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Tocotrienol isoforms:The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials

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Journal of Integrative Medicine 2024年第1期22卷 1-11页

作者： Maria Younes Ghady Loubnane Christopher Sleiman sandra Rizk Department of Natural Sciences Lebanese American UniversityByblosLebanon

Tocotrienols are found in a variety of natural sources,like rice bran,annatto seeds and palm oil,and have been shown to have several health-promoting properties,particularly against chronic diseases such as cancer.The incidence of cancer is rapidly increasing around the world,not only a result of continued aging and population growth,but also due to the adoption of aspects of the Western lifestyle,such as high-fat diets and low-physical activity.The literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers,including breast,lung,ovarian,prostate,liver,brain,colon,myeloma and pancreatic cancers.These findings,along with the reported safety profile of tocotrienols in healthy human volunteers,encourage further research into these compounds’potential use in cancer prevention and treatment.The current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks,such as cellular proliferation,apoptosis,angiogenesis and metastasis.MEDLINE/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive benefits.Following an overview of pre-clinical studies,we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.

关键词： Vitamin E Tocotrienols Cancer Molecular mechanism Clinical trials

Targeting KRAS in pancreatic cancer

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Oncology Research 2024年第5期32卷 799-805页

作者： sandra STICKLER BARBARA RATH GERHARD HAMILTON Institute of Pharmacology Medical University of ViennaViennaA-1090Austria

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient therapies.The Kirsten rat sarcoma virus(KRAS)oncogene is mutated in up to 90%of all pancreatic ductal adenocarcinomas(PDACs)and constitutes an attractive target for therapy.However,the most common KRAS mutations in PDAC are G12D(44%),G12V(34%)and G12R(20%)that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung cancer.KRAS G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3%of PDAC.Recently,the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in development.The other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor(GEF)Son of Sevenless 1 that drives KRAS.These agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.

关键词： Pancreatic cancer PDAC KRAS SOS1 PROTAC

Pandemic punch:SARS-CoV-2 hits pancreas

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1779-1780页

作者： Ninel Azoitei sandra Heller Alexander Kleger Institute of Molecular Oncology and Stem Cell Biology Ulm UniversityUlmGermany Division of Interdisciplinary Pancreatology Clinic of Internal Medicine IUniversity Hospital UlmUlmGermany

The COVID-19 pandemic has profoundly impacted global health systems,revealing the extensive repercussions of SARS-CoV-2 beyond respiratory symptoms.Indeed,traditionally considered a respiratory virus,SARS-CoV-2’s showcased the ability to target multiple organ systems including pancreas,an organ crucial for regulating blood sugar levels and aiding digestion.

关键词： pancreas respiratory traditionally

Design multifunctional Mg–Zr coatings regulating Mg alloy bioabsorption

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Journal of Magnesium and Alloys 2024年第4期12卷 1461-1478页

作者： Zohra Benzarti Sandesh Itani JoséDavid Castro sandra Carvalho Ana Sofia Ramos University of Coimbra CEMMPREARISEDepartment of Mechanical EngineeringRua Luís Reis Santos3030-788CoimbraPortugal Laboratory of Multifunctional Materials and Applications(LaMMA) Department of PhysicsFaculty of Sciences of SfaxUniversity of SfaxSoukra Road km 3.5B.P.1171Sfax3000Tunisia

Magnesium(Mg)alloys are widely used for temporary bone implants due to their favorable biodegradability,cytocompatibility,hemocompatibility,and close mechanical properties to bone.However,rapid degradation and inadequate strength limit their applicability.To overcome this,the direct current magnetron sputtering technique is employed for surface coating in Mg-based alloys using various zirconium(Zr)content.This approach presents a promising strategy for simultaneously improving corrosion resistance,maintaining biocompatibility,and enhancing strength without compromising osseointegration.By leveraging Mg’s inherent biodegradability,it has the potential to minimize the need for secondary surgeries,thereby reducing costs and resources.This paper is a systematic study aimed at understanding the corrosion mechanisms of Mg–Zr coatings,denoted Mg-xZr(x=0–5 at.%).Zr-doped coatings exhibited columnar growth leading to denser and refined structures with increasing Zr content.XRD analysis confirmed the presence of the Mg(00.2)basal plane,shifting towards higher angles(1.15°)with 5 at.%Zr doping due to lattice parameter changes(i.e.,decrease and increase of“c”and“a”lattice parameters,respectively).Mg–Zr coatings exhibited“liquidphilic”behavior,while Young’s modulus retained a steady value around 80 GPa across all samples.However,the hardness has significantly improved across all samples’coating,reaching the highest value of(2.2±0.3)GPa for 5 at.%Zr.Electrochemical testing in simulated body fluid(SBF)at 37℃ revealed a significant enhancement in corrosion resistance for Mg–Zr coatings containing 1.0–3.4 at.%Zr.Compared with the 5 at.%Zr coating which exhibited a corrosion rate of 32 mm/year,these coatings displayed lower corrosion rates,ranging from 1 to 12 mm/year.This synergistic enhancement in mechanical properties and corrosion resistance,achieved with 2.0–3.4 at.%Zr,suggests potential ability for reducing stress shielding and controlled degradation performance,and consequently,promising functional biodegradable materials f

关键词： Mg-Zr coatings Magnetron sputtering Nanoindentation Corrosion resistance Bone implants

High-resolution multi-scale air pollution system:Evaluation of modelling performance and emission control strategies

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Journal of Environmental Sciences 2024年第3期137卷 65-81页

作者： Diogo Lopes Joana Ferreira sandra Rafael Ka In Hoi Xin Li Yuan Liu Ka-Veng Yuen Kai Meng Mok Ana Isabel Miranda Department of Environment and Planning&CESAM University of AveiroAveiroPortugal Department of Civil&Environmental Engineering Faculty of Science and TechnologyUniversity of MacaoMacao SARChina

A high percentage of the world's population lives in areas where air pollutant concentrations exceed the World Health Organization guidelines.This work aims to develop and test,a high-resolution multi-scale air pollution modelling system by integrating a set of adequate tools.This system is able to provide detailed air pollutant concentrations in urban areas and support air quality management strategies through a better identification of different atmospheric processes.It also allows furthering the design and assessment of air pollution control measures for a specific area.To evaluate its performance and suitability,the system was applied to the Macao Special Administrative Region(SAR),China,one of the most densely populated areas on earth,during a winter period when this area is affected by high levels of Particulate Matter(PM).Although the developed system tends to underestimate the PM concentrations,it revealed a good performance in reproducing the temporal and spatial air pollution patterns.Several exceedances of the Chinese air quality standards were calculated and high population exposure to PM pollution was estimated.The tested urban atmospheric emission reduction scenarios have shown air quality improvements,indicating that emission reduction measures at urban level should focus on the domestic sector.However,it is crucial to implement joint pollution prevention strategies with neighbouring regions to improve the air quality in Macao SAR.The approach developed in this work can support policymakers in defining new strategies to reduce atmospheric pollution in urban areas.

关键词： Urban areas High-resolution emission inventory Particulate matter Population exposure

Geochemical elements in suspended particulate matter of Ensenada de La Paz Lagoon,Baja California Peninsula,Mexico:Sources,distribution,mass balance and ecotoxicological risks

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Journal of Environmental Sciences 2024年第2期136卷 422-436页

作者： sandra Soledad Morales-García Pilar de Acacia Pérez-Escamilla Suresh Babu Sujitha Pichaimani Godwyn-Paulson Andrés Felipe Zuniga-Cabezas Muthuswamy Ponniah Jonathan Instituto Politécnico Nacional(IPN) Centro Mexicano para la Producción más Limpia(CMPL)Av.Acueducto s/nCol.Barrio la Laguna TicománDel Gustavo A.MaderoC.P.07340Ciudad de MéxicoMexico Instituto Politécnico Nacional(IPN) Escuela Superior de Ingeniería y Arquitectura(ESIA)Unidad Ticomán***án 600Delg.Gustavo A.MaderoC.P.07340Ciudad de México(CDMX)Mexico Instituto Politécnico Nacional(IPN) Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo(CIIEMAD)Calle 30 de Junio de 1520Barrio la Laguna TicománDel.Gustavo A.MaderoC.P.07340Ciudad de MéxicoMéxico

The present study aimed to evaluate multi-element concentrations(Al,As,Ca,Cd,Co,Cr,Cu,Fe,Mg,Mn,Mo,Ni,Pb,Sr)in suspended particulate material(SPM)collected from Ensenada de La Paz(ELP)lagoon,Baja California Sur,Mexico in two different periods(September and May)to comprehend their origin,geochemical behavior,mass transfer and associated ecotoxicological risks.The 24 hr variation coefficient of volumetric SPM levels were found to be 51.7%in September and 40.5%in May,signifying the effects of oceanic waters.The calculated enrichment factor(EF)values for all the studied elements were of higher magnitude because of the high surface area and oxide nature of SPM,and in this study,Mo had the highest EF of 46.77 probably due to its origin from continental weathering.From the ecotoxicological perspective,the integrated toxic risk index revealed low toxic risk to the benthic community.However,the mean-ERM-Quotient calculated using the particulate concentrations of As,Cd,Cr,Cu,Ni,Pb indicated 9%probability of toxicity to biota.The comprehensive geochemical and ecotoxicological assessment of particulate metal concentrations in the ELP lagoon signify low to moderate contamination.

关键词： Suspended particulate material Heavy metals Risk assessment Mass transfer Ensenada de La Paz

Reproductive ecology of the black rat (Rattus rattus) in Madagascar: the influence of density-dependent and -independent effects

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Integrative Zoology 2024年第1期19卷 66-86页

作者： Kathryn SCOBIE Soanandrasana RAHELINIRINA Voahangy SOARIMALALA Fehivola Mandanirina ANDRIAMIARIMANANA Corinne RAHAINGOSOAMAMITIANA Toky RANDRIAMORIA Soloandry RAHAJANDRAIBE Xavier LAMBIN Minoarisoa RAJERISON sandra TELFER School of Biological Sciences University of AberdeenAberdeenUK Plague Unit Institut Pasteur de MadagascarAntananarivoMadagascar Association Vahatra AntananarivoMadagascar

The black rat(Rattus rattus)poses a severe threat to food security and public health in Madagascar,where it is a major cause of pre-and post-harvest crop losses and an important reservoir for many zoonotic diseases,including plague.Elsewhere,ecologically based rodent management(EBRM)strategies have been developed using ecologi-cal information to inform decisions on where and when to target control.EBRM could deliver improved health and well-being outcomes in Madagascar if adapted to the local ecological context.Using data collected from removal studies,we explored spatio-temporal patterns in the breeding activity of the black rat(R.rattus)in domestic and agricultural habitats across Madagascar and investigated to what extent these trends are influenced by rainfall and rat density.We identified clear spatio-temporal variation in the seasonality of R.rattus reproduction.Reproduction was highly seasonal both inside and outside of houses,but seasonal trends varied between these two habitats.Sea-sonal trends were explained,in part,by variation in rainfall;however,the effect of rainfall on reproductive rates did itself vary by season and habitat type.A decline in breeding intensity with increasing rat density was recorded outside of houses.This has important implications for control,as populations may compensate for removal through increased reproduction.We recommend that sustained control initiated before the main breeding season,combined with improved hygiene and adequate rodent-proofing in homes and grain stores,could curtail population growth and reduce pre-and post-harvest losses provided that these measures overcome the compensatory response of rodent populations.

关键词： Madagascar Rattus rattus reproductive ecology rodent control

Exploring the effects of dietary inulin in rainbow trout fed a high‑starch,100%plant‑based diet

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Journal of Animal Science and Biotechnology 2024年第2期15卷 713-732页

作者： Raphaël Defaix Jep Lokesh Laura Frohn Mickael Le Bechec Thierry Pigot Vincent Veron Anne Surget sandra Biasutti Frederic Terrier Sandrine Skiba-Cassy Jerome Roy Stephane Panserat Karine Ricaud Universite de Pau Et Des Pays de L’Adour E2S UPPAINRAENUMEASaint‑Pee‑Sur‑NivelleFrance Universite de Pau Et Des Pays de L’Adour E2S UPPACNRSIMT Mines AlesIPREMPauFrance Universite de Pau Et Des Pays de L’Adour E2S UPPAIUT des Pays de l’AdourDepartement Genie BiologiqueMont de MarsanFrance.

Background High dietary carbohydrates can spare protein in rainbow trout(Oncorhynchus mykiss)but may affect growth and health.Inulin,a prebiotic,could have nutritional and metabolic effects,along with anti-inflammatory properties in teleosts,improving growth and welfare.We tested this hypothesis in rainbow trout by feeding them a 100%plant-based diet,which is a viable alternative to fishmeal and fish oil in aquaculture feeds.In a two-factor design,we examined the impact of inulin(2%)as well as the variation in the carbohydrates(CHO)/plant protein ratio on rainbow trout.We assessed the influence of these factors on zootechnical parameters,plasma metabolites,gut microbiota,production of short-chain fatty acids and lactic acid,as well as the expression of free-fatty acid receptor genes in the mid-intestine,intermediary liver metabolism,and immune markers in a 12-week feeding trial.Results The use of 2%inulin did not significantly change the fish intestinal microbiota,but interestingly,the high CHO/protein ratio group showed a change in intestinal microbiota and in particular the beta diversity,with 21 bacterial genera affected,including Ralstonia,Bacillus,and 11 lactic-acid producing bacteria.There were higher levels of butyric,and valeric acid in groups fed with high CHO/protein diet but not with inulin.The high CHO/protein group showed a decrease in the expression of pro-inflammatory cytokines(il1b,il8,and tnfa)in liver and a lower expression of the genes coding for tight-junction proteins in mid-intestine(tjp1a and tjp3).However,the 2%inulin did not modify the expression of plasma immune markers.Finally,inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary carbohydrates.Conclusions With a 100%plant-based diet,inclusion of high levels of carbohydrates could be a promising way for fish nutrition in aquaculture through a protein sparing effect whereas the supplementation of 2%inulin does not appear to improve the use of CHO when combined with a 100%plant-based diet.

关键词： Aquaculture Fish nutrition Gut microbiota Immune markers Intermediary metabolism Inulin Prebiotic Rainbow trout Short-chain fatty acids

采用碳酸酐酶的微藻直接空气碳捕集固碳性能强化研究

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西安交通大学学报 2024年

作者：王睿龙李明佳 sandra Kentish 北京理工大学机械与车辆工程学院西安交通大学能源与动力工程学院热流科学与工程教育部重点实验室 Department of Chemical Engineering The University of Melbourne

为了解决低浓度二氧化碳(CO2)环境下微藻光生物反应器内CO2传质效率差、溶解度低的问题，制备了碳酸酐酶(CA)附着的尼龙纤维膜，利用CA催化转化CO2为碳酸氢根的性质，提出了一种可以改善微藻溶液中CO2溶解度及转化率的新型光生物反应器... 详细信息

为了解决低浓度二氧化碳(CO2)环境下微藻光生物反应器内CO2传质效率差、溶解度低的问题，制备了碳酸酐酶(CA)附着的尼龙纤维膜，利用CA催化转化CO2为碳酸氢根的性质，提出了一种可以改善微藻溶液中CO2溶解度及转化率的新型光生物反应器，测试了该反应器放置CA附着尼龙纤维漂浮膜前后的微藻培养和固碳性能，并进一步探究了膜的开孔率及CA附着量对微藻固碳效率的影响。结果表明：所制备的CA附着的尼龙纤维膜对CO2转化速率提升了62.7%，通过耐久性测试，CA的活性在5个培养周期后仍保持良好，性能衰减仅为11.3%；与传统气石鼓气方式相比，提出的新型光生物反应器的微藻生物质产量提高了29.7%，固碳效率提升了65%；随着膜开孔率的增加和透光率的增加，单位CA负载量的固碳效率提高，开孔面积占比24.75%的对照组的单位CA固碳率相比不开孔提高了13%。该研究为进一步提高微藻直接空气捕集的固碳效率提供了一种新的方法。

关键词：微藻光生物反应器直接空气碳捕集碳酸酐酶尼龙纤维膜