AXL – a new player in resistance to HER2 blockade

Cancer; HER2 disease; ResistanceCàncer; Malaltia HER2; ResistènciaCáncer; Enfermedad HER2; ResistenciaHER2 is a driver in solid tumors, mainly breast, oesophageal and gastric cancer, through activation of oncogenic signaling pathways such as PI3K or MAPK. HER2 overexpression associates with aggressive disease and poor prognosis. Despite targeted anti-HER2 therapy has improved outcomes and is the current standard of care, resistance emerge in some patients, requiring additional therapeutic strategies. Several mechanisms, including the upregulation of receptors tyrosine kinases such as AXL, are involved in resistance. AXL signaling leads to cancer cell proliferation, survival, migration, invasion and angiogenesis and correlates with poor prognosis. In addition, AXL overexpression accompanied by a mesenchymal phenotype result in resistance to chemotherapy and targeted therapies. Preclinical studies show that AXL drives anti-HER2 resistance and metastasis through dimerization with HER2 and activation of downstream pathways in breast cancer. Moreover, AXL inhibition restores response to HER2 blockade in vitro and in vivo. Limited data in gastric and oesophageal cancer also support these evidences. Furthermore, AXL shows a strong value as a prognostic and predictive biomarker in HER2+ breast cancer patients, adding a remarkable translational relevance. Therefore, current studies enforce the potential of co-targeting AXL and HER2 to overcome resistance and supports the use of AXL inhibitors in the clinic

Translation, Cross-Cultural Adaptation, and Psychometric Validation of the Positive Body Image among Adolescents Scale (PBIAS) into Spanish and Catalan

The Positive Body Image among Adolescents Scale (PBIAS) explores the factors that bolster and interfere with developing and maintaining a positive body image during adolescence. The aim of this study was to translate, adapt, and validate the PBIAS into Spanish and Catalan. A cross-sectional study was conducted for the instrument's translation, cross-cultural adaptation, and psychometric validation. A process of translation, back-translation, expert consultation, and piloting was followed. The reliability and statistical validity were evaluated. The Cronbach's alpha was 0.95 in both the Spanish and Catalan versions. Pearson's correlation coefficients were statistically significant (r > 0.087) for all items analyzed. The resulting values of the Spanish and Catalan versions indicate a good level of concordance (p < 0.001) with the original questionnaire, the comparative fit index being 0.914 and 0.913, the Tucker-Lewis index being 0.893 and 0.892, the root mean square error of approximation being 1.31 and 1.28, and the standardized root mean square residual being 0.051 and 0.060, respectively. The instrument presents a good level of internal consistency, a high level of reliability, and statistical validity compared to the original instrument. The PBIAS in Spanish and Catalan can be a useful assessment instrument for educators and health professionals in the context of adolescent mental health literacy. This work contributes to the Sustainable Development Goals (Goal 3) of the United Nations 2030 Agenda

Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 α-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein

[EN] Cell viability requires adaptation to changing environmental conditions. Ubiquitin-mediated endocytosis plays a crucial role in this process, because it provides a mechanism to remove transport proteins from the membrane. Arrestin-related trafficking proteins are important regulators of the endocytic pathway in yeast, facilitating selective ubiquitylation of target proteins by the E3 ubiquitin ligase, Rsp5. Specifically, Rod1 (Art4) has been reported to regulate the endocytosis of both the Hxt1, Hxt3, and Hxt6 glucose transporters and the Jen1 lactate transporter. Also, the AMP kinase homologue, Snf1, and 14-3-3 proteins have been shown to regulate Jen1 via Rod1. Here, we further characterized the role of Rod1, Snf1, and 14-3-3 in the signal transduction route involved in the endocytic regulation of the Hxt6 high affinity glucose transporter by showing that Snf1 interacts specifically with Rod1 and Rog3 (Art7), that the interaction between the Bmh2 and several arrestin-related trafficking proteins may be modulated by carbon source, and that both the 14-3-3 protein Bmh2 and the Snf1 regulatory domain interact with the arrestin-like domain containing the N-terminal half of Rod1 (amino acids 1-395). Finally, using both co-immunoprecipitation and bimolecular fluorescence complementation, we demonstrated the interaction of Rod1 with Hxt6 and showed that the localization of the Rod1-Hxt6 complex at the plasma membrane is affected by carbon source and is reduced upon overexpression of SNF1 and BMH2.Supported by a predoctoral fellowship from the Polytechnic University of Valencia.Llopis Torregrosa, V.; Ferri-Blazquez, A.; Adam-Artigues, A.; Deffontaines, E.; Van Heusden, GPH.; Yenush, L. (2016). Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 α-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein. Journal of Biological Chemistry. 291(29):14973-14985. https://doi.org/10.1074/jbc.M116.733923S149731498529129Mulet, J. M., Llopis-Torregrosa, V., Primo, C., Marqués, M. C., & Yenush, L. (2013). Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants. 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Journal of Biological Chemistry, 288(33), 24063-24080. doi:10.1074/jbc.m113.478511O’Donnell, A. F., McCartney, R. R., Chandrashekarappa, D. G., Zhang, B. B., Thorner, J., & Schmidt, M. C. (2014). 2-Deoxyglucose Impairs Saccharomyces cerevisiae Growth by Stimulating Snf1-Regulated and α-Arrestin-Mediated Trafficking of Hexose Transporters 1 and 3. Molecular and Cellular Biology, 35(6), 939-955. doi:10.1128/mcb.01183-14Becuwe, M., Vieira, N., Lara, D., Gomes-Rezende, J., Soares-Cunha, C., Casal, M., … Léon, S. (2012). A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis. The Journal of Cell Biology, 196(2), 247-259. doi:10.1083/jcb.201109113Alvaro, C. G., Aindow, A., & Thorner, J. (2016). Differential Phosphorylation Provides a Switch to Control How α-Arrestin Rod1 Down-regulates Mating Pheromone Response inSaccharomyces cerevisiae. Genetics, 203(1), 299-317. doi:10.1534/genetics.115.186122Alvaro, C. G., O’Donnell, A. F., Prosser, D. C., Augustine, A. A., Goldman, A., Brodsky, J. L., … Thorner, J. (2014). Specific  -Arrestins Negatively Regulate Saccharomyces cerevisiae Pheromone Response by Down-Modulating the G-Protein-Coupled Receptor Ste2. Molecular and Cellular Biology, 34(14), 2660-2681. doi:10.1128/mcb.00230-14Shinoda, J., & Kikuchi, Y. (2007). Rod1, an arrestin-related protein, is phosphorylated by Snf1-kinase in Saccharomyces cerevisiae. Biochemical and Biophysical Research Communications, 364(2), 258-263. doi:10.1016/j.bbrc.2007.09.134Ichimura, T., Yamamura, H., Sasamoto, K., Tominaga, Y., Taoka, M., Kakiuchi, K., … Isobe, T. (2005). 14-3-3 Proteins Modulate the Expression of Epithelial Na+Channels by Phosphorylation-dependent Interaction with Nedd4-2 Ubiquitin Ligase. Journal of Biological Chemistry, 280(13), 13187-13194. doi:10.1074/jbc.m412884200Bhalla, V., Daidié, D., Li, H., Pao, A. C., LaGrange, L. P., Wang, J., … Pearce, D. (2005). Serum- and Glucocorticoid-Regulated Kinase 1 Regulates Ubiquitin Ligase Neural Precursor Cell-Expressed, Developmentally Down-Regulated Protein 4-2 by Inducing Interaction with 14-3-3. Molecular Endocrinology, 19(12), 3073-3084. doi:10.1210/me.2005-0193Jiang, R., & Carlson, M. (1996). Glucose regulates protein interactions within the yeast SNF1 protein kinase complex. Genes & Development, 10(24), 3105-3115. doi:10.1101/gad.10.24.3105Proszynski, T. J., Klemm, R. W., Gravert, M., Hsu, P. P., Gloor, Y., Wagner, J., … Walch-Solimena, C. (2005). A genome-wide visual screen reveals a role for sphingolipids and ergosterol in cell surface delivery in yeast. Proceedings of the National Academy of Sciences, 102(50), 17981-17986. doi:10.1073/pnas.0509107102MacGurn, J. A., Hsu, P.-C., & Emr, S. D. (2012). Ubiquitin and Membrane Protein Turnover: From Cradle to Grave. Annual Review of Biochemistry, 81(1), 231-259. doi:10.1146/annurev-biochem-060210-093619Becuwe, M. , and Léon, S. (2014) Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and the ubiquitin ligase Rsp5. Elife 3, 03307Alvarez, C. E. (2008). On the origins of arrestin and rhodopsin. BMC Evolutionary Biology, 8(1), 222. doi:10.1186/1471-2148-8-222Chutkow, W. A., Patwari, P., Yoshioka, J., & Lee, R. T. (2007). Thioredoxin-interacting Protein (Txnip) Is a Critical Regulator of Hepatic Glucose Production. Journal of Biological Chemistry, 283(4), 2397-2406. doi:10.1074/jbc.m708169200Sheth, S. S., Castellani, L. W., Chari, S., Wagg, C., Thipphavong, C. K., Bodnar, J. S., … Lusis, A. J. (2004). Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic transition. Journal of Lipid Research, 46(1), 123-134. doi:10.1194/jlr.m400341-jlr200Bodnar, J. S., Chatterjee, A., Castellani, L. W., Ross, D. A., Ohmen, J., Cavalcoli, J., … Lusis, A. J. (2001). Positional cloning of the combined hyperlipidemia gene Hyplip1. 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AMPK-Dependent Degradation of TXNIP upon Energy Stress Leads to Enhanced Glucose Uptake via GLUT1. Molecular Cell, 49(6), 1167-1175. doi:10.1016/j.molcel.2013.01.035Patwari, P., Chutkow, W. A., Cummings, K., Verstraeten, V. L. R. M., Lammerding, J., Schreiter, E. R., & Lee, R. T. (2009). Thioredoxin-independent Regulation of Metabolism by the α-Arrestin Proteins. Journal of Biological Chemistry, 284(37), 24996-25003. doi:10.1074/jbc.m109.018093Paumi, C. M., Menendez, J., Arnoldo, A., Engels, K., Iyer, K. R., Thaminy, S., … Stagljar, I. (2007). Mapping Protein-Protein Interactions for the Yeast ABC Transporter Ycf1p by Integrated Split-Ubiquitin Membrane Yeast Two-Hybrid Analysis. Molecular Cell, 26(1), 15-25. doi:10.1016/j.molcel.2007.03.011Zonneveld, B. J. M. (1986). Cheap and simple yeast media. Journal of Microbiological Methods, 4(5-6), 287-291. doi:10.1016/0167-7012(86)90040-0Mayordomo, I., Regelmann, J., Horak, J., & Sanz, P. (2003). 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Eliminació simultània de fòsfor i nitrogen en aigües residuals, utilitzant microorganismes DPAO en un reactor discontinu seqüencial (SBR)

En aquest estudi es realitzà eliminació biològica simultània de fòsfor i nitrogen en un Reactor Discontinu Seqüencial (SBR), el qual conté una biomassa enriquida amb Organismes Desnitrificadors Acumuladors de Fòsfor (DPAO) que utilitzen com a única font de carboni l'àcid propiònic i com acceptors d'electrons: nitrit en la fase anòxica i oxigen en l'aeròbica. L'SBR opera amb cicle de 8 h alternant fase anaeròbica, anòxica i aeròbica. El seguiment del sistema es realitzà mitjançant mesures on-line (titrimetria) i off-line (quantificació d'àcid propiònic, nitrit i fòsfor), utilitzant l'HPLC per quantificar l'àcid propiònic i cromatografia iònica per les mesures de nitrit i fòsfor. Amb aquest sistema es pretén augmentar la captació de fòsfor en la fase anòxica fet que s'aconseguí realitzant diferents canvis al reactor per tal de maximitzar el consum de nitrit en aquesta fase, ja fos allargant el temps de fase o augmentant la concentració de biomassa. Aquest experiment ha suposat un augment de la captació de fòsfor (33 mg P-PO4 3-/L), de l'eliminació neta de fòsfor (17 mg P-PO4 3-/L) i de consum de nitrit (27 mg N-NO2-). Per altra banda, es pretenia veure els efectes a curt termini de l'eliminació de la fase aeròbica a partir del seguiment de 2 cicle puntuals i d'un cicle de 32 h sense fase aeròbica. En ambdós casos s'aconseguí una eliminació neta de fòsfor.En este estudio se llevó a cabo eliminación biológica simultanea de fósforo y nitrógeno en un reactor discontinuo secuencial (SBR) el cual contenía una biomasa enriquecida con Organismos Desnitrificantes Acumuladores de Fósforo (DPAO) que utilizan como única fuente de carbono el acido propiónico y como aceptor de electrones: nitrito en la fase anóxica y oxígeno en la aeróbica. El seguimiento del sistema se realizó mediante medidas on-line (titrimetria) y off-line (cuantificación de acido propiónico, nitrito y fósforo), utilitzando HPLC para cuantificar el acido propiónico i cromatografía iónica para las medidas de nitrito y fósforo. Con este sistema se pretende augmentar la captación de fósforo en la fase anóxica. Para conseguirlo se realizan diferentes cambios en el sistema para maximizar el consumo de nitrito en esta fase, ya sea alargando el tiempo de fase o aumentando la biomasa. Este experimento ha supuesto un aumento de la captación de fósforo (33 mg P-PO4 3-/L), de la eliminación neta de fósforo (17 mg P-PO4 3-/L) y del consumo de nitrito (27 mg N-NO2-). Por otro lado, se pretendía ver los efectos a corto plazo de la eliminación de la fase aeróbica a partir del seguimiento de 2 ciclos puntuales y de un ciclo de 32 h sin fase aeróbica. En ambos casos se consiguió una eliminación neta de fósforo.In this study, simultaneous biological phosphorus and nitrogen removal was performed in a Sequential Batch Reactor (SBR), which contained a biomass enriched with Denitrifying Phosphorus Accumulating Organisms (DPAO). These organisms are able to use propionic acid as carbon source and nitrite or oxygen as electron acceptors. The system was monitored with on-line measurements (respirometry and titrimetry) and off-line measurementss (propionic acid, nitrite and phosphorus) using a HPLC and an ionic chromatography equipment. The objective of the system is to increase the amount of phosphorus uptaken under anoxic conditions. For this purpose, the system operation was modified by increasing the anoxic phase length and increasing the biomass. This experiment has resulted in the increase of phosphorus uptake (33 mg P-PO4 3-/L), net phosphorus removal (17 mg P-PO4 3-/L) and nitrite consumption (27 mg N-NO2-). On the other hand, the short-term effect of the suppression of the aerobic phase was studied with two cycles and a period of 32 h. In both cases, net phosphorus elimination was obtained

L'assentament de la Plaça de la Gardunya a inicis del II mil·lenni: noves dades sobre les ocupacions de l'Edat del Bronze inicial al pla de Barcelona

Les excavacions preventives realitzades entre el 2011 i 2012 en la meitat nord de la plaça de la Gardunya han proporcionat, de nou, un ampli registre arqueològic d'època prehistòrica. Els treballs efectuats en una àrea de més de 950 m2 varen permetre documentar una dinàmica intensa de les ocupacions humanes en un ampli espai, fet que enriqueix de manera molt important el coneixement de les etapes de la prehistòria recent. En aquest article es revisa d'una part la cronologia de la sepultura del període neolític, i de l'altre les dades que corresponen a les ocupacions de l'època del bronze inicial. Es realitza una presentació general de les ocupacions amb una síntesi de les estructures d'hàbitat i d'enterrament, la seva articulació espacial i estratigràfica. Complementant aquestes dades s'analitzen els principals registres recuperats, principalment els materials ceràmics i la cronologia tan relativa com absoluta.Las excavaciones preventivas realizadas entre 2011 y 2012 en la mitad norte de la plaza de la Gardunya han proporcionado, de nuevo, un amplio registro arqueológico de época prehistórica. Los trabajos efectuados en un área de más de 950 m² permitieron documentar una dinámica intensa de las ocupaciones humanas en un amplio espacio, lo que enriquece de manera muy importante el conocimiento de las etapas de la Prehistoria reciente. En este artículo se revisa por un lado la cronología de la sepultura del neolítico, y por otro, los datos que corresponden a las ocupaciones de la época del Bronce Inicial. Se realiza una presentación general de las ocupaciones con una síntesis de las estructuras de hábitat y los contextos funerarios, su articulación espacial y estratigráfica. Complementando estos datos se analizan los principales registros recuperados, principalmente los materiales cerámicos y la cronología tanto relativa como absoluta.Preventive fieldwork carried out between 2011 and 2012 in the northern half of the square called Plaça de la Gardunya has again provided a large prehistoric archaeological record. The excavations developed in an area of over 950 m² have enabled us to document intense dynamics of human settlements in a large space, which significantly enriches knowledge of Late Prehistory. This article mainly reviews, on the one hand, the date corresponding to Neolithic burial and, on the other hand, the Early Bronze Age settlement. The paper is a general presentation of human occupations with a summary of the households and burials and their stratigraphic and spatial distribution. Complementing this data, the main records, mainly of pottery and chronology, are analysed

Targeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer

Breast cancer; HeterodimerizationCáncer de mama; HeterodimerizaciónCàncer de mama; HeterodimeritzacióAnti-HER2 therapies have markedly improved prognosis of HER2-positive breast cancer. However, different mechanisms play a role in treatment resistance. Here, we identified AXL overexpression as an essential mechanism of trastuzumab resistance. AXL orchestrates epithelial-to-mesenchymal transition and heterodimerizes with HER2, leading to activation of PI3K/AKT and MAPK pathways in a ligand-independent manner. Genetic depletion and pharmacological inhibition of AXL restored trastuzumab response in vitro and in vivo. AXL inhibitor plus trastuzumab achieved complete regression in trastuzumab-resistant patient-derived xenograft models. Moreover, AXL expression in HER2-positive primary tumors was able to predict prognosis. Data from the PAMELA trial showed a change in AXL expression during neoadjuvant dual HER2 blockade, supporting its role in resistance. Therefore, our study highlights the importance of targeting AXL in combination with anti-HER2 drugs across HER2-amplified breast cancer patients with high AXL expression. Furthermore, it unveils the potential value of AXL as a druggable prognostic biomarker in HER2-positive breast cancer.A.A.-A., E.J.A., and F.B.-M. were supported by Asociación Española contra el Cáncer AECC (PRDVA18013LLUC to A.A.-A., POSTD211413AREN to E.J.A., and AECC_Postdoctoral17-1062 to F.B.-M.). A.M.-S. was funded by the Spanish Government (PFIS FI20/00188). J.Ar. is supported by Breast Cancer Research Foundation (BCRF-20-08), Instituto de Salud Carlos III Project reference number AC15/00062, and the EC under the framework of the ERA-NET TRANSCAN-2 initiative cofinanced by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181), and Asociación Española Contra el Cáncer (AECC). A.P. was supported by Instituto de Salud Carlos III—PI19/01846, Breast Cancer Now—2018NOVPCC1294. P.E. and A.L. were funded by Instituto de Salud Carlos III and cofinanced by FEDER (PI18/01219 to P.E. and CB16/12/00481 to A.L.). J.M.C. was funded by Sociedad Española de Oncología Médica (Rio Hortega-SEOM) and Compromiso ADAMED

Delivery of miR-200c-3p Using Tumor-Targeted Mesoporous Silica Nanoparticles for Breast Cancer Therapy

[EN] Despite advancesin breast cancer treatment, it remainsthe leadingcause of cancer-related death in women worldwide. In this context,microRNAs have emerged as potential therapeutic targets but stillpresent some limitations for in vivo applications.Particularly, miR-200c-3p is a well-known tumor suppressor microRNAthat inhibits tumor progression and metastasis in breast cancer throughdownregulating ZEB1 and ZEB2. Basedon the above, we describe the design and validation of a nanodeviceusing mesoporous silica nanoparticles for miR-200c-3p delivery forbreast cancer treatment. We demonstrate the biocompatibility of thesynthesized nanodevices as well as their ability to escape from endosomes/lysosomesand inhibit tumorigenesis, invasion, migration, and proliferationof tumor cells in vitro. Moreover, tumor targetingand effective delivery of miR-200c-3p from the nanoparticles in vivo are confirmed in an orthotopic breast cancer mousemodel, and the therapeutic efficacy is also evidenced by a decreasein tumor size and lung metastasis, while showing no signs of toxicity.Overall, our results provide evidence that miR-200c-3p-loaded nanoparticlesare a potential strategy for breast cancer therapy and a safe andeffective system for tumor-targeted delivery of microRNAs.This research was supported by project PID2021-126304OB-C41 funded by MCIN/AEI/10.13039/501100011033/ and by European Regional Development Fund A way of doing Europe. Also, this study forms part of the Advanced Materials program (MFA/2022/049) and was supported by MCIN with funding from European Union NextGeneration EU(PRTR-C17.I1) and by Generalitat Valenciana. This study was also supported by Generalitat Valenciana (CIPROM/2021/007). This research was also supported by CIBER Consorcio Centro de Investigación Biomédica en Red CIBER-BBN(CB07/01/2012), CIBERONC(CB16/12/00481), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación. This work was also supported by Spanish Government and cofinanced by FEDER Funds (PI18/01219, PI21/01351) .I.G.-C. was funded by Margarita Salas post doctoral grant (European Union-Nextgeneration EU). A.A.-A. and A.L. were funded by Asociación Española Contra el Cancer.J.F.B. was funded by Instituto de Salud Carlos III and the European Social Fund for the financial support 'Sara Borrell' (CD19/00038). V.C.-N. was funded by Ministerio de Ciencia e Innovacio¿n (FPU grant), and J.M.C. was funded by Sociedad Española de Oncología Médica (Río Hortega-SEOM)Garrido-Cano, I.; Adam-Artigues, A.; Lameirinhas, A.; Blandez, JF.; Candela-Noguera, V.; Lluch, A.; Bermejo, B.... (2023). Delivery of miR-200c-3p Using Tumor-Targeted Mesoporous Silica Nanoparticles for Breast Cancer Therapy. ACS Applied Materials & Interfaces. 15(32):38323-38334. https://doi.org/10.1021/acsami.3c075413832338334153

MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma

Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial-mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the cell proliferation processes. We aim to evaluate the implication of miR-33b in the EMT pathway in HER2+ breast cancer (BC) and to analyze the role of EZH2 in this process as well as the interaction between them. miR-33b is downregulated in HER2+ BC cells vs healthy controls, where EZH2 has an opposite expression in vitro and in patients' samples. The upregulation of miR-33b suppressed proliferation, induced apoptosis, reduced invasion, migration and regulated EMT by an increase of E-cadherin and a decrease of ß-catenin and vimentin. The silencing of EZH2 mimicked the impact of miR-33b overexpression. Furthermore, the inhibition of miR-33b induces cell proliferation, invasion, migration, EMT, and EZH2 expression in non-tumorigenic cells. Importantly, the Kaplan-Meier analysis showed a significant association between high miR-33b expression and better overall survival. These results suggest miR-33b as a suppressive miRNA that could inhibit tumor metastasis and invasion in HER2+ BC partly by impeding EMT through the repression of the MYC-EZH2 loop

Characterisation and adding value to agro-forestry biomass products obtained from thermochemical processes

L’aprofitament de biomassa per produir biocombustibles i bioproductes a partir de fonts renovables està despertant un gran interès en els últims anys motivat per la oportunitat de convertir un residu en una font primària d’energia fàcilment accessible a escala local i regional. Catalunya és una regió amb una gran massa forestal i que genera molts residus agrícoles. L’aprofitament d’aquesta biomassa permet la millora del sector agro-forestal, la preservació i conservació del paisatge tradicional, reduir el risc d’incendis i incrementa la diversificació energètica reduint la dependència dels combustibles fòssils i mitigant els efectes del escalfament global. En aquest context, l’objectiu principal d’aquesta tesi és la valorització de residus de biomassa agro-forestal com a biocombustibles d’alta densitat energètica mitjançant processos de torrefacció i piròlisis per tal d’avançar cap a un model energètic més sostenible. En primer lloc, s’avaluà la valorització dels residus de biomassa agrària com a pellets torrefactes mitjançant un procés de torrefacció participant en una prova pilot desenvolupada en una zona rural per tal de demostrar la viabilitat tècnica i econòmica d’implementar aquest procés com a una estratègia local d’aprofitament d’aquest residu, en el que es coneix com economia circular i bioeconomia. En primer lloc, es caracteritzà la biomassa original i els productes de torrefacció. Els pellets torrefactes obtinguts tenen característiques dins estàndards europeus del pellets comercialitzables. El líquid de torrefacció és un producte aquós amb alts continguts d’àcid acètic i furfural, sent un potencial pesticida biodegradable o un protector de fusta. A més a més, es demostrà la viabilitat econòmica d’implementar una planta mòbil de torrefacció en un zona rural. El bio-oil és un producte líquid procedent de la piròlisi rapida de la biomassa amb un gran potencial com a combustible líquid i plataforma química per a la obtenció de bio-productes, sent així una potencial matèria prima en una biorefineria. Actualment, el bio-oil és un biocombustible pobre degut a la seva corrosivitat, alta viscositat, alt contingut en oxigen i la seva inestabilitat tèrmica i química. Per aquest motiu, es requereixen processos de millora d’aquest producte, encara que aquest redueixen la seva viabilitat econòmica. En aquest context, dos processos de millora del bio-oil han estat estudiats utilitzant processos amb un consum energètic assumible aprofitant la temperatura de sortida del bio-oil durant el procés de producció i el temps d’emmagatzematge. En primer lloc, es caracteritzà el bio-oil i s’avaluà un mètode de quantificació i identificació de la composició química del bio-oil mitjançant l’anàlisi per GC-MS per tal d’aconseguir una millor caracterització d’aquest producte així com la monitorització dels canvis químics que puguin tenir lloc durant els processos de millora. Posteriorment, s’avaluà un procés catalític de millora del bio-oil utilitzant bentonites i zeolites a 60 ºC. Aquest procés mostrà una reducció de l’acidesa del bio-oil encara que no degut a la catàlisi de reaccions sinó al caràcter bàsic d'aquests materials a aquesta temperatura. Finalment, nous processos d’hidrogenació del bio-oil a temperatura ambient aprofitant l’alta reactivitat de l’hidrogen naixent han estat avaluats per tal de reduir el contingut d’oxigen d’aquest i augmentar el seu poder calorífic. L’hidrogen naixent ha estat produït in situ via l’oxidació d’un metall utilitzant el bio-oil com a medi àcid i via l’electròlisi de l’aigua continguda en el bio-oil, resultant el primer mètode més simple i efectiu. Així, el procés d’hidrogenació via oxidació del zinc s’ha realitzat a diferents condicions experimentals mostrant uns resultats molt esperançadors ja que s'observen diferències significatives entre el bio-oil d'abans i de després del procés de millora. Per concloure, Aquest treball mostra el potencial, present i futur, de valoritzar residus agro-forestals mitjançant processos termoquímics com a biocombustible i bioproductes.Biomass use to produce biofuels and bio-products from a renewable source is raising a high interest in recent years motivated by the opportunity of converting biomass residues into a primary energy source easily available at local and regional scale. Catalonia is a region with large forest area and generates large amounts of agro-forestry residues. Their use might improve the agro-forestry sector by the preservation and restoration of traditional landscapes, reduce forest fire risk and increase energy diversification reducing fossil fuels dependency and mitigating the global warning effects. In this direction, the main aim of this thesis is to add-value to agro-forestry biomass residues as enhanced biofuels by means of torrefaction and pyrolysis biomass conversion processes in order to move towards a more sustainable energy model. A study of adding value to agricultural waste biomass as torrefied pellets by means of torrefaction process is performed participating in a pilot scale test carried out in a rural region to demonstrate the technic-economic viability implementing of this process as a local strategy to make use of this residue moving towards a circular and bioeconomy. Firstly, raw and torrefied products are characterised. The obtained torrefied pellets characteristics are within the European law standards of pellets demonstrating they are marketable products. Torrefaction liquid is an aqueous product with high contents of acetic acid and furfural making it a potential biodegradable pesticide or wood preservative. Moreover, the economic viability of implementing this mobile torrefaction plant in a rural region is proved being highly dependent on the scenario considered. Bio-oil is a liquid product produced by fast pyrolysis process of biomass with a great potential as liquid biofuel product and chemical platform to obtain bio-products, being a potential feedstock from a biorefinery scenarios. Currently, bio-oil is a low value biofuel due to its corrosiveness, high viscosity, high oxygen content and its thermal and chemical instability. Because of that, its upgrading is required to obtain an enhanced product, even though bio-oil upgrading processes reduce the economic viability of bio-oil as a marketable product. In this context, two novel bio-oil upgrading processes are explored to obtain an enhanced bio-oil using reduced energy and resources cost upgrading process in comparison to conventional. Firstly, bio-oil characterisation is performed, as well as it is assessed and reached a reliable quantitative analysis of bio-oil chemical compounds by means of GC-MS to achieve a further characterization of this product and to permit a proper monitoring of bio-oil properties changes during the upgrading processes. Then, it is tested a catalytic upgrading process using bentonite and zeolite HZSM-5 at 60 ºC to avoid the necessity of a bio-oil external heating due to bio-oil coming out of the fast pyrolysis at this temperature. Results show an acidity reduction of treated bio-oil, although a reduced catalytic reaction is observed due to the quick deactivation of these catalysts at this temperature. Finally, novel hydrogenation procedures to hydrogenate bio-oil at ambient temperature in order to reduce its oxygen content and increase its calorific value using the high reactivity of nascent hydrogen are explored. Nascent hydrogen is generated via metal oxidation using bio-oil as acidic medium and via water electrolysis contained in bio-oi resulting nascent hydrogen via zinc metal oxidation the simplest and more effective process relative to the other tested ones. An extended study of this hydrogenation process is assessed at different experimental conditions showing the potentially of this cheap and simple novel hydrogenation process. In conclusion, this research shows the current and future potential of adding value to agro-forestry waste biomass by means of thermochemical processes as biofuels and bioproducts to move towards a bioeconomy strategy