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SERS sensing for cancer biomarker:Approaches and directions

Bioactive Materials 2024年第4期34卷 248-268页

作者： lorena vázquez-iglesias Giovanna Maria Stanfoca Casagrande Daniel García-Lojo Letícia Ferro Leal Tien Anh Ngo Jorge Pérez-Juste Rui Manuel Reis Krishna Kant Isabel Pastoriza-Santos CINBIO Universidade de VigoCampus Universitario As Lagoas MarcosendeVigo 36310Spain Galicia Sur Health Research Institute(IIS Galicia Sur) 36310VigoSpain Molecular Oncology Research Center Barretos Cancer HospitalBarretosBrazil Barretos School of Medicine Dr.Paulo Prata-FACISB Barretos14785-002Brazil vinmec Tissue Bank Vinmec Health Care SystemHanoiViet Nam Life and Health Sciences Research Institute(ICvS) School of MedicineCampus de GualtarUniversity of Minho4710-057 BragaPortugal ICvS/3B’s-PT Government Associate Laboratory 4710-057BragaPortugal

These days,cancer is thought to be more than just one illness,with several complex subtypes that require different screening *** subtypes can be distinguished by the distinct markings left by metabolites,proteins,miRNA,and *** illness management may be possible if cancer is categorized according to its *** order to stop cancer from spreading and posing a significant risk to patient survival,early detection and prompt treatment are *** cancer screening techniques are tedious,time-consuming,and require expert personnel for *** has led scientists to reevaluate screening methodologies and make use of emerging technologies to achieve better *** time and money saving techniques,these methodologies integrate the procedures from sample preparation to detection in small devices with high accuracy and *** its proven potential for biomedical use,surface-enhanced Raman scattering(SERS)has been widely used in biosensing applications,particularly in biomarker *** was given especially to the potential of SERS as a portable clinical diagnostic *** approaches to SERS-based sensing technologies for both invasive and non-invasive samples are reviewed in this article,along with sample preparation techniques and *** from these significant constraints in the detection approach and techniques,the review also takes into account the complexity of biological fluids,the availability of biomarkers,and their sensitivity and selectivity,which are generally *** ways to maintain sensing capabilities in clinical samples are being developed recently to get over this *** is known to be a reliable diagnostic method for treatment ***,there is still room for advancement in terms of portability,creation of diagnostic apps,and interdisciplinary AI-based ***,we will outline the current state of technological maturity f

关键词： Surface-enhanced Raman scattering(SERS) Cancer biomarkers Invasive and non-invasive biomarkers Point of care detection Microfluidic devices

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Cryptic exon inclusion in TDP-43 proteinopathies:opportunities and challenges

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Neural Regeneration Research 2025年第7期20卷 2003-2004页

作者： lorena Decker Sonja Menge Axel Freischmidt Department of Neurology Ulm UniversityUlmGermany

TDP-43 proteinopathies and cryptic exons:Transactive response DNA binding protein of 43 kDa(TDP-43)is a ubiquitously expressed RNA/DNA binding protein crucial for coding and non-coding RNA metabolism including transcription,splicing,transport,translation,and ***-43 shuttles between the nucleus and cytoplasm,but is predominantly localized in the *** diseases(NDs)may be accompanied by nuclear loss and possible cytoplasmic accumulation and aggregation of TDP-43 in vulnerable neurons and *** neuropathology is the hallmark of most individuals suffering from amyotrophic lateral sclerosis(ALS),frontotemporal dementia(FTD)with TDP-43-immunoreactive pathology(FTD-TDP),limbic-predominant age-related TDP-43 encephalopathy(LATE)and Perry syndrome,but also coexists with the primary pathology in subsets of patients suffering from other NDs,such as Alzheimer’s disease,Lewy body dementias,or Huntington’s *** in the gene encoding TDP-43(TARDBP)are the cause of ALS and/or FTD in some rare cases substantiating the importance of this protein in aging *** is still controversial if loss of nuclear,or increased cytoplasmic and/or aggregating TDP-43 is more harmful to neurons(Nag and Schneider,2023).Recently,the role of nuclear TDP-43 in repressing the inclusion of intronic sequences,named cryptic exons(CEs),into mature mRNAs gained much attention.

关键词： Huntington metabolism TDP

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Effect of intensity and duration of anthropic noises on European mink locomotor activity and fecal cortisol metabolite levels

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Current Zoology 2022年第6期68卷 688-699页

作者： lorena ORTIZ-JIMENEZ Carlos iglesias-MERCHAN Alba Itzel MARTıNEZ-SALAZAR Isabel BARJA Department of Biology Zoology UnitUniversidad Autonoma de MadridMadrid28049Spain Department of Forest and Environmental Engineering and Management Universidad Politecnica de MadridMadridSpain Geographic Information Systems Laboratory Institute of BiologyUniversidad Nacional Autonoma de MexicoMexico CityMexico Biodiversity and Global Change Research Centre(CIBC-UAM) Universidad Autonoma de MadridMadridSpain

Human activities involving noise emission can affect wild *** mink was exposed to road noise and human voice playbacks to analyze how sound intensity level and duration of both noises altered the time that individuals were active and if their fecal cortisol metabolite(FCM)levels varied.A Hierarchical Analysis Cluster was performed to establish 2 mink groups with respect to both noise source type:short duration/low intensity(SL)and long duration/high intensity(LH).We performed general linear mixed models to evaluate the variation in locomotor activity duration(s)and FCM(nanogram per gram)levels,*** results showed both road noise and human voices decreased locomotor activity duration in SL more sharply compared with LH,and human voices were the triggers that induced the most pronounced response to both exposure ***(ng/g)levels increased in SL compared with LH during road noise while the opposite happened during human *** based on sex and age of individuals were *** conclusion,noise characteristics given by the sound type determined the variations in locomotor activity duration while noise exposure level determined the variations in FCM(ng/g)*** should be paid to noisy activities(e.g.,recreational activities for visitors in protected natural areas)and loud groups of people to conserve wildlife,especially noise sensitive species.

关键词： anthropic disturbances European mink fecal cortisol metabolites noise exposure locomotor activity behavioral response

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Site-directed cysteine coupling of disulfide-containing non-antibody carrier proteins(THIOCAPs)

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Science China Materials 2023年第10期66卷 4109-4120页

作者： Ariana Rueda Julian I.Mendoza lorena Alba-Castellon Eloi Parladé Eric voltà-Durán David Paez Anna Avino Ramon Eritja Esther vázquez Antonio villaverde Ramón Mangues Ugutz Unzueta Institut d'Investigació Biomèdica Sant Pau(IIB Sant Pau) Sant Quintí 77-7908041 BarcelonaSpain Josep Carreras Leukaemia Research Institute(IJC Campus Sant Pau) 08041 BarcelonaSpain CIBER de Bioingeniería Biomateriales y NanomedicinaInstituto de Salud Carlos Ⅲ28029 MadridSpain Institut de Biotecnologia i de Biomedicina Universitat Autònoma de Barcelona08193 BellaterraSpain Departament de Genètica i de Microbiologia Universitat Autònoma de Barcelona08193 BellaterraSpain Department of Medical Oncology Hospital de la Santa Creu i Sant Pau.Barcelona08025 BarcelonaSpain CIBER de Enfermedades Raras(CIBERER) Instituto de Salud Carlos Ⅲ28029 MadridSpain Institute for Advanced Chemistry of Catalonia(IQAC) CSIC08034 BarcelonaSpain

The development of a new generation of nonantibody protein drug delivery systems requires site-directed conjugation strategies to produce homogeneous,reproducible and scalable *** that,the genetic addition of cysteine residues into solvent-exposed positions allows the thiol-mediated cysteine coupling of therapeutic drugs into protein-based ***,the high reactivity of unpaired cysteine residues usually reduces protein stability,consequently imposing the use of more methodologically demanding purification *** is especially relevant for disulfide-containing nanocarriers,as previously observed in ***,although many protein scaffolds and targeting ligands are also rich in disulfide bridges,the use of these methodologies over emerging non-antibody carrier proteins has been completely ***,we report the development of a simple and straightforward procedure for a onestep production and site-directed cysteine conjugation of disulfide-containing non-antibody thiolated carrier proteins(THIOCAPs).This method is validated in a fluorescent C-X-C chemokine receptor 4(CXCR4)-targeted multivalent nanocarrier containing two intramolecular disulfide bridges and one reactive cysteine residue strategically placed into a solvent-exposed position(THIO-T22-GFP-H6)for drug conjugation and in a humanized alternative intended for clinical applications(T22-HSNBT-H6).Thus,we produce very stable,homogeneous and fully functional antitumoral nanoconjugates(THIO-T22-GFP-H6-MMAE and T22-HSNBT-H6-MMAE)that selectively eliminate target cancer cells via ***,the developed methodology appears as a powerful tool for the rational engineering of emerging non-antibody,cell-targeted protein nanocarriers that contain disulfide bridges together with a solvent-exposed reactive cysteine(THIOCAP).This should pave the way for the development of a new generation of stable,homogeneous and efficient nanomedicines.

关键词： disulfide directed bridges

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Endocytic Trafficking towards the vacuole Plays a Key Role in the Auxin Receptor SCF^TIR-Independent Mechanism of Lateral Root Formation in A. thaliana

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Molecular Plant 2012年第6期5卷 1195-1209页

作者： Patricio Perez-Henrique Natasha v. Raikhel lorena Norambuena Plant Molecular Biology Laboratory Department of Biology Faculty of Sciences University of Chile Santiago Chile Millenium Nucleus in Plant Cell Biotechnology Chile Center for Plant Cell Biology and Department of Botany and Plant Sciences University of California Riverside CA 92521 USA

Plants＇ developmental plasticity plays a pivotal role in responding to environmental conditions. One of the most plastic plant organs is the root system. Different environmental stimuli such as nutrients and water deficiency may induce lateral root formation to compensate for a low level of water and/or nutrients. It has been shown that the hor- mone auxin tunes lateral root development and components for its signaling pathway have been identified. Using chemi- cal biology, we discovered an Arabidopsis thaliana lateral root formation mechanism that is independent of the auxin receptor SCFTM. The bioactive compound Sortin2 increased lateral root occurrence by acting upstream from the morpho- logical marker of lateral root primordium formation, the mitotic activity. The compound did not display auxin activity. At the cellular level, Sortin2 accelerated endosomal trafficking, resulting in increased trafficking of plasma membrane recy- cling proteins to the vacuole. Sortin2 affected Late endosome/PvC/MvB trafficking and morphology. Combining Sortin2 with well-known drugs showed that endocytic trafficking of Late E/PvC/MvB towards the vacuole is pivotal for Sortin2- induced SCFTm-independent lateral root initiation. Our results revealed a distinctive role for endosomal trafficking in the promotion of lateral root formation via a process that does not rely on the auxin receptor complex SCFTM.

关键词： lateral root development endocytic trafficking Sortin2 endosomes Arabidopsis.

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Self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4^(+) head and neck squamous cell carcinoma tumors

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2578-2591页

作者： Elisa Rioja-Blanco Irene Arroyo-Solera Patriciaálamo Isolda Casanova Alberto Gallardo Ugutz Unzueta Naroa Serna Laura Sánchez-García Miquel Quer Antonio villaverde Esther vázquez Ramon Mangues lorena Alba-Castellón Xavier León Institut d'InvestigacióBiomèdica Sant Pau(IIB-Sant Pau) Barcelona 08041Spain Institut de Recerca contra la Leucèmia Josep Carreras Barcelona 08025Spain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)Madrid 28029Spain Department of Pathology Hospital de la Santa Creu i Sant PauBarcelona 08041Spain Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra 08193Spain Departament de Genètica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra 08193Spain Department of Otorhinolaryngology Hospital de la Santa Creu i Sant PauBarcelona 08041Spain

Loco-regional recurrences and distant metastases represent the main cause of head and neck squamous cell carcinoma(HNSCC) mortality. The overexpression of chemokine receptor 4(CXCR4) in HNSCC primary tumors associates with higher risk of developing loco-regional recurrences and distant metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated the self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target CXCR4. This study aimed to validate T22-GFP-H6 as a suitable nanocarrier to selectively deliver cytotoxic agents to CXCR4^(+)tumors in a HNSCC model. Here we demonstrate that T22-GFP-H6 selectively internalizes in CXCR4^(+)HNSCC cells, achieving a high accumulation in CXCR4^(+)tumors in vivo, while showing negligible nanocarrier distribution in non-tumor bearing organs. Moreover, this T22-empowered nanocarrier can incorporate bacterial toxin domains to generate therapeutic nanotoxins that induce cell death in CXCR4-overexpressing tumors in the absence of histological alterations in normal organs. Altogether, these results show the potential use of this T22-empowered nanocarrier platform to incorporate polypeptidic domains of choice to selectively eliminate CXCR4^(+)cells in HNSCC. Remarkably, to our knowledge, this is the first study testing targeted proteinonly nanoparticles in this cancer type, which may represent a novel treatment approach for HNSCC patients.

关键词： Targeted drug delivery Protein nanoparticles CXCR4 receptor HNSCC Cell targeting Recombinant proteins Nanotoxins Cancer therapy

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Restoring expression of Stathmin-2:a novel strategy to treat TDP-43 proteinopathies

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3553-3554页

作者： Sonja Menge lorena Decker Axel Freischmidt Department of Neurology Ulm University89081 UlmGermany

In a recent study published in Science,Baughn et *** that TDP-43 acts as a steric block in STMN2 pre-mRNA processing preventing inclusion of a deleterious cryptic exon,and present strategies for substituting this function to compensate for the loss of nuclear TDP-43 in a variety of neurodegenerative diseases(NDs)including amyotrophic lateral sclerosis(ALS).1 Stathmin-2(STMN2)is a microtubule-associated protein speci-fically expressed in neurons and required for axon outgrowth and maintenance,as well as for axon regeneration after injury in vitro.

关键词： Stathmin diseases

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Baculovirus RNA Polymerase: Activities, Composition, and Evolution

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中国病毒学 2007年第2期22卷 94-107页

作者： A.lorena Passarelli Molecular Cellular and Developmental Biology Program Division of Biology 116 Ackert Hall Kansas State University Manhattan KS 66506-4901 USA

Baculoviruses are the only nuclear replicating DNA-containing viruses that encode their own DNA-directed RNA polymerase (RNAP). The baculovirus RNAP is specific for the transcription of genes expressed after virus DNA replication. It is composed of four subunits, making it the simplest multisubunit RNAP known. Two subunits contain motifs found at the catalytic center of other RNAPs and a third has capping enzyme functions. The function of the fourth subunit is not known. Structural studies on this unique RNAP will provide new insights into the functions of this enzyme and the regulation of viral genes and may be instrumental to optimize the baculovirus gene expression system.

关键词：杆状病毒聚合酶病毒复制病毒基因

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New discriminant-function-based multidimensional discrimination of mid-ocean ridge and oceanic plateau

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Geoscience Frontiers 2020年第5期11卷 1681-1693页

作者： Surendra P.verma lorena Diaz-Gonzalez Instituto de Energias Renovables Universidad Nacional Autonoma de MexicoPriv.Xochicalco S/no.Col.CentroApartado Postal 34TemixcoMor62580Mexico Centro de Investigacion en Ciencias Universidad Autonoma de Estado de MorelosCuernavacaMorelos62209Mexico

From a compilation of geochemical data for the discrimination of the tectonic settings of mid-ocean ridge(MOR;3730 samples)and oceanic plateau(OP;3656 samples),we present two new discriminant functions and diagrams obtained from censored multivariate discordant outlier-free *** different sets of data(original concentrations as well as isometric log-ratio transformed(ilr)variables;all 10 major(M)elements as well as all 10 major and 6 trace elements MT)were used to evaluate the quality of discrimination from linear discriminant analysis(LDA)and canonical *** selected multidimensional models ilrM(9 ilr transformed variables of multi-normally distributed 10 major elements)and ilrMT(15 ilr transformed variables of multi-normally distributed combined 10 major and 6 trace elements),considered as the best or most representative(total of5650 samples for ilrM and 2858 for ilrMT),provided percent success values,respectively,of 80.9%for the MOR and 81.1%for the OP(ilrM)and 88.5%for the MOR and 90.1%for the OP(ilrMT).Both processes(log-ratio transformation and multi-normality)rendered the percent success values similar for both groups(MOR and OP).The respective discriminant functions were successfully used for four tests from known tectonic settings and four application cases(two for ophiolites and two for Precambrian rocks),documenting thus the utility of the new discrimination procedure for the MOR and OP tectonic ***,we showed that our multidimensional procedure is robust against analytical errors or uncertainties,as well as post-emplacement compositional changes caused by element mobility from both low or high temperature *** robustness against the gain or loss of a single element at a time was also documented,from which the ilrMT model was evaluated as more robust than the ilrM model.A new online computer program MOROPdisc was written in Java Framework ZK,which is freely available for use at our web portal http://***

关键词： MORB Multivariate discordant outliers Log-ratio transformation Multidimensional discrimination Analytical uncertainties Post-emplacement changes

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Chemical-Abrasion U-Pb zircon geochronology reveals 150 Myr of partial melting events in the Archean crust of the São Francisco Craton

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Geoscience Frontiers 2022年第5期13卷 169-189页

作者： lorena Martins Cristiano Lana Ariela Mazoz Tiago Novo Applied Isotope Research Group Departamento de GeologiaEscola de MinasUniversidade Federal de Ouro PretoMorro do CruzeiroOuro PretoMG35400-000Brazil Universidade Federal de Minas Gerais Programa de Pós-Graduação em GeologiaIGC-CPMTCCampus PampulhaAv.Antônio Carlos 6627Belo HorizonteMG31270-901Brazil

Field observations and CA-LA-ICP-MS U–Pb zircon ages and Hf isotope compositions obtained from migmatitic orthogneisses and granitoids from the Belo Horizonte Complex,southern São Francisco Craton,indicate a major period of partial melting and production of felsic rocks in the *** observations show that the complex is an important site for studying partial melting processes of Archean crystalline *** of the complex exposes fine-grained stromatic migmatites that are intruded by multiple leucogranitic veins and sheeted *** migmatites and leucogranite sheets are crosscut by several phases of granitoid batholiths and small granitic bodies;both of which are closely associated with the host banded *** abrasion followed by detailed cathodoluminescence imaging revealed a wide variety of zircon textures that are consistent with a long-lived period of partial melting and crustal *** of U-Pb and Hf isotopes disclose the complex as part of a much wider crustal segment,encompassing the entire southern part of the São Francisco *** of available U-Pb ages suggests that this crustal segment was consolidated sometime between 3000 Ma and 2900 Ma and that it experienced three main episodes of partial melting before stabilization at 2600 *** partial melting episodes took place between 2750 Ma and 2600 Ma as a result of tectonic accretion and peeling off the lithospheric mantle and lower *** process is likely responsible for the emplacement of voluminous potassic granitoids across the entire São Francisco *** believe that the partial melting of Meso-Archean crystalline crust and production of potassic granitoids are linked to a fundamental shift in the tectonics of the craton,which was also responsible for the widespread intrusion of large syenitic bodies in the northern part of the craton,and the construction of layered mafic–ultramafic intrusions to the south of the BHC.

关键词： Archean São Francisco Craton Crustal reworking U-Pb geochronology Lu-Hf isotopes

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