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A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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Bio-Design and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.O.Beeren g.Dos Santos P.J.Dijkstra C.Mota J.Bauer H.Ferreira Rui l.Reis N.Neves S.Camarero-Espinosa M.B.Baker l.Moroni Department of Complex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s Research group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT government Associate laboratory 4806-909 Braga/GuimarãesPortugal POlYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKERBASQUE Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering ***,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell *** of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface ***,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCl5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCl75k at different *** porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCl *** a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was *** two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated *** addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface *** together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material ***,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(m

关键词： Additive manufacturing Blending Surface functionalization Surface density Click chemistry Human

RNF26 up-reg.l.tes PD-l1 to reg.l.te the cancer immune response in ccRCC

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BIOCEll 2024年第9期48卷 1323-1330页

作者： Ren, Weigang.l., Jing Zeng, Ruijiang Zhu, l. iang Hunan Normal Univ Hunan Prov Peoples Hosp Dept Urol Changsha 410000 Peoples R China Cent South Univ Second Xiangya Hosp Dept Rehabil Changsha 410000 Peoples R China Cent South Univ Second Xiangya Hosp Dept Urol Changsha 410000 Peoples R China Cent South Univ Urooncol Inst Changsha 410000 Peoples R China

Background: Clear cell renal cell carcinoma (ccRCC) stands as the most prevalent form of kidney cancer, accounting for a significant proportion of malignancies affecting the kidneys. ccRCC is well known as a type of tumour with immunogenicity. Immune checkpoint inhibitors (ICIs) aim to enhance the anticancer immune response in ccRCC by blocking programmed cell death 1 ligand 1/programmed death 1 (PD-l1/PD-1) pathways. In a previous study, we showed that RINg finger protein 26 (RNF26) degrades chromobox 7 (CBX7) to activate the tumor necrosis factor (TNF) in ccRCC. Methods: We analyzed The Cancer genome Atlas (TCgA) database using the R package ESTIMATE and found that RNF26 was significantly associated with ccRCC immune infiltration. The relationship between RNF26 and the PD1 checkpoint signaling pathway was detected by enrichment analysis. In addition, the molecular mechanism of RNF26 up-reg.l.tion of PD-l1 was detected by transcriptome sequencing, RT-qPCR, and Western Blot in ccRCC cell lineages 786-O and A498 cells. The transplantation tumor experiments in C57Bl/6 mice were used to test the efficacy of anti-PD1 and knockdown of RNF26 in vivo. Results: We showed that RNF26 suppressed the immune response to ccRCC. Next, we revealed that RNF26 activated the PD-1 checkpoint pathway to suppress the immune response to ccRCC, possibly via the CBX7/PD-l1 axis. Conclusion: The suggestion derived from our results is that targeting RNF26 holds the potential to amplify the efficacy of anticancer immunotherapies in the treatment of ccRCC.

关键词： Clear cell renal cell carcinoma Ring fi nger protein 26 chromobox 7 PD-l1 RENAl-CEll CARCINOMA PROTEIN INSIgHTS

Nitrogen mineralization in the oldest climax communities in the eastern Mediterranean region

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Journal of Forestry Research 2024年第1期35卷 213-228页

作者： Fatma Selcen Sakar gürcan g.l.ryüz Department of Biology Section Ecology GörükleGraduate School of Natural and Applied ScienceUniversity of Bursa Uludağ16059 NilüferBursaTurkey Department of Biology Section Ecology GörükleFaculty of Science and ArtsUniversity of Bursa Uludağ16059 NilüferBursaTurkey

In this study,we investigated how tree species affect N mineralization in connection to some soil properties and seconder metabolite levels of litter,in the soil of the old-est native forest *** the oldest pure communi-ties of Pinus nigra(PN),Fagus orientalis(FO),and Abies bornmuelleriana(AB)in the mountain range of Mount Uludağ,Bursa,Turkey,annual net yield and N mineraliza-tion in the 0-5-and 5-20-cm soil layers were determined in a field incubation study over 1 *** locations were chosen from 1300 to 1600 m a.s.l.,and moisture content(%),pH,water-holding capacity(%),organic C,total N,and C/N ratio,and annual net mineral N yield of the soil and hydro-lyzed tannic acid and total phenolic compounds in litter were compared for these forest *** had the highest annual net Nmin yield(43.9±4.8 kg ha^(-1) a^(-1)),*** the lowest(30.5±4.2 kg ha^(-1) a^(-1)).Our findings show that in the oldest forest ecosystems,the seasonal soil moisture content and tree species play an essential role in N cycling and that hydrolyzed tannic acids and total phenolic compounds effectively control N *** acid and total phenolics in the litter were found to inhibit nitrification,but total phenolics were found to stimulate ammonification.

关键词： Oldest forest communities Nitrogen mineralization Nitrification Tannic acid Total phenolic litter

Dynamics and cytokinic reg.l.tion of immune cell infiltration in genetically engineered mouse models of pancreatic cancer dictate the sensitivity to immunotherapy

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Cancer Communications 2024年第1期44卷 178-182页

作者： Okan Safak Shenghan Wang Carmen Mota Reyes Ibrahim Halil gürcinar Sergey Tokalov Nedim Can Cevik Kivanc görg.l. Bengi Su Yilmaz Emre Erdogan linhan Ye Qiaolin li Elif Arik Sever SamedÖzer g.l.al Süyen Helmut Friess güralp Onur Ceyhan Rouzanna Istvanffy Hana Alg.l.Ihsan Ekin Demir Department of Surgery Klinikum rechts der IsarTechnical University of MunichSchool of MedicineMunichBavariaGermany Department of general Surgery HPB-UnitSchool of MedicineAcibadem Mehmet Ali Aydinlar UniversityIstanbulIstanbulTurkey Comprehensive Cancer Center München Klinikum rechts der IsarTechnical University of MunichSchool of MedicineMunichBavariaGermany Department of Hematology Oncology and Tumor ImmunologyCharitéUniversity Medicine BerlinCampus Virchow ClinicBerlinBerlinGermany graduate School of Health Sciences Acibadem Mehmet Ali Aydinlar UniversityIstanbulIstanbulTurkey Department of Physiology Acibadem Mehmet Ali Aydinlar UniversityIstanbulIstanbulTurkey Else Kröner Clinician Scientist Professorship for Translational Pancreatic Surgery MunichGermany Neural Influences in Cancer(NIC)International Research Consortium MunichGermany

Dear Editor,Targeting the immune compartment in pancreatic duc-tal adenocarcinoma(PDAC)holds promise for prognostic improvement,yet our knowledge on the spatial and tem-poral dynamics and the molecular modulators of t... 详细信息

关键词： immune adenocarcinoma immunotherapy

On the functions of astrocyte-mediated neuronal slow inward currents

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Neural Regeneration Research 2024年第12期19卷 2602-2612页

作者： Balázs Pál Department of Physiology Faculty of MedicineUniversity of DebrecenDebrecenHungary

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of *** events are significantly slower than the excitatory postsynaptic *** of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto *** are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback *** as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological *** is a growing body of evidence on the roles of slow inward currents on a single neuron or local network *** events often occur in synchro ny on neurons located in the same astrocytic *** synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic *** addition,slow inward currents are also subject to non-synaptic plasticity triggered by long.l. sting stimulation of the excitatory *** note,there might be important regionspecific differences in the roles and actions triggering slow inward *** greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological *** inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural *** inward currents are significant contributors to paroxysmal depolarizational shifts/interictal *** events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive *** with features overlapping with slow inward currents(excitatory,N-methyl-Dasp

关键词： astrocyte cortical spreading depolarization gliotransmission glutamate neural synchronization NMDA receptor paroxysmal depolarizational shift slow inward current

On calculating glacial isostatic adjustment

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geodesy and geodynamics 2024年第5期15卷 441-452页

作者： l.M.Cathles Cornell University IthacaNY 14853USA

Modeling the earth's fluid and elastic response to the melting of the glaciers of the last ice age is the most direct way to infer the earth's radial viscosity ***,we compare two methods for calculating the viscoelastic response to surface *** one,the elastic equation of motion is converted to a viscoelastic equation using the Correspondence *** the other,elastic deformation is added to the viscous flow as isostatic adjustment *** two modeling methods predict adjustment histories that are different enough to potentially impact the interpretation of the observed glacial isostatic adjustment(gIA).The differences arise from buoyancy and whether fluid displacements are subjected to hydrostatic *** methods agree if they use the same equations and boundary *** origin of the differences is determined by varying the boundary conditions and pre-stress application.

关键词： glacial isostatic adjustment Viscoelastic normal modes Hydrostatic pre-stress Elastic buoyancy Correspondence principle

Effect of radiative loss mechanisms on FIR thermometric parameters of Nd^(3+)-doped lithium tellurite glasses

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Journal of Rare Earths 2024年第7期42卷 1250-1257,I0002页

作者： C.Y.Morassuti A.P.l Silva l.A.O.Nunes S.M.lima l.H.C.Andrade Optical and Photothermal Spectroscopy group(gEOF) Center for Studies in Natural Resources(CERNA)State University of Mato Grosso do Sul(UEMS)C.P.351DouradosMSBrazil Renato Archer Information Technology Center Dom Pedro I Highway(SP-65)Km 1436-Chácaras Campos dos AmaraisCampinasSPBrazil Institute of Physics of São Carlos University of São PauloSão CarlosSPBrazil

Nd^(3+)-doped tellurite glasses are promising materials for thermometers based on the fluorescence intensity ratio(FIR)***,at high Nd^(3+)concentrations,energy transfer(ET)processes such as optical reabsorption and cross-relaxation can affect the Nd^(3+)emission,which has been little explored in the ***,the present work investigated the use of Nd^(3+)-doped tellurite glass(samples doped with Nd^(3+)at 0.2 mol%,0.5 mol%,2.0 mol%,and 4.0 mol%)in fluorescence thermometers,in the temperature range from 299 to 371 *** results indicate a strong dependence of the FIR parameters on the Nd^(3+)concentration,due to changes in the emission band profiles caused by optical reabsorption of the Nd^(3+)emissions and cross-relaxation processes.A decrease of the relative sensitivity of the ratio^(4)F_(5/2)→^(4)I_(9/2)/^(4)F_(3/2)→^(4)I_(9/2)is observed for samples doped with higher amounts of Nd^(3+).The maximum relative sensitivity at 299 K is 3.00%/K,which is the highest value among the reported Nd^(3+)ions.

关键词： Nd^(3+)-doped tellurite glass Fluorescence intensity ratio Optical thermometry Judd-Ofelt Rare earths

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Solid-liquid extraction for yttrium recovery using porous polymeric resin(XAD-7) functionalized with D_(2)EHPA

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Journal of Rare Earths 2024年第9期42卷 1764-1773,I0005页

作者： P.A.Martínez-Montoya R.g.Sanchez-Alvarado D.Y.Medina-Velazquez M.l.Carrera-Jota P.garnica-Chávez A.de J.Morales-Ramirez Higher School of Chemical Engineering and Extractive Industries ESIQIEIPNDepartment of Metallurgical EngineeringUPALM S/NCol.LindavistaGustavo A.Madero Cd.de MéxicoC.P07738Mexico Metropolitan Autonomous University Department of MaterialsBasic Sciences and EngineeringAv.San Pablo No.180Col.Reynosa TamaulipasCd.de MéxicoC.P02200Mexico Center for Research and Technological Innovation CIITECIPNCda.de CECATIs/nSanta CatarinaAzcapotzalcoC.P02250CDMXMexico

The recovery of yttrium is proposed by applying a solid-liquid extraction process using di-2-ethyl hexylphosphoric acid(D2EHPA) as extracting *** extracting agents were supported on a macro porous polymeric resin XAD-7(solid phase).Yttrium ions extraction and discharge tests were performed,firstly from a synthetic aqueous solution of 100 mg.l.Y(liquid phase) at 25℃ with *** effects of pH of aqueous solutions bearing yttrium,volume fraction of extracting agents and the solid/liquid(S/l)ratio on the yttrium recovery were *** most favorable conditions for yttrium ions extraction are;20 vol% D_(2)EHPA functionalized resin,pH=1.5 and an S/l ratio of 10 mg/ml The discharge of yttrium ions was done under the same conditions of extraction stage,using a 2 mol/l [H_(2)SO_(4)] as stripping *** to 80% yttrium is extracted,while 75% yttrium is recovered in the striping *** all experiments,the reaction equilibrium is reached after 20 min,and the kinetics for the extraction stage was determined as a second-order ***,experiments were carried out to discharge the yttriumloaded resins,and it has been determined that the best pH value to strip the Y ions is *** tests of extraction and discharge for yttrium ions show that the functionalized resin can work at least five cycles without decreasing its ***,the proposed process was tested in a real solution with Y ions fro m a waste fluorescent la mp powder leached in H_(2)SO_(4),demonstrating the ability to effectively recover yttrium,separating it from various metals from the studied residue.

关键词： Yttrium recovery Rare earth solid-liquid extraction XAD-7 resin Fluorescent lamps recycling Solid-liquid kinetics extraction

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

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World Journal of Diabetes 2024年第8期15卷 1717-1725页

作者： Jorge M Molina Patricia g Medina Rita A gomez Julia R Herrera Nancy l Martínez Brenda Hernández Yesenia garcía Department of Endocrinology Children’s Hospital Federico GomezMexico 06720Mexico National Medical Center"Siglo XXI" UMAE Hosp EspecialidadesUnidad Invest Med Epidemiol ClinMexican Social Security InstituteMexico 06720Mexico Research Division UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIMexican Institute of Social SecurityMexico 06720Mexico Epidemiology Research Unit in Endocrinology and Nutrition Federico Gómez Children’s HospitalMexico 06720Mexico Department of Endocrinology Comprehensive Health Unit for Trans PersonsMexico 11340Mexico

BACKgROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-gAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin *** To evaluate anti-gAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of *** This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 ***,blood pressure,glucose,insulin,C-peptide,glycated hemoglobin A1c,and lipid profiles were *** was used to measure anti-gAD65,anti-IA2,and anti-Zn8T *** statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.Plly *** There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 *** presence of anti-gAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,*** the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-gAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).CONClUSION Anti-gAD65 positivity was high in our ***-gAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

关键词： Diabetes Obesity Adolescents Autoimmunity Beta cell Insulin requirements