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CIS controls the functional polarization of GM-CSF-derived macrophages

Cellular & Molecular Immunology 2023年第1期20卷 65-79页

作者： Shengbo Zhang Jai Rautela Naiara G.Bediaga Tatiana B.Kolesnik Yue You Junli Nie Laura F.Dagley Justin Bedo Hanqing Wang Li Sun Robyn Sutherland elliot Surgenor Nadia Iannarella Rhys Allan Fernando Souza-Fonseca-Guimaraes Yi Xie Qike Wang Yuxia Zhang Yuekang Xu Stephen L.Nutt Andrew M.Lew Nicholas D.Huntington sandra e.nicholson Michaël Chopin Yifan Zhan Walter and eliza Hall Institute of Medical Research ParkvilleVICAustralia Department of Medical Biology University of MelbourneParkvilleVICAustralia Department of Biochemistry and Molecular Biology Biomedicine Discovery InstituteMonash UniversityClaytonVICAustralia oNKo-Innate Pty Ltd Moonee PondsVICAustralia Department of Computing and Information Systems University of MelbourneParkvilleVICAustralia Department of Respiratory Medicine Guangzhou Institute of PediatricsGuangzhou Women and Children’s Medical CentreState Key Laboratory of Respiratory DiseasesGuangzhou Medical UniversityGuangzhouGuangdongChina College of Biological Science Anhui Normal UniversityHefeiChina University of Queensland Diamantina Institute University of QueenslandTranslational Research InstituteBrisbaneQLDAustralia Program in Cardiovascular and Metabolic Disorders Duke-NUS Medical SchoolDukeSingapore Drug Discovery Shanghai Huaota BiopharmShanghaiChina

The cytokine granulocyte-macrophage-colony stimulating factor (GM-CSF) possesses the capacity to differentiate monocytes into macrophages (MØs) with opposing functions, namely, proinflammatory M1-like MØs and immunosuppressive M2-like MØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of MØs under GM-CSF signaling remains elusive. Here, we showed that GM-CSF-induced MØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive M2-like MØs. CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway, consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8 (IRF8). Loss- and gain-of-function approaches highlighted IRF8 as a critical regulator of the M1-like polarization program. In vivo, CIS deficiency induced the differentiation of M2-like macrophages, which promoted strong Th2 immune responses characterized by the development of severe experimental asthma. Collectively, our results reveal a CIS-modulated mechanism that clarifies the opposing actions of GM-CSF in MØ differentiation and uncovers the role of GM-CSF in controlling allergic inflammation.

关键词： CIS GM-CSF Macrophage M2 M1

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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 *** 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 *** 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 *** 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 *** 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 ***/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 *** 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

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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 ***,rapid degradation and inadequate strength limit their *** overcome this,the direct current magnetron sputtering technique is employed for surface coating in Mg-based alloys using various zirconium(Zr)*** approach presents a promising strategy for simultaneously improving corrosion resistance,maintaining biocompatibility,and enhancing strength without compromising *** leveraging Mg’s inherent biodegradability,it has the potential to minimize the need for secondary surgeries,thereby reducing costs and *** 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 *** 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 ***,the hardness has significantly improved across all samples’coating,reaching the highest value of(2.2±0.3)GPa for 5 at.%*** 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.%*** 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/*** 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 consequentl

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

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Quasilinear elliptic problems with exponential growth via the Nehari manifold method: existence of nonnegative and nodal solutions

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Acta Mathematica Sinica,english Series 2024年

作者： Giovany FIGUeIReDO sandra Moreira Ricardo Ruviaro Address Departamento de Matematica Universidade de Brasilia Departamento de Matematica e Informatica Universidade Estadual do Maranhao Departamento de Matematica Universidade de Brasilia

In this paper we will be concerned with the problem -Δu-1/2Δ(a（x）u2)u+V（x）u=f（u）,x∈R2，where V is a potential continuous and f : R → R is a superlinear continuous function with exponential subcritical or exponential critical growth. We use as a main tool the Nehari manifold method in order to show existence of nonnegative solutions and existence of nodal solutions. Our results complement the classical result of solutions for quasilinear Schrodinger equations via the Nehari method due to Jia-quan Liu, Ya-qi Wang and Zhi-Qiang Wang in the sense that in this article we are considering nonlinearity of the exponential type.

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Towards trustworthy multi-modal motion prediction:Holistic evaluation and interpretability of outputs

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CAAI Transactions on Intelligence Technology 2024年第3期9卷 557-572页

作者： sandra Carrasco Limeros Sylwia Majchrowska Joakim Johnander Christoffer Petersson MiguelÁngel Sotelo David Fernández Llorca Computer engineering Department Polytechnic SchoolUniversity of AlcalaMadridSpain AI Sweden GothenburgSweden Zenseact AB GothenburgSweden Department of electrical engineering Linköping UniversityLinköpingSweden Chalmers University of Technology GothenburgSweden european Commission Joint Research CentreSevilleSpain

Predicting the motion of other road agents enables autonomous vehicles to perform safe and efficient path *** task is very complex,as the behaviour of road agents depends on many factors and the number of possible future trajectories can be consid-erable(multi-modal).Most prior approaches proposed to address multi-modal motion prediction are based on complex machine learning systems that have limited ***,the metrics used in current benchmarks do not evaluate all aspects of the problem,such as the diversity and admissibility of the *** authors aim to advance towards the design of trustworthy motion prediction systems,based on some of the re-quirements for the design of Trustworthy Artificial *** focus is on evaluation criteria,robustness,and interpretability of ***,the evaluation metrics are comprehensively analysed,the main gaps of current benchmarks are identified,and a new holistic evaluation framework is ***,a method for the assessment of spatial and temporal robustness is introduced by simulating noise in the perception *** enhance the interpretability of the outputs and generate more balanced results in the proposed evaluation framework,an intent prediction layer that can be attached to multi-modal motion prediction models is *** effectiveness of this approach is assessed through a survey that explores different elements in the visualisation of the multi-modal trajectories and *** proposed approach and findings make a significant contribution to the development of trustworthy motion prediction systems for autono-mous vehicles,advancing the field towards greater safety and reliability.

关键词： autonomous vehicles evaluation interpretability multi-modal motion prediction robustness trustworthy AI

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Supramolecular Polymerization of Hydrogen-Bonded Trimers in Bulk and Aqueous Medium

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CCS Chemistry 2024年第6期6卷 1458-1465页

作者： Freek V.de Graaf Stef A.H.Jansen sandra M.C.Schoenmakers Bas van Genabeek Marle e.J.Vleugels Bart W.L.van den Bersselaar e.W.Meijer Ghislaine Vantomme Institute for Complex Molecular Systems Laboratory of Macromolecular and Organic ChemistryEindhoven University of Technology5600 MBEindhoven School of Chemistry and RNA Institute University of New South WalesSydneyNew South Wales 2052

Synthetic molecules that form functional noncovalent assemblies in water have received much attention for their potential applications as *** this work,we introduce a novel water-compatible monomer based on the phthalhydrazide moiety that assembles into hydrogen-bonded trimeric *** bulk,the material exhibits a cylindrical nanostructure in the liquid-crystalline phase at elevated temperatures,morphologically distinct from the crystalline lamellar *** water,these molecules effectively form cylinders in a one-dimensional fashion,yielding fibrous *** formation of these supramolecular polymers follows a cooperative mechanism,as evidenced by denaturation *** trimerized pattern represents a new category of aqueous su pramolecular polymers with future prospects for functional complex molecular systems.

关键词： noncovalent chemistry supramolecular polymers hydrogen bonding cooperativity nanostructure

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Development of PROTACS degrading KRAS and SOS1

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Oncology Research 2024年第8期32卷 1257-1264页

作者： GeRHARD HAMILTON MARIe-THeReSe eGGeRSTORFeR sandra STICKLeR Institute of Pharmacology Medical University of ViennaVienna1090Austria

The Kirsten rat sarcoma virus—son of sevenless 1(KRAS-SOS1)axis drives tumor growth preferentially in pancreatic,colon,and lung ***,KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of ***,the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%,lasting for a mean period of 8 *** approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras(PROTACs),which degrade the proteins of interest and exhibit much higher antitumor activity through multiple cycles of ***,PROTACs have been developed based on KRAS-or SOS1-directed inhibitors coupled to either von Hippel-Lindau(VHL)or Cereblon(CRBN)ligands that invoke the proteasomal *** of these PROTACs show increased activity in vitro and in vivo compared to their cognate inhibitors but their toxicity in normal tissues is not *** CRBN PROTACs containing thalidomide derivatives cannot be tested in experimental *** to such PROTACS arises through downregulation or inactivation of CRBN or factors of the functional VHL e3 ubiquitin *** highly active KRAS and SOS1 PROTACs have been formulated their clinical application remains difficult.

关键词： Proteolysis-targeting chimeras(PROTACs) Kirsten rat sarcoma virus(KRAS) Son of sevenless 1(SOS1) Von Hippel-Lindau Cereblon

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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 ***,a prebiotic,could have nutritional and metabolic effects,along with anti-inflammatory properties in teleosts,improving growth and *** 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 *** 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 *** 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 *** 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 *** were higher levels of butyric,and valeric acid in groups fed with high CHO/protein diet but not with *** 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 ***,inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary *** 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 wh

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

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epidemiological and Paraclinical Aspects of Helicobacter pylori Infection among Hepatitis B Virus Carriers in the Republic of Congo

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Open Journal of Gastroenterology 2024年第5期14卷 184-191页

作者： Jile Florient Mimiesse Monamou Nuptia Kanoha elenga Ngala Itoua Ngaporo Clausina Ahoui Apendi Marlyse Ngalessami Mouakosso Arnaud Mongo Onkouo Mauria Ibobi Rody Stéphane Ngami Mardoché Motoula Latou Hostaud Atipo Ibara Céline sandra Adoua Déby Gassaye Blaise Irénée Atipo Ibara Department of Gastroenterology and Internal Medicine Brazzaville University Hospital Brazzaville The Republic of Congo Faculty of Health Sciences Marien Ngouabi University Brazzaville The Republic of Congo

Objective: Describe the epidemiological and paraclinical aspects of HP infection in hepatitis B virus carriers. Population and Method: This was a descriptive cross-sectional study running from January 1 to August 30, 2019, a period of 8 months. It took place in the Hospital Centers of the two major cities of Congo (Brazzaville and Pointe-Noire). The target population of our study consists of patients carrying HBV under antiviral treatment or not. Patients aged at least 18 years and consenting with a biological and morphological assessment were included. We did not include in our study patients taking or having taken antibiotics and/or PPIs less than 4 weeks ago. We excluded all patients who did not deposit fresh stools and those in whom stool extraction could not be done manually. The variables studied covered sociodemographic, clinical and paraclinical aspects. Data entry was done using excel 8.0 software. Statistical analysis was carried out with SPSS 20.0 software. Results: During our study, we included 169 patients. The frequency of HPAG in the stools of HBV carriers in our study population was 63.9% (n = 109). Male patients represented 69% (n = 75) and female patients represented 31% (n = 34). The average age of the patients is 43.92 ± 13.51 years with extremes of 18 years and 80 years. Concerning profession, unemployed patients and those working in the private sector were the most represented in respectively 28.4% (n = 31) and 22.9% (n = 25) without statistical link. Households comprising between 4 - 10 people and the use of public latrines were the risk factors most represented in respectively 69% (n = 75) and 88% (n = 96) without statistical link. Clinically, hepatomegaly and signs of portal hypertension were most represented in 53% (n = 58) and 47% (n = 51). Biologically, HBV DNA was detectable in 60.5% of cases (n = 66).

关键词： Helicobacter pylori Hepatitis B Virus Congo

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The acceleration of a high-charge electron bunch to 10 GeV in a 10-cm nanoparticle-assisted wakefield accelerator

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Matter and Radiation at extremes 2024年第1期9卷 15-24页

作者： Constantin Aniculaesei Thanh Ha Samuel Yoffe Lance Labun Stephen Milton edward McCary Michael M.Spinks Hernan J.Quevedo Ou Z.Labun Ritwik Sain Andrea Hannasch Rafal Zgadzaj Isabella Pagano Jose A.Franco-Altamirano Martin L.Ringuette erhart Gaul Scott V.Luedtke Ganesh Tiwari Bernhard ersfeld enrico Brunetti Hartmut Ruhl Todd Ditmire sandra Bruce Michael e.Donovan Michael C.Downer Dino A.Jaroszynski Bjorn Manuel Hegelich University of Texas at Austin AustinTexas 78712USA SUPA Department of Physics University of StrathclydeGlasgowScotland G4 ONGUnited Kingdom Tau Systems Inc.AustinTexas 78701USA Lawrence Livermore National Laboratory LivermoreCalifornia 94550USA Los Alamos National Laboratory Los AlamosNew Mexico 87545USA Brookhaven National Laboratory UptonNew York 11973USA Ludwig-Maximilians-Universität MunichGermany

An intense laser pulse focused onto a plasma can excite nonlinear plasma *** appropriate conditions,electrons from the background plasma are trapped in the plasma wave and accelerated to ultra-relativistic *** scheme is called a laser wakefield *** this work,we present results from a laser wakefield acceleration experiment using a petawatt-class laser to excite the wakefields as well as nanoparticles to assist the injection of electrons into the accelerating phase of the *** find that a 10-cm-long,nanoparticle-assisted laser wakefield accelerator can generate 340 pC,10±1.86 GeV electron bunches with a 3.4 GeV rms convolved energy spread and a 0.9 mrad rms *** can also produce bunches with lower energies in the 4–6 GeV range.

关键词： acceleration nanoparticle charge

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