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Dietary docosahexaenoic acid (DHA) downregulates liver DHA synthesis by inhibiting eicosapentaenoic acid elongation

JOURNAL OF LIPID RESEARcH 2024年第6期65卷 100548页

作者： Metherel, Adam H. Valenzuela, Rodrigo Klievik, Brinley J. cisbani, Giulia Rotarescu, Ruxandra D. Gonzalez-Soto, Melissa cruciani-Guglielmacci, celine Laye, Sophie Magnan, christophe Mutch, David M. Bazinet, Richard P. Univ Toronto Dept Nutr Sci Toronto ON Canada Univ Chile Dept Nutr Santiago Chile Univ Guelph Dept Human Hlth & Nutr Sci Guelph ON Canada Univ Paris Cite BFA UMR8251 CNRS Paris France Univ Bordeaux INRA Bordeaux INP NutriNeuro Bordeaux France

DHA is abundant in the brain where it regulates cell survival, neurogenesis, and neuroinflammation. DHA can be obtained from the diet or synthesized from alpha-linolenic acid (ALA;18:3n-3) via a series of desaturation and elongation reactions occurring in the liver. Tracer studies suggest that dietary DHA can downregulate its own synthesis, but the mechanism remains undetermined and is the primary objective of this manuscript. First, we show by tracing 13 c content ( delta 13 c) of DHA via compoundspecific isotope analysis, that following low dietary DHA, the brain receives DHA synthesized from ALA. We then show that dietary DHA increases mouse liver and serum EPA, which is dependant on ALA. Furthermore, by compound -specific isotope analysis we demonstrate that the source of increased EPA is slowed EPA metabolism, not increased DHA retroconversion as previously assumed. DHA feeding alone or with ALA lowered liver elongation of very long chain (ELOVL2, EPA elongation) enzyme activity despite no change in protein content. To further evaluate the role of ELOVL2, a liver -specific Elovl2 KO was generated showing that DHA feeding in the presence or absence of a functional liver ELOVL2 yields similar results. An enzyme competition assay for EPA elongation suggests both uncompetitive and noncompetitive inhibition by DHA depending on DHA levels. To translate our findings, we show that DHA supplementation in men and women increases EPA levels in a manner dependent on a SNP (rs953413) in the ELOVL2 gene. In conclusion, we identify a novel feedback inhibition pathway where dietary DHA downregulates its liver synthesis by inhibiting EPA elongation.

关键词： dietary fat kinetics liver nutrition omega-3 fatty acids enzyme inhibition polyunsaturated fatty acid fatty acid metabolism elongation of very long-chain δ 13 c carbon-13 abundance ALA α-linolenic acid c-IRMS combustion-isotope ratio mass spectrometry cSIA compound-specific isotope analysis ELOVL elongation of very long chain DPAn-3 n-3 docosapentaenoic acid FADS fatty acid desaturase FAMEs fatty acid methyl esters FID flame ionization detection RcT randomized controlled trial

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color-tunable blue-emitting Na2MgSiO4:ce3+phosphors for white light-emitting diodes

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cERAMIcS INTERNATIONAL 2023年第3期49卷 5431-5436页

作者： chen, Mengfang Liao, Shuzhen Han, Yue Lian, Shixun Zhang, Jilin Hunan Normal Univ Key Lab Light Energy Convers Mat Hunan Prov Coll Key Lab Chem Biol & Tradit Chinese Med Res Minist Educ China Changsha 410081 Peoples R China Hunan Inst Engn Coll Mat & Chem Engn Hunan Prov Key Lab Environm Catalysis & Waste Recy Xiangtan 411104 Peoples R China

Phosphor-converted white light-emitting diodes (pc-wLEDs) based on near-UV LED chip demand efficient blue -emitting phosphors, because the pc-wLED uses either multi phosphors or single-phase white-emitting phosphor both needs blue-emitting component. When using ce3+ as the activator, the host structure usually has rare earth ions or alkaline earth ion such as ca2+ for ce3+ to occupy, due to similar ionic radius and charge. This work is going to report a blue-emitting phosphor Na2MgSiO4:ce3+, where ce3+ occupies the Na+ sites. The phosphor exhibits characteristic of tunable emission color upon increasing ce3+ content or introducing Li+ as charge compensator. The relationship between the crystal structure and the luminescent properties was studied in detail based on structural refinement and in-depth luminescent studies. The phosphor with a proper ce3+ content showed a high absolute quantum efficiency of 86.0% and acceptable thermal stability. The pc-wLED made of 365 nm UV chip, the as-prepared Na2MgSiO4:ce3+,Li+, and commercial green and red phosphors showed good performance with color rendering index of 93.3.

关键词： Phosphor c Optical properties D Silicate A Powders solid state reaction

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Validity and measurement equivalence of EQ-5D-5L questionnaire among heart failure patients in Malaysia: a cohort study

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JOURNAL OF MEDIcAL EcONOMIcS 2024年第1期27卷 607-617页

作者： Kuan, Wai chee chee, Kok Han Kasim, Sazzli Lim, Ka Keat Dujaili, Juman Abdulelah Lee, Kenneth Kwing-chin Teoh, Siew Li Monash Univ Malaysia Sch Pharm Jalan Lagoon Selatan Bandar Sunway Selangor Malaysia Univ Malaya Fac Med Dept Med Kuala Lumpur Malaysia Univ Teknol MARA UITM Fac Med Dept Internal Med Cardiol Jalan Hosp Shah Alam Selangor Malaysia Univ Teknol MARA UITM Cardiac Vasc & Lung Res Inst CaVaLRI Jalan Hosp Shah Alam Selangor Malaysia Kings Coll London Sch Life Course & Populat Sci Dept Populat Hlth Sci London England Swansea Univ Med Sch Swansea Wales Taylors Univ Sch Pharm Subang Jaya Selangor Malaysia Monash Univ Malaysia Sch Pharm Jalan Lagoon Selatan Bandar Sunway 47500 Selangor Malaysia

AimThis study aimed to examine the validity of EQ-5D-5L among HFrEF patients in Malaysia, and to explore the measurement equivalence of three main language *** surveyed HFrEF patients from two hospitals in Malaysia, using Malay, English or chinese versions of EQ-5D-5L. EQ-5D-5L dimensional scores were converted to utility scores using the Malaysian value set. A confirmatory factor analysis longitudinal model was constructed. The utility and visual analog scale (VAS) scores were evaluated for validity (convergent, known-group, responsiveness), and measurement equivalence of the three language ***200 HFrEF patients (mean age = 61 years), predominantly male (74%) of Malay ethnicity (55%), completed the admission and discharge EQ-5D-5L questionnaire in Malay (49%), English (26%) or chinese (25%) languages. 173 patients (86.5%) were followed up at 1-month post-discharge (1MPD). The standardized factor loadings and average variance extracted were >= 0.5 while composite reliability was >= 0.7, suggesting convergent validity. Patients with older age and higher New York Heart Association (NYHA) class reported significantly lower utility and VAS scores. The change in utility and VAS scores between admission and discharge was large, while the change between discharge and 1MPD was minimal. The minimal clinically important difference for utility and VAS scores was +/- 0.19 and +/- 11.01, respectively. Malay and English questionnaire were equivalent while the equivalence of Malay and chinese questionnaire was *** study only sampled HFrEF patients from two teaching hospitals, thus limiting the generalizability of results to the entire heart failure ***-5D-5L is a valid questionnaire to measure health-related quality of life and estimate utility values among HFrEF patients in Malaysia. The Malay and English versions of EQ-5D-5L appear equivalent for clinical and economic assessments. EQ-5D is the most commonly

关键词： Heart failure health-related quality of life validity responsiveness measurement equivalence EQ-5D c52 c5 c I19 I1 I

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A cost-consequence model of using the 21-gene assay to identify patients with early-stage node-positive breast cancer who benefit from adjuvant chemotherapy in the Netherlands

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JOURNAL OF MEDIcAL EcONOMIcS 2024年第1期27卷 445-454页

作者： Simons, Martijn J. H. G. Machielsen, Peter M. Spoorendonk, Jelle A. Ignacio, Tim Drost, Pieter B. Jacobs, Tim de Jongh, Felix E. OPEN Hlth Evidence & Access Rotterdam Netherlands Exact Sci Lindenstr 2 CH-6340 Baar Switzerland Ikazia Ziekenhuis Rotterdam Rotterdam Netherlands

BackgroundPatients with early-stage hormone receptor positive, human epidermal growth factor receptor-2 (HER2) negative invasive breast cancer with 1-3 positive lymph nodes (N1) often undergo surgical excisions followed by adjuvant chemotherapy (AcT). Many patients have no benefit from AcT and receive unnecessary, costly treatment often associated with short- and long-term adverse events (AEs). Gene expression profiling (GEP) assays, such as the 21-gene assay (i.e. the Oncotype DX assay), can identify patients at higher risk for recurrence who may benefit from AcT. However, the budgetary consequence of using the Oncotype DX assay versus no GEP testing in the Netherlands is unknown. Our study therefore assessed it using a cost-consequence *** validated model was used to create the N1 model. The model compared the costs and consequences of using the Oncotype DX assay versus no GEP testing and MammaPrint, and subsequent AcT use with corresponding costs for chemotherapy, treatment of AEs, productivity losses, GEP testing, and treatment of recurrences, according to the Oncotype DX results. The model time horizon was 5 *** for the total population amounted to euro8.0 million (M), euro16.2 M, and euro9.5 M, and cost per patient amounted to euro13,540, euro27,455, and euro16,154 for using the Oncotype DX assay, no GEP testing, and MammaPrint, respectively. Total cost savings of using the Oncotype DX assay amounted to euro8.2 M versus no GEP testing and euro1.5 M versus MammaPrint. Using the Oncotype DX assay would result in fewer patients receiving AcT and thus fewer AEs, sick days, and hospitalizations, leading to overall cost savings compared with no GEP testing and *** Oncotype DX testing in this population can prevent unnecessary overtreatment, reducing clinical and economic burden on the patient and Dutch healthcare system. Early-stage invasive breast cancer patients often undergo surgery followed by adjuvant che

关键词： 21-gene gene expression profiling early stage hormone receptor human epidermal growth factor receptor 2 breast cancer lymph node positive adjuvant chemotherapy cost-consequence analysis A11 A1 A c21 c2 c c51 c5

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components of thermal protection mechanism of carbon/phenolic composites exposed to severe aerodynamic heat

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POLYMER cOMPOSITES 2023年第1期44卷 136-147页

作者： Huang, Jie Guo, Jin Huang, Haiming Wang, Qing Li, Weijie Beijing Jiaotong Univ Inst Engn Mech Beijing Peoples R China COMAC Beijing Aircraft Technol Res Inst Beijing Key Lab Civil Aircraft Struct & Composite Beijing Peoples R China Univ Durham Dept Engn Durham England

In order to improve the thermal protection efficiency of carbon/phenolic (c/Ph) composites used as the heatshield of hypersonic vehicles, it is essential to find out the components of its thermal protection mechanism. In this study, a pyrolysis layer model considering pressure is established to simulate the percentages of heat dissipated by different thermal protection mechanisms. Numerical results reveal that the thermal protection mechanism of c/Ph composites mainly comprises of surface radiation, the heat absorbed by the heat capacity and thermal blockage effect (TBE) of pyrolysis gas, but the TBE weakens as heating time increases. Furthermore, the evolution laws of different thermal protection mechanisms of c/Ph composites with resin content are given. Based on the components of thermal protection mechanisms, both reducing the thermal conductivity of the resin matrix composites and increasing the material emissivity are effective approaches to enhancing the thermal protection efficiency of c/Ph composites exposed to severe aerodynamic heat.

关键词： c Ph composites pyrolysis pyrolysis layer model thermal protection mechanism

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From simple factors to artificial intelligence: evolution of prognosis prediction in childhood cancer: a systematic review and meta-analysis

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EcLINIcALMEDIcINE 2024年 78卷 102902-102902页

作者： Varga, Petra Obeidat, Mahmoud Mate, Vanda Koi, Tamas Kiss-Dala, Szilvia Major, Greta Szilvia Timar, agnes Eszter Li, Ximeng Szilagyi, Adam csaki, Zsofia Engh, Marie Anne Garami, Miklos Hegyi, Peter Turi, Ibolya Tuboly, Eszter SemmelweisUniv Ctr Translat Med Budapest Hungary Heim Pal Natl Pediat Inst Budapest Hungary Semmelweis Univ Pediat Ctr Budapest Hungary Budapest Univ Technol & Econ Inst Math Dept Stochast Budapest Hungary Semmelweis Univ Inst Pancreat Dis Budapest Hungary Univ Pecs Inst Translat Med Med Sch Pecs Hungary Semmelweis Univ Peto Andras Fac Budapest Hungary Hungarian Pediat Oncol Network Budapest Hungary

Background current paediatric cancer care requires innovative approaches to predict prognosis that facilitates personalised stratification, yet studies on the performance, composition and limitations of contemporary prognostic models are lacking. We aimed to compare the accuracy of traditional and advanced prognostic models. Methods A systematic search for this systematic review and meta-analysis (cRTN42022370251) was conducted in PubMed, Embase, Scopus, and the cochrane Library databases on 28 June 2024. Studies on the accuracy of prognostic markers or models used in paediatric haematological malignancies, central nervous system (cNS), or non-cNS solid tumours (NcNSST) were included. Three model categories were defined using: 1-clinical parameters, 2-genomic-transcriptomic data, and 3-artificial intelligence (AI). Primary outcomes were area under the receiver operating characteristic curve with a 95% confidence interval (cI) for various overall survival intervals and event-free survival. Two independent groups performed selection and data extraction. We used data published by the authors and publicly available databases. Findings Of 12,982 studies, 358 were included in the meta-analysis and 27 in the systematic review, with limited data on AI-approaches. Most data were reported on NcNSST at 5-year OS, where a statistically significant difference was observed between category-1 (0.75 cI: 0.72-0.79) and category-2 (0.85 cI: 0.82-0.88) (p < 0.001), but not between categories-2 and-3 (p = 0.2834) (0.82 cI: 0.77-0.88). Internal validation studies showed significantly better performance compared to those using external validation, highlighting the high risk of bias (ROB) inherent in internal validation. High ROB was most commonly experienced in the outcomes and statistical analysis domains, assessed using PROBAST and QUIPS. Interpretation It is advisable to introduce category-2 and-3 models in a clinical setting, especially for NcNSST prognostic for aiding risk-stratific

关键词： Paediatric oncology Prognosis prediction Prognostic model Next-generation sequencing Artificial intelligence Public database Biobank data AI artificial intelligence AUROc area under the receiver operating characteristic curve c composite (validation) c-index concordance index cI confidence interval cNS central nervous system cNST central nervous system tumours cSS cancer-specific survival E external (validation) EFS event-free survival I internal (validation) HM haematological malignancies ML machine learning NB neuroblastoma NcNSST non-cNS solid tumours NGS next-generation sequencing OS overall survival pAUROc pooled area under the receiver operating characteristics curve Pc paediatric cancer pc-index pooled concordance index PIcO patients, intervention, control, outcomes PO paediatric oncology PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses PROBAST Prediction model Risk Of Bias Assessment Tool QUIPS Quality In Prognosis Studies RoB risk of bias SD standard deviation SE standard error SEER Surveillance, Epidemiology, and End Results TARGET Therapeutically Applicable Research to Generate Effective Treatments

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Greater Neighborhood Disadvantage Is Associated with Alterations in Fetal Functional Brain Network Structure

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JOURNAL OF PEDIATRIcS 2024年 274卷 114201-114201页

作者： cook, Kevin Michael De Asis-cruz, Josepheen Sitrin, chloe Barnett, Scott D. Krishnamurthy, Dhineshvikram Limperopoulos, catherine Childrens Natl Hosp Developing Brain Inst Washington DC USA Univ Michigan Coll Literature Sci & Arts Dept Psychol Ann Arbor MI USA

Objective To determine the association between neighborhood disadvantage (ND) and functional brain development of in utero fetuses. Study design We conducted an observational study using Social Vulnerability Index (SVI) scores to assess the impact of ND on a prospectively recruited sample of healthy pregnant women from Washington, Dc. Using 79 functional magnetic resonance imaging scans from 68 healthy pregnancies at a mean gestational age of 33.12 weeks, we characterized the overall functional brain network structure using a graph metric approach. We used linear mixed effects models to assess the relationship between SVI and gestational age on 5 graph metrics, adjusting for multiple scans. Results Exposure to greater ND was associated with less well integrated functional brain networks, as observed by longer characteristic path lengths and diminished global efficiency (GE), as well as diminished small world propensity (SWP). Across gestational ages, however, the association between SVI and network integration diminished to a negligible relationship in the third trimester. conversely, SWP was significant across pregnancy, but the relationship changed such that there was a negative association with SWP earlier in the second trimester that inverted around the transition to the third trimester to a positive association. conclusions These data directly connect ND and altered functional brain maturation in fetuses. Our results suggest that, even before birth, proximity to environmental stressors in the wider neighborhood environment are associated with altered brain development. (J Pediatr 2024;274:114201).

关键词： brain maturation fMRI socioeconomic status graph theory c clustering coefficient EPI Echo planar images FDR False discovery rate GA Gestational age GE Global efficiency L characteristic path length LE Local efficiency MRI Magnetic resonance imaging ND Neighborhood disadvantage SES Socioeconomic status SVI Social Vulnerability Index SWP Small world propensity

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Real-world total cost of care by line of therapy in relapsed/refractory diffuse large B-cell lymphoma

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JOURNAL OF MEDIcAL EcONOMIcS 2024年第1期27卷 738-745页

作者： Gatwood, Justin Masaquel, Anthony Fox, David Sheinson, Daniel James, cameron Li, Jia Hossain, Farah Ross, Ryan Univ Tennessee Hlth Sci Ctr Coll Pharm Memphis TN USA Genentech Inc South San Francisco CA USA Genesis Res LLC Hoboken NJ USA GSK US Hlth Outcomes Vaccines Philadelphia PA 19104 USA

AimsThere are multiple recently approved treatments and a lack of clear standard-of-care therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBcL). While total cost of care (Tcc) by the number of lines of therapy (LoTs) has been evaluated, more recent cost estimates using real-world data are needed. This analysis assessed real-world Tcc of R/R DLBcL therapies by LoT using the IQVIA PharMetrics Plus database (1 January 2015-31 December 2021), in US patients aged >= 18 years treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-cHOP) or an R-cHOP-like regimen as first-line *** costs and resources in the R/R setting were assessed by LoT. A sensitivity analysis identified any potential confounding of the results caused by the impact of the cOVID-19 pandemic on healthcare utilization and costs. Overall, 310 patients receiving a second- or later-line treatment were included;baseline characteristics were similar across LoTs. Inpatient costs represented the highest percentage of total costs, followed by outpatient and pharmacy *** Tcc per-patient-per-month generally increased by LoT ($40,604, $48,630, and $59,499 for second-, third- and fourth-line treatments, respectively). costs were highest for fourth-line treatment for all healthcare resource utilization categories. Sensitivity analysis findings were consistent with the overall analysis, indicating results were not confounded by the cOVID-19 *** was potential misclassification of LoT;claims data were processed through an algorithm, possibly introducing errors. A low number of patients met the inclusion criteria. Patients who switched insurance plans, had insurance terminated, or whose enrollment period met the end of data availability may have had truncated follow-up, potentially resulting in underestimated *** healthcare costs increased with each additional LoT in the R/R DLBcL setting. Fur

关键词： Diffuse large B-cell lymphoma refractory relapse R-chop real-world IQVIA cost analysis c02 c c14 c1

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cutting performance and wear mechanism of zirconia toughened alumina ceramic cutting tools formed by vat photopolymerization-based 3D printing

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cERAMIcS INTERNATIONAL 2023年第14期49卷 23238-23247页

作者： Liu, Wei Wu, Haidong Xu, Yuerui Lin, Lifu Li, Yehua Wu, Shanghua Dongguan Univ Technol Neutron Scattering Tech Engn Res Ctr Sch Mech Engn Dongguan 523808 Guangdong Peoples R China Guangdong Univ Technol Sch Electromech Engn Guangzhou 510006 Guangdong Peoples R China

Zirconia toughened alumina (ZTA) cutting tools are widely used for machining hard and wear-resistant mate-rials. However, the processing of ZTA ceramic cutting tools with complex shapes using traditional methods is difficult and time-consuming. Until now, to the best of our knowledge, commercial ceramic cutting tools do not contain grooves because it is very difficult to process grooves on the ceramic cutting tool, resulting from the feature of high hardness and brittle attribute of ceramics. This study investigated high-performance, complex-shaped zirconia-toughened alumina (ZTA) ceramic cutting tools equipped with a chip breaker for the first time. The investigated samples were prepared using vat photopolymerization based 3D printing combined with a hot isostatic sintering process. The relative density of 99.34%, Vickers hardness of 17.98 & PLUSMN;0.20 GPa, bending strength of 779 & PLUSMN;47 MPa and fracture toughness of 5.41 & PLUSMN;0.29 MPa m1/2 of the ZTA cutting tools were obtained. The effects of three cutting parameters, namely the cutting speed vc, feed rate f, and back cutting depth ap, on the cutting performances of the cutting tools were investigated, and the wear mechanisms of the cutting tools were examined. We believe that our study makes a significant contribution to the literature because this study provides an in-depth investigation of the properties and wear mechanisms of ZTA ceramic cutting tools with chip breaker grooves. The findings of this study provide insight into the preparation of high-performance, complex-shaped ZTA ceramic cutting tools. Further, the preparation methods investigated in this study and the evaluation of the properties of the fabricated specimens in comparison with a commercially available cutting tool illustrate the potential advantages that may be obtained via the further development of these materials.

关键词： A Finishing Hot isostatic pressing B composites c Mechanical properties E cutting tools 3D printing

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Microwave application as an alternative method to increase the efficiency of Ptc catalyst in PEMFcs

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PROcEEDINGS OF THE INSTITUTION OF MEcHANIcAL ENGINEERS PART A-JOURNAL OF POWER AND ENERGY 2023年第6期237卷 1329 - 1336页

作者： Sahin, Omer Yilmaz, Adem Ekinci, Arzu Istanbul Tech Univ Fac Chem & Met Engn Dept Chem Engn Istanbul Turkiye Batman Univ Fac Technol Dept Energy Syst Engn Batman Turkiye Siirt Univ Fac Hlth Sci Dept Occupat Hlth & Safety Siirt Turkiye Batman Univ Fac Technol Dept Energy Syst Engn Batman Bati Raman Kampusu TR-72060 Batman Turkiye

This study aims to develop a high-performance Pt/c catalyst for the cathode and anode parts of a modified Proton exchange membrane (PEM) fuel cell in nitrogen and argon gases at different microwave radiation powers. The pure and modified forms of the synthesized Pt/c catalysts were characterised using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The XRD results revealed that the crystal structure of the modified Pt/c catalyst was perfect and that the particle size of the catalytic material grew significantly as a consequence of the modification. Furthermore, the durability of PEM fuel cell electrocatalysts was investigated using the cyclic voltammetry (cV) technique. The experimental results indicated that microwave radiation had a significant effect on the particle size of the Pt/c catalyst. Additionally, the modified Pt/c catalyst exhibited a decreased activation potential loss and increased the cathode and anode power density values by 34% and 47%, respectively, compared to the Pt/c catalyst.

关键词： Microwave irradiation modified proton exchange membrane fuel cell polarization curves Pt c

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