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Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy piglets

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Journal of Animal Science and Biotechnology 2024年第1期15卷 313-328页

作者： Dirkjan Schokker Soumya K.Kar Els Willems Alex Bossers Ruud A.Dekker Alfons J.M.Jansman Wageningen Bioveterinary Research LelystadThe Netherlands Wageningen Livestock Research Wageningen University&ResearchWageningenThe Netherlands Royal Agrifirm Group ApeldoornThe Netherlands Institute for Risk Assessment Sciences Utrecht UniversityUtrechtThe Netherlands

Background To improve our understanding of host and intestinal microbiome interaction,this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning piglets.In study 1,piglets received either a high concentration of zinc(Zn)as zinc oxide(Zn O,Zn,2,690 mg/kg)or a low Zn concentration(100 mg/kg)in the diet during the post weaning period(d 14–23).The effects on the piglet's small intestinal microbiome and functionality of intestinal tissue were investigated.In study 2,the impact of timing of the dietary zinc intervention was investigated,i.e.,between d 0–14 and/or d 14–23 post weaning,and the consecutive effects on the piglet's intestinal functionality,here referring to microbiota composition and diversity and gene expression profiles.Results Differences in the small intestinal functionality were observed during the post weaning period between piglets receiving a diet with a low or high concentration Zn O content.A shift in the microbiota composition in the small intestine was observed that could be characterized as a non-pathological change,where mainly the commensals inter-changed.In the immediate post weaning period,i.e.,d 0–14,the highest number of differentially expressed genes(DEGs)in intestinal tissue were observed between animals receiving a diet with a low or high concentration Zn O content,i.e.,23 DEGs in jejunal tissue and 11 DEGs in ileal tissue.These genes are involved in biological processes related to immunity and inflammatory responses.For example,genes CD59 and REG3G were downregulated in the animals receiving a diet with a high concentration Zn O content compared to low Zn O content in both jejunum and ileum tissue.In the second study,a similar result was obtained regarding the expression of genes in intestinal tissue related to immune pathways when comparing piglets receiving a diet with a high concentration Zn O content compared to low Zn O content.Conclusions Su

关键词： Immune system Intestinal functionality Microbiota Piglets Zinc oxide

CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse models.We recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy.Here,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in humans.Activated CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses.In cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response induction.IFN-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T cells.In agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

The olfactory system of Pieris brassicae caterpllars:from receptors to glomeruli

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Insect Science 2024年第2期31卷 469-488页

作者： Qi Wang Hans M.Smid Marcel Dicke Alexander Haverkamp Laboratory of Entomology Wageningen University and ResearchWageningenthe Netherlands

Tolfactory system of adult lepidopterans is among the best described neuronal circuits.However,comparatively little is known about the organization of the olfactory system in the larval stage of these insects.Here,we explore the expression of olfactory receptors and the organization of olfactory sensory neurons in caterpillars of Pieris brassicae,a significant pest species in Europe and a well-studied species for its chemical ecology.To describe the larval olfactory system in this species,we first analyzed the head transcriptome of third-instar larvae(L3)and identified 16 odorant receptors(ORs)including the OR coreceptor(Orco),13 ionotropic receptors(IRs),and 8 gustatory receptors(GRs).We then quantified the expression of these 16 ORs in different life stages,using qPCR,and found that the majority of ORs had significantly higher expression in the L4 stage than in the L3 and L5 stages,indicating that the larval olfactory system is not static throughout caterpillar development.Using an Orco-specific antibody,we identified all olfactory receptor neurons(ORNs)expressing the Orco protein in L3,L4,and L5 caterpillars and found a total of 34 Orco-positive ORNs,distributed among three sensilla on the antenna.The number of Orco-positive ORNs did not differ among the three larval instars.Finally,we used retrograde axon tracing of the antennal nerve and identified a mean of 15 glomeruli in the larval antennal center(LAC),suggesting that the caterpillar olfactory system follows a similar design as the adult olfactory system,although with a lower numerical redundancy.Taken together,our results provide a detailed analysis of the larval olfactory neurons in P brassicae,highlighting both the differences as well as the commonalities with the adult olfactory system.These findings contribute to a better understanding of the development of the olfactory system in insects and its life-stage-specific adaptations.

关键词： glomeruli larvae Lepidoptera odorant receptor olfactory receptor neurons sensilla

Cognition and movement in neurodegenerative disorders:a dynamic duo

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Neural Regeneration Research 2024年第10期19卷 2101-2102页

作者： Marit F.L.Ruitenberg Department of Health Medical and NeuropsychologyLeiden UniversityLeidenthe Netherlands Leiden Institute for Brain and Cognition Leidenthe Netherlands

People with neurodegenerative disorders often experience problems across a variety of functional domains,including cognition,movement,and psychosocial functioning.The classification of these disorders is based on the phenotypical manifestations that represent the most prominent clinical features.For example,Parkinson's disease and Huntington's disease are typically regarded as movement disorders,whereas Alzheimer's disease(AD) and other dementias are regarded as cognitive disorders.

关键词： disorders Huntington degenerative

Highly-sensitive wafer-scale transfer-free graphene MEMS condenser microphones

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Microsystems & Nanoengineering 2024年第1期10卷 267-275页

作者： Roberto Pezone Sebastian Anzinger Gabriele Baglioni Hutomo Suryo Wasisto Pasqualina M.Sarro Peter G.Steeneken Sten Vollebregt Laboratory of Electronic Components Technology and Materials(ECTM)Department of MicroelectronicsDelft University of TechnologyDelftThe Netherlands Infineon Technologies AG Am Campeon 1-15Neubiberg 85579Germany Kavli Institue of Nanoscience Department of Quantum NanoscienceDelft University of TechnologyDelftthe Netherlands Department of Precision and Microsystems Engineering(PME) Delft University of TechnologyDelftThe Netherlands

Since the performance of micro-electro-mechanical system(MEMS)-based microphones is approaching fundamental physical,design,and material limits,it has become challenging to improve them.Several works have demonstrated graphene’s suitability as a microphone diaphragm.The potential for achieving smaller,more sensitive,and scalable onchip MEMS microphones is yet to be determined.To address large graphene sizes,graphene-polymer heterostructures have been proposed,but they compromise performance due to added polymer mass and stiffness.This work demonstrates the first wafer-scale integrated MEMS condenser microphones with diameters of 2R=220-320μm,thickness of 7 nm multi-layer graphene,that is suspended over a back-plate with a residual gap of 5μm.The microphones are manufactured with MEMS compatible wafer-scale technologies without any transfer steps or polymer layers that are more prone to contaminate and wrinkle the graphene.Different designs,all electrically integrated are fabricated and characterized allowing us to study the effects of the introduction of a back-plate for capacitive read-out.The devices show high mechanical compliances C_(m)=0.081-1.07μmPa^(−1)(10-100×higher than the silicon reported in the state-of-the-art diaphragms)and pull-in voltages in the range of 2-9.5 V.In addition,to validate the proof of concept,we have electrically characterized the graphene microphone when subjected to sound actuation.An estimated sensitivity of S_(1kHz)=24.3-321 mV Pa^(−1)for a V_(bias)=1.5 V was determined,which is 1.9-25.5×higher than of state-of-the-art microphone devices while having a~9×smaller area.

关键词： transfer plate approaching

Perspectives for delivery of therapeutics by extravasation of biodegradable microspheres in the brain

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Neural Regeneration Research 2024年第5期19卷 969-970页

作者： Anne-Eva van der Wijk Ed VanBavel Amsterdam UMC location University of Amsterdam Department of Biomedical Engineering and PhysicsAmsterdamThe Netherlands Amsterdam Neuroscience Neurovascular Disorders ProgramAmsterdamThe Netherlands Amsterdam Cardiovascular Sciences Microcirculation ProgramAmsterdamThe Netherlands

Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is limited to small,lipid-soluble drugs and there is a lack of options for treating neuroblastomas,Alzheimer’s disease,and many other devastating pathologies.Despite the advances in strategies for crossing the blood-brain barrier such as the use of nanoparticles(Hersh et al.,2022;Duan et al.,2023),such delivery systems have not yet reached clinical practice.Therefore,novel platforms for the transport of therapeutics across the blood-brain barrier remain highly desired.This specifically holds for large molecules such as monoclonal antibodies and recombinant proteins,as well as nucleotide-based therapeutics and cell therapies.Research efforts in this field are increasing exponentially,with thousands of publications in the last few years.

关键词： therapeutics holds spite

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

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World Journal of Gastroenterology 2024年第8期30卷 811-816页

作者： Mike de Jong Foke van Delft Christine Roozen Erwin-Jan van Geenen Tanya Bisseling Peter Siersema Marco Bruno Department of Gastroenterology and Hepatology Radboud University Medical CenterNijmegen 6525 GANetherlands Department of Gastroenterology and Hepatology Erasmus University Medical CenterRotterdam 3015 GDNetherlands

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

关键词： Pancreatitis Endoscopic ultrasound Tissue acquisition Nonsteroidal antiinflammatory drugs Pancreatic cancer

Reply to the note by Li Piani et al.

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Defence Technology（防务技术） 2024年第1期31卷 603-606页

作者： T.Li Piani J.Weerheijm L.J.Sluys TU Delft Stevinweg 12628 CNDelftthe Netherlands TNO PO Box 452280 AARijswijkthe Netherlands NLDA Faculty of Military Sciences1781 CADen Helderthe Netherlands

In 2017,a ballistic phenomenological model was proposed by the authors of Ref.[1] to numerically simulate the experimental depths of small caliber projectiles impacting walls made of adobe.The opportunity for a new model in the field revealed from the observation that two older models recently used by the authors of Ref.[2] shared a linear relationship between the penetration depth P and the impacting velocity v_(O).

关键词： Penetration Adobe Modeling

A tribo-chemical view on astringency of plant-based food substances

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Friction 2024年第7期12卷 1392-1407页

作者： Samuel S.GAMANIEL Paloma S.DUEÑAS ROBLES Hans TROMP Els H.A.de HOOG Sissi de BEER Emile van der HEIDE Laboratory for Surface Technology and Tribology Faculty of Engineering TechnologyUniversity of TwenteEnschede 7522 LWthe Netherlands NIZO Food Research B.V. Ede6710 BAthe Netherlands Department of Molecules and Materials MESA+Institute for Nanotechnology University of TwenteEnschede 7500 AEthe Netherlands

Consumption of plant-based food products having high composition of polyphenols leads to the sensation of astringency.For sliding oral surfaces,friction is an essential property during the oral perception of roughness and dryness which are attributes associated with astringency.Different factors including the chemical composition of interacting layers,structure and operation of interfaces have an effect on the astringency development process.The manner of interactions occurring at oral interfaces suggest there is a system dependence of astringency and highlights the importance of adopting a tribosystems approach.Available measurement techniques have shown an existing relationship between salivary protein-polyphenol interaction and an astringent mouthfeel.Nevertheless,the tribo-chemistry involved in this multifaceted sensation remains largely unexplored in a comprehensive manner.In this review the underlying tribo-chemical processes useful in understanding the mechanism of astringency are highlighted and discussed considering current techniques employed to investigate astringency perception.Loss of lubrication on oral surfaces owing to the tribo-chemical interactions involving saliva and astringent plant proteins requires subsequent deformations of oral tissues which are significant enough to induce strains at mechanoreceptor locations,leading to the sensation of astringency.It is proposed that micro-scale contact modelling on the interaction of food particles/aggregates,boundary layers and oral surfaces shows potential in addressing the knowledge gap between tribo-chemical measurement techniques and panel tests,making it possible to attain a predictor for astringency.

关键词： oral lubrication astringency tribo-chemistry tribology