页

作者： Megan Grinlinton Chris Furkert andrew Maurice Neville Angelo Michael Booth Department of General Surgery North Shore HospitalAuckland 0620New Zealand Department of pathology North Shore HospitalAuckland 0620New Zealand

BACKGROUND Upper gastrointestinal(GI)signet ring cell carcinomas(SRCC)confer a poor *** benefit of operative intervention for this patient group is contro-versial in terms of overall *** To investigate factors relating to survival in patients with upper GI *** A retrospective,tertiary,single-centre review of patients who were diagnosed with oesophageal,gastroesophageal junction and gastric SRCC was *** primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative ***-dary outcomes included assessing the relationship between demographic and histopathological factors,and *** One hundred and thirty-one patients were *** one-year survival for the operative group was 81%and for the nonoperative group was 19.1%.The five-year survival in the operative group was 28.6%vs 1.5%in the nonoperative *** difference in overall survival between groups was statistically significant(HR 0.19,95%CI(0.13-0.30),ppatients who underwent surgical management,those with a lower stage of disease,and those with a lower Charlson Comorbidity Index(CCI)had significantly improved *** Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following *** surgery to a carefully selected patient group may improve the outcome for this disease.

关键词： Signet ring cell carcinoma Gastric cancer Oesophageal cancer poorly cohesive gastric cancer Diffuse gastric cancer